FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Clipperton-Allen, AE Page, DT AF Clipperton-Allen, Amy E. Page, Damon T. TI Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; SPECTRUM DISORDERS; SYNAPTIC PLASTICITY; HEAD CIRCUMFERENCE; TENSIN HOMOLOG; KNOCKOUT MICE; MOUSE MODEL; NEURODEVELOPMENTAL DISORDERS; SOCIAL INFORMATION; DOPAMINE NEURONS AB Accelerated head and brain growth (macrocephaly) during development is a replicated biological finding in a subset of individuals with autism spectrum disorder (ASD). However, the relationship between brain overgrowth and the behavioral and cognitive symptoms of ASD is poorly understood. The PI3K-Akt-mTOR pathway regulates cellular growth; several genes encoding negative regulators of this pathway are ASD risk factors, including PTEN. Mutations in PTEN have been reported in individuals with ASD and macrocephaly. We report that brain overgrowth is widespread in Pten germline haploinsufficient (Pten(+/-)) mice, reflecting Pten mRNA expression in the developing brain. We then ask if broad brain overgrowth translates into general or specific effects on the development of behavior and cognition by testing Pten(+/-) mice using assays relevant to ASD and comorbidities. Deficits in social behavior were observed in both sexes. Males also showed abnormalities related to repetitive behavior and mood/anxiety. Females exhibited circadian activity and emotional learning phenotypes. Widespread brain overgrowth together with selective behavioral impairments in Pten(+/-) mice raises the possibility that most brain areas and constituent cell types adapt to an altered trajectory of growth with minimal impact on the behaviors tested in our battery; however, select areas/cell types relevant to social behavior are more vulnerable or less adaptable, thus resulting in social deficits. Probing dopaminergic neurons as a candidate vulnerable cell type, we found social behavioral impairments in mice with Pten conditionally inactivated in dopaminergic neurons that are consistent with the possibility that desynchronized growth in key cell types may contribute to ASD endophenotypes. C1 [Clipperton-Allen, Amy E.; Page, Damon T.] Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA. RP Page, DT (reprint author), Scripps Res Inst, Dept Neurosci, 130 Scripps Way, Jupiter, FL 33458 USA. EM paged@scripps.edu FU Scripps Research Institute FX We are grateful for gift funds from Mrs Nancy Lurie Marks and startup funds from The Scripps Research Institute for support. 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Mol. Genet. PD JUL PY 2014 VL 23 IS 13 BP 3490 EP 3505 DI 10.1093/hmg/ddu057 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AK0ST UT WOS:000338126300012 PM 24497577 ER PT J AU Sinzig, J Vinzelberg, I Evers, D Lehmkuhl, G AF Sinzig, Judith Vinzelberg, Isabella Evers, Dagmar Lehmkuhl, Gerd TI Executive function and attention profiles in preschool and elementary school children with autism spectrum disorders or ADHD SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE ADHD; attention; autism; executive functions; neuropsychology; preschool age ID DEFICIT-HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT/HYPERACTIVITY DISORDER; SUSTAINED ATTENTION; PSYCHIATRIC-DISORDERS; COMORBIDITY; PERFORMANCE; SYMPTOMS; METHYLPHENIDATE; BEHAVIOR AB Both autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) show executive function and attention problems. By now, these are well described in school children and adolescents, but not in preschool or elementary school children. The goal of this study was to compare the neuropsychological profiles of executive and attention functions in an ADHD, an ASD, and a typically-developing group. Eighty-five children aged 4-9 years old with ADHD (n=30) or ASD (n=26) and healthy children (n=29) were included consecutively. Psychopathology was evaluated using the KIDDIE-SADS, the Child Behaviour Checklist (CBCL), and symptom checklists for ADHD according to DSM-IV. Assessment of neuropsychological functioning included tasks from the Amsterdam Neuropsychological Tasks (ANT), namely, inhibition (GoNoGo), flexibility (shifting attentional set visual), and sustained attention (sustained attention objects). A MANOVA with age and IQ as covariates revealed statistically significant group effects for the variable 'flexibility errors compatible'. Effect sizes showed clear deficits of children with ASD and ADHD in inhibition and, furthermore, impairments in sustained attention in ASD children. Pearson correlations revealed associations between social problems and aggressive behaviour with all three tasks in the ADHD group and between thought problems and sustained attention in the ASD group. Our hypothesis was partly confirmed as ADHD children showed more deficits in inhibition tasks than healthy children. However, there was no evidence that children with ASD have a specific profile in comparison to ADHD children. C1 [Sinzig, Judith; Evers, Dagmar; Lehmkuhl, Gerd] Univ Cologne, Dept Child & Adolescent Psychiat, Cologne, Germany. [Sinzig, Judith; Vinzelberg, Isabella] LVR Klin Bonn, Dept Child & Adolescent Psychiat, D-53111 Bonn, Germany. [Evers, Dagmar] LVR Klin Viersen, Dept Child & Adolescent Psychiat, Viersen, Germany. 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J. Dev. Disabil. PD JUL PY 2014 VL 60 IS 3 BP 144 EP 154 DI 10.1179/2047387714Y.0000000040 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK4YG UT WOS:000338429900004 ER PT J AU Geurts, H Sinzig, J Booth, R Happe, F AF Geurts, Hilde Sinzig, Judith Booth, Rhonda Happe, Francesca TI Neuropsychological heterogeneity in executive functioning in autism spectrum disorders SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; heterogeneity; executive functions; ADHD ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; ASPERGER-SYNDROME; CENTRAL COHERENCE; CHILDREN; ADHD; PSYCHOPATHOLOGY; INDIVIDUALS; IMPAIRMENTS AB In most research it is common to report results on a group level. For example, various studies report that children and adults with autism show executive function deficits. However, studies often differ in the pattern of findings. We believe this might be partly due to the heterogeneity of the autism population. Put differently, some people with autism might indeed have executive dysfunctions, but this does not mean that everybody with autism has such a deficit. In the current study we re-analysed published data from children with autism, children with Attention Deficit/Hyperactivity Disorder (also associated with executive dysfunction) and children without a clinical diagnosis. A surprisingly small number of children did indeed have executive function deficits. However, children with a clinical diagnosis had executive function deficits more often than those without a diagnosis. These findings show us that besides reporting findings on a group level, researchers need to report findings on an individual level. Understanding the differences between individuals with autism might help us in pinpointing differences in etiology, prognosis, and treatment response. Different subsets of autism symptoms might be genetically partly independent. With respect to cognition, this may imply that one cognitive theory is unlikely to explain all symptoms and that there will be large individual differences in cognitive deficits/assets between individuals with autism. However, most journal articles report only group differences, treating individual differences more or less as 'noise' in the data. In the current study, we reanalyzed data from three independent studies (totaling 93 children with autism spectrum disorders (ASDs), 104 children with attention deficit hyperactivity disorder (ADHD), and 93 typically developing children) to examine the degree of heterogeneity in executive function deficits. The three main findings were that (1) only a small percentage of children with ASD had a significant deficit in measured executive function; (2) there is not just heterogeneity within ASD groups, but also across studies, and (3) in line with Nigg and colleagues (2005), only a small number of children with ADHD showed a significant inhibitory control deficit. Executive (dys)function cannot be a marker for ASD as defined in the DSM, but might have potential as a specifier like IQ and language. This is in line with the idea that the executive function account cannot be a sole explanation for ASD. The findings do suggest that an individual differences approach might give us more information on potential subtypes within the autism spectrum. Future research is needed to define and test neuropsychological subtypes and their external correlates, including etiology, prognosis, and treatment response. C1 [Geurts, Hilde] Univ Amsterdam, Dept Psychol, Dutch Autism & ADHD Res Ctr dArc, Amsterdam, Netherlands. [Geurts, Hilde] Dr Leo Kannerhuis, Autism Clin, Amsterdam, Netherlands. [Sinzig, Judith] LVR Klin, Dept Child & Adolescent Psychiat, Bonn, Germany. [Booth, Rhonda] UCL, Inst Child Hlth, London WC1E 6BT, England. [Happe, Francesca] Kings Coll London, Inst Psychiat, Med Res Council Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Geurts, H (reprint author), Univ Amsterdam, Dept Psychol, Dutch Autism & ADHD Res Ctr dArc, Amsterdam, Netherlands. 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PD JUL PY 2014 VL 60 IS 3 BP 155 EP 162 DI 10.1179/2047387714Y.0000000047 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK4YG UT WOS:000338429900005 ER PT J AU Willfors, C Poltrago, L Berggren, S Coco, C Anckarsater, H Lichtenstein, P Ronald, A Bolte, S AF Willfors, Charlotte Poltrago, Lina Berggren, Steve Coco, Christina Anckarsater, Henrik Lichtenstein, Paul Ronald, Angelica Bolte, Sven TI On the role of non-shared environment for executive functioning in ADHD: a twin-differences design study SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE Neurodevelopmental disorders; NDD; attention deficit hyperactivity disorder; neuropsychology; neuropsychiatry; discordant twin pair design; autism spectrum disorders; impulsivity; inhibition; concordance; discordance; monozygotic twin pairs ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CARD SORTING TEST; EARLY ADOLESCENCE; BIRTH-WEIGHT; CHILDREN; INHIBITION; CHILDHOOD; METAANALYSIS; SPECIFICITY AB Introduction: The study of differences between monozygotic (MZ) twin pairs with respect to ADHD may provide novel leads to disentangle the environmental contribution driving its phenotypes. Objectives: To examine non-shared environmental influences on executive function in dimensionally defined ADHD. Methods: This study included 27 MZ twin pairs (7 female) aged 11-20 years being moderately to substantially discordant for ADHD traits as assessed by the Attention Problem (AP) scale of the Child Behavior Checklist/Adult Behavior Checklist. The twins completed the Wisconsin Card Sorting Test (WCST) for cognitive flexibility and the Tower Test (TT) for foresighted planning. Two statistical approaches were used to analyze the data. First, correlations between ADHD trait intra-pair differences and WCST and TT scores were calculated. Second, the significance of those intra-pair differences on WCST and TT, using ADHD as categorical variable in clinically discordant pairs, was tested. Results: Both analysing strategies revealed a link between ADHD on one hand, and foresighted planning and inhibitory control on the other hand mediated by non-shared environmental factors. The first statistical approach yielded positive correlations between intra-pairs differences on the AP scale and intra-pair differences on two subscales of the TT: total rule violation (r(s)=0.41) and rule-violation-per-item-ratio (r(s)=0.38). Findings in categorically discordant pairs were consistent, showing within-pair differences on the same subtests (z-1.63, P=0.05, one-tailed and z=-1.60, P=0.05, one-tailed). Conclusions: Findings confirm previous research suggesting ADHD to be a quantitative extreme on a continuum with executive functions being a cognitive marker of ADHD traits. Non-shared environmental factors appear to influence planning skills and inhibitory control. C1 [Willfors, Charlotte; Poltrago, Lina; Berggren, Steve; Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders, Pediat Neuropsychiat Unit, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Poltrago, Lina] Prima Barn & Vuxenpsykiatri AB, Stockholm, Sweden. [Berggren, Steve; Coco, Christina; Bolte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. [Anckarsater, Henrik] Univ Gothenburg, Gothenburg, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ronald, Angelica] Birkbeck Univ London, Dept Psychol Sci, London, England. RP Bolte, S (reprint author), Karolinska Inst, Ctr Neurodev Disorders, Neuropsychiat Unit, Stockholm, Sweden. 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PD JUL PY 2014 VL 60 IS 3 BP 163 EP 173 DI 10.1179/2047387714Y.0000000041 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK4YG UT WOS:000338429900006 ER PT J AU Kretschmer, A Lampmann, SA Altgassen, M AF Kretschmer, Anett Lampmann, Sara-Ann Altgassen, Mareike TI Relations between moral reasoning, theory of mind and executive functions in children with autism spectrum disorders SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE moral reasoning; executive functioning; autism spectrum disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; INHIBITORY CONTROL; ASPERGER-SYNDROME; SOCIAL-BEHAVIOR; EMPATHY; JUDGMENT; ADULTS; COGNITION AB The aims of the present study were to investigate relations between moral reasoning, executive functioning and Theory of Mind in children with autism spectrum disorders (ASD) compared to typically developing children and to apply the dual aspect theory of Lind (1978, 2008) to moral reasoning in individuals with and without ASD. Overall, 21 children with ASD (age: M=10.22, SD=1.55) and 21 controls (age: M=9.83, SD=2.36) participated and completed the Moral Reasoning Test for children from Zierer (2006), which tests affective and cognitive aspects of moral reasoning. In addition, participants completed two Theory of Mind tasks, a working memory and an inhibition test. Correlational analyses revealed significant relations between cognitive moral reasoning and inhibitory control as well as between Theory of Mind and inhibition for the ASD group. Thus, inhibitory control, but not working memory and Theory of Mind, might be one key mechanism underlying moral reasoning, and possibly ToM development in children with ASD. Analyses of variance revealed no significant differences in cognitive and affective aspects of moral reasoning between individuals with ASD and typically developing children. Both groups did also not differ in Theory of Mind and executive functioning. Findings are discussed in light of the heterogeneous literature. C1 [Kretschmer, Anett; Lampmann, Sara-Ann; Altgassen, Mareike] Tech Univ Dresden, Dresden, Germany. [Altgassen, Mareike] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Kretschmer, A (reprint author), Tech Univ Dresden, Dresden, Germany. EM anett.kretschmer@tu-dresden.de RI Altgassen, Mareike/J-3048-2012 CR American Psychiatric Association (APA), 2000, DIAGNOSTIC AND STATI Baird JA, 2004, NEW DIR CHILD ADOLES, V103, P37, DOI 10.1002/cd.96 Barnes JL, 2009, AUTISM RES, V2, P148, DOI 10.1002/aur.79 BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Blair J. R. 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J. Dev. Disabil. PD JUL PY 2014 VL 60 IS 3 BP 174 EP 183 DI 10.1179/2047387714Y.0000000045 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK4YG UT WOS:000338429900007 ER PT J AU Altgassen, M Koch, A AF Altgassen, Mareike Koch, Andrea TI Impact of inhibitory load on remembering delayed intentions in autism SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; PDD; prospective memory; executive function; inhibition ID PROSPECTIVE MEMORY; SPECTRUM DISORDER; EXECUTIVE FUNCTIONS; RETROSPECTIVE-MEMORY; FUNCTIONING AUTISM; ASPERGERS-SYNDROME; ADULTS; CHILDREN; RECOGNITION; RETRIEVAL AB Objective: Research on prospective memory (PM) in autism spectrum disorders (ASD) is scarce and inconsistent. Differences in results have been attributed to differences in executive control demands of the respective PM tasks. However, so far no study has systematically and experimentally manipulated executive control load. The present study set out to explore the impact of varying inhibitory control demands on PM performance in ASD. Method: Twenty-two adults with ASD and 22 age-, gender- and cognitive ability-matched controls were asked to work on a computerised word categorization task into which an event-based PM task was embedded. In addition, they were required to work on a task that put either low or high load on inhibitory resources. Results: With regards to the event-based PM task, no significant effects emerged. Controls outperformed individuals with ASD on the ongoing task performance and ongoing task performance varied with inhibition load. Similarly, inhibition load affected performance on the inhibition task; here, no group effects were found. Conclusion: Findings suggest spared event-based PM performance in ASD regardless of inhibition load. 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Williams, Nigel O'Donovan, Michael C. Thapar, Anita Holmans, Peter TI Biological Overlap of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: Evidence From Copy Number Variants SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; ASD; pathway analysis; CNVs; comorbidity ID DEFICIT-HYPERACTIVITY-DISORDER; GENOME-WIDE ANALYSIS; MENTAL-RETARDATION; TWIN SAMPLE; ADHD; DUPLICATIONS; ASSOCIATION; RELIABILITY; INTERVIEW; DELETIONS AB Objective: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur and share genetic risks. The aim of this analysis was to determine more broadly whether ADHD and ASD share biological underpinnings. Method: We compared copy number variant (CNV) data from 727 children with ADHD and 5,081 population controls to data from 996 individuals with ASD and an independent set of 1,287 controls. Using pathway analyses, we investigated whether CNVs observed in individuals with ADHD have an impact on genes in the same biological pathways as on those observed in individuals with ASD. Results: The results suggest that the biological pathways affected by CNVs in ADHD overlap with those affected by CNVs in ASD more than would be expected by chance. Moreover, this was true even when specific CNV regions common to both disorders were excluded from the analysis. After correction for multiple testing, genes involved in 3 biological processes (nicotinic acetylcholine receptor signalling pathway, cell division, and response to drug) showed significant enrichment for case CNV hits in the combined ADHD and ASD sample. Conclusion: The results of this study indicate the presence of significant overlap of shared biological processes disrupted by large rare CNVs in children with these 2 neurodevelopmental conditions. C1 [Martin, Joanna; Cooper, Miriam; Hamshere, Marian L.; Pocklington, Andrew; Owen, Michael J.; Williams, Nigel; O'Donovan, Michael C.; Thapar, Anita; Holmans, Peter] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci,Sch Med, Cardiff CF24 4HQ, S Glam, Wales. [Scherer, Stephen W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Scherer, Stephen W.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Kent, Lindsey] Univ St Andrews, Bute Med Sch, St Andrews KY16 9AJ, Fife, Scotland. [Gill, Michael] Trinity Ctr Hlth Sci, Dublin, Ireland. RP Martin, J (reprint author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci,Sch Med, Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. RI Scherer, Stephen /B-3785-2013; Holmans, Peter/F-4518-2015 OI Scherer, Stephen /0000-0002-8326-1999; Holmans, Peter/0000-0003-0870-9412 FU Medical Research Council (UK); Baily Thomas Charitable Trust; Wellcome Trust and Action Research; University of Toronto McLaughlin Centre; Canadian Institutes of Health Research; Genome Canada FX This work has been supported by the Medical Research Council (UK), Baily Thomas Charitable Trust, the Wellcome Trust and Action Research, the University of Toronto McLaughlin Centre, the Canadian Institutes of Health Research, and Genome Canada. 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TI Copy number variation in schizophrenia in Sweden SO MOLECULAR PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; DE-NOVO CNVS; BIPOLAR DISORDER; PSYCHIATRIC-DISORDERS; GENES; GENETICS; RISK; VARIANTS; DISEASE; PARTICIPATION AB Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations (CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for SCZ CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with SCZ using a Swedish national sample (4719 cases and 5917 controls). High-confidence CNV calls were generated using genotyping array intensity data, and their effect on risk of SCZ was measured. Our data confirm increased burden of large, rare CNVs in SCZ cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio = 4.16, P = 0.018), previously associated with autism and mental retardation but not SCZ. Intriguingly, gene set association analyses implicate biological pathways previously associated with SCZ through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500 kb) in genes present in the postsynaptic density, in genomic regions implicated via SCZ genome-wide association studies and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry-genome-wide screens for CNVs, common variation and exonic variation-are converging on similar sets of pathways and/or genes. C1 [Szatkiewicz, J. P.; Chen, G.; Kim, Y.; Crowley, J. J.; Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [O'Dushlaine, C.; Chambert, K.; Moran, J. L.; Neale, B. M.; Bergen, S. E.; Scolnick, E.; Purcell, S.; McCarroll, S. A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Fromer, M.; Ruderfer, D.; Sklar, P.; Purcell, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Akterin, S.; Bergen, S. E.; Kaehler, A.; Magnusson, P. K. E.; Hultman, C. M.; Sullivan, P. F.] Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. [Rees, E.; Kirov, G.; O'Donovan, M. C.; Owen, M. J.; Walters, J.] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, Wales. [McCarroll, S. A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264,5097 Genom Med Bldg, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu FU NIMH [R01 MH077139, R01 MH095034, K01 MH093517]; Stanley Center for Psychiatric Research; Stanley Medical Research Institute; Sylvan Herman Foundation; Karolinska Institutet; Karolinska University Hospital; Swedish Research Council; Swedish County Council; Soderstrom Konigska Foundation; Netherlands Scientific Organization [NWO 645-000-003]; Medical Research Council (MRC) Centre Grant [G0800509]; Medical Research Council (MRC) Program Grant [G0801418]; European Community [HEALTH-F2-2010-241909]; MRC; MRC/Welsh Assembly Government; British Medical Association FX We are deeply grateful for the participation of all subjects contributing to this research and to the team that conducted the fieldwork (Emma Flordal-Thelander, Ann-Britt Holmgren, Marie Hallin, Marie Lundin, Ann-Kristin Sundberg, Christina Pettersson, Radja Satgunanthan-Dawoud, Sonja Hassellund, Malin Radstrom, Birgitta Ohlander, Leila Nyren and Isabelle Kizling). Funding support was provided by NIMH R01 MH077139 (Sullivan), NIMH R01 MH095034 (Sklar), NIMH K01 MH093517 Szatklewicz), the Stanley Center for Psychiatric Research, the Stanley Medical Research Institute, the Sylvan Herman Foundation, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Swedish County Council, the Soderstrom Konigska Foundation and the Netherlands Scientific Organization (NWO 645-000-003). The work at UK was funded by Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418), the European Community's Seventh Framework Programme (HEALTH-F2-2010-241909 (Project EU-GEI), an MRC PhD Studentship to ER, a clinical research fellowship to JTRW from the MRC/Welsh Assembly Government and the Margaret Temple Award from the British Medical Association. The UK samples were genotyped at the Broad Institute, USA, funded by a philanthropic gift to the Stanley Center for Psychiatric Research. The funders had no role in study design, execution, analysis and manuscript preparation. We thank two anonymous reviewers for their helpful comments. All authors reviewed and approved the final version of the manuscript. The corresponding authors had access to the full data set. 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Psychiatr. PD JUL PY 2014 VL 19 IS 7 BP 762 EP 773 DI 10.1038/mp.2014.40 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AK1OV UT WOS:000338185300005 PM 24776740 ER PT J AU Toma, C Torrico, B Hervas, A Valdes-Mas, R Tristan-Noguero, A Padillo, V Maristany, M Salgado, M Arenas, C Puente, XS Bayes, M Cormand, B AF Toma, C. Torrico, B. Hervas, A. Valdes-Mas, R. Tristan-Noguero, A. Padillo, V. Maristany, M. Salgado, M. Arenas, C. Puente, X. S. Bayes, M. Cormand, B. TI Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations SO MOLECULAR PSYCHIATRY LA English DT Article DE autism spectrum disorder; exome sequencing; multiplex families; novel candidate genes; rare genetic variants; truncating mutations ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; DEVELOPMENTAL DELAY; GENES; SCHIZOPHRENIA; IDENTIFICATION; PHENOTYPES; 17P13.3; RISK; BTK AB Autism is a severe neurodevelopmental disorder, the aetiology of which remains mainly unknown. Family and twin studies provide strong evidence that genetic factors have a major role in the aetiology of this disease. Recently, whole exome sequencing (WES) efforts have focused mainly on rare de novo variants in singleton families. Although these studies have provided pioneering insights, de novo variants probably explain only a small proportion of the autism risk variance. In this study, we performed exome sequencing of 10 autism multiplex families with the aim of investigating the role of rare variants that are coinherited in the affected sibs. The pool of variants selected in our study is enriched with genes involved in neuronal functions or previously reported in psychiatric disorders, as shown by Gene Ontology analysis and by browsing the Neurocarta database. Our data suggest that rare truncating heterozygous variants have a predominant role in the aetiology of autism. Using a multiple linear regression model, we found that the burden of truncating mutations correlates with a lower non- verbal intelligence quotient (NVIQ). Also, the number of truncating mutations that were transmitted to the affected sibs was significantly higher (twofold) than those not transmitted. Protein-protein interaction analysis performed with our list of mutated genes revealed that the postsynaptic YWHAZ is the most interconnected node of the network. Among the genes found disrupted in our study, there is evidence suggesting that YWHAZ and also the X-linked DRP2 may be considered as novel autism candidate genes. C1 [Toma, C.; Torrico, B.; Tristan-Noguero, A.; Cormand, B.] Univ Barcelona, Dept Genet, Barcelona 08028, Spain. [Toma, C.; Torrico, B.; Cormand, B.] Biomed Network Res Ctr Rare Dis CIBERER, Barcelona, Spain. [Hervas, A.] Hosp Univ Mutua Terrassa, Child & Adolescent Mental Hlth Unit, Barcelona, Spain. [Valdes-Mas, R.; Puente, X. S.] Univ Oviedo IUOPA, Dept Biochem & Mol Biol, Barcelona, Spain. [Padillo, V.; Maristany, M.] Hosp San Juan Dios, Dev Disorders Unit UETD, Barcelona, Spain. [Arenas, C.] Univ Barcelona, Dept Stat, Barcelona 08028, Spain. [Bayes, M.] Natl Ctr Genom Anal CNAG, Barcelona, Spain. [Cormand, B.] Univ Barcelona, Inst Biomed, Barcelona 08028, Spain. RP Cormand, B (reprint author), Univ Barcelona, Fac Biol, Dept Genet, Avinguda Diagonal 643,Edifici Prevosti,3a Planta, Barcelona 08028, Spain. EM bcormand@ub.edu RI Toma, Claudio/L-7853-2014 OI Toma, Claudio/0000-0003-3901-7507 FU European Union [PIEF-GA-2009-254930]; AGAUR [2009SGR00971]; Fundacio La Marato de TV3 [092010]; Fundacion Alicia Koplowitz; Ministerio de Economia y Competitividad, Spain [SAF2012-33484, SAF2010-21165] FX We are grateful to all families for their participation in our study. We thank Patricia Romaris (Hospital Universitari Mutua de Terrassa) for contributing to clinical delineation of patients and Lara Nonell and Eulalia Puigdecanet (Servei d'Analisi de Micorarrays, IMIM-Hospital del Mar, Parc de Recerca Biomedica de Barcelona) for their contribution to the CNV studies. Exome sequencing services were provided by the National Centre for Genomic Analysis (CNAG). CT was supported by the European Union (Marie Curie, PIEF-GA-2009-254930) and BT by AGAUR (FI grant). Financial support was received from 'Fundacio La Marato de TV3' (092010), 'Fundacion Alicia Koplowitz', AGAUR (2009SGR00971) and 'Ministerio de Economia y Competitividad, Spain' (SAF2012-33484, SAF2010-21165). 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Forty-one children aged 7-12 years, 20 with a formal diagnosis of ASD and 21 TD peers, were taught 16 low-frequency concrete science words, such as "breccia". Half of the stimuli had the written word presented alongside a picture of the target item (orthography present: OP) while the remaining items were taught with orthography absent (OA). During the learning phase, eye movements were recorded; there were no group differences in the time spent fixating the written form. Production, comprehension, and recognition of orthographic forms of new words were assessed immediately after learning and again after a 24-hour delay. The vocabulary learning of both groups was facilitated by the presence of orthography. Overall, the groups did not differ in comprehension of new words or recognition of new orthographic forms, although the children with ASD demonstrated superior phonological learning (as measured by a picture naming task) relative to TD peers. 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J. Exp. Psychol. PD JUL PY 2014 VL 67 IS 7 BP 1317 EP 1334 DI 10.1080/17470218.2013.859714 PG 18 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA AJ9FP UT WOS:000338013400005 PM 24313313 ER PT J AU Birnbaum, R Jaffe, AE Hyde, TM Kleinman, JE Weinberger, DR AF Birnbaum, Rebecca Jaffe, Andrew E. Hyde, Thomas M. Kleinman, Joel E. Weinberger, Daniel R. TI Prenatal Expression Patterns of Genes Associated With Neuropsychiatric Disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSTETRIC COMPLICATIONS; HUMAN BRAIN; SCHIZOPHRENIA; RISK; NEUROPATHOLOGY; TRANSCRIPTOME; METAANALYSIS; DISRUPTION; MUTATIONS; ISOFORM AB Objective: Neurodevelopmental disorders presumably involve events that occur during brain development. The authors hypothesized that neuropsychiatric disorders considered to be developmental in etiology are associated with susceptibility genes that are relatively upregulated during fetal life (i.e., differentially expressed). Method: The authors investigated the presence of prenatal expression enrichment of susceptibility genes systematically, as composite gene sets associated with six neuropsychiatric disorders in the microarray-based "BrainCloud" dorsolateral prefrontal cortex transcriptome. Results: Using a fetal/postnatal log2-fold change threshold of 0.5, genes associated with syndromic neurodevelopmental disorders (N=31 genes, p=3.37x10(-3)), intellectual disability (N=88 genes, p=5.53x10(-3)), and autism spectrum disorder (N=242 genes, p=3.45x10(-4)) were relatively, enriched in prenatal transcript abundance, compared with the overall transcriptome. Genes associated with schizophrenia by genome-wide association studies were not preferentially fetally expressed (N=106 genes, p=0.46), nor were genes associated with schizophrenia by exome sequencing (N=2.12 genes, p=0.21), but specific genes within copy-number variant regions associated with schizophrenia were relatively enriched in prenatal transcript abundance, and genes associated with schizophrenia by meta-analysis were functionally enriched for some neurodevelopmental processes. In contrast, genes associated with neurode-generative disorders were significantly underexpressed during fetal life (N=46 genes, p=1.67x10(-3)). Conclusions: The authors found evidence for relative prenatal enrichment of putative susceptibility genes for syndromic neurodevelopmental disorders, intellectual disability, and autism spectrum disorder. 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J. Psychiat. PD JUL PY 2014 VL 171 IS 7 BP 758 EP 767 DI 10.1176/appi.ajp.2014.13111452 PG 10 WC Psychiatry SC Psychiatry GA AJ9AD UT WOS:000337998300015 PM 24874100 ER PT J AU Skakkebk, A Bojesen, A Kristensen, MK Cohen, A Hougaard, DM Hertz, JM Fedder, J Laurberg, P Wallentin, M Ostergaard, JR Pedersen, AD Gravholt, CH AF Skakkebk, A. Bojesen, A. Kristensen, M. K. Cohen, A. Hougaard, D. M. Hertz, J. M. Fedder, J. Laurberg, P. Wallentin, M. Ostergaard, J. R. Pedersen, A. D. Gravholt, C. H. TI Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics SO ANDROLOGY LA English DT Article DE brain morphology; Epigenetics; Klinefelter syndrome; neuropsychology; testosterone ID ANDROGEN RECEPTOR GENE; X-CHROMOSOME INACTIVATION; CAG REPEAT POLYMORPHISM; PERSONALITY-TRAITS; COGNITIVE FUNCTION; CANDIDATE GENES; OLDER MEN; TESTOSTERONE; PHENOTYPE; ASSOCIATION AB Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X-chromosome inactivation pattern, CAG repeat length and parent-of-origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls. Grey matter (GM) volume of left insula was significantly decreased in KS patients with skewed X-inactivation (z=5.78) and we observed a borderline significant difference in global brain matter volume where KS patients with skewed X-chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG repeat length and parent-of-origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression and anxiety or cognitive function. Interestingly our results regarding brain volumes indicate that X-inactivation has an influence on GM volume in left insula and might also be related to global GM volume, indicating a possible effect of X-linked genes on the development of GM volume in KS patient. Skewed X-inactivation, CAG repeat length and parent-of-origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310)). C1 [Skakkebk, A.; Gravholt, C. H.] Aarhus Univ Hosp, Dept Endocrinol & Internal Med MEA, DK-8000 Aarhus C, Denmark. [Bojesen, A.] Sygehus Lillebaelt, Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Kristensen, M. K.] Odense Univ Clin, Dept Mental Hlth, Odense, Denmark. [Cohen, A.; Hougaard, D. M.] Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark. [Hertz, J. M.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Laurberg, P.] Odense Univ Hosp, Dept Gynecol & Obstet, Fertil Clin, DK-5000 Odense, Denmark. [Laurberg, P.] Aalborg Univ Hosp, Dept Endocrinol, Aalborg, Denmark. [Wallentin, M.] Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, DK-8000 Aarhus, Denmark. [Wallentin, M.] Aarhus Univ, Ctr Semiot, Aarhus, Denmark. [Ostergaard, J. R.] Aarhus Univ Hosp, Dept Pediat, Ctr Rare Dis, DK-8000 Aarhus, Denmark. [Pedersen, A. D.] Vejleford Rehabil Ctr, Stouby, Denmark. [Pedersen, A. D.] Aarhus Univ, Dept Psychol & Behav Sci, Aarhus, Denmark. [Gravholt, C. H.] Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark. RP Skakkebk, A (reprint author), Aarhus Univ Hosp, Dept Endocrinol & Internal Med MEA, DK-8000 Aarhus C, Denmark. EM asj@ki.au.dk FU Lundbeck Foundation; Augustinus Foundation; Aase and Einar Danielsen Foundation; University of Aarhus; Novo Nordisk Foundation FX This study was supported by grants from the Lundbeck Foundation, the Augustinus Foundation and Aase and Einar Danielsen Foundation. A. S. received a research fellowship from the University of Aarhus. C. H. G. was supported by a personal clinical research grant from the Novo Nordisk Foundation. We would like to thank Eva Schriver, Merete Moller, Dorte Wulff, Susanne Sorensen, Lone Kvist Dora Zeidler, Michael Geneser and Kaja Skovgard Jensen for their technical assistance. 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Fazili, Zia Xu, Yingying Liddy, Stacey Yolton, Kimberly Savitz, David A. Lanphear, Bruce P. Braun, Joseph M. TI Serum cotinine and whole blood folate concentrations in pregnancy SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Epidemiology; Folic acid; Pregnancy; Tobacco smoke pollution; Smoking ID ENVIRONMENTAL TOBACCO-SMOKE; INFANT BIRTH-WEIGHT; PERICONCEPTIONAL FOLIC-ACID; AUTISM SPECTRUM DISORDERS; TANDEM MASS-SPECTROMETRY; DIETARY-SUPPLEMENT USE; UNITED-STATES; ELIMINATION KINETICS; TOTAL HOMOCYSTEINE; MATERNAL SMOKING AB Purpose: Prenatal tobacco smoke exposure may be associated with low maternal folate levels that increase the risk of adverse infant and child health outcomes by reducing folate availability during fetal development. Methods: Using data from the Health Outcomes and Measures of the Environment Study, we examined the relationship between secondhand or active tobacco smoke exposure and whole blood folate concentrations in pregnant women from Cincinnati, Ohio (n = 362) at approximately 16-week gestation. We used multivariable linear regression to examine the association between continuous or categorical serum cotinine levels and whole blood folate levels, adjusting for sociodemographic, dietary, and perinatal variables. Results: After adjustment for potential confounders, an interquartile range increases in serum cotinine concentration (0.012-0.224 ng/mL) was suggestively associated with decreased whole blood folate levels (beta, -23 nmol/L; 95% confidence interval (Cl), -49, 3; P value = .08). Compared with unexposed women, reductions in mean whole blood folate were observed among active smokers (beta, -94, 95% Cl, 195, 6 nmol/L; P value = .40); smaller reductions were observed among women with secondhand exposure (0, 26; Cl. 84, 32 nmol/L; P value = .07). Conclusions: Consistent with prior studies, active smoking was associated with reduced whole blood folate levels among these pregnant women. Secondhand tobacco smoke exposures were associated with small and imprecise reductions in whole blood folate levels. (C) 2014 Elsevier Inc. All rights reserved. C1 [Prasodjo, Adila; Savitz, David A.; Braun, Joseph M.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Pfeiffer, Christine M.; Fazili, Zia] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Nutr Biomarkers Branch, Atlanta, GA USA. [Xu, Yingying; Liddy, Stacey; Yolton, Kimberly] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. 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PD JUL PY 2014 VL 24 IS 7 BP 498 EP 503 DI 10.1016/j.annepidem.2014.04.004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AJ7AW UT WOS:000337850400002 PM 24854185 ER PT J AU Burnell, L Verchere, C Pugash, D Loock, C Robertson, S Lehman, A AF Burnell, Lindsay Verchere, Cynthia Pugash, Denise Loock, Christine Robertson, Sandra Lehman, Anna TI Additional post-natal diagnoses following antenatal diagnosis of isolated cleft lip plus /- palate SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID HARD PALATE; ULTRASOUND; ANOMALIES; ABNORMALITIES; FETUSES AB Introduction Cleft lip with or without palate (CLP) can be diagnosed antenatally through ultrasound, and may be categorised as apparently isolated versus associated with other malformations. Limited data exist on the long-term outcomes following antenatal diagnosis of apparently isolated CLP. Aim This study examined the long-term post-natal outcomes of CLP when found in isolation antenatally, in order to determine the rates of unexpected additional anomalies, developmental delay or genetic syndromes. Patients and methods A retrospective chart review of antenatal and post-natal medical charts was completed for a ten-year period between January 2000 and December 2009. At least 2 years of available post-natal clinical information was required for inclusion in the study. Results A total of 97 cases of antenatally isolated CLP were ascertained. Fifteen pregnancies were terminated. Follow-up data were available for 81 liveborns, though 4 were lost to follow-up prior to 2 years of age. Twelve of the 77 children meeting study criteria were identified to have other major malformations and/or developmental disability either later in the pregnancy or post-natally. Findings included familial clefting syndromes, trisomy 21, autism spectrum disorders, brain malformations, fetal alcohol syndrome and Kabuki syndrome, among other findings. Another 11 children had additional anomalies of minor impact. Examples of findings include a perimembranous ventricular septal defect, mild unilateral optic nerve hypoplasia, mild pulmonary artery stenosis with a small atrial septal defect, and transient delays in fine and gross motor skills. No children with clefting of the lip only had major additional diagnoses. Conclusions The frequency of an associated complex developmental disorder following an otherwise reassuring fetal ultrasound is around 15%. A few diagnoses could be suspected at the antenatal assessment based on family history or exposures. Our study is lacking comprehensive assessment on the yield of genomic microarray testing for this population. C1 [Burnell, Lindsay; Lehman, Anna] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H3N1, Canada. [Burnell, Lindsay; Verchere, Cynthia; Loock, Christine; Robertson, Sandra; Lehman, Anna] British Columbia Childrens Hosp, Vancouver, BC V6H3N1, Canada. [Verchere, Cynthia; Robertson, Sandra] Univ British Columbia, Dept Surg, Vancouver, BC V6H3N1, Canada. [Pugash, Denise] Univ British Columbia, Dept Radiol, Vancouver, BC V6H3N1, Canada. [Pugash, Denise] British Columbia Womens Hosp, Vancouver, BC, Canada. [Loock, Christine] Univ British Columbia, Dept Pediat, Vancouver, BC V6H3N1, Canada. RP Lehman, A (reprint author), Univ British Columbia, Dept Med Genet, C234 4500 Oak St, Vancouver, BC V6H3N1, Canada. 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Dis. Child.-Fetal Neonatal Ed. PD JUL PY 2014 VL 99 IS 4 BP F286 EP F290 DI 10.1136/archdischild-2013-305390 PG 5 WC Pediatrics SC Pediatrics GA AJ7XU UT WOS:000337915600009 PM 24625434 ER PT J AU Hezel, DM McNally, RJ AF Hezel, Dianne M. McNally, Richard J. TI Theory of Mind Impairments in Social Anxiety Disorder SO BEHAVIOR THERAPY LA English DT Article DE social anxiety disorder; theory of mind; social cognition; anxiety disorders ID COMORBIDITY SURVEY REPLICATION; NEGATIVE SELF-IMAGERY; DSM-IV DISORDERS; COGNITIVE REMEDIATION; MEMORY BIAS; PHOBIA; SCHIZOPHRENIA; EMOTION; AUTISM; SCALE AB Social anxiety disorder (SAD) is a common psychiatric disorder characterized by a persistent, excessive fear and avoidance of social and performance situations. Research on cognitive biases indicates individuals with SAD may lack an accurate view of how they are perceived by others, especially in social situations when they allocate important attentional resources to monitoring their own actions as well as external threat. In the present study, we explored whether socially anxious individuals also have impairments in theory of mind (ToM), or the ability to comprehend others' mental states, including emotions, beliefs, and intentions. Forty socially anxious and 40 non-socially-anxious comparison participants completed two ToM tasks: the Reading the Mind in the Eyes and the Movie for the Assessment of Social Cognition. Participants with SAD performed worse on ToM tasks than did non-socially-anxious participants. Relative to comparison participants, those with SAD were more likely to attribute more intense emotions and greater meaning to what others were thinking and feeling. These group differences were not due to interpretation bias. The ToM impairments in people with SAD are in the opposite direction of those in people with autism spectrum conditions whose inferences about the mental states of other people are absent or very limited. This association between SAD and ToM may have important implications for our understanding of both the maintenance and treatment of social anxiety disorder. C1 [Hezel, Dianne M.; McNally, Richard J.] Harvard Univ, Cambridge, MA 02138 USA. RP Hezel, DM (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. 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Therapy PD JUL PY 2014 VL 45 IS 4 BP 530 EP 540 PG 11 WC Psychology, Clinical SC Psychology GA AJ7EQ UT WOS:000337860400007 PM 24912465 ER PT J AU Parma, V Bulgheroni, M Tirindelli, R Castiello, U AF Parma, Valentina Bulgheroni, Maria Tirindelli, Roberto Castiello, Umberto TI Facilitation of action planning in children with autism: The contribution of the maternal body odor SO BRAIN AND COGNITION LA English DT Article DE Action planning; Autism; Automatic imitation; Maternal odor; Visuomotor priming ID HIGH-FUNCTIONING AUTISM; MIRROR NEURON SYSTEM; SPECTRUM-DISORDERS; DEVELOPMENTAL DISORDERS; COGNITIVE NEUROSCIENCE; MOTOR FACILITATION; SOCIAL-BEHAVIOR; YOUNG-ADULTS; IMITATION; MOVEMENT AB Imitation is a key socio-cognitive skill impaired in individuals with Autism Spectrum Conditions (ASC). It is known that the familiarity with an actor facilitates the appearance of imitative abilities. Here, we explore whether a highly familiar and socially relevant stimulus presented in the olfactory modality is able to improve spontaneous imitation as early as at the level of action planning. A group of 20 children with ASC and 20 controls observed their own mother or the mother of another child performing a reach-to-grasp action towards an object, under the exposure to their maternal odor, the odor of the mother of another child or no odor. Subsequently, children acted upon the same object with no specific instruction to imitate. Child's movement initiation time (MIT) served as an indicator of motor planning facilitation induced by action observation. Results suggest that for children with ASC (but not controls) MIT was significantly lower when exposed to the maternal odor both when interacting with a familiar or an unfamiliar model. In the former case, the performance is comparable to controls. The familiar model in the absence of any olfactory cue is able to induce a facilitation effect, but the maximal facilitation on MIT is evident when maternal odor and familiar model are paired. We hypothesize that for children with ASC the maternal odor provides relevant social motivation for taking advantage of others' actions when planning movements in an imitative context. (C) 2014 Elsevier Inc. All rights reserved. C1 [Parma, Valentina; Castiello, Umberto] Univ Padua, Dept Gen Psychol, I-35131 Padua, Italy. [Bulgheroni, Maria] Ab Acus Srl, I-20155 Milan, Italy. [Tirindelli, Roberto] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. RP Parma, V (reprint author), Monell Chem Senses Ctr, Philadelphia, PA 19146 USA. EM valentina.parma@unipd.it FU UC from the Ministero dell'Istruzione, dell'Universita e della Ricerca, Italy FX This research was supported by a Grant to UC from the Ministero dell'Istruzione, dell'Universita e della Ricerca, Italy. The funding source did not have any involvement in the study design, in data collection, analysis and interpretation, in the writing and dissemination process. We are especially grateful to the children that participated in this research and their parents as well as the colleagues and the students who helped with data gathering. The authors report no conflict of interest. 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PD JUL PY 2014 VL 88 BP 73 EP 82 DI 10.1016/j.bandc.2014.05.002 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AJ6CQ UT WOS:000337777700010 PM 24861501 ER PT J AU Kadak, MT Demirel, OF Yavuz, M Demir, T AF Kadak, Muhammed Tayyib Demirel, Omer Faruk Yavuz, Mesut Demir, Turkay TI Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID QUOTIENT AQ; FUNCTIONING AUTISM; FACES; INDIVIDUALS; RELATIVES; PERSONALITY; INFORMATION; SIBLINGS; FAMILIES AB Objective: Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism. Method: Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen's. Results: In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106) = 6.095; p < .05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106) = 4.068, p = .046; F(1, 106) = 4.068, p = .046; F(1, 106) = 6.064, p = .016). Conclusion: According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kadak, Muhammed Tayyib; Demir, Turkay] Istanbul Univ, Cerrahpasa Med Sch, Dept Child & Adolescent Psychiat, TR-34100 Istanbul, Turkey. [Demirel, Omer Faruk] Siverek State Hosp, Dept Psychiat, Sanliurfa, Turkey. [Yavuz, Mesut] Kanuni State Hosp, Dept Child & Adolescent Psychiat, Istanbul, Turkey. RP Kadak, MT (reprint author), Istanbul Univ, Cerrahpasa Med Sch, Dept Child & Adolescent Psychiat, TR-34100 Istanbul, Turkey. 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Psychiat. PD JUL PY 2014 VL 55 IS 5 BP 1146 EP 1151 DI 10.1016/j.comppsych.2014.03.004 PG 6 WC Psychiatry SC Psychiatry GA AJ7AV UT WOS:000337850300013 PM 24742718 ER PT J AU Slane, MM Lusk, LG Boomer, KB Hare, AE King, MK Evans, DW AF Slane, Mylissa M. Lusk, Laina G. Boomer, K. B. Hare, Abby E. King, Margaret K. Evans, David W. TI Social cognition, face processing, and oxytocin receptor single nucleotide polymorphisms in typically developing children SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Social cognition; Oxytocin; Autism spectrum disorder; Typically developing children; Event-related potential-N170 ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; GENE OXTR; SPECTRUM DISORDERS; MIND; ASSOCIATION; ATTRIBUTION; BEHAVIOR; ADULTS; SCHIZOPHRENIA AB Recent research has provided evidence of a link between behavioral measures of social cognition (SC) and neural and genetic correlates. Differences in face processing and variations in the oxytocin receptor (OXTR) gene have been associated with SC deficits and autism spectrum disorder (ASD) traits. Much work has examined the qualitative differences between those with ASD and typically developing (TD) individuals, but very little has been done to quantify the natural variation in ASD-like traits in the typical population. The present study examines this variation in TD children using a multidimensional perspective involving behavior assessment, neural electroencephalogram (EEG) testing, and OXTR genotyping. Children completed a series of neurocognitive assessments, provided saliva samples for sequencing, and completed a face processing task while connected to an EEG. No clear pattern emerged for EEG covariates or genotypes for individual OXTR single nucleotide polymorphisms (SNPs). However, SNPs rs2254298 and rs53576 consistently interacted such that the AG/GG allele combination of these SNPs was associated with poorer performance on neurocognitive measures. These results suggest that neither SNP in isolation is risk-conferring, but rather that the combination of rs2254298(A/G) and rs53576(G/G) confers a deleterious effect on SC across several neurocognitive measures. (C) 2014 Published by Elsevier Ltd. C1 [Slane, Mylissa M.; Lusk, Laina G.; Evans, David W.] Bucknell Univ, Dept Psychol, Program Neurosci, Lewisburg, PA 17837 USA. [Boomer, K. B.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. [Hare, Abby E.; King, Margaret K.] Geisinger Bucknell Autism & Dev Med Ctr, Lewisburg, PA 17837 USA. RP Evans, DW (reprint author), Geisinger Bucknell Autism & Dev Med Ctr, 120 Hamm Dr,Suite 2, Lewisburg, PA 17837 USA. EM dwevans@bucknell.edu FU Bucknell University Graduate Summer Research Stipend FX This work was supported by a Bucknell University Graduate Summer Research Stipend. 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PD JUL PY 2014 VL 50 IS 7 BP 1862 EP 1877 DI 10.1037/a0036654 PG 16 WC Psychology, Developmental SC Psychology GA AJ8HC UT WOS:000337942900003 PM 24798505 ER PT J AU Chen, YW Bundy, A Cordier, R Einfeld, S AF Chen, Yu-Wei Bundy, Anita Cordier, Reinie Einfeld, Stewart TI Feasibility and usability of experience sampling methodology for capturing everyday experiences of individuals with autism spectrum disorders SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Asperger's syndrome; Ecological momentary assessment; Client-centered practice; Social experience ID ECOLOGICAL MOMENTARY ASSESSMENT; HIGH-FUNCTIONING CHILDREN; ASPERGER SYNDROME; DAILY-LIFE; TIME-USE; ADOLESCENTS; VALIDITY; ADULTS; SCHIZOPHRENIA; INTERVENTIONS AB Background: Understanding experiences from the perspective of adults with autism spectrum disorders (ASD), in the myriad of circumstances in which they find themselves every day, is crucial for developing client-centered interventions. However, capturing these experiences can be difficult. Objective: To investigate the feasibility and usability of experience sampling method (ESM), an ecological momentary assessment, for studying individuals with ASD. Methods: Four participants (2 males) with Asperger's syndrome or high functioning autism aged 16-32 years carried an iPod touch or iPhone with a pre-installed ESM survey exploring the situation and their perceived internal experiences. Participants were asked to respond to the survey 7 times daily, at random times generated by the device, for 7 days. Results: A high signal response rate (mean = 71%) and a short average time required for survey completion (mean = 1 min 42 s) supported feasibility of the ESM for use in research with individuals with ASD. Participants reported that the questions were straightforward and that survey completion interfered very little with everyday activities, supporting acceptability of the method. Results of a split-week analysis revealed consistency of experiences; correlations among experiences that are linked logically provided evidence of the internal logic of data gathered using the ESM. Through graphic analysis, we illustrated the usability of ESM for capturing the influence of everyday contexts on internal experiences/perceptions. Conclusions: The ESM holds promise for examining the impact of social context on the everyday experiences of individuals with ASD. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chen, Yu-Wei; Bundy, Anita; Einfeld, Stewart] Univ Sydney, Fac Hlth Sci, Lidcombe, NSW 2141, Australia. [Cordier, Reinie] Curtin Univ, Sch Occupat Therapy & Social Work, Perth, WA 6845, Australia. [Einfeld, Stewart] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. RP Chen, YW (reprint author), Univ Sydney, Fac Hlth Sci, Lidcombe, NSW 2141, Australia. EM yu-wei.chen@sydney.edu.au FU Faculty of Health Sciences, University of Sydney FX The study was completed by the first author as part of the requirements for the completion of PhD under supervision of the other authors. The authors would like to acknowledge the Faculty of Health Sciences, University of Sydney for the Mary Frances Stephens Scholarship and Postgraduate Research Support Scheme. The authors also wish to express their gratitude to the people who participated in the research, Autism Spectrum Australia (Aspect) and other autism related associations in Australia for assistance in research advertisement and recruitment. 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PD JUL PY 2014 VL 7 IS 3 BP 361 EP 366 DI 10.1016/j.dhjo.2014.04.004 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA AJ8UR UT WOS:000337983800015 PM 24947579 ER PT J AU Ruthsatz, J Ruthsatz, K Stephens, KR AF Ruthsatz, Joanne Ruthsatz, Kyle Stephens, Kimberly Ruthsatz TI Putting practice into perspective: Child prodigies as evidence of innate talent SO INTELLIGENCE LA English DT Article DE Child prodigy; Intelligence; Working memory; Autism ID FAMILY-HISTORY; AUTISM; MEMORY; INTELLIGENCE; PERFORMANCE; ABILITIES; PHENOTYPE; EXPERT AB The debate over whether exceptional abilities are primarily the product of nature or nurture began centuries ago - and continues to this day. Recently, much of this debate took place within the context of considering the abilities of exceptional musicians. Several of such studies suggested that general intelligence and domain specific skills, both of which fall on the nature side of the spectrum, play a significant role in the development of musical abilities. In this paper, the author demonstrates that those studies which attempted to argue for a purely nurture-driven account of such musical talent, moreover, merely showed that practice has some role to play in the development of talent; they failed to rule out the possibility that factors such as general intelligence and domain specific skills also contribute to the development of exceptional performance abilities. If the evidence generated by studies of exceptional musicians provides a strong basis for believing that nature is the primary driver of exceptional talent, that evidence receives a powerful boost from recent studies of child prodigies. Child prodigies provide a particularly fascinating view on the nature versus nurture debate because of the extremely young age at which the prodigies demonstrate their remarkable abilities, thus, limiting the extent to which their abilities can be solely the result of extreme dedication to practice. Despite this fact, some have still argued that child prodigies' abilities are nurture-driven. Recent research, however, demonstrates that child prodigies' skills are highly dependent on a few features of their cognitive profiles, including elevated general IQs, exceptional working memories, and elevated attention to detail. Other innate characteristics of the child prodigies predict the domain in which the prodigies will excel. Music prodigies, for example, tend to score better with respect to their general IQs, visual spatial abilities, and working memories, than art prodigies. 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Method: Ninety-five individuals, 41 with schizophrenia and 54 with Asperger syndrome, were included. Self-rating of adult ADHD symptoms with the Wender-Reimherr Adult Attention Deficit Diagnostic Rating Scale (WRAADDS), parent rating of proband's ADHD childhood and adult life symptoms using the Swanson, Nolan, and Pelham Questionnaire (SNAP), and report of clinical ADHD diagnosis were included as ADHD measures. Nicotine use data were compared with data from a population sample. Results: In all, 10% of the schizophrenia group and 30% of the Asperger syndrome group had a clinical ADHD diagnosis. Nicotine dependency in the whole sample was closely linked to ADHD. Conclusion: The prevalence of comorbid ADHD was high in schizophrenia and Asperger syndrome. The WRAADDS self-rating scale for ADHD can be one useful tool for assessing comorbid ADHD in these patient groups. C1 [Hallerback, Maria Unenge; Lugnegard, Tove; Gillberg, Christopher] Cent Hosp Karlstad, S-65185 Karlstad, Sweden. 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PD JUL PY 2014 VL 18 IS 5 BP 425 EP 433 DI 10.1177/1087054712439099 PG 9 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA AJ5GD UT WOS:000337709800004 PM 22498753 ER PT J AU Adamo, N Di Martino, A Esu, L Petkova, E Johnson, K Kelly, S Castellanos, FX Zuddas, A AF Adamo, Nicoletta Di Martino, Adriana Esu, Lidia Petkova, Eva Johnson, Katherine Kelly, Simon Castellanos, Francisco Xavier Zuddas, Alessandro TI Increased Response-Time Variability Across Different Cognitive Tasks in Children With ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; childhood psychiatric symptoms; cognitive control; neurobiology ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; INTRA-SUBJECT VARIABILITY; INTRAINDIVIDUAL VARIABILITY; SUSTAINED ATTENTION; ITALIAN CHILDREN; FLUCTUATIONS; PERFORMANCE; SUBTYPES; AUTISM AB Objective: Increased response-time (RT) fluctuations below 0.2 Hz have been reported as characteristic of ADHD in some but not all studies, possibly due to methodological differences. Accordingly, We contrasted two tasks and two analytical approaches in the same sample of children with ADHD. Method: Fifty-two children with ADHD and 49 typically developing children completed an Eriksen Flanker Task and a fixed-sequence version of the sustained attention to response task. RT fluctuations with two different frequency analyses were examined. Results: Robust ADHD-related increases of slow RT fluctuations within all frequencies were found in both tasks. Tasks were significantly correlated in both groups for frequencies above 0.07 Hz. RT fluctuations across all frequencies were greatest in children with ADHD with abnormally elevated omissions. Conclusion: We observed significantly increased fluctuations of RT in children with ADHD across two different tasks and methods supporting the hypothesis that slow frequency RT fluctuations reflect neurophysiological processes underlying ADHD. C1 [Adamo, Nicoletta; Di Martino, Adriana; Castellanos, Francisco Xavier] NYU, Ctr Child Study, Inst Pediat Neurosci, New York, NY 10016 USA. [Esu, Lidia] Univ Cagliari, Cagliari, Italy. [Zuddas, Alessandro] Univ Cagliari, Dept Neurosci, Cagliari, Italy. [Petkova, Eva] NYU, Ctr Child Study, Div Biostat, New York, NY 10016 USA. [Johnson, Katherine] Univ Melbourne, Melbourne, Vic 3010, Australia. [Kelly, Simon] CUNY City Coll, Dept Biomed Engn, New York, NY USA. [Petkova, Eva; Castellanos, Francisco Xavier] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. RP Di Martino, A (reprint author), NYU, Ctr Child Study, Inst Pediat Neurosci, 215 Lexington Ave,14th Floor, New York, NY 10016 USA. 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Atten. Disord. PD JUL PY 2014 VL 18 IS 5 BP 434 EP 446 DI 10.1177/1087054712439419 PG 13 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA AJ5GD UT WOS:000337709800005 PM 22508759 ER PT J AU Schaaf, RC Benevides, T Mailloux, Z Faller, P Hunt, J van Hooydonk, E Freeman, R Leiby, B Sendecki, J Kelly, D AF Schaaf, Roseann C. Benevides, Teal Mailloux, Zoe Faller, Patricia Hunt, Joanne van Hooydonk, Elke Freeman, Regina Leiby, Benjamin Sendecki, Jocelyn Kelly, Donna TI An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Intervention; Sensory functions ID OCCUPATIONAL-THERAPY; SPECTRUM DISORDERS; MODULATION DISORDER; YOUNG-CHILDREN; INTEGRATION; FIDELITY; BEHAVIOR; OUTCOMES; RESPONSIVENESS; ASSOCIATION AB This study evaluated a manualized intervention for sensory difficulties for children with autism, ages 4-8 years, using a randomized trial design. Diagnosis of autism was confirmed using gold standard measures. Results show that the children in the treatment group (n = 17) who received 30 sessions of the occupational therapy intervention scored significantly higher (p = 0.003, d = 1.2) on Goal Attainment Scales (primary outcome), and also scored significantly better on measures of caregiver assistance in self-care (p = 0.008 d = 0.9) and socialization (p = 0.04, d = 0.7) than the Usual Care control group (n = 15). The study shows high rigor in its measurement of treatment fidelity and use of a manualized protocol, and provides support for the use of this intervention for children with autism. Findings are discussed in terms of their implications for practice and future research. C1 [Schaaf, Roseann C.] Thomas Jefferson Univ, Fac Farber Inst Neurosci, Dept Occupat Therapy, Philadelphia, PA 19107 USA. [Benevides, Teal] Jefferson Sch Hlth Profess, Dept Occupat Therapy, Philadelphia, PA 19107 USA. [Mailloux, Zoe] Pediat Therapy Network, Torrance, CA USA. [Faller, Patricia; van Hooydonk, Elke; Freeman, Regina] Childrens Specialized Hosp, Toms River, NJ 08755 USA. [Hunt, Joanne] Childrens Specialized Hosp, Mountainside, NJ 07092 USA. [Leiby, Benjamin; Sendecki, Jocelyn] Thomas Jefferson Univ, Div Biostat, Philadelphia, PA 19107 USA. [Kelly, Donna] Childrens Specialized Hosp, New Brunswick, NJ USA. RP Schaaf, RC (reprint author), Thomas Jefferson Univ, Fac Farber Inst Neurosci, Dept Occupat Therapy, 901 Walnut St,Suite 605, Philadelphia, PA 19107 USA. EM Roseann.schaaf@jefferson.edu CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT [Anonymous], 2012, PSYCHIAT NEWS Ashburner J, 2008, AM J OCCUP THER, V62, P564 Ayres A. J., 1989, SENSORY INTEGRATION Ayres A. J., 1972, SENSORY INTEGRATION Ayres A. 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P., 2000, NEURONS NEIGHBORHOOD Smith Roley S., AM J OCCUPATIONAL TH Sparrow SS, 2005, VINELAND ADAPTIVE BE Stahmer AC, 2011, BRAIN RES, V1380, P229, DOI 10.1016/j.brainres.2010.09.043 Watling R, 1999, AM J OCCUP THER, V53, P498 Watling R, 2011, OCCUPATIONAL THERAPY Watson LR, 2011, J SPEECH LANG HEAR R, V54, P1562, DOI 10.1044/1092-4388(2011/10-0029) Weschler D, 2003, WECHSLER INTELLIGENC Wong VCN, 2010, ALTERN MED REV, V15, P136 NR 69 TC 6 Z9 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1493 EP 1506 DI 10.1007/s10803-013-1983-8 PG 14 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800001 PM 24214165 ER PT J AU Pierce, NP O'Reilly, MF Sorrells, AM Fragale, CL White, PJ Aguilar, JM Cole, HA AF Pierce, Nigel P. O'Reilly, Mark F. Sorrells, Audrey M. Fragale, Christina L. White, Pamela J. Aguilar, Jeannie M. Cole, Heather A. TI Ethnicity Reporting Practices for Empirical Research in Three Autism-Related Journals SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Ethnicity; Race; Demographics; Autism spectrum disorder; Reporting practices ID SPECTRUM DISORDERS; SPECIAL-EDUCATION; YOUNG-CHILDREN; LANGUAGE LEARNERS; MOTHERS; HEALTH; ADOLESCENTS; DIAGNOSIS; SERVICES; STRESS AB This review examines ethnicity reporting in three autism-related journals (Autism, Focus on Autism and Other Developmental Disabilities, and Journal of Autism and Developmental Disorders) over a 6-year period. A comprehensive multistep search of articles is used to identify ethnicity as a demographic variable in these three journals. Articles that identified research participants' ethnicity were further analyzed to determine the impact of ethnicity as a demographic variable on findings of each study. The results indicate that ethnicity has not been adequately reported in these three autism related journals even though previous recommendations have been made to improve inadequacies of descriptive information of research participants in autism research (Kistner and Robbins in J Autism Dev Disord 16:77-82, 1986). Implications for the field of autism spectrum disorders are discussed in addition to further recommendations for future research. C1 [Pierce, Nigel P.] Univ N Carolina, Chapel Hill, NC USA. [Pierce, Nigel P.; O'Reilly, Mark F.; Sorrells, Audrey M.; Fragale, Christina L.; White, Pamela J.; Aguilar, Jeannie M.; Cole, Heather A.] Univ Texas Austin, Austin, TX 78712 USA. [Pierce, Nigel P.] Frank Porter Graham Child Dev Inst, Carrboro, NC 27510 USA. RP Pierce, NP (reprint author), Frank Porter Graham Child Dev Inst, 517 S Greensboro St, Carrboro, NC 27510 USA. 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PD JUL PY 2014 VL 44 IS 7 BP 1507 EP 1519 DI 10.1007/s10803-014-2041-x PG 13 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800002 PM 24488183 ER PT J AU Butterworth, TW Hodge, MAR Sofronoff, K Beaumont, R Gray, KM Roberts, J Horstead, SK Clarke, KS Howlin, P Taffe, JR Einfeld, SL AF Butterworth, Thomas W. Hodge, M. Antoinette Redoblado Sofronoff, Kate Beaumont, Renae Gray, Kylie M. Roberts, Jacqueline Horstead, Sian K. Clarke, Kristina S. Howlin, Patricia Taffe, John R. Einfeld, Stewart L. TI Validation of the Emotion Regulation and Social Skills Questionnaire for Young People with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ERSSQ; Social skills; Autism Spectrum Disorders; ASD; Validation ID PERVASIVE DEVELOPMENTAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; ASPERGER-SYNDROME; RESPONSIVENESS SCALE; DIAGNOSTIC INTERVIEW; CHILDREN; INTERVENTION; ADOLESCENTS; MANAGEMENT; BEHAVIOR AB The current study aims to evaluate the psychometric properties of the Emotion Regulation and Social Skills Questionnaire (ERSSQ), a rating scale designed specifically to assess the social skills of young people with Autism Spectrum Disorder (ASD). The participants were 84 children and young adolescents with ASD, aged between 7.97 and 14.16 years with a mean IQ score of 90.21 (SD = 18.82). The results provide evidence for the concurrent and criterion validity of the ERSSQ Parent form, and the concurrent validity of the ERSSQ Teacher form. The clinical and theoretical implications are discussed, including the necessity of ratings across multiple contexts and the potential use of the ERSSQ in identifying individuals most in need of intervention and for planning and assessing the outcomes of social skills interventions. C1 [Butterworth, Thomas W.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Hodge, M. Antoinette Redoblado] Childrens Hosp Westmead, Child Dev Unit, Westmead, NSW, Australia. [Sofronoff, Kate; Beaumont, Renae] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia. [Gray, Kylie M.; Taffe, John R.] Monash Univ, Southern Clin Sch, Dept Psychiat, Ctr Dev Psychiat & Psychol, Clayton, Vic, Australia. [Roberts, Jacqueline] Griffith Univ, Sch Educ & Profess Studies, Autism Ctr Excellence, Mt Gravatt, Qld 4122, Australia. [Horstead, Sian K.; Clarke, Kristina S.; Howlin, Patricia; Einfeld, Stewart L.] Univ Sydney, Brain & Mind Res Inst, Camperdown, NSW 2050, Australia. 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H., 1995, SOCIAL SKILLS TRAINI Tantam D, 2003, CHILD ADOL PSYCH CL, V12, P143, DOI 10.1016/S1056-4993(02)00053-6 Wechsler D, 1999, WECHSLER ABBREVIATED White SW, 2007, J AUTISM DEV DISORD, V37, P1858, DOI 10.1007/s10803-006-0320-x NR 30 TC 2 Z9 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1535 EP 1545 DI 10.1007/s10803-013-2014-5 PG 11 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800004 PM 24337829 ER PT J AU Lyall, K Ashwood, P Van de Water, J Hertz-Picciotto, I AF Lyall, Kristen Ashwood, Paul Van de Water, Judy Hertz-Picciotto, Irva TI Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autoimmune disease; Asthma; Allergy; Autism; Developmental delay; Maternal risk factors ID AUTOIMMUNE-DISEASES; CHILDREN; AUTOANTIBODIES; ANTIBODIES; PREGNANCY; BEHAVIOR; FAMILY; RISK AB The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk from Genetics and the Environment (CHARGE) study. Results from conditional logistic regression demonstrated few significant associations overall. Maternal autoimmune disease was significantly associated with a modest increase in odds of developmental disorders (combined ASD + DD; OR = 1.46, 95 % CI 1.01, 2.09) but not of ASD alone. Associations with certain allergens and onset periods were also suggested. These findings suggest maternal autoimmune disease may modestly influence childhood developmental disorders (ASD + DD). C1 [Lyall, Kristen; Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. 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PD JUL PY 2014 VL 44 IS 7 BP 1546 EP 1555 DI 10.1007/s10803-013-2017-2 PG 10 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800005 PM 24337796 ER PT J AU Ronconi, L Facoetti, A Bulf, H Franchin, L Bettoni, R Valenza, E AF Ronconi, Luca Facoetti, Andrea Bulf, Hermann Franchin, Laura Bettoni, Roberta Valenza, Eloisa TI Paternal Autistic Traits are Predictive of Infants Visual Attention SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Broader autism phenotype; Spatial attention; Temporal attention; Frontoparietal network; Right temporoparietal junction; Social brain development ID EVENT-RELATED POTENTIALS; SPECTRUM DISORDERS; GENERAL-POPULATION; HUMAN BRAIN; CHILDREN; PERCEPTION; NETWORKS; MECHANISMS; PHENOTYPE; QUOTIENT AB Since subthreshold autistic social impairments aggregate in family members, and since attentional dysfunctions appear to be one of the earliest cognitive markers of children with autism, we investigated in the general population the relationship between infants' attentional functioning and the autistic traits measured in their parents. Orienting and alerting attention systems were measured in 8-month-old infants using a spatial cueing paradigm. Results showed that only paternal autistic traits were linked to their children's: (1) attentional disengagement; (2) rapid attentional orienting and (3) alerting. Our findings suggest that an early dysfunction of orienting and alerting systems might alter the developmental trajectory of future ability in social cognition and communication. C1 [Ronconi, Luca; Facoetti, Andrea; Bettoni, Roberta] Univ Padua, Dept Gen Psychol, Dev & Cognit Neurosci Lab, I-35131 Padua, Italy. [Facoetti, Andrea] Sci Inst E Medea, Dev Neuropsychol Unit, Bosisio Parini, Italy. [Bulf, Hermann] Univ Milano Bicocca, Dept Psychol, Milan, Italy. [Franchin, Laura; Valenza, Eloisa] Univ Padua, Dept Dev & Socializat Psychol, Infant Cognit Lab, I-35131 Padua, Italy. [Valenza, Eloisa] Univ Padua, Interdept Ctr Cognit Sci CISC, I-35131 Padua, Italy. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1556 EP 1564 DI 10.1007/s10803-013-2018-1 PG 9 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800006 PM 24356849 ER PT J AU Sun, X Allison, C Auyeung, B Matthews, FE Norton, S Baron-Cohen, S Brayne, C AF Sun, Xiang Allison, Carrie Auyeung, Bonnie Matthews, Fiona E. Norton, Samuel Baron-Cohen, Simon Brayne, Carol TI Psychometric Properties of the Mandarin Version of the Childhood Autism Spectrum Test (CAST): An Exploratory Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum conditions; Categorical data factor analysis; Item response theory; CAST; China ID CONFIRMATORY FACTOR-ANALYSIS; ADULT ASPERGER ASSESSMENT; ITEM RESPONSE THEORY; SCREENING QUESTIONNAIRE; GENERAL-POPULATION; RATING-SCALE; TRAITS; CHILDREN; ASSOCIATION; VALIDITY AB Limited studies have investigated the latent autistic traits in the mainland Chinese population for autism spectrum conditions (ASC). This study explored the psychometric properties of a Mandarin Chinese version of the CAST in a sample consisting of 737 children in mainstream schools and 50 autistic cases. A combination of categorical data factor analysis and item response theory suggested a good-fit model of a two-factor solution for 28 items on the Mandarin CAST including social and communication, and inflexible/stereotyped language and behaviours (Goodness-of-fit indices: RMSEA = 0.029, CFI = 0.957, TLI = 0.950, SRMR = 0.064). The correlation between the two factors was moderate (GFC = 0.425). This study provided evidence for the CAST as a multidimensional measure for ASC screening in a Chinese population and also showed that the symptom manifestation of ASC in Chinese children shares similarity with western populations. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England. [Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 2AH, England. [Sun, Xiang] Chinese Univ Hong Kong, Jockey Club Sch Publ Hlth & Primary Care, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. [Auyeung, Bonnie] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Matthews, Fiona E.] Cambridge Inst Publ Hlth, Biostat Unit, MRC, Cambridge CB2 0SR, England. [Norton, Samuel] Kings Coll London, Inst Psychiat, Dept Psychol, London SE1 9RT, England. RP Sun, X (reprint author), Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Forvie Site,Robinson Way, Cambridge CB2 0SR, England. 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Cheung, Ying Kuen Brown, Alice Li, Huacheng TI A Meta-Analysis of Differences in IQ Profiles Between Individuals with Asperger's Disorder and High-Functioning Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger syndrome; Asperger's disorder; High-functioning autism; IQ; Cognitive profile; DSM; Meta-analysis; Autistic disorder ID PERVASIVE DEVELOPMENTAL DISORDERS; COGNITIVE PROFILES; SPECTRUM DISORDERS; SOCIAL ATTRIBUTION; WAIS-III; CHILDREN; ADULTS; MOTOR; DISABILITIES; ADOLESCENTS AB A meta-analysis was performed to examine differences in IQ profiles between individuals with Asperger's disorder (AspD) and high-functioning autism (HFA). Fifty-two studies were included for this study. The results showed that (a) individuals with AspD had significantly higher full-scale IQ, verbal IQ (VIQ), and performance IQ (PIQ) than did individuals with HFA; (b) individuals with AspD had significantly higher VIQ than PIQ; and (c) VIQ was similar to PIQ in individuals with HFA. These findings seem to suggest that AspD and HFA are two different subtypes of Autism. The implications of the present findings to DSM-5 Autism Spectrum Disorder are discussed. C1 [Chiang, Hsu-Min; Brown, Alice] Columbia Univ, Dept Hlth & Behav Studies, Teachers Coll, New York, NY 10027 USA. [Chiang, Hsu-Min] Columbia Univ, Intellectual Disabil Autism Program, Teachers Coll, New York, NY 10027 USA. [Tsai, Luke Y.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Cheung, Ying Kuen] Columbia Univ, Dept Biostat, Sch Publ Hlth, New York, NY 10027 USA. [Li, Huacheng] Columbia Univ, Dept Human Dev, Teachers Coll, Measurement Evaluat & Stat Program, New York, NY 10027 USA. RP Chiang, HM (reprint author), Columbia Univ, Intellectual Disabil Autism Program, Teachers Coll, 525 West 120th St,Box 223, New York, NY 10027 USA. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1577 EP 1596 DI 10.1007/s10803-013-2025-2 PG 20 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800008 PM 24362849 ER PT J AU Jimenez, L Lorda, MJ Mendez, C AF Jimenez, Luis Jose Lorda, Maria Mendez, Castor TI Emulation and Mimicry in School Students with Typical Development and with High Functioning Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Imitation; Mimicry; Emulation; Automatic imitation; Overimitation ID SPECTRUM DISORDER; IMITATION; CHILDREN; COMPATIBILITY; HYPOTHESIS; RESPONSES; QUOTIENT; VERSION; MOTOR; TASK AB Two samples of participants with typical development (TD) and high functioning autism performed an imitation task where the goal was of high or low salience, and where the modeled action complied with or was contrary to the end-state comfort (ESC) effect. 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EM luis.jimenez@usc.es; marialordasanchez@gmail.com; castor.mendez@usc.es RI Jimenez, Luis/C-6050-2011 OI Jimenez, Luis/0000-0002-0763-4220 CR Auyeung B, 2008, J AUTISM DEV DISORD, V38, P1230, DOI 10.1007/s10803-007-0504-z Baron-Cohen S, 2006, J AUTISM DEV DISORD, V36, P343, DOI 10.1007/s10803-006-0073-6 Behrmann M, 2006, TRENDS COGN SCI, V10, P258, DOI 10.1016/j.tics.2006.05.001 Cattaneo L, 2007, P NATL ACAD SCI USA, V104, P17825, DOI 10.1073/pnas.0706273104 Cook JL, 2012, J AUTISM DEV DISORD, V42, P1045, DOI 10.1007/s10803-011-1341-7 Dunn L. M., 1997, BRIT PICTURE VOCABUL, V2nd Giganti F., 2009, CURRENT PSYCHOL LETT, V25 Hamilton A. F., 2007, ATTENTION PERFORMANC, V22 Hamilton AFD, 2007, NEUROPSYCHOLOGIA, V45, P1859, DOI 10.1016/j.neuropsychologia.2006.11.022 Hamilton AFDC, 2008, Q J EXP PSYCHOL, V61, P101, DOI 10.1080/17470210701508798 Helt MS, 2010, CHILD DEV, V81, P1620, DOI 10.1111/j.1467-8624.2010.01495.x Heyes C, 2011, PSYCHOL BULL, V137, P463, DOI 10.1037/a0022288 Hobson J. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1597 EP 1608 DI 10.1007/s10803-013-2027-0 PG 12 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800009 PM 24362850 ER PT J AU Rivard, M Terroux, A Parent-Boursier, C Mercier, C AF Rivard, Melina Terroux, Amelie Parent-Boursier, Claudel Mercier, Celine TI Determinants of Stress in Parents of Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Preschoolers; Parental stress; Early intervention ID PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIOR PROBLEMS; INTELLECTUAL-DISABILITY; FAMILY STRESS; MENTAL-HEALTH; DOWN-SYNDROME; CHILDHOOD AUTISM; SYMPTOM SEVERITY; MATERNAL STRESS; FATHERS AB Parents of children with autism spectrum disorder are known to experience more stress than parents of children with any other conditions. The current study describes the parental stress of 118 fathers and 118 mothers at the onset of their children's Early Intensive Behavioral Intervention program. The objectives of the study were to compare and analyze each parent's stress and to identify factors that might predict their stress. Results indicated that fathers reported higher levels of stress than mothers. Correlations indicated that the stress levels of both parents were associated with their child's age, intellectual quotient, severity of autistic symptoms, and adaptive behaviors. Paternal stress, but not maternal stress, was predicted by severity of autistic symptoms and child's gender. Results are discussed in terms of their implications for services and early interventions. C1 [Rivard, Melina; Parent-Boursier, Claudel] Univ Quebec, Dept Psychol, Montreal, PQ H3C 3P8, Canada. [Terroux, Amelie] Ctr Readaptat Deficience Intellectuelle & Trouble, Quebec City, PQ, Canada. 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Rosen, Nila Anderson, Meredith C. Grether, Judith K. Coolman, Richard B. Harris, Stephen TI Autism and Developmental Screening in a Public, Primary Care Setting Primarily Serving Hispanics: Challenges and Results SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Developmental screening; M-CHAT; ASQ; Hispanics; Children's health ID SPECTRUM DISORDERS; MODIFIED CHECKLIST; YOUNG-CHILDREN; TODDLERS; QUESTIONNAIRES; PREVALENCE; COMMUNITY; RISK AB We implemented screening of children 16-30 months of age (n = 1,760) from a typically under-served, primarily Hispanic, population, at routine pediatric appointments using the modified checklist for autism in toddlers (M-CHAT) and Ages and Stages Questionnaire. Screen positive rates of 26 and 39 %, respectively, were higher than previous reports. Hispanics were more likely to score M-CHAT positive than non-Hispanics (adjusted OR 1.7, 95 % CI 1.2-2.4), as were those screened in Spanish. About 30 % of screen-positive children were referred for further assessment, but only half were seen. Thus screening in this population is feasible, but may require additional resources. Attention to the cultural applicability of screening instruments, as well as to explaining the results or need for additional services to parents, is critical to serve the growing Hispanic population. C1 [Windham, Gayle C.; Grether, Judith K.] Calif Dept Publ Hlth, Div Environm & Occupat Dis Control, Richmond, CA 94804 USA. [Smith, Karen S.; Rosen, Nila; Anderson, Meredith C.] Impact Assessment Inc, La Jolla, CA USA. [Coolman, Richard B.; Harris, Stephen] Santa Clara Cty Hlth & Hosp Syst, San Jose, CA USA. [Rosen, Nila] Univ Calif, Berkeley, CA USA. RP Windham, GC (reprint author), Calif Dept Publ Hlth, Div Environm & Occupat Dis Control, 850 Marina Bay Pkwy,Bldg P, Richmond, CA 94804 USA. 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Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2-3 years old toddlers. C1 [Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping] Nanjing Med Univ, Nanjing Brain Hosp, Child Mental Hlth Res Ctr, Nanjing 210029, Jiangsu, Peoples R China. [Huang, Haiqing; Liu, Yijun] Univ Florida, McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32601 USA. RP Ke, XY (reprint author), Nanjing Med Univ, Nanjing Brain Hosp, Child Mental Hlth Res Ctr, Nanjing GuangZhou Rd 264, Nanjing 210029, Jiangsu, Peoples R China. 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Participants identified the emotion of a facial expression displayed at varied levels of intensity by a computer generated avatar. The system assessed performance (i.e., accuracy, confidence ratings, response latency, and stimulus discrimination) as well as how participants used their gaze to process facial information using an eye tracker. Participants in both groups were similarly accurate at basic facial affect recognition at varied levels of intensity. Despite similar performance characteristics, ASD participants endorsed lower confidence in their responses and substantial variation in gaze patterns in absence of perceptual discrimination deficits. These results add support to the hypothesis that deficits in emotion and face recognition for individuals with ASD are related to fundamental differences in information processing. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1651 EP 1658 DI 10.1007/s10803-014-2038-5 PG 8 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800014 PM 24442835 ER PT J AU Nijmeijer, JS Arias-Vasquez, A Rommelse, NNJ Altink, ME Buschgens, CJM Fliers, EA Franke, B Minderaa, RB Sergeant, JA Buitelaar, JK Hoekstra, PJ Hartman, CA AF Nijmeijer, Judith S. Arias-Vasquez, Alejandro Rommelse, Nanda N. J. Altink, Marieke E. Buschgens, Cathelijne J. M. Fliers, Ellen A. Franke, Barbara Minderaa, Ruud B. Sergeant, Joseph A. Buitelaar, Jan K. Hoekstra, Pieter J. Hartman, Catharina A. TI Quantitative Linkage for Autism Spectrum Disorders Symptoms in Attention-Deficit/Hyperactivity Disorder: Significant Locus on Chromosome 7q11 SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; ADHD; Comorbidity; Genetics ID DEFICIT HYPERACTIVITY DISORDER; WILLIAMS-BEUREN-SYNDROME; GENERAL-POPULATION; GENETIC INFLUENCES; SOCIAL-BEHAVIOR; TWIN SAMPLE; SIB PAIRS; GENOME; TRAITS; SCAN AB We studied 261 ADHD probands and 354 of their siblings to assess quantitative trait loci associated with autism spectrum disorder symptoms (as measured by the Children's Social Behavior Questionnaire (CSBQ)) using a genome-wide linkage approach, followed by locus-wide association analysis. A genome-wide significant locus for the CSBQ subscale addressing social interaction was found on chromosome 7q11, with suggestive signals supporting this locus on three other CSBQ subscales. We identified two other suggestive loci for the CSBQ total scale and individual subscales on chromosomes 4q35 and 7p12. Fine-mapping the significantly linked locus resulted in interesting candidate genes, although their association was not significant after permutation testing. C1 [Minderaa, Ruud B.; Hoekstra, Pieter J.; Hartman, Catharina A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AR Groningen, Netherlands. [Nijmeijer, Judith S.] Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, NL-9700 AR Groningen, Netherlands. [Arias-Vasquez, Alejandro; Altink, Marieke E.; Fliers, Ellen A.; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. [Arias-Vasquez, Alejandro; Buschgens, Cathelijne J. M.; Fliers, Ellen A.; Franke, Barbara; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Rommelse, Nanda N. J.; Buschgens, Cathelijne J. M.; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Rommelse, Nanda N. J.; Altink, Marieke E.; Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Med Ctr, Nijmegen, Netherlands. [Rommelse, Nanda N. J.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. [Fliers, Ellen A.] Parnassia BAVO Grp, Youth Dept, Rotterdam, Netherlands. [Sergeant, Joseph A.] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands. RP Nijmeijer, JS (reprint author), Univ Groningen, Dept Child & Adolescent Psychiat, Hanzepl 1,POB 660, NL-9700 AR Groningen, Netherlands. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1671 EP 1680 DI 10.1007/s10803-014-2039-4 PG 10 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800016 PM 24526336 ER PT J AU Suh, J Eigsti, IM Naigles, L Barton, M Kelley, E Fein, D AF Suh, Joyce Eigsti, Inge-Marie Naigles, Letitia Barton, Marianne Kelley, Elizabeth Fein, Deborah TI Narrative Performance of Optimal Outcome Children and Adolescents with a History of an Autism Spectrum Disorder (ASD) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Outcome; Optimal; Narrative; Language; Pragmatics; Dysfluency ID HIGH-FUNCTIONING AUTISM; LANGUAGE DISORDERS; ASPERGER-SYNDROME; BEHAVIORAL TREATMENT; INDIVIDUALS; IMPAIRMENTS; ADULTS; DISCOURSE; ABILITY; AGE AB Autism Spectrum Disorders (ASDs) have traditionally been considered a lifelong condition; however, a subset of people makes such significant improvements that they no longer meet diagnostic criteria for an ASD. The current study examines whether these "optimal outcome" (OO) children and adolescents continue to have subtle pragmatic language deficits. The narratives of 15 OO individuals, 15 high-functioning individuals with an ASD (HFA), and 15 typically developing (TD) peers were evaluated. Despite average cognitive functioning, the ASD group produced narratives with fewer central "gist" descriptions, more ambiguous pronominal referents, idiosyncratic language, speech dysfluency (more repetitions and self-corrections), and were less likely to name story characters. The OO participants displayed only very subtle pragmatic and higher-level language deficits (idiosyncratic language and self-correction dysfluency). C1 [Suh, Joyce; Eigsti, Inge-Marie; Naigles, Letitia; Barton, Marianne; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. [Kelley, Elizabeth] Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. [Fein, Deborah] Univ Connecticut, Dept Pediat, Farmington, CT USA. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1681 EP 1694 DI 10.1007/s10803-014-2042-9 PG 14 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800017 PM 24500659 ER PT J AU Moss, AHB Gordon, JE O'Connell, A AF Moss, Alicia H. B. Gordon, Jocelynne E. O'Connell, Annie TI Impact of Sleepwise: An Intervention for Youth with Developmental Disabilities and Sleep Disturbance SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Children; Adolescents; Sleep problem; Treatment; Developmental disabilities; Parent ID AUTISM SPECTRUM DISORDERS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; INDEX-SHORT FORM; NEURODEVELOPMENTAL DISORDERS; ASPERGER-SYNDROME; CONDUCT PROBLEMS; YOUNG-CHILDREN; DOWN-SYNDROME; INTELLECTUAL DISABILITY AB The prevalence of sleep disturbance among children with developmental disabilities is known to be considerably higher than the typical population. The current study examined the effectiveness of the Sleepwise intervention program (O'Connell and Vannan in Aust Occup Ther J 55:212-214, 2008): a parent-assisted group-based treatment for sleep disturbance which was recently adapted for older children and adolescents with DD. Twenty-six families with children aged 8-17 years participated. The study compared a treatment and a wait-list control group at baseline, post-treatment and 2 months post-treatment on measures of child and parent functioning. Results demonstrated that the Sleepwise approach was effective in reducing sleep disturbance and parent stress. Limitations and future research directions are discussed. C1 [Moss, Alicia H. B.; Gordon, Jocelynne E.] Monash Univ, Fac Educ, Melbourne, Vic 3800, Australia. [O'Connell, Annie] Govt South Australia, Dept Commun & Social Inclus, Disabil Serv, Adelaide, SA, Australia. RP Gordon, JE (reprint author), Monash Univ, Fac Educ, Bldg 6, Melbourne, Vic 3800, Australia. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1695 EP 1707 DI 10.1007/s10803-014-2040-y PG 13 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800018 PM 24442795 ER PT J AU Zuckerman, KE Hill, AP Guion, K Voltolina, L Fombonne, E AF Zuckerman, Katharine E. Hill, Alison P. Guion, Kimberly Voltolina, Lisa Fombonne, Eric TI Overweight and Obesity: Prevalence and Correlates in a Large Clinical Sample of Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Obesity; Overweight; Children ID BODY-MASS INDEX; SCHOOL-AGED CHILDREN; CHILDHOOD OBESITY; SLEEP PROBLEMS; RISK-FACTORS; ADOLESCENTS; POPULATION; MORTALITY; DEPRESSION; WEIGHT AB Autism Spectrum Disorders (ASDs) and childhood obesity (OBY) are rising public health concerns. This study aimed to evaluate the prevalence of overweight (OWT) and OBY in a sample of 376 Oregon children with ASD, and to assess correlates of OWT and OBY in this sample. We used descriptive statistics, bivariate, and focused multivariate analyses to determine whether socio-demographic characteristics, ASD symptoms, ASD cognitive and adaptive functioning, behavioral problems, and treatments for ASD were associated with OWT and OBY in ASD. Overall 18.1 % of children met criteria for OWT and 17.0 % met criteria for OBY. OBY was associated with sleep difficulties, melatonin use, and affective problems. Interventions that consider unique needs of children with ASD may hold promise for improving weight status among children with ASD. C1 [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Dept Pediat, Portland, OR 97239 USA. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1708 EP 1719 DI 10.1007/s10803-014-2050-9 PG 12 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800019 PM 24488158 ER PT J AU Siller, M Swanson, M Gerber, A Hutman, T Sigman, M AF Siller, Michael Swanson, Meghan Gerber, Alan Hutman, Ted Sigman, Marian TI A Parent-Mediated Intervention That Targets Responsive Parental Behaviors Increases Attachment Behaviors in Children with ASD: Results from a Randomized Clinical Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Randomized clinical trial; Parent child communication; Attachment; Intervention ID AUTISM SPECTRUM DISORDER; AT-RISK MOTHERS; JOINT ATTENTION; DEVELOPMENTAL DISORDERS; IRRITABLE INFANTS; YOUNG-CHILDREN; DOWN-SYNDROME; MISSING DATA; COMMUNICATION; LANGUAGE AB The current study is a randomized clinical trial evaluating the efficacy of Focused Playtime Intervention (FPI) in a sample of 70 children with Autism Spectrum Disorder. This parent-mediated intervention has previously been shown to significantly increase responsive parental communication (Siller et al. in J Autism Dev Disord 43:540-555, 2013a). The current analyses focus on children's attachment related outcomes. Results revealed that children who were randomly assigned to FPI showed bigger increases in attachment-related behaviors, compared to children assigned to the control condition. Significant treatment effects of FPI were found for both an observational measure of attachment-related behaviors elicited during a brief separation-reunion episode and a questionnaire measure evaluating parental perceptions of child attachment. The theoretical and clinical implications of these findings are discussed. C1 [Siller, Michael; Hutman, Ted; Sigman, Marian] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Siller, Michael; Swanson, Meghan; Gerber, Alan] CUNY, Hunter Coll, Dept Psychol, New York, NY 10065 USA. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1720 EP 1732 DI 10.1007/s10803-014-2049-2 PG 13 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800020 PM 24488157 ER PT J AU Bauminger-Zviely, N Agam-Ben-Artzi, G AF Bauminger-Zviely, Nirit Agam-Ben-Artzi, Galit TI Young Friendship in HFASD and Typical Development: Friend Versus Non-friend Comparisons SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE High-functioning children with autism spectrum disorder (ASD); Preschool; Friendship; Dyads; Peer relations; Peer interaction ID HIGH-FUNCTIONING CHILDREN; AUTISM SPECTRUM DISORDER; ASPERGER-SYNDROME; PEER INTERACTION; SCHOOL; ADOLESCENTS; BEHAVIOR; BOYS; LONELINESS; ADJUSTMENT AB This study conducted comparative assessment of friendship in preschoolers with high-functioning autism spectrum disorder (HFASD, n = 29) versus preschoolers with typical development (n = 30), focusing on interactions with friends versus acquaintances. Groups were matched on SES, verbal/nonverbal MA, IQ, and CA. Multidimensional assessments included: mothers' and teachers' reports about friends' and friendship characteristics and observed individual and dyadic behaviors throughout interactions with friends versus non-friends during construction, drawing, and free-play situations. Findings revealed group differences in peer interaction favoring the typical development group, thus supporting the neuropsychological profile of HFASD. However, both groups' interactions with friends surpassed interactions with acquaintances on several key socio-communicative and intersubjective capabilities, thus suggesting that friendship may contribute to enhancement and practice of social interaction in HFASD. C1 [Bauminger-Zviely, Nirit; Agam-Ben-Artzi, Galit] Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. RP Bauminger-Zviely, N (reprint author), Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. 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PD JUL PY 2014 VL 44 IS 7 BP 1733 EP 1748 DI 10.1007/s10803-014-2052-7 PG 16 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800021 PM 24488120 ER PT J AU Deschamps, PKH Been, M Matthys, W AF Deschamps, Peter K. H. Been, Marieke Matthys, Walter TI Empathy and Empathy Induced Prosocial Behavior in 6-and 7-Year-Olds with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Children; Cognitive empathy; Affective empathy; Empathy induced prosocial behavior ID HIGH-FUNCTIONING AUTISM; EMOTION RECOGNITION; ASPERGER-SYNDROME; COMPLEX EMOTION; FUTURE-RESEARCH; FILMS TASK; CHILDREN; INDIVIDUALS; ADULTS; MIND AB The present study aimed to assess empathy and prosocial behavior in 6-7 year old children with autism spectrum disorders (ASDs). Results showed, first, lower levels of parent- and teacher-rated cognitive empathy, and similar levels of affective empathy in children with ASD compared to typically developing (TD) children. Second, emotion recognition for basic emotions, one aspect of cognitive empathy, in a story task was adequate in ASD children, but ASD children with severe impairments in social responsiveness had difficulties in recognizing fear. Third, prosocial behavior in response to signals of distress of a peer in a computer task was similar in ASD as in TD children. In conclusion, early elementary school children with ASD show specific impairments in cognitive empathy. C1 [Deschamps, Peter K. H.; Been, Marieke; Matthys, Walter] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3508 GA Utrecht, Netherlands. [Matthys, Walter] Univ Utrecht, Dept Child & Adolescent Studies, Utrecht, Netherlands. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1749 EP 1758 DI 10.1007/s10803-014-2048-3 PG 10 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800022 PM 24488118 ER PT J AU Schwartz, C Dratsch, T Vogeley, K Bente, G AF Schwartz, Caroline Dratsch, Thomas Vogeley, Kai Bente, Gary TI Brief Report: Impression Formation in High-Functioning Autism: Role of Nonverbal Behavior and Stereotype Activating Information SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE High-functioning autism (HFA); Impression formation; Nonverbal behavior; Stereotype; Virtual characters ID ASPERGER-SYNDROME; PERCEPTION AB Little is known about whether stereotypes influence social judgments of autistic individuals, in particular when they compete with tacit face-to-face cues. We compared impression formation of 17 subjects with high-functioning autism (HFA) and 17 age-, gender- and IQ-matched controls. Information about the profession of a job applicant served as stereotype activating information. The target person's nonverbal behavior was presented as a computer animation showing two virtual characters in interaction. Contrary to our hypothesis, HFA participants were as sensitive to nonverbal cues as controls. Moreover, HFA showed a tendency to evaluate persons more positively. This might indicate a routine HFA apply in impression formation in order to compensate for their deficit in intuitive understanding of nonverbal communication cues. C1 [Schwartz, Caroline; Dratsch, Thomas; Bente, Gary] Univ Cologne, Dept Social Psychol, D-50931 Cologne, Germany. [Schwartz, Caroline] Klinikum Univ Munchen, Klin Psychiat & Psychotherapie, D-80336 Munich, Germany. [Vogeley, Kai] Univ Hosp Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany. [Vogeley, Kai] Res Ctr Juelich, Inst Neurosci & Med, Julich, Germany. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1759 EP 1765 DI 10.1007/s10803-013-2021-6 PG 7 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800023 PM 24362848 ER PT J AU Samson, AC Phillips, JM Parker, KJ Shah, S Gross, JJ Hardan, AY AF Samson, Andrea C. Phillips, Jennifer M. Parker, Karen J. Shah, Shweta Gross, James J. Hardan, Antonio Y. TI Emotion Dysregulation and the Core Features of Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorder; Core features; Emotion regulation; Restricted/repetitive behaviors; Social/communication deficits; Sensory abnormalities ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; REPETITIVE BEHAVIOR; ASPERGERS SYNDROME; SENSORY PROFILE; YOUNG-PEOPLE; CHILDREN; COMMUNICATION; INDIVIDUALS AB The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child Behavior Checklist. Compared to typically developing controls, children and adolescents with ASD showed more emotion dysregulation and had significantly greater symptom severity on all scales. Within ASD participants, emotion dysregulation was related to all core features of the disorder, but the strongest association was with repetitive behaviors. These findings may facilitate the development of more effective therapeutic strategies targeting emotion dysregulation in order to optimize long-term outcomes for individuals with ASD. C1 [Samson, Andrea C.; Shah, Shweta; Gross, James J.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Phillips, Jennifer M.; Parker, Karen J.; Hardan, Antonio Y.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. RP Samson, AC (reprint author), Stanford Univ, Dept Psychol, 450 Serra Mall,Bldg 420, Stanford, CA 94305 USA. EM andrea.samson@stanford.edu CR Achenbach T. 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PD JUL PY 2014 VL 44 IS 7 BP 1766 EP 1772 DI 10.1007/s10803-013-2022-5 PG 7 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800024 PM 24362795 ER PT J AU Choque Olsson, N Bolte, S AF Choque Olsson, Nora Bolte, Sven TI Brief Report: "Quick and (not so) Dirty" Assessment of Change in Autism: Cross-Cultural Reliability of the Developmental Disabilities CGAS and the OSU Autism CGI SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Intervention; Outcome; Longitudinal; Asperger syndrome; Psychometrics ID GLOBAL ASSESSMENT SCALE; SOCIAL RESPONSIVENESS SCALE; STANDARDIZED ADOS SCORES; SPECTRUM DISORDERS; SEVERITY; SRS; CHILDREN; ADULTS AB There are few evaluated economic tools to assess change in autism. This study examined the inter-rater reliability of the Developmental Disabilities Children's Global Assessment Scale (DD-CGAS), and the OSU Autism Clinical Global Impression (OSU Autism CGI) in a European setting. Using these scales, 16 clinicians with multidisciplinary background and varying experience independently rated eight vignettes of autism spectrum disorder for severity and general psychosocial functioning at referral and discharge. Intraclass correlation coefficient (ICCs) for experienced clinicians were .75 for the DD-CGAS and .72 for the OSU Autism CGI. In inexperienced clinicians these ICCs were .58 and .59. Results confirm previous North American studies, and further extents the reliability of the instruments to untrained, less experienced clinicians with different professions. C1 [Choque Olsson, Nora; Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders KIND, Pediat Neuropsychiat Unit, Dept Womens & Childrens Hlth,CAP Res Ctr, S-11330 Stockholm, Sweden. [Choque Olsson, Nora; Bolte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. RP Bolte, S (reprint author), Karolinska Inst, Ctr Neurodev Disorders KIND, Pediat Neuropsychiat Unit, Dept Womens & Childrens Hlth,CAP Res Ctr, Gavlegatan 22, S-11330 Stockholm, Sweden. EM nora.choque-olsson@ki.se; sven.bolte@ki.se CR Abel KM, 2013, AM J PSYCHIAT, V170, P391, DOI 10.1176/appi.ajp.2012.12040543 American Psychiatric Association APA, 2013, DIAGN STAT MAN MENT, V5th Arnold LE, 2000, J AUTISM DEV DISORD, V30, P99, DOI 10.1023/A:1005451304303 Bolte S, 2008, AUTISM RES, V1, P354, DOI 10.1002/aur.49 Bolte S, 2012, J AUTISM DEV DISORD, V42, P1998, DOI 10.1007/s10803-011-1424-5 Charman T, 2013, CHILD ADOL MENT H-UK, V18, P52, DOI 10.1111/j.1475-3588.2012.00664.x Constantino J. 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Autism Dev. Disord. PD JUL PY 2014 VL 44 IS 7 BP 1773 EP 1778 DI 10.1007/s10803-013-2029-y PG 6 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800025 PM 24379174 ER PT J AU Evers, K de-Wit, L Van der Hallen, R Haesen, B Steyaert, J Noens, I Wagemans, J AF Evers, Kris de-Wit, Lee Van der Hallen, Ruth Haesen, Birgitt Steyaert, Jean Noens, Ilse Wagemans, Johan TI Brief Report: Reduced Grouping Interference in Children with ASD: Evidence from a Multiple Object Tracking Task SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Attention; Autism spectrum disorder (ASD); Global interference; Grouping; Multiple object tracking; Weak central coherence ID AUTISM SPECTRUM DISORDERS; PERCEPTUAL ORGANIZATION; VISUAL-PERCEPTION; SPATIAL PROXIMITY; WEAK COHERENCE; MOTION; ATTENTION; INDIVIDUALS; INTEGRATION; COLLINEARITY AB This study was inspired by the more locally oriented processing style in autism spectrum disorders (ASD). A modified multiple object tracking (MOT) task was administered to a group of children with and without ASD. Participants not only had to distinguish moving targets from distracters, but they also had to track targets when they were visually grouped to distracters, a manipulation which has a detrimental effect on tracking performance in adults. MOT performance in the ASD group was also affected by grouping, but this effect was significantly reduced. This result highlights how the reduced bias towards more global processing in ASD could influence further stages of cognition by altering the way in which attention selects information for further processing. C1 [Evers, Kris; de-Wit, Lee; Van der Hallen, Ruth; Haesen, Birgitt; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Leuven, Belgium. [Evers, Kris; Van der Hallen, Ruth; Haesen, Birgitt; Steyaert, Jean; Noens, Ilse; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Leuven, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, B-3000 Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Evers, K (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, Tiensestr 102,Box 3711, B-3000 Leuven, Belgium. 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PD JUL PY 2014 VL 44 IS 7 BP 1779 EP 1787 DI 10.1007/s10803-013-2031-4 PG 9 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800026 PM 24398878 ER PT J AU Waterhouse, L Gillberg, C AF Waterhouse, Lynn Gillberg, Christopher TI Why Autism Must be Taken Apart SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Brain dysfunction; DSM-5; Pathophysiology; RDoC ID TUBEROUS SCLEROSIS COMPLEX; SPECTRUM DISORDERS; CLASSIFICATION; METAANALYSIS; CEREBELLUM; HYPOPLASIA; CHILDREN; INFANTS; FUTURE; CORTEX AB Although accumulated evidence has demonstrated that autism is found with many varied brain dysfunctions, researchers have tried to find a single brain dysfunction that would provide neurobiological validity for autism. However, unitary models of autism brain dysfunction have not adequately addressed conflicting evidence, and efforts to find a single unifying brain dysfunction have led the field away from research to explore individual variation and micro-subgroups. Autism must be taken apart in order to find neurobiological treatment targets. Three research changes are needed. The belief that there is a single defining autism spectrum disorder brain dysfunction must be relinquished. The noise caused by the thorny brain-symptom inference problem must be reduced. Researchers must explore individual variation in brain measures within autism. C1 [Waterhouse, Lynn] Coll New Jersey, Global Grad Programs, Child Behav Study, Ewing, NJ 08628 USA. [Gillberg, Christopher] Gothenburg Univ, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. RP Waterhouse, L (reprint author), Coll New Jersey, Global Grad Programs, Child Behav Study, Ewing, NJ 08628 USA. 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PD JUL PY 2014 VL 44 IS 7 BP 1788 EP 1792 DI 10.1007/s10803-013-2030-5 PG 5 WC Psychology, Developmental SC Psychology GA AJ5TY UT WOS:000337752800027 PM 24390538 ER PT J AU O'Nions, E Christie, P Gould, J Viding, E Happe, F AF O'Nions, Elizabeth Christie, Phil Gould, Judith Viding, Essi Happe, Francesca TI Development of the "Extreme Demand Avoidance Questionnaire' (EDA-Q): preliminary observations on a trait measure for Pathological Demand Avoidance SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorder; ASD; pathological demand avoidance; PDA; pervasive developmental disorder; conduct problems; oppositional defiant disorder; ODD; disruptive behaviour ID DIFFICULTIES QUESTIONNAIRE; DISORDERS; STRENGTHS AB Background Pathological Demand Avoidance (PDA) is a term increasingly used in the United Kingdom to describe children who obsessively resist everyday demands, going to extreme lengths to avoid these. There is debate about its relationship with both autism spectrum disorder (ASD) and oppositional defiant disorder (ODD). Unlike ASD, children with PDA are said to use socially manipulative avoidance strategies; and unlike ODD, they resort to extreme, embarrassing or age-inappropriate behaviour. To date, there has been little research into PDA, and it remains contentious. Currently, there are no questionnaire instruments available to aid consistency in description. This study reports the development and preliminary validation of the Extreme Demand Avoidance Questionnaire' (EDA-Q), designed to quantify PDA traits based on parent-reported information. Methods The validation study involved data from 326 parents of children aged 5-17 allocated to six groups based on information reported by parents about received diagnoses and behavioural difficulties: (a) typically developing children (N=102), (b) children with ASD without disruptive behaviour (N=36), (c) children with ASD with disruptive behaviour (N=48), (d) children for whom PDA was suspected by parents (irrespective of other diagnoses) (N=67), (e) children who had, according to parents, been identified as having PDA by a health professional, irrespective of other diagnoses (N=50), and (6) disruptive behaviour or behavioural problems without suspected/identified ASD or PDA (N=23). Results Although the Strengths and Difficulties Questionnaire (SDQ) did not differentiate PDA from those with ASD plus disruptive behaviour; score on the EDA-Q was significantly higher in PDA than all comparison groups. ROC analysis indicated good sensitivity (.80) and specificity (.85). Across all case groups, females scored higher than males on the EDA-Q. Separate cut-off scores were identified for older and younger age-groups. Conclusions Our findings highlight the potential utility of the EDA-Q to assist the identification of this unusual profile for future research. C1 [O'Nions, Elizabeth; Happe, Francesca] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Christie, Phil] Sutherland House Childrens Serv NORSACA, Elizabeth Newson Ctr, Southwold, Notts, England. [Gould, Judith] NAS Lorna Wing Ctr Autism, Bromley, Kent, England. [Viding, Essi] UCL, Dev Risk & Resilience Unit, Div Psychol & Language Sci, Clin Educ & Hlth Psychol Res Dept, London, England. RP O'Nions, E (reprint author), Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat, Denmark Hill, London SE5 8AF, England. EM elizabeth.onions@kcl.ac.uk FU ESRC FX E. O'N is supported by an ESRC PhD studentship. P. C. receives payment for consultancy and training from voluntary and statutory bodies. The authors have declared that they have no competing or potential conflicts of interest. The authors are very grateful to the clinicians who assisted in developing the measure. They are also very grateful to the parents who took part in this study; and to the schools, parent groups and web groups who assisted with recruitment and supported this research. CR Christie P., 2007, GOOD AUTISM PRACTICE, V8, P3 Frick P J, 1999, Clin Child Fam Psychol Rev, V2, P149, DOI 10.1023/A:1021803005547 Goodman R, 2001, J AM ACAD CHILD PSY, V40, P1337, DOI 10.1097/00004583-200111000-00015 Goodman R, 1997, J CHILD PSYCHOL PSYC, V38, P581, DOI 10.1111/j.1469-7610.1997.tb01545.x Gould J., 2011, GOOD AUTISM PRACTICE, V12, P34 Kopp S, 2011, RES DEV DISABIL, V32, P2875, DOI 10.1016/j.ridd.2011.05.017 Newson E, 2003, ARCH DIS CHILD, V88, P595, DOI 10.1136/adc.88.7.595 O'Nions E., AUTISM INT IN PRESS Viding E, 2012, J ROY SOC MED, V105, P195, DOI 10.1258/jrsm.2011.110223 Wing L, 2002, J CHILD PSYCHOL PSYC, V43, P307, DOI 10.1111/1469-7610.00023 NR 10 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUL PY 2014 VL 55 IS 7 BP 758 EP 768 DI 10.1111/jcpp.12149 PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AJ9DW UT WOS:000338008300003 PM 24117718 ER PT J AU Musser, ED Hawkey, E Kachan-Liu, SS Lees, P Roullet, JB Goddard, K Steiner, RD Nigg, JT AF Musser, Erica D. Hawkey, Elizabeth Kachan-Liu, Svetlana S. Lees, Paul Roullet, Jean-Baptiste Goddard, Katrina Steiner, Robert D. Nigg, Joel T. TI Shared familial transmission of autism spectrum and attention-deficit/hyperactivity disorders SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Attention-deficit; hyperactivity disorder; autism spectrum disorder; shared familial transmission ID DEFICIT-HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; GENETIC INFLUENCES; TWIN SAMPLE; CHILDREN; SYMPTOMS; ADHD; ADOLESCENTS; PREVALENCE; PSYCHOPATHOLOGY AB Background To determine whether familial transmission is shared between autism spectrum disorders and attention-deficit/hyperactivity disorder, we assessed the prevalence, rates of comorbidity, and familial transmission of both disorders in a large population-based sample of children during a recent 7 year period. Methods Study participants included all children born to parents with the Kaiser Permanente Northwest (KPNW) Health Plan between 1 January 1998 and 31 December 2004 (n=35,073). Children and mothers with physician-identified autism spectrum disorders (ASD) and/or attention-deficit/hyperactivity disorder (ADHD) were identified via electronic medical records maintained for all KPNW members. Results Among children aged 6-12years, prevalence was 2.0% for ADHD and 0.8% for ASD; within those groups, 0.2% of the full sample (19% of the ASD sample and 9.6% of the ADHD sample) had co-occurring ASD and ADHD, when all children were included. When mothers had a diagnosis of ADHD, first born offspring were at 6-fold risk of ADHD alone (OR=5.02, p<.0001) and at 2.5-fold risk of ASD alone (OR=2.52, p<.01). Results were not accounted for by maternal age, child gestational age, child gender, and child race. Conclusions Autism spectrum disorders shares familial transmission with ADHD. ADHD and ASD have a partially overlapping diathesis. C1 [Musser, Erica D.; Hawkey, Elizabeth; Roullet, Jean-Baptiste; Nigg, Joel T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Musser, Erica D.] Univ Oregon, Eugene, OR 97403 USA. [Kachan-Liu, Svetlana S.] Johns Hopkins Sch Med, Baltimore, MD USA. [Lees, Paul; Goddard, Katrina] Kaiser Permanente Northwest, Portland, OR USA. [Steiner, Robert D.] Univ Wisconsin, Marshfield Clin Res Fdn, Marshfield, WI USA. RP Musser, ED (reprint author), Coll Arts & Sci, Dept Psychol, 11200 SW 8th St,AHC4-455, Miami, FL 33199 USA. EM mussere@ohsu.edu FU NIMH [R01-MH59105] FX This research was supported in part by NIMH R01-MH59105, awarded to J.T.N. E.D.M co-conceptualized the study, carried out the analyses, drafted the initial manuscript; E. H assisted with data assembly and data set preparation; S. S. K assisted in analysis, reviewed the manuscript; P. L assisted with the retrieval and organization of the data; J-B.R assisted in conceptualization of the study; K. G assisted with the retrieval and organization of the data; R. D. S assisted in conceptualization of the study, helped obtain the data; J.T.N co-conceptualized the study, oversaw the analyses, critically reviewed and helped draft the manuscript. The authors thank Jennifer Stubbs and Oregon Clinical & Translational Research for regulatory assistance, as well as Kaiser Permanente Northwest for their support and access to the data. All the authors critically reviewed and approved the final manuscript. All authors declare that they have no potential or competing conflicts of interest. CR Akinbami L. J., 2011, CTR DIS CONTROL, V70, P1 American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bakker SC, 2003, AM J HUM GENET, V72, P1251, DOI 10.1086/375143 Boyle CA, 2011, PEDIATRICS, V127, P1034, DOI 10.1542/peds.2010-2989 Brieber S, 2007, J CHILD PSYCHOL PSYC, V48, P1251, DOI 10.1111/j.1469-7610.2007.01799.x CANTWELL DP, 1988, J AM ACAD CHILD PSY, V27, P521, DOI 10.1097/00004583-198809000-00001 Centers for Disease Control, 2013, STAT BAS PREV DAT PA Clark T, 1999, EUR CHILD ADOLES PSY, V8, P50 Erskine HE, 2013, J CHILD PSYCHOL PSYC, V54, P1263, DOI 10.1111/jcpp.12144 Farley MA, 2009, AUTISM RES, V2, P109, DOI 10.1002/aur.69 Fombonne E, 2005, J APPL RES INTELLECT, V18, P281, DOI 10.1111/j.1468-3148.2005.00266.x Frazier J. A., 2001, J ATTEN DISORD, V4, P203, DOI DOI 10.1177/108705470100400402 Freitag CM, 2007, MOL PSYCHIATR, V12, P2, DOI 10.1038/sj.mp.4001896 Gaub M, 1997, J AM ACAD CHILD PSY, V36, P1036, DOI 10.1097/00004583-199708000-00011 Gershon J, 2002, J Atten Disord, V5, P143, DOI 10.1177/108705470200500302 Kogan MD, 2009, PEDIATRICS, V124, P1395, DOI 10.1542/peds.2009-1522 Lee DO, 2006, J CHILD ADOL PSYCHOP, V16, P737, DOI 10.1089/cap.2006.16.737 Leyfer OT, 2006, J AUTISM DEV DISORD, V36, P849, DOI 10.1007/s10803-006-0123-0 Lichtenstein P, 2010, AM J PSYCHIAT, V167, P1357, DOI 10.1176/appi.ajp.2010.10020223 Mulligan A, 2009, J AUTISM DEV DISORD, V39, P197, DOI 10.1007/s10803-008-0621-3 Muthen & Muthen, 2012, M PLUS VERS 6 11 Nijmeijer JS, 2009, J ABNORM CHILD PSYCH, V37, P443, DOI 10.1007/s10802-008-9282-0 Nyden A, 2010, RES DEV DISABIL, V31, P1659, DOI 10.1016/j.ridd.2010.04.010 Pamplona FA, 2009, PROG NEURO-PSYCHOPH, V33, P1153, DOI 10.1016/j.pnpbp.2009.06.012 Reiersen AM, 2008, TWIN RES HUM GENET, V11, P579, DOI 10.1375/twin.11.6.579 Reiersen AM, 2007, J CHILD PSYCHOL PSYC, V48, P464, DOI 10.1111/j.1469-7610.2006.01720.x Reiersen AM, 2008, J AM ACAD CHILD PSY, V47, P662, DOI 10.1097/CHI.0b013e31816bff88 Rommelse NNJ, 2010, EUR CHILD ADOLES PSY, V19, P281, DOI 10.1007/s00787-010-0092-x Rommelse NNJ, 2011, NEUROSCI BIOBEHAV R, V35, P1363, DOI 10.1016/j.neubiorev.2011.02.015 Ronald A, 2008, J CHILD PSYCHOL PSYC, V49, P535, DOI 10.1111/j.1469-7610.2007.01857.x Rowlandson PH, 2009, CHILD CARE HLTH DEV, V35, P681, DOI 10.1111/j.1365-2214.2009.00956.x Sandin S, 2012, J AM ACAD CHILD PSY, V51, P477, DOI 10.1016/j.jaac.2012.02.018 Santosh PJ, 2004, EUR CHILD ADOLES PSY, V13, P141, DOI 10.1007/s00787-004-0372-4 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Sinzig J, 2009, J ATTEN DISORD, V13, P117, DOI 10.1177/1087054708326261 Smalley SL, 1997, AM J HUM GENET, V60, P1276, DOI 10.1086/515485 Stone JL, 2004, AM J HUM GENET, V75, P1117, DOI 10.1086/426034 van Steijn DJ, 2012, J CHILD PSYCHOL PSYC, V53, P954, DOI 10.1111/j.1469-7610.2012.02556.x Weiss LA, 2009, EXPERT REV MOL DIAGN, V9, P795, DOI [10.1586/erm.09.59, 10.1586/ERM.09.59] NR 40 TC 4 Z9 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUL PY 2014 VL 55 IS 7 BP 819 EP 827 DI 10.1111/jcpp.12201 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AJ9DW UT WOS:000338008300011 PM 24444366 ER PT J AU Belling, R McLaren, S Paul, M Ford, T Kramer, T Weaver, T Hovish, K Islam, Z White, S Singh, SP AF Belling, Ruth McLaren, Susan Paul, Moli Ford, Tamsin Kramer, Tami Weaver, Tim Hovish, Kimberly Islam, Zoebia White, Sarah Singh, Swaran P. TI The effect of organisational resources and eligibility issues on transition from child and adolescent to adult mental health services SO JOURNAL OF HEALTH SERVICES RESEARCH & POLICY LA English DT Article DE resources; transition from child/adolescent to adult mental health services ID CARE AB Objectives: To investigate the organisational factors that impede or facilitate transition of young people from child and adolescent (CAMHS) to adult mental health services (AMHS). Methods: Thirty-four semi-structured interviews were conducted with health and social care professionals working in child and adult services in four English NHS Mental Health Trusts and voluntary organisations. Data were analysed thematically using a structured framework. Results: Findings revealed a lack of clarity on service availability and the operation of different eligibility criteria between child and adult mental health services, with variable service provision for young people with attention deficit hyperactivity disorder, autism spectrum disorders and learning disabilities. High workloads and staff shortages were perceived to influence service thresholds and eligibility criteria. Conclusions: A mutual lack of understanding of services and structures together with restrictive eligibility criteria exacerbated by perceived lack of resources can impact negatively on the transition between CAMHS and AMHS, disrupting continuity of care for young people. C1 [Belling, Ruth] Evaluat Works, Bedford, England. [McLaren, Susan] London S Bank Univ, Fac Hlth & Social Care, London SE1 0AA, England. [Paul, Moli; Singh, Swaran P.] Univ Warwick, Warwick Med Sch, Div Mental Hlth & Well Being, Coventry CV4 7AL, W Midlands, England. [Ford, Tamsin] Univ Exeter, Sch Med, Exeter EX4 4QJ, Devon, England. [Kramer, Tami; Weaver, Tim] Imperial Coll London, Fac Med, London, England. [Hovish, Kimberly] Univ London, Inst Educ, Dept Childhood Families & Hlth, London WC1E 7HU, England. [Islam, Zoebia] Leicestershire & Rutland & Birmingham & Solihull, LOROS Hosp Care Leicester, Birmingham, W Midlands, England. [White, Sarah] Univ London, Sect Mental Hlth, Div Populat Hlth Sci & Educ, London WC1E 7HU, England. RP McLaren, S (reprint author), London S Bank Univ, Fac Hlth & Social Care, London SE1 0AA, England. 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Health Serv. Res. Policy PD JUL PY 2014 VL 19 IS 3 BP 169 EP 176 DI 10.1177/1355819614527439 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA AJ8MK UT WOS:000337958800007 ER PT J AU Casanova, MF AF Casanova, Manuel F. TI Autism as a sequence: From heterochronic germinal cell divisions to abnormalities of cell migration and cortical dysplasias SO MEDICAL HYPOTHESES LA English DT Article ID LEMLI-OPITZ-SYNDROME; PERIVENTRICULAR NODULAR HETEROTOPIA; TUBEROUS SCLEROSIS COMPLEX; PRENATAL COCAINE EXPOSURE; EHLERS-DANLOS-SYNDROME; FINAL COMMON PATHWAY; SPECTRUM DISORDERS; NEURONAL MIGRATION; PREFRONTAL CORTEX; BRAIN AB The considerable heterogeneity in the number and severity of symptoms observed in autism spectrum disorders (ASD) has been regarded as an obstacle to any future research. Some authors believe that clinical heterogeneity results from the complex interplay of the many genetic and environmental factors that themselves define a condition as multifactorial. However, it is important to note that neuropathological findings in both idiopathic and syndromic autism suggests a single pathophysiological mechanism acting during brain development: the heterochronic division of germinal cells and subsequent migrational abnormalities of daughter cells to their target fields. Multiple exogenous (e.g., viruses, drugs) and endogenous (e.g., genetic mutations) factors are known to disrupt the division of germinal cells and provide for an autism phenotype. The variety of endogenous and exogenous factors, their timing of action during brain development, and the genetic susceptibility of affected individuals (a Triple Hit hypothesis) may all account for the clinical heterogeneity of ASD. Published by Elsevier Ltd. C1 Univ Louisville, Dept Psychiat, Louisville, KY 40202 USA. RP Casanova, MF (reprint author), Univ Louisville, Dept Psychiat, 500 South Preston St,Bldg A,Room 217, Louisville, KY 40202 USA. EM m0casa02@louisville.edu FU National Institutes of Health [R01 MH-86784] FX The author received funding from National Institutes of Health grant R01 MH-86784 "Building a selective inhibitory control tone in autism: an rTMS study". 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TI Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder SO NATURE GENETICS LA English DT Article ID COPY-NUMBER VARIATION; INTELLECTUAL DISABILITY; FUNCTIONAL IMPACT; VARIANTS; EXOMES; SCHIZOPHRENIA; EVOLUTION; DELETIONS; PATHWAYS; PARADIGM AB A universal challenge in genetic studies of autism spectrum disorders (ASDs) is determining whether a given DNA sequence alteration will manifest as disease. Among different population controls, we observed, for specific exons, an inverse correlation between exon expression level in brain and burden of rare missense mutations. For genes that harbor de novo mutations predicted to be deleterious, we found that specific critical exons were significantly enriched in individuals with ASD relative to their siblings without ASD (P < 1.13 x 10(-38); odds ratio (OR) = 2.40). Furthermore, our analysis of genes with high exonic expression in brain and low burden of rare mutations demonstrated enrichment for known ASD-associated genes (P < 3.40 x 10(-11); OR = 6.08) and ASD-relevant fragile-X protein targets (P < 2.91 x 10(-157); OR = 9.52). Our results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions. C1 [Uddin, Mohammed; Tammimies, Kristiina; Pellecchia, Giovanna; Hui, Pingzhao; Wang, Zhuozhi; Lau, Lynette; Nalpathamkalam, Thomas; Marshall, Christian R.; Merico, Daniele; Yuen, Ryan K. C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Tammimies, Kristiina] Karolinska Inst, Dept Womens & Childrens Hlth, Neuropsychiat Unit, Ctr Neurodev Disorders KIND, Stockholm, Sweden. [Alipanahi, Babak; Frey, Brendan J.] Univ Toronto, Dept Elect & Comp Engn, Toronto, ON, Canada. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Blencowe, Benjamin J.; Frey, Brendan J.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada. [Blencowe, Benjamin J.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Scherer, SW (reprint author), Hosp Sick Children, Ctr Appl Genom, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM stephen.scherer@sickkids.ca RI Scherer, Stephen /B-3785-2013; Yuen, Ryan/J-4876-2012 OI Scherer, Stephen /0000-0002-8326-1999; FU University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada; Ontario Genomics Institute [4445]; Canadian Institutes for Health Research (CIHR) [FEN 74527, FRNXGG818]; Canadian Institute for Advanced Research; Canada Foundation for Innovation; government of Ontario [GL2-01-013]; Ontario Brain Institute; Autism Speaks Meixner; Swedish Research Council FX We thank the Centre for Applied Genomics for informatics support, the Allen Institute of Brain Science, the National Heart, Lung, and Blood Institute (NHLBI) and the Autism Genome Project for sharing data. We thank J. Buchanan for critical review and editing of the manuscript. This work was supported by grants from the University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada and the Ontario Genomics Institute (project 4445), the Canadian Institutes for Health Research (CIHR) (FEN 74527 and FRNXGG818), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the government of Ontario (GL2-01-013), the Ontario Brain Institute and Autism Speaks. R.K.C.Y. holds an Autism Speaks Meixner Fellowship in Translational Research. K.T. holds a fellowship from the Swedish Research Council. S.W.S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children. 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PD JUL PY 2014 VL 46 IS 7 BP 742 EP 747 DI 10.1038/ng.2980 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AK0HP UT WOS:000338093800017 PM 24859339 ER PT J AU Ezegwui, IR Lawrence, L Aghaji, AE Okoye, OI Okoye, O Onwasigwe, EN Ebigbo, PO AF Ezegwui, I. R. Lawrence, L. Aghaji, A. E. Okoye, O. I. Okoye, O. Onwasigwe, E. N. Ebigbo, P. O. TI Refractive errors in children with autism in a developing country SO NIGERIAN JOURNAL OF CLINICAL PRACTICE LA English DT Article DE Autism; developing country; refractive error ID DISORDERS; NEEDS AB Background: In a resource-limited country visual problems of mentally challenged individuals are often neglected. Aim: The present study aims to study refractive errors in children diagnosed with autism in a developing country. Materials and Methods: Ophthalmic examination was carried out on children diagnosed with autism attending a school for the mentally challenged in Enugu, Nigeria between December 2009 and May 2010. Visual acuity was assessed using Lea symbols. Anterior and posterior segments were examined. Cycloplegic refraction was performed. Data was entered on the protocol prepared for the study and analyzed using Statistical Package for the Social Sciences version 17 (Chicago IL, USA). Results: A total of 21 children with autism were enrolled in the school; 18 of whom were examined giving coverage of 85.7%. The age range was 5-15 years, with a mean of 10.28 years (standard deviation +/- 3.20). There were 13 boys and 5 girls. One child had bilateral temporal pallor of the disc and one had bilateral maculopathy with diffuse chorioretinal atrophy. Refraction revealed 4 children (22.2%) had astigmatism and 2 children (11.1%) had hypermetropia. Conclusion: Significant refractive error mainly astigmatism was noted in the children with autism. Identifying refractive errors in these children early and providing appropriate corrective lenses may help optimize their visual functioning and impact their activities of daily life in a positive way. C1 [Ezegwui, I. R.; Aghaji, A. E.; Okoye, O. I.; Okoye, O.; Onwasigwe, E. N.] Univ Nigeria, Teaching Hosp, Dept Ophthalmol, Enugu, Nigeria. [Ebigbo, P. O.] Univ Nigeria, Teaching Hosp, Dept Psychol Med, Enugu, Nigeria. RP Ezegwui, IR (reprint author), Univ Nigeria, Teaching Hosp, Dept Ophthalmol, Enugu, Nigeria. EM ifeoma.ezegwui@unn.edu.ng CR Aghaji AE, 2013, EUR J OPHTHALMOL, V23, P394, DOI 10.5301/ejo.5000222 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th [Anonymous], 2011, P WORKSH US DAT EV C Autism Speaks, WHAT IS AUT Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Denis D, 1997, J FR OPHTALMOL, V20, P103 Eze BI, 2009, HUM RESOUR HEALTH, V7, DOI 10.1186/1478-4491-7-38 Ezegwui IR, 2011, INT J OPHTHALMOL-CHI, V4, P66, DOI 10.3980/j.issn.2222-3959.2011.01.15 Gogate P, 2011, INDIAN J OPHTHALMOL, V59, P223, DOI 10.4103/0301-4738.81036 Ikeda J, 2013, J AUTISM DEV DISORD, V43, P1447, DOI 10.1007/s10803-012-1475-2 Kemner C, 1998, J AUTISM DEV DISORD, V28, P61, DOI 10.1023/A:1026015120128 Miller Marilyn T, 2004, Trans Am Ophthalmol Soc, V102, P107 Miller M T, 1998, Trans Am Ophthalmol Soc, V96, P369 Nowinski CV, 2005, PSYCHIAT RES, V137, P11, DOI 10.1016/j.psychres.2005.07.005 Odusote K A, 1998, West Afr J Med, V17, P1 Omoti A E, 2007, Niger Postgrad Med J, V14, P310 Pensiero S, 2009, FUNCT NEUROL, V24, P153 SCHARRE JE, 1992, OPTOMETRY VISION SCI, V69, P433, DOI 10.1097/00006324-199206000-00004 Stanley-Cary C, 2011, CEREBELLUM, V10, P70, DOI 10.1007/s12311-010-0229-y Trachtman Joseph N, 2008, Optometry, V79, P391, DOI 10.1016/j.optm.2007.10.015 NR 20 TC 0 Z9 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1119-3077 J9 NIGER J CLIN PRACT JI Niger. J. Clin. Pract. PD JUL-AUG PY 2014 VL 17 IS 4 BP 467 EP 470 DI 10.4103/1119-3077.134042 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AJ7YW UT WOS:000337919200013 PM 24909471 ER PT J AU Elmose, M Trillingsgaard, A Jorgensen, M Nielsen, A Bruhn, SS Sorensen, EU AF Elmose, Mette Trillingsgaard, Anegen Jorgensen, Meta Nielsen, Asta Bruhn, Susanne S. Sorensen, Ester U. TI Follow-up at mid-school age (9-13 years) of children assessed for autism spectrum disorder before the age of four SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Diagnostic stability; Follow-up; Outcome; Prediction ID DIAGNOSTIC-OBSERVATION-SCHEDULE; PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIORAL INTERVENTION; REVISED ALGORITHMS; YOUNG-CHILDREN; PRESCHOOL; PREDICTORS; STABILITY; VALIDITY; TIME AB Background : Studies of diagnosis and outcome in mid-school age children (9-13 years) referred early in life for a suspected autism spectrum disorder (ASD) are scarce. Aims : This study aimed to describe outcome, developmental change and the stability of the early diagnosis in mid-school age. Methods : Children consecutively referred to a specialized autism unit at a regional psychiatric diagnostic centre in Denmark before the age of 4 were contacted in mid-school age (9-13 years). 14 children with ASD and 9 children diagnosed outside the spectrum were included. Current clinical diagnosis, autism characteristics, intellectual abilities and adaptive functioning were assessed at follow-up, and investigated in relation to early measures of intellectual abilities and difficulties in social and communicative situations. Results : The stability of an early ASD diagnosis was confirmed. However, a high degree of change into the autism spectrum was found for children who were initially diagnosed with another developmental disorder. A positive change with regard to IQ level was evident at the individual level. At group level, there was a tendency for lower functioning in the children diagnosed early with ASD. Early measures of intellectual abilities, and of social and communicative difficulties, predicted between 16% and 50% of the variance in intellectual abilities and adaptive functioning. Conclusions: The findings are in line with follow-up studies in preschool and early school age but highlight the need to monitor early diagnostic decisions, and the need for more nuanced baseline and outcome measures that may help increase our prognostic understanding. C1 [Elmose, Mette] Univ Southern Denmark, Dept Psychol, DK-5230 Odense M, Denmark. [Elmose, Mette; Trillingsgaard, Anegen] Univ Aarhus, Dept Psychol, Aarhus C, Denmark. [Trillingsgaard, Anegen; Jorgensen, Meta; Nielsen, Asta; Bruhn, Susanne S.; Sorensen, Ester U.] Aarhus Univ Hosp, Reg Ctr Child & Adolescent Psychiat, Risskov, Denmark. RP Elmose, M (reprint author), Univ Southern Denmark, Dept Psychol, Campusvej 55, DK-5230 Odense M, Denmark. 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Kim, Kwang-Soo Chung, Sangmi TI Efficient Specification of Interneurons from Human Pluripotent Stem Cells by Dorsoventral and Rostrocaudal Modulation SO STEM CELLS LA English DT Article DE Pluripotent stem cells; Medial ganglionic eminence; Interneurons; Differentiation ID SONIC HEDGEHOG; FUNCTIONAL MATURATION; CORTICAL INTERNEURONS; NEURAL DEVELOPMENT; GENE-FUNCTION; MOUSE MODEL; HUMAN ES; DIFFERENTIATION; SCHIZOPHRENIA; EXPRESSION AB GABAergic interneurons regulate cortical neural networks by providing inhibitory inputs, and their malfunction, resulting in failure to intricately regulate neural circuit balance, is implicated in brain diseases such as Schizophrenia, Autism, and Epilepsy. During early development, GABAergic interneuron progenitors arise from the ventral telencephalic area such as medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) by the actions of secreted signaling molecules from nearby organizers, and migrate to their target sites where they form local synaptic connections. In this study, using combinatorial and temporal modulation of developmentally relevant dorsoventral and rostrocaudal signaling pathways (SHH, Wnt, and FGF8), we efficiently generated MGE cells from multiple human pluripotent stem cells. Most importantly, modulation of FGF8/FGF19 signaling efficiently directed MGE versus CGE differentiation. Human MGE cells spontaneously differentiated into Lhx6-expressing GABAergic interneurons and showed migratory properties. These human MGE-derived neurons generated GABA, fired action potentials, and displayed robust GABAergic postsynaptic activity. Transplantation into rodent brains results in well-contained neural grafts enriched with GABAergic interneurons that migrate in the host and mature to express somatostatin or parvalbumin. Thus, we propose that signaling modulation recapitulating normal developmental patterns efficiently generate human GABAergic interneurons. This strategy represents a novel tool in regenerative medicine, developmental studies, disease modeling, bioassay, and drug screening. C1 [Kim, Tae-Gon; Yao, Ruiqin; Monnell, Travis; Koh, Alice; Moon, Minho; Datta, Debkanya; Kim, Kwang-Soo; Chung, Sangmi] Harvard Univ, Sch Med, McLean Hosp, Mol Neurobiol Lab,Dept Psychiat, Belmont, MA 02178 USA. [Kim, Tae-Gon; Yao, Ruiqin; Monnell, Travis; Koh, Alice; Moon, Minho; Datta, Debkanya; Kim, Kwang-Soo; Chung, Sangmi] Harvard Univ, Sch Med, McLean Hosp, Program Neurosci, Belmont, MA 02178 USA. [Kim, Tae-Gon; Yao, Ruiqin; Monnell, Travis; Koh, Alice; Moon, Minho; Datta, Debkanya; Kim, Kwang-Soo; Chung, Sangmi] Harvard Univ, Sch Med, McLean Hosp, Harvard Stem Cell Inst, Belmont, MA 02178 USA. [Cho, Jun-Hyeong; Bolshakov, Vadim Y.] Harvard Univ, Sch Med, McLean Hosp, Cellular Neurobiol Lab,Dept Psychiat, Belmont, MA 02178 USA. [Vasudevan, Anju; Kumar, Peeyush T.] Harvard Univ, Sch Med, McLean Hosp, Angiogenesis & Brain Dev Lab,Dept Psychiat, Belmont, MA 02178 USA. RP Kim, KS (reprint author), Harvard Univ, Sch Med, McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. EM kskim@mclean.harvard.edu; schung@mclean.harvard.edu FU NIH [NS079977, MH048866, MH087903, NS070577]; Harvard Stem Cell Institute FX We thank Dr. Pachnis for kindly providing us with anti-Lhx6 antibodies. This study was supported by NIH grants (NS079977, MH048866, MH087903, and NS070577) and Harvard Stem Cell Institute Seed Grant. 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J. Med. Genet. A PD JUL PY 2014 VL 164 IS 7 DI 10.1002/ajmg.a.36645 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HB UT WOS:000337633300003 ER PT J AU Guilherme, RS Soares, KC Simioni, M Vieira, TP Gil-da-Silva-Lopes, VL Kim, CA Brunoni, D Spinner, NB Conlin, LK Christofolini, DM Kulikowski, LD Steiner, CE Melaragno, MI AF Guilherme, Roberta Santos Soares, Karina Cunha Simioni, Milena Vieira, Tarsis Paiva Gil-da-Silva-Lopes, Vera Lucia Kim, Chong Ae Brunoni, Decio Spinner, Nancy Bettina Conlin, Laura Kathleen Christofolini, Denise Maria Kulikowski, Leslie Domenici Steiner, Carlos Eduardo Melaragno, Maria Isabel TI Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE ring chromosome 22; 22q11; 2 deletion; 22q13 deletion; speech delay and SNP array ID SUBTELOMERIC SEQUENCES; AUTISTIC SYNDROME; 22Q13.3; FISH; DISORDERS AB We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpointsunique for each patientcould be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder. (c) 2014 Wiley Periodicals, Inc. C1 [Guilherme, Roberta Santos; Brunoni, Decio; Melaragno, Maria Isabel] Univ Fed Sao Paulo, Div Genet, Dept Morphol & Genet, BR-04023900 Sao Paulo, Brazil. [Soares, Karina Cunha; Simioni, Milena; Vieira, Tarsis Paiva; Gil-da-Silva-Lopes, Vera Lucia; Steiner, Carlos Eduardo] Univ Estadual Campinas UNICAMP, Dept Med Genet, Campinas, SP, Brazil. [Kim, Chong Ae] Univ Sao Paulo, Dept Pediat, Inst Crianca HC FMUSP, Sao Paulo, Brazil. [Spinner, Nancy Bettina; Conlin, Laura Kathleen] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Spinner, Nancy Bettina; Conlin, Laura Kathleen] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Christofolini, Denise Maria] ABC, Fac Med, Div Obstet & Gynecol, Sao Paulo, Brazil. [Kulikowski, Leslie Domenici] Univ Sao Paulo, Dept Pathol, Lab Citogenom, Sao Paulo, Brazil. RP Guilherme, RS (reprint author), Univ Fed Sao Paulo, Dept Morphol & Genet, Rua Botucatu 740, BR-04023900 Sao Paulo, Brazil. EM robertaguilherme@hotmail.com RI Kulikowski, Leslie/F-4524-2012; Vieira, Tarsis/A-2551-2015 OI Kulikowski, Leslie/0000-0003-2236-3956; FU FAPESP, Brazil [2012/51150-0, 2012/15572-7] FX Grant sponsor: FAPESP, Brazil; Grant numbers: 2012/51150-0, 2012/15572-7. 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J. Med. Genet. A PD JUL PY 2014 VL 164 IS 7 BP 1659 EP 1665 DI 10.1002/ajmg.a.36512 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HB UT WOS:000337633300010 PM 24700634 ER PT J AU Tinker, J Carbone, PS Viskochil, D Mathiesen, A Ma, KN Stevenson, DA AF Tinker, Jade Carbone, Paul S. Viskochil, David Mathiesen, Amber Ma, Khe-Ni Stevenson, David A. TI Screening children with neurofibromatosis type 1 for autism spectrum disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurofibromatosis type 1; autism spectrum disorders; Modified Checklist for Autism in Toddlers; Childhood Autism Spectrum Test ID CAST CHILDHOOD ASPERGER; MODIFIED CHECKLIST; BEHAVIORAL-PHENOTYPE; TODDLERS; ADOLESCENTS; POPULATION; DIAGNOSIS AB Autism spectrum disorder (ASD) is reported to be increased in neurofibromatosis type 1 (NF1), but it's unknown if ASD screening tools are sensitive and specific for NF1. This study compared the rate at which children with NF1 screen-positive for two ASD screening tools [Modified Checklist for Autism in Toddlers (M-CHAT) and Childhood Autism Spectrum Test (CAST)] to the screen-positive rate of the general population. A retrospective cross-sectional observational design to investigate the association between children with NF1 and at risk status for ASD was used. Medical records of children between 16 months and 11 years of age seen in an NF Clinic were reviewed for an ASD screening questionnaire. There were no statistically significant differences in the screen-positive rate for ASD in NF1 compared to published controls, but mean CAST scores were higher in NF1. (c) 2014 Wiley Periodicals, Inc. C1 [Tinker, Jade; Carbone, Paul S.; Viskochil, David; Mathiesen, Amber; Ma, Khe-Ni; Stevenson, David A.] Univ Utah, Dept Pediat, Salt Lake City, UT 84132 USA. RP Stevenson, DA (reprint author), Univ Utah, Div Med Genet, 2C412 SOM, Salt Lake City, UT 84132 USA. EM david.stevenson@hsc.utah.edu FU University of Utah Genetic Counseling Master's Program; Thrasher Research Fund; Department of Defense [W81XWH-11-1-0250] FX Grant sponsor: University of Utah Genetic Counseling Master's Program; Grant sponsor: Thrasher Research Fund; Grant sponsor: Department of Defense; Grant number: DOD Award W81XWH-11-1-0250. 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J. Med. Genet. A PD JUL PY 2014 VL 164 IS 7 BP 1706 EP 1712 DI 10.1002/ajmg.a.36549 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HB UT WOS:000337633300016 PM 24715629 ER PT J AU Andersen, EF Baldwin, EE Ellingwood, S Smith, R Lamb, AN AF Andersen, Erica F. Baldwin, Erin E. Ellingwood, Sara Smith, Rosemarie Lamb, Allen N. TI Xq28 duplication overlapping the int22h-1/int22h-2 region and including RAB39B and CLIC2 in a family with intellectual and developmental disability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Xq28 duplication; Xp22.33 deletion; int22h; RAB39B; CLIC2 ID COPY NUMBER VARIANTS; MENTAL-RETARDATION; AUTISM; GENE; MUTATIONS; PHENOTYPE; DELETION; GTPASES; EXOME; TMLHE AB Duplications involving terminal Xq28 are a known cause of intellectual disability (ID) in males and in females with unfavorable X-inactivation patterns. Within Xq28, functional disomy of MECP2 causes a severe ID syndrome, however the dosage sensitivity of other Xq28 duplicated genes is less certain. Duplications involving the int22h-1/int22h-2 LCR-flanked region in distal Xq28 have recently been linked to a novel ID-associated phenotype. While evidence for the dosage sensitivity of this region is emerging, the phenotypic contribution of individual genes within the int22h-1/int22h-2-flanked region has yet to be determined. We report a familial case of a novel 774kb Xq28-qter duplication, detected by cytogenomic microarray analysis, that partially overlaps the int22h-1/int22h-2-flanked region. This duplication and a 570kb Xpter-p22.33 loss within the pseudoautosomal region were identified in three siblings, one female and two males, who presented with developmental delays/intellectual disability, mild dysmorphic features and short stature. Although unconfirmed, these results are suggestive of maternal inheritance of a recombinant X. We compare our clinical findings to patients with int22h-1/int22h-2-mediated duplications and discuss the potential pathogenicity of genes within the duplicated region, including those within the shared region of overlap, RAB39B and CLIC2. (c) 2014 Wiley Periodicals, Inc. C1 [Andersen, Erica F.; Baldwin, Erin E.; Lamb, Allen N.] ARUP Labs, Salt Lake City, UT 84108 USA. [Andersen, Erica F.; Lamb, Allen N.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Ellingwood, Sara; Smith, Rosemarie] Maine Med Ctr, Div Genet, Dept Pediat, Portland, ME 04102 USA. RP Andersen, EF (reprint author), ARUP Labs, 500 Chipeta Way, Salt Lake City, UT 84108 USA. 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J. Med. Genet. A PD JUL PY 2014 VL 164 IS 7 BP 1795 EP 1801 DI 10.1002/ajmg.a.36524 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HB UT WOS:000337633300028 PM 24700761 ER PT J AU Schwartzberg, ET Silverman, MJ AF Schwartzberg, Edward T. Silverman, Michael J. TI Music therapy song repertoire for children with autism spectrum disorder: A descriptive analysis by treatment areas, song types, and presentation styles SO ARTS IN PSYCHOTHERAPY LA English DT Article DE Autism; Music therapy; Music; Songs; Repertoire ID SCERTS MODEL; RESPONSIVENESS; INTERVENTIONS; BEHAVIORS AB The purpose of this descriptive study was to identify the song types, presentation styles, and song repertoire utilized within specific treatment areas with children with autism spectrum disorder (ASD). The researchers sent surveys to 257 music therapists who worked with children between the ages of birth through 19 years diagnosed with ASD. Ninety-one music therapists participated in the survey, resulting in a 35% return rate. The number of participants responding to each question ranged from 72 to 91. Overall, the majority of respondents indicated they utilized more pre-existing songs, followed by original compositions and lyric replacement (piggyback) songs. However, when asked questions about song types used to address specific treatment areas, respondents indicated they utilized live original compositions across all treatment domains more frequently than live pre-existing and live lyric replacement songs. Developing protocols to choose song types may be helpful for the acceptance of music therapy as an evidence-based treatment modality for children with ASD. Future research is warranted to determine the type of songs most conducive to facilitating improvement in specific treatment areas. Implications for clinical practice, educational preparation, and limitations of this study are provided. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Schwartzberg, Edward T.; Silverman, Michael J.] Univ Minnesota, Minneapolis, MN 55455 USA. RP Schwartzberg, ET (reprint author), Univ Minnesota, Sch Mus, 100 Ferguson Hall,2106 Fourth St South, Minneapolis, MN 55455 USA. EM schwa155@umn.edu CR American Music Therapy Association, 2013, WORKF AN Autism Society, 2013, AUT DIAGN Brownell MD, 2002, J MUSIC THER, V39, P117 Buday E. M., 1995, J MUSIC THER, V32, P373 Buysse V., 2006, ZERO 3, V27, P50 Cevasco A. M., 2010, MUSIC THERAPY PERSPE, V28, P37 Finnigan E, 2010, AUTISM, V14, P321, DOI 10.1177/1362361309357747 Gadberry AL, 2011, J MUSIC THER, V48, P74 GIBBONS AC, 1977, J MUSIC THER, V14, P180 Kaplan R. 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PD JUL PY 2014 VL 41 IS 3 BP 240 EP 249 DI 10.1016/j.aip.2014.03.007 PG 10 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA AJ4QB UT WOS:000337659800002 ER PT J AU Chandler, F Dissanayake, C AF Chandler, Felicity Dissanayake, Cheryl TI An investigation of the security of caregiver attachment during middle childhood in children with high-unctioning autistic disorder SO AUTISM LA English DT Article DE attachment; high-functioning autism; security ID PERVASIVE DEVELOPMENTAL DISORDERS; PEER ATTACHMENT; YOUNG-CHILDREN; MOTHER; PARENT; ASSOCIATIONS; METAANALYSIS; ADOLESCENCE; PERCEPTIONS; BEHAVIORS AB Previous research has investigated caregiver attachment relationships in children with autism during early childhood, with few differences found from matched control groups. However, little is known of this relationship during middle childhood (ages 8-12 years). In this study, the aim was to establish whether there are differences in the security of attachment in children with high-functioning autism compared to typically developing children. A secondary aim was to establish whether caregivers' perceptions of their child's attachment to them accorded with the children's own reports. Twenty-one children with high-functioning autism and 17 typically developing children were administered the Kerns Security Scale and the Inventory of Parent and Peer Attachment-Revised, and caregivers completed the same questionnaires from the viewpoint of their child. There were no differences between the groups in the children's and parents' reports of attachment security. Parents' and children's reports were moderately correlated on the Kerns Security Scale but were not correlated on the Inventory of Parent and Peer Attachment-Revised. 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Schreiber, Dana R. Olino, Thomas M. Minshew, Nancy J. TI The association between emotional and behavioral problems and gastrointestinal symptoms among children with high-functioning autism SO AUTISM LA English DT Article DE abdominal pain; autism spectrum disorder; behavior; Child Behavior Checklist; gastrointestinal ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; YOUNG-PEOPLE; PREVALENCE; INDIVIDUALS; ADOLESCENTS; ASDS AB This study investigated the association between gastrointestinal symptoms and a broad set of emotional and behavioral concerns in 95 children with high-functioning autism and IQ scores >= 80. Gastrointestinal symptoms were assessed via the Autism Treatment Network's Gastrointestinal Symptom Inventory, and data were gathered on autism symptom severity, adaptive behavior, and multiple internalizing and externalizing problems. The majority (61%) of children had at least one reported gastrointestinal symptom. Emotional and behavioral problems were also common but with a high degree of variability. Children with and without gastrointestinal problems did not differ in autism symptom severity, adaptive behavior, or total internalizing or externalizing problem scores. However, participants with gastrointestinal problems had significantly higher levels of affective problems. This finding is consistent with a small body of research noting a relationship between gastrointestinal problems, irritability, and mood problems in autism spectrum disorder. More research to identify the mechanisms underlying this relationship in autism spectrum disorder is warranted. Future research should include a medical assessment of gastrointestinal concerns, longitudinal design, and participants with a range of autism spectrum disorder severity in order to clarify the directionality of this relationship and to identify factors that may impact heterogeneity in the behavioral manifestation of gastrointestinal concerns. C1 [Mazefsky, Carla A.; Schreiber, Dana R.; Olino, Thomas M.; Minshew, Nancy J.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. RP Mazefsky, CA (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 OHara St,Webster Hall,Suite 300, Pittsburgh, PA 15213 USA. 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Dissanayake, Cheryl Scheeren, Anke Koot, Hans M. Begeer, Sander TI Parenting stress and autism: The role of age, autism severity, quality of life and problem behaviour of children and adolescents with autism SO AUTISM LA English DT Article DE age; autism; autism severity; parenting stress; problem behaviour; quality of life ID DOUBLE ABCX MODEL; SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; PRESCHOOL-CHILDREN; SYMPTOM SEVERITY; MENTAL-HEALTH; CHALLENGING BEHAVIORS; SOCIAL SUPPORT; RISK MARKERS; MOTHERS AB While stress is a common experience for parents caring for a child with a developmental disability, current measures fail to distinguish between general stress in parents and the demands of parenting and perceptions of parenting skills (parenting stress). This study examined differences in 'parenting stress' reported by parents of children with autism and typically developing children. This study examined the role of child characteristics (age, autism severity, child quality of life and problem behaviour) on parenting stress in 150 parents of cognitively able children and adolescents with autism. The results revealed that child hyperactivity was the only factor significantly related to parenting stress in parents of children with autism, overruling measures of autism severity and child quality of life. This finding indicates the significant influence of problematic behaviours on parenting demands and perceptions of parenting skills in parents of children with autism, over other child characteristics conceived as within the parent's control. Study implications for future research are discussed. C1 [McStay, Rebecca L.; Dissanayake, Cheryl] La Trobe Univ, Bundoora, Vic 3086, Australia. [Scheeren, Anke; Koot, Hans M.; Begeer, Sander] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Begeer, Sander] Univ Sydney, Sydney, NSW 2006, Australia. 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Elder, Lauren Gulsrud, Amanda Kasari, Connie TI The association between parental interaction style and children's joint engagement in families with toddlers with autism SO AUTISM LA English DT Article DE autism spectrum disorder; joint engagement; parental directiveness; parental responsivity; social initiations; toddlers ID ATTENTION AB Purpose: This study examines the relationship between parental interaction style (responsive vs directive) and child-initiated joint engagement within caregiver-child interactions with toddlers diagnosed with autism spectrum disorders. Method: Videotaped interactions of 85 toddler-caregiver dyads were coded for child engagement and both parental responsiveness and directiveness. Results: Altogether, children spent less than one-third of the interaction jointly engaged. After controlling for child characteristics, parental style was associated with the initiator (child or parent) of joint engagement. Specifically, responsiveness predicted total time in child-initiated joint engagement, while directiveness predicted total time in parent-initiated joint engagement. Children's social behaviours were associated with child-initiated joint engagement. Discussion: Social initiations are a key target for children with autism spectrum disorders. Results demonstrate that child initiations and global social behaviour ratings are associated with parental responsivity. Responsivity may be a critical factor to facilitate children's initiations. C1 [Patterson, Stephanie Y.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Elder, Lauren] Autism Speaks, New York, NY USA. [Gulsrud, Amanda; Kasari, Connie] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA. RP Patterson, SY (reprint author), Univ Calif Los Angeles, Grad Sch Educ & Informat Studies, Moore Hall,2027,Box 951521, Los Angeles, CA 90095 USA. EM sypatterson@ucla.edu CR Adamson LB, 2004, CHILD DEV, V75, P1171, DOI 10.1111/j.1467-8624.2004.00732.x Adamson LB, 2001, J APPL DEV PSYCHOL, V22, P439, DOI 10.1016/S0193-3973(01)00089-2 Adamson LB, 2009, J AUTISM DEV DISORD, V39, P84, DOI 10.1007/s10803-008-0601-7 Fey ME, 2006, J SPEECH LANG HEAR R, V49, P526, DOI 10.1044/1092-4388(2006/039) Kasari C, 2012, J AM ACAD CHILD PSY, V51, P487, DOI 10.1016/j.jaac.2012.02.019 Kasari C, 2010, J AUTISM DEV DISORD, V40, P1045, DOI 10.1007/s10803-010-0955-5 Lord C., 1999, AUTISM DIAGNOSTIC OB Mahoney G, 2003, TOPICS EARLY CHILD S, V23, P74, DOI DOI 10.1177/02711214030230020301 Mullen E, 1995, MULLEN SCALES EARLY Ruble LA, 2007, J AUTISM DEV DISORD, V37, P1457, DOI 10.1007/s10803-006-0222-y Tomasello M., 2001, LANG ACQUIS, P133 Warren SF, 2007, MENT RETARD DEV D R, V13, P330, DOI 10.1002/mrdd.20177 NR 12 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD JUL PY 2014 VL 18 IS 5 BP 511 EP 518 DI 10.1177/1362361313483595 PG 8 WC Psychology, Developmental SC Psychology GA AJ3JP UT WOS:000337562700005 PM 24104518 ER PT J AU Freuler, AC Baranek, GT Tashjian, C Watson, LR Crais, ER Turner-Brown, LM AF Freuler, Ashley C. Baranek, Grace T. Tashjian, Christene Watson, Linda R. Crais, Elizabeth R. Turner-Brown, Lauren M. TI Parent reflections of experiences of participating in a randomized controlled trial of a behavioral intervention for infants at risk of autism spectrum disorders SO AUTISM LA English DT Article DE autism; early intervention; parent experience; qualitative ID CHILDREN; STRESS; DIAGNOSIS; MOTHERS AB Background: Despite the mounting evidence of efficacy of early intervention for children with autism spectrum disorders, there is little research that considers the various perceptions and resources with which parents respond to the pressures and opportunities associated with participation in early intervention. Research is particularly lacking surrounding experiences of parents with infants who are at risk of autism spectrum disorders but do not (yet) have a diagnosed condition. Objectives: This qualitative study aimed to explore the experiences of caregivers following their participation in a randomized controlled trial of Adapted Responsive Teaching, a parent-infant relationship-focused intervention for infants at risk of autism spectrum disorders in a community sample. Parents were randomized into either the treatment group, in which they participated in the Adapted Responsive Teaching intervention, or the community services group, in which they were provided with information regarding local early intervention services and were encouraged, but not required to, seek community services as part of their inclusion in the randomized controlled trial. Methods: Semistructured interviews were conducted with families following the completion of the randomized controlled trial. Participants consisted of 13 mothers and 4 fathers. Five dyads were interviewed together for a total of 14 families. Child ages ranged from 39 to 46 months at the time of interview. Analysis was conducted on 14 interviews from 10 families who were randomized into the treatment group and 4 families randomized into the community services group. Analysis was informed by a thematic analysis approach, which involved a systematic process of coding and theme identification both across and within groups. Results: Themes that emerged across groups included Working against all odds, Value of the personal relationship, Getting the ball rolling, and Getting dad on board. One broad theme represented the data within the groups: Win-win (Adapted Responsive Teaching group) and Navigating amidst ambiguity (community services group). Conclusions: This study illuminates the personal experiences and contextual influences affecting families who are participating in the randomized controlled trial through early identification of "risk" status for autism spectrum disorders in their infants. Insights gained from these interviews may serve to refine and enhance intervention models and to enhance early intervention services for families. C1 [Freuler, Ashley C.; Baranek, Grace T.; Tashjian, Christene; Watson, Linda R.; Crais, Elizabeth R.; Turner-Brown, Lauren M.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Freuler, AC (reprint author), Univ N Carolina, Div Occupat Sci & Occupat Therapy, Dept Allied Hlth Sci, Bondurant Hall,CB 7122, Chapel Hill, NC 27599 USA. 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Mazurek, Micah O. TI Video game access, parental rules, and problem behavior: A study of boys with autism spectrum disorder SO AUTISM LA English DT Article DE autism; in-room media; oppositional behavior; video game rules; video games ID MEDIA USE; CHILDREN; TELEVISION; ADOLESCENTS; BEDROOM; OVERWEIGHT; HABITS; RISK; TIME; AGE AB Environmental correlates of problem behavior among individuals with autism spectrum disorder remain relatively understudied. The current study examined the contribution of in-room (i.e. bedroom) access to a video game console as one potential correlate of problem behavior among a sample of 169 boys with autism spectrum disorder (ranging from 8 to 18 years of age). Parents of these children reported on (1) whether they had specific rules regulating their child's video game use, (2) whether their child had in-room access to a variety of screen-based media devices (television, computer, and video game console), and (3) their child's oppositional behaviors. Multivariate regression models showed that in-room access to a video game console predicted oppositional behavior while controlling for in-room access to other media devices (computer and television) and relevant variables (e. g. average number of video game hours played per day). Additionally, the association between in-room access to a video game console and oppositional behavior was particularly large when parents reported no rules on their child's video game use. The current findings indicate that both access and parental rules regarding video games warrant future experimental and longitudinal research as they relate to problem behavior in boys with autism spectrum disorder. C1 [Engelhardt, Christopher R.; Mazurek, Micah O.] Univ Missouri, Columbia, MO 65203 USA. RP Engelhardt, CR (reprint author), Univ Missouri, Dept Psychol Sci, 210 McAlester Hall, Columbia, MO 65203 USA. 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Ronald, Angelica Happe, Francesca TI Pathological demand avoidance: Exploring the behavioural profile SO AUTISM LA English DT Article DE atypical autism; autism spectrum disorder; conduct problems and callous-unemotional traits; pathological demand avoidance; phenotype ID CONDUCT PROBLEMS; CHILDREN; DISORDERS; CHILDHOOD; AUTISM; PSYCHOPATHOLOGY; ADHD; TWIN AB 'Pathological Demand Avoidance' is a term increasingly used by practitioners in the United Kingdom. It was coined to describe a profile of obsessive resistance to everyday demands and requests, with a tendency to resort to 'socially manipulative' behaviour, including outrageous or embarrassing acts. Pathological demand avoidance is thought to share aspects of social impairment with autism spectrum disorders, but autism spectrum disorder-appropriate strategies, such as routine and repetition, are described as unhelpful. Outrageous acts and lack of concern for their effects draw parallels with conduct problems and callous-unemotional traits. However, reward-based techniques, effective with conduct problems and callous-unemotional traits, seem not to work in pathological demand avoidance. Despite increasing interest and controversy over the pathological demand avoidance label, there is only one published study to date. We present the first systematic comparison of the behavioural profile of children receiving the term pathological demand avoidance (N = 25) to children with autism spectrum disorders (N = 39) or conduct problems and callous-unemotional traits (N = 28), using parent-report indices of psychopathology. The pathological demand avoidance group displayed comparable levels of autistic traits and peer problems to the autism spectrum disorders group and anti-social traits approaching those seen in the conduct problems and callous-unemotional traits group. Emotional symptoms in pathological demand avoidance exceeded both comparison groups. Findings highlight the extreme behavioural impairment associated with pathological demand avoidance and the need to explore whether behavioural overlap reflects a similar neurocognitive basis to existing groups. C1 [O'Nions, Elizabeth; Viding, Essi; Greven, Corina U.; Happe, Francesca] Kings Coll London, London SE5 8AF, England. [Viding, Essi] UCL, London WC1E 6BT, England. [Greven, Corina U.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Ronald, Angelica] Birkbeck, London, England. RP O'Nions, E (reprint author), Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, Denmark Hill, London SE5 8AF, England. 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Hunter, Samuel T. TI Enhancing work outcomes of employees with autism spectrum disorder through leadership: Leadership for employees with autism spectrum disorder SO AUTISM LA English DT Article DE autism; job attitudes; leadership; performance ID TRANSFORMATIONAL LEADERSHIP; CHARISMATIC LEADERSHIP; TRANSACTIONAL LEADERSHIP; TASK PREFERENCES; ADULTS; EMPLOYMENT; CONSEQUENCES; ORGANIZATION; METAANALYSIS; ANTECEDENTS AB The focus of this study was to identify leader behaviors that elicit successful engagement of employees with autism spectrum disorder, a population that is powerfully emerging into the workplace. The ultimate goal was to improve the quality of life of employees with autism spectrum disorder by facilitating an environment leading to their success. 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A., 2010, LEADERSHIP ORG NR 48 TC 1 Z9 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD JUL PY 2014 VL 18 IS 5 BP 545 EP 554 DI 10.1177/1362361313483020 PG 10 WC Psychology, Developmental SC Psychology GA AJ3JP UT WOS:000337562700009 PM 23886575 ER PT J AU Swanson, AR Warren, ZE Stone, WL Vehorn, AC Dohrmann, E Humberd, Q AF Swanson, Amy R. Warren, Zachary E. Stone, Wendy L. Vehorn, Alison C. Dohrmann, Elizabeth Humberd, Quentin TI The diagnosis of autism in community pediatric settings: Does advanced training facilitate practice change? SO AUTISM LA English DT Article DE autism spectrum disorders; diagnosis; screening ID SPECTRUM DISORDERS; MODIFIED CHECKLIST; CHILDREN; TODDLERS; STAT; AGE AB The increased prevalence of autism spectrum disorder and documented benefits of early intensive intervention have created a need for flexible systems for determining eligibility for autism-specific services. This study evaluated the effectiveness of a training program designed to enhance autism spectrum disorder identification and assessment within community pediatric settings across the state. Twenty-seven pediatric providers participated in regional trainings across a 3.5-year period. Trainings provided clinicians with strategies for conducting relatively brief within-practice interactive assessments following positive autism spectrum disorder screenings. Program evaluation was measured approximately 1.5 years following training through (a) clinician self-reports of practice change and (b) blind diagnostic verification of a subset of children assessed. Pediatric providers participating in the training reported significant changes in screening and consultation practices following training, with a reported 85% increase in diagnostic identification of children with autism spectrum disorder within their own practice setting. In addition, substantial agreement (86%-93%) was found between pediatrician diagnostic judgments and independent, comprehensive blinded diagnostic evaluations. Collaborative training methods that allow autism spectrum disorder identification within broader community pediatric settings may help translate enhanced screening initiatives into more effective and efficient diagnosis and treatment. C1 [Swanson, Amy R.; Warren, Zachary E.; Vehorn, Alison C.; Dohrmann, Elizabeth] Vanderbilt Univ, Nashville, TN 37203 USA. 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Shattuck, Paul T. Cooper, Benjamin P. Roux, Anne M. Wagner, Mary TI Prevalence and correlates of postsecondary residential status among young adults with an autism spectrum disorder SO AUTISM LA English DT Article DE adult; autism; residence; transition ID EMERGING ADULTHOOD; UNITED-STATES; TRANSITION; CHILDREN; HOME; POPULATION; PATTERNS; SCHOOL; YOUTH; LIFE AB This study examined the prevalence and correlates of three living arrangements (with a parent or guardian, independently or with a roommate, or in a supervised setting) among a nationally representative sample of postsecondary young adults with an autism spectrum disorder. We assessed living arrangements since leaving high school. Compared with young adults with other disability types (learning disabilities, intellectual disabilities, or emotional disturbances), those with an autism spectrum disorder were more likely to have lived with a parent or guardian and least likely ever to have lived independently since leaving high school. Members of the autism spectrum disorder group were less likely to have ever lived elsewhere and more likely to live under supervision since leaving high school compared to persons with emotional disturbances and learning disabilities. Group differences persisted after controlling for functional ability and demographic characteristics. Correlates of residential independence included being White, having better conversation ability and functional skills, and having a higher household income. Further research is needed to investigate how these residential trends relate to the quality of life among families and young adults. C1 [Anderson, Kristy A.] Univ Wisconsin, Madison, WI 53705 USA. 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Eng, Charis TI Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis SO AUTISM LA English DT Article DE autism spectrum disorder; autism symptoms; diagnosis; prediction ID SOCIAL RESPONSIVENESS SCALE; GENERAL-POPULATION; CHILDREN; TRAITS; DISORDERS; VALIDATION; VALIDITY; CRITERIA; TWIN; AGE AB Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the Social Responsiveness Scale. Demographic and clinical correlates were covariates in regression models predicting social communication and interaction and restricted/repetitive behavior symptoms. Logistic regression and receiver operating characteristic curve analyses evaluated the incremental validity of social communication and interaction and restricted/repetitive behavior domains over and above global autism symptoms. Autism spectrum disorder diagnosis was the strongest correlate of caregiver-reported social communication and interaction and restricted/repetitive behavior symptoms. The presence of comorbid diagnoses also increased symptom levels. Social communication and interaction and restricted/repetitive behavior symptoms provided significant, but modest, incremental validity in predicting diagnosis beyond global autism symptoms. These findings suggest that autism spectrum disorder diagnosis is by far the largest determinant of quantitatively measured autism symptoms. Externalizing (attention deficit hyperactivity disorder) and internalizing (anxiety) behavior, low cognitive ability, and demographic factors may confound caregiver-report of autism symptoms, potentially necessitating a continuous norming approach to the revision of symptom measures. Social communication and interaction and restricted/repetitive behavior symptoms may provide incremental validity in the diagnosis of autism spectrum disorder. C1 [Frazier, Thomas W.; Embacher, Rebecca; Eng, Charis] Cleveland Clin, Cleveland, OH 44104 USA. [Youngstrom, Eric A.] Univ N Carolina, Chapel Hill, NC USA. [Hardan, Antonio Y.] Stanford Univ, Stanford, CA 94305 USA. [Constantino, John N.] Washington Univ, St Louis, MO USA. [Law, Paul] Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Findling, Robert L.] Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. RP Frazier, TW (reprint author), Cleveland Clin, Ctr Autism CRS10, 2801 Martin Luther King Jr Dr, Cleveland, OH 44104 USA. 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Swanson, Amy Sarkar, Nilanjan Warren, Zachary E. TI Pilot clinical application of an adaptive robotic system for young children with autism SO AUTISM LA English DT Article DE autism spectrum disorder; joint attention; robotics; technology ID SPECTRUM DISORDERS; JOINT ATTENTION; MOBILE ROBOT; INTERVENTIONS; IMITATION AB It has been argued that clinical applications of advanced technology may hold promise for addressing impairments associated with autism spectrum disorders. This pilot feasibility study evaluated the application of a novel adaptive robot-mediated system capable of both administering and automatically adjusting joint attention prompts to a small group of preschool children with autism spectrum disorders (n = 6) and a control group (n = 6). Children in both groups spent more time looking at the humanoid robot and were able to achieve a high level of accuracy across trials. 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Rampton, T. Rosemann, J. Peterson, M. Mandleco, B. Dyches, T. Roper, S. TI Snapshots reflecting the lives of siblings of children with autism spectrum disorders SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE autism spectrum disorder; qualitative; siblings ID BEHAVIORAL-ADJUSTMENT; PHOTO-ELICITATION; DEVELOPMENTAL-DISABILITIES; COPING STRATEGIES; INDIVIDUALS; PHOTOGRAPHY; PERCEPTIONS; STRESS; LIFE; EXPERIENCES AB Background Past research focused on the effects of raising a child with autism spectrum disorder on families. However, most research examined parents' perspectives rather than siblings' perspectives. Therefore, the purpose of this qualitative descriptive design was to use photo elicitation to capture perspectives of siblings living with a child with autism spectrum disorder. Methods Fourteen siblings (nine male) of 13 children with autism spectrum disorder received disposable cameras with 24-27 colour exposures, and were asked to photograph what was important to them within 2 weeks. After developing snapshots, investigators interviewed siblings about their photographs, and used open, axial and selective coding to determine photograph categories and subcategories. Results Two major categories were found: people (family members, non-family members) and non-people (personal items/objects, animals, buildings, scenery). Interviews about photographs reflected experiences siblings had with people/non-people in the snapshots and their normal everyday activities. Most photographs revealed family life and activities any sibling would experience whether or not they lived in a family raising a child with autism spectrum disorder. Conclusions Photo elicitation facilitates communication between children and health-care professionals, and provides information about living with a child with autism spectrum disorder from the sibling's perspective. This information contributes to our knowledge base and allows development of specific intervention plans for siblings of these children. C1 [Latta, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rampton, T.] Alaska Hlth Fairs, Anchorage, AK USA. [Rosemann, J.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Peterson, M.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Mandleco, B.] Brigham Young Univ, Coll Nursing, Provo, UT 84602 USA. [Dyches, T.] Brigham Young Univ, Dept Counseling Psychol & Special Educ, Provo, UT 84602 USA. [Roper, S.] Brigham Young Univ, Coll Family Home & Social Sci, Provo, UT 84602 USA. RP Mandleco, B (reprint author), Brigham Young Univ, Coll Nursing, 474 SWKT, Provo, UT 84602 USA. 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PD JUL PY 2014 VL 40 IS 4 BP 515 EP 524 DI 10.1111/cch.12100 PG 10 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA AJ3EC UT WOS:000337547500008 PM 23952538 ER PT J AU Huber, S Fieder, M AF Huber, Susanne Fieder, Martin TI Advanced paternal age is associated with lower facial attractiveness SO EVOLUTION AND HUMAN BEHAVIOR LA English DT Article DE Paternal age; Education; Early life; Attractiveness; Wisconsin Longitudinal Study ID DE-NOVO MUTATIONS; PHYSICAL ATTRACTIVENESS; EVOLUTIONARY PSYCHOLOGY; RISK; SCHIZOPHRENIA; POPULATION; DEPRESSION; AUTISM; COHORT AB In view of disease risk, Kong et al. (2012) demonstrated that most of the new mutations are explained by the age of the father at conception. Accordingly, paternal age effects have been found for a variety of offspring traits, from physical and mental health to intelligence. Here, we investigated whether facial attractiveness is significantly associated with paternal age. We used the Wisconsin Longitudinal Study (n = 4018 male and 4416 female high school graduates) to analyze the association between an individual's father's age at birth and that individual's facial attractiveness (estimated by rating the high school yearbook photographs from 1957), controlling for sex, age as well as mother's age. We find that subject's facial attractiveness decreased with advancing paternal but not maternal age, suggesting that facial attractiveness might be a cue of an individual's new mutation load. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huber, Susanne; Fieder, Martin] Univ Vienna, Dept Anthropol, A-1090 Vienna, Austria. RP Huber, S (reprint author), Univ Vienna, Dept Anthropol, Althanstr 14, A-1090 Vienna, Austria. EM susanne.huber@univie.ac.at FU National Institute of Aging [AG-9775, AG-21079, AG-033285]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison FX We thank Geoffrey Miller and the other anonymous reviewers for their constructive and helpful comments and suggestions. This research uses data from the Wisconsin Longitudinal Study (WLS) of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute of Aging (AG-9775 AG-21079 and AG-033285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the Wisconsin Longitudinal Study is available from the Wisconsin Longitudinal Study, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, Wisconsin 53706 and at http://www.ssc.wisc.edu/wlsresearch/data/. The opinions expressed herein are those of the authors. 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PD JUL PY 2014 VL 35 IS 4 BP 298 EP 301 DI 10.1016/j.evolhumbehav.2014.02.011 PG 4 WC Psychology, Biological; Behavioral Sciences; Social Sciences, Biomedical SC Psychology; Behavioral Sciences; Biomedical Social Sciences GA AJ5IB UT WOS:000337714800007 ER PT J AU Gizzonio, V Avanzini, P Fabbri-Destro, M Campi, C Rizzolatti, G AF Gizzonio, Valentina Avanzini, Pietro Fabbri-Destro, Maddalena Campi, Cristina Rizzolatti, Giacomo TI Cognitive abilities in siblings of children with autism spectrum disorders SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Autism; Siblings; Cognitive profile; Endophenotype; WISC ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; SOCIAL RESPONSIVENESS SCALE; SCHIZOPHRENIC CHILDREN; 1ST-DEGREE RELATIVES; ASPERGER-SYNDROME; FOLLOW-UP; PATTERNS; PROFILES; INDIVIDUALS AB The aim of the present study was to assess the cognitive profiles of children with autistic spectrum disorder and of their healthy siblings (Siblings). With the term cognitive profile, we indicate the relationship extant among the values of verbal and performance subtests of the Wechsler Intelligence Scale. The conducted statistical analyses indicated that, although siblings showed a normal intelligent quotient and did not differ in this aspect from typically developing group, their cognitive profile was amazingly similar to that of their relatives affected by autism. A k-means clustering analysis on the values of single subtests further confirmed this result, showing a clear separation between typically developing children on the one side, and autistics and their siblings on the other. We suggest that the common cognitive profile observed in autistic children and their siblings could represent a marker of liability to autism and, thus, a possible intermediate phenotype of this syndrome. C1 [Gizzonio, Valentina; Avanzini, Pietro; Campi, Cristina; Rizzolatti, Giacomo] Univ Parma, Dipartimento Neurosci, Sez Fisiol, I-43100 Parma, Italy. [Fabbri-Destro, Maddalena; Rizzolatti, Giacomo] Italian Inst Technol, Brain Ctr Social & Motor Cognit, I-43100 Parma, Italy. RP Rizzolatti, G (reprint author), Univ Parma, Dipartimento Neurosci, Sez Fisiol, Via Volturno 39-E, I-43100 Parma, Italy. EM giacomo.rizzolatti@unipr.it FU ERC [250013] FX VG, PA and CC were supported by ERC Grant Cogsystem to GR, contract no. 250013. We thank Dr. Fabio Sambataro and Sonia Boria for critical reading and for their remarks on previous versions of the manuscript. A special thanks to the staff of the Pediatric Neuropsychiatry of Empoli, of the rehabilitation center for autism "Centro Mai Soli" in Genova, of the Institute of Rehabilitation "Village Eugenio Litta," Grottaferrata, Roma, and of the Autism Center of Parma for their invaluable collaboration in data collection. We also thank the staff and families of IV Circolo "Risorgimento - San Berardo" primary school in Teramo for providing the control group. Last but not least, thanks to all the children and their families for the availability and patience. 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Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 males, 12 females). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age. (c) 2014 Wiley Periodicals, Inc. C1 [Hunsaker, Michael R.; Scott, Julia A.; Bauman, Melissa D.; Schumann, Cynthia M.; Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Med Ctr, Sacramento, CA 95817 USA. [Hunsaker, Michael R.; Bauman, Melissa D.; Schumann, Cynthia M.; Amaral, David G.] Univ Calif Davis, Med Ctr, MIND Inst, Sacramento, CA 95817 USA. [Scott, Julia A.] Univ Calif Davis, Program Neurosci, MIND Inst, Sacramento, CA 95817 USA. [Bauman, Melissa D.; Amaral, David G.] Univ Calif Davis, Calif Natl Primate Res Ctr, MIND Inst, Sacramento, CA 95817 USA. RP Amaral, DG (reprint author), Univ Calif Davis, Dept Psychiat & Behav Sci, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM dgamaral@ucdavis.edu FU NIH [R01 NS016980, R37 MH57502] FX Grant sponsor: NIH; Grant number: R01 NS016980 and R37 MH57502. 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Liu, Yongzhuang Zhu, Xiaolin Guo, Hongzhe Jiang, Qinghua Allen, Andrew S. Zhu, Mingfu TI An Evaluation of Copy Number Variation Detection Tools from Whole-Exome Sequencing Data SO HUMAN MUTATION LA English DT Article DE copy number variation; whole-exome sequencing; whole-genome sequencing; evaluation studies ID STRUCTURAL VARIATION; HUMAN GENOME; COMPUTATIONAL METHODS; POPULATION-SCALE; DISCOVERY; AUTISM; SPECTRUM; DISEASE; POLYMORPHISM; ALGORITHM AB Copy number variation (CNV) has been found to play an important role in human disease. Next-generation sequencing technology, including whole-genome sequencing (WGS) and whole-exome sequencing (WES), has become a primary strategy for studying the genetic basis of human disease. Several CNV calling tools have recently been developed on the basis of WES data. However, the comparative performance of these tools using real data remains unclear. An objective evaluation study of these tools in practical research situations would be beneficial. Here, we evaluated four well-known WES-based CNV detection tools (XHMM, CoNIFER, ExomeDepth, and CONTRA) using real data generated in house. After evaluation using six metrics, we found that the sensitive and accurate detection of CNVs in WES data remains challenging despite the many algorithms available. Each algorithm has its own strengths and weaknesses. None of the exome-based CNV calling methods performed well in all situations; in particular, compared with CNVs identified from high coverage WGS data from the same samples, all tools suffered from limited power. Our evaluation provides a comprehensive and objective comparison of several well-known detection tools designed for WES data, which will assist researchers in choosing the most suitable tools for their research needs. C1 [Tan, Renjie; Wang, Yadong; Liu, Yongzhuang; Guo, Hongzhe; Jiang, Qinghua] Harbin Inst Technol, Sch Comp Sci & Technol, Ctr Biomed Informat, Harbin 150001, Heilongjiang, Peoples R China. [Tan, Renjie; Kleinstein, Sarah E.; Liu, Yongzhuang; Zhu, Xiaolin; Guo, Hongzhe; Allen, Andrew S.; Zhu, Mingfu] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA. [Kleinstein, Sarah E.] Duke Univ, Sch Med, Dept Mol Genet & Microbiol, Durham, NC USA. [Allen, Andrew S.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Zhu, Mingfu] Tute Genom, Provo, UT USA. RP Wang, YD (reprint author), Harbin Inst Technol, Sch Comp Sci & Technol, Ctr Biomed Informat, Harbin 150001, Heilongjiang, Peoples R China. EM ydwang@hit.edu.cn; mingfu@tutegenomics.com FU Natural Science Foundation of China [61102149, 61173085]; China Scholarship Council FX Contract grant sponsors: The Natural Science Foundation of China (61102149 and 61173085); The China Scholarship Council. 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Mutat. PD JUL PY 2014 VL 35 IS 7 BP 899 EP 907 DI 10.1002/humu.22537 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AJ5EQ UT WOS:000337705500016 PM 24599517 ER PT J AU El Khatib, AA El Tekeya, MM El Tantawi, MA Omar, T AF El Khatib, Amira A. El Tekeya, Magda M. El Tantawi, Maha A. Omar, Tarek TI Oral health status and behaviours of children with Autism Spectrum Disorder: a case-control study SO INTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY LA English DT Article ID DENTAL PATIENTS; MANAGEMENT AB Background. Autism Spectrum Disorder (ASD) is a lifelong neuro-developmental disorder characterized by abnormalities in social interactions and communication and by stereotyped, repetitive activities. Purpose. Assess the oral health status and behaviours of children with ASD. Methods. The study included 100 children with ASD and 100 healthy children from Alexandria, Egypt. Data were collected using a questionnaire and clinical examination. Questionnaire assessed socio-demographics, medical history, dental history, oral hygiene, dietary habits, and presence of self-injurious behaviours. Clinical examination assessed behaviour during examination, gingival condition, plaque accumulation, caries, and other oral conditions. Results. Children with ASD had significantly poorer oral hygiene and gingival condition than healthy children (P < 0.001 for both). No significant differences were found in caries prevalence or experience in primary or permanent dentition. More children with ASD behaved 'negatively' or 'definitely negatively' (37% and 11%) than did healthy controls (11% and 2%) (P < 0.0001). Self-injurious behaviour and bruxism were more practised by children with ASD (32% of children with ASD and 2% of healthy children, P < 0.001). More children with ASD had difficulty in accessing dental care (P = 0.002). Conclusions. The oral condition of children with ASD might increase the risk of developing dental diseases. Their behaviour and life factors may complicate provision of services and limit access to dental care. Therefore, individualized oral health education programmes should be implemented for those children. C1 [El Khatib, Amira A.] Univ Alexandria, Fac Dent, Dept Pediat Dent, Alexandria 21121, Egypt. [El Tekeya, Magda M.; El Tantawi, Maha A.] Univ Alexandria, Fac Dent, Dent Publ Hlth Dept, Alexandria 21121, Egypt. [Omar, Tarek] Univ Alexandria, Fac Med, Dept Pediat, Alexandria 21121, Egypt. RP El Khatib, AA (reprint author), Univ Alexandria, Fac Dent, Dept Pediat Dent, Meroza Compound Villa 11B, Alexandria 21121, Egypt. 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O'Hara, Ruth Hallmayer, Joachim TI Prenatal and perinatal risk factors in a twin study of autism spectrum disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Autism; Prenatal; Perinatal; Pregnancy complications; Twins; Environment ID TRAUMATIC BRAIN-INJURY; LOW-BIRTH-WEIGHT; SEX-DIFFERENCES; COMPREHENSIVE METAANALYSIS; COGNITIVE RECOVERY; MATERNAL AGE; FETAL SEX; HYPOXIA; PROGESTERONE; OUTCOMES AB Introduction: Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently. Methods: Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed. Results: Shared factors including parental age, prenatal use of medications, uterine bleeding, and prematurity did not increase concordance risks for ASDs in twins. Among the individual factors, respiratory distress demonstrated the strongest association with increased risk for ASDs in the group as a whole (OR 2.11, 95% CI 1.27-3.51). Furthermore, respiratory distress (OR 2.29, 95% CI 1.12-4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04-3.80) were associated with increased risks for ASDs in males, while jaundice was associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28-6.74). Conclusions: Perinatal factors associated with respiratory distress and other markers of hypoxia appear to increase risk for autism in a subgroup of twins. Future studies examining potential gender differences and additional prenatal, perinatal and postnatal environmental factors are required for elucidating the etiology of ASDs and suggesting new methods for treatment and prevention. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Froehlich-Santino, Wendy; Tobon, Amalia Londono; Cleveland, Sue; Torres, Andrea; Phillips, Jennifer; Lotspeich, Linda; O'Hara, Ruth; Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Cohen, Brianne; Torigoe, Tiffany; Miller, Janet; Fedele, Angie; Lajonchere, Clara] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA USA. [Collins, Jack; Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Smith, Karen] Impact Assessment Inc, La Jolla, CA USA. [Ozonoff, Sally] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Grether, Judith K.] Calif Dept Publ Hlth, Environm Hlth Invest Branch, Richmond, CA USA. 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PD JUL PY 2014 VL 32 IS 4 BP 283 EP 294 DI 10.1177/0734282913511051 PG 12 WC Psychology, Educational SC Psychology GA AJ3VV UT WOS:000337596900001 ER PT J AU Ghaleiha, A Ghyasvand, M Mohammadi, MR Farokhnia, M Yadegari, N Tabrizi, M Hajiaghaee, R Yekehtaz, H Akhondzadeh, S AF Ghaleiha, Ali Ghyasvand, Mohammad Mohammadi, Mohammad-Reza Farokhnia, Mehdi Yadegari, Noorollah Tabrizi, Mina Hajiaghaee, Reza Yekehtaz, Habibeh Akhondzadeh, Shahin TI Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Acetylcholinesterase inhibitor; autism; cholinergic; galantamine; irritability; nicotinic receptor; randomized controlled trial; risperidone; social withdrawal ID NICOTINIC ACETYLCHOLINE-RECEPTORS; ALLOSTERIC POTENTIATING LIGAND; SPECTRUM DISORDERS; ABERRANT BEHAVIOR; RISPERIDONE; BRAIN; ABNORMALITIES; ATTENTION; SYSTEMS; DYSFUNCTION AB The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms. C1 [Ghaleiha, Ali] Hamadan Univ Med Sci, Res Ctr Behav Disorders & Substance Abuse, Hamadan, Iran. [Ghyasvand, Mohammad; Mohammadi, Mohammad-Reza; Farokhnia, Mehdi; Yadegari, Noorollah; Yekehtaz, Habibeh; Akhondzadeh, Shahin] Univ Tehran Med Sci, Roozbeh Hosp, Psychiat Res Ctr, Tehran 13337, Iran. [Tabrizi, Mina] Univ Tehran Med Sci, Dept Med Genet, Tehran 13337, Iran. [Hajiaghaee, Reza] Inst Med Plants, Med Plants Res Ctr, Karaj, Iran. RP Akhondzadeh, S (reprint author), Univ Tehran Med Sci, Roozbeh Psychiat Hosp, Psychiat Res Ctr, South Kargar St, Tehran 13337, Iran. EM s.akhond@neda.net FU Tehran University of Medical Sciences [13216] FX This work was supported by Tehran University of Medical Sciences (grant number 13216 to SA). The funding organization had no role in the design and conduct of the study; nor in the collection, analysis and interpretation of the data; nor in the preparation, review or approval of the manuscript; nor in the decision to submit the paper for publication. 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Psychopharmacol. PD JUL PY 2014 VL 28 IS 7 BP 677 EP 685 DI 10.1177/0269881113508830 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AJ3PX UT WOS:000337580300008 ER PT J AU Feinstein, NW AF Feinstein, Noah Weeth TI Making sense of autism: Progressive engagement with science among parents of young, recently diagnosed autistic children SO PUBLIC UNDERSTANDING OF SCIENCE LA English DT Article DE engagement mapping; lay expertise; public engagement; public understanding of science; scientific literacy; sociology of health and illness ID PARTICIPATION; BEHAVIOR AB This exploratory study examines the significance of science to parents whose children were recently diagnosed with an autism spectrum disorder. It asks: (1) In what manner did science emerge in parents' concerns and resources as they attempted to understand and advocate for their children? (2) Did some parents engage with science in a qualitatively deeper or more intense manner? Using longitudinal data from interviews and a novel data collection strategy called engagement mapping, it shows that parents asked questions and used resources that were strongly associated with science, but these were vastly outnumbered by "near-science" concerns and resources that mingled meanings from science and daily life. Several parents in the study wove together concerns and resources in an iterative pattern referred to here as progressive engagement with science. C1 [Feinstein, Noah Weeth] Univ Wisconsin, Dept Curriculum & Instruct, Madison, WI 53706 USA. [Feinstein, Noah Weeth] Univ Wisconsin, Dept Community & Environm Sociol, Madison, WI 53706 USA. RP Feinstein, NW (reprint author), Univ Wisconsin, Dept Curriculum & Instruct, 225 North Mills St, Madison, WI 53706 USA. 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Sci. PD JUL PY 2014 VL 23 IS 5 BP 592 EP 609 DI 10.1177/0963662512455296 PG 18 WC Communication; History & Philosophy Of Science SC Communication; History & Philosophy of Science GA AJ3PA UT WOS:000337577800007 PM 25414924 ER PT J AU Sarasua, SM Boccuto, L Sharp, JL Dwivedi, A Chen, CF Rollins, JD Rogers, RC Phelan, K DuPont, BR AF Sarasua, Sara M. Boccuto, Luigi Sharp, Julia L. Dwivedi, Alka Chen, Chin-Fu Rollins, Jonathan D. Rogers, R. Curtis Phelan, Katy DuPont, Barbara R. TI Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome SO HUMAN GENETICS LA English DT Article ID 22Q13.3 DELETION SYNDROME; AUTISM SPECTRUM DISORDERS; INVERTED DUPLICATION; TERMINAL DELETION; SHANK3; GENE; MUTATIONS; IDENTIFICATION; BREAKPOINT; GROWTH AB This study is the first to describe age-related changes in a large cohort of patients with Phelan-McDermid syndrome (PMS), also known as 22q13 deletion syndrome. Over a follow-up period of up to 12 years, physical examinations and structured interviews were conducted for 201 individuals diagnosed with PMS, 120 patients had a focused, high-resolution 22q12q13 array CGH, and 92 patients' deletions were assessed for parent-of-origin. 22q13 genomic anomalies include terminal deletions of 22q13 (89 %), terminal deletions and interstitial duplications (9 %), and interstitial deletions (2 %). Considering different age groups, in older patients, behavioral problems tended to subside, developmental abilities improved, and some features such as large or fleshy hands, full or puffy eyelids, hypotonia, lax ligaments, and hyperextensible joints were less frequent. However, the proportion reporting an autism spectrum disorder, seizures, and cellulitis, or presenting with lymphedema or abnormal reflexes increased with age. Some neurologic and dysmorphic features such as speech and developmental delay and macrocephaly correlated with deletion size. Deletion sizes in more recently diagnosed patients tend to be smaller than those diagnosed a decade earlier. Seventy-three percent of de novo deletions were of paternal origin. Seizures were reported three times more often among patients with a de novo deletion of the maternal rather than paternal chromosome 22. This analysis improves the understanding of the clinical presentation and natural history of PMS and can serve as a reference for the prevalence of clinical features in the syndrome. C1 [Sarasua, Sara M.; Boccuto, Luigi; Dwivedi, Alka; Chen, Chin-Fu; Rollins, Jonathan D.; Rogers, R. Curtis; DuPont, Barbara R.] Greenwood Genet Ctr, Off Bioinformat & Epidemiol, Greenwood, SC 29646 USA. [Sharp, Julia L.] Clemson Univ, Dept Math Sci, Clemson, SC 29634 USA. [Phelan, Katy] Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. [Phelan, Katy] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. RP Sarasua, SM (reprint author), Greenwood Genet Ctr, Off Bioinformat & Epidemiol, 101 Gregor Mendel Circle, Greenwood, SC 29646 USA. EM ssarasua@ggc.org FU Phelan-McDermid Syndrome Foundation; Genetics Endowment of South Carolina; South Carolina Department of Disabilities and Special Needs FX This work was supported, in part, by a fellowship to SMS from the Phelan-McDermid Syndrome Foundation; the Genetics Endowment of South Carolina; and the South Carolina Department of Disabilities and Special Needs. 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Genet. PD JUL PY 2014 VL 133 IS 7 BP 847 EP 859 DI 10.1007/s00439-014-1423-7 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AI7QD UT WOS:000337088600002 PM 24481935 ER PT J AU Martoccio, TL Brophy-Herb, HE Onaga, EE AF Martoccio, Tiffany L. Brophy-Herb, Holly E. Onaga, Esther E. TI Road to Readiness Pathways From Low-Income Children's Early Interactions to School Readiness Skills SO INFANTS & YOUNG CHILDREN LA English DT Article DE joint attention; low-income; parent-child interaction; school readiness ID EARLY LITERACY DEVELOPMENT; INFANT JOINT ATTENTION; EARLY HEAD-START; INDIVIDUAL-DIFFERENCES; PRESCHOOL-CHILDREN; EMOTION REGULATION; LANGUAGE; AUTISM; PREDICTORS; TODDLERS AB This study utilized data from the Michigan component of the National Early Head Start Research and Evaluation study to examine toddlers' joint attention at 14 months (parent report measure of toddlers' initiating behaviors, e. g., extends arm to show you something he or she is holding, reaches out and gives you a toy he or she has been holding, and points at something interesting) as a mediator of the relations between early mother-child interactions (e. g., mother and child behaviors in response to one another's cues) and later school readiness skills in a low-income sample (N = 127 mother-child dyads). Understanding relations between early parent-child interactions, joint attention, and later school readiness skills is critical to identifying developmental paths of economically at-risk children. Results showed that toddlers' joint attention behaviors at 14 months partially mediated the path between mother-child interaction at 14 months and later school readiness, measured by children's emotion regulation, social-cognition, language development, and literacy and mathematics academic outcomes, at approximately 5 years of age. Results suggest the important roles of early mother-child interactions in low-income families and joint attention in promoting school readiness skills. C1 [Martoccio, Tiffany L.; Brophy-Herb, Holly E.; Onaga, Esther E.] Michigan State Univ, E Lansing, MI 48824 USA. RP Martoccio, TL (reprint author), Michigan State Univ, 552 W Circle Dr,7 Human Ecol Bldg, E Lansing, MI 48824 USA. 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PD JUL-SEP PY 2014 VL 27 IS 3 BP 193 EP 206 DI 10.1097/IYC.0000000000000014 PG 14 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AI9YF UT WOS:000337303100001 ER PT J AU Vilaseca, R Ferrer, F Olmos, JG AF Vilaseca, Rosa Ferrer, Fina Guardia Olmos, Joan TI Gender differences in positive perceptions, anxiety, and depression among mothers and fathers of children with intellectual disabilities: a logistic regression analysis SO QUALITY & QUANTITY LA English DT Article DE Positive perceptions; Anxiety; Depression; Children with intellectual disabilities; Families; Logistic regression ID SCHOOL-AGED CHILDREN; MENTAL-HEALTH; DEVELOPMENTAL-DISABILITIES; BEHAVIOR PROBLEMS; HOSPITAL ANXIETY; PARENTAL STRESS; EARLY INTERVENTION; SOCIAL SUPPORT; AUTISM; POPULATION AB This study explores gender differences in positive perceptions, anxiety, and depression among mothers and fathers of children with intellectual disabilities (IDs). We examined the relationship between these variables and certain characteristics of both the child (age and severity of disability) and the parents (age, educational level, and employment status). A sample of 60 mother/father couples who had children with IDs completed the Positive Contributions Scale to measure their positive perceptions, and the Hospital Anxiety and Depression Scale to assess their level of anxiety and depression. Bivariate analyses were used to determine differences between fathers and mothers as regards their positive perceptions and levels of anxiety and depression. A logistic regression model was then applied to identify which of the variables might be significant predictors of the gender differences observed among parents. Both mothers and fathers had positive perceptions of their children with IDs that co-existed with symptoms of anxiety and depression, with scores being higher among mothers. 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Lobbestael, Jill TI Comparing cognitive functioning in schizophrenia and autism using WAIS-III SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Schizophrenia; Autism; Cognitive functioning; WAIS-III; Processing speed ID WORKING-MEMORY IMPAIRMENTS; ONSET SCHIZOPHRENIA; DISORDER; ADULTS; NEUROCOGNITION; METAANALYSIS; INDIVIDUALS; PERFORMANCE; INTERVIEW; DEFICITS AB The main goal of this study was to investigate differences and similarities in general cognitive functioning between adults with schizophrenia and autism, because this has not been systematically investigated. We used a cross-sectional design to compare adults with schizophrenia (n = 27), with autism (n = 114) and a healthy control group (n = 30). Schizophrenia diagnoses were based on the Structured Clinical Interview for the DSM-IV Axis I (SCID-I) and behavioral symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Autism was diagnosed with a DSM-IV questionnaire for autism spectrum disorders and the Autistic Diagnostic Interview, revised version. The Wechsler Adult Intelligence Scale, third version (WAIS-III) was used to assess cognitive functions. All participants were between 18 and 65 years of age and had a minimum full scale intelligence of 80. Results showed that patients with schizophrenia scored significantly lower on processing speed than patients with autism and the healthy control group. Differences on other index scales were not found. In participants with schizophrenia a correlation was found between processing speed impairment and negative symptoms. Diagnosis could be predicted correctly with WAIS-III profile in 70.4% of the cases with schizophrenia compared to 56.7% of the healthy control group and 22.8% of the autism group. (C) 2014 Elsevier Ltd. All rights reserved. C1 [de Boer, Marion] Mental Hlth Inst GGZ Eindhoven, NL-5600 AX Eindhoven, Netherlands. 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Scharf, Alexa Aum, SangWeon TI Perception of the prosody and content of sentences in an unfamiliar language in children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Receptive prosody; Language; Computer game; Attention; Prioritization deficit hypothesis ID HIGH-FUNCTIONING AUTISM; STIMULUS OVERSELECTIVITY; FACIAL EXPRESSIONS; ADOLESCENTS; CUES; DISCRIMINATION; COMMUNICATION; COMPREHENSION; PERFORMANCE; ATTENTION AB Prior research suggests that children with autism spectrum disorders (ASD) show atypical patterns of attention to the prosody (intonation and emotional tone of voice) and content (words) of spoken sentences. Using a discrimination-choice procedure embedded in a custom-made videogame, we examined attention to these features of sentences in 15 children with ASD (ages 5 years, 5 months-18 years) and 15 age-matched typical controls (TYP). Using an unfamiliar language (German) to remove semantics, we assessed the role of meaning in promoting attention to content over prosody. As in a previous study with English sentences, TYP children attended to content to a greater extent than children with ASD while maintaining equivalent levels of discrimination based on prosody. However, in contrast to previous results, TYP children did not show a preference for enthusiastic over grouchy tone of voice, which suggests that the unfamiliar language rendered affective valence less salient. The results confirm intact perception of prosody in children with ASD, and a more selective pattern of attention to content in TYP children. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ploog, Bertram O.; Brooks, Patricia J.] CUNY Coll Staten Isl, Staten Isl, NY 10314 USA. [Ploog, Bertram O.; Brooks, Patricia J.] CUNY, Grad Ctr, New York, NY USA. [Scharf, Alexa] Columbia Univ, Teachers Coll, New York, NY 10027 USA. 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PD JUL PY 2014 VL 8 IS 7 BP 775 EP 787 DI 10.1016/j.rasd.2014.03.014 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600005 ER PT J AU Nopprapun, M Holloway, J AF Nopprapun, Michael Holloway, Jennifer TI A comparison of fluency training and discrete trial instruction to teach letter sounds to children with ASD: Acquisition and learning outcomes SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Fluency training (FT); Discrete trial instruction (DTI); Autism; Phonics instruction ID AUTISM SPECTRUM DISORDERS; BEHAVIORAL FLUENCY; OSHIELDS 2004; LITERACY; INTERVENTIONS; INDIVIDUALS; KNOWLEDGE; STUDENTS; DOUGHTY; CHASE AB The study investigated the efficacy of fluency training (FT) and discrete trial instruction (DTI) to teach phonic reading to individuals with Autism Spectrum Disorder (ASD), with particular emphasis on the acquisition of correct letter-sound correspondence and the learning outcomes of behavioural fluency instruction. An alternating-treatment design was employed to compare the treatment effects of FT versus DTI for the acquisition, retention, stability, endurance, and application of phonics in four children with ASD. The results showed that for two participants, FT was more efficient for the acquisition of correct letter-sound correspondence. For the remaining two participants, DTI resulted in more rapid acquisition. For all four participants, FT produced better results during post-test retention, endurance, stability, and application checks. The implications of these findings are discussed in relation to reading instruction, as well as the use of rate-building procedures with individuals with ASD. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Nopprapun, Michael; Holloway, Jennifer] Natl Univ Ireland, Galway, Ireland. RP Holloway, J (reprint author), Natl Univ Ireland, Galway, Ireland. 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PD JUL PY 2014 VL 8 IS 7 BP 788 EP 802 DI 10.1016/j.rasd.2014.03.015 PG 15 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600006 ER PT J AU Anzalone, SM Tilmont, E Boucenna, S Xavier, J Jouen, AL Bodeau, N Maharatna, K Chetouani, M Cohen, D AF Anzalone, Salvatore Maria Tilmont, Elodie Boucenna, Sofiane Xavier, Jean Jouen, Anne-Lise Bodeau, Nicolas Maharatna, Koushik Chetouani, Mohamed Cohen, David CA MICHELANGELO Study Grp TI How children with autism spectrum disorder behave and explore the 4-dimensional (spatial 3D+time) environment during a joint attention induction task with a robot SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Development; Social engagement; Joint attention; Social robots ID YOUNG-CHILDREN; SOCIAL ROBOTS; INDIVIDUALS; PEOPLE; CAREGIVERS; IMITATION; TODDLERS; THERAPY; SPEECH; ORIENT AB We aimed to compare, during a joint attention (JA) elicitation task, how children with autism spectrum disorder (ASD) and children with typical development (TD) behave and explore their 4 dimensional (meaning spatial 3D + time) when interacting with a human or with a robotic agent. We built a system that employed a Nao robot and a perception system based on a RGB-D sensor (Kinect) to capture social engagement cues. A JA induction experiment was performed in which children with ASD (N = 16) and matched TD children (N = 16) had a 3-mm interaction with the robot or with a therapist. Nao induced JA by gazing; by gazing and pointing; and by gazing, pointing and vocalizing at pictures. Both groups of children performed well with the therapist. However, with Nao, both groups had lower JA scores, and the children with ASD had a significantly lower score than the TD children. We found that (i) multimodal JA induction was more efficient in both groups; (ii) the 3D spatial world gaze exploration showed less accuracy; and (iii) the trunk position in ASD showed less stability in the 4 dimensions compared to TD controls. We conclude that, in ASD, JA skill depends on the interaction partner, and implies a higher motor and cognitive cost. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Anzalone, Salvatore Maria; Tilmont, Elodie; Boucenna, Sofiane; Jouen, Anne-Lise; Chetouani, Mohamed; Cohen, David] Univ Paris 06, Inst Syst Intelligents & Robot, F-75005 Paris, France. [Tilmont, Elodie; Xavier, Jean; Bodeau, Nicolas; Cohen, David] Grp Hosp Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, F-75013 Paris, France. [Tilmont, Elodie; Xavier, Jean; Bodeau, Nicolas; Cohen, David] Univ Paris 06, F-75013 Paris, France. [Maharatna, Koushik] Univ Southampton, Southampton, Hants, England. RP Anzalone, SM (reprint author), Univ Paris 06, Inst Syst Intelligents & Robot, Pyramide Tour 55,4 Pl Jussieu, F-75005 Paris, France. 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PD JUL PY 2014 VL 8 IS 7 BP 814 EP 826 DI 10.1016/j.rasd.2014.03.002 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600008 ER PT J AU Kristen, S Rossmann, F Sodian, B AF Kristen, Susanne Rossmann, Franziska Sodian, Beate TI Theory of own mind and autobiographical memory in adults with ASD SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Theory of mind; Autobiographical memory; Autism Spectrum Disorder ID AUTISM SPECTRUM DISORDER; HIGH-FUNCTIONING AUTISM; STRANGE STORIES TEST; ASPERGER-SYNDROME; EPISODIC MEMORY; AUTONOETIC CONSCIOUSNESS; SELF-AWARENESS; QUOTIENT AQ; CHILDREN; ADOLESCENTS AB While there is solid evidence of other-related theory of mind (TOM) deficits in autism, there is less research addressing self-related ToM impairments. To date, relations between self-related ToM and other cognitive skills related to representing own mental states such as autobiographical memory have scarcely been investigated. Thus, the purpose of this study was to investigate the differential relations of self-and other-related theory of mind skills and autobiographical memory in n = 20 adults with Autism Spectrum Disorder and n = 20 matched controls using standardized measures. The overall results indicated a specific relation between recalled episodic autobiographical memories on the episodic and semantic autobiographical memory interview and the performance on the mind-mindedness for oneself task in adults with ASD, which proved to be largely independent of verbal and nonverbal IQ. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Kristen, Susanne; Rossmann, Franziska; Sodian, Beate] Univ Munich, D-80802 Munich, Germany. RP Kristen, S (reprint author), Univ Munich, Dept Psychol, Leopoldstr 13, D-80802 Munich, Germany. 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PD JUL PY 2014 VL 8 IS 7 BP 827 EP 837 DI 10.1016/j.rasd.2014.03.009 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600009 ER PT J AU Kuo, CC Liang, KC Tseng, CC Gau, SSF AF Kuo, Ching-Chih Liang, Keng-Chen Tseng, Christine Chifen Gau, Susan Shur-Fen TI Comparison of the cognitive profiles and social adjustment between mathematically and scientifically talented students and students with Asperger's syndrome SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Mathematically and scientifically talented; Asperger's syndrome; Cognitive profiles; Social adjustment; Overexcitability traits ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; PSYCHOMETRIC PROPERTIES; RESPONSIVENESS SCALE; DIAGNOSTIC INTERVIEW; CHINESE VERSION; CHILDREN; INDIVIDUALS; ADOLESCENTS; OTHERS AB This study compared the cognitive profiles and social adjustment of mathematically and scientifically talented (MST) students and students with Asperger's syndrome (AS) as compared to typically developing students. The applied instruments were the Wechsler Adult Intelligence Scale, 3rd version, Me Scale II, Social Responsiveness Scale (SRS), Adult Autism Spectrum Quotient (AQ), and autism diagnostic interview-revised. Eighty-four male students, aged 16-26, were assigned to four groups according to a talent in mathematics and science, diagnosis of AS, and the IQ level. The results showed that the high-IQ MST group exhibited balanced development in cognitive and affective aspects, the average-IQ MST group demonstrated weakness in perceptual organization and working memory, and problems with social awareness and socialness, and the AS group had weakness in performance IQ particularly in digit symbol-coding and symbol search and a wide-range of autistic-like social deficits (SRS) and autistic trait (AQ), and reported lower empathetic and higher emotional and creative overexcitability. Our findings support differential cognitive profiles and social adjustment between the MST and AS groups, and the influence of IQ on these manifestations in MST students. More attention should be paid to the social difficulty of average-IQ MST students in addition to AS students. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Kuo, Ching-Chih] Natl Taiwan Normal Univ, Dept Special Educ, Taipei 106, Taiwan. [Liang, Keng-Chen; Gau, Susan Shur-Fen] Natl Taiwan Univ, Neurobiol & Cognit Sci Ctr, Dept Psychol, Taipei 100, Taiwan. [Liang, Keng-Chen; Gau, Susan Shur-Fen] Natl Taiwan Univ, Grad Inst Brain & Mind Sci, Taipei 100, Taiwan. [Tseng, Christine Chifen] Natl Taichung Univ Sci & Technol, Dept Appl English, Taichung 403, Taiwan. [Gau, Susan Shur-Fen] Natl Taiwan Univ Hosp & Coll Med, Dept Psychiat, Taipei 100, Taiwan. [Gau, Susan Shur-Fen] Natl Taiwan Univ, Sch Occupat Therapy, Coll Med, Taipei 100, Taiwan. 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C., 2005, STUDY OVEREXCITABILI NR 80 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUL PY 2014 VL 8 IS 7 BP 838 EP 850 DI 10.1016/j.rasd.2014.04.004 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600010 ER PT J AU Hagenmuller, F Rossler, W Wittwer, A Haker, H AF Hagenmuller, Florence Roessler, Wulf Wittwer, Amrei Haker, Helene TI Empathic resonance in Asperger syndrome SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Salivation; Autism spectrum disorder; Perception-action link; Contagion; Coping; Empathy ID TORONTO-ALEXITHYMIA-SCALE; SPECTRUM DISORDER; SEX-DIFFERENCES; AUTISM; INDIVIDUALS; SALIVATION; IMITATION; VOLUNTARY; CHILDREN; DEFICITS AB Reports on theory-of-mind deficits have led to the common belief that autism spectrum disorders (ASD) are associated with a lack of empathy. Resonance is a basic empathy-related process, linking two interacting individuals at the physiological level. Findings in ASD have been inconclusive regarding basic empathy. We investigated resonance at the autonomic level - the salivation-inducing effect of watching a person eating a lemon. Salivation-induction was assessed in 29 individuals with ASD and 28 control participants. Cotton rolls placed in the mouth were weighed before and after the video stimulation. Orientation to the stimulus was assessed with eye-tracking, autistic and empathic traits through self-reports. Group comparisons revealed lower salivation-induction in individuals with ASD. Linear regressions revealed different predictors of induction in each group: self-reported empathic fantasizing and age in ASD versus self-reported empathic concern plus orientation to the stimulus' face in the control. In both groups the social component was relevant: in ASD in terms of intellectual involvement with social contents and in controls in terms of the mere presence of a social vis-A-vis. Individuals with ASD may use explicitly acquired intellectual strategies whereas individuals with typical development can rely on intuitive processes for social responsivity. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Hagenmuller, Florence] Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, CH-8021 Zurich, Switzerland. [Hagenmuller, Florence; Roessler, Wulf; Wittwer, Amrei; Haker, Helene] Univ Zurich, Coll Helveticum, CH-8021 Zurich, Switzerland. [Hagenmuller, Florence; Roessler, Wulf; Wittwer, Amrei; Haker, Helene] ETH, Zurich, Switzerland. [Haker, Helene] Univ Zurich, Inst Biomed Engn, Translat Neuromodeling Unit, CH-8021 Zurich, Switzerland. [Roessler, Wulf] Univ Sao Paulo, Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo, Brazil. RP Hagenmuller, F (reprint author), Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, POB 1930, CH-8021 Zurich, Switzerland. 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PD JUL PY 2014 VL 8 IS 7 BP 851 EP 859 DI 10.1016/j.rasd.2014.04.008 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600011 ER PT J AU Lang, R Machalicek, W Rispoli, M O'Reilly, M Sigafoos, J Lancioni, G Peters-Scheffer, N Didden, R AF Lang, Russell Machalicek, Wendy Rispoli, Mandy O'Reilly, Mark Sigafoos, Jeff Lancioni, Giulio Peters-Scheffer, Nienke Didden, Robert TI Play skills taught via behavioral intervention generalize, maintain, and persist in the absence of socially mediated reinforcement in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Play; Stereotypy; Lag schedules; Behavioral intervention ID YOUNG-CHILDREN; PRETEND PLAY; VERBAL RESPONSIVENESS; SPECTRUM DISORDERS; SYMBOLIC PLAY; DISABILITIES; STEREOTYPY; LEISURE; LIFE; PRESCHOOLERS AB We measured generalization, maintenance and parent reports of child happiness in the context of a behavioral intervention to teach toy-play skills to three young children with autism. Lag schedules of reinforcement were implemented for two participants whose play did not initially generalize. The play skills intervention was conducted within the participants' early childhood classroom and the utility of teaching play as a means to reduce stereotypy within this setting was also evaluated. A multiple baseline design across participants demonstrated that play taught via behavioral intervention may be maintained after programmed reinforcement is discontinued, generalize across settings and toys (i.e., response and stimulus generalization), and occasion a decrease in stereotypy. Further, the occurrence of play in the absence of socially mediated reinforcement suggested that play taught via behavioral interventions may come to be automatically reinforced. Finally, parent responses on rating scales suggested that two of the participants were happier, in a better mood, and were more interested in appropriate toy-play following behavioral intervention. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Lang, Russell] SW Texas State Univ, Clin Autism Res Evaluat & Support, San Marcos, TX 78666 USA. [Machalicek, Wendy] Univ Oregon, Coll Educ, Eugene, OR 97403 USA. [Rispoli, Mandy] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. [Lang, Russell; O'Reilly, Mark] Univ Texas Austin, Meadows Ctr Preventing Educ Risk, Austin, TX 78712 USA. [Sigafoos, Jeff] Victoria Univ Wellington, Sch Educ Psychol, Wellington, New Zealand. [Lancioni, Giulio] Univ Bari, Dept Neurosci & Sense Organs, Bari, Italy. [Peters-Scheffer, Nienke; Didden, Robert] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. RP Lang, R (reprint author), Dept Curriculum & Instruct, 601 Univ Dr, San Marcos, TX 78666 USA. 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TI Age of autism spectrum disorder diagnosis is associated with child's variables and parental experience SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Age of diagnosis; Social impairments; Restricted and repetitive behaviors; Developmental regression; Adaptive functioning; First born child ID YOUNG-CHILDREN; FOLLOW-UP; REGRESSION; IDENTIFICATION; RECOGNITION; RECURRENCE; BEHAVIORS; SEVERITY; SAMPLE; RISK AB Early diagnosis of autism spectrum disorder (ASD) is highly important as it enables an early start to intervention. The current study examined familial (parental ages; education; having an older sibling) and child (gender; reported and observed autism symptoms severity; adaptive skills) related variables that might predict the age of ASD diagnosis. The study included 551 participants, age range 15-72 months, diagnosed with ASD who underwent comprehensive medical and behavioral assessment using standardized tests. Of the child's examined variables, the severity of the social interaction impairment reported by the parents and having a history of developmental regression was associated with an earlier age of ASD diagnosis. In contrast, the severity of the restricted and repetitive behaviors was associated with delayed age of ASD diagnosis. Vineland Adaptive Behavior Scales scores lower or higher than the group's mean (70 points) were associated with a relatively delayed age of ASD diagnosis. Of the familial variables, only having an older sibling was associated with an earlier diagnosis. Professionals should be aware that subtle signs of ASD, developmental delay and close to normal adaptive functioning might delay age of ASD diagnosis. Educating parents on "red flags" for ASD and periodic surveillance in early childhood are important. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Mishaal, Ram A.; Ben-Itzchak, Esther; Zachor, Ditza A.] Assaf Harofeh Med Ctr, Dept Pediat, Autism Ctr, IL-70300 Zerifin, Israel. [Ben-Itzchak, Esther] Ariel Univ, Dept Commun Disorders, IL-40700 Ariel, Israel. [Zachor, Ditza A.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Zachor, DA (reprint author), 12 Hatizmoret St, IL-55556 Kiryat Ono, Israel. 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Autism Spectr. Disord. PD JUL PY 2014 VL 8 IS 7 BP 873 EP 880 DI 10.1016/j.rasd.2014.04.001 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600013 ER PT J AU Chien, YL Gau, SSF Chiu, YN Tsai, WC Shang, CY Wu, YY AF Chien, Yi-Ling Gau, Susan Shur-Fen Chiu, Yen-Nan Tsai, Wen-Che Shang, Chi-Yung Wu, Yu-Yu TI Impaired sustained attention, focused attention, and vigilance in youths with autistic disorder and Asperger's disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autistic disorder; Asperger's disorder; ADHD; Oppositional symptoms; Attention performance; Continuous performance test ID DEFICIT HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; CONTINUOUS PERFORMANCE-TEST; DEFICIT/HYPERACTIVITY DISORDER; PSYCHOMETRIC PROPERTIES; SPECTRUM DISORDERS; CHINESE VERSION; EXECUTIVE FUNCTIONS; CHILDREN AB The study compared the attention-deficit/hyperactivity disorder (ADHD) related clinical symptoms and a wide-ranging attention performance in 216 youths with autistic disorder (autism), 138 youths with Asperger's disorder (AD) and 255 typically-developing youths. The diagnosis of autism and AD were made based on the clinical assessments according to the DSM-IV criteria and confirmed by the Autism Diagnostic Interview-Revised. All the participants were assessed with the Conners' Continuous Performance Test (CCPT) and the questionnaires about ADHD, oppositional, and autistic symptoms. All indices of the CCPT were analyzed based on a recently developed factor structure, including focused attention, cognitive impulsivity, sustained attention, and vigilance. We found that compared with typically-developing youths, youths with autism and AD showed more inattentive, hyperactive/impulsive, and oppositional symptoms, and performed worse in focused attention and sustained attention as assessed by the CCPT. Youths with AD also showed more oppositional symptoms than youths with autism. Moreover, youths with autism had poorer focused attention than youths with AD; but, youths with AD had more impaired sustained attention. Our results validate different manifestations of ADHD-related symptoms and attention performance between youths with autism and youths with AD and suggest intervention for youths with autism spectrum disorders should consider these specific measures. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Chien, Yi-Ling; Gau, Susan Shur-Fen; Chiu, Yen-Nan; Tsai, Wen-Che; Shang, Chi-Yung] Natl Taiwan Univ Hosp & Coll Med, Dept Psychiat, Taipei 10002, Taiwan. [Chien, Yi-Ling; Gau, Susan Shur-Fen] Natl Taiwan Univ, Coll Med, Grad Inst Brain & Mind Sci, Taipei 10764, Taiwan. [Chien, Yi-Ling; Gau, Susan Shur-Fen] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10764, Taiwan. [Wu, Yu-Yu] Chang Gung Univ, Coll Med, Linkou Med Ctr, Dept Psychiat,Chang Gung Mem Hosp, Taoyuan, Taiwan. RP Gau, SSF (reprint author), Natl Taiwan Univ Hosp & Coll Med, Dept Psychiat, 7 Chung Shan South Rd, Taipei 10002, Taiwan. 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PD JUL PY 2014 VL 8 IS 7 BP 881 EP 889 DI 10.1016/j.rasd.2014.04.006 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600014 ER PT J AU Goin-Kochel, RP Esler, AN Kanne, SM Hus, V AF Goin-Kochel, Robin P. Esler, Amy N. Kanne, Stephen M. Hus, Vanessa TI Developmental regression among children with autism spectrum disorder: Onset, duration, and effects on functional outcomes SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Regression; Skill loss; Cognition; Adaptive functioning; Outcomes ID LANGUAGE; PHENOTYPE; PATTERNS AB Studies using varied methods report that developmental regression occurs in a sizeable proportion of children with autism spectrum disorder (ASD). Findings are equivocal as to whether regression is associated with poorer cognitive and adaptive functioning. This study examined retrospective parent report in 2105 Simons Simplex Collection participants with ASD. Children were classified as having "full" or "subthreshold" losses on language and/or other skills using items from the Autism Diagnostic Interview-Revised (ADI-R) and a supplemental interview to capture more subtle regressions. Overall, 36.9% of children had some type of regression (27.8% language, 27.0% other-skill loss), with the supplemental interview capturing 11.7% of losses that would have been missed using the ADI-R alone. This figure is consistent with previous parent-report studies but lower than clinician-observed rates in prospective investigations. Early language losses either full or subthreshold and full other-skill losses appear to be associated with more deleterious outcomes by middle childhood. Findings may signify the need for more immediate and/or intense therapies for children who have even minor skill losses, particularly in language skills. 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McCormack, Teresa Carty, Clare Coyle, Lisa Crozier, Naomi Robinson, Johanna McPhillips, Martin TI Attention during social interaction in children with autism: Comparison to specific language impairment, typical development, and links to social cognition SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Specific language impairment; Eye-tracking; Social interaction; Implicit mentalising ID SPECTRUM DISORDERS; WILLIAMS-SYNDROME; EYE-MOVEMENTS; COMMUNICATION IMPAIRMENTS; ATYPICAL DEVELOPMENT; GAZE AVERSION; TRACKING; FACES; MIND; INDIVIDUALS AB Eye-tracking studies have shown how people with autism spend significantly less time looking at socially relevant information on-screen compared to those developing typically. This has been suggested to impact on the development of socio-cognitive skills in autism. We present novel evidence of how attention atypicalities in children with autism extend to real-life interaction, in comparison to typically developing (TD) children and children with specific language impairment (SLI). We explored the allocation of attention during social interaction with an interlocutor, and how aspects of attention (awareness checking) related to traditional measures of social cognition (false belief attribution). We found divergent attention allocation patterns across the groups in relation to social cognition ability. Even though children with autism and SLI performed similarly on the socio-cognitive tasks, there were syndrome-specific atypicalities of their attention patterns. Children with SLI were most similar to TD children in terms of prioritising attention to socially pertinent information (eyes, face, awareness checking). Children with autism showed reduced attention to the eyes and face, and slower awareness checking. This study provides unique and timely insight into real-world social gaze (a)typicality in autism, SLI and typical development, its relationship to socio-cognitive ability, and raises important issues for intervention. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Hanley, Mary; Riby, Deborah M.] Univ Durham, Dept Psychol, Durham DH1 3LE, England. [McCormack, Teresa; Carty, Clare; Coyle, Lisa; Crozier, Naomi; Robinson, Johanna; McPhillips, Martin] Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland. RP Hanley, M (reprint author), Univ Durham, Dept Psychol, Sci Labs, S Rd, Durham DH1 3LE, England. 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TI The relationship between ethnicity and age of first concern in toddlers with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; First concern; Ethnicity/race ID INTENSIVE BEHAVIORAL INTERVENTION; PERVASIVE DEVELOPMENTAL DISORDER; YOUNG-CHILDREN; FOLLOW-UP; PDD-NOS; DIAGNOSIS; INFANTS; RECOGNITION; ASD; DISABILITIES AB The current study examined the relationship between ethnicity and the age at which parents first become concerned about their children's development in 1478 toddlers with autism spectrum disorder (ASD) and atypical development. Based on the current findings, there were no racial/ethnic differences in age of parent's first concerns. Caregivers of toddlers with ASD first developed concerns around the same time independent of which ethnic groups they belong to. 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PD JUL PY 2014 VL 8 IS 7 BP 925 EP 932 DI 10.1016/j.rasd.2014.04.003 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AI8UX UT WOS:000337203600018 ER PT J AU Klein, BY Tamir, H Hirschberg, DL Glickstein, SB Ludwig, RJ Welch, MG AF Klein, Benjamin Y. Tamir, Hadassah Hirschberg, David L. Glickstein, Sara B. Ludwig, Robert J. Welch, Martha G. TI Oxytocin modulates markers of the unfolded protein response in Caco2BB gut cells SO CELL STRESS & CHAPERONES LA English DT Article DE Autism spectrum disorder; Inflammatory bowel disease (IBD); Crohn's disease; Ulcerative colitis; Signaling; Translation factors; X-box protein 1; Simon ID ENDOPLASMIC-RETICULUM STRESS; INITIATION-FACTOR EIF2-ALPHA; INFLAMMATORY-BOWEL-DISEASE; ER STRESS; TRANSLATIONAL CONTROL; MAMMALIAN TARGET; MESSENGER-RNA; INTESTINAL EPITHELIUM; TRANSCRIPTION FACTOR; AUTISTIC DISORDER AB We have shown that oxytocin receptor (OTR) expression in neonatal rat enterocytes is robust from birth to weaning, but OTR function during this period is unknown. We previously reported that oxytocin (OT) stimulation of Caco2BB cells (enterocytes in vitro) inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling. The unfolded protein response (UPR) is known to protectively reduce translation during endoplasmic reticulum (ER) stress. Because the mTORC1 pathway is linked to cellular stress, we investigated markers of UPR in OT-stimulated Caco2BB cells. We report that OT modulates several factors involved in sensing and translation of ER stress. High OT (62.5 nM) reduced translation initiation factor 4E-BP1 phosphorylation (Ser65), which is known to inhibit cap-dependent translation via its rate-limiting eukaryotic translation initiation factor 4E (eIF4E). Importantly, high OT increased phosphorylation of eukaryotic translation initiation factor 2a (eIF2a) phospho-Ser51, which inhibits eIF2a. High OT also increased protein kinase RNA-like endoplasmic reticulum kinase phosphorylation, a sensor of ER stress and a kinase of eIF2a. Both high and low OT activated inositol requiring enzyme1 (IRE1), which generates the transcription factor X-box binding protein 1 (XBP1) and induces the UPR. We also show that OT modulates XBP1 splicing and induces tribbles 3 (TRIB3; a negative regulator of Akt and protein involved in autophagy) and immunoglobulin binding protein (BiP; ER-chaperone). Taken together, these results indicate that OT modulates sensors of ER stress and autophagy. These findings support our hypothesis that transiently elevated OTR expression in neonatal gut may serve a protective function during a critical postnatal developmental period. C1 [Klein, Benjamin Y.; Ludwig, Robert J.; Welch, Martha G.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Tamir, Hadassah; Hirschberg, David L.; Welch, Martha G.] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Hirschberg, David L.] Columbia Univ Coll Phys & Surg, Ctr Infect & Immunol, New York, NY 10032 USA. [Tamir, Hadassah] New York State Psychiat Inst & Hosp, Div Mol Imaging & Neuropathol, New York, NY 10032 USA. [Glickstein, Sara B.] EB Sci, Oakland, CA 94611 USA. [Klein, Benjamin Y.; Welch, Martha G.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Klein, BY (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 40, New York, NY 10032 USA. EM bk2348@columbia.edu; mgw13@columbia.edu FU Einhorn Family Charitable Trust [UL1 RR024156] FX We thank Chris Heger for Simon (TM) automated western blotting consultation and analysis, as well as with help in manuscript preparation. We thank Maurice Manning for supplying the oxytocin antagonist. The research was funded by the Einhorn Family Charitable Trust (UL1 RR024156). 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Connor-Stroud, Fawn Landgraf, Rainer Young, Larry J. Parr, Lisa A. TI Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Oxytocin; Vasopressin; Social cognition; Intranasal; Autism; Rhesus monkey ID AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; VASOPRESSIN RELEASE; PLASMA OXYTOCIN; SOCIAL-BEHAVIOR; BRAIN; NASAL; BLOOD; NEUROPEPTIDES; INTRANUCLEAR AB Intranasal (IN) administration is a widely used method for examining the effect of oxytocin (OT) on social behavior and cognition in healthy subjects and psychiatric populations. IN-OT in humans enhances trust, emotional perception, and empathetic behavior and is under investigation as a potential pharmacotherapy to enhance social functioning in a variety of neuropsychiatric disorders, including autism spectrum disorders (ASD). Nonhuman primates (NHP) are an important model for understanding the effect of OT on social cognition, its neural mechanisms, and the development of IN-OT as a pharmacotherapy for treating social deficits in humans. However, NHP and even some human populations, such as very young infants and children, cannot easily follow the detailed self-administration protocol used in the majority of human IN-OTstudies. Therefore, we evaluated the efficacy of several OT-administration routes for elevating central OT concentrations in rhesus macaques. First, we examined the effect of IN and intravenous (IV) routes of OT administration on concentrations of OT and vasopressin (AVP) in plasma and lumbar CSF. Second, we examined these same measures in monkeys after an aerosolized (AE) OT delivery route. All three administration routes significantly increased plasma OT concentrations, but only the AE-OT route significantly increased concentrations of CSF OT. No route affected concentrations of AVP in plasma or CSF. This study confirms that the AE route is the most effective method for increasing central OT concentrations in monkeys, and may also be an effective route, alternative to IN, for administering OT to some human populations. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Modi, Meera E.; Young, Larry J.; Parr, Lisa A.] Emory Univ, Silvio O Conte Ctr Oxytocin & Social Cognit, Ctr Translat Social Neurosci, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Modi, Meera E.; Connor-Stroud, Fawn; Young, Larry J.; Parr, Lisa A.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Landgraf, Rainer] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Modi, ME (reprint author), 610 Main St, Cambridge, MA 02139 USA. EM meera.modi@pfizer.com FU NSF Center for Behavioral Neuroscience Pilot Grant (LAP); Emory Neuroscience Initiative Seed Grant; Center for Translational Social Neuroscience Pilot Grant; NIH [MH068791, MH064692, P50MH100023]; National Center for Research Resources YNPRC [P51RR165]; Office of Research Infrastructure Programs/OD [P510D11132] FX The authors would like to thank the YNPRC veterinary staff for their vital participation in the collection of samples and Dr. Mar Sanchez for her advice and assistance. We would also like to acknowledge funding support from NSF Center for Behavioral Neuroscience Pilot Grant (LAP), Emory Neuroscience Initiative Seed Grant (MEM, LJY, LAP), Center for Translational Social Neuroscience Pilot Grant (LAP, LJY), NIH MH068791 (LAP) and MH064692 (LJY), P50MH100023 (LJY and LAP) and National Center for Research Resources P51RR165 to YNPRC, which is currently supported by the Office of Research Infrastructure Programs/OD P510D11132. 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Inoue, Kiyoshi Smith, Aaron L. Goodman, Mark M. Young, Larry J. TI The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta) SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Oxytocin receptor; Neuropeptide; Neuroanatomy; Nonhuman primate; Autism ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; GUIDED SACCADE TASKS; SUPERIOR COLLICULUS; SOCIAL-BEHAVIOR; MICROTUS-OCHROGASTER; INTRANASAL OXYTOCIN; PRIMATE BRAIN; VASOPRESSIN; NEURONS; EXPRESSION AB The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin la receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Freeman, Sara M.; Inoue, Kiyoshi; Smith, Aaron L.; Young, Larry J.] Emory Univ, Yerkes Natl Primate Res Ctr, Silvio O Conte Ctr Oxytocin & Social Cognit, Dept Psychiat & Behav Sci,Ctr Translat Social Neu, Atlanta, GA 30029 USA. [Smith, Aaron L.; Goodman, Mark M.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30029 USA. RP Freeman, SM (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr BMB, One Shields Ave, Davis, CA 95616 USA. EM smfreem@ucdavis.edu FU NIH grants [MH090776, 1P50MH100023]; Office of Research Infrastructure Programs/OD [P510D011132, P51RR000165]; [T32MH073525-06] FX This work was supported by NIH grants MH090776 and 1P50MH100023 to L.J.Y. Training support for S.M.F was provided by T32MH073525-06. Additional support was provided by Office of Research Infrastructure Programs/OD P510D011132 (formerly NCRR P51RR000165) to YNPRC. 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J. Sala-Hamrick, K. J. Carducci, N. M. Frazer, M. Halsey, K. E. Sutton, M. A. Dolan, D. F. Murphy, G. G. Todd, P. K. TI Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Fragile X; Premutation carrier; Prepulse inhibition; Sensorimotor gating ID PREPULSE INHIBITION; STARTLE RESPONSE; HEARING-LOSS; BEHAVIORAL-PHENOTYPE; MENTAL-RETARDATION; C57BL/6J MICE; MOUSE MODEL; AUTISM; ABNORMALITIES; PLASTICITY AB Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG 10 mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms. Published by Elsevier B.V. C1 [Halsey, K. E.; Dolan, D. F.] Kresge Hearing Res Inst, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI USA. [Sutton, M. A.; Murphy, G. G.] Mol & Behav Neurosci Inst, Ann Arbor, MI USA. RP Todd, PK (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA. EM petertod@umich.edu FU National Institutes of Mental Health [F31MH097451]; National Fragile X Foundation FX We thank Peter Ghisleni for technical assistance. CGG KI mice were donated by Karen Usdin (NIH). Fmr1 KO mice were obtained from Cara Westmark (University of Wisconsin) and Jim Malter (UT Southwestern). This work was supported by the National Institutes of Mental Health (F31MH097451) to AJR; the National Fragile X Foundation student fellowship to MF; core testing facilities provided by NIH (P30 DC05188) to KEH and DFD; National Institute on Aging (R01AG028488) to GGM; and by the Veterans Administration (BLRD #1I01BX001689) and NIH (1K08NS069809) to PKT. 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Brain Res. PD JUL 1 PY 2014 VL 267 BP 42 EP 45 DI 10.1016/j.bbr.2014.03.013 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AI2UK UT WOS:000336713400007 PM 24657592 ER PT J AU Dejanovic, BL Lal, D Catarino, CB Arjune, S Belaidi, AA Trucks, H Vollmar, C Surges, R Kunz, WS Motameny, S Altmuller, J Kohler, A Neubauer, BA Nurnberg, P Noachtar, S Schwarz, G Sander, T AF Dejanovic, Boris Lav Lal, Dennis Catarino, Claudia B. Arjune, Sita Belaidi, Abdel A. Trucks, Holger Vollmar, Christian Surges, Rainer Kunz, Wolfram S. Motameny, Susanne Altmueller, Janine Koehler, Anna Neubauer, Bernd A. Nuernberg, Peter Noachtar, Soheyl Schwarz, Gunter Sander, Thomas CA EPICURE Consortium TI Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Idiopathic generalized epilepsy; Microdeletion; GPHN; Gephyrin ID MOLYBDENUM COFACTOR DEFICIENCY; TRANSCRANIAL MAGNETIC STIMULATION; CLUSTERING PROTEIN GEPHYRIN; MOTOR CORTEX EXCITABILITY; GABA(A) RECEPTOR SUBTYPES; DIRECT BINDING; NEURODEVELOPMENTAL DISEASE; 16P13.11 PREDISPOSE; GAMMA-2 SUBUNIT; DOWN-REGULATION AB Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and gamma-aminobutyric acid type-A receptors (GABA(A)Rs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have been associated with neurodevelopmental disorders including autism spectrum disorder, schizophrenia and epileptic seizures. Here we report the identification of novel exonic GPHN microdeletions in two patients with idiopathic generalized epilepsy (ICE), representing the most common group of genetically determined epilepsies. The identified GPHN microdeletions involve exons 5-9 (Delta 5-9) and 2-3 (Delta 2-3), both affecting the gephyrin G-domain. Molecular characterization of the GPHN Delta 5-9 variant demonstrated that it perturbs the clustering of regular gephyrin at inhibitory synapses in cultured mouse hippocampal neurons in a dominant-negative manner, resulting in a significant loss of gamma(2)-subunit containing GABAARs. GPHN Delta 2-3 causes a frameshift resulting in a premature stop codon (p.V22Gfs*7) leading to haplo-insufficiency of the gene. Our results demonstrate that structural exonic microdeletions affecting the GPHN gene constitute a rare genetic risk factor for IGE and other neuropsychiatric disorders by an impairment of the GABAergic inhibitory synaptic transmission. (C) 2014 Published by Elsevier Inc. C1 [Dejanovic, Boris Lav; Arjune, Sita; Belaidi, Abdel A.; Koehler, Anna; Schwarz, Gunter] Univ Cologne, Inst Biochem, Dept Chem, D-50674 Cologne, Germany. [Lal, Dennis; Trucks, Holger; Motameny, Susanne; Altmueller, Janine; Nuernberg, Peter; Sander, Thomas] Univ Cologne, CCG, D-50931 Cologne, Germany. [Lal, Dennis; Schwarz, Gunter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany. [Lal, Dennis; Neubauer, Bernd A.] Univ Med Ctr Giessen & Marburg, Dept Neuropediat, D-35392 Giessen, Germany. [Vollmar, Christian; Noachtar, Soheyl] Univ Munich, Dept Neurol, Epilepsy Ctr, D-81377 Munich, Germany. [Surges, Rainer; Kunz, Wolfram S.] Univ Clin Bonn, Dept Epileptol, D-53105 Bonn, Germany. [Nuernberg, Peter; Schwarz, Gunter] Univ Cologne, Ctr Mol Med CMMC, D-50931 Cologne, Germany. RP Schwarz, G (reprint author), Univ Cologne, Inst Biochem, Zulpicher Str 47, D-50674 Cologne, Germany. EM gschwarz@uni-koeln.de; thomas.sander@uni-koeln.de RI baykan, betul/J-5307-2014; Catarino, Claudia/A-7719-2010 OI Catarino, Claudia/0000-0002-6528-7570 FU European Community [LSHM-CT-2006-037315]; German Research Foundation (DFG) [NE416/5-1, SA434/5-1, NU50/8-1]; German Federal Ministry of Education and Research; National Genome Research Network [NGENplus: EMINet] [01GS08120, 01GS08121, 01DL12011]; PopGenbiobank; Center for Molecular Medicine Cologne; Fonds der Chemischen Industrie; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; State of Bavaria; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; [SFB635] FX This work was supported by grants from the European Community [FP6 Integrated Project EPICURE, grant LSHM-CT-2006-037315 to T.S.], the German Research Foundation (DFG) within the EUROCORES Programme EuroEPINOMICS [grants NE416/5-1 to B.N., SA434/5-1 to T.S., NU50/8-1 to P.N.], the SFB635 [grant All to G.S.]; the German Federal Ministry of Education and Research, National Genome Research Network [NGENplus: EMINet, grants 01GS08120 to T.S., and 01GS08121 to P.N.; IntenC, grant 01DL12011 to T.S.]: the PopGen biobank [grant to A.F.],the Center for Molecular Medicine Cologne [to G.S.] and the Fonds der Chemischen Industrie [to G.S.]. The PopGen project received infrastructure support through the German Research Foundation excellence cluster "Inflammation at Interfaces". The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria; this research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. 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Dis. PD JUL PY 2014 VL 67 BP 88 EP 96 DI 10.1016/j.nbd.2014.02.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AH9PU UT WOS:000336475100010 PM 24561070 ER PT J AU Ben-Sasson, A Gill, SV AF Ben-Sasson, Ayelet Gill, Simone V. TI Motor and language abilities from early to late toddlerhood: Using formalized assessments to capture continuity and discontinuity in development SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE MSEL; Developmental tests; Developmental change; Toddler; Discontinuity; ASD ID AUTISM SPECTRUM DISORDER; FOLLOW-UP; CHILDREN; INFANTS; STABILITY; CHILDHOOD; VARIABILITY; OUTCOMES; RISK AB Developmental tests reflect the premise that decreases in skills over time should be a sign of atypical development. In contrast, from a psychological perspective, discontinuity may be viewed as a normal part of typical development. This study sought to describe the variability in patterns of continuity and discontinuity in developmental scores over time. Seventy-six toddlers (55% boys) from a larger screening study were evaluated at 13 and 30 months using the Mullen Scales of Early Development (MSEL) in five areas: gross motor, fine motor, visual perception, receptive language, and expressive language. Parents completed the First Year Inventory (FYI) at 12 months as well. At 30 months, 23.68% of the sample received a clinical diagnosis (e.g., developmental delay, autism spectrum disorder [ASD]). Toddlers were classified as stable, increasing, or decreasing by at least 1.5 standard deviations (SD) on their scores in each of the five MSEL areas from 13 to 30 months. Between 3.9% and 51.3% of the sample was classified as increasing and 0-23.7% as decreasing across areas. Decreases in motor areas were associated with increases in language areas. None of the toddlers showed decreases greater than 1.5 SD on their MSEL composite scores. There was no single pattern that characterized a certain diagnosis. Higher FYI sensory-regulatory risk was associated with decreases in gross motor. Lower FYI risk was linked with increases in receptive language. Developmental discontinuity in specific developmental areas was the rule rather than the exception. Interpretations of decreases in developmental levels must consider concurrent increases in skill during this emerging period. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ben-Sasson, Ayelet] Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-31905 Haifa, Israel. [Gill, Simone V.] Boston Univ, Coll Hlth & Rehabil Sci, Sargent Coll, Dept Occupat Therapy, Boston, MA 02215 USA. RP Ben-Sasson, A (reprint author), Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-31905 Haifa, Israel. 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Riley, Catharine Bolen, Julie Bishop, Ellen Raspa, Melissa Bailey, Donald B., Jr. TI A comparison of family financial and employment impacts of fragile X syndrome, autism spectrum disorders, and intellectual disability SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Fragile X syndrome; Intellectual disability; Autism spectrum disorders; Caregiver impacts ID NATIONAL PROFILE; CHILDHOOD AUTISM; UNITED-STATES; DOWN-SYNDROME; CHILDREN; HEALTH; CARE; BURDEN; POPULATION; VARIABLES AB This study compares the family financial and employment impacts of having a child with fragile X syndrome (FXS), autism spectrum disorder (ASD), or intellectual disabilities (ID). Data from a 2011 national survey of families of children with FXS were matched with data from the National Survey of Children with Special Health Care Needs 2009-2010 to form four analytic groups: children with FXS (n = 189), children with special health care needs with ASD only (n = 185), ID only (n= 177), or both ASD and ID (n = 178). Comparable percentages of parents of children with FXS (60%) and parents of children with both ASD and ID (52%) reported that their families experienced a financial burden as a result of the condition, both of which were higher than the percentages of parents of children with ASD only (39%) or ID only (29%). Comparable percentages of parents of children with FXS (40%) and parents of children with both ASD and ID (46%) reported quitting employment because of the condition, both of which were higher than the percentages of parents of children with ID only (25%) or ASD only (25%). In multivariate analyses controlling for co-occurring conditions and functional difficulties and stratified by age, adjusted odds ratios for the FXS group aged 12-17 years were significantly elevated for financial burden (2.73, 95% CI 1.29-5.77), quitting employment (2.58, 95% CI 1.18-5.65) and reduced hours of work (4.34, 95% CI 2.08-9.06) relative to children with ASD only. Among children aged 5 11 years, the adjusted odds ratios for the FXS group were elevated but statistically insignificant for financial burden (1.63, 95% CI 0.85-3.14) and reducing hours of work (1.34, 95% CI 0.68-2.63) relative to children with ASD only. Regardless of condition, co-occurring anxiety or seizures, limits in thinking, reasoning, or learning ability, and more irritability were significantly associated with more caregiver financial and employment impacts. Proper management of anxiety or seizures and functional difficulties of children with FXS or other developmental disabilities may be important in alleviating adverse family caregiver impacts. Published by Elsevier Ltd. C1 [Ouyang, Lijing; Grosse, Scott D.; Riley, Catharine; Bolen, Julie] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Bishop, Ellen; Raspa, Melissa; Bailey, Donald B., Jr.] RTI Int, Res Triangle Pk, NC USA. RP Ouyang, LJ (reprint author), 1600 Clifton Rd NE,Mail Stop E-88, Atlanta, GA 30329 USA. EM louyang@cdc.gov CR Aman M., 1994, ABERRANT BEHAV CHECK Bailey D. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1518 EP 1527 DI 10.1016/j.ridd.2014.04.009 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500008 PM 24755230 ER PT J AU Poon, KK Ooi, N Bull, R Bailey, DB AF Poon, Kenneth K. Ooi, Nona Bull, Rebecca Bailey, Donald B., Jr. TI Psychometric validation of the Family Outcome Survey-Revised in Singapore SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Early childhood intervention; Family Outcomes Survey-Revised; Singapore ID AUTISM SPECTRUM DISORDERS; EARLY INTERVENTION; CHILDREN; DISABILITIES; DIAGNOSIS; SERVICES; PARENTS; FATHERS; MOTHERS; STRESS AB This study sought to examine the construct validity of the Family Outcomes Survey-Revised (FOS-R) in Singapore, describe the extent to which family outcomes of early childhood intervention (ECI) are attained, and obtain caregivers perception on the extent to which ECI has served their needs. The FOS-R was translated into Chinese (simplified) and Malay for use in Singapore. Bilingual (i.e., English-Chinese and English-Malay) versions of the instrument were distributed to caregivers of young children with disabilities receiving ECI in four centers in Singapore. A total of 291 surveys were available for analyses (response rate of 43.1%). Confirmatory factor analyses indicated that there was a fit between the current data set and the FOS-R structure proposed by the developers. Overall, the participants reported moderately high attainment of family outcomes. They also reported that the ECI programs were mostly helpful. Other aspects of the cross-cultural application of instruments were considered and implications for local service provision as well as directions for future research were discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Poon, Kenneth K.; Ooi, Nona; Bull, Rebecca] Nanyang Technol Univ, Natl Inst Educ, Singapore 637616, Singapore. 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PD JUL PY 2014 VL 35 IS 7 BP 1534 EP 1543 DI 10.1016/j.ridd.2014.03.047 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500010 PM 24763378 ER PT J AU Tsai, WH Hwang, YS Hung, TY Weng, SF Lin, SJ Chang, WT AF Tsai, Wen-Hui Hwang, Yea-Shwu Hung, Te-Yu Weng, Shih-Feng Lin, Shio-Jean Chang, Wen-Tsan TI Association between mechanical ventilation and neurodevelopmental disorders in a nationwide cohort of extremely low birth weight infants SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Cerebral palsy; Extremely low birth weight infants; Intellectual disability; Mechanical ventilation ID DEFICIT-HYPERACTIVITY DISORDER; NEONATAL RESEARCH NETWORK; POSITIVE AIRWAY PRESSURE; CEREBRAL-PALSY; PRETERM INFANTS; RISK-FACTORS; BRONCHOPULMONARY DYSPLASIA; INTELLECTUAL DISABILITY; SEX STRATIFICATIONS; HEALTH-INSURANCE AB Mechanical ventilation for preterm infants independently contributes to poor neurodevelopmental performance. However, few studies have investigated the association between the duration of mechanical ventilation and the risk for various developmental disorders in extremely low birth weight (ELBW) (<1000 g) infants. Using a large nationwide database, we did a 10-year retrospective follow-up study to explore the effect of mechanical ventilation on the incidence of cerebral palsy (CP), autism spectrum disorder (ASD), intellectual disability (ID), and attention-deficit/hyperactivity disorder (ADHD) in ELBW infants born between 1998 and 2001. Seven hundred twenty-eight ELBW infants without diagnoses of brain insults or focal brain lesions in the initial hospital stay were identified and divided into three groups (days on ventilator: <= 2, 3-14, >= 15 days). After adjusting for demographic and medical factors, the infants in the 15 days group had higher risks for CP (adjusted hazard ratio: 2.66; 95% confidence interval: 1.50-4.59; p < 0.001) and ADHD (adjusted hazard ratio: 1.95; 95% confidence interval: 1.02-3.76; p < 0.05), than did infants in the 2 days group. The risk for ASD or ID was not significantly different between the three groups. We conclude that mechanical ventilation for 15 days increased the risk for CP and ADHD in ELBW infants even without significant neonatal brain damage. Developing a brain-protective respiratory support strategy in response to real-time cerebral hemodynamic and oxygenation changes has the potential to improve neurodevelopmental outcomes in ELBW infants. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tsai, Wen-Hui] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 701, Taiwan. [Tsai, Wen-Hui] Chi Mei Med Ctr, Div Neonatol, Tainan 710, Taiwan. [Hwang, Yea-Shwu] Natl Cheng Kung Univ, Coll Med, Dept Occupat Therapy, Tainan 701, Taiwan. [Hung, Te-Yu; Lin, Shio-Jean] Chi Mei Med Ctr, Dept Pediat, Tainan 710, Taiwan. [Weng, Shih-Feng] Chi Mei Med Ctr, Dept Med Res, Tainan 710, Taiwan. [Chang, Wen-Tsan] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 701, Taiwan. [Chang, Wen-Tsan] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan. RP Chang, WT (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, 1 Univ Rd, Tainan 701, Taiwan. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1544 EP 1550 DI 10.1016/j.ridd.2014.03.048 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500011 PM 24769371 ER PT J AU Hsu, CF AF Hsu, Ching-Fen TI Modality effect on contextual integration in people with Williams syndrome SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Modality effect; Contextual integration; Central coherence; Syndrome-general deficiency; Williams syndrome ID INFORMATION INTEGRATION; COHERENCE; AUTISM; WEAK AB In this study meaningful social stimuli were used as probes in a task requiring the judgment of semantic appropriateness to investigate contextual integration ability to test the ability of people with Williams syndrome (WS) to integrate information, as opposed to the use of meaningless syllables in audiovisual studies (the McGurk effect). Participants were presented with background auditory primes followed by targets that were either congruent or incongruent with the prime. Two modes of target were presented: a visual target (AV task) or an auditory target (AA task). Participants were asked to respond yes to contextually appropriate pairs and no to those that were contextually inappropriate. The congruency effect was measured as an index of successful central coherence. Similar to normally developing controls, people with WS showed shorter response latencies and greater accuracy in recognizing congruent pairs compared with incongruent pairs. Their performance did not differ from that of controls matched by mental age, but was inferior to that of controls matched by chronological age. The results revealed generalized contextual integration for auditory primes in both tasks, consistent with previous studies using visual presentation of social-related stimuli in people with WS (Hsu, 2013a, 2013c). 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TI The effect of motor load on planning and inhibition in developmental coordination disorder SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Executive function; Developmental coordination disorder; Planning; Inhibition; Motor development ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; AUTISM SPECTRUM DISORDERS; WORKING-MEMORY; CHILDREN; PROFILES; PERFORMANCE; DYSFUNCTION; LANGUAGE; ABILITY AB Previous research has reported mixed findings regarding executive function (EF) abilities in developmental coordination disorder (DCD), which is diagnosed on the basis of significant impairments in motor skills. The current study aimed to assess whether these differences in study outcomes could result from the relative motor loads of the tasks used to assess EF in DCD. Children with DCD had significant difficulties on measures of inhibition and planning compared to a control group, although there were no significant correlations between motor skills and EF task performance in either group. The complexity of the response, as well as the component skills required in EF tasks, should be considered in future research to ensure easier comparison across studies and a better understanding of EF in DCD over development. (C )2014 Elsevier Ltd. All rights reserved. C1 [Pratt, Michelle L.; Leonard, Hayley C.; Adeyinka, Hanna; Hill, Elisabeth L.] Univ London, Dept Psychol, London SE14 6NW, England. RP Hill, EL (reprint author), Univ London, Dept Psychol, London SE14 6NW, England. 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Zhang, Zhixiang Baron-Cohen, Simon Brayne, Carol TI Comparison between a Mandarin Chinese version of the Childhood Autism Spectrum Test and the Clancy Autism Behaviour Scale in mainland China SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Screening; Diagnosis; Epidemiology; CAST; CABS; China ID PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGER-SYNDROME TEST; DIAGNOSTIC INTERVIEW; MENTAL-RETARDATION; TEST CAST; PREVALENCE; CHILDREN; IDENTIFICATION; QUOTIENT; UK AB A Mandarin Chinese version of the Childhood Autism Spectrum Test (CAST) and Clancy Autism Behaviour Scale (CABS) were applied to 150 children aged 4-11 years old from clinical settings and mainstream schools in Beijing. All the children were further assessed using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The validity of two instruments on screening of ASC was examined and compared using receiver operating characteristic (ROC) curve analysis. The validity of CAST (sensitivity: 89%, specificity: 80%, PPV: 70%) was better than the CABS (sensitivity: 58%, specificity: 84%, PPV: 65%). The area under the curve (AUC) of the CAST (AUC = 0.90) was significantly higher than the CABS (AUC = 0.79, p = 0.0002). The Mandarin CAST demonstrated a better validity in distinguishing children with ASC from children without ASC. It is an acceptable candidate as a screening instrument for ASC in large epidemiological study in Chinese population. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Sch Clin Med, Cambridge Inst Publ Hlth, Cambridge CB2 0SR, England. [Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 2AH, England. [Sun, Xiang] Chinese Univ Hong Kong, Prince Wales Hosp, Jockey Club Sch Publ Hlth & Primary Care, Shatin, Hong Kong, Peoples R China. [Auyeung, Bonnie] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Matthews, Fiona E.] Cambridge Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England. [Zhang, Zhixiang] Peking Univ, Hosp 1, Dept Paediat, Beijing, Peoples R China. RP Sun, X (reprint author), Univ Cambridge, Sch Clin Med, Cambridge Inst Publ Hlth, Forvie Site,Cambridge Biomed Campus, Cambridge CB2 0SR, England. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1599 EP 1608 DI 10.1016/j.ridd.2014.02.005 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500017 PM 24769432 ER PT J AU Hodge, D Carollo, TM Lewin, M Hoffman, CD Sweeney, DP AF Hodge, Danelle Carollo, Tanner M. Lewin, Michael Hoffman, Charles D. Sweeney, Dwight P. TI Sleep patterns in children with and without autism spectrum disorders: Developmental comparisons SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Sleep; Melatonin; Development ID HABITS QUESTIONNAIRE; TYPICAL DEVELOPMENT; AGE-CHILDREN; MELATONIN; ADOLESCENTS; CHILDHOOD; ADULTS; DELAY AB The present study examined age-related changes in the sleep of children with autism spectrum disorders (ASD) compared to age-related changes in the sleep of typically developing (TD) children. Participants were 108 mothers of children with ASD and 108 mothers of TD children. Participants completed a questionnaire on children's overall sleep quality that also tapped specific sleep-domains (i.e., bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, disordered breathing, daytime sleepiness). Results confirm significantly poorer sleep quantity and quality in children with ASD, particularly children age 6-9 years. Unlike TD children, the sleep problems of children with ASD were unlikely to diminish with age. Our findings suggest that it is important to exam specific domains of sleep as well as overall sleep patterns. Finding of significant age-related interactions suggests that the practice of combining children from wide age-ranges into a single category obfuscates potentially important developmental differences. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hodge, Danelle; Carollo, Tanner M.; Lewin, Michael; Hoffman, Charles D.; Sweeney, Dwight P.] Calif State Univ San Bernardino, Dept Psychol, San Bernardino, CA 92407 USA. RP Hodge, D (reprint author), Calif State Univ San Bernardino, Dept Psychol, 5500 Univ Pkwy, San Bernardino, CA 92407 USA. EM dhodge@csusb.edu CR Allik H, 2008, J AUTISM DEV DISORD, V38, P1625, DOI 10.1007/s10803-008-0543-0 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Arendt J, 2005, J BIOL RHYTHM, V20, P291, DOI 10.1177/0748730405277492 Arendt J., 1995, MELATONIN MAMMALIAN, p[201, 27] Autism Society of America, 2003, DEFINING AUTISM Arbelle S, 2001, RESEARCH BASIS FOR AUTISM INTERVENTION, P219 Didden R, 2001, RES DEV DISABIL, V22, P255, DOI 10.1016/S0891-4222(01)00071-3 Gilliam J. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1631 EP 1638 DI 10.1016/j.ridd.2014.03.037 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500020 PM 24780146 ER PT J AU Samadi, SA McConkey, R Bunting, B AF Samadi, Sayyed Ali McConkey, Roy Bunting, Brendan TI Parental wellbeing of Iranian families with children who have developmental disabilities SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Intellectual disability; Autism spectrum disorder; Iran; Parents; Health; Stress; Family functioning ID AUTISM SPECTRUM DISORDERS; BEHAVIOR PROBLEMS; YOUNG-CHILDREN; INTELLECTUAL DISABILITIES; DOWN-SYNDROME; STRESS; MOTHERS; IMPACT; SUPPORT; ADJUSTMENT AB To date, most research with families who have a child with developmental disabilities has been undertaken in English speaking countries. Poorer health, allied with increased levels of stress has been commonly reported for mothers but less is known about the impact on fathers and on overall family functioning. This study aimed to document the correlates of these parental impacts with Iranian mothers and fathers who had children with either intellectual disabilities (ID) or with autism spectrum disorders (ASD). In all 121 parents (69 mothers and 52 fathers from 94 families) who had a child with a diagnosis of ADS, along with 115 parents of children with ID (83 mothers and 32 fathers from 101 families) volunteered to take part in the study. Each participant completed through interview standardised rating scales of parenting stress, emotional well-being, family functioning and satisfaction with caring role along with demographic information and details of informal supports. Structural Equation Modeling identified that family functioning was much poorer in families whose child had ASD and both mothers and fathers reported higher levels of stress. Poorer emotional well-being contributed to higher stress and was more frequent among mothers, single parents and those whose children had behaviour problems. Having other dependents living at home and more sources of informal support improved the emotional wellbeing of parents but not their stress or family functioning. Parents who derived greater satisfaction from their caring role tended to have better emotional health and less stress. Although the impact on Iranian parents of having a child with developmental disabilities is broadly similar to those of parents in other cultures, there are indications that children with ASD present distinct challenges to these families. The model derived in this study is a useful guide both for further research as well as family-centred interventions. (C) 2014 Elsevier Ltd. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1639 EP 1647 DI 10.1016/j.ridd.2014.04.001 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500021 PM 24814475 ER PT J AU Gadow, KD Pinsonneault, JK Perlman, G Sadee, W AF Gadow, Kenneth D. Pinsonneault, Julia K. Perlman, Greg Sadee, Wolfgang TI Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Autism spectrum disorder; Depression; Emotion dysregulation; ADHD; DAT1; DRD2 ID DEFICIT HYPERACTIVITY DISORDER; CHILD SYMPTOM INVENTORY-4; SCORING ALGORITHMS; NUCLEUS-ACCUMBENS; CLINICAL UTILITY; DEPRESSION; EXPRESSION; ANXIETY; SAMPLES; SYSTEM AB The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1)polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on a priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD Was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents' ratings) was associated with DAT1 intron8 (eta p(2)=.063) and rs2283265 (eta p(2)=.044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (eta p(2)=.065) and depression (eta p(2)=.059), and for DRD2 rs2283265, depression (eta p(2)=.053). DRD2 rs2283265 was associated with teachers' global ratings of ADHD (eta p(2) =.052). DAT1 intron8 was associated with parent-rated hyperactivity (eta p(2) =.045) and both DAT1 9/10 VNTR (eta p(2)=.105) and DRD2 rs2283265 (eta p(2)=.069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Gadow, Kenneth D.; Perlman, Greg] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Pinsonneault, Julia K.; Sadee, Wolfgang] Ohio State Univ, Wexner Med Ctr, Ctr Pharmacogen, Dept Pharmacol, Columbus, OH 43210 USA. RP Gadow, KD (reprint author), SUNY Stony Brook, Dept Psychiat, Putnam Hall, Stony Brook, NY 11794 USA. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1658 EP 1665 DI 10.1016/j.ridd.2014.04.007 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500023 PM 24780147 ER PT J AU Li, XM Wang, K Wu, JX Hong, YF Zhao, JP Feng, XJ Xu, M Wang, M Ndasauka, Y Zhang, XC AF Li, Xiaoming Wang, Kai Wu, Jianxian Hong, Yongfeng Zhao, Jingpu Feng, Xiaojun Xu, Mei Wang, Min Ndasauka, Yamikani Zhang, Xiaochu TI The link between impaired theory of mind and executive function in children with cerebral palsy SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Cerebral palsy; Theory of mind; Executive function ID AUTISM SPECTRUM DISORDERS; LATENT VARIABLE ANALYSIS; WORKING-MEMORY; ASPERGER-SYNDROME; PERFORMANCE; BELIEFS; SCHIZOPHRENIA; COMPREHENSION; PRESCHOOLERS; DISABILITIES AB The aim of the study was to explore the relationship between theory of mind (ToM) deficits and executive function (EF) impairments in children with cerebral palsy (CP), 42 CP with children and 42 typically developing (TD) children, acting as controls, were assessed on the tasks of ToM (false belief and faux pas) and EF (inhibition, updating and shifting). Results showed that CP children had deficits both in ToM and EF tasks. The correlation analyses showed that two EF components (inhibition and updating) were strongly related to false belief and faux pas in both two groups. We also found correlation between shifting and false belief and faux pas. However, this correlation was only found in TD children and not in children with CP. These findings suggest that children with CP lag behind TD children in both ToM and EF. Further, the results reveal, interestingly, that ToM deficits in CP children might be related to their inhibition and updating impairments, but not to shifting impairments. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Li, Xiaoming; Zhang, Xiaochu] Univ Sci & Technol China, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui Province, Peoples R China. [Li, Xiaoming; Zhang, Xiaochu] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui Province, Peoples R China. [Li, Xiaoming; Wang, Kai] Anhui Med Univ, Dept Med Psychol, Hefei 230032, Anhui Province, Peoples R China. [Wu, Jianxian; Hong, Yongfeng; Zhao, Jingpu; Feng, Xiaojun; Xu, Mei] Anhui Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Hefei 230032, Anhui Province, Peoples R China. [Wang, Min] Anhui Med Univ, Affiliated Hosp 1, Dept Rehabil Med, Hefei 230032, Anhui Province, Peoples R China. [Ndasauka, Yamikani; Zhang, Xiaochu] Univ Sci & Technol China, Sch Humanities & Social Sci, Hefei 230026, Anhui, Peoples R China. RP Li, XM (reprint author), Univ Sci & Technol China, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui Province, Peoples R China. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1686 EP 1693 DI 10.1016/j.ridd.2014.03.017 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500026 PM 24685096 ER PT J AU Machalicek, W McDuffie, A Oakes, A Ma, M Thurman, AJ Rispoli, MJ Abbeduto, L AF Machalicek, Wendy McDuffie, Andrea Oakes, Ashley Ma, Monica Thurman, Angela John Rispoli, Mandy J. Abbeduto, Leonard TI Examining the operant function of challenging behavior in young males with fragile X syndrome: A summary of 12 cases SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Challenging behavior; Fragile X syndrome; Functional analysis; Functional behavior assessment ID SELF-INJURIOUS-BEHAVIOR; AUTISM SPECTRUM DISORDERS; ABERRANT BEHAVIOR; CHILDREN; INDIVIDUALS; PHENOTYPE; ATTENTION; TOPOGRAPHIES; DISABILITIES; QUESTIONS AB This study used experimental functional analyses to examine the operant function of challenging behaviors exhibited by 12 males (ages 27-51 months) with fragile X syndrome (FXS). Eight children met criteria for negatively reinforced challenging behavior in the form of escape from demands and/or escape from social interactions. Nine children met criteria for positively reinforced challenging behavior in the form of obtaining access to highly preferred items. Attention was identified as a maintaining consequence for three children. The functional analysis was inconclusive for one child. Results suggest that, for young males with FXS, challenging behaviors may more likely be tangibly and escape maintained than attention maintained. Our findings affirm past research suggesting a unique behavioral phenotype for this population. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Machalicek, Wendy] Univ Oregon, Eugene, OR 97403 USA. [McDuffie, Andrea; Oakes, Ashley; Ma, Monica; Thurman, Angela John; Abbeduto, Leonard] Univ Calif Davis, MIND Inst, Davis, CA USA. [Rispoli, Mandy J.] Texas A&M Univ, College Stn, TX 77843 USA. RP Machalicek, W (reprint author), Univ Oregon, Dept Special Educ & Clin Sci, 901 East 18th Ave, Eugene, OR 97403 USA. 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TI Deeper processing is beneficial during episodic memory encoding for adults with Williams syndrome SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Williams Syndrome; Ageing; Cognition; Episodic memory; Semantic memory; Depths of processing; Encoding ID LONG-TERM-MEMORY; AGE-DIFFERENCES; DOWN-SYNDROME; OLDER-ADULTS; RECOLLECTION; FAMILIARITY; TASK; INDIVIDUALS; RECOGNITION; PERFORMANCE AB Previous research exploring declarative memory in Williams syndrome (WS) has revealed impairment in the processing of episodic information accompanied by a relative strength in semantic ability. The aim of the current study was to extend this literature by examining how relatively spared semantic memory may support episodic remembering. Using a level of processing paradigm, older adults with WS (aged 35-61 years) were compared to typical adults of the same chronological age and typically developing children matched for verbal ability. In the study phase, pictures were encoded using either a deep (decide if a picture belongs to a particular category) or shallow (perceptual based processing) memory strategy. Behavioural indices (reaction time and accuracy) at retrieval were suggestive of an overall difficulty in episodic memory for WS adults. Interestingly, however, semantic support was evident with a greater recall of items encoded with deep compared to shallow processing, indicative of an ability to employ semantic encoding strategies to maximise the strength of the memory trace created. Unlike individuals with autism who find semantic elaboration strategies problematic, the pattern of findings reported here suggests in those domains that are relatively impaired in WS, support can be recruited from relatively spared cognitive processes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Greer, Joanna; Hamiliton, Colin; Riby, Leigh M.] Northumbria Univ, Dept Psychol, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1720 EP 1726 DI 10.1016/j.ridd.2014.03.004 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500030 PM 24679545 ER PT J AU Mertz, LGB Thaulov, P Trillingsgaard, A Christensen, R Vogel, I Hertz, JM Ostergaard, JR AF Mertz, Line Granild Bie Thaulov, Per Trillingsgaard, Anegen Christensen, Rikke Vogel, Ida Hertz, Jens Michael Ostergaard, John R. TI Neurodevelopmental outcome in Angelman syndrome: Genotype-phenotype correlations SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Angelman syndrome; 15q11.2-q13; Language skills; Autism; ADDS; Mullen; Intellectual disability ID AUTISM SPECTRUM DISORDERS; DISTINCT PHENOTYPES; DELETION; DIAGNOSIS; FEATURES AB Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mertz, Line Granild Bie; Ostergaard, John R.] Aarhus Univ Hosp, Dept Pediat, Ctr Rare Dis, Aarhus, Denmark. [Thaulov, Per] Aarhus Univ Hosp, Psychiat Hosp Children & Adolescents, Aarhus, Denmark. [Trillingsgaard, Anegen] Aarhus Univ, Dept Psychol, DK-8000 Aarhus C, Denmark. [Christensen, Rikke; Vogel, Ida] Aarhus Univ Hosp, Dept Clin Genet, Aarhus, Denmark. [Hertz, Jens Michael] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. RP Mertz, LGB (reprint author), Aarhus Univ Hosp, Dept Pediat, Ctr Rare Dis, Aarhus, Denmark. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1742 EP 1747 DI 10.1016/j.ridd.2014.02.018 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500033 PM 24656292 ER PT J AU Tureck, K Matson, JL Cervantes, P Konst, MJ AF Tureck, Kim Matson, Johnny L. Cervantes, Paige Konst, Matthew J. TI An examination of the relationship between autism spectrum disorder, intellectual functioning, and comorbid symptoms in children SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Intellectual functioning; Comorbid symptoms; Autism Spectrum Disorders-Comorbidity for; Children (ASD-CC) ID PSYCHIATRIC-DISORDERS; PDD-NOS; CHALLENGING BEHAVIORS; REPETITIVE BEHAVIORS; DIAGNOSTIC FIDELITY; ANXIETY SYMPTOMS; INFANT SCREEN; ASD-CC; ADULTS; DEPRESSION AB There is a deficiency of research looking at how rates of comorbid psychopathology are effected by autism spectrum disorder (ASD) and intellectual functioning level. The present study aimed to extend the literature in this area by evaluating how ASD and IQ scores are related to ratings on a measure of comorbid symptoms. Twenty-three children with ASD and 87 children without ASD participated in this study. Rates of tantrum behavior, avoidant behavior, worry/depressed, repetitive behavior, under-eating, over-eating, and conduct behavior were examined utilizing the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). Correlational and multiple regression analyses were then conducted. ASD diagnosis significantly predicted rates of tantrum behavior, avoidant behavior, and repetitive behavior. Children with ASD tended to have higher rates of all three of these comorbid symptoms than children without ASD. Although not statistically significant, there was a negative correlation between IQ and rates of comorbid symptoms, such that children with higher IQ scores tended to have lower rates of comorbid symptoms. The implications of these findings on assessment and intervention are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tureck, Kim; Matson, Johnny L.; Cervantes, Paige; Konst, Matthew J.] Louisiana State Univ, Baton Rouge, LA 70803 USA. 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Adams, Hilary TI Prevalence of co-occurring disorders in a sample of adults with mild and moderate intellectual disabilities who reside in a residential treatment setting SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Intellectual disability; Developmental disabilities; Dual diagnosis; Comorbidity; Co-occurring conditions; Adults ID PERVASIVE DEVELOPMENTAL DISORDER; ABERRANT BEHAVIOR CHECKLIST; PROFOUND MENTAL-RETARDATION; AUTISM SPECTRUM DISORDERS; SELF-INJURIOUS-BEHAVIOR; II DASH-II; DIAGNOSTIC-ASSESSMENT; SOCIAL-SKILLS; COMORBID PSYCHOPATHOLOGY; PSYCHIATRIC-DISORDERS AB The presence of an intellectual disability (ID) is associated with a myriad of co-occurring conditions, including psychiatric and genetic disorders, behavior problems, physical disabilities, and seizure disorders. Often the most severely affected individuals reside in residential treatment facilities, where they may obtain specialized treatment and management of their challenging behavior. 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Dev. Disabil. PD JUL PY 2014 VL 35 IS 7 BP 1802 EP 1808 DI 10.1016/j.ridd.2014.01.027 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3GK UT WOS:000336011500040 PM 24656808 ER PT J AU O'Dwyer, L Tanner, C van Dongen, EV Greven, CU Braten, J Zwiersl, MP Franke, B Oosterlaan, J Heslenfeld, D Hoekstra, P Hartman, CA Rommelse, N Buitelaar, JK AF O'Dwyer, Laurence Tanner, Colby van Dongen, Eelco V. Greven, Corina U. Braten, Janita Zwiersl, Marcel P. Franke, Barbara Oosterlaan, Jaap Heslenfeld, Dirk Hoekstra, Pieter Hartman, Catharina A. Rommelse, Nanda Buitelaar, Jan K. TI Brain Volumetric Correlates of Autism Spectrum Disorder Symptoms in Attention Deficit/Hyperactivity Disorder SO PLOS ONE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIOR QUESTIONNAIRE CSBQ; LARGE MULTICENTER ADHD; REPETITIVE BEHAVIORS; DIAGNOSTIC-APPROACH; LANGUAGE DISORDER; CORPUS-CALLOSUM; CAUDATE-NUCLEUS; FAMILIAL TRAIT AB Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disord (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has nvestigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children's Social and Behavioural Questionnaire (CSBQ) in ADHD subject n = 180) their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview K-SADS-PL) and the Conners' ADHD questionnaires. Whole brain T1 Weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to bot h controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress he need. to account for issues of ASD comorbidity ADHD. C1 [O'Dwyer, Laurence; van Dongen, Eelco V.; Greven, Corina U.; Braten, Janita; Zwiersl, Marcel P.; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Tanner, Colby] Univ Lausanne, Dept Ecol & Evolut, Lausanne, Switzerland. [Greven, Corina U.] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England. [Braten, Janita; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Franke, Barbara; Rommelse, Nanda] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. [Oosterlaan, Jaap; Heslenfeld, Dirk] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands. [Heslenfeld, Dirk] Vrije Univ Amsterdam, Dept Cognit Psychol, Amsterdam, Netherlands. [Hoekstra, Pieter; Hartman, Catharina A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Rommelse, Nanda; Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr Nij, Nijmegen, Netherlands. RP O'Dwyer, L (reprint author), Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. EM larodwyer@gmail.com RI Zwiers, Marcel/D-2968-2009; Franke, Barbara/D-4836-2009 OI Zwiers, Marcel/0000-0001-5483-2935; Franke, Barbara/0000-0003-4375-6572 FU National Institutes of Health [RO1MH62873]; NWO Large Investment Grant [1750102007010]; Radboud University Nijmegen Medical Center; University Medical Center Groningen and Accare; Vrije Universiteit Amsterdam; European Community's Seventh Framework Programme [278948]; Innovative Medicines Initiative Joint Undertaking (IMI) under (EU-AIMS) [115300-01]; Irish Research Council for Science, Engineering and Technology (IRCSET) FX The NeuroIMAGE study was supported by National Institutes of Health grant RO1MH62873 (to Stephen V. Faraone), NWO Large Investment Grant 1750102007010 (to Jan Buitelaar) and matching grants from Radboud University Nijmegen Medical Center, University Medical Center Groningen and Accare, and Vrije Universiteit Amsterdam. The research leading to these results also received support from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 278948 (TACTICS), and from the Innovative Medicines Initiative Joint Undertaking (IMI) under grant agreement number 115300-01 (EU-AIMS). CT was supported by a fellowship from the Irish Research Council for Science, Engineering and Technology (IRCSET). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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C. de la Torre, Rafael Farre, Magi Yubero-Lahoz, Samanta Dziobek, Isabel Van den Bos, Wouter Ramaekers, Johannes G. TI No Evidence that MDMA-Induced Enhancement of Emotional Empathy Is Related to Peripheral Oxytocin Levels or 5-HT1a Receptor Activation SO PLOS ONE LA English DT Article ID HIGH-FUNCTIONING AUTISM; SOCIAL-BEHAVIOR; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; INTRANASAL OXYTOCIN; PROSOCIAL FEELINGS; HEALTHY-VOLUNTEERS; VERBAL MEMORY; BETA-BLOCKER; ECSTASY; HUMANS AB The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. C1 [Kuypers, Kim P. C.; Ramaekers, Johannes G.] Maastricht Univ, Fac Psychol & Neurosci, Dept Neuropsychol & Psychopharmacol, Maastricht, Netherlands. [de la Torre, Rafael; Farre, Magi; Yubero-Lahoz, Samanta] Hosp Mar, IMIM, Res Inst, Human Pharmacol & Clin Neurosci Res Grp, Barcelona, Spain. [Dziobek, Isabel] Free Univ Berlin, Berlin, Germany. [Van den Bos, Wouter] Max Planck Inst Human Dev, Ctr Adapt Rational ARC, Berlin, Germany. RP Kuypers, KPC (reprint author), Maastricht Univ, Fac Psychol & Neurosci, Dept Neuropsychol & Psychopharmacol, Maastricht, Netherlands. EM k.kuypers@maastrichtuniversity.nl FU Netherlands Organization for Scientific Research (NWO) [400-07-2013] FX This work was supported by the Netherlands Organization for Scientific Research (NWO), Grant number: 400-07-2013, awarded to JR and KK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Here, we investigated whether this bias might also be demonstrated by individuals who exhibit sub-clinical levels of autistic traits, as has been found for other aspects of autistic cognition. The eye-movements of 71 university students were monitored as they completed a reading comprehension task. Consistent with previous studies, participants made shorter fixations on words that were highly predicted on the basis of preceding sentence context. However, contrary to the weak central coherence account, this effect was not reduced amongst individuals with high levels of autistic traits, as measured by the Autism Spectrum Quotient (AQ). Further exploratory analyses revealed that participants with high AQ scores fixated longer on words that resolved the meaning of an earlier homograph. However, this was only the case for sentences where the two potential meanings of the homograph result in different pronunciations. The results provide tentative evidence for differences in reading style that are associated with autistic traits, but fail to support the notion of weak central coherence extending into the non-autistic population. C1 [Caruana, Nathan; Brock, Jon] Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. [Brock, Jon] Macquarie Univ, Dept Psychol, Sydney, NSW 2109, Australia. EM jon.brock@mq.edu.au FU Australian Research Council Australian Research Fellowship [DP098466]; Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021] FX Jon Brock was supported by an Australian Research Council Australian Research Fellowship (Grant DP098466). He is a Chief Investigator at the Australian Research Council Centre of Excellence in Cognition and its Disorders (Grant CE110001021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1-9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42-56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development. C1 [Wu, Xiaoyan; Bai, Yanrui; Tan, Tao; Li, Hongjie; Zhou, Weihui; Li, Tingyu; Wang, Yu Tian; Dong, Zhifang] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Childrens Hosp, Chongqing 400014, Peoples R China. [Wu, Xiaoyan; Bai, Yanrui; Tan, Tao; Li, Hongjie; Zhou, Weihui; Li, Tingyu; Dong, Zhifang] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Translat Med Res Cognit Dev & L, Chongqing 400014, Peoples R China. [Xia, Shuting; Chang, Xinxia; Zhou, Zikai] Southeast Univ, Inst Life Sci, Minist Educ, Key Lab Dev Genes & Human Dis, Nanjing, Jiangsu, Peoples R China. [Wang, Yu Tian] Univ British Columbia, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada. RP Dong, ZF (reprint author), Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Childrens Hosp, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China. EM zfdong@cqmu.edu.cn FU Ministry of Science and Technology of China [2012CB517903, 2014CB548100]; National Natural Science Foundation of China [81271221, 31040085, 31200805, 81070269, 81161120498]; Chongqing International Science and technology Cooperation Foundation [cstc201110003] FX We thank Dr. Loren W. Oschipok for his excellent editorial assistance. This work was supported by 973 Program of the Ministry of Science and Technology of China (2012CB517903 to Zhifang Dong and Weihui Zhou, 2014CB548100 to Zhifang Dong), the National Natural Science Foundation of China (81271221 and 31040085 to Zhifang Dong, 31200805 to Zikai Zhou, 81070269 to Weihui Zhou and 81161120498 to Tingyu Li), and the Chongqing International Science and technology Cooperation Foundation (cstc201110003 to Zhifang Dong). Yu Tian Wang is the holder of the HSFBC/Y chair in stroke research. 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PD JUN 26 PY 2014 VL 8 AR 234 DI 10.3389/fnbeh.2014.00234 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AK1SC UT WOS:000338195200001 PM 25018711 ER PT J AU Chen, CH Huang, CC Cheng, MC Chiu, YN Tsai, WC Wu, YY Liu, SK Gau, SSF AF Chen, Chia-Hsiang Huang, Chia-Chun Cheng, Min-Chih Chiu, Yen-Nan Tsai, Wen-Che Wu, Yu-Yu Liu, Shih-Kai Gau, Susan Shur-Fen TI Genetic analysis of GABRB3 as a candidate gene of autism spectrum disorders SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorders; GABRB3; Rare variants; Genetics; Case-control association ID RECEPTOR SUBUNIT GENES; AMINOBUTYRIC-ACID RECEPTOR; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PERVASIVE DEVELOPMENTAL DISORDERS; CHILDHOOD ABSENCE EPILEPSY; MESSENGER-RNA LEVELS; GABA(A) RECEPTOR; LINKAGE-DISEQUILIBRIUM; CHROMOSOME 15Q11-Q13; PSYCHOMETRIC PROPERTIES AB Background: GABRB3 is a position candidate gene at chromosome 15q12 that has been implicated in the neurobiology of autism spectrum disorders (ASD). The aim of this study was to examine the genetic association of GABRB3 with ASD. Methods: The sample consisted of 356 patients with clinical diagnosis of ASD according to the DSM-IV diagnostic criteria and confirmed by the Autism Diagnostic Interview-Revised and 386 unrelated controls. We searched for mutations at all the exonic regions and 1.6 Kb of the 5' region of GABRB3 in the genomic DNA of all the participants using the Sanger sequencing. We implemented a case-control association analysis of variants detected in this sample, and conducted a reporter gene assay to assess the functional impact of variants at the 5' regulatory region. Results: We detected six known common SNPs; however, they were not associated with ASD. Besides, a total of 22 rare variants (12 at 5' regulatory, 4 at intronic, and 6 at exonic regions) were detected in 18 patients and 6 controls. The frequency of rare variants was significantly higher in the patient group than in the control group (18/356 versus 6/386, odds ratio = 3.37, P = 0.007). All the 12 rare variants at the 5' regulatory region were only detected in 7 patients, but not in any of the controls (7/356 versus 0/386, Fisher's exact test, P = 0.006). Two patients carried multiple rare variants. Family studies showed that most of these rare variants were transmitted from their parents. Reporter gene assays revealed that four rare variants at the 5' regulatory region and 1 at exon 1a untranslated region had elevated reporter gene activities compared to two wild type alleles. Conclusions: Our data suggest rare variants of GABRB3 might be associated with ASD, and increased GABRB3 expression may contribute to the pathogenesis of ASD in some patients. C1 [Chen, Chia-Hsiang; Wu, Yu-Yu] Chang Gung Mem Hosp Linkou, Dept Psychiat, Taoyuan, Taiwan. [Chen, Chia-Hsiang] Chang Gung Univ, Dept & Grad Inst Biomed Sci, Taoyuan, Taiwan. [Chen, Chia-Hsiang; Chiu, Yen-Nan; Tsai, Wen-Che; Gau, Susan Shur-Fen] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10002, Taiwan. [Chen, Chia-Hsiang; Chiu, Yen-Nan; Tsai, Wen-Che; Gau, Susan Shur-Fen] Coll Med, Taipei 10002, Taiwan. [Huang, Chia-Chun] Tzu Chi Univ, Inst Med Sci, Hualien, Taiwan. [Cheng, Min-Chih] Yuli Vet Hosp, Yuli Mental Hlth Res Ctr, Dept Psychiat, Hualien, Taiwan. [Liu, Shih-Kai] Minist Hlth & Welf, Taoyaun Psychiat Ctr, Dept Child & Adolescent Psychiat, Taoyuan, Taiwan. [Gau, Susan Shur-Fen] Natl Taiwan Univ, Grad Inst Brain & Mind Sci, Taipei 10764, Taiwan. [Gau, Susan Shur-Fen] Natl Taiwan Univ, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan. RP Gau, SSF (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan South Rd, Taipei 10002, Taiwan. EM gaushufe@ntu.edu.tw FU National Science Council [NSC96-3112-B-002-033, NSC97-3112-B-002-009, NSC98-3112-B-002-004, NSC 99-3112-B-002-036]; National Taiwan University [10R81918-03, 101R892103, 102R892103] FX This work was supported by grants from National Science Council (NSC96-3112-B-002-033, NSC97-3112-B-002-009, NSC98-3112-B-002-004, and NSC 99-3112-B-002-036 to SSG) and National Taiwan University (AIM for Top University Excellent Research Project: 10R81918-03, 101R892103, 102R892103 to SSG). This work was approved by the Research Ethics Committee of National Taiwan University Hospital (approved number: 9561709027), Taipei, Taiwan; Chang Gung Memorial Hospital (approved number, 93-6244), Taoyuan, Taiwan; and Taoyuan Mental Hospital (approved number C20060905), Taoyuan, Taiwan. 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Autism PD JUN 25 PY 2014 VL 5 AR 36 DI 10.1186/2040-2392-5-36 PG 13 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AK8HY UT WOS:000338669700001 PM 24999380 ER PT J AU Carver, AR Andrikopoulou, M Lei, J Tamayo, E Gamble, P Hou, ZP Zhang, JY Mori, S Saade, GR Costantine, MM Burd, I AF Carver, Alissa R. Andrikopoulou, Maria Lei, Jun Tamayo, Esther Gamble, Phyllis Hou, Zhipeng Zhang, Jiangyang Mori, Susumu Saade, George R. Costantine, Maged M. Burd, Irina TI Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model SO PLOS ONE LA English DT Article ID COA REDUCTASE INHIBITORS; NEONATAL HYPOXIA-ISCHEMIA; AUTISM SPECTRUM DISORDER; SEX-DIFFERENCES; IN-UTERO; CARDIOVASCULAR FUNCTION; PRENATAL EXPOSURE; GENE-TRANSFER; BIRTH-WEIGHT; MURINE MODEL AB Objective: Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention. Materials and Methods: For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group'') or water (sFlt-1 "positive control'') until weaning. The mFc group ("negative control'') received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis. Results: Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes. Conclusion: Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model. C1 [Carver, Alissa R.; Tamayo, Esther; Gamble, Phyllis; Saade, George R.; Costantine, Maged M.] Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med, Galveston, TX 77555 USA. [Andrikopoulou, Maria; Lei, Jun; Burd, Irina] Johns Hopkins Univ, Dept Gynecol & Obstet, Integrated Res Ctr Fetal Med, Div Maternal Fetal Med, Baltimore, MD USA. [Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Carver, AR (reprint author), Univ Texas Med Branch, Dept Obstet & Gynecol, Div Maternal Fetal Med, Galveston, TX 77555 USA. EM arcarver@utmb.edu FU NICHD [K08 HD073315]; NIH [RO1 EB003543]; Brain Science Institute, Johns Hopkins FX This work was supported by NICHD K08 HD073315 (www.nichd.nih.gov), NIH RO1 EB003543 (www.nih.gov) and grant support from Brain Science Institute, Johns Hopkins (www.brainscienceinstitute.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2014 VL 9 IS 6 AR e100873 DI 10.1371/journal.pone.0100873 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK8WO UT WOS:000338709500093 PM 24963809 ER PT J AU Austin, G Groppe, K Elsner, B AF Austin, Gina Groppe, Karoline Elsner, Birgit TI The reciprocal relationship between executive function and theory of mind in middle childhood: a 1-year longitudinal perspective SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE executive function; theory of mind; longitudinal; middle childhood; attention shifting; inhibition; working memory updating ID INDIVIDUAL-DIFFERENCES; INHIBITORY CONTROL; CHILDRENS THEORY; WORKING-MEMORY; BELIEF; PRESCHOOLERS; AUTISM; ADULTS; TASKS; LINKS AB There is robust evidence showing a link between executive function (EF) and theory of mind (ToM) in 3-to 5-year-olds. However, it is unclear whether this relationship extends to middle childhood. In addition, there has been much discussion about the nature of this relationship. Whereas some authors claim that ToM is needed for EF, others argue that ToM requires EF. To date, however, studies examining the longitudinal relationship between distinct sub components of EF [i.e., attention shifting, working memory (WM) updating, inhibition] and ToM in middle childhood are rare. The present study examined (1) the relationship between three EF subcomponents (attention shifting, WM updating, inhibition) and ToM in middle childhood, and (2) the longitudinal reciprocal relationships between the EF subcomponents and ToM across a 1-year period. EF and ToM measures were assessed experimentally in a sample of 1,657 children (aged 6-11 years) at time point one (t1) and 1 year later at time point two (t2). Results showed that the concurrent relationships between all three EF subcomponents and ToM pertained in middle childhood at t1 and t2, respectively, even when age, gender, and fluid intelligence were partialle dout. Moreover, cross-lagged structural equation modeling (again, controlling for age, gender, and fluid intelligence, as well as for the earlier levels of the target variables), revealed partial support for the view that early ToM predictslater EF, but stronger evidence for the assumption that early EF predictslater ToM. The latter was found for attention shifting and WM updating, but not for inhibition. This reveals the importance of studying the exact interplay of ToM and EF across childhood development, especially with regard to different EF subcomponents. Most likely, understanding others' mental states at different levels of perspective-taking requires specific EF subcomponents, suggesting developmental change in the relations between EF and ToM across childhood. 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Psychol. PD JUN 24 PY 2014 VL 5 AR 655 DI 10.3389/fpsyg.2014.00655 PG 11 WC Psychology, Multidisciplinary SC Psychology GA AK9CG UT WOS:000338724500001 PM 25009527 ER PT J AU Kessler, K Cao, LY O'Shea, KJ Wang, HF AF Kessler, Klaus Cao, Liyu O'Shea, Kieran J. Wang, Hongfang TI A cross-culture, cross-gender comparison of perspective taking mechanisms SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE perspective taking; embodied transformation; line of sight; culture differences; gender differences; egocentric bias ID SOCIAL COGNITION; SPECIES FOLLOW; CHILDREN; HUMANS; GAZE; DISSOCIATION; PERCEPTION; AUTISM; ADULTS; SKILLS AB Being able to judge another person's visuo-spatial perspective is an essential social skill, hence we investigated the generalizability of the involved mechanisms across cultures and genders. Developmental, cross-species, and our own previous research suggest that two different forms of perspective taking can be distinguished, which are subserved by two distinct mechanisms. The simpler form relies on inferring another's line-of-sight, whereas the more complex form depends on embodied transformation into the other's orientation in form of a simulated body rotation. Our current results suggest that, in principle, the same basic mechanisms are employed by males and females in both, East-Asian (EA; Chinese) and Western culture. However, we also confirmed the hypothesis that Westerners show an egocentric bias, whereas EAs reveal an other-oriented bias. Furthermore, Westerners were slower overall than EAs and showed stronger gender differences in speed and depth of embodied processing. Our findings substantiate differences and communalities in social cognition mechanisms across genders and two cultures and suggest that cultural evolution or transmission should take gender as a modulating variable into account. C1 [Kessler, Klaus; Cao, Liyu; O'Shea, Kieran J.; Wang, Hongfang] Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland. [Kessler, Klaus; Wang, Hongfang] Aston Univ, Aston Brain Ctr, Birmingham B4 7ET, W Midlands, England. RP Kessler, K (reprint author), Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland. EM k.kessler@aston.ac.uk FU ESRC [RES-000-22-4325] FX This research was supported by ESRC funding to K.K. (RES-000-22-4325). 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R. Soc. B-Biol. Sci. PD JUN 22 PY 2014 VL 281 IS 1785 AR 20140388 DI 10.1098/rspb.2014.0388 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA AH0LT UT WOS:000335812100020 PM 24807256 ER PT J AU Zerbo, O Yoshida, C Grether, JK Van de Water, J Ashwood, P Delorenze, GN Hansen, RL Kharrazi, M Croen, LA AF Zerbo, Ousseny Yoshida, Cathleen Grether, Judith K. Van de Water, Judy Ashwood, Paul Delorenze, Gerald N. Hansen, Robin L. Kharrazi, Marty Croen, Lisa A. TI Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Newborn; Cytokines; Chemokines; Autism spectrum disorders ID HISTORIC BIRTH COHORT; IMMUNE-RESPONSE; CHILDREN; BRAIN; DYSFUNCTION; PREGNANCY; IMMUNOGLOBULIN; PREVALENCE; ACTIVATION; INFECTION AB Background: Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles. Objective: To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism. Methods: We conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, California, USA. The study population included children ascertained from the California Department of Developmental Services with Autism Spectrum Disorder (ASD, n = 84), or developmental delay but not ASD (DD, n = 49), and general population controls randomly sampled from the birth certificate files and frequency matched to ASD cases on sex, birth month and birth year (GP, n = 159). Cytokine and chemokine concentrations were measured in archived neonatal blood specimens collected for routine newborn screening. Results: Cytokines were not detected in the vast majority of newborn samples regardless of case or control status. However, the chemokine monocyte chemotactic protein-1 (MCP-1) was elevated and the chemokine Regulated upon Activation Normal T-Cell Expressed and Secreted (RANTES) was decreased in ASD cases compared to GP controls. The chemokines macrophage inflammatory protein-1alpha (MIP-1 alpha) and RANTES were decreased in children with DD compared to GP controls. Conclusion: Measurement of immune system function in the first few days of life may aid in the early identification of abnormal neurodevelopment and shed light on the biologic mechanisms underlying normal neurodevelopment. C1 [Zerbo, Ousseny; Yoshida, Cathleen; Grether, Judith K.; Delorenze, Gerald N.; Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Grether, Judith K.; Kharrazi, Marty] Calif Dept Publ Hlth, Environm Hlth Invest Branch, Richmond, CA 94804 USA. [Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Van de Water, Judy; Ashwood, Paul; Hansen, Robin L.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Hansen, Robin L.] Dept Pediat, Sacramento, CA 95817 USA. RP Zerbo, O (reprint author), Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. EM ousseny.x.zerbo@kp.org FU National Institute of Environmental Health Sciences [3R01ES016669]; National Institute of Mental Health [5R01MH072565] FX The study was supported by grants 3R01ES016669 from National Institute of Environmental Health Sciences; 5R01MH072565 from the National Institute of Mental Health. 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Swerdfeger, Amy L. Eslick, Guy D. TI Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies SO VACCINE LA English DT Article DE Vaccine; Vaccination; Immunisation; Autism; Autism spectrum disorder; Thimerosal; Mercury ID THIMEROSAL-CONTAINING VACCINES; MUMPS-RUBELLA VACCINATION; EVENT REPORTING SYSTEM; SPECTRUM DISORDER; DEVELOPMENTAL DISORDERS; PRISMA STATEMENT; MEASLES; POPULATION; CHILDREN; BIAS AB There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a 'link' between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), nor was there a relationship between autism and MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p = 0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p = 0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Taylor, Luke E.; Swerdfeger, Amy L.; Eslick, Guy D.] Univ Sydney, Nepean Hosp, Whiteley Martin Res Ctr, Discipline Surg, Penrith, NSW 2751, Australia. RP Eslick, GD (reprint author), Univ Sydney, Nepean Hosp, Whiteley Martin Res Ctr, Discipline Surg, Level 3,Clin Bldg,POB 63, Penrith, NSW 2751, Australia. 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Moran, John E. Olszewski, Amy Pawluk, Lesley Jacobson, Daniel Mansour, Alfred Vogt, Kelly Erdodi, Laszlo A. Moore, Aimee M. Bowyer, Susan M. TI Neural synchrony examined with magnetoencephalography (MEG) during eye gaze processing in autism spectrum disorders: preliminary findings SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Eye gaze; Neural synchrony; Coherence; Magnetoencephalography; Social cognition ID HIGH-FUNCTIONING AUTISM; GAMMA-BAND RESPONSES; JOINT ATTENTION; 1ST-DEGREE RELATIVES; VISUAL-ATTENTION; YOUNG-CHILDREN; CONNECTIVITY; BRAIN; INDIVIDUALS; LANGUAGE AB Background: Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. Methods: This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M-Age = 16.6) compared to neurotypicals (NT) (M-Age = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), and low gamma (30 to 45 Hz)) was calculated. Results: Significantly higher coherence and synchronization in posterior brain regions (temporo-parietal-occipital) across all frequencies was evident in ASD, particularly within the low 0 to 15 Hz frequency range. Higher coherence in fronto-temporo-parietal regions was noted in NT. A significantly higher number of low frequency cross-hemispheric synchronous connections and a near absence of right intra-hemispheric coherence in the beta frequency band were noted in ASD. Significantly higher low frequency coherent activity in bilateral temporo-parieto-occipital cortical regions and higher gamma band coherence in right temporo-parieto-occipital brain regions during averted gaze was related to more severe symptomology as reported on the Autism Diagnostic Interview-Revised (ADI-R). Conclusions: The preliminary results suggest a pattern of aberrant connectivity that includes higher low frequency synchronization in posterior cortical regions, lack of long-range right hemispheric beta and gamma coherence, and decreased coherence in fronto-temporo-parietal regions necessary for orienting to shifts in eye gaze in ASD; a critical behavior essential for social communication. C1 [Lajiness-O'Neill, Renee; Richard, Annette E.; Olszewski, Amy; Pawluk, Lesley; Mansour, Alfred; Vogt, Kelly; Moore, Aimee M.] Eastern Michigan Univ, Ypsilanti, MI 48197 USA. [Lajiness-O'Neill, Renee] Univ Michigan Hlth Syst, Neuropsychol Sect, Dept Psychiat, Ann Arbor, MI USA. [Lajiness-O'Neill, Renee; Moran, John E.; Pawluk, Lesley; Bowyer, Susan M.] Henry Ford Hosp, Detroit, MI 48202 USA. [Olszewski, Amy] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Jacobson, Daniel] USMS, US Air Force, Biloxi, MS USA. [Erdodi, Laszlo A.] Geisel Sch Med Dartmouth, Dept Psychiat, Lebanon, NH USA. [Bowyer, Susan M.] Wayne State Univ, Detroit, MI USA. [Bowyer, Susan M.] Oakland Univ, Rochester, MI 48063 USA. RP Lajiness-O'Neill, R (reprint author), Eastern Michigan Univ, Ypsilanti, MI 48197 USA. EM rlajines@gmail.com FU Eastern Michigan University FX This research was supported in part by grants from a new faculty award (NFA) and a faculty research fellowship award (FRF) from Eastern Michigan University awarded to the first author. 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Glial cystine/glutamate exchange (system Xc(-)), which exchanges extracellular cystine for intracellular glutamate, plays a significant role in the maintenance of extracellular glutamate. N-acetylcysteine (NAC) is a cystine prodrug that restores extracellular glutamate by stimulating system Xc(-). In this study, we examined the effects of NAC on autism-like phenotypes and neurotransmission in the thalamic amygdala synapses, as well as the involvement of metabotropic glutamate receptors 2/3 (mGluR2/3). Valproate-treated rats received a single intraperitoneal injection of 500 mg/kg NaVPA on E12.5. On postnatal day 21 (P21), NAC or saline was administered once daily for 10 days. From day 8 to 10, NAC was given 1/2 h prior to behavioral testing. Chronic administration of NAC restored the duration and frequency of social interaction and ameliorated anxiety-like behaviors in VPA-exposed offspring. In amygdala slices, NAC treatment normalized the increased frequency of mEPSCs and decreased the paired pulse facilitation (PPF) induced by VPA exposure. The effects of NAC on social interaction and anxiety-like behavior in the VPA-exposed offspring were blocked after intra-amygdala infusion of mGluR2/3 antagonist LY341495. The expressions of mGluR2/3 protein and mGluR2 mRNA were significantly lower in the VPA-exposed offspring. In contrast, the mGluR3 mRNA level did not differ between the saline- and VPA-exposed offspring. These results provide the first evidence that the disruption of social interaction and enhanced presynaptic excitatory transmission in VPA-exposed offspring could be rescued by NAC, which depends on the activation of mGluR2/3. C1 [Chen, Yu-Wen; Hsiao, Ya-Hsin; Gean, Po-Wu] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70403, Taiwan. [Lin, Hui-Ching] Natl Yang Ming Univ, Sch Med, Dept & Inst Physiol, Taipei 112, Taiwan. [Lin, Hui-Ching] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan. [Ng, Ming-Chong; Chen, Po See] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Psychiat, Tainan 70403, Taiwan. [Wang, Chao-Chuan] Kaohsiung Med University, Coll Med, Dept Anat, Kaohsiung, Taiwan. [Chen, Po See] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70403, Taiwan. RP Gean, PW (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, 138 Sheng Li Road, Tainan 70403, Taiwan. EM powu@mail.ncku.edu.tw; chenps@mail.ncku.edu.tw FU National Science Council [NSC 99-2628-B-006-013, NSC 101-2321-B-006-025, NSC 102-2321-B-010-025, NSC 102-2320-B-010-009]; National Health Research Institute of Taiwan [NHRI-EX102-10117NI]; Brain Research Center, National Yang-Ming University; Ministry of Education, Aim for the Top University Plan; Headquarters of University Advancement at the National Cheng Kung University [D103-35A09]; Ministry of Education, Taiwan, ROC FX This study was supported by grants NSC 99-2628-B-006-013, NSC 101-2321-B-006-025, NSC 102-2321-B-010-025, NSC 102-2320-B-010-009 from the National Science Council and NHRI-EX102-10117NI from the National Health Research Institute of Taiwan. This study was also supported by Brain Research Center, National Yang-Ming University and a grant from Ministry of Education, Aim for the Top University Plan. This research also received funding (D102-35001 and D103-35A09) from the Headquarters of University Advancement at the National Cheng Kung University, which is sponsored by the Ministry of Education, Taiwan, ROC. The funding institutions of this study had no further role in the study design, the collection, analysis, and interpretation of data, the writing of this paper, or the decision to submit it for publication. 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Behav. Neurosci. PD JUN 17 PY 2014 VL 8 AR 219 DI 10.3389/fnbeh.2014.00219 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AK0OY UT WOS:000338114900001 PM 24987341 ER PT J AU Allegra, M Genovesi, S Maggia, M Cenni, MC Zunino, G Sgado, P Caleo, M Bozzi, Y AF Allegra, Manuela Genovesi, Sacha Maggia, Marika Cenni, Maria C. Zunino, Giulia Sgado, Paola Caleo, Matteo Bozzi, Yuri TI Altered GABAergic markers, increased binocularity and reduced plasticity in the visual cortex of Engrailed-2 knockout mice SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE plasticity; inhibition; monocular deprivation; critical period; neurodevelopmental disorder ID OCULAR DOMINANCE PLASTICITY; EXPERIENCE-DEPENDENT PLASTICITY; AUTISM SPECTRUM DISORDERS; CRITICAL-PERIOD PLASTICITY; FRAGILE-X-SYNDROME; MUTANT MICE; INTRACORTICAL INHIBITION; ENVIRONMENTAL ENRICHMENT; MONOCULAR DEPRIVATION; RECEPTIVE FIELDS AB The maturation of the GABAergic system is a crucial determinant of cortical development during early postnatal life, when sensory circuits undergo a process of activity-dependent refinement. An altered excitatory/inhibitory balance has been proposed as a possible pathogenic mechanism of autism spectrum disorders (ASD). The homeobox-containing transcription factor Engrailed-2 (En2) has been associated to ASD, and En2 knockout (En(2-/-)) mice show ASD-like features accompanied by a partial loss of cortical GABAergic interneurons. Here we studied GABAergic markers and cortical function in En(2-/-) mice, by exploiting the well-known anatomical and functional features of the mouse visual system. En2 is expressed in the visual cortex at postnatal day 30 and during adulthood. When compared to age-matched En(2+/+) controls, En(2-/-) mice showed an increased number of parvalbumin (PV+), somatostatin (SOM+), and neuropeptide Y (NPY+) positive interneurons in the visual cortex at P30, and a decreased number of SOM+ and NPY+ interneurons in the adult. At both ages, the differences in distinct interneuron populations observed between En(2+/+)and En(2-/-) mice were layer-specific. Adult En(2-/-) mice displayed a normal eye-specific segregation in the retino-geniculate pathway, and in vivo electrophysiological recordings showed a normal development of basic functional properties (acuity, response latency, receptive field size) of the En(2-/-) primary visual cortex. However, a significant increase of binocularity was found in P30 and adult En(2-/-) mice, as compared to age-matched controls. Differently from what observed in En(2+/+) mice, the En(2-/-) primary visual cortex did not respond to a brief monocular deprivation performed between P26 and P29, during the so-called "critical period." These data suggest that altered GABAergic circuits impact baseline binocularity and plasticity in En(2-/-) mice, while leaving other visual functional properties unaffected. C1 [Allegra, Manuela; Cenni, Maria C.; Caleo, Matteo; Bozzi, Yuri] CNR, Inst Neurosci, I-56100 Pisa, Italy. [Allegra, Manuela] Scuola Normale Super Pisa, Neurobiol Lab, Pisa, Italy. [Genovesi, Sacha; Maggia, Marika; Zunino, Giulia; Sgado, Paola; Bozzi, Yuri] Univ Trento, Ctr Integrat Biol, Lab Mol Neuropathol, I-38123 Mattarello, Trento, Italy. RP Bozzi, Y (reprint author), Univ Trento, Ctr Integrat Biol, Lab Mol Neuropathol, Via Regole 101, I-38123 Mattarello, Trento, Italy. EM bozzi@science.unitn.it FU Italian Ministry of University and Research [200894SYW2_002, 2010N8PBAA_002]; University of Trento; Telethon [GGP11116]; PRIN [2012MKKTNW_002]; Provincia Autonoma di Trento (Italy) under the Marie Curie-People cofunding action of the European Community FX We are grateful to the technical/administrative staff of the Centre for Integrative Biology (University of Trento) and CNR Neuroscience Institute for excellent assistance. This work was funded by grants from the Italian Ministry of University and Research (PRIN 2008 grant 200894SYW2_002 and PRIN 2010-11 grant 2010N8PBAA_002) and the University of Trento (CIBIO start-up) to Yuri Bozzi, and Telethon project GGP11116 and PRIN grant 2012MKKTNW_002 to Matteo Ca leo. Paola Sgada is supported by Provincia Autonoma di Trento (Italy) under the Marie Curie-People cofunding action of the European Community. 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PD JUN 17 PY 2014 VL 8 AR 163 DI 10.3389/fncel.2014.00163 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AJ5MF UT WOS:000337726600001 PM 24987331 ER PT J AU Mouti, A Reddihough, D Marraffa, C Hazell, P Wray, J Lee, K Kohn, M AF Mouti, Anissa Reddihough, Dinah Marraffa, Catherine Hazell, Philip Wray, John Lee, Katherine Kohn, Michael TI Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism SO TRIALS LA English DT Article DE Autism Spectrum Disorder (ASD); Autism; Serotonin Reuptake Inhibitors (SSRIs); Fluoxetine; Repetitive and Restricted Behaviors; Randomized Controlled Trial (RCT); Drug Therapy; Children; Adolescents; Safety and Efficacy ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; PSYCHOMETRIC PROPERTIES; PSYCHOACTIVE MEDICINES; REPETITIVE BEHAVIORS; INDIVIDUALS; SCALE; PREVALENCE; CHILDHOOD; ANXIETY AB Background: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. Methods/Design: The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government's National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. Discussion: The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD. C1 [Mouti, Anissa; Kohn, Michael] Univ Sydney, Ctr Res Adolescents Hlth CRASH, Sydney Childrens Hosp Network, Westmead Sydney Med Sch, Sydney, NSW 2145, Australia. [Hazell, Philip] Univ Sydney, Sydney Med Sch, Discipline Psychiat, Sydney, NSW 2138, Australia. [Reddihough, Dinah; Lee, Katherine] Univ Melbourne, Dept Pediat, Parkville, Vic 3052, Australia. [Reddihough, Dinah; Marraffa, Catherine; Lee, Katherine] Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Wray, John] State Child Dev Ctr, Perth 6872, Australia. RP Mouti, A (reprint author), Univ Sydney, Ctr Res Adolescents Hlth CRASH, Sydney Childrens Hosp Network, Westmead Sydney Med Sch, Hawkesbury Rd, Sydney, NSW 2145, Australia. EM anissa.mouti@health.nsw.gov.au FU National Health and Medical Research Council [NHMRC 607332]; Australian Government FX The study is funded by a National Health and Medical Research Council (NHMRC 607332) grant by the Australian Government. All study-related expenses including publication costs for manuscripts are to be covered by this grant. We would like to acknowledge the following staff for their work on this study: Steve Kloprogge, Molly O'Sullivan and Joanna Granich; Francesca Orsini, Paul Lockhart, David Dossetor and his team from Psychological Medicine, Sydney Children's Hospital Network, Westmead, Andrew Whitehouse, Paramala Santosh, Paul Lockhart, Simon Clarke, Alison Poulton, Jane Ho, Sue Reid, John Carlin, Natalie Silove and Roshan Virasinghe. 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Ercument Roeder, Kathryn Ozsoyoglu, Gultekin TI MIRA: mutual information-based reporter algorithm for metabolic networks SO BIOINFORMATICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; EXPRESSION PROFILES; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; ASPERGILLUS-NIDULANS; INTEGRATED ANALYSIS; SYSTEMS BIOLOGY; MICROARRAY DATA AB Motivation: Discovering the transcriptional regulatory architecture of the metabolism has been an important topic to understand the implications of transcriptional fluctuations on metabolism. The reporter algorithm (RA) was proposed to determine the hot spots in metabolic networks, around which transcriptional regulation is focused owing to a disease or a genetic perturbation. Using a z-score-based scoring scheme, RA calculates the average statistical change in the expression levels of genes that are neighbors to a target metabolite in the metabolic network. The RA approach has been used in numerous studies to analyze cellular responses to the downstream genetic changes. In this article, we propose a mutual information-based multivariate reporter algorithm (MIRA) with the goal of eliminating the following problems in detecting reporter metabolites: (i) conventional statistical methods suffer from small sample sizes, (ii) as z-score ranges from minus to plus infinity, calculating average scores can lead to canceling out opposite effects and (iii) analyzing genes one by one, then aggregating results can lead to information loss. MIRA is a multivariate and combinatorial algorithm that calculates the aggregate transcriptional response around a metabolite using mutual information. We show that MIRA's results are biologically sound, empirically significant and more reliable than RA. Results: We apply MIRA to gene expression analysis of six knockout strains of Escherichia coli and show that MIRA captures the underlying metabolic dynamics of the switch from aerobic to anaerobic respiration. We also apply MIRA to an Autism Spectrum Disorder gene expression dataset. Results indicate that MIRA reports metabolites that highly overlap with recently found metabolic biomarkers in the autism literature. Overall, MIRA is a promising algorithm for detecting metabolic drug targets and understanding the relation between gene expression and metabolic activity. C1 [Cicek, A. Ercument; Roeder, Kathryn] Carnegie Mellon Univ, Sch Comp Sci, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Ozsoyoglu, Gultekin] Case Western Reserve Univ, Sch Engn, Dept Elect Engn & Comp Sci, Cleveland, OH 44106 USA. RP Cicek, AE (reprint author), Carnegie Mellon Univ, Sch Comp Sci, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. EM cicek@cs.cmu.edu FU National Science Foundation [DBI 0743705, DBI 0849956, CRI 0551603]; National Institute of Health [GM088823] FX This research has been supported by the National Science Foundation grants DBI 0743705, DBI 0849956, CRI 0551603 and by the National Institute of Health grant GM088823. A. Ercument Cicek has also been supported by Ray and Stephanie Lane Fellowship. CR Agren R, 2012, PLOS COMPUT BIOL, V8, DOI 10.1371/journal.pcbi.1002518 Albert R, 2005, J CELL SCI, V118, P4947, DOI 10.1242/jcs.02714 Aziz A, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0014547 Boccuto L, 2013, MOL AUTISM, V4, DOI 10.1186/2040-2392-4-16 Brosche M, 2005, GENOME BIOL, V6, DOI 10.1186/gb-2005-6-12-r101 Butte A. 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Gaugler, Mary K. Yu, Qi Romigh, Todd Yu, Wanfeng Miller, Robert H. Frazier, Thomas W., II Eng, Charis TI Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production SO HUMAN MOLECULAR GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; ATP-BINDING MOTIFS; IN-VIVO; SUBCELLULAR-LOCALIZATION; CHROMOSOME-10 PTEN; TUMOR-SUPPRESSOR; NUCLEAR IMPORT; MUTATIONS; BRAIN AB PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal-dominant genetic condition underlying a subset of autism spectrum disorder (ASD) with macrocephaly. Caused by germline mutations in PTEN, PHTS also causes increased risks of multiple cancers via dysregulation of the PI3K and MAPK signaling pathways. Conditional knockout models have shown that neural Pten regulates social behavior, proliferation and cell size. Although much is known about how the intracellular localization of PTEN regulates signaling in cancer cell lines, we know little of how PTEN localization influences normal brain physiology and behavior. To address this, we generated a germline knock-in mouse model of cytoplasm-predominant Pten and characterized its behavioral and cellular phenotypes. The homozygous Pten(m3m4) mice have decreased total Pten levels including a specific drop in nuclear Pten and exhibit region-specific increases in brain weight. The Pten(m3m4) model displays sex-specific increases in social motivation, poor balance and normal recognition memory-a profile reminiscent of some individuals with high functioning ASD. The cytoplasm-predominant protein caused cellular hypertrophy limited to the soma and led to increased NG2 cell proliferation and accumulation of glia. The animals also exhibit significant astrogliosis and microglial activation, indicating a neuroinflammatory phenotype. At the signaling level, Pten(m3m4) mice show brain region-specific differences in Akt activation. These results demonstrate that differing alterations to the same autism-linked gene can cause distinct behavioral profiles. The Pten(m3m4) model is the first murine model of inappropriately elevated social motivation in the context of normal cognition and may expand the range of autism-related behaviors replicated in animal models. C1 [Tilot, Amanda K.; Frazier, Thomas W., II; Eng, Charis] Cleveland Clin, Dept Mol Med, Howard Hughes Med Inst, Mol Med Program,Lerner Coll Med, Cleveland, OH 44195 USA. [Tilot, Amanda K.; Gaugler, Mary K.; Yu, Qi; Romigh, Todd; Yu, Wanfeng; Frazier, Thomas W., II; Eng, Charis] Cleveland Clin, Genom Med Inst, Cleveland, OH 44195 USA. [Tilot, Amanda K.; Gaugler, Mary K.; Yu, Qi; Romigh, Todd; Yu, Wanfeng; Eng, Charis] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA. [Frazier, Thomas W., II] Cleveland Clin, Ctr Autism, Inst Pediat, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin, Stanley Shalom Zielony Inst Nursing Excellence, Cleveland, OH 44195 USA. [Miller, Robert H.] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. [Eng, Charis] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. [Eng, Charis] Case Western Reserve Univ, Sch Med, CASE Comprehens Canc Ctr, Cleveland, OH 44106 USA. RP Eng, C (reprint author), Cleveland Clin, Genom Med Inst, 9500 Euclid Ave NE 50, Cleveland, OH 44195 USA. EM engc@ccf.org FU National Institutes of Health [R01CA118989] FX This work was supported, in part, by the National Institutes of Health (R01CA118989 to C. E.), and a generous gift from Sam H. Miller. 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Mol. Genet. PD JUN 15 PY 2014 VL 23 IS 12 BP 3212 EP 3227 DI 10.1093/hmg/ddu031 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AI7CJ UT WOS:000337038600013 PM 24470394 ER PT J AU Ludwig, AL Espinal, GM Pretto, DI Jamal, AL Arque, G Tassone, F Berman, RF Hagerman, PJ AF Ludwig, Anna Lisa Espinal, Glenda M. Pretto, Dalyir I. Jamal, Amanda L. Arque, Gloria Tassone, Flora Berman, Robert F. Hagerman, Paul J. TI CNS expression of murine fragile X protein (FMRP) as a function of CGG-repeat size SO HUMAN MOLECULAR GENETICS LA English DT Article ID TREMOR/ATAXIA SYNDROME FXTAS; KNOCK-IN MICE; MESSENGER-RNA; MOUSE MODEL; PREMUTATION CARRIERS; FULL-MUTATION; FRAGILE-X-MENTAL-RETARDATION-1 GENE; INTRANUCLEAR INCLUSIONS; ELEVATED LEVELS; NEURAL CELLS AB Large expansions of a CGG-repeat element (> 200 repeats; full mutation) in the fragile X mental retardation 1 (FMR1) gene cause fragile X syndrome (FXS), the leading single-gene form of intellectual disability and of autism spectrum disorder. Smaller expansions (55-200 CGG repeats; premutation) result in the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Whereas FXS is caused by gene silencing and insufficient FMR1 protein (FMRP), FXTAS is thought to be caused by 'toxicity' of expanded-CGG-repeat mRNA. However, as FMRP expression levels decrease with increasing CGG-repeat length, lowered protein may contribute to premutation-associated clinical involvement. To address this issue, we measured brain Fmr1 mRNA and FMRP levels as a function of CGG-repeat length in a congenic (CGG-repeat knock-in) mouse model using 57 wild-type and 97 expanded-CGG-repeat mice carrying up to similar to 250 CGG repeats. While Fmr1 message levels increased with repeat length, FMRP levels trended downward over the same range, subject to significant inter-subject variation. Human comparisons of protein levels in the frontal cortex of 7 normal and 17 FXTAS individuals revealed that the mild FMRP decrease in mice mirrored the more limited data for FMRP expression in the human samples. In addition, FMRP expression levels varied in a subset of mice across the cerebellum, frontal cortex, and hippocampus, as well as at different ages. These results provide a foundation for understanding both the CGG-repeat-dependence of FMRP expression and for interpreting clinical phenotypes in premutation carriers in terms of the balance between elevated mRNA and lowered FMRP expression levels. C1 [Ludwig, Anna Lisa; Espinal, Glenda M.; Pretto, Dalyir I.; Tassone, Flora; Hagerman, Paul J.] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Pretto, Dalyir I.; Tassone, Flora; Berman, Robert F.; Hagerman, Paul J.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Jamal, Amanda L.; Arque, Gloria; Berman, Robert F.] Univ Calif Davis, Sch Med, Dept Neurol Surg, Davis, CA 95616 USA. RP Hagerman, PJ (reprint author), Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, 4303 Tupper Hall,One Shields Ave, Davis, CA 95616 USA. EM pjhagerman@ucdavis.edu FU National Institutes of Health [R01HD040661, R01NS079775] FX This work was supported by the National Institutes of Health (grant numbers R01HD040661 to P.J.H. and R01NS079775 to R.F.B.). 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Mol. Genet. PD JUN 15 PY 2014 VL 23 IS 12 BP 3228 EP 3238 DI 10.1093/hmg/ddu032 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AI7CJ UT WOS:000337038600014 PM 24463622 ER PT J AU Burette, AC Park, H Weinberg, RJ AF Burette, Alain C. Park, Haram Weinberg, Richard J. TI Postsynaptic Distribution of IRSp53 in Spiny Excitatory and Inhibitory Neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE dendritic spine; PSD; BAIAP2; Rho GTPase; GABAergic neurons ID INSULIN-RECEPTOR SUBSTRATE; LONG-TERM DEPRESSION; MEDIATED SYNAPTIC-TRANSMISSION; TYROSINE KINASE; PROTEOMIC ANALYSIS; DENDRITIC SPINE; NMDA RECEPTORS; NERVOUS-SYSTEM; ACTIN DYNAMICS; RAT-BRAIN AB The 53 kDa insulin receptor substrate protein (IRSp53) is highly enriched in the brain. Despite evidence that links mutations of IRSp53 with autism and other neuropsychiatric problems, the functional significance of this protein remains unclear. We used light and electron microscopic immunohistochemistry to demonstrate that IRSp53 is expressed throughout the adult rat brain. Labeling concentrated selectively in dendritic spines, where it was associated with the postsynaptic density (PSD). Surprisingly, its organization within the PSD of spiny excitatory neurons of neocortex and hippocampus differed from that within spiny inhibitory neurons of neostriatum and cerebellar cortex. The present data support previous suggestions that IRSp53 is involved in postsynaptic signaling, while hinting that its signaling role may differ in different types of neurons. J. Comp. Neurol. 522:2164-2178, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Burette, Alain C.; Weinberg, Richard J.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Park, Haram] Korea Adv Inst Sci & Technol, Inst Basic Sci, Ctr Synapt Brain Dysfunct, Taejon 305701, South Korea. 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PD JUN 15 PY 2014 VL 522 IS 9 BP 2164 EP 2178 DI 10.1002/cne.23526 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AF1QS UT WOS:000334489000012 PM 24639075 ER PT J AU Sadakata, T Kakegawa, W Shinoda, Y Hosono, M Katoh-Semba, R Sekine, Y Sato, Y Saruta, C Ishizaki, Y Yuzaki, M Kojima, M Furuichi, T AF Sadakata, Tetsushi Kakegawa, Wataru Shinoda, Yo Hosono, Mayu Katoh-Semba, Ritsuko Sekine, Yukiko Sato, Yumi Saruta, Chihiro Ishizaki, Yasuki Yuzaki, Michisuke Kojima, Masami Furuichi, Teiichi TI Axonal Localization of Ca2+- Dependent Activator Protein for Secretion 2 Is Critical for Subcellular Locality of Brain-Derived Neurotrophic Factor and Neurotrophin-3 Release Affecting Proper Development of Postnatal Mouse Cerebellum SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDER; CORE VESICLE TRAFFICKING; DIFFERENTIAL REGULATION; CADPS2-KNOCKOUT MICE; SYNAPTIC PLASTICITY; RETT-SYNDROME; CADPS2; BDNF; CALCIUM; CAPS1 AB Ca2+-dependent activator protein for secretion 2 (CAPS2) is a protein that is essential for enhanced release of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from cerebellar granule cells. We previously identified dex3, a rare alternative splice variant of CAPS2, which is overrepresented in patients with autism and is missing an exon 3 critical for axonal localization. We recently reported that a mouse model CAPS2(Delta ex3/Delta ex3) expressing dex3 showed autistic-like behavioral phenotypes including impaired social interaction and cognition and increased anxiety in an unfamiliar environment. Here, we verified impairment in axonal, but not somato-dendritic, localization of dex3 protein in cerebellar granule cells and demonstrated cellular and physiological phenotypes in postnatal cerebellum of CAPS2(Delta ex3/Delta ex3) mice. Interestingly, both BDNF and NT-3 were markedly reduced in axons of cerebellar granule cells, resulting in a significant decrease in their release. As a result, dex3 mice showed developmental deficits in dendritic arborization of Purkinje cells, vermian lobulation and fissurization, and granule cell precursor proliferation. Paired-pulse facilitation at parallel fiber-Purkinje cell synapses was also impaired. Together, our results indicate that CAPS2 plays an important role in subcellular locality (axonal vs. somato-dendritic) of enhanced BDNF and NT-3 release, which is indispensable for proper development of postnatal cerebellum. C1 [Sadakata, Tetsushi; Hosono, Mayu] Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gunma, Japan. [Sadakata, Tetsushi; Shinoda, Yo; Kojima, Masami; Furuichi, Teiichi] JST CREST, Kawaguchi, Saitama, Japan. [Kakegawa, Wataru; Yuzaki, Michisuke] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan. [Shinoda, Yo; Katoh-Semba, Ritsuko; Sekine, Yukiko; Sato, Yumi; Saruta, Chihiro; Furuichi, Teiichi] Tokyo Univ Sci, Dept Appl Biol Sci, Noda, Chiba 278, Japan. [Ishizaki, Yasuki] Gunma Univ, Grad Sch Med, Dept Mol & Cellular Neurobiol, Maebashi, Gunma, Japan. [Kojima, Masami] Natl Inst Adv Ind Sci & Technol, Hlth Res Inst, Biointerface Res Grp, Ikeda, Osaka, Japan. RP Sadakata, T (reprint author), Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gunma, Japan. EM sadakata-1024@umin.ac.jp; tfuruichi@rs.tus.ac.jp RI Yuzaki, Michisuke/K-5328-2013 OI Yuzaki, Michisuke/0000-0002-5750-3544 FU Japan Foundation for Neuroscience and Mental Health; Uehara Memorial Foundation; Takeda Science Foundation; Nakajima Foundation; Yamada Science Foundation; Mother and Child Health Foundation; NOVARTIS Foundation for the Promotion of Science; Inamori Foundation; Scientific Research on Innovative Areas "Foundation of Synapse and Neurocircuit Pathology''; Japan Science and Technology Agency; Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) [25110707]; Japan Society for the Promotion of Science (JSPS) [25430061]; Institute of Physical and Chemical Research (RIKEN); Program to Disseminate Tenure Tracking System of MEXT FX This study was supported by Grants-in-Aid for Scientific Research from the Japan Foundation for Neuroscience and Mental Health, the Uehara Memorial Foundation, the Takeda Science Foundation, the Nakajima Foundation, the Yamada Science Foundation, the Mother and Child Health Foundation, the NOVARTIS Foundation for the Promotion of Science, the Inamori Foundation, Scientific Research on Innovative Areas "Foundation of Synapse and Neurocircuit Pathology'', the Japan Science and Technology Agency, the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT; grant number 25110707), the Japan Society for the Promotion of Science (JSPS; grant numbers 25430061), the Institute of Physical and Chemical Research (RIKEN), and the Program to Disseminate Tenure Tracking System of MEXT granted to Gunma University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Data from 127 children with ASD (13.5 +/- 6.0 years) and 153 age- and gender-matched typically developing children (14.5 +/- 5.7 years) were selected from the multi-center Functional Connectome Project. Regional gray matter volume and cortical thickness increased, whereas white matter volume decreased in ASD compared to controls. Small-world network analysis of quantitative MRI data demonstrated decreased global efficiency based on gray matter cortical thickness but not with functional connectivity MRI (fcMRI) or volumetry. An integrative model of 22 quantitative imaging features was used for classification and prediction of phenotypic features that included the autism diagnostic observation schedule, the revised autism diagnostic interview, and intelligence quotient scores. 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However, little is known about when and how mTOR is involved in the pathogenesis of these diseases, due to a lack of animal models that directly increase mTOR activity. Here, we generated transgenic mice expressing a gain-of-function mutant of mTOR in the forebrain in a temporally controlled manner. Selective activation of mTORC1 in embryonic stages induced cortical atrophy caused by prominent apoptosis of neuronal progenitors, associated with upregulation of HIF-1 alpha. In striking contrast, activation of the mTORC1 pathway in adulthood resulted in cortical hypertrophy with fatal epileptic seizures, recapitulating human TSC. Activated mTORC1 in the adult cortex also promoted rapid accumulation of cytoplasmic inclusions and activation of microglial cells, indicative of progressive neurodegeneration. Our findings demonstrate that mTORC1 plays different roles in developmental and adult stages and contributes to human neurological diseases. C1 [Kassai, Hidetoshi; Noda, Shoko; Nakao, Kazuki; Aiba, Atsu] Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Lab Anim Resources, Tokyo 1130033, Japan. [Sugaya, Yuki; Kano, Masanobu] Univ Tokyo, Grad Sch Med, Dept Neurophysiol, Tokyo 1130033, Japan. [Nakao, Kazuki] RIKEN Ctr Dev Biol, Lab Anim Resources & Genet Engn, Kobe, Hyogo 6500047, Japan. [Maeda, Tatsuya] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan. RP Aiba, A (reprint author), Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Lab Anim Resources, Tokyo 1130033, Japan. EM aiba@m.u-tokyo.ac.jp FU Japan Society for the Promotion of Science [22300106, 21220006, 25000015, 25291042, 23700368]; Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), MEXT, Japan FX We thank Drs. Shigeo Okabe (The University of Tokyo) and Makoto Sato (Osaka University) for providing valuable advice and plasmids for in utero electroporation experiments. We also thank Drs. Terunao Takahara and Yoichiro Ohne for helpful discussions. This study was supported in part by Grants-in-Aid for Scientific Research (22300106 to A. A., 21220006 and 25000015 to M. K., and 25291042 to T. M.) and for Young Scientists (B) (23700368 to H. K.) from the Japan Society for the Promotion of Science. This study was also partially supported by the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior), MEXT, Japan. 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Psychol. PD JUN 12 PY 2014 VL 5 AR 585 DI 10.3389/fpsyg.2014.00585 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AJ7TG UT WOS:000337899500001 PM 24971072 ER PT J AU Jung, M Kosaka, H Saito, DN Ishitobi, M Morita, T Inohara, K Asano, M Arai, S Munesue, T Tomoda, A Wada, Y Sadato, N Okazawa, H Iidaka, T AF Jung, Minyoung Kosaka, Hirotaka Saito, Daisuke N. Ishitobi, Makoto Morita, Tomoyo Inohara, Keisuke Asano, Mizuki Arai, Sumiyoshi Munesue, Toshio Tomoda, Akemi Wada, Yuji Sadato, Norihiro Okazawa, Hidehiko Iidaka, Tetsuya TI Default mode network in young male adults with autism spectrum disorder: relationship with autism spectrum traits SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder (ASD); Autism spectrum traits; Autism-spectrum quotient (AQ); Default mode network (DMN); Resting-state functional connectivities (rs-FCs); Anterior medial prefrontal cortex (aMPFC); Posterior cingulate cortex (PCC) ID FUNCTIONAL CONNECTIVITY MRI; COMMUNICATION DISORDERS; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; SOCIAL COGNITION; HEAD MOTION; HUMAN BRAIN; CORTEX; PSYCHOPATHOLOGY; ABNORMALITIES AB Background: Autism spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development (TD). Social cognition properties that are deeply associated with autism spectrum traits have been linked to functional connectivity between regions within the brain's default mode network (DMN). Previous studies have shown that the resting-state functional connectivities (rs-FCs) of DMN are low and show negative correlation with the level of autism spectrum traits in individuals with autism spectrum disorder (ASD). However, it is unclear whether individual differences of autism spectrum traits are associated with the strength of rs-FCs of DMN in participants including the general population. Methods: Using the seed-based approach, we investigated the rs-FCs of DMN, particularly including the following two core regions of DMN: the anterior medial prefrontal cortex (aMPFC) and posterior cingulate cortex (PCC) in 19 young male adults with high-functioning ASD (mean age = 25.3 +/- 6.9 years; autism-spectrum quotient (AQ) = 33.4 +/- 4.2; full scale IQ (F-IQ) = 109.7 +/- 12.4) compared with 21 age- and IQ-matched young male adults from the TD group (mean age = 24.8 +/- 4.3 years; AQ = 18.6 +/- 5.7; F-IQ = 109.5 +/- 8.7). We also analyzed the correlation between the strength of rs-FCs and autism spectrum traits measured using AQ score. Results: The strengths of rs-FCs from core regions of DMN were significantly lower in ASD participants than TD participants. Under multiple regression analysis, the strengths of rs-FCs in brain areas from aMPFC seed showed negative correlation with AQ scores in ASD participants and TD participants. Conclusions: Our findings suggest that the strength of rs-FCs in DMN is associated with autism spectrum traits in the TD population as well as patients with ASD, supporting the continuum view. The rs-FCs of DMN may be useful biomarkers for the objective identification of autism spectrum traits, regardless of ASD diagnosis. C1 [Jung, Minyoung; Kosaka, Hirotaka; Arai, Sumiyoshi; Munesue, Toshio; Tomoda, Akemi] Chiba Univ, Hamamatsu Univ, Kanazawa Univ,Osaka Univ,Div Dev Higher Brain Fun, Sch Med,United Grad Sch Child Dev,Dept Child Dev, Fukui, Eiheiji 9101193, Japan. [Jung, Minyoung; Kosaka, Hirotaka; Arai, Sumiyoshi; Munesue, Toshio; Tomoda, Akemi] Univ Fukui, Fukui, Eiheiji 9101193, Japan. [Kosaka, Hirotaka; Saito, Daisuke N.; Asano, Mizuki; Tomoda, Akemi; Wada, Yuji; Okazawa, Hidehiko] Univ Fukui, Res Ctr Child Mental Dev, Fukui, Eiheiji 9101193, Japan. [Kosaka, Hirotaka; Ishitobi, Makoto; Inohara, Keisuke; Asano, Mizuki; Wada, Yuji] Univ Fukui, Fac Med Sci, Dept Neuropsychiat, Fukui, Eiheiji 9101193, Japan. [Kosaka, Hirotaka; Saito, Daisuke N.; Sadato, Norihiro; Okazawa, Hidehiko] Univ Fukui, Biomed Imaging Res Ctr, Fukui, Eiheiji 9101193, Japan. [Ishitobi, Makoto] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Child & Adolescent Mental Hlth, Kodaira, Tokyo 1878553, Japan. [Morita, Tomoyo] Osaka Univ, Grad Sch Engn, Suita, Osaka 5650871, Japan. [Munesue, Toshio] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa 9208641, Japan. [Sadato, Norihiro] Natl Inst Physiol Sci, Dept Cerebral Res, Okazaki, Aichi 4448585, Japan. [Iidaka, Tetsuya] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4668550, Japan. RP Kosaka, H (reprint author), Chiba Univ, Hamamatsu Univ, Kanazawa Univ,Osaka Univ,Div Dev Higher Brain Fun, Sch Med,United Grad Sch Child Dev,Dept Child Dev, Fukui, Eiheiji 9101193, Japan. EM hirotaka@u-fukui.ac.jp FU Japan Society for the Promotion of Science [21220005, 21591509, 21791120, 25293248]; Japan Research Foundation for Clinical Pharmacology; Takeda Science Foundation FX We would like to express our sincere appreciation to the participants and their families, who generously and courageously participated in this research. This research was funded in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (21220005, 21591509, 21791120, 25293248), the Japan Research Foundation for Clinical Pharmacology, and the Takeda Science Foundation. Part of this research was the result of 'Development of biomarker candidates for social behavior' and 'Integrated research on neuropsychiatric disorders' performed under the Strategic Research Program for Brain Sciences by the MEXT of Japan. 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Autism PD JUN 11 PY 2014 VL 5 AR 35 DI 10.1186/2040-2392-5-35 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AK8HV UT WOS:000338669400001 PM 24955232 ER PT J AU Mottolese, R Redoute, J Costes, N Le Bars, D Sirigu, A AF Mottolese, Raphaelle Redoute, Jerome Costes, Nicolas Le Bars, Didier Sirigu, Angela TI Switching brain serotonin with oxytocin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; TIME-OF-FLIGHT; RECEPTOR-BINDING; PLASMA OXYTOCIN; AMYGDALA REACTIVITY; 5-HT1A RECEPTORS; SOCIAL COGNITION; NEURAL CIRCUITRY; TEMPORAL-LOBE; F-18-MPPF PET AB Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[F-18]fluoro-benzamidoethylpiperazine ([F-18]MPPF), an antagonist of 5-HT1A receptors. OXT increased [F-18]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [F-18]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders. C1 [Mottolese, Raphaelle; Sirigu, Angela] CNRS, Unite Mixte Rech 5229, Ctr Cognit Neurosci, F-69675 Bron, France. [Mottolese, Raphaelle; Redoute, Jerome; Le Bars, Didier; Sirigu, Angela] Univ Lyon 1, F-69609 Lyon, France. [Redoute, Jerome; Costes, Nicolas; Le Bars, Didier] Ctr Etud & Rech Multimodal & Pluridisciplinaire I, F-69003 Lyon, France. RP Sirigu, A (reprint author), CNRS, Unite Mixte Rech 5229, Ctr Cognit Neurosci, F-69675 Bron, France. EM sirigu@isc.cnrs.fr FU Region Rhone-Alpes; Centre National de la Recherche Scientifique; Fondation de France; Labex Cortex; French Ministry of Research fellowship FX We thank Region Rhone-Alpes for supporting Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire PET/CT scanner acquisition, A. Lefevre for help in testing subjects, Rolf Heckemann for performing MRI segmentation, M. Desmurget and J.-R. Duhamel for helpful suggestions, S. Thobois for clinical support during the project ethical approval, and C. Billotey for performing subjects' clinical examinations. This research was funded by Centre National de la Recherche Scientifique (A. S.), Fondation de France (A. S.), Labex Cortex (A. S.), Region Rhone-Alpes (A. S.), and a French Ministry of Research fellowship (to R.M.). 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Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2014 VL 111 IS 23 BP 8637 EP 8642 DI 10.1073/pnas.1319810111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI6IJ UT WOS:000336976000079 PM 24912179 ER PT J AU aan het Rot, M Hogenelst, K AF aan het Rot, Marije Hogenelst, Koen TI The Influence of Affective Empathy and Autism Spectrum Traits on Empathic Accuracy SO PLOS ONE LA English DT Article ID EMOTIONAL FACIAL EXPRESSIONS; HIGH-FUNCTIONING ADULTS; ASPERGER-SYNDROME; QUOTIENT AQ; DISORDER; CHILDREN; FACETS; ALEXITHYMIA; COGNITION; OXYTOCIN AB Autism spectrum disorder is characterized by interpersonal deficits and has been associated with limited cognitive empathy, which includes perspective taking, theory of mind, and empathic accuracy (EA). The capacity for affective empathy may also be impaired. In the present study we aimed to determine if EA in normally developing individuals with varying levels of autism spectrum traits is moderated by trait affective empathy. Fifty male and fifty female participants ('perceivers') completed the Autism-Spectrum Quotient and the Balanced Emotional Empathy Scale to assess autism spectrum traits and trait affective empathy, respectively. EA was assessed using a Dutch-language version of a previously developed task and involved rating the feelings of others ('targets') verbally recounting autobiographical emotional events. Targets varied in trait emotional expressivity, assessed using the Berkeley Expressivity Questionnaire. Perceivers with more autism spectrum traits performed worse on the EA task, particularly when their trait affective empathy was relatively low. Interpersonal deficits in autism spectrum disorder may be partially explained by low cognitive empathy. Further, they might be aggravated by a limited capacity for affective empathy. C1 [aan het Rot, Marije] Univ Groningen, Dept Psychol, NL-9712 TS Groningen, Netherlands. Univ Groningen, Sch Behav & Cognit Neurosci, Groningen, Netherlands. RP aan het Rot, M (reprint author), Univ Groningen, Dept Psychol, Grote Kruisstr 2-1, NL-9712 TS Groningen, Netherlands. EM m.aan.het.rot@rug.nl FU Innovational Research Incentives Scheme Veni from the Netherlands Organisation for Scientific Research (NWO, Veni) [451-09-013] FX The work was supported by the Innovational Research Incentives Scheme Veni from the Netherlands Organisation for Scientific Research (NWO, Veni grant 451-09-013 awarded to Dr. aan het Rot). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Christopher Lanza, Matthew R. Daina, Aleksandra B. Monroe, Justin F. Khan, Sarah Y. Blaskey, Lisa Cannon, Katelyn M. Jenkins, Julian, III Qasmieh, Saba Levy, Susan E. Roberts, Timothy P. L. TI Missing and delayed auditory responses in young and older children with autism spectrum disorders SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism spectrum disorders; M50; M100; superior temporal gyrus; magnetoencephalography ID EVOKED MAGNETIC-FIELDS; SYSTEM ACTIVITY; HUMAN BRAIN; N1 WAVE; POTENTIALS; MIDDLE; MATURATION; P50; MEG; EEG AB Background:The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities). Methods: Thirty-five TD controls, 63 ASD without language impairment (ASD LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old). Results: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p= 0.04), with no differences between TD and ASD LI (90 versus 76%, p= 0.14) or between ASD LI and ASD + LI (76 versus 66%, p= 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups. Conclusion: Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment. C1 [Edgar, J. Christopher; Lanza, Matthew R.; Daina, Aleksandra B.; Monroe, Justin F.; Khan, Sarah Y.; Blaskey, Lisa; Cannon, Katelyn M.; Jenkins, Julian, III; Qasmieh, Saba; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Lurie Family Fdn MEG Imaging Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Blaskey, Lisa; Qasmieh, Saba; Levy, Susan E.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Edgar, JC (reprint author), Childrens Hosp Philadelphia, Dept Radiol, Wood Bldg,Suite 2115,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM edgarj@email.chop.edu FU NIH [R01DC008871, R01DC008871-02S1, K08 MH085100]; Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH [P30HD026979]; Nancy Lurie Marks Family Foundation (NLMFF); Pennsylvania Department of Health; Autism Speaks; Oberkircher Family FX This study was supported in part by NIH grant R01DC008871 (Timothy P. L. Roberts), NIH grant R01DC008871-02S1, a NIH grant K08 MH085100 (J. Christopher Edgar), Award number P30HD026979 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH, and grants from the Nancy Lurie Marks Family Foundation (NLMFF) and Autism Speaks. This research has been funded (in part) by a grant from the Pennsylvania Department of Health. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Dr. Roberts gratefully acknowledges the Oberkircher Family for the Oberkircher Family Chair in Pediatric Radiology at CHOP. 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Phillips, Christophe Chura, Lindsay Baron-Cohen, Simon Suckling, John TI Identifying endophenotypes of autism: a multivariate approach SO FRONTIERS IN COMPUTATIONAL NEUROSCIENCE LA English DT Article DE autism spectrum condition; MRI; support vector machine; searchlight; endophenotype ID VOXEL-BASED MORPHOMETRY; SPECTRUM DISORDER; LIKELIHOOD ESTIMATION; GRAY-MATTER; BRAIN; MRI; ACTIVATION; CHILDREN; METAANALYSIS; SVM AB The existence of an endophenotype of autism spectrum condition (ASC) has been recently suggested by several commentators. It can be estimated by finding differences between controls and people with ASC that are also present when comparing controls and the unaffected siblings of ASC individuals. In this work, we used a multivariate methodology applied on magnetic resonance images to look for such differences. The proposed procedure consists of combining a searchlight approach and a support vector machine classifier to identify the differences between three groups of participants in pairwise comparisons: controls, people with ASC and their unaffected siblings. Then we compared those differences selecting spatially collocated as candidate endophenotypes of ASC. C1 [Segovia, Fermin; Phillips, Christophe] Univ Liege, Cyclotron Res Ctr, Liege, Belgium. [Segovia, Fermin; Holt, Rosemary; Spencer, Michael; Chura, Lindsay; Baron-Cohen, Simon; Suckling, John] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge, England. [Gorriz, Juan M.; Ramirez, Javier] Univ Granada, Dept Signal Theory Networking & Commun, Granada, Spain. [Puntonet, Carlos G.] Univ Granada, Dept Comp Architecture & Technol, Granada, Spain. RP Segovia, F (reprint author), Ctr Rech Cyclotron, Bat B30,Allee 6 Aout 8, B-4000 Liege 1, Belgium. EM fsegovia@ulg.ac.be RI Gorriz, Juan/C-2385-2012; Ramirez, Javier/B-1836-2012 OI Ramirez, Javier/0000-0002-6229-2921 FU University of Granada under the Genil PYR [2012-10, CEB09-0010]; University of Liege; Clinical Scientist Fellowship from the UK Medical Research Council (MRC) [G0701919]; UK National Institute for Health Research Cambridge Biomedical Research Centre; Medical Research Council; Wellcome Trust; Autism Research Trust FX This work was partly supported by the University of Granada under the Genil PYR 2012-10 project (CEI BioTIC GENIL CEB09-0010) and the University of Liege. The study was also funded by a Clinical Scientist Fellowship from the UK Medical Research Council (MRC (G0701919)) to Michael Spencer and by the UK National Institute for Health Research Cambridge Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Baron-Cohen was supported by the Medical Research Council, the Wellcome Trust, and the Autism Research Trust during the period of this work. 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Comput. Neurosci. PD JUN 6 PY 2014 VL 8 AR 60 DI 10.3389/fncom.2014.00060 PG 8 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA AI4JU UT WOS:000336832300002 PM 24936183 ER PT J AU Blumenthal, I Ragavendran, A Erdin, S Klei, L Sugathan, A Guide, JR Manavalan, P Zhou, JQ Wheeler, VC Levin, JZ Ernst, C Roeder, K Devlin, B Gusella, JF Talkowski, ME AF Blumenthal, Ian Ragavendran, Ashok Erdin, Serkan Klei, Lambertus Sugathan, Aarathi Guide, Jolene R. Manavalan, Poornima Zhou, Julian Q. Wheeler, Vanessa C. Levin, Joshua Z. Ernst, Carl Roeder, Kathryn Devlin, Bernie Gusella, James F. Talkowski, Michael E. TI Transcriptional Consequences of 16p11.2 Deletion and Duplication in Mouse Cortex and Multiplex Autism Families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DE-NOVO MUTATIONS; DIFFERENTIAL EXPRESSION ANALYSIS; LONG-RANGE INTERACTIONS; COPY-NUMBER VARIATIONS; SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; MICRODELETION SYNDROME; ENRICHMENT ANALYSIS; FUNCTIONAL IMPACT; R PACKAGE AB Reciprocal copy-number variation (CNV) of a 593 kb region of 16p11.2 is a common genetic cause of autism spectrum disorder (ASD), yet it is not completely penetrant and can manifest in a wide array of phenotypes. To explore its molecular consequences, we performed RNA sequencing of cerebral cortex from mouse models with CNV of the syntenic 7qF3 region and lymphoblast lines from 34 members of 7 multiplex ASD-affected families harboring the 16p11.2 CNV. Expression of all genes in the CNV region correlated well with their DNA copy number, with no evidence of dosage compensation. We observed effects on gene expression outside the CNV region, including apparent positional effects in cis and in trans at genomic segments with evidence of physical interaction in Hi-C chromosome conformation data. One of the most significant positional effects was telomeric to the 16p11.2 CNV and includes the previously described "distal" 16p11.2 microdeletion. Overall, 16p11.2 CNV was associated with altered expression of genes and networks that converge on multiple hypotheses of ASD pathogenesis, including synaptic function (e.g., NRXN1, NRXN3), chromatin modification (e.g., CHD8, EHMT1, MECP2), transcriptional regulation (e.g., TCF4, SATB2), and intellectual disability (e.g., FMR1, CEP290). However, there were differences between tissues and species, with the strongest effects being consistently within the CNV region itself. Our analyses suggest that through a combination of indirect regulatory effects and direct effects on nuclear architecture, alteration of 16p11.2 genes disrupts expression networks that involve other genes and pathways known to contribute to ASD, suggesting an overlap in mechanisms of pathogenesis. C1 [Blumenthal, Ian; Ragavendran, Ashok; Erdin, Serkan; Sugathan, Aarathi; Guide, Jolene R.; Manavalan, Poornima; Wheeler, Vanessa C.; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Blumenthal, Ian; Ragavendran, Ashok; Erdin, Serkan; Sugathan, Aarathi; Guide, Jolene R.; Manavalan, Poornima; Wheeler, Vanessa C.; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Levin, Joshua Z.; Gusella, James F.; Talkowski, Michael E.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02141 USA. [Ernst, Carl] McGill Univ, Dept Psychiat, Douglas Hosp, Res Inst, Verdun, PQ H4H 1R3, Canada. [Zhou, Julian Q.; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02141 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02141 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02141 USA. [Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02141 USA. [Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Boston, MA 02141 USA. RP Talkowski, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. EM talkowski@chgr.mgh.harvard.edu RI Erdin, Serkan/B-4988-2008 OI Erdin, Serkan/0000-0001-6587-2625 FU National Institute of Mental Health [MH095867, R37 MH057881, 1U24MH081810]; Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation; Brain and Behavorial Research Foundation (NARSAD); Autism Genetic Resource Exchange (AGRE) and Autism Speaks FX We thank A. Mills for development of the mouse models and AGRE for providing biological materials. These studies were supported by the National Institute of Mental Health (MH095867 to M.E.T., R37 MH057881 to B.D. and K.R.), the Simons Foundation for Autism Research (M.E.T., J.F.G.), the Nancy Lurie Marks Family Foundation (M.E.T., J.F.G.), and the Brain and Behavorial Research Foundation (NARSAD; M.E.T.). We also acknowledge support from the Autism Genetic Resource Exchange (AGRE) and Autism Speaks (to J.F.G.). We gratefully acknowledge the resources provided by the AGRE consortium and the participating AGRE families. The Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). 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PD JUN 5 PY 2014 VL 12 AR 45 DI 10.1186/1741-7007-12-45 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI4DH UT WOS:000336815300001 PM 24903674 ER PT J AU Pineda, JA Carrasco, K Datko, M Pillen, S Schalles, M AF Pineda, Jaime A. Carrasco, Karen Datko, Mike Pillen, Steven Schalles, Matt TI Neurofeedback training produces normalization in behavioural and electrophysiological measures of high-functioning autism SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE mirror neuron system; sensorimotor systems; electroencephalogram mu rhythms; mu suppression index ID MIRROR-NEURON SYSTEM; SPECTRUM DISORDERS; MU-RHYTHMS; CORTICAL RHYTHMS; EEG BIOFEEDBACK; ALPHA RHYTHMS; BRAIN; CHILDREN; SUPPRESSION; MOVEMENT AB Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains. C1 [Pineda, Jaime A.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Grp Neurosci, La Jolla, CA 92093 USA. RP Pineda, JA (reprint author), Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. EM pineda@cogsci.ucsd.edu FU Congressionally Directed Medical Research Programme [AR093335] FX We thank the Congressionally Directed Medical Research Programme for an Autism Research Programme (ARP) Idea Award (AR093335) to J.P. 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Trans. R. Soc. B-Biol. Sci. PD JUN 5 PY 2014 VL 369 IS 1644 SI SI AR 20130183 DI 10.1098/rstb.2013.0183 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AG6XY UT WOS:000335563600010 PM 24778378 ER PT J AU Weltzin, MM Huang, YZ Schulte, MK AF Weltzin, Maegan M. Huang, Yanzhou Schulte, Marvin K. TI Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Alpha4beta2; Alpha7; Nicotinic acetylcholine receptor; Ligand gated ion channels; Positive allosteric modulation; HEPES; desformylflustrabromine; dFbr; Two-electrode voltage clamp; Mutagenesis ID ALTERNATE STOICHIOMETRIES; CRYSTAL-STRUCTURE; RB-86(+) EFFLUX; ION-CHANNEL; ALPHA-4-BETA-2; BINDING; SUBUNIT; BUFFER; TRIS; DESFORMYLFLUSTRABROMINE AB A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands.PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10 mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2 1/ beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. (C) 2012 Elsevier B.V. Allrightsreserved. C1 [Weltzin, Maegan M.; Huang, Yanzhou; Schulte, Marvin K.] Univ Alaska Fairbanks, Dept Chem & Biochem, Fairbanks, AK 99775 USA. RP Schulte, MK (reprint author), Univ Alaska Fairbanks, Dept Chem & Biochem, Fairbanks, AK 99775 USA. EM mkschulte@alaska.edu FU National Center for Research Resources [5P20RR016466]; National Institutes of Neurological Disorders and Stroke [1R01NS057366, 1R01NS066059]; Components of the National Institutes of Health (NIH) FX This research was supported by grants from the National Center for Research Resources (5P20RR016466, Alaska INBRE Program) and The National Institutes of Neurological Disorders and Stroke[1R01NS066059 and 1R01NS057366], Components of the National Institutes of Health (NIH). 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PD JUN PY 2014 VL 12 IS 2 BP 355 EP 374 PG 20 WC Literary Theory & Criticism SC Literature GA CB4FO UT WOS:000349583800009 ER PT J AU Nakai, Y Takashima, R Takiguchi, T Takada, S AF Nakai, Yasushi Takashima, Ryoichi Takiguchi, Tetsuya Takada, Satoshi TI Speech intonation in children with autism spectrum disorder SO BRAIN & DEVELOPMENT LA English DT Article DE Autism spectrum disorder; Intonation; Acoustic analysis; Pitch; Coefficient of variation; ASQ ID HIGH-FUNCTIONING AUTISM; PROSODY; QUESTIONNAIRE; SPEAKERS; MELODY; PITCH AB Objective: The prosody of children with autism spectrum disorder (ASD) has several abnormal features. We assessed the speech tone of children with ASD and of children with typical development (TD) by using a new quantitative acoustic analysis. Methods: Our study participants consisted of 63 children (26 with ASD and 37 with TD). The participants were divided into 4 groups based on their developmental features and age. We assessed the variety of the fundamental frequency (F0) pattern quantitatively, using pitch coefficient of variation (CV), considering the different F0 mean for each word. Results: (1) No significant difference was observed between the ASD and TD group at pre-school age. However, the TD group exhibited significantly greater pitch CV than the ASD group at school age. (2) In pitch CV, range and standard deviation of the whole speech of each participant, no significant differences were observed between the type of participants and age. (3) No significant correlation was found between the pitch CV of each word and the Japanese Autism Screening Questionnaire total score, or between the pitch CV of each word and the intelligence quotient levels in the ASD group. A significant correlation was observed between the pitch CV of each word and social reciprocal interaction score. Conclusions: We assessed the speech tone of children with ASD by using a new quantitative method. Monotonous speech in school-aged children with ASD was detected. The extent of monotonous speech was related to the extent of social reciprocal interaction in children with ASD. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. C1 [Nakai, Yasushi; Takada, Satoshi] Kobe Univ, Grad Sch Hlth Sci, Kobe, Hyogo 657, Japan. [Nakai, Yasushi] Kawasaki Coll Allied Hlth Profess, Dept Nursing Childcare, Kurashiki, Okayama 7010194, Japan. [Takashima, Ryoichi; Takiguchi, Tetsuya] Kobe Univ, Grad Sch Syst Informat, Kobe, Hyogo 657, Japan. RP Nakai, Y (reprint author), Kawasaki Coll Allied Hlth Profess, Dept Nursing Childcare, 316 Matsushima, Kurashiki, Okayama 7010194, Japan. EM nakai@jc.kawasaki-m.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology [21700565] FX This study was supported by the Ministry of Education, Culture, Sports, Science and Technology (21700565). 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The present study assessed younger and older adults' orbicularis oculi (O.oculi; eye) and zygomaticus major (Z.major; cheek) reactions to images of individuals displaying enjoyment and nonenjoyment smiles. Both age groups mimicked displays of enjoyment smiles, and there were no age differences in O.oculi and Z.major activity to these expressions. However, compared with younger participants, older adults showed extended O.oculi activity to nonenjoyment smiles. In an explicit ratings task, older adults were also more likely than younger participants to attribute feelings of happiness to individuals displaying both nonenjoyment and enjoyment smiles. However, participants' ratings of the happiness expressed in images of enjoyment and nonenjoyment smiles were independent of their O.oculi responding to these expressions, suggesting that mimicry and emotion recognition may reflect separate processes. Potential mechanisms underlying these findings, as well as implications for social affiliation in older adulthood, are considered. C1 [Slessor, Gillian; Miles, Lynden K.] Univ Aberdeen, Sch Psychol, Aberdeen AB24 2UB, Scotland. [Bailey, Phoebe E.] Univ Western Sydney, Sch Social Sci & Psychol, Sydney, NSW, Australia. [Bailey, Phoebe E.; Henry, Julie D.] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. [Rendell, Peter G.] Australian Catholic Univ, Sch Psychol, Sydney, NSW 2059, Australia. [Ruffman, Ted] Univ Otago, Dept Psychol, Dunedin, New Zealand. [Henry, Julie D.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. RP Slessor, G (reprint author), Univ Aberdeen, Sch Psychol, Coll Life Sci & Med, William Guild Bldg, Aberdeen AB24 2UB, Scotland. 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TI Oxytocin and Vasopressin Receptor Polymorphisms Interact With Circulating Neuropeptides to Predict Human Emotional Reactions to Stress SO EMOTION LA English DT Article DE OXTR rs53576; oxytocin; AVPR1A RS1; vasopressin; emotion ID AUTISM SPECTRUM DISORDERS; HAMSTERS MESOCRICETUS-AURATUS; ADRENAL AXIS RESPONSES; SOCIAL-BEHAVIOR; ARGININE-VASOPRESSIN; AGGRESSIVE-BEHAVIOR; GENE OXTR; PSYCHOSOCIAL STRESS; LACTATING WOMEN; GOLDEN-HAMSTERS AB Oxytocin (OT) and a polymorphism (rs53576) in the oxytocin receptor gene (OXTR) have been independently associated with stress reactivity, whereas oxytocin's sister peptide, arginine vasopressin (AVP) and polymorphisms in the vasopressin receptor gene (AVPR1A) have been independently associated with aggressive behavior. In this study, 68 men and 98 women were genotyped for the OXTR rs53576 polymorphism and the AVPR1A RS1 polymorphism. Baseline and poststressor levels of plasma OT, plasma AVP, positive affect, and anger were assessed. Women, but not men, with high levels of poststressor OT and the GG genotype of rs53576 felt the most positive affect after the stressor. Men, but not women, with high levels of poststressor AVP and the 320 allele of the RS1 polymorphism reported more poststressor anger than noncarriers. These data constitute the first evidence that oxytocin and vasopressin receptor genes interact with levels of OT and AVP to predict sex-specific emotional stress responses. C1 [Moons, Wesley G.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Way, Baldwin M.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Taylor, Shelley E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Moons, WG (reprint author), Univ Calif Davis, Dept Psychol, 1 Shields Ave, Davis, CA 95616 USA. 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The purpose of this study was to examine the functional relation between bug-in-ear coaching and the frequency of educators' correct use of targeted communication strategies, as well as associations with children's expressive communication. Four multiple-baseline single-case intervention design experiments were completed. Dependent variables were educators' use of communication strategies and the expressive communication of children with delays or disabilities. Bug-in-ear improved educators' implementation of at least one communication strategy for each educator. Effect sizes were large for three educators and moderate for one. Each behavior successfully implemented during intervention was maintained at moderate levels or better, while behaviors implemented with greater variability during intervention were not maintained. Associations with children's expressive communication were questionable/small during both intervention and maintenance. 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TI The Effects of Constant Time Delay and Instructive Feedback on the Acquisition of English and Spanish Sight Words SO JOURNAL OF EARLY INTERVENTION LA English DT Article DE constant time delay; instructive feedback; observational learning ID SOCIAL VALIDATION; VALIDITY; CHILDREN; AUTISM AB The authors of this study evaluated the acquisition of instructive feedback information presented to four kindergarten children with mild delays taught in dyads using a constant time delay (CTD) procedure. They also assessed the learning of observational (dyadic partner) information within this instructional arrangement. A multiple probe design across word sets, replicated across the four participants, was used to evaluate the efficacy of the CTD procedure and instructive feedback on the students' expressive English sight word identification, the corresponding Spanish translations, and other students' target words. 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PD JUN PY 2014 VL 36 IS 2 BP 131 EP 148 DI 10.1177/1053815114563613 PG 18 WC Education, Special; Psychology, Educational; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AX4FT UT WOS:000346889800004 ER PT J AU van der Meer, L Sigafoos, J Sutherland, D McLay, L Lang, R Lancioni, GE O'Reilly, MF Marschik, PB AF van der Meer, Larah Sigafoos, Jeff Sutherland, Dean McLay, Laurie Lang, Russell Lancioni, Giulio E. O'Reilly, Mark F. Marschik, Peter B. TI Preference-Enhanced Communication Intervention and Development of Social Communicative Functions in a Child With Autism Spectrum Disorder SO CLINICAL CASE STUDIES LA English DT Article DE augmentative and alternative communication; autism spectrum disorder; iPad (R); preference; speech-generating devices ID SPEECH-GENERATING DEVICES; ALTERNATIVE COMMUNICATION; PICTURE EXCHANGE; LANGUAGE; DISABILITIES; PATHOLOGY; INDIVIDUALS; TECHNOLOGY; STUDENTS; MODES AB Individuals with autism spectrum disorder (ASD) who exhibit limited speech can learn to communicate using augmentative and alternative communication (AAC) systems. We describe the case of Ian, a 10-year-old boy with ASD who had learned to use an Apple iPod (R)- and iPad (R)-based speech-generating device (SGD)(Note 1), picture exchange (PE), and manual signing (MS) for functional communication (e.g., requesting), but had difficulty in using these AAC systems for spontaneous and socially oriented functions of communication. His difficulties were originally conceptualized as reflecting the social interaction and communication deficits characteristic of ASD. Alternatively, we suggest that the intervention did not allow for the development of more advanced communication. A preference-enhanced intervention was introduced with Ian's chosen AAC system only, that is the iPad (R)-based SGD. Opportunities for communication were created using highly motivating activities and behavioral strategies. Results suggest that the approach facilitated development of spontaneous and socially oriented communication. C1 [van der Meer, Larah; Sigafoos, Jeff] Victoria Univ Wellington, Sch Educ Psychol, Wellington 6005, New Zealand. [Sutherland, Dean; McLay, Laurie] Univ Canterbury, Sch Hlth Sci, Christchurch 1, New Zealand. [Lang, Russell] Texas State Univ, Dept Curriculum & Instruct, San Marcos, TX USA. [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, I-70121 Bari, Italy. [O'Reilly, Mark F.] Univ Texas Austin, Coll Educ, Austin, TX 78712 USA. [Marschik, Peter B.] Med Univ Graz, Inst Physiol, Graz, Austria. [O'Reilly, Mark F.] Univ Texas Austin, Dept Special Educ, Austin, TX 78712 USA. RP Sigafoos, J (reprint author), Victoria Univ Wellington, Sch Educ Psychol, POB 17-310,Karori 6147, Wellington 6005, New Zealand. 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Case Stud. PD JUN PY 2014 VL 13 IS 3 BP 282 EP 295 DI 10.1177/1534650113508221 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9PG UT WOS:000346588900006 ER PT J AU Milovancevic, MP Tenjovic, L Ispanovic, V Mitkovic, M Kircanski, JR Mincic, T Miletic, V Gajic, SD Tosevski, DL AF Milovancevic, Milica Pejovic Tenjovic, Lazar Ispanovic, Veronika Mitkovic, Marija Kircanski, Jelena Radosavljev Mincic, Teodora Miletic, Vladimir Gajic, Saveta Draganic Tosevski, Dusica Lecic TI Psychopathology and resilience in relation to abuse in childhood among youth first referred to the psychiatrist SO VOJNOSANITETSKI PREGLED LA English DT Article DE psychopathology; resilience, psychological; child abuse; adolescent psyhiatry ID CHILDREN; MECHANISMS; ASSOCIATIONS; MALTREATMENT; ADOLESCENTS; VIOLENCE; AUTISM; HEALTH AB Background/Aim. Child abuse may be related to adverse psychological outcomes in adult life. However, little is known about specific clinical, family and resilience profiles of adolescents that have experienced child abuse. The aim of this study was to investigate clinical symptoms, family functioning and resilience characteristics of adolescents with the experience of abuse, first referred to psychiatrists. Methods. The study included 84 young participants (mean age 14.90 +/- 3.10, ranging from 11 to 18 years) as consecutive first referrals to the Clinic for Children and Youth of the Institute of Mental Health, Belgrade, Serbia. The sample consisted of two groups, based on the Child Abuse Matrices of Risks. The first group included adolescents with the experience of abuse in childhood (n = 38, 13 males, 25 females), whereas the second, control group, comprised of non-abused adolescents (n = 47, 20 males, 27 females). The presence of abuse was evaluated by the Child Abuse Matrices of Risks. The study used the following questionnaires: Youth Self-Report (YSR), Adolescent Resilience Attitudes Scale (ARAS), and Self-Report Family Inventory (SFI). Results. Significant differences were found only among females. According to YSR, the abused girls had significantly higher scores on the Delinquent Behavior scale and marginally higher scores on Anxious/Depressed and Social Problems scales. Analyses of the SFI showed significantly lower family functioning among the girls with the child abuse history for all scales except for the Directive Leadership. The abused girls also showed significantly lower scores on the Insight scale, and marginally lower Initiative scores at the ARAS. Conclusions. These findings may have practical application in the creation of specific preventive and treatment strategies, particularly focused on delinquent tendencies, as well as on enhancing resilience through providing positive environments within families, schools and communities. C1 [Milovancevic, Milica Pejovic; Gajic, Saveta Draganic; Tosevski, Dusica Lecic] Univ Belgrade, Fac Med, Belgrade, Serbia. [Milovancevic, Milica Pejovic; Mitkovic, Marija; Kircanski, Jelena Radosavljev; Mincic, Teodora; Gajic, Saveta Draganic; Tosevski, Dusica Lecic] Inst Mental Hlth, Belgrade, Serbia. [Tenjovic, Lazar] Univ Belgrade, Dept Psychol, Fac Philosophy, Belgrade, Serbia. [Ispanovic, Veronika; Kircanski, Jelena Radosavljev] Univ Singidunum, Dept Psychol, Fac Media & Commun, Belgrade, Serbia. [Miletic, Vladimir] Assoc Mental Hlth Promot, Belgrade, Serbia. RP Milovancevic, MP (reprint author), Univ Belgrade, Inst Mental Hlth, Fac Med, Belgrade, Serbia. 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Pregl. PD JUN PY 2014 VL 71 IS 6 BP 565 EP 570 DI 10.2298/VSP1406565P PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AU7YH UT WOS:000345813700007 PM 25039111 ER PT J AU Drapeau, E Dorr, NP Elder, GA Buxbaum, JD AF Drapeau, Elodie Dorr, Nate P. Elder, Gregory A. Buxbaum, Joseph D. TI Absence of strong strain effects in behavioral analyses of Shank3-deficient mice SO DISEASE MODELS & MECHANISMS LA English DT Article DE Shank3; Phelan-McDermid syndrome; Autism spectrum disorders; 22q13; Mouse strain; Genetic modifier; Behavior ID AUTISM SPECTRUM DISORDERS; 22Q13 DELETION SYNDROME; COPY NUMBER VARIATION; INBRED MOUSE STRAINS; POSTSYNAPTIC DENSITY PROTEINS; KNOCKOUT MICE; MUTANT MICE; SYNAPTIC FUNCTION; LABORATORY MICE; SHANK FAMILY AB Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent. C1 [Drapeau, Elodie; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Drapeau, Elodie; Dorr, Nate P.; Elder, Gregory A.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Syst Biol Ctr New York, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu FU National Institutes of Health [R01MH093725]; Beatrice and Samuel A. Seaver Foundation; Simons Foundation Autism Research Initiative FX This work was supported by the National Institutes of Health [grant number: R01MH093725], the Beatrice and Samuel A. Seaver Foundation, and the Simons Foundation Autism Research Initiative. 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Model. Mech. PD JUN PY 2014 VL 7 IS 6 BP 667 EP 681 DI 10.1242/dmm.013821 PG 15 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AT5SQ UT WOS:000345002600008 PM 24652766 ER PT J AU An, JY Cristino, AS Zhao, Q Edson, J Williams, SM Ravine, D Wray, J Marshall, VM Hunt, A Whitehouse, AJO Claudianos, C AF An, J. Y. Cristino, A. S. Zhao, Q. Edson, J. Williams, S. M. Ravine, D. Wray, J. Marshall, V. M. Hunt, A. Whitehouse, A. J. O. Claudianos, C. TI Towards a molecular characterization of autism spectrum disorders: an exome sequencing and systems approach SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID DE-NOVO MUTATIONS; GENETIC-VARIANTS; ASSOCIATION; DISEASE; FEATURES; SNPS; NEUROLIGINS; ANNOTATION; NEUREXINS; PHENOTYPE AB The hypothetical 'AXAS' gene network model that profiles functional patterns of heterogeneous DNA variants overrepresented in autism spectrum disorder (ASD), X-linked intellectual disability, attention deficit and hyperactivity disorder and schizophrenia was used in this current study to analyze whole exome sequencing data from an Australian ASD cohort. An optimized DNA variant filtering pipeline was used to identify loss-of-function DNA variations. Inherited variants from parents with a broader autism phenotype and de novo variants were found to be significantly associated with ASD. Gene ontology analysis revealed that putative rare causal variants cluster in key neurobiological processes and are overrepresented in functions involving neuronal development, signal transduction and synapse development including the neurexin trans-synaptic complex. We also show how a complex gene network model can be used to fine map combinations of inherited and de novo variations in families with ASD that converge in the L1CAM pathway. Our results provide an important step forward in the molecular characterization of ASD with potential for developing a tool to analyze the pathogenesis of individual affected families. C1 [An, J. Y.; Cristino, A. S.; Zhao, Q.; Edson, J.; Williams, S. M.; Marshall, V. M.; Claudianos, C.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia. [Ravine, D.] Sch Pathol & Lab Med, Perth, WA, Australia. [Wray, J.] Princess Margaret Hosp Children, State Child Dev Ctr, Child & Adolescent Hlth Serv, Perth, WA, Australia. [Hunt, A.; Whitehouse, A. J. O.] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Subiaco, WA, Australia. [Whitehouse, A. J. O.; Claudianos, C.] Cooperat Res Ctr Living Autism Spectrum Disorders, Brisbane, Qld, Australia. RP Claudianos, C (reprint author), Univ Queensland, Queensland Brain Inst, Bldg 79, St Lucia, Qld 4072, Australia. EM c.claudianos@uq.edu.au RI Zhao, Qiongyi/B-4106-2014; Cristino, Alexandre/A-5834-2012 OI Zhao, Qiongyi/0000-0002-6341-0416; Cristino, Alexandre/0000-0002-3468-0919 FU Commonwealth Department of Social Services; Cooperative Research Centre for Living; Autism Spectrum Disorders the Autism CRC; Australian Government's Cooperative Research Centres program; Australian Research Council [FT110100292]; National Health and Medical Research Council [APP1008125, APP1004065]; University of Queensland PhD scholarship; Australian Postgraduate Award FX We thank the families that participated in our study and R Tweedale, J Reinhard and A Larkin for critical reading of the manuscript. We acknowledge the financial support of the Commonwealth Department of Social Services (formerly the Department of Families, Housing, Community Services and Indigenous Affairs) and the Cooperative Research Centre for Living with Autism Spectrum Disorders the Autism CRC, established and supported under the Australian Government's Cooperative Research Centres program. CC was supported by funding from the Australian Research Council (FT110100292) and CC and AJOW by funding from the National Health and Medical Research Council (APP1008125; APP1004065). JYA was supported by a University of Queensland PhD scholarship and SMW by an Australian Postgraduate Award. We also thank John Beilby and PathWest for facilitating collection of samples and patient data. 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Psychiatr. PD JUN PY 2014 VL 4 AR e394 DI 10.1038/tp.2014.38 PG 9 WC Psychiatry SC Psychiatry GA AT3HN UT WOS:000344826500002 PM 24893065 ER PT J AU Naviaux, JC Schuchbauer, MA Li, K Wang, L Risbrough, VB Powell, SB Naviaux, RK AF Naviaux, J. C. Schuchbauer, M. A. Li, K. Wang, L. Risbrough, V. B. Powell, S. B. Naviaux, R. K. TI Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID PRENATAL IMMUNE ACTIVATION; SPECTRUM DISORDERS; PYRIMIDINE METABOLISM; NEURODEVELOPMENTAL DISORDERS; PURINE METABOLISM; AREA POSTREMA; SCHIZOPHRENIA; RECEPTORS; ABNORMALITIES; CHILDREN AB Autism spectrum disorders (ASDs) now affect 1-2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg(-1) intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 mu M pmol mu l(-1) (+/-0.50) and 5.15 pmol mg(-1) (+/-0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults. C1 [Naviaux, J. C.; Schuchbauer, M. A.; Risbrough, V. B.; Powell, S. B.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Li, K.; Wang, L.; Naviaux, R. K.] Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, San Diego, CA 92103 USA. [Li, K.; Wang, L.; Naviaux, R. K.] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. [Risbrough, V. B.; Naviaux, R. K.] Vet Affairs Ctr Excellence Stress & Mental Hlth C, La Jolla, CA USA. [Naviaux, R. K.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Naviaux, R. K.] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. RP Naviaux, JC (reprint author), Univ Calif San Diego, Sch Med, Dept Med, 214 Dickinson St,Bldg CTF,Room C102, San Diego, CA 92103 USA. EM naviaux@ucsd.edu FU Jane Botsford Johnson Foundation (RKN); National Institute of Health [MH091407]; UCSD Christini Foundation; Wright Family Foundation; It Takes Guts Foundation FX We thank Dewleen Baker, Sophia Colamarino, Richard Haas, William Nyhan, Maya Shetreat-Klein, Leanne Chukoskie, Jeanne Townsend, Will Alaynick, Andrea Chiba, Ben Murrell, Jim Adams and Steve Edelson for helpful discussions and comments on the manuscript. We thank Laura Dugan for providing the rotarod and comments on the manuscript. We thank two anonymous reviewers for helpful comments. This research was supported by grants from the Jane Botsford Johnson Foundation (RKN) and National Institute of Health grant MH091407 (SBP), with additional support from the UCSD Christini Foundation, the Wright Family Foundation and the It Takes Guts Foundation to RKN. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. 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Bryant, Danielle Sanders, Katie Baldus, Nicole Algier, Katherine Lewis, Audrey Traber, Jordan Layden, Paige Amin, Aneeqa TI Fitting and Verification of Frequency Modulation Systems on Children with Normal Hearing SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Fitting; FM systems; normal hearing ID AUTISM SPECTRUM DISORDERS; PERSONAL FM SYSTEMS; FRIEDREICH ATAXIA; SPEECH; NOISE; INDIVIDUALS; DYSLEXIA AB Background: Several recent investigations support the use of frequency modulation (FM) systems in children with normal hearing and auditory processing or listening disorders such as those diagnosed with auditory processing disorders, autism spectrum disorders, attention-deficit hyperactivity disorder, Friedreich ataxia, and dyslexia. The American Academy of Audiology (AAA) published suggested procedures, but these guidelines do not cite research evidence to support the validity of the recommended procedures for fitting and verifying nonoccluding open-ear FM systems on children with normal hearing. Documenting the validity of These fitting procedures is critical to maximize the potential FM-system benefit in the abovementioned populations of children with normal hearing and those with auditory-listening problems. Purpose: The primary goal of this investigation was to determine the validity of the AAA real-ear approach to fitting FM systems on children with normal hearing. The secondary goal of this study was to examine speech-recognition performance in noise and loudness ratings without and with FM systems in children with normal hearing sensitivity. Research Design: A two-group, cross-sectional design was used in the present study. Study Sample: Twenty-six typically functioning children, ages 5-12 yr, with normal hearing sensitivity participated in the study. Intervention: Participants used a nonoccluding open-ear FM receiver during laboratory-based testing. Data Collection and Analysis: Participants completed three laboratory tests: (1) real-ear measures, (2) speech recognition performance in noise, and (3) loudness ratings. Four real-ear measures were conducted to (1) verify that measured output met prescribed-gain targets across the 1000-4000 Hz frequency range for speech stimuli, (2) confirm that the FM-receiver volume did not exceed predicted uncomfortable loudness levels, and (3 and 4) measure changes to the real-ear unaided response when placing the FM receiver in the child's ear. After completion of the fitting, speech recognition in noise at a 5 signal-to-noise ratio and loudness ratings at a +5 signal-to-noise ratio were measured in four conditions: (1) no FM system, (2) FM receiver on the right ear, (3) FM receiver on the left ear, and (4) bilateral FM system. Results: The results of this study suggested that the slightly modified AAA real-ear measurement procedures resulted in a valid fitting of one FM system on children with normal hearing. On average, prescriptive targets were met for 1000, 2000, 3000, and 4000 Hz within 3 dB, and maximum output of the FM system never exceeded and was significantly lower than predicted uncomfortable loudness levels for the children. There was a minimal change in the real-ear unaided response when the open-ear FM receiver was placed into the ear. Use of the FM system on one-or both ears resulted in significantly better speech recognition in noise relative to a no-FM condition, and the unilateral and bilateral FM receivers resulted in a comfortably loud signal when listening in background noise. Conclusions: Real-ear measures are critical for obtaining an appropriate fit of an FM system on children with normal hearing. C1 [Schafer, Erin C.; Bryant, Danielle; Sanders, Katie; Baldus, Nicole; Algier, Katherine; Lewis, Audrey; Traber, Jordan; Layden, Paige; Amin, Aneeqa] Univ N Texas, Dept Speech & Hearing Sci, Denton, TX 76203 USA. RP Schafer, EC (reprint author), Univ N Texas, Dept Speech & Hearing Sci, 1155 Union Circle 305010, Denton, TX 76203 USA. EM Erin.Schafer@unt.edu FU Phonak AG FX Funding for this study was provided by Phonak AG. The funds were used to compensate participants for their time, efforts, and mileage to the test center. The authors of this manuscript received no monetary compensation related to the study. The equipment for the study was loaned to the investigators by Phonak AG and returned after the study was completed. 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PD JUN PY 2014 VL 19 IS 2 SI SI BP 73 EP 83 DI 10.1080/0969725X.2014.950863 PG 11 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA AP5QF UT WOS:000342133000008 ER PT J AU Verkhratsky, A Parpura, V AF Verkhratsky, Alexei Parpura, Vladimir TI Neurological and psychiatric disorders as a neuroglial failure SO PERIODICUM BIOLOGORUM LA English DT Article DE neuroglia; astrocyte; oligodendrocyte; microglia; reactive gliosis; NG2 glia; neurological diseases; neurodegeneration; psychiatric diseases ID AMYOTROPHIC-LATERAL-SCLEROSIS; AUTISM SPECTRUM DISORDERS; TRANSGENIC ANIMAL-MODEL; DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; REACTIVE GLIOSIS; FRONTOTEMPORAL DEMENTIA; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; KYNURENIC ACID AB Neuroglia are a diverse non-neuronal population of cells in the central and peripheral nervous system. These cells have a variety of functions that can all be summed up as the maintenance of homeostasis of the nervous system. It is the loss of homeostasis that represents the culprit of all disorders. Thus, neuroglia can be envisioned as the pivotal element in all neural disorders, be that neurological or psychiatric. In this review, we discuss the role of glia in homeostasis and defence of the nervous system as well as changes in the morpho-functional characteristics of these cells in various disorders. C1 [Verkhratsky, Alexei] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Verkhratsky, Alexei] Basque Fdn Sci, Ikerbasque, Achucarro Ctr Neurosci, Bilbao 48011, Spain. [Verkhratsky, Alexei] Univ Nizhny Novgorod, Nizhnii Novgorod 603022, Russia. [Parpura, Vladimir] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Ctr Glial Biol Med, Dept Neurobiol,Atom Force Microscopy Lab, Birmingham, AL 35294 USA. [Parpura, Vladimir] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Civilan Int Res Ctr, Nanotechnol Lab, Birmingham, AL 35294 USA. 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TI The Effects of Robot-Enhanced Psychotherapy: A Meta-Analysis SO REVIEW OF GENERAL PSYCHOLOGY LA English DT Article DE robot-enhanced/assisted therapy; psychological outcomes; meta-analysis ID REALITY EXPOSURE THERAPY; ANXIETY DISORDERS; ELDERLY-PEOPLE; SOCIAL ROBOTS; CHILDREN; AUTISM; CARE; ASD AB Through this meta-analysis we aimed to provide an estimation of the overall effect of robot-enhanced therapy on psychological outcome for different populations, to provide average effect sizes on different outcomes, such as cognitive, behavioral and subjective, and to test possible moderators of effect size. From a total of 861 considered studies for this meta-analysis, only 12 were included because of the lack of studies that have reported quantitative data in this area and because of their primary focus on describing the process of robotic development rather than measuring psychological outcomes. We calculated Cohen's d effect sizes for every outcome measure for which sufficient data were reported. The results show that robot-enhanced therapy yielded a medium effect size overall and, specifically on the behavioral level, indicating that 69% of patients in the control groups did worse than the average number of participants in the intervention group. More studies are needed with regard to specific outcomes to prove the efficacy of robot-enhanced therapy, but the overall results clearly support the use of robot-enhanced therapy for different populations. C1 [Costescu, Cristina A.; David, Daniel O.] Univ Babes Bolyai, Dept Clin Psychol & Psychotherapy, Cluj Napoca 400015, Cluj, Romania. [Vanderborght, Bram] Vrije Univ Brussel, Robot & Multibody Mech Res Grp, Brussels, Belgium. [David, Daniel O.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. 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Gen. Psychol. PD JUN PY 2014 VL 18 IS 2 BP 127 EP 136 DI 10.1037/gpr0000007 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AN3FQ UT WOS:000340471200007 ER PT J AU Christinaki, E Vidakis, N Triantafyllidis, G AF Christinaki, Eirini Vidakis, Nikolas Triantafyllidis, Georgios TI A Novel Educational Game for teaching Emotion Identification Skills to Preschoolers with Autism Diagnosis SO COMPUTER SCIENCE AND INFORMATION SYSTEMS LA English DT Article DE autism; facial emotion recognition; gesture-based interaction; Kinect; natural user interface ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; COMMUNICATION-SKILLS; RECOGNITION SKILLS; ASPERGER-SYNDROME; YOUNG-CHILDREN; INTERVENTION; INDIVIDUALS; PERCEPTION; ADULTS AB Emotion recognition is essential in human communication and social interaction. Children with autism have been reported to exhibit deficits in understanding and expressing emotions. 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PD JUN PY 2014 VL 11 IS 2 BP 723 EP 743 DI 10.2298/CSIS140215039C PG 21 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA AM7VO UT WOS:000340077000016 ER PT J AU David, D Matu, SA David, OA AF David, Daniel Matu, Silviu-Andrei David, Oana Alexandra TI Robot-Based Psychotherapy: Concepts Development, State of the Art, and New Directions SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID AUTISM SPECTRUM DISORDERS; REALITY EXPOSURE THERAPY; ANIMAL-ASSISTED THERAPY; ELDERLY-PEOPLE; ANXIETY DISORDERS; JOINT ATTENTION; METAANALYSIS; CHILDREN; CARE; IMITATION AB In this article we propose new concepts and a framework of robot-based psychotherapy (or robotics-based psychotherapy; i.e., Robo-Therapist, Robo-Mediator, Robo-Assistant). We also review the state of the art of the field based on this framework and delineate possible but also needed future developments and integrations in the field. 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J. Cogn. Ther. PD JUN PY 2014 VL 7 IS 2 BP 192 EP 210 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AM1NI UT WOS:000339612800008 ER PT J AU Sidorov, MS Krueger, DD Taylor, M Gisin, E Osterweil, EK Bear, MF AF Sidorov, M. S. Krueger, D. D. Taylor, M. Gisin, E. Osterweil, E. K. Bear, M. F. TI Extinction of an instrumental response: a cognitive behavioral assay in Fmr1 knockout mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Fragile X; instrumental extinction; intellectual disability; lovastatin; metabotropic glutamate receptor 5 ID FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; MOUSE MODEL; KO MICE; MGLUR5; DYSFUNCTION; TRANSLATION; LOVASTATIN; RELAPSE AB Fragile X (FX) is the most common genetic cause of intellectual disability and autism. Previous studies have shown that partial inhibition of metabotropic glutamate receptor signaling is sufficient to correct behavioral phenotypes in a mouse model of FX, including audiogenic seizures, open-field hyperactivity and social behavior. These phenotypes model well the epilepsy (15%), hyperactivity (20%) and autism (30%) that are comorbid with FX in human patients. Identifying reliable and robust mouse phenotypes to model cognitive impairments is critical considering the 90% comorbidity of FX and intellectual disability. Recent work characterized a five-choice visuospatial discrimination assay testing cognitive flexibility, in which FX model mice show impairments associated with decreases in synaptic proteins in prefrontal cortex (PFC). In this study, we sought to determine whether instrumental extinction, another process requiring PFC, is altered in FX model mice, and whether downregulation of metabotropic glutamate receptor signaling pathways is sufficient to correct both visuospatial discrimination and extinction phenotypes. We report that instrumental extinction is consistently exaggerated in FX model mice. However, neither the extinction phenotype nor the visuospatial discrimination phenotype is corrected by approaches targeting metabotropic glutamate receptor signaling. This work describes a novel behavioral extinction assay to model impaired cognition in mouse models of neurodevelopmental disorders, provides evidence that extinction is exaggerated in the FX mouse model and suggests possible limitations of metabotropic glutamate receptor-based pharmacotherapy. C1 [Sidorov, M. S.; Krueger, D. D.; Taylor, M.; Gisin, E.; Osterweil, E. K.; Bear, M. F.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Bear, MF (reprint author), MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mbear@mit.edu FU Fraxa Research Foundation; Autism Science Foundation; National Institute of Mental Health [2T32MH074249]; National Institute of Child Health and Development [5RO1HD046903] FX This research was supported by grants from the Fraxa Research Foundation, Autism Science Foundation, National Institute of Mental Health training grant 2T32MH074249, and National Institute of Child Health and Development grant 5RO1HD046903. We thank Dawna Bagherian for her contributions in testing performance on the visuospatial discrimination assay. M. F. B. holds patents on the use of mGluR-based pharmacotherapy for the treatment of fragile X syndrome. 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PD JUN PY 2014 VL 13 IS 5 BP 451 EP 458 DI 10.1111/gbb.12137 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AL8JE UT WOS:000339383600001 ER PT J AU van Rijn, S Stockmann, L van Buggenhout, G van Ravenswaaij-Arts, C Swaab, H AF van Rijn, S. Stockmann, L. van Buggenhout, G. van Ravenswaaij-Arts, C. Swaab, H. TI Social cognition and underlying cognitive mechanisms in children with an extra X chromosome: a comparison with autism spectrum disorder SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Autism; facial expressions; Klinefelter; theory of mind; Trisomy X ID KLINEFELTER-SYNDROME; HIGH-RISK; MIND; SCHIZOPHRENIA; LANGUAGE; BOYS; XYY; XXY; ABNORMALITIES; METAANALYSIS AB Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Trisomy X), 56 children with autism spectrum disorder (ASD) and 88 non-clinical controls, aged 9-18 years, were included. Similar to children with ASD, children with an extra X chromosome showed significant impairments in social cognition. Regression analyses showed that different cognitive functions predicted social cognitive skills in the extra X and ASD groups. The social cognitive deficits were similar for boys and girls with an extra X chromosome, and not specific for a subgroup with high Autism Diagnostic Interview Revised autism scores. Thus, children with an extra X chromosome show social cognitive deficits, which may contribute to social dysfunction, not only in children showing a developmental pattern that is 'typical' for autism but also in those showing mild or late presenting autism symptoms. Our findings may also help explain variance in type of social deficit: children may show similar social difficulties, but these may arise as a consequence of different underlying information processing deficits. C1 [van Rijn, S.; Stockmann, L.; Swaab, H.] Leiden Univ, NL-2333 AK Leiden, Netherlands. [van Rijn, S.; Swaab, H.] Leiden Inst Brain & Cognit, Leiden, Netherlands. [Stockmann, L.] Autism Ctr Rivierduinen, Leiden, Netherlands. [van Buggenhout, G.] Univ Hosp Leuven, Ctr Human Genet, Leuven, Belgium. [van Ravenswaaij-Arts, C.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. RP van Rijn, S (reprint author), Leiden Univ, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands. EM srijn@fsw.leidenuniv.nl FU VENI grant from the Netherlands Organization for Scientific Research (NWO) [016.095.060] FX This work was supported by a VENI grant (grant number 016.095.060 to SvR) from the Netherlands Organization for Scientific Research (NWO). 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PD JUN PY 2014 VL 13 IS 5 BP 459 EP 467 DI 10.1111/gbb.12134 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AL8JE UT WOS:000339383600002 ER PT J AU Olson, H Shen, YP Avallone, J Sheidley, BR Pinsky, R Bergin, AM Berry, GT Duffy, FH Eksioglu, Y Harris, DJ Hisama, FM Ho, E Irons, M Jacobsen, CM James, P Kothare, S Khwaja, O Lipton, J Loddenkemper, T Markowitz, J Maski, K Megerian, JT Neilan, E Raffalli, PC Robbins, M Roberts, A Roe, E Rollins, C Sahin, M Sarco, D Schonwald, A Smith, SE Soul, J Stoler, JM Takeoka, M Tan, WH Torres, AR Tsai, P Urion, DK Weissman, L Wolff, R Wu, BL Miller, DT Poduri, A AF Olson, Heather Shen, Yiping Avallone, Jennifer Sheidley, Beth R. Pinsky, Rebecca Bergin, Ann M. Berry, Gerard T. Duffy, Frank H. Eksioglu, Yaman Harris, David J. Hisama, Fuki M. Ho, Eugenia Irons, Mira Jacobsen, Christina M. James, Philip Kothare, Sanjeev Khwaja, Omar Lipton, Jonathan Loddenkemper, Tobias Markowitz, Jennifer Maski, Kiran Megerian, J. Thomas Neilan, Edward Raffalli, Peter C. Robbins, Michael Roberts, Amy Roe, Eugene Rollins, Caitlin Sahin, Mustafa Sarco, Dean Schonwald, Alison Smith, Sharon E. Soul, Janet Stoler, Joan M. Takeoka, Masanori Tan, Wen-Han Torres, Alcy R. Tsai, Peter Urion, David K. Weissman, Laura Wolff, Robert Wu, Bai-Lin Miller, David T. Poduri, Annapurna TI Copy Number Variation Plays an Important Role in Clinical Epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID IDIOPATHIC GENERALIZED EPILEPSY; CONTIGUOUS-GENE-SYNDROME; COMPARATIVE-GENOMIC-HYBRIDIZATION; FAMILIAL NEONATAL SEIZURES; AUTISM SPECTRUM DISORDERS; SEVERE MYOCLONIC EPILEPSY; INTELLECTUAL DISABILITY; CHROMOSOMAL MICROARRAY; 15Q13.3 MICRODELETIONS; MOLECULAR CHARACTERIZATION AB Objective: To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods: We identified patients with International Classification of Diseases, ninth revision (ICD-9) codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children's Hospital. We reviewed medical records and included patients who met criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results: Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18kb to 142Mb, and 34% were >500kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or "hotspots." We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation: Copy number abnormalities play an important role in patients with epilepsy. Because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. C1 [Olson, Heather; Sheidley, Beth R.; Pinsky, Rebecca; Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Epilepsy Genet Program, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. [Olson, Heather; Sheidley, Beth R.; Pinsky, Rebecca; Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Neurogenet Program, Boston, MA 02115 USA. [Olson, Heather; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Miller, David T.; Poduri, Annapurna] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Yiping; Wu, Bai-Lin] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping; Wu, Bai-Lin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Shen, Yiping; Wu, Bai-Lin; Miller, David T.] Claritas Genom Inc, Cambridge, MA USA. [Avallone, Jennifer; Bergin, Ann M.; Duffy, Frank H.; Eksioglu, Yaman; Loddenkemper, Tobias; Sarco, Dean; Takeoka, Masanori] Boston Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Dept Neurol, Boston, MA 02115 USA. [Berry, Gerard T.; Harris, David J.; Hisama, Fuki M.; Irons, Mira; Jacobsen, Christina M.; James, Philip; Neilan, Edward; Roberts, Amy; Smith, Sharon E.; Stoler, Joan M.; Tan, Wen-Han; Miller, David T.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Hisama, Fuki M.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Ho, Eugenia; Khwaja, Omar; Lipton, Jonathan; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Raffalli, Peter C.; Robbins, Michael; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Soul, Janet; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Wolff, Robert] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Ho, Eugenia] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Neurol, Los Angeles, CA 90033 USA. [Jacobsen, Christina M.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Kothare, Sanjeev] NYU, Dept Neurol, New York, NY 10016 USA. [Roberts, Amy] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Schonwald, Alison; Torres, Alcy R.] Boston Univ, Boston Med Ctr, Dept Pediat, Boston, MA 02215 USA. [Schonwald, Alison; Torres, Alcy R.] Boston Univ, Boston Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Weissman, Laura] Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. RP Poduri, A (reprint author), Boston Childrens Hosp, Fegan 9,300 Longwood Ave, Boston, MA 02115 USA. EM annapurna.poduri@childrens.harvard.edu FU NIH National Institute of Neurologic Disorders and Stroke [1K23NS069784, 5K12NS079414-02]; NIH National Human Genome Research Institute FX This study was supported by the NIH National Institute of Neurologic Disorders and Stroke (1K23NS069784, A. P.; 5K12NS079414-02, H.O.) and NIH National Human Genome Research Institute (D.T.M.). 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PD JUN PY 2014 VL 75 IS 6 BP 943 EP 958 DI 10.1002/ana.24178 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AK9UE UT WOS:000338772200015 PM 24811917 ER PT J AU Huang, JP Cui, SS Han, Y Irva, HP Qi, LH Zhang, X AF Huang Jun Ping Cui Shan Shan Han Yu Irva, Hertz-Picciotto Qi Li Hong Zhang Xin TI Prevalence and Early Signs of Autism Spectrum Disorder (ASD) among 18-36 Month Old Children in Tianjin of China SO BIOMEDICAL AND ENVIRONMENTAL SCIENCES LA English DT Article DE Autism spectrum disorder; Prevalence; Early signs; Discriminant function analysis ID PERVASIVE DEVELOPMENTAL DISORDERS; EARLY IDENTIFICATION; SCREENING INSTRUMENT; MENTAL-RETARDATION; EARLY RECOGNITION; FOLLOW-UP; 2ND YEAR; DIAGNOSIS; AGE; POPULATION AB Objective The aim of this study is to estimate the prevalence of autism spectrum disorder (ASD) among 18-36 month old children in the Tianjin Municipality of China, and to identify early signs of autistic children and the predictability of each individual symptom. Methods A total of 8 000 children were screened to do a questionnaire based on CHAT modified to include more early signs of autism at the age of 18-36 months. Then the at-risk children were reexamined 1.5 years later and ASD children were identified based on DSM-IV. Early signs of autism were analyzed retrospectively by using discriminant function analysis performed among ASD children, children not followed up and children followed up but failing to meet ASD criteria. Results Three hundred and sixty seven children were screened as being at-risk to ASD, and 22 of them were identified as having ASD in the subsequent diagnosis. The prevalence of ASD was 27.5 per 10 000 in Tianjin of China with a male to female ratio of 4:1. Items addressing social interactions and communications had higher predictability than other items to distinguish autistic children from non-autistic ones. Pretend play, functional play, showing and reading parents' facial expressions distinguished autistic children from those not followed up, nevertheless those followed up but failing to meet ASD criteria were not included. Conclusion The prevalence of ASD found in our study was lower than that reported in some studies by western researchers. Autism has its specific symptoms, such as deficits in social awareness, social relatedness, and social referencing. C1 [Huang Jun Ping; Cui Shan Shan; Han Yu; Zhang Xin] Tianjin Med Univ, Sch Publ Hlth, Tianjin 300070, Peoples R China. [Irva, Hertz-Picciotto; Qi Li Hong] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Zhang, X (reprint author), Tianjin Med Univ, Sch Publ Hlth, Tianjin 300070, Peoples R China. EM zhangxin@tmu.edu.cn FU National Natural Science Foundation of China [81072313] FX The study was support by the National Natural Science Foundation of China Grant No. 81072313. 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TI Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase SO NATURE COMMUNICATIONS LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; NEURAL PROGENITOR CELLS; DOWN-SYNDROME; NERVE-TERMINALS; NEUROMUSCULAR-JUNCTION; COGNITIVE DEFICITS; PLASMA-MEMBRANE; ADAPTER PROTEIN; DYNAMIN-I; DYRK1A AB Phosphorylation has emerged as a crucial regulatory mechanism in the nervous system to integrate the dynamic signalling required for proper synaptic development, function and plasticity, particularly during changes in neuronal activity. Here we present evidence that Minibrain (Mnb; also known as Dyrk1A), a serine/threonine kinase implicated in autism spectrum disorder and Down syndrome, is required presynaptically for normal synaptic growth and rapid synaptic vesicle endocytosis at the Drosophila neuromuscular junction (NMJ). We find that Mnb-dependent phosphorylation of Synaptojanin (Synj) is required, in vivo, for complex endocytic protein interactions and to enhance Synj activity. Neuronal stimulation drives Mnb mobilization to endocytic zones and triggers Mnb-dependent phosphorylation of Synj. Our data identify Mnb as a synaptic kinase that promotes efficient synaptic vesicle recycling by dynamically calibrating Synj function at the Drosophila NMJ, and in turn endocytic capacity, to adapt to conditions of high synaptic activity. C1 [Chen, Chun-Kan; Bregere, Catherine; Lu, Jason F.; Chang, Karen T.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. [Chen, Chun-Kan] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Paluch, Jeremy; Dickman, Dion K.] Univ So Calif, Dept Neurobiol, Los Angeles, CA 90089 USA. [Chang, Karen T.] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. RP Chang, KT (reprint author), Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. EM changkt@usc.edu FU National Institutes of Health [NS080946]; Jerome Lejeune Foundation; Alzheimer's Association; Global Down Syndrome Foundation; NIMH [R00 MH092351]; Ellison Medical Foundation FX We thank Martin Heisenberg (University of Wuzburg, Germany) for the mnb1 stock. We are grateful to Hugo Bellen (Baylor, TX, USA) for his generous sharing of UAS-PLC delta 1-PH-GFP flies and multiple antibodies used in this manuscript, including the Synj antibody that we renamed here to p-Synj for clarification purposes. We thank Julie Simpson (HHMI Janelia Farm, VA, USA) for gift of the nSyb-Gal4 stock and the Developmental Hybridoma Bank (Iowa, USA) for antibodies. We thank the Proteomics Core at USC for assistance with mass spectrometry data collection and analyses. We also thank Dr K.-T. Min for critical reading of the manuscript, John W. 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Ann. PD JUN PY 2014 VL 44 IS 6 BP 293 EP 298 DI 10.3928/00485713-20140609-07 PG 6 WC Psychiatry SC Psychiatry GA AL0PB UT WOS:000338827700007 ER PT J AU Bavarva, JH Tae, H McIver, L Karunasena, E Garner, HR AF Bavarva, Jasmin H. Tae, Hongseok McIver, Lauren Karunasena, Enusha Garner, Harold R. TI The Dynamic Exome: acquired variants as individuals age SO AGING-US LA English DT Article DE Aging; dynamic exome; exome sequencing; personalized genomics; personalized medicine ID DE-NOVO MUTATIONS; DNA-SEQUENCING DATA; GENETIC-VARIANTS; GENOME; AUTISM; EXPRESSION; EVOLUTION; DATABASE; CANCER; DAMAGE AB A singular genome used for inference into population-based studies is a standard method in genomics. Recent studies show that spontaneous genomic variants can propagate into new generations and these changes can contribute to individual cell aging with environmental and evolutionary elements contributing to cumulative genomic variation. However, the contribution of aging to genomic changes in tissue samples remains uncharacterized. Here, we report the impact of aging on individual human exomes and their implications. We found the human genome to be dynamic, acquiring a varying number of mutations with age (5,000 to 50,000 in 9 to 16 years). This equates to a variation rate of 9.6x10(-7) to 8.4x10(-6) bp(-1) year(-1) for nonsynonymous single nucleotide variants and 2.0x10(-4) to 1.0x10(-3) locus(-1) year(-1) for microsatellite loci in these individuals. These mutations span across 3,000 to 13,000 genes, which commonly showed association with Wnt signaling and Gonadotropin releasing hormone receptor pathways, and indicated for individuals a specific and significant enrichment for increased risk for diabetes, kidney failure, cancer, Rheumatoid arthritis, and Alzheimer's disease- conditions usually associated with aging. The results suggest that "age" is an important variable while analyzing an individual human genome to extract individual-specific clinically significant information necessary for personalized genomics. C1 [Bavarva, Jasmin H.; Tae, Hongseok; McIver, Lauren; Karunasena, Enusha; Garner, Harold R.] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. RP Bavarva, JH (reprint author), Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. EM jasmin.spu@gmail.com; garner@vbi.vt.edu FU Medical Informatics and Systems Division at Virginia Bioinformatics Institute; National Science Foundation [OCI-1124123] FX This work was supported by the Medical Informatics and Systems Division director's annual fund at Virginia Bioinformatics Institute. The high performance computing infrastructure on which microsatellite analysis was conducted was supported by a grant from the National Science Foundation (OCI-1124123). We thank Heather Lewenczuk for technical help. The Genomics Research Laboratory (GRL), Virginia Bioinformatics Institute performed exome sequencing. 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Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P <= 2.40E - 09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P <= 3.83E - 23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P <= 4.16E - 04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions. C1 [Hadley, Dexter; Wu, Zhi-liang; Kao, Charlly; Kini, Akshata; Mohamed-Hadley, Alisha; Thomas, Kelly; Vazquez, Lyam; Qiu, Haijun; Mentch, Frank; Pellegrino, Renata; Kim, Cecilia; Connolly, John; Glessner, Joseph; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. EM hakonarson@email.chop.edu RI Duque, Frederico/H-3692-2014; Bailey, Anthony/J-2860-2014; Jacob, Suma/J-7941-2013; Scherer, Stephen /B-3785-2013; Bolton, Patrick/E-8501-2010 OI Duque, Frederico/0000-0001-5684-1472; Bailey, Anthony/0000-0003-4257-972X; Jacob, Suma/0000-0001-7434-7398; Scherer, Stephen /0000-0002-8326-1999; Bolton, Patrick/0000-0002-5270-6262 FU Institutional Development Fund from The Children's Hospital of Philadelphia; Margaret Q Landenberger Foundation; Lurie Family Foundation; Kubert Estate Fund [U01HG005830]; National Institute of Mental Health [1U24MH081810]; [MH64547] FX We thank all study participants and their families. We thank all the staff at the Center for Applied Genomics at CHOP for their invaluable contributions to recruitment of study subjects and genotyping of samples. We also gratefully acknowledge the resources provided by the AGRE Consortium and their participating families, and by the Autism Genome Project (AGP) Consortium and their participating families. The study was funded by an Institutional Development Fund from The Children's Hospital of Philadelphia; The Margaret Q Landenberger Foundation; The Lurie Family Foundation; The Kubert Estate Fund and by U01HG005830. AGRE is a program of Autism Speaks and is at present supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to C.M. Lajonchere (PI) and formerly by grant MH64547 to D.H. Geschwind (PI). AGRE-approved academic researchers can acquire the data sets from AGRE at http://www.agre.org. There were 1,693 cases of the full AGP data sets that were genotyped by the AGP consortium. The full AGP data sets are made available from dbGaP at http://www.ncbi.nlm.nih.gov/gap. 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It was at this time that one of the most salient and lasting diagnoses in child psychiatry, autism, was established through a network of intellectual, institutional, and legal changes in Britain. This article argues that the work of child psychiatrists at the Maudsley Hospital was central in driving these changes and uses archival sources from this hospital, along with other legal and intellectual sources, to explore attempts to conceptualize pathological thought in infants in the 1950s and 1960s. When the first epidemiological study of autism was published in 1966, this finally established the autistic child as a scientific, demographic, and social reality in Britain. C1 Univ London, London WC1E 7HU, England. RP Evans, B (reprint author), Univ London, London WC1E 7HU, England. EM b.evans@qmul.ac.uk FU Wellcome Trust [077889, 086071] FX The author wishes to thank Professor John Forrester and Edgar Jones. Many thanks also go to Professor Sir Michael Rutter, Professor Patrick Bolton, and all the staff at the MRC Social, Genetic and Developmental Psychiatry Centre for their assistance with the project. Thanks are also due to the staff of the U.K. National Archives. Finally, the author wishes to thank the Wellcome Trust for supporting this research under grant numbers 077889 and 086071. 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PD SUM PY 2014 VL 88 IS 2 BP 253 EP 286 PG 34 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA AK1IQ UT WOS:000338169200002 PM 24976162 ER PT J AU Pacheva, I Panov, G Gillberg, C Neville, B AF Pacheva, Iliyana Panov, Georgi Gillberg, Christopher Neville, Brian TI A Girl with Tuberous Sclerosis Complex Presenting with Severe Epilepsy and Electrical Status Epilepticus During Sleep, and with High-Functioning Autism and Mutism SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE tuberous sclerosis complex; high-functioning autism; hyperlexia; mutism; electrical status epilepticus ID SPECTRUM DISORDERS; CHILDREN; APRAXIA; SPEECH; SEIZURES; TARGET AB Most patients with tuberous sclerosis complex (TSC) suffer from epilepsy, and many have cognitive and behavioral problems like severe intellectual disability, autism, and hyperactivity. Only rare patients with TSC and autism have a normal intelligence quotient. We report a 13-year-old girl with definite TSC who had early-onset severe epilepsy, autistic behavior, and moderate developmental delay. By school age, however, she had normal intelligence; her intelligence quotient was at least 70 based on a Stanford-Binet test that she refused to complete. She showed good reading, writing, and language comprehension skills, and the special abilities of hyperlexia, hypermnesia, and hypercalculia. However, she did not speak. Criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and her Childhood Autism Rating Scale score of 36 indicated mild to moderate autism. She had severe electroencephalographic abnormalities: hypsarrhythmia, multifocal or generalized epileptiform discharges, and electrical status epilepticus during sleep, with a continuous left temporal focus. Magnetic resonance imaging showed many cortical tubers in all brain lobes, and subependymal nodules. We discuss possible explanations for her lack of speech. Considered as speech apraxia, her mutism could be either a symptom of her TSC or a component of her autism. Another possibility is that long-lasting electrical status epilepticus during sleep led to her autistic behavior and language arrest. Still another possibility is that a disinhibited mammalian target of rapamycin (mTOR) pathway was at the root of all of her neuropsychiatric symptoms. C1 [Pacheva, Iliyana] Med Univ, Dept Pediat & Med Genet, Plovdiv, Bulgaria. [Panov, Georgi] Hosp Stoyan Kirkovich, Neurol & Neurophysiol Unit, Stara Zagora, Bulgaria. [Gillberg, Christopher] Gothenburg Univ, Dept Child & Adolescent Psychiat, Gothenburg, Sweden. [Gillberg, Christopher; Neville, Brian] UCL, Inst Child Hlth, Neurosci Unit, London, England. [Gillberg, Christopher; Neville, Brian] Young Epilepsy, Lingfield, Surrey, England. RP Pacheva, I (reprint author), 10 Rozhen Str, Plovdiv 4000, Bulgaria. 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TI Serotonin 2A Receptor Gene (HTR2A) Regulatory Variants: Possible Association with Severity of Depression Symptoms in Children with Autism Spectrum Disorder SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE autism spectrum disorder; depression; HTR2A; rs6311; rs6314 ID POSITRON-EMISSION-TOMOGRAPHY; COMORBID PSYCHIATRIC-DISORDERS; SEASONAL AFFECTIVE-DISORDER; FAMILY-BASED ASSOCIATION; 5-HT2A RECEPTOR; MAJOR DEPRESSION; PLATELET SEROTONIN; SCORING ALGORITHMS; CLINICAL UTILITY; MESSENGER-RNA AB Objective and Background: Our aim was to characterize the association of 2 functional single nucleotide polymorphisms (rs6311 and rs6314) in the serotonin 2A receptor gene (HTR2A) with severity of depression symptoms in children with autism spectrum disorder. These polymorphisms have been shown to be associated with depression symptom severity and response to selective serotonin reuptake inhibitor drugs in adults with diagnosed depressive disorder. Methods: Parents of 104 children with autism spectrum disorder rated their children's depressive symptoms using a validated scale based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. We compared severity of depression symptoms across the rs6311 and rs6314 genotypes, measured from the children's genomic DNA. Results: Children homozygous for the G allele of rs6311 had significantly more severe depression symptoms than those with G/A or A/A genotypes (P=0.025). The effect size (partial eta-squared) was small (eta p(2)=0.047) but was somewhat larger when we controlled for severity of generalized anxiety disorder symptoms (P=0.006, eta p(2)=0.072). When we restricted our analyses to white participants, our results were essentially the same as for the entire sample (P=0.004, eta p(2)=0.086). There was no significant association between rs6314 (C/C versus T carriers) and severity of depression. Conclusions: Our findings suggest that the HTR2A functional rs6311 polymorphism, which other studies have associated with differential HTR2A mRNA expression, may modulate the severity of depression symptoms in children with autism spectrum disorder. These tentative, hypothesis-generating findings need replication with larger, independent samples. C1 [Gadow, Kenneth D.] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Smith, Ryan M.; Pinsonneault, Julia K.] Ohio State Univ, Dept Pharmacol, Wexner Med Ctr, Ctr Pharmacogen, Columbus, OH 43210 USA. RP Gadow, KD (reprint author), SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. 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Behav. Neurol. PD JUN PY 2014 VL 27 IS 2 BP 107 EP 116 PG 10 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA AK0VS UT WOS:000338134800007 PM 24968012 ER PT J AU Luxton, GWG Starr, DA AF Luxton, G. W. Gant Starr, Daniel A. TI KASHing up with the nucleus: novel functional roles of KASH proteins at the cytoplasmic surface of the nucleus SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PERINUCLEAR ACTIN CAP; SUN PROTEINS; LINC COMPLEXES; ENVELOPE; MIGRATION; MECHANOTRANSDUCTION; MOVEMENT; CYTOSKELETON; CONNECTIONS; CENTROSOME AB Nuclear-cytoskeletal connections are central to fundamental cellular processes, including nuclear positioning and chromosome movements in meiosis. The cytoskeleton is coupled to the nucleoskeleton through conserved KASH-SUN bridges, or LING complexes, that span the nuclear envelope. KASH proteins localize to the outer nuclear membrane where they connect the nucleus to the cytoskeleton. New findings have expanded the functional diversity of KASH proteins, showing that they interact with microtubule motors, actin, intermediate filaments, a nonconventional myosin, RanGAP, and each other. The role of KASH proteins in cellular mechanics is discussed. Genetic mutations in KASH proteins are associated with autism, hearing loss, cancer, muscular dystrophy and other diseases. C1 [Luxton, G. W. Gant] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Starr, Daniel A.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. RP Luxton, GWG (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM gwgluxton@umn.edu; dastarr@ucdavis.edu FU National Institutes of Health NIGMS [R01 GM073874]; University of Minnesota; Paul and Sheila Wellstone Muscular Dystrophy Center FX DAS thanks David Fay for hosting him at the University of Wyoming, Laramie while on sabbatical. Studies in the Starr lab are supported by grant R01 GM073874 from the National Institutes of Health NIGMS. GWGL thanks the members of his laboratory, Meg Titus, and Melissa Gardner for insightful discussions. Studies in the Luxton lab are supported by start up funding from the University of Minnesota and P30 Pilot and Feasibility Grant from the Paul and Sheila Wellstone Muscular Dystrophy Center. 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Fam. Pract. PD JUN PY 2014 VL 63 IS 6 BP 316 EP 320 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AK2YA UT WOS:000338285100010 PM 25061621 ER PT J AU McClintic, AM King, BH Webb, SJ Mourad, PD AF McClintic, Abbi M. King, Bryan H. Webb, Sara J. Mourad, Pierre D. TI Mice Exposed to Diagnostic Ultrasound In Utero Are Less Social and More Active in Social Situations Relative to Controls SO AUTISM RESEARCH LA English DT Article DE diagnostic ultrasound; mouse social behavior; autistic-like behavior; risk factor ID AUTISM SPECTRUM DISORDERS; RANDOMIZED CONTROLLED-TRIAL; BEHAVIORAL TASKS RELEVANT; PRENATAL ULTRASOUND; FETAL PERIOD; FOLLOW-UP; MOUSE; RISK; AGE; ASSOCIATION AB Clinical use of diagnostic ultrasound imaging during pregnancy has a long history of safety and diagnostic utility, as supported by numerous human case reports and epidemiological studies. However, there exist in vivo studies linking large but clinically relevant doses of ultrasound applied to mouse fetuses in utero to altered learning, memory, and neuroanatomy of those mice. Also, there exists a well-documented significant increase in the likelihood of non-right-handedness in boys exposed to diagnostic ultrasound in utero, potentially relevant given the increased prevalence of autism in males, and reports of excess non-right-handedness in this population. Motivated by these observations, we applied 30minutes of diagnostic ultrasound to pregnant mice at embryonic day 14.5 and assayed the social behavior of their male pups 3 weeks after their birth. The ultrasound-exposed pups were significantly (P<0.01) less interested in social interaction than sham-exposed pups in a three-chamber sociability test. In addition, they demonstrated significantly (P<0.05) more activity relative to the sham-exposed pups, but only in the presence of an unfamiliar mouse. These results suggest that fetal exposure to diagnostic ultrasound applied in utero can alter typical social behaviors in young mice that may be relevant for autism. There exist meaningful differences between the exposure of diagnostic ultrasound to mice versus humans that require further exploration before this work can usefully inform clinical practice. Future work should address these differences as well as clarify the extent, mechanisms, and functional effects of diagnostic ultrasound's interaction with the developing brain. Autism Res 2014, 7: 295-304. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [McClintic, Abbi M.; Mourad, Pierre D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [King, Bryan H.] Seattle Childrens Hosp, Seattle Childrens Autism Ctr, Seattle, WA USA. [King, Bryan H.] Seattle Childrens Hosp, Seattle, WA USA. [King, Bryan H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Webb, Sara J.] Univ Washington, Seattle, WA 98195 USA. [Webb, Sara J.] Univ Washington, Autism Ctr, Seattle, WA 98195 USA. [Webb, Sara J.] Univ Washington, Ctr Human Dev & Disabil, Seattle, WA 98195 USA. [Mourad, Pierre D.] Univ Washington, Appl Phys Lab, Dept Engn & Math, Seattle, WA 98195 USA. [Mourad, Pierre D.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. RP Mourad, PD (reprint author), Univ Washington, Dept Neurol Surg, Box 356470, Seattle, WA 98195 USA. EM pierre@apl.washington.edu FU National Institute of Child Health and Human Development [P30 HD002274] FX We thank the Mouse Behavior Core in the Center for Human Development and Disability at the University of Washington, supported by grant P30 HD002274 from the National Institute of Child Health and Human Development, for the resources to perform the behavioral studies. We also thank Dr. Sean Murphy and Dr. Toby Cole, who manage the Mouse Behavior Core for their considerable assistance. 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PD JUN PY 2014 VL 7 IS 3 BP 295 EP 304 DI 10.1002/aur.1349 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AJ9KD UT WOS:000338027900001 PM 24249575 ER PT J AU Dalton, N Chandler, S Turner, C Charman, T Pickles, A Loucas, T Simonoff, E Sullivan, P Baird, G AF Dalton, Neil Chandler, Susie Turner, Charles Charman, Tony Pickles, Andrew Loucas, Tom Simonoff, Emily Sullivan, Peter Baird, Gillian TI Gut Permeability in Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE autism; autism spectrum disorders; gut permeability; lactulose; mannitol ratio ID INTESTINAL PERMEABILITY; GASTROINTESTINAL SYMPTOMS; CHILDREN; DISEASE; INDIVIDUALS; ASSOCIATION; PREVALENCE; LACTULOSE; MANNITOL; FAMILIES AB Objective To test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population-derived cohort of children with ASD compared with age- and intelligence quotient-matched controls without ASD but with special educational needs (SEN). Patients and Methods One hundred thirty-three children aged 10-14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6hr. Gut permeability was assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry-mass spectrometry. The ASD group was subcategorized for comparison into those without (n=83) and with (n=20) regression. Results There was no significant difference in L/M recovery ratio (mean (95% confidence interval)) between the groups with ASD: 0.015 (0.013-0.018), and SEN: 0.014 (0.009-0.019), nor in lactulose, mannitol, or creatinine recovery. No significant differences were observed in any parameter for the regressed versus non-regressed ASD groups. Results were consistent with previously published normal ranges. Eleven children (9/103=8.7% ASD and 2/30=6.7% SEN) had L/M recovery ratio >0.03 (the accepted normal range cut-off), of whom two (one ASD and one SEN) had more definitely pathological L/M recovery ratios >0.04. Conclusion There is no statistically significant group difference in small intestine permeability in a population cohort-derived group of children with ASD compared with a control group with SEN. Of the two children (one ASD and one SEN) with an L/M recovery ratio of >0.04, one had undiagnosed asymptomatic celiac disease (ASD) and the other (SEN) past extensive surgery for gastroschisis. Autism Res 2014, 7: 305-313. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Dalton, Neil; Turner, Charles] Evelina Childrens Hosp, WellChild Lab, London, England. [Dalton, Neil; Turner, Charles] Kings Coll London, London WC2R 2LS, England. [Chandler, Susie; Baird, Gillian] Guys & St Thomas NHS Fdn Trust, Newcomen Ctr, London, England. [Chandler, Susie; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Baird, Gillian] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Loucas, Tom] Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 2AH, Berks, England. [Sullivan, Peter] Univ Oxford, Dept Paediat, Oxford Childrens Hosp, Oxford OX1 2JD, England. RP Baird, G (reprint author), St Thomas Hosp, Childrens Neurosci Ctr, Block D,Westminster Bridge Rd, London SE1 7EH, England. EM gillian.baird@gstt.nhs.uk RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU Wellcome Trust [GR045093MA]; Department of Health [039/0026]; Remedi [22] FX The study was funded as follows:Grant sponsor: Wellcome Trust; Grant number: GR045093MA; Grant sponsor: the Department of Health; Grant number: 039/0026; Grant sponsor: Remedi; Grant number: 22 CR Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Baird G, 2008, J AUTISM DEV DISORD, V38, P1827, DOI 10.1007/s10803-008-0571-9 BJARNASON I, 1995, GASTROENTEROLOGY, V108, P1566, DOI 10.1016/0016-5085(95)90708-4 Buie T, 2010, PEDIATRICS, V125, pS1, DOI 10.1542/peds.2009-1878C Buie T, 2010, PEDIATRICS, V125, pS19, DOI 10.1542/peds.2009-1878D Campbell DB, 2009, PEDIATRICS, V123, P1018, DOI 10.1542/peds.2008-0819 Chandler S, 2013, J AUTISM DEV DISORD, V43, P2737, DOI 10.1007/s10803-013-1768-0 de Magistris L, 2010, J PEDIATR GASTR NUTR, V51, P418, DOI 10.1097/MPG.0b013e3181dcc4a5 DEufemia P, 1996, ACTA PAEDIATR, V85, P1076, DOI 10.1111/j.1651-2227.1996.tb14220.x Erickson CA, 2005, J AUTISM DEV DISORD, V35, P713, DOI 10.1007/s10803-005-0019-4 Gorrindo P, 2012, AUTISM RES, V5, P101, DOI 10.1002/aur.237 Halme L, 2000, SCAND J CLIN LAB INV, V60, P695, DOI 10.1080/00365510050216420 Horvath Karoly, 2002, Curr Gastroenterol Rep, V4, P251, DOI 10.1007/s11894-002-0071-6 Horvath Karoly, 2000, JPGN, V31, pS30 Ibrahim SH, 2009, PEDIATRICS, V124, P680, DOI 10.1542/peds.2008-2933 Knivsberg AM, 2002, NUTR NEUROSCI, V5, P251, DOI 10.1080/10281450290028945 LECOUTEUR A, 1988, J AUTISM DEV DISORD, V18, P181 Levy SE, 2008, CHILD ADOL PSYCH CL, V17, P803, DOI 10.1016/j.chc.2008.06.004 Liu Z, 2005, ACTA PAEDIATR, V94, P386, DOI 10.1080/08035250410023304 LORD C, 1994, J AUTISM DEV DISORD, V24, P659, DOI 10.1007/BF02172145 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Marsilio R, 1998, CLIN CHEM, V44, P1685 Millward C, 2004, COCHRANE DB SYST REV, DOI DOI 10.1002/14651858.CD003498.PUB2 PANKSEPP J, 1979, TRENDS NEUROSCI, V2, P174, DOI 10.1016/0166-2236(79)90071-7 Raven JC, 1990, COLOURED PROGR MATRI Raven John C., 1990, STANDARD PROGR MATRI REICHELT K-L, 1990, Journal of Applied Nutrition, V42, P1 Reichelt K L, 1981, Adv Biochem Psychopharmacol, V28, P627 Robertson MA, 2008, J AUTISM DEV DISORD, V38, P1066, DOI 10.1007/s10803-007-0482-1 Rutter M., 2003, SCQ SOCIAL COMMUNICA Shattock Paul, 2002, Expert Opin Ther Targets, V6, P175 Shattock Paul, 1991, Brain Dysfunction, V4, P323 Smith RA, 2009, AUTISM, V13, P343, DOI 10.1177/1362361309106418 Valicenti-McDermott M, 2006, J DEV BEHAV PEDIATR, V27, pS128, DOI 10.1097/00004703-200604002-00011 Vickery S, 2006, NEPHROL DIAL TRANSPL, V21, P2439, DOI 10.1093/ndt/gfl249 Wang LW, 2011, J DEV BEHAV PEDIATR, V32, P351, DOI 10.1097/DBP.0b013e31821bd06a Wechsler D., 1992, WECHSLER INTELLIGENC WYATT J, 1993, LANCET, V341, P1437, DOI 10.1016/0140-6736(93)90882-H NR 38 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 EI 1939-3806 J9 AUTISM RES JI Autism Res. PD JUN PY 2014 VL 7 IS 3 BP 305 EP 313 DI 10.1002/aur.1350 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AJ9KD UT WOS:000338027900002 PM 24339339 ER PT J AU Stockbridge, MD Happe, FGE White, SJ AF Stockbridge, Melissa D. Happe, Francesca G. E. White, Sarah J. TI Impaired Comprehension of Alternating Syntactic Constructions in Autism SO AUTISM RESEARCH LA English DT Article DE autism; language development; syntax; dative alternation ID SPECTRUM DISORDERS; DATIVE ALTERNATION; LANGUAGE PROFILES; COGNITIVE-STYLE; CHILDREN; ENGLISH AB Individuals on the higher-functioning end of the autism spectrum have significant impairments in communication. Language delay can occur, particularly in syntactic or structural linguistic knowledge. However, classically observed semantic deficits generally overshadow these structural deficits. This research examined the potential effects on comprehension of dative expressions that exhibited syntactic alternation versus those that were restricted, whether in syntactic construction or through marked semantic differences in construction. Children with autism and matched neurotypical control participants were presented with a sentence battery of dative statements representing these variations in construction and were asked to display basic comprehension of the sentence meaning by identifying the recipient, or indirect object, of the dative verb. Construction, restriction, and semantic differentiation variables were analyzed for potential effects on the rate of accurate comprehension. Both groups performed with greater accuracy when dative expressions used a prepositional phrase than when the dative action was expressed in the syntax. The autism group performed more poorly when the dative expression could syntactically alternate than when it was restricted. These effects improve our knowledge of how children with autism understand alternating grammatical constructions. Autism Res 2014, 7: 314-321. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Stockbridge, Melissa D.; White, Sarah J.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Happe, Francesca G. E.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP White, SJ (reprint author), UCL, Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. EM s.white@ucl.ac.uk RI White, Sarah/C-4084-2008 OI White, Sarah/0000-0001-6946-9155 FU British Academy Fellowship [PDF/2009/213] FX Grant sponsors: This work was supported by a British Academy Fellowship PDF/2009/213 to S. J. W. CR Anderson J. 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PD JUN PY 2014 VL 7 IS 3 BP 314 EP 321 DI 10.1002/aur.1348 PG 8 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AJ9KD UT WOS:000338027900003 PM 24227788 ER PT J AU Lane, AE Molloy, CA Bishop, SL AF Lane, Alison E. Molloy, Cynthia A. Bishop, Somer L. TI Classification of Children With Autism Spectrum Disorder by Sensory Subtype: A Case for Sensory-Based Phenotypes SO AUTISM RESEARCH LA English DT Article DE sensory; autism; phenotypes; subtypes; children; classification; model-based cluster analysis; Short Sensory Profile ID DEVELOPMENTAL DELAYS; TYPICAL DEVELOPMENT; YOUNG-CHILDREN; BEHAVIORS; ABNORMALITIES; MOTOR; INTEGRATION; RESPONSES; PATTERNS; FEATURES AB This study examines whether sensory differences can be used to classify meaningful subgroups of children with autism spectrum disorder (ASD). Caregivers of children with ASD aged 2-10 years (n=228) completed the Short Sensory Profile. Model-based cluster analysis was used to extract sensory subtypes. The relationship of these subtypes to age, gender, autism symptom severity, and nonverbal intelligence quotient (IQ) was further explored. Four distinct sensory subtypes were identified: (a) sensory adaptive; (b) taste smell sensitive; (c) postural inattentive; and (d) generalized sensory difference. The sensory subtypes differ from each other on two dimensions: (a) the severity of reported sensory differences; and (b) the focus of differences across auditory, taste, smell, vestibular and proprioceptive domains. Examination of the clinical features of each subtype reveals two possible mechanisms of sensory disturbance in autism: (a) sensory hyperreactivity; and (b) difficulties with multisensory processing. Further, the sensory subtypes are not well explained by other variables such as age, gender, IQ, and autism symptom severity. We conclude that classification of children using sensory differences offers a promising method by which to identify phenotypes in ASD. Sensory-based phenotypes may be useful in identifying behavioral features responsive to specific interventions thereby improving intervention effectiveness. Further validation of the sensory-based phenotypes by establishing neural and physiological correlates is recommended. Autism Res 2014, 7: 322-333. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Lane, Alison E.] Univ Newcastle, Sch Hlth Sci, Callaghan, NSW 2308, Australia. [Molloy, Cynthia A.] Harrison Community Network, Harrison, OH USA. [Bishop, Somer L.] Weill Cornell Med Coll, CADB, White Plains, NY USA. RP Lane, AE (reprint author), Univ Newcastle, Sch Hlth Sci, Univ Dr, Callaghan, NSW 2308, Australia. EM alison.lane@newcastle.edu.au FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054]; [R01HD065277] FX The authors acknowledge the members of the Autism Speaks Autism Treatment Network (AS ATN) for use of the data. The data for the study was collected as part of the AS ATN. Further support came from a cooperative agreement (UA3 MC 11054) from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. The AS ATN includes these members: Cincinnati Children's Hospital Medical Center, Patricia Manning-Courtney, MD. The views expressed in this publication do not necessarily reflect the views of the Autism Speaks, Inc.Other acknowledgments: Dr. Bishop received support from R01HD065277. 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PD JUN PY 2014 VL 7 IS 3 BP 322 EP 333 DI 10.1002/aur.1368 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AJ9KD UT WOS:000338027900004 PM 24639147 ER PT J AU Carson, AM Salowitz, NMG Scheidt, RA Dolan, BK Van Hecke, AV AF Carson, Audrey M. Salowitz, Nicole M. G. Scheidt, Robert A. Dolan, Bridget K. Van Hecke, Amy V. TI Electroencephalogram Coherence in Children With and Without Autism Spectrum Disorders: Decreased Interhemispheric Connectivity in Autism SO AUTISM RESEARCH LA English DT Article DE electroencephaolography; EEG coherence; school age2.0.CO;2 Arbuckle J. 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S., 1981, SIBLING INVENTORY BE Stoneman Z, 2005, MENT RETARD, V43, P339 NR 15 TC 0 Z9 0 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD JUN PY 2014 VL 32 IS 2 BP 241 EP 246 DI 10.1037/fsh0000047 PG 6 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA AJ8HI UT WOS:000337943600020 PM 24818514 ER PT J AU Dalsgaard, S Leckman, JF Nielsen, HS Simonsen, M AF Dalsgaard, Soren Leckman, James F. Nielsen, Helena Skyt Simonsen, Marianne TI Gender and Injuries Predict Stimulant Medication Use SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD BEHAVIOR DISORDERS; TRAUMATIC BRAIN-INJURY; UNINTENTIONAL INJURY; INCREASED RISK; DRUG-USE; CHILDREN; POPULATION; PREVALENCE AB Objective: The purpose of this article was to examine whether injuries in early childhood and gender predict prescriptions of stimulant medication in three groups of children: With attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and other psychiatric disorders (OPD). Methods: This was a population-based study with prospective and complete follow-up of children with ADHD (n=11,553), ASD (n=9698), and OPD (n=48,468), of whom 61%, 16%, and 3%, respectively, were treated with stimulants. For all 69,719 individual children data on psychiatric diagnoses, injuries, and drug prescriptions were obtained from national registers and merged. Results: Having sustained an injury before 5 years of age increased the likelihood of later stimulant treatment, in children with ADHD (odds ratio [OR]=1.09; 95% confidence interval [CI]=1.01-1.21), ASD (OR=1.19; 95% CI=1.02-1.40), and OPD (OR=1.24; 95% CI=1.08-1.42), with each injury increasing the likelihood by 3%, 10%, and 7%, respectively. Head injury did not increase the likelihood of later stimulant treatment. Within each of the three groups, ADHD, ASD, and OPD boys were more likely than girls to receive stimulant medication, OR=1.17 (95% CI=1.07-1.28); OR=1.71 (95% CI=1.47-2.01), and OR=2.41 (95% CI=2.16-2.71), respectively. Conclusions: To our knowledge, this is the first prospective study assessing early life predictors of later ADHD medication in children with a psychiatric disorder, taken from a national cohort with complete follow-up of all cases. We found that the number of injuries prior to diagnosis was associated with initiation of stimulant treatment in all three groups of patients. In addition, male gender predicted treatment with ADHD medications. Our results suggest that the number of injuries early in life prior to diagnosis is associated with stimulant treatment, and may serve as a proxy for the level of later severity of ADHD symptoms, as it is universally associated with pharmacological treatment for ADHD. C1 [Dalsgaard, Soren] Aarhus Univ, Dept Econ & Business, Natl Ctr Register Based Res, DK-8210 Aarhus V, Denmark. [Dalsgaard, Soren] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark. [Dalsgaard, Soren] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Copenhagen, Denmark. [Dalsgaard, Soren] Hosp Telemark, Dept Child & Adolescent Psychiat, Kragero, Norway. [Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Nielsen, Helena Skyt; Simonsen, Marianne] Aarhus Univ, Sch Business & Social Sci, Deparment Econ & Business, DK-8210 Aarhus V, Denmark. RP Dalsgaard, S (reprint author), Aarhus Univ, Natl Ctr Register Ased Res, Fuglesangs Alle 4,Bldg K, DK-8210 Aarhus V, Denmark. EM sdalsgaard@ncrr.dk FU Lundbeck Foundation; Danish Council for Independent Research [10-079597]; Slagtermester Max Worzner and Inger Worzners Foundation FX The study was funded by grants from the Lundbeck Foundation, the Danish Council for Independent Research (Sapere Aude Starting Grant, 10-079597) and Slagtermester Max Worzner and Inger Worzners Foundation. 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Child Adolesc. Psychopharmacol. PD JUN PY 2014 VL 24 IS 5 BP 253 EP 259 DI 10.1089/cap.2013.0101 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AJ9EP UT WOS:000338010400004 PM 24813570 ER PT J AU Holmes, KJ Gathright, MM Morris, EM Coffey, B AF Holmes, Khiela J. Gathright, Molly M. Morris, Edwin M. Coffey, Barbara TI Psychotic Symptoms and Catatonia in a Preadolescent Boy with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ELECTROCONVULSIVE-THERAPY; SCHIZOPHRENIA; CHILDHOOD; LORAZEPAM; CHILDREN C1 [Holmes, Khiela J.; Gathright, Molly M.; Morris, Edwin M.] UAMS Coll Med, Inst Psychiat Res, Dept Psychiat, Little Rock, AZ USA. [Coffey, Barbara] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Coffey, B (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Barbara.coffey@mssm.edu FU Eli Lily Pharmaceutical; NIMH; NINDS; Tourette Syndrome Association; Otsuka; Shire; Bristol-Myers; Pfizer; Boehringer Ingelheim FX Dr. Holmes, Dr. Gathright, and Mr. Morris have no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Eli Lily Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers, Pfizer, and Boehringer Ingelheim. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bush G, 1996, ACTA PSYCHIAT SCAND, V93, P137, DOI 10.1111/j.1600-0447.1996.tb09815.x Cannon M, 2002, ARCH GEN PSYCHIAT, V59, P449, DOI 10.1001/archpsyc.59.5.449 Dhossche DM, 2013, NEUROPSYCHIATRY-LOND, V3, P401, DOI 10.2217/npy.13.42 Dhossche DM, 2009, J ECT, V25, P19, DOI 10.1097/YCT.0b013e3181957363 Green WH., 2007, CHILD ADOLESCENT CLI Jensen PS, 2007, EUR CHILD ADOLES PSY, V16, P104, DOI 10.1007/s00787-006-0580-1 Konstantareas MM, 2001, J AUTISM DEV DISORD, V31, P19, DOI 10.1023/A:1005605528309 Mejia NI, 2010, EXPERT REV NEUROTHER, V10, P893, DOI [10.1586/ern.10.58, 10.1586/ERN.10.58] Rapoport J, 2009, J AM ACAD CHILD PSY, V48, P10, DOI 10.1097/CHI.0b013e31818b1c63 Seethalakshmi R, 2008, ANN CLIN PSYCHIATRY, V20, P5, DOI 10.1080/10401230701844786 Singh NN, 1989, MASONS DIFFERENTIAL Sullivan PF, 2012, ARCH GEN PSYCHIAT, V69, P1099, DOI 10.1001/archgenpsychiatry.2012.730 Turner M, 1999, J CHILD PSYCHOL PSYC, V40, P839, DOI 10.1017/S0021963099004278 Watt N, 2009, J AUTISM DEV DISORD, V38, P1518 Wing L, 2000, BRIT J PSYCHIAT, V176, P357, DOI 10.1192/bjp.176.4.357 NR 16 TC 0 Z9 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2014 VL 24 IS 5 BP 288 EP 292 DI 10.1089/cap.2014.2453 PG 5 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AJ9EP UT WOS:000338010400009 PM 24945087 ER PT J AU Pearl, PL Sable, C Evans, S Knight, J Cunningham, P Lotrecchiano, GR Gropman, A Stuart, S Glass, P Conway, A Ramadan, I Paiva, T Batshaw, ML Packer, RJ AF Pearl, Phillip L. Sable, Craig Evans, Sarah Knight, Joseph Cunningham, Parker Lotrecchiano, Gaetano R. Gropman, Andrea Stuart, Sheela Glass, Penny Conway, Anne Ramadan, Issam Paiva, Tania Batshaw, Mark L. Packer, Roger J. TI International Telemedicine Consultations for Neurodevelopmental Disabilities SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telemedicine; telehealth; technology; distance learning; education ID TELEVISION AB Background: A telemedicine program was developed between the Children's National Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum of on-site training conferences were devised preparatory to an ongoing telemedicine consultation program for children with neurodevelopmental disabilities in the underserved eastern region of the UAE. Materials and Methods: Weekly telemedicine consultations are provided by a multidisciplinary faculty. Patients are presented in the UAE with their therapists and families. Real-time (video over Internet protocol; average connection, 768 kilobits/s) telemedicine conferences are held weekly following previews of medical records. A full consultation report follows each telemedicine session. Results: Between February 29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine consultations were conducted on 48 patients (28 males, 20 females; age range, 8 months-22 years; median age, 5.4 years). The primary diagnoses were cerebral palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital anomalies, global developmental delay, systemic disease, and epilepsy. Common comorbidities were cognitive impairment, communication disorders, and behavioral disorders. Specific recommendations included imaging and DNA studies, antiseizure management, spasticity management including botulinum toxin protocols, and specific therapy modalities including taping techniques, customized body vests, and speech/language and behavioral therapy. Improved outcomes reported were in clinician satisfaction, achievement of therapy goals for patients, and requests for ongoing sessions. Conclusions: Weekly telemedicine sessions coupled with triannual training conferences were successfully implemented in a clinical program dedicated to patients with neurodevelopmental disabilities by the Center for Neuroscience at CNMC and the UAE government. International consultations in neurodevelopmental disabilities utilizing telemedicine services offer a reliable and productive method for joint clinical programs. C1 [Pearl, Phillip L.; Evans, Sarah; Knight, Joseph; Cunningham, Parker; Gropman, Andrea; Stuart, Sheela; Glass, Penny; Conway, Anne; Batshaw, Mark L.; Packer, Roger J.] Childrens Natl Med Ctr, Ctr Neurosci & Behav Hlth, Washington, DC 20010 USA. [Sable, Craig; Ramadan, Issam; Paiva, Tania] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Lotrecchiano, Gaetano R.] George Washington Univ, Sch Med & Hlth Sci, Dept Clin Res & Leadership, Washington, DC 20052 USA. RP Pearl, PL (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Fegan 9, Boston, MA 02115 USA. EM Phillip.Pearl@childrens.harvard.edu FU Sheikh Khalifa bin Zayed Foundation of the United Arab Emirates government FX The telemedicine program is supported by the Sheikh Khalifa bin Zayed Foundation of the United Arab Emirates government. CR Bar-on ME, 2001, PEDIATRICS, V107, P423 American Telemedicine Association, 2008, COR STAND TEL OP Bynum AB, 2011, INT J TELEMEDICINE A, V2011 Hancox RJ, 2005, ARCH PEDIAT ADOL MED, V159, P614, DOI 10.1001/archpedi.159.7.614 Kvedar J, 2006, ANN ONCOL, V17, P37, DOI 10.1093/annonc.mdl986 Locatis C, 2012, TELEMED J E-HEALTH, V19, P19 Saliba V, 2012, INT J MED INFORM, V81, P793, DOI 10.1016/j.ijmedinf.2012.08.003 World Health Organization, 2011, GLOB OBS EHEALTH SER, V2 NR 8 TC 0 Z9 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUN PY 2014 VL 20 IS 6 BP 559 EP 562 DI 10.1089/tmj.2013.0275 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AJ8IA UT WOS:000337945500009 PM 24660879 ER PT J AU Qin, MY Wong, A Seguin, D Gerlai, R AF Qin, Meiying Wong, Albert Seguin, Diane Gerlai, Robert TI Induction of Social Behavior in Zebrafish: Live Versus Computer Animated Fish as Stimuli SO ZEBRAFISH LA English DT Article ID DANIO-RERIO RESPONDS; SHOALING BEHAVIOR; FEAR RESPONSES; IMAGES; MODEL; NEUROCHEMISTRY; DISORDERS; COGNITION; ETHANOL; AUTISM AB The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish. C1 [Qin, Meiying; Seguin, Diane; Gerlai, Robert] Univ Toronto, Dept Psychol, Mississauga, ON L5L 1C6, Canada. [Qin, Meiying; Wong, Albert] Univ Toronto, Dept Comp Sci, Mississauga, ON L5L 1C6, Canada. [Gerlai, Robert] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada. RP Gerlai, R (reprint author), Univ Toronto, Dept Psychol, 3359 Mississauga Rd North,Rm DV4023C, Mississauga, ON L5L 1C6, Canada. EM robert_gerlai@yahoo.com FU NSERC; NIH/NIAAA FX This study was supported by an NSERC and an NIH/NIAAA grant to R. G. We would like to thank Steven Tran, Michele Taffs, James Ng, Yohaan Fernandes, and Mindy Rampersad for their help. We are also thankful for Noam Miller who wrote the first version of our GFA software application several years ago. 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Bain, Nicole Scherer, Stephen W. Hunter, Matthew TI Outfoxed by RBFOX1-A caution about ascertainment bias SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE RBFOX1; A2BP1; FOX1; genetic susceptibility; autism spectrum disorder; DNA copy number variation; ascertainment bias ID AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; MENTAL-RETARDATION; GENE; POPULATION; PHENOTYPE; DELETIONS; EPILEPSY; COMMON AB We report on two patients with intragenic deletions of RBFOX1 and one patient with an intragenic duplication of RBFOX1. These patients, by report, all had autism spectrum disorder and/or developmental delay and had strong family histories of these conditions. We initially hypothesized that RBFOX1 was another susceptibility locus for autism spectrum disorder or developmental delay. However, epidemiological evidence examining large numbers of individuals did not support this hypothesis and the data presented here suggests that RBFOX1 intragenic copy number variants are not pathogenic. This contradicts previous reports that examined smaller numbers of patients and controls. (c) 2014 Wiley Periodicals, Inc. C1 [Kamien, Benjamin; Hunter, Matthew] Hunter Genet, Newcastle, NSW, Australia. [Kamien, Benjamin; Hunter, Matthew] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Lionel, Anath C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Bain, Nicole] Hunter Area Pathol Serv, Dept Mol Med, Newcastle, NSW, Australia. [Hunter, Matthew] Genet Learning Disabil GOLD Serv, Newcastle, NSW, Australia. RP Kamien, B (reprint author), Hunter Genet, POB 84, Waratah 2298, Australia. EM benkamien@yahoo.com.au RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU University of Toronto McLaughlin Centre; NeuroDevNet; Genome Canada Ontario Genomics Institute; Canadian Institutes for Health Research (CIHR); Canadian Institute for Advanced Research; Canada Foundation for Innovation; Government of Ontario, Autism Speaks; Hospital for Sick Children Foundation FX Grant sponsor: University of Toronto McLaughlin Centre; Grant sponsor: NeuroDevNet; Grant sponsor: Genome Canada Ontario Genomics Institute; Grant sponsor: Canadian Institutes for Health Research (CIHR); Grant sponsor: Canadian Institute for Advanced Research; Grant sponsor: Canada Foundation for Innovation; Grant sponsor: Government of Ontario, Autism Speaks; Grant sponsor: Hospital for Sick Children Foundation. 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J. Med. Genet. A PD JUN PY 2014 VL 164 IS 6 BP 1411 EP 1418 DI 10.1002/ajmg.a.36458 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AH2BV UT WOS:000335926600007 PM 24664471 ER PT J AU Samuels, J Shugart, YY Wang, Y Grados, MA Bienvenu, OJ Pinto, A Rauch, SL Greenberg, BD Knowles, JA Fyer, AJ Piacentini, J Pauls, DL Cullen, B Rasmussen, SA Stewart, SE Geller, DA Maher, BS Goes, FS Murphy, DL McCracken, JT Riddle, MA Nestadt, G AF Samuels, Jack Shugart, Yin Yao Wang, Ying Grados, Marco A. Bienvenu, O. Joseph Pinto, Anthony Rauch, Scott L. Greenberg, Benjamin D. Knowles, James A. Fyer, Abby J. Piacentini, John Pauls, David L. Cullen, Bernadette Rasmussen, Steven A. Stewart, S. Evelyn Geller, Dan A. Maher, Brion S. Goes, Fernando S. Murphy, Dennis L. McCracken, James T. Riddle, Mark A. Nestadt, Gerald TI Clinical Correlates and Genetic Linkage of Social and Communication Difficulties in Families with Obsessive-Compulsive Disorder: Results From the OCD Collaborative Genetics Study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive-compulsive disorder; OCD; pragmatics; genetic linkage ID BROAD AUTISM PHENOTYPE; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; CHILDREN; PARENTS; INDIVIDUALS; PERSONALITY; BEHAVIORS; TRAITS; SCAN AB Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD. (C) 2014 Wiley Periodicals, Inc. C1 [Samuels, Jack; Wang, Ying; Grados, Marco A.; Bienvenu, O. Joseph; Cullen, Bernadette; Goes, Fernando S.; Riddle, Mark A.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. [Pinto, Anthony; Fyer, Abby J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Pinto, Anthony; Fyer, Abby J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rauch, Scott L.; Geller, Dan A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, James A.] Univ So Calif, Dept Psychiat, Sch Med, Los Angeles, CA USA. [Piacentini, John; McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Pauls, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, S. Evelyn] Univ British Columbia, Fac Med, Dept Psychiat, Vancouver Fac Med, Vancouver, BC, Canada. [Maher, Brion S.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Samuels, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 550 N Broadway 901, Baltimore, MD 21205 USA. EM jacks@jhmi.edu FU National Institutes of Health [R01-MH-50214, R01MH071507, K23-MH-64543, NIH/NCRR/OPD-GCRC RR00052]; James E. Marshall OCD Foundation FX Grant sponsor: National Institutes of Health; Grant numbers: R01-MH-50214, R01MH071507, K23-MH-64543, NIH/NCRR/OPD-GCRC RR00052; Grant sponsor: James E. Marshall OCD Foundation. 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J. Med. Genet. B PD JUN PY 2014 VL 165 IS 4 BP 326 EP 336 DI 10.1002/ajmg.b.32235 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AJ4UX UT WOS:000337674600006 PM 24798771 ER PT J AU Costain, G Lionel, AC Fu, F Stavropoulos, DJ Gazzellone, MJ Marshall, CR Scherer, SW Bassett, AS AF Costain, Gregory Lionel, Anath C. Fu, Fiona Stavropoulos, Dimitri J. Gazzellone, Matthew J. Marshall, Christian R. Scherer, Stephen W. Bassett, Anne S. TI Adult Neuropsychiatric Expression and Familial Segregation of 2q13 Duplications SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE chromosome 2q13; copy number variation; schizophrenia; obsessive-compulsive; genomic disorder; genetic counseling; GABA; SLC1A1; RHOA; microRNA; chromosome 16p13.11 ID COPY NUMBER VARIANTS; CHROMOSOMAL MICROARRAY; DEVELOPMENTAL DELAY; SCHIZOPHRENIA; DISORDER; REARRANGEMENTS; GENES; RISK AB New genomic disorders associated with large, rare, recurrent copy number variations (CNVs) are being discovered at a rapid pace. Detailed phenotyping and family studies are rare, however, as are data on adult phenotypic expression. Duplications at 2q13 were recently identified as risk factors for developmental delay/autism and reported in the prenatal setting, yet few individuals (all children) have been extensively phenotyped. During a genome-wide CNV study of schizophrenia, we identified two unrelated probands with 2q13 duplications. In this study, detailed phenotyping and genotyping using high-resolution microarrays was performed for 12 individuals across their two families. 2q13 duplications were present in six adults, and co-segregated with clinically significant later-onset neuropsychiatric disorders. Convergent lines of evidence implicated GABAminergic dysfunction. Analysis of the genic content revealed promising candidates for neuropsychiatric disease, including BCL2L11, ANAPC1, and MERTK. Intrafamilial genetic heterogeneity and "second hits" in one family may have been the consequence of assortative mating. Clinical genetic testing for the 2q13 duplication and the associated genetic counseling was well received. In summary, large rare 2q13 duplications appear to be associated with variable adult neuropsychiatric and other expression. The findings represent progress toward clinical translation of research results in schizophrenia. There are implications for other emerging genomic disorders where there is interest in lifelong expression. (C) 2014 Wiley Periodicals, Inc. C1 [Costain, Gregory; Fu, Fiona; Bassett, Anne S.] Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON M5S 2S1, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Stavropoulos, Dimitri J.] Hosp Sick Children, Dept Pediat Lab Med, Cytogenet Lab, Toronto, ON M5G 1X8, Canada. [Stavropoulos, Dimitri J.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Bassett, Anne S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Bassett, Anne S.] Univ Hlth Network, Dept Psychiat, Toronto, ON, Canada. [Bassett, Anne S.] Univ Hlth Network, Dept Med, Div Cardiol, Toronto, ON, Canada. RP Bassett, AS (reprint author), Ctr Addict & Mental Hlth, 33 Russell St,Room 1100, Toronto, ON M5S 2S1, Canada. EM anne.bassett@utoronto.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU Canadian Institutes of Health Research (CIHR) [MOP-89066, MOP-111238]; McLaughlin Centre Accelerator Grant FX Grant sponsor: Canadian Institutes of Health Research (CIHR), Grant numbers: MOP-89066, MOP-111238; Grant sponsor: McLaughlin Centre Accelerator Grant. 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J. Med. Genet. B PD JUN PY 2014 VL 165 IS 4 BP 337 EP 344 DI 10.1002/ajmg.b.32236 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AJ4UX UT WOS:000337674600007 PM 24807792 ER PT J AU Mirzaa, GM Poduri, A AF Mirzaa, Ghayda M. Poduri, Annapurna TI Megalencephaly and hemimegalencephaly: Breakthroughs in molecular etiology SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE megalencephaly; hemimegalencephaly; polymicrogyria; somatic mosaicism; overgrowth; PI3K-AKT-mTOR pathway; Ras; MAPK pathway ID AUTISM SPECTRUM DISORDERS; MARMORATA TELANGIECTATICA CONGENITA; RILEY-RUVALCABA-SYNDROME; ACTIVATING MUTATIONS; CUTIS MARMORATA; PTEN GENE; CYCLIN D2; BEHAVIORAL ABNORMALITIES; CAPILLARY MALFORMATION; GERMLINE MUTATIONS AB Megalencephaly (MEG) is a developmental disorder characterized by brain overgrowth that occurs due to either increased number or size of neurons and glial cells. The former may be due to either increased neuronal proliferation or decreased apoptosis. The degree of brain overgrowth may be extensive, ranging from generalized MEG affecting the entire cortex-as with mutations in PTEN (phosphatase and tensin homolog on chromosome ten)-to unilateral hemispheric malformations-as in classic hemimegalencephaly (HME). On the other hand, some lesions are more focal or segmental. These developmental brain abnormalities may occur in isolation in some individuals, whereas others occur in the context of a syndrome involving dysmorphic features, skin findings, or other organ system involvement. Brain overgrowth disorders are often associated with malformations of cortical development, resulting in increased risk of epilepsy, intellectual disability, and autistic features, and some are associated with hydrocephalus. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of brain overgrowth, particularly the identification of mosaic (or post-zygotic) mutations in core components of key cellular pathways such as the phosphatidylinositol 3-kinase (PI3K)-vakt murine thymoma viral oncogene homolog (AKT)-mTOR pathway. These molecular insights have broadened our view of brain overgrowth disorders that now appear to span a wide spectrum of overlapping phenotypic, neuroimaging, and neuropathologic features and molecular pathogenesis. These molecular advances also bring to light the possibility of pathway-based therapies for these often medically devastating developmental disorders. (c) 2014 Wiley Periodicals, Inc. C1 [Mirzaa, Ghayda M.] Seattle Childrens Hosp, Dept Human Genet, Seattle, WA USA. [Mirzaa, Ghayda M.] Seattle Childrens Res Inst, Seattle, WA USA. [Poduri, Annapurna] Boston Childrens Hosp, Div Epilepsy & Clin Electrophysiol, Dept Neurol, Hosp Epilepsy Genet Program, Boston, MA USA. [Poduri, Annapurna] NINDS, Supported Ctr, Bethesda, MD 20892 USA. RP Mirzaa, GM (reprint author), Univ Washington, Div Med Genet, Dept Pediat, Ctr Integrat Brain Res,Seattle Childrens Res Inst, 1900 9th Ave, Seattle, WA 98101 USA. EM gmirzaa@uw.edu; annapurna.poduri@childrens.harvard.edu FU NINDS [NS069784] FX The authors thank our patients and their families for their valuable and ongoing contributions and support of our research. A. P. was supported by the NINDS (NS069784). 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J. Med. Genet. C PD JUN PY 2014 VL 166 IS 2 SI SI BP 156 EP 172 DI 10.1002/ajmg.c.31401 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HF UT WOS:000337633800004 PM 24888963 ER PT J AU Palmer, EE Mowat, D AF Palmer, Elizabeth Emma Mowat, David TI Agenesis of the corpus callosum: A clinical approach to diagnosis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE agenesis of the corpus callosum; prenatal; postnatal; review; genetics; clinical; genetic counseling ID INTELLECTUAL DISABILITY; MENTAL-RETARDATION; CHILDREN; POPULATION; DYSGENESIS; MICROARRAY; C12ORF57; AUTISM AB This review article aims to guide the clinician in establishing a diagnosis in patients with agenesis of the corpus callosum (ACC), presenting antenatally or postnatally. ACC may be isolated, or occur in association with other neuroanatomical lesions and/or congenital anomalies, and has many different genetic causes. Neuropsychological outcome varies considerably from normal to profound intellectual disability depending on the etiology. Approximately 25% of individuals with antenatally diagnosed apparently isolated ACC have intellectual disability. Subtle neurological, social, and learning deficits may still occur in those with normal intelligence and longitudinal neurocognitive follow-up is recommended for all children with ACC. The finding of ACC should prompt detailed clinical assessment in order to determine and manage the underlying condition. It is recognized that genetic factors contribute to ACC in the vast majority of cases. Less commonly ACC can result from antenatal infections, vascular or toxic insults, and it is increasingly recognized that ACC, particularly isolated ACC, may be due to an interaction of a number of modifier genetic and environmental factors. There are a large number of genetic conditions in which ACC may be a feature. We suggest a diagnostic algorithm to help guide the clinician towards diagnosis, to provide outcome advice and to aid in genetic counseling. (c) 2014 Wiley Periodicals, Inc. C1 [Palmer, Elizabeth Emma] Genet Learning Disabil GOLD Serv, Sydney, NSW, Australia. RP Palmer, EE (reprint author), Sydney Childrens Hosp, Dept Med Genet, High St, Randwick, NSW, Australia. 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J. Med. Genet. C PD JUN PY 2014 VL 166 IS 2 SI SI BP 184 EP 197 DI 10.1002/ajmg.c.31405 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HF UT WOS:000337633800006 PM 24866859 ER PT J AU King, AM Thomeczek, M Voreis, G Scott, V AF King, Amie M. Thomeczek, Melissa Voreis, Grayce Scott, Victoria TI iPad (R) use in children and young adults with Autism Spectrum Disorder: An observational study SO CHILD LANGUAGE TEACHING & THERAPY LA English DT Article DE Augmentative and alternative communication (AAC); autism spectrum disorders (ASDs); digital technology; iPad (R); schools ID ACADEMIC SKILLS; STUDENTS; INDIVIDUALS AB This exploratory study was conducted to describe how children and young adults with autism spectrum disorder (ASD) are currently using iPads (R) and applications, to explore the role of education professionals on iPad (R) and application use, and to determine potential research needs regarding iPad (R) use in children with ASD. Naturalistic observations were conducted on six individuals (ages 6;6 to 20;8) with ASD while they were using iPads (R) in their school environment. The data suggest that (1) the participants used iPads (R) and applications for a variety of purposes, (2) there was considerable variability regarding whether or not the application was used consistent with its intended function, and (3) the presence of an education professional and the type of application impacted the variability in functional use of the application. Pertinent lines of research that are needed to expand the base of evidence regarding effective iPad (R) use in children with ASD are discussed. C1 [King, Amie M.; Voreis, Grayce; Scott, Victoria] So Illinois Univ, Dept Special Educ & Commun Disorders, Edwardsville, IL 62232 USA. [Thomeczek, Melissa] So Illinois Univ, Dept Educ Leadership, Edwardsville, IL 62232 USA. RP King, AM (reprint author), So Illinois Univ, Dept Special Educ & Commun Disorders, 1147 Founders Hall, Edwardsville, IL 62232 USA. 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Teach. Ther. PD JUN PY 2014 VL 30 IS 2 BP 159 EP 173 DI 10.1177/0265659013510922 PG 15 WC Education, Special; Linguistics; Language & Linguistics SC Education & Educational Research; Linguistics GA AJ3EQ UT WOS:000337549700003 ER PT J AU Kimple, KS Bartelt, EA Wysocki, KL Steiner, MJ AF Kimple, Kelly S. Bartelt, Erica A. Wysocki, Karen L. Steiner, Michael J. TI Performance of the Modified Checklist for Autism in Toddlers in Spanish-Speaking Patients SO CLINICAL PEDIATRICS LA English DT Article DE autism; screening; Modified Checklist for Autism in Toddlers (M-CHAT); Spanish; Latino ID PERVASIVE DEVELOPMENTAL DISORDERS; NON-HISPANIC WHITE; SPECTRUM DISORDERS; CHILDRENS-HEALTH; NATIONAL-SURVEY; PRIMARY-CARE; RISK; IDENTIFICATION; PREVALENCE; COMMUNITY AB Objective. To compare abnormal screening rates of 2 different Spanish versions of the Modified Checklist for Autism in Toddlers (M-CHAT) in US Spanish-speaking patients. Method. Quasi-experimental design was used with historical and English language controls. Abnormal screening rates were compared between Spain and Western-hemisphere Spanish versions, as well as to English controls during the same time periods using chi square analysis. Results. M-CHAT questionnaires were scored from 589 subjects (English n = 415, Spanish n = 174). There was little difference between Spanish versions. Overall, the Spanish abnormal screening rate was double that of English (23.6% vs 11.3%, P < .001). Conclusions. Spanish M-CHAT questionnaires are abnormal more often than those in English even after changing to appropriate translation, despite lower prevalence of autism in Latinos. Issues with translation, interpretation, or cultural understanding of behaviors may contribute. Given abnormal screening rates for Latinos, the use of the M-CHAT follow-up interview in Spanish-speaking patients is beneficial but may be more time-consuming. C1 [Kimple, Kelly S.; Bartelt, Erica A.; Wysocki, Karen L.; Steiner, Michael J.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Kimple, KS (reprint author), Univ N Carolina, Dept Social Med, 121 MacNider Hall,CB 7240, Chapel Hill, NC 27599 USA. 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We identified a novel intragenic deletion of maternal origin in two siblings with mild ID and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). Mutation screening of 223 additional patients (187 with ASD and 36 with ID) identified a missense change of maternal origin disrupting CADPS2/D2DR interaction. CADPS2 allelic expression was tested in blood and different adult human brain regions, revealing that the gene was monoallelically expressed in blood and amygdala, and the expressed allele was the one of maternal origin. Cadps2 gene expression performed in mice at different developmental stages was biallelic in the postnatal and adult stages; however, a monoallelic (maternal) expression was detected in the embryonal stage, suggesting that CADPS2 is subjected to tissue- and temporal-specific regulation in human and mice. We suggest that CADPS2 variants may contribute to ID/ASD development, possibly through a parent-of-origin effect. C1 [Bonora, Elena; Graziano, Claudio; Minopoli, Fiorella; Magini, Pamela; Diquigiovanni, Chiara; Bianco, Francesca; Vargiolu, Manuela; Mantovani, Vilma; Tortora, Giada; Seri, Marco; Romeo, Giovanni] Univ Bologna, S Orsola M Malpighi Hosp, Dept Med & Surg Sci, Unit Med Genet, Bologna, Italy. [Minopoli, Fiorella; Bacchelli, Elena; Lomartire, Silvia; Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. [Parchi, Piero; Parmeggiani, Antonia] Univ Bologna, Dept Neurol, Bologna, Italy. [Marasco, Elena; Mantovani, Vilma] St Orsola Marcello Malpighi Hosp, CRBA, Bologna, Italy. [Rampoldi, Luca; Trudu, Matteo] Ist Sci San Raffaele, Div Genet & Cell Biol, Mol Genet Renal Disorders Unit, I-20132 Milan, Italy. [Battaglia, Agatino] Stella Maris Clin Res Inst Child & Adolescent Neu, Pisa, Italy. [Mazzone, Luigi] IRCCS Osped Pediat Bambino Gesu, Unit Child Neuropsychiat, Rome, Italy. [IMGSAC] Newcastle Univ, IMGSAC Inst Neurosci & Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Seri, M (reprint author), Univ Bologna, S Orsola M Malpighi Hosp, Dept Med & Surg Sci, Unit Med Genet, Bologna, Italy. EM marco.seri@unibo.it RI Bailey, Anthony/J-2860-2014 OI Bailey, Anthony/0000-0003-4257-972X FU FP7-EU [223692] FX We thank all the patients, families, and healthy volunteers that participated in the study. We thank Prof. A. Contestabile for the support in mouse brain expression analysis and Ms. M. Giambartolomei and Dr. M. Vidone for technical help. This work was supported by FP7-EU Grant No 223692 "CHERISH" to G. R. 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SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE animal models; behavioural phenotyping; genes; mouse; neuropsychiatric disorders ID COPY NUMBER VARIATION; TOUCHSCREEN OPERANT PLATFORM; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION; FRAGILE-X-SYNDROME; MOUSE MODEL; ALZHEIMERS-DISEASE; KLEEFSTRA SYNDROME; KNOCKOUT MICE AB Rodent models are a key factor in the process of translating psychiatric genetics and genomics findings, allowing us to shed light on how risk-genes confer changes in neurobiology by merging different types of data across fields, from behavioural neuroscience to the burgeoning omics (e.g. genomics, epigenomics, proteomics, etc.). Moreover, they also provide an indispensable first step for drug discovery. 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J. Neurosci. PD JUN PY 2014 VL 39 IS 11 SI SI BP 1933 EP 1942 DI 10.1111/ejn.12607 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AJ3BT UT WOS:000337540800020 PM 24862335 ER PT J AU Abu-Hamour, B Muhaidat, M AF Abu-Hamour, Bashir Muhaidat, Mohammad TI Parents' attitudes towards inclusion of students with autism in Jordan SO INTERNATIONAL JOURNAL OF INCLUSIVE EDUCATION LA English DT Article DE special education; autism spectrum disorder; inclusion; students with special needs ID SEVERE DISABILITIES; SPECTRUM DISORDERS; YOUNG-CHILDREN; PERCEPTIONS; TEACHERS; SCHOOL; PERSPECTIVES; INTEGRATION; EDUCATION; SETTINGS AB This study investigated the attitudes of parents in Jordan towards the inclusion of students with autism spectrum disorder (ASD) in public schools and what the parents believed to be the most important prerequisite of child-based skills for successful inclusion. A total of 148 parents were selected to complete the survey. The researchers explored whether variable demographic characteristics such as age, student's gender, parent's gender, education levels, monthly income, and high-or low-function ASD correlated with the attitudes of parents towards inclusion of students with ASD in public schools. The analyses revealed that the variables that correlated with parents' attitudes towards inclusion were education levels and high-or low-function ASD. The themes behind the parents' attitude for inclusion are discussed. With regard to the prerequisite skills for successful inclusion, the results indicated that parents recommended independent skills, playing skills, behavioural skills, imitation skills, routine skills, social skills, paying attention skills, language skills, and pre-academic and academic skills in that order. C1 [Abu-Hamour, Bashir] Mutah Univ, Dept Counseling & Special Educ, Fac Educ Sci, Mutah Al Karak 61710, Jordan. [Muhaidat, Mohammad] Al Yarmouk Univ, Dept Counseling & Educ Psychol, Irbid, Jordan. RP Abu-Hamour, B (reprint author), Mutah Univ, Dept Counseling & Special Educ, Fac Educ Sci, POB 6, Mutah Al Karak 61710, Jordan. EM dr.abuhamourwj@gmail.com CR Al-Rossan F., 2012, INTRO SPECIAL ED Al-Zyoudi M., 2006, INT J SPECIAL ED, V21, P55 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Avramidis E., 2000, EDUC PSYCHOL, V20, P191, DOI DOI 10.1080/713663717 Baker E. T., 1994, EDUC LEADERSHIP, V52, P3 Balboni G, 2000, EDUC TRAIN MENT RET, V35, P148 Bennett T, 1997, EXCEPT CHILDREN, V64, P115 BUYSSE V, 1993, J SPEC EDUC, V26, P434 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Cole K. N., 1991, EXCEPT CHILDREN, V58, P1 De Boer A. 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P., 1997, FAMILIES PROFESSIONA Turnbull R., 2002, EXCEPTIONAL LIVES SP NR 46 TC 0 Z9 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-3116 EI 1464-5173 J9 INT J INCLUSIVE EDUC JI Int. J. Incl. Educ. PD JUN PY 2014 VL 18 IS 6 BP 567 EP 579 DI 10.1080/13603116.2013.802026 PG 13 WC Education & Educational Research SC Education & Educational Research GA AJ3HW UT WOS:000337558100002 ER PT J AU Carroll, RA Kodak, T AF Carroll, Regina A. Kodak, Tiffany TI An evaluation of interrupted and uninterrupted measurement of vocal stereotypy on perceived treatment outcomes SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE automatic reinforcement; noncontingent reinforcement; response interruption and redirection; vocal stereotypy; data analysis ID AUTISM SPECTRUM DISORDERS; RESPONSE INTERRUPTION; MATCHED STIMULATION; REPETITIVE BEHAVIOR; REDIRECTION; CHILDREN; REPLICATION; PREFERENCE; IMMEDIATE AB The type of procedure used to measure a target behavior may directly influence the perceived treatment outcomes. In the present study, we examined the influence of different data-analysis procedures on the outcomes of two commonly used treatments on the vocal stereotypy of 2 children with an autism spectrum disorder. In Study 1, we compared an interrupted and uninterrupted data-analysis procedure to measure vocal stereotypy during the implementation of response interruption and redirection (RIRD). The results showed that the interrupted data-analysis procedure overestimated the effectiveness of RIRD. In Study 2, we examined the influence of different data-analysis procedures on the interpretation of the relative effects of 2 different treatments for vocal stereotypy. Specifically, we compared interrupted and uninterrupted data-analysis procedures during the implementation of RIRD and noncontingent reinforcement (NCR) as a treatment for vocal stereotypy. The results showed that, as in Study 1, the interrupted data-analysis procedure overestimated the effectiveness of RIRD; however, this effect was not apparent with NCR. These findings suggest that different types of data analysis can influence the perceived success of a treatment. C1 [Carroll, Regina A.] W Virginia Univ, Morgantown, WV 26506 USA. [Kodak, Tiffany] Univ Oregon, Eugene, OR 97403 USA. RP Carroll, RA (reprint author), W Virginia Univ, Dept Psychol, Life Sci Room 1232,53 Campus Dr, Morgantown, WV 26506 USA. EM racarroll@mail.wvu.edu CR Ahearn WH, 2007, J APPL BEHAV ANAL, V40, P263, DOI 10.1901/jaba.2007.30-06 Ahrens EN, 2011, J APPL BEHAV ANAL, V44, P95, DOI 10.1901/jaba.2011.44-95 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Cassella MD, 2011, J APPL BEHAV ANAL, V44, P169, DOI 10.1901/jaba.2011.44-169 Colon CL, 2012, J APPL BEHAV ANAL, V45, P107, DOI 10.1901/jaba.2012.45-107 Cooper J. O., 2007, APPL BEHAV ANAL Cummings AR, 2009, J APPL BEHAV ANAL, V42, P57, DOI 10.1901/jaba.2009.42-57 Giles AF, 2012, RES DEV DISABIL, V33, P1691, DOI 10.1016/j.ridd.2012.05.008 Iwata Brian A, 2008, Behav Anal Pract, V1, P3 KOEGEL RL, 1972, J APPL BEHAV ANAL, V5, P381, DOI 10.1901/jaba.1972.5-381 Lang R, 2010, BEHAV MODIF, V34, P267, DOI 10.1177/0145445510370713 Lanovaz MJ, 2009, BEHAV MODIF, V33, P682, DOI 10.1177/0145445509344972 Lanovaz MJ, 2012, BEHAV MODIF, V36, P146, DOI 10.1177/0145445511427192 Lewis MH, 1998, MENT RETARD DEV D R, V4, P80, DOI 10.1002/(SICI)1098-2779(1998)4:2<80::AID-MRDD4>3.0.CO;2-0 Liu-Gitz L, 2010, BEHAV INTERVENT, V25, P77, DOI 10.1002/bin.297 Love JJ, 2012, J APPL BEHAV ANAL, V45, P549, DOI 10.1901/jaba.2012.45-549 Miguel CF, 2009, J APPL BEHAV ANAL, V42, P883, DOI 10.1901/jaba.2009.42-883 Mudford OC, 2009, J APPL BEHAV ANAL, V42, P165, DOI 10.1901/jaba.2009.42-165 Piazza CC, 2000, J APPL BEHAV ANAL, V33, P13, DOI 10.1901/jaba.2000.33-13 Rapp JT, 2007, J APPL BEHAV ANAL, V40, P73, DOI 10.1901/jaba.2007.142-05 Rapp JT, 2013, BEHAV MODIF, V37, P543, DOI 10.1177/0145445512461650 Rapp JT, 2005, RES DEV DISABIL, V26, P527, DOI 10.1016/j.ridd.2004.11.005 Rapp JT, 2001, BEHAV MODIF, V25, P79, DOI 10.1177/0145445501251005 Rapp JT, 2008, BEHAV INTERVENT, V23, P237, DOI 10.1002/bin.269 Rapp JT, 2006, J APPL BEHAV ANAL, V39, P137, DOI 10.1901/jaba.2006.37-05 Roane HS, 1998, J APPL BEHAV ANAL, V31, P605, DOI 10.1901/jaba.1998.31-605 Schumacher BI, 2011, J APPL BEHAV ANAL, V44, P681, DOI 10.1901/jaba.2011.44-681 NR 28 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 264 EP 276 DI 10.1002/jaba.118 PG 13 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500004 PM 24764249 ER PT J AU Garcia-Albea, E Reeve, SA Reeve, KF Brothers, KJ AF Garcia-Albea, Elena Reeve, Sharon A. Reeve, Kenneth F. Brothers, Kevin J. TI Using audio script fading and multiple-exemplar training to increase vocal interactions in children with autism SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; multiple-exemplar training; scripts; script fading; spontaneous language ID SOCIAL-INTERACTION SKILLS; GENERALIZED REPERTOIRE; TEACHING-CHILDREN; ACQUISITION; LANGUAGE AB Script-fading procedures have been shown to be effective for teaching children with autism to initiate and participate in social interactions without vocal prompts from adults. In previous script and script-fading research, however, there has been no demonstration of a generalized repertoire of vocal interactions under the control of naturally occurring relevant stimuli. In this study, 4 boys with autism were taught to initiate a conversation in the presence of toys through the use of a script and script-fading procedure. Training with multiple categories and exemplars of toys was used to increase the likelihood of generalization of vocal interactions across novel toys. A multiple-probe design across participants was used to assess the effects of these procedures. The intervention successfully brought interactions by children with autism under the control of relevant stimuli in the environment. Future research pertaining to the specific implementation of these procedures (e.g., fading, script placement, participant characteristics) is discussed. C1 [Garcia-Albea, Elena; Reeve, Sharon A.; Reeve, Kenneth F.] Caldwell Coll, Caldwell, NJ 07006 USA. [Brothers, Kevin J.] Somerset Hills Learning Inst, Bedminster Township, NJ USA. RP Reeve, SA (reprint author), Caldwell Coll, Dept Appl Behav Anal, 120 Bloomfield Ave, Caldwell, NJ 07006 USA. EM sreeve@caldwell.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Brown JL, 2008, RES AUTISM SPECT DIS, V2, P480, DOI 10.1016/j.rasd.2007.08.006 CARR EG, 1983, J APPL BEHAV ANAL, V16, P297, DOI 10.1901/jaba.1983.16-297 Carr JE, 2000, J APPL BEHAV ANAL, V33, P353, DOI 10.1901/jaba.2000.33-353 CHARLOP MH, 1985, J APPL BEHAV ANAL, V18, P155, DOI 10.1901/jaba.1985.18-155 CHARLOP MH, 1991, J APPL BEHAV ANAL, V24, P747, DOI 10.1901/jaba.1991.24-747 Cowan RJ, 2007, PSYCHOL SCHOOLS, V44, P701, DOI 10.1002/pits.20259 Engelmann S., 1982, THEORY INSTRUCTION P Horner R. H., 1982, DESIGN HIGH SCH PROG, P61 Krantz PJ, 1998, J APPL BEHAV ANAL, V31, P191, DOI 10.1901/jaba.1998.31-191 KRANTZ PJ, 1993, J APPL BEHAV ANAL, V26, P121, DOI 10.1901/jaba.1993.26-121 MacDuff JL, 2007, RES AUTISM SPECT DIS, V1, P281, DOI 10.1016/j.rasd.2006.11.003 Marzullo-Kerth D, 2011, J APPL BEHAV ANAL, V44, P279, DOI 10.1901/jaba.2011.44-279 MATSON JL, 1990, J APPL BEHAV ANAL, V23, P227, DOI 10.1901/jaba.1990.23-227 MCGEE GG, 1983, J APPL BEHAV ANAL, V16, P329, DOI 10.1901/jaba.1983.16-329 Osnes P. G., 2003, BEHAV ANAL TODAY, V3, P364 Reagon KA, 2009, J APPL BEHAV ANAL, V42, P659, DOI 10.1901/jaba.2009.42-659 Reeve SA, 2007, J APPL BEHAV ANAL, V40, P123, DOI 10.1901/jaba.2007.11-05 Reimers T. M., 1988, BEHAVIORAL DISORDERS, V14, P7 Sarokoff RA, 2001, J APPL BEHAV ANAL, V34, P81, DOI 10.1901/jaba.2001.34-81 Stevenson CL, 2000, BEHAV INTERVENT, V15, P1, DOI 10.1002/(SICI)1099-078X(200001/03)15:1<1::AID-BIN41>3.0.CO;2-V STOKES TF, 1977, J APPL BEHAV ANAL, V10, P349, DOI 10.1901/jaba.1977.10-349 Zimmerman I.L., 1992, PRESCHOOL LANGUAGE S NR 23 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 325 EP 343 DI 10.1002/jaba.125 PG 19 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500008 PM 24763913 ER PT J AU Armstrong, A Knapp, VM McAdam, DB AF Armstrong, Amy Knapp, Vicki Madaus McAdam, David B. TI Functional analysis and treatment of the diurnal bruxism of a 16-year-old girl with autism SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE bruxism; functional analysis; vocal reprimand ID ABERRANT BEHAVIOR; INTERVENTION AB Bruxism is defined as the clenching and grinding of teeth. This study used a functional analysis to examine whether the bruxism of a 16-year-old girl with autism was maintained by automatic reinforcement or social consequences. A subsequent component analysis of the intervention package described by Barnoy, Najdowski, Tarbox, Wilke, and Nollet (2009) showed that a vocal reprimand (e.g., stop grinding) effectively reduced the participant's bruxism. Results were maintained across time, and effects extended to novel staff members. C1 [Armstrong, Amy; Knapp, Vicki Madaus] Summit Educ Resources, Getzville, NY 14068 USA. [McAdam, David B.] Univ Rochester, Sch Med, Rochester, NY 14627 USA. RP Knapp, VM (reprint author), Summit Educ Resources, 150 Stahl Rd, Getzville, NY 14068 USA. EM vmknapp@summited.org CR BARLOW DH, 1979, J APPL BEHAV ANAL, V12, P199, DOI 10.1901/jaba.1979.12-199 Barnoy EL, 2009, J APPL BEHAV ANAL, V42, P845, DOI 10.1901/jaba.2009.42-845 DeMattei R., 2007, J DENT HYGIENE, V81, P1 IWATA BA, 1994, J APPL BEHAV ANAL, V27, P197, DOI 10.1901/jaba.1994.27-197 Lang R, 2009, RES DEV DISABIL, V30, P809, DOI 10.1016/j.ridd.2008.12.006 Lang R, 2013, J APPL BEHAV ANAL, V46, P322, DOI 10.1002/jaba.5 Paclawskyj TR, 2000, RES DEV DISABIL, V21, P223, DOI 10.1016/S0891-4222(00)00036-6 Shirley MJ, 1999, J APPL BEHAV ANAL, V32, P201, DOI 10.1901/jaba.1999.32-201 THOMPSON BA, 1994, AM FAM PHYSICIAN, V49, P1617 Vollmer TR, 1995, J APPL BEHAV ANAL, V28, P561, DOI 10.1901/jaba.1995.28-561 NR 10 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 415 EP 419 DI 10.1002/jaba.122 PG 5 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500014 PM 24740489 ER PT J AU Loughrey, TO Betz, AM Majdalany, LM Nicholson, K AF Loughrey, Tara Olivia Betz, Alison M. Majdalany, Lina M. Nicholson, Katie TI Using instructive feedback to teach category names to children with autism SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; instructive feedback; verbal behavior AB We evaluated the effects of instructive feedback (IF) on the emergence of spoken category names with 2 children who had been diagnosed with autism. IF stimuli were presented during listener discrimination training and consisted of presenting the category name associated with each target stimulus. Results suggest that participants acquired the speaker relations in the absence of prompting and reinforcement. Clinical implications and future research on the use of IF as a teaching procedure for children with autism are discussed. C1 Florida Inst Technol, Melbourne, FL 32901 USA. Scott Ctr Autism Treatment, Melbourne, FL USA. RP Betz, AM (reprint author), Florida Inst Technol, Sch Psychol, 150 W Univ Blvd, Melbourne, FL 32901 USA. EM abetz@fit.edu CR Carr JE, 2000, J APPL BEHAV ANAL, V33, P353, DOI 10.1901/jaba.2000.33-353 Reichow B, 2011, J APPL BEHAV ANAL, V44, P327, DOI 10.1901/jaba.2011.44-327 Sundberg M. L., 2008, VBMAPP VERBAL BEHAV Werts M. G., 1995, J BEHAV ED, V5, P55, DOI 10.1007/BF02110214 Wynn JW, 2003, BEHAV INTERVENT, V18, P245, DOI 10.1002/bin.142 NR 5 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 425 EP 430 DI 10.1002/jaba.123 PG 6 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500016 PM 24740544 ER PT J AU Kobari-Wright, VV Miguel, CF AF Kobari-Wright, Vissy V. Miguel, Caio F. TI The effects of listener training on the emergence of categorization and speaker behavior in children with autism SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; categorization; listener; naming; verbal behavior AB We evaluated the effects of listener training on the emergence of categorization and speaker behavior (i.e., tacts) using a nonconcurrent multiple baseline design. Four children with autism learned to select pictures given their dictated category names. We assessed whether they could match and tact pictures by category. After training, 3 participants tacted and categorized all pictures, and 1 participant failed both tests. After tact training, this participant categorized. These results suggest that listener training may be an efficient way to produce speaker behavior and categorization in children who have been diagnosed with autism. C1 [Kobari-Wright, Vissy V.; Miguel, Caio F.] Calif State Univ Sacramento, Sacramento, CA 95819 USA. RP Miguel, CF (reprint author), Calif State Univ Sacramento, Dept Psychol, 6000 J St, Sacramento, CA 95819 USA. EM miguelc@csus.edu CR Greer R. D., 2007, EUROPEAN J BEHAV ANA, V8, P109 Horne PJ, 2004, J EXP ANAL BEHAV, V81, P267, DOI 10.1901/jeab.2004.81-267 Horne PJ, 1996, J EXP ANAL BEHAV, V65, P185, DOI 10.1901/jeab.1996.65-185 Miguel C. F., 2009, DERIVED RELATIONAL R, P129 Miguel CF, 2008, J EXP ANAL BEHAV, V89, P383, DOI 10.1901/jeab.2008-89-383 Miguel CF, 2013, J APPL BEHAV ANAL, V46, P669, DOI 10.1002/jaba.62 Petursdottir AI, 2011, J APPL BEHAV ANAL, V44, P859, DOI 10.1901/jaba.2011.44-859 Sprinkle Evelyn C, 2012, Anal Verbal Behav, V28, P111 Sundberg M. L., 2008, VERBAL BEHAV MILESTO Voress J, 1998, DEV ASSESSMENT YOUNG VORT Corporation, 1995, HELP PRESCH ASS STRA NR 11 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 431 EP 436 DI 10.1002/jaba.115 PG 6 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500017 PM 24740431 ER PT J AU Rosales, R Maderitz, C Garcia, YA AF Rosales, Rocio Maderitz, Cecelia Garcia, Yors A. TI Comparison of simple and complex auditory-visual conditional discrimination training SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE complex samples; conditional discriminations ID SAMPLES; BEHAVIOR; CHILDREN; AUTISM AB We investigated the relative effects of simple and complex auditory-visual discrimination training using an adapted alternating treatments design to establish derived stimulus relations in 2 children who had been diagnosed with autism and 1 typically developing peer. Emergence of untrained conditional relations was observed after training in both conditions, with a possible advantage of simple-sample training for 1 participant. Results of generalization and follow-up probes were mixed. C1 [Rosales, Rocio; Maderitz, Cecelia] Youngstown State Univ, Youngstown, OH USA. [Garcia, Yors A.] Fdn Univ Konrad Lorenz, Urbana, IL USA. RP Rosales, R (reprint author), Univ Massachusetts, Dept Psychol, 113 Wilder St,Suite 300, Lowell, MA 01854 USA. EM rocio_rosales@uml.edu CR Groskreutz NC, 2010, J APPL BEHAV ANAL, V43, P131, DOI 10.1901/jaba.2010.43-131 Harper Dittlinger L., 2011, J APPL BEHAV ANAL, V44, P341, DOI [10.1901/jaba.2011.44-341, DOI 10.1901/JABA.2011.44-341] Horne PJ, 1996, J EXP ANAL BEHAV, V65, P185, DOI 10.1901/jeab.1996.65-185 Lane SD, 1998, J APPL BEHAV ANAL, V31, P21, DOI 10.1901/jaba.1998.31-21 MAGUIRE RW, 1994, J AUTISM DEV DISORD, V24, P753, DOI 10.1007/BF02172284 Rehfeldt RA, 2011, J APPL BEHAV ANAL, V44, P109, DOI 10.1901/jaba.2011.44-109 SIDMAN M, 1971, J SPEECH HEAR RES, V14, P5 STROMER R, 1992, J APPL BEHAV ANAL, V25, P893, DOI 10.1901/jaba.1992.25-893 NR 8 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2014 VL 47 IS 2 BP 437 EP 442 DI 10.1002/jaba.121 PG 6 WC Psychology, Clinical SC Psychology GA AJ3YO UT WOS:000337604500018 PM 24764261 ER PT J AU Loe, IM Feldman, HM Huffman, LC AF Loe, Irene M. Feldman, Heidi M. Huffman, Lynne C. TI Executive Function Mediates Effects of Gestational Age on Functional Outcomes and Behavior in Preschoolers SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE premature birth; preterm; executive function; adaptive function; reading; behavior; mediation ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; BIRTH-WEIGHT CHILDREN; WORKING-MEMORY; PRETERM CHILDREN; ACADEMIC-ACHIEVEMENT; FUNCTION IMPAIRMENT; PROCESSING SPEED; RATING INVENTORY; BRAIN-INJURY AB Objective: To investigate the role of executive function (EF) skills, measured by parent-rating and performance-based instruments, as mediators of the effects of gestational age (GA) on functional outcomes and behavior symptoms in preterm (PT) and full-term (FT) preschoolers. Patients and Methods: Children born PT (n = 70; mean GA, 29.6 weeks; mean birth weight, 1365 g) were compared to children born FT (n 5 79) on composite measures of EF (using the Behavior Rating Inventory of Executive Function and a performance-based EF battery), adaptive function, prereading skills, and behavior symptoms. For the entire sample, mediation analyses examined the effect of GA on the outcomes with EF as mediator. Results: Compared to children born FT, children born PT had significantly higher parent-rated EF scores and lower performance-based EF scores, both indicating more problems; furthermore, children born PT had lower adaptive function and prereading scores and more problematic behavior. GA contributed to adaptive function, prereading skills, and behavior symptoms for all children. EF acted as a mediator of GA for all 3 outcomes; different patterns emerged for parent-rated and performance-based EF evaluations. For adaptive function, both EF measures significantly mediated the effects of GA; for prereading skills, only performance-based EF was significant; for behavior symptoms, only parent-rated EF was significant. Conclusions: We propose standard assessment of EF, using both parent-rating and performance-based EF measures, in young PT children and other children at the risk of EF impairments. EF skills are measurable, mediate important functional outcomes, and may serve as intervention targets. C1 [Loe, Irene M.; Feldman, Heidi M.; Huffman, Lynne C.] Stanford Univ, Dept Pediat, Sch Med, Div Neonatal & Dev Med, Stanford, CA 94305 USA. RP Loe, IM (reprint author), Stanford Univ, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM iloe@stanford.edu FU Child Health Research Institute of Stanford University; Lucile Packard Foundation for Children's Health; Society for Developmental-Behavioral Pediatrics under the Young Investigator Award; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [K23HD071971]; National Center for Research Resources, National Institutes of Health under the Stanford Clinical and Translational Science Award [UL1 TR001085] FX The work was supported by the Child Health Research Institute of Stanford University and Lucile Packard Foundation for Children's Health under a Pilot Early Career Grant, the Society for Developmental-Behavioral Pediatrics under the Young Investigator Award, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, under the Mentored Patient-oriented Research Career Development Award Grant (K23HD071971) to I.M.L.; and the National Center for Research Resources, National Institutes of Health under the Stanford Clinical and Translational Science Award (UL1 TR001085). 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Dev. Behav. Pediatr. PD JUN PY 2014 VL 35 IS 5 BP 323 EP 333 PG 11 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AJ0PL UT WOS:000337357400003 PM 24906034 ER PT J AU Hall, GC Hill, F AF Hall, Gillian C. Hill, Fiona TI Descriptive investigation of the recording of influenza vaccination details on The Health Information Network database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pharmacoepidemiology; influenza; vaccination; batch number; primary care database; validation ID BELLS-PALSY; RISK; VACCINES; AUTISM; SAFETY AB BackgroundThe UK primary care databases are used in pharmacoepidemiology studies of vaccination type. We investigated vaccine recording and whether, and how, exposure to specific brands and batches can be identified. MethodsDetails of influenza vaccinations given in the 2010-2011 or 2011-2012 seasons were identified from coded and text fields in The Health Information Network UK primary care database. The proportion of people over 64years of age vaccinated against influenza was compared with published regional rates. Searches for Fluvirin (Novartis Vaccines and Diagnostics GmbH, Marburg, Germany) batch numbers and name identified exposure to this specific vaccine. The recording of any brand name and batch number was described for a sample of 1000 vaccinations across 472 practices. ResultsA total of 767904 influenza vaccinations were identified during the 2010-2011 season and 784518 in 2011-2012. Vaccination rates for people aged over 64years were 75.6%, 80.9%, 78.4% and 71.9% in England, Northern Ireland, Scotland and Wales, respectively (2011-2012 season), compared with published figures of 74.0%, 77.0%, 76.2% and 67.7%. Rates were slightly lower in 2010-2011 in both data sources. A Fluvirin brand was identified for 3.6% of all UK vaccinations but 26.2% of those in Scottish practices. Vaccination brand could be identified for 94.3% of the sample, 93.6% with a batch number. Batch number (98.5%) and brand name (50.3%) were most frequently recorded in an immunisation batch' text field. ConclusionPatients exposed to an influenza vaccine in primary care can be identified from The Health Information Network. Identification of brand or batch number requires a text search. Regional variation in brand of vaccine should be considered when estimating sample size. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Hill, Fiona] Cegedim Strateg Data Med Res Ltd, London, England. RP Hall, GC (reprint author), Grimsdyke House, London EN5 4ND, England. 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Drug Saf. PD JUN PY 2014 VL 23 IS 6 BP 595 EP 600 DI 10.1002/pds.3515 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ2YS UT WOS:000337532000007 PM 24123471 ER PT J AU Imai, K Iida, T Yamamoto, M Komatsu, K Nukui, Y Yoshizawa, A AF Imai, Koubun Iida, Toshiharu Yamamoto, Maki Komatsu, Kensuke Nukui, Yuko Yoshizawa, Atsuto TI Psychological and mental health problems in patients with thalidomide embryopathy in Japan SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE cognitive performance; electroencephalography; Mini-International Neuropsychiatric Interview; psychological tests; thalidomide embryopathy AB Aim The aim of the study was to examine the presence of psychological and mental health problems in patients with thalidomide embryopathy in Japan in order to develop and build future support systems. Methods The present study examined the presence/absence of electroencephalographic abnormalities, intellectual/cognitive functions, and mental health problems in 22 participants (nine men, 13 women) with thalidomide embryopathy. Participants completed the electroencephalograph instrument. Participants were also assessed using the Wechsler Adult Intelligence Scale-III; the Autism-Spectrum Quotient; the General Health Questionnaire-28, and the Mini-International Neuropsychiatric Interview. Results The results suggest the following: (i) electroencephalographic abnormality observed in several thalidomide embryopathy participants is unlikely to be the direct result of thalidomide; (ii) the cognitive functions of working memory and processing speed are lower in thalidomide embryopathy patients than in healthy individuals; and (iii) 40.9% of the thalidomide embryopathy participants have possible mental disorders, with more mental problems observed than in healthy individuals. Conclusions Deterioration of mental health in patients with thalidomide embryopathy is indicated. Anxiety, insomnia, and physical symptoms were especially remarkable and may have resulted in restriction of social activities. Therefore, careful examination and active support of patients' psychological and mental problems is essential. C1 [Imai, Koubun; Iida, Toshiharu; Yamamoto, Maki; Nukui, Yuko] Natl Ctr Global Hlth & Med Hosp, Dept Psychiat, Tokyo 1628655, Japan. [Komatsu, Kensuke] Natl Ctr Global Hlth & Med Hosp, AIDS Clin Ctr, Tokyo 1628655, Japan. [Yoshizawa, Atsuto] Natl Ctr Global Hlth & Med Hosp, Dept Gen Internal Med, Tokyo 1628655, Japan. [Iida, Toshiharu] Yamanashi Eiwa Coll, Dept Humanities, Yamanashi, Japan. RP Imai, K (reprint author), Natl Ctr Global Hlth & Med Hosp, Dept Psychiat, Shinjyuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan. 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This expertise has been linked to 2 coding mechanisms: holistic integration of information across the face and adaptive coding of face identity using norms tuned by experience. Recently, individual differences in face recognition ability have been discovered and linked to differences in holistic coding. Here we show that they are also linked to individual differences in adaptive coding of face identity, measured using face identity aftereffects. Identity aftereffects correlated significantly with several measures of face-selective recognition ability. They also correlated marginally with own-race face recognition ability, suggesting a role for adaptive coding in the well-known other-race effect. More generally, these results highlight the important functional role of adaptive face-coding mechanisms in face expertise, taking us beyond the traditional focus on holistic coding mechanisms. 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PD JUN PY 2014 VL 40 IS 3 BP 897 EP 903 DI 10.1037/a0035939 PG 7 WC Psychology; Psychology, Experimental SC Psychology GA AI3TP UT WOS:000336786900001 PM 24684315 ER PT J AU Kopec, J Hillier, A Frye, A AF Kopec, Justin Hillier, Ashleigh Frye, Alice TI THE VALENCY OF MUSIC HAS DIFFERENT EFFECTS ON THE EMOTIONAL RESPONSES OF THOSE WITH AUTISM SPECTRUM DISORDERS AND A COMPARISON GROUP SO MUSIC PERCEPTION LA English DT Article DE Asperger's syndrome; autism; music perception; valence; emotional response ID BASIC EMOTIONS; ALEXITHYMIA; FACES; FELT; CHILDREN; VALIDITY; DISABILITIES; RECOGNITION; CONVERGENT; ABILITIES AB EMOTION PERCEPTION DEFICITS ARE COMMONLY observed in individuals with autism spectrum disorders (ASD). Numerous studies have documented deficits in emotional recognition of social stimuli among those with ASD, such as faces and voices, while far fewer have investigated emotional recognition of nonsocial stimuli in this population. In this study, participants with ASD and a comparison group of typically developing (TD) control participants listened to song clips that varied in levels of pleasantness (valence) and arousal. Participants then rated emotions they felt or perceived in the music, using a list of eight emotion words for each song. Results showed that individuals with ASD gave significantly lower ratings of negative emotions in both the felt and perceived categories compared to TD controls, but did not show significant differences in ratings of positive emotions. These findings suggest that deficits in processing emotions in music among those with ASD may be valence specific. C1 [Kopec, Justin; Hillier, Ashleigh; Frye, Alice] Univ Massachusetts Lowell, Lowell, MA 01854 USA. RP Hillier, A (reprint author), Univ Massachusetts Lowell, Dept Psychol, 131 Wilder St,Suite 300, Lowell, MA 01854 USA. 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PD JUN PY 2014 VL 31 IS 5 BP 436 EP 443 DI 10.1525/MP.2014.31.5.436 PG 8 WC Music; Psychology, Experimental SC Music; Psychology GA AI8YM UT WOS:000337212900003 ER PT J AU Reilly, C Atkinson, P Das, KB Chin, RFMC Aylett, SE Burch, V Gillberg, C Scott, RC Neville, BGR AF Reilly, Colin Atkinson, Patricia Das, Krishna B. Chin, Richard F. M. C. Aylett, Sarah E. Burch, Victoria Gillberg, Christopher Scott, Rod C. Neville, Brian G. R. TI Neurobehavioral Comorbidities in Children With Active Epilepsy: A Population-Based Study SO PEDIATRICS LA English DT Article DE epilepsy; children; cognition; behavior; screening ID CHILDHOOD-ONSET EPILEPSY; PEDIATRIC EPILEPSY; PSYCHIATRIC COMORBIDITY; DISORDERS; OUTCOMES; UPDATE AB BACKGROUND: In addition to recurrent epileptic seizures, children with epilepsy can have coexisting cognitive and behavioral difficulties but the spectrum and prevalence of such difficulties are uncertain. METHODS: The Children with Epilepsy in Sussex Schools study is a prospective, community-based study involving school-aged children (5-15 years) with active epilepsy in a defined geographical area in the United Kingdom. Participants underwent comprehensive psychological assessment, including measures of cognition, behavior, and motor functioning. Consensus neurobehavioral diagnoses were made with respect to Diagnostic and Statistical Manual, Fourth Edition-Text Revision (DSM-IV-TR) criteria. RESULTS: A total of 85 children (74% of eligible population) were enrolled; 80% of children with active epilepsy had a DSM-IV-TR behavioral disorder and/or cognitive impairment (IQ < 85). Intellectual disability (ID) (IQ < 70) (40%), attention-deficit/hyperactivity disorder (ADHD) (33%), and autism spectrum disorder (ASD) (21%) were the most common neurobehavioral diagnoses. Of those who met criteria for a DSM-IV-TR behavioral disorder, only one-third had previously been diagnosed. Logistic regression revealed that seizures in the first 24 months compared with first seizures at 24 to 60 or 61+ months (odds ratio [OR] 13, 95% confidence interval 2.2-76.9; OR 21.3, 3.2-148.9) and polytherapy (OR 7.7, 1.6-36.3) were independently associated with ID and the presence of ID was associated with a diagnosis of ASD (OR 14.1, 2.3-87.1) after Bonferroni adjustment. Epilepsy-related factors did not independently predict the presence of behavioral disorders. CONCLUSIONS: Screening for neurobehavioral comorbidities should be an integral part of management in children with "active" epilepsy. There is a need for research to identify neurobiological mechanisms underpinning neurobehavioral impairments and studies to evaluate possible treatments. C1 [Reilly, Colin; Das, Krishna B.; Burch, Victoria; Neville, Brian G. R.] Young Epilepsy, Res Dept, Surrey RH7 6PW, England. [Atkinson, Patricia] Crawley Hosp, Child Dev Ctr, Crawley, W Sussex, England. [Das, Krishna B.; Aylett, Sarah E.; Gillberg, Christopher; Scott, Rod C.; Neville, Brian G. R.] UCL, Inst Child Hlth, Neurosci Unit, London, England. [Das, Krishna B.; Aylett, Sarah E.; Scott, Rod C.] Great Ormond St Hosp Sick Children, London, England. [Chin, Richard F. M. C.] Univ Edinburgh, Edinburgh Neurosci, Muir Maxwell Epilepsy Ctr, Edinburgh, Midlothian, Scotland. [Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Scott, Rod C.] Univ Vermont, Coll Med, Burlington, VT USA. RP Reilly, C (reprint author), Young Epilepsy, Res Dept, Surrey RH7 6PW, England. EM creilly@youngepilepsy.org.uk FU Esmee Fairbairn Foundation; Great Ormond Street Hospital Children's Charity FX The Children with Epilepsy in Sussex Schools study was funded by the Esmee Fairbairn Foundation and an anonymous donor to Young Epilepsy. Professor Scott is supported by the Great Ormond Street Hospital Children's Charity. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Austin JK, 2007, EPILEPSIA, V48, P1639, DOI 10.1111/j.1528-1167.2007.01154.x Berg AT, 2008, EPILEPSIA, V49, P608, DOI 10.1111/j.1528-1167.2007.01461.x Berg AT, 2011, EPILEPSY BEHAV, V20, P550, DOI 10.1016/j.yebeh.2010.12.038 Berg AT, 2010, EPILEPSIA, V51, P676, DOI 10.1111/j.1528-1167.2010.02522.x Blocher JB, 2013, EPILEPSY BEHAV, V27, P70, DOI 10.1016/j.yebeh.2012.12.014 Camfield CS, 1996, EPILEPSIA, V37, P19, DOI 10.1111/j.1528-1157.1996.tb00506.x Canitano R, 2007, EUR CHILD ADOLES PSY, V16, P61, DOI 10.1007/s00787-006-0563-2 Chin RFM, 2011, EPILEPSIA, V52, P1513, DOI 10.1111/j.1528-1167.2011.03170.x Davies S, 2003, DEV MED CHILD NEUROL, V45, P292, DOI 10.1017/S0012162203000550 Elger CE, 2004, LANCET NEUROL, V3, P663, DOI 10.1016/S1474-4422(04)00906-8 Geerts A, 2011, EPILEPSIA, V52, P2192, DOI 10.1111/j.1528-1167.2011.03294.x Gonzalez-Heydrich J, 2010, EPILEPSY BEHAV, V18, P229, DOI 10.1016/j.yebeh.2010.02.022 Hamiwka L, 2011, EPILEPSIA, V52, P870, DOI 10.1111/j.1528-1167.2011.03074.x Helmstaedter C., 2011, NEUROPSYCHOLOGY CARE Hermann B, 2008, LANCET NEUROL, V7, P151, DOI 10.1016/S1474-4422(08)70018-8 Hoie B, 2005, SEIZURE-EUR J EPILEP, V14, P223, DOI 10.1016/j.seizure.2004.10.006 Jensen FE, 2011, EPILEPSIA, V52, P1, DOI 10.1111/j.1528-1167.2010.02904.x Jones JE, 2007, DEV MED CHILD NEUROL, V49, P493 Kadesjo B, 1999, J AM ACAD CHILD PSY, V38, P820, DOI 10.1097/00004583-199907000-00011 Lin JJ, 2012, LANCET, V380, P1180, DOI 10.1016/S0140-6736(12)61455-X Martinos MM, 2013, EPILEPSIA, V54, P1012, DOI 10.1111/epi.12136 Martinovic Z, 2006, EPILEPSY BEHAV, V9, P619, DOI 10.1016/j.yebeh.2006.08.017 Ott D, 2003, EPILEPSIA, V44, P591, DOI 10.1046/j.1528-1157.2003.25002.x Plioplys S, 2007, J AM ACAD CHILD PSY, V46, P1389, DOI 10.1097/chi.0b013e31815597fc Rai D, 2012, EPILEPSIA, V53, P1095, DOI 10.1111/j.1528-1167.2012.03500.x Rantanen K, 2011, EPILEPSIA, V52, P1499, DOI 10.1111/j.1528-1167.2011.03092.x Rodenburg R, 2006, EPILEPSIA, V47, P601, DOI 10.1111/j.1528-1167.2006.00475.x Russ SA, 2012, PEDIATRICS, V129, P256, DOI 10.1542/peds.2010-1371 Shinnar S, 2002, J CHILD NEUROL, V17, pS4, DOI 10.1177/08830738020170010201 NR 30 TC 14 Z9 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUN PY 2014 VL 133 IS 6 BP E1586 EP E1593 DI 10.1542/peds.2013-3787 PG 8 WC Pediatrics SC Pediatrics GA AI8MY UT WOS:000337172600014 PM 24864167 ER PT J AU Sukenik-Halevy, R Reches, A Bar-Shira, A Simchoni, S Goldstein, M Orr-Ortreger, A Yaron, Y Ben-Shachar, S AF Sukenik-Halevy, Rivka Reches, Adi Bar-Shira, Anat Simchoni, Sharon Goldstein, Myriam Orr-Ortreger, Avi Yaron, Yuval Ben-Shachar, Shay TI Microscopic chromosome Xp distal deletions - a challenging issue in prenatal genetic counseling SO PRENATAL DIAGNOSIS LA English DT Article ID CYTOGENETIC ANALYSIS; FEMALES; PHENOTYPE; AUTISM; SHOX AB ObjectiveA prenatal diagnosis of chromosome X short arm deletions may present a challenge in prenatal genetic counseling. We present clinical and molecular data of carriers of Xp distal deletions. MethodsWe assessed prenatal and postnatal phenotypes of individuals from three families with large Xp distal deletions and from a fourth family with a small Xp distal deletion. The work-up included karyotyping, chromosomal microarray analysis, and assessment of the X inactivation pattern. ResultsFive out of eight women with large deletions had a short stature (<3rd percentile). Subjects from one family had developmental and emotional problems. All female carriers with small deletions had markedly short stature, whereas the men had mildly short stature. Chromosomal microarray analysis revealed 11.7-19.3Mb deletions in three families and a small similar to 1Mb deletion in the fourth. The pseudoautosomal region 1 of the X chromosome was deleted in two families with large deletions. X inactivation was skewed in all tested cases with large deletions. ConclusionXp distal deletions are mainly associated with short stature. Skewing of the abnormal X chromosome may attenuate the phenotype in cases with large deletions. We suggest that prenatal evaluation in such cases should include sonographic follow-up and assessment of the X inactivation pattern. (c) 2014 John Wiley & Sons, Ltd. C1 [Sukenik-Halevy, Rivka; Reches, Adi; Bar-Shira, Anat; Simchoni, Sharon; Goldstein, Myriam; Orr-Ortreger, Avi; Yaron, Yuval; Ben-Shachar, Shay] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel. [Sukenik-Halevy, Rivka; Reches, Adi; Bar-Shira, Anat; Simchoni, Sharon; Goldstein, Myriam; Orr-Ortreger, Avi; Yaron, Yuval; Ben-Shachar, Shay] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Prenatal Genet Diag Unit, IL-69978 Tel Aviv, Israel. [Orr-Ortreger, Avi; Yaron, Yuval] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RP Ben-Shachar, S (reprint author), Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel. 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Diagn. PD JUN PY 2014 VL 34 IS 6 BP 592 EP 597 DI 10.1002/pd.4354 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA AJ3UG UT WOS:000337592500014 PM 24609917 ER PT J AU Farrelly, LA Dicker, P Wynne, K English, J Cagney, G Focking, M Cotter, DR AF Farrelly, Lorna A. Dicker, Patrick Wynne, Kieran English, Jane Cagney, Gerard Foecking, Melanie Cotter, David R. TI Adolescent Risperidone treatment alters protein expression associated with protein trafficking and cellular metabolism in the adult rat prefrontal cortex SO PROTEOMICS LA English DT Article DE Antipsychotics; Biomedicine; LC-MS/MS; Prefrontal cortex; Risperidone ID ATYPICAL ANTIPSYCHOTICS; SCHIZOPHRENIA-PATIENTS; WORKING-MEMORY; FRONTAL-CORTEX; BRAIN; PHARMACOKINETICS; DYSFUNCTION; MECHANISM; PSYCHOSIS; DRUGS AB The prefrontal cortex (PFC) is associated with mental health illnesses including schizophrenia, depression, bipolar disorder, and autism spectrum disorders. It richly expresses neuroreceptors which are the target for antipsychotics. However, as the precise mechanism of action of antipsychotic medications is not known, proteomic studies of the effects of antipsychotic drugs on the brain are warranted. In the current study, we aimed to characterize protein expression in the adult rodent PFC (n = 5 per group) following low-dose treatment with Risperidone or saline in adolescence (postnatal days 34-47). The PFC was examined by triplicate 1 h runs of label-free LC-MS/MS. The raw mass spectral data were analyzed with the MaxQuant (TM) software. Statistical analysis was carried out using SAS (R) Version 9.1. Pathway and functional analysis was performed with Ingenuity Pathway Analysis and in the Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively, the most implicated pathways were found to be related to mitochondrial function, protein trafficking, and the cytoskeleton. This report adds to the current repertoire of data available concerning the effects of antipsychotic drugs on the brain and sheds light on their biological mechanisms. The MS data have been deposited with the ProteomeXchange Consortium with dataset identifier PXD000480. C1 [Farrelly, Lorna A.; English, Jane; Foecking, Melanie; Cotter, David R.] Beaumont Hosp, Royal Coll Surg Ireland, Dept Psychiat, Educ & Res Ctr, Dublin 9, Ireland. [Dicker, Patrick] Royal Coll Surgeons Ireland, Dept Epidemiol & Publ Hlth, Dublin 2, Ireland. [Wynne, Kieran; Cagney, Gerard] Univ Coll Dublin, Sch Biomol & Biomed Res, Conway Inst, Dublin 2, Ireland. RP Focking, M (reprint author), Beaumont Hosp, Royal Coll Surg Ireland, Dept Psychiat, Educ & Res Ctr, Dublin 9, Ireland. EM mfocking@rcsi.ie FU Science Foundation Ireland [RFP1304] FX Animal tissue was provided by Professor Ina Weiner in the School of Psychological Sciences in the University of Tel Aviv. We thank the staff of the Mass Spectrometry Core Unit in the Conway Institute in the University College of Dublin for technical assistance. This work was supported by Science Foundation Ireland (RFP1304 to D.R.C.). 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Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes. C1 [Bolte, Sven; Willfors, Charlotte; Berggren, Steve; Norberg, Joakim; Poltrago, Lina; Mevel, Katell; Coco, Christina; Borg, Jacqueline; Tammimies, Kristiina] Karolinska Inst, Pediat Neuropsychiat Unit, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders, SE-11330 Stockholm, Sweden. [Bolte, Sven; Berggren, Steve; Coco, Christina] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. [Poltrago, Lina] PRIMA Barn & Vuxenpsykiatri, Stockholm, Sweden. [Mevel, Katell] CNRS, Lab Psychol Child Dev & Educ, U3521, Paris, France. [Mevel, Katell] Paris Descartes Univ, Paris, France. [Mevel, Katell] Sorbonne Paris Cite, Paris, France. [Fransson, Peter; Borg, Jacqueline] Karolinska Inst, Dept Clin Neurosci, SE-11330 Stockholm, Sweden. [Sitnikov, Rouslan] Karolinska Univ Hosp, Neuroradiol Clin, MRI Res Ctr, Stockholm, Sweden. [Toro, Roberto] Inst Pasteur, Paris, France. [Anderlid, Britt-Marie; Nordgren, Ann] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Anderlid, Britt-Marie; Nordgren, Ann] Karolinska Inst, Dept Mol Med & Surg, SE-11330 Stockholm, Sweden. [Falk, Anna] Karolinska Inst, Dept Neurosci, SE-11330 Stockholm, Sweden. [Meyer, Urs] Swiss Fed Inst Technol, Physiol & Behav Lab, Zurich, Switzerland. [Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. [Landen, Mikael] Sahlgrens Acad, Sect Psychiat & Neurochem, Gothenburg, Sweden. [Dalman, Christina] Karolinska Inst, Dept Publ Hlth Sci, SE-11330 Stockholm, Sweden. [Ronald, Angelica] Univ London, Dept Psychol Sci, Ctr Brain & Cognit Dev, London, England. [Anckarsater, Henrik] Univ Gothenburg, Gothenburg, Sweden. [Landen, Mikael; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-11330 Stockholm, Sweden. RP Bolte, S (reprint author), Karolinska Inst, CAP Res Ctr, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders,Pediat Neuropsychiat Unit, Gavlegatan 22 Entre B,Floor 8, SE-11330 Stockholm, Sweden. EM sven.bolte@ki.se RI Ronald, Angelica/C-7812-2009; Fransson, Peter/M-5679-2014 OI Ronald, Angelica/0000-0002-9576-2176; Fransson, Peter/0000-0002-1305-9875 FU Swedish Research Council; FAS; FORMAS; VINNOVA (a cross-disciplinary research program concerning children's and youth's mental health) [259-2012-24]; Innovative Medicines Initiative Joint Undertaking [115300]; European Union [FP7/2007-2013]; EFPIA; Stockholm County Council; Sallskapet Barnavard; Swedish Order of Freemasons Grand Loge Stockholm; Stiftelsen Sunnerdahls Handikappfond; Hjarnfonden; Autism and Asperger Society Stockholm; Tore Nilssons Stiftelsen; Jeanssons Stiftelse; Magnus Bergvalls Stiftelse; PRIMA Barn- och Vuxenpsykiatri FX We greatly acknowledge Kerstin Andersson, Elodie Cauvet, Ann-Charlotte Engstrom, Anna Lange Nilsson, Martin Hammar, and Anna Rade for data collection in RATSS. Furthermore, we sincerely thank all twins and their relatives who participate in RATSS. The RATSS project is supported by the Swedish Research Council; the Swedish Research Council in partnership with FAS, FORMAS, and VINNOVA (a cross-disciplinary research program concerning children's and youth's mental health, grant no. 259-2012-24); Innovative Medicines Initiative Joint Undertaking (under grant agreement no. 115300), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (grant no. FP7/2007-2013) and EFPIA companies' in kind contribution; Stockholm County Council, Sallskapet Barnavard, The Swedish Order of Freemasons Grand Loge Stockholm, Stiftelsen Sunnerdahls Handikappfond, Hjarnfonden, Autism and Asperger Society Stockholm, Tore Nilssons Stiftelsen, Jeanssons Stiftelse, Magnus Bergvalls Stiftelse, and PRIMA Barn- och Vuxenpsykiatri. 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TI Autism traits in children and adolescents with Cornelia de Lange syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Cornelia de Lange syndrome; autism; behavioral phenotype; repetitive behaviors; communication; social cognition ID FRAGILE-X-SYNDROME; SELF-INJURIOUS-BEHAVIOR; TUBEROUS SCLEROSIS COMPLEX; SPECTRUM DISORDER; DELANGE-SYNDROME; MENTAL-RETARDATION; NIPPED-B; PHENOTYPE; MUTATIONS; BRAIN AB Cornelia de Lange syndrome (CdLS) is a cohesinopathy causing delayed growth and limb deficits. Individuals with CdLS have mild to profound intellectual disability and autistic features. This study characterizes the behavioral phenotype of children with CdLS, focusing on autistic features, maladaptive behaviors, and impact of age. Children with CdLS (5-18 years) were administered normed instruments to characterize autism features (Childhood Autism Rating Scale, CARS), maladaptive behaviors (Aberrant Behavior Checklist), and adaptive skills (Vineland Adaptive Behaviors Scales). CdLS features and severity were rated with Diagnostic Criteria for CdLS. Forty-one children with CdLS (23 females, 18 males) were classified as having "no autism" (n = 7; 17.1%), "mild autism" (n = 17; 41.4%), and "severe autism" (n = 17; 41.4%), using CARS scores. Characteristic items were abnormal emotional response, stereotypies, odd object use, rigidity, lack of verbal communication, and low intellectual functioning. Verbal communication deficits and repetitive behaviors were higher compared to sensory, social cognition, and behavior abnormalities (P <= 0.0001). Maladaptive behaviors associated with autism traits were stereotypies (P = 0.003), hyperactivity (P = 0.01), and lethargy (P = 0.03). Activities of daily living were significantly affected; socialization adaptive skills were a relative strength. However, with advancing age, both socialization (P < 0.0001) and communication (P = 0.001) domains declined significantly. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. While other adaptive skills are impacted, socialization adaptive skills are less affected. Advancing age can worsen communication and socialization deficits relative to neurotypical peers. (c) 2014 Wiley Periodicals, Inc. C1 [Srivastava, Siddharth] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD USA. [Landy-Schmitt, Colleen] PerkinElmer Diagnost Lab Serv, Frederick, MD USA. [Clark, Bennett] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kline, Antonie D.] Greater Baltimore Med Ctr, Harvey Inst Human Genet, Baltimore, MD USA. 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Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity. (c) 2014 Wiley Periodicals, Inc. C1 [Kuroda, Yukiko; Ohashi, Ikuko; Tominaga, Makiko; Ida, Kazumi; Naruto, Takuya; Kurosawa, Kenji] Kanagawa Childrens Med Ctr, Div Med Genet, Yokohama, Kanagawa 2328555, Japan. [Saito, Toshiyuki; Nagai, Jun-ichi] Kanagawa Childrens Med Ctr, Dept Clin Lab, Yokohama, Kanagawa 2328555, Japan. [Masuno, Mitsuo] Kawasaki Univ Med Welf, Genet Counseling Program, Kurashiki, Okayama, Japan. RP Kurosawa, K (reprint author), Kanagawa Childrens Med Ctr, Div Med Genet, Minami Ku, 2-138-4 Mutsukawa, Yokohama, Kanagawa 2328555, Japan. EM kkurosawa@kcmc.jp FU The Ministry of Health, Labour and Welfare of Japan FX Grant sponsor: The Ministry of Health, Labour and Welfare of Japan. 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J. Med. Genet. A PD JUN PY 2014 VL 164 IS 6 BP 1550 EP 1554 DI 10.1002/ajmg.a.36477 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA AH2BV UT WOS:000335926600026 PM 24668897 ER PT J AU Wilkinson, KM Mitchell, T AF Wilkinson, Krista M. Mitchell, Teresa TI Eye Tracking Research to Answer Questions about Augmentative and Alternative Communication Assessment and Intervention SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Eye tracking; Overview; Research; AAC; Developmental disabilities; Acquired disabilities ID VISUAL SCENE DISPLAYS; AUTISM SPECTRUM DISORDERS; WILLIAMS-SYNDROME; INTELLECTUAL DISABILITIES; INATTENTIONAL BLINDNESS; DOWN-SYNDROME; ATTENTION; INDIVIDUALS; MOVEMENTS; AAC AB Recently, eye tracking technologies (i.e., technologies that automatically track the point of an individual's gaze while that person views or interacts with a visual image) have become available for research purposes. Based on the sampling of the orientation of the individual's eyes, researchers can quantify which locations within the visual image were fixated (viewed), for how long, and how many times. These automated eye tracking research technologies open up a wealth of avenues for investigating how individuals with developmental or acquired communication disabilities may respond to aided augmentative and alternative communication (AAC) systems. In this paper, we introduce basic terminology and explore some of the special challenges of conducting eye tracking research with populations with disabilities who might use AAC, including challenges of inferring attention from the presence of fixation and challenges related to calibration that may result from participant characteristics, behavioral idiosyncracies, and/or the number of calibration points. We also examine how the technology can be applied to ask well-structured experimental questions that have direct clinical relevance, with a focus on the unique contributions that eye tracking research can provide by (a) allowing evaluation of skills in individuals who are difficult to assess via traditional methods, and (b) facilitating access to information on underlying visual cognitive processes that is not accessible via traditional behavioral measures. C1 [Wilkinson, Krista M.] Penn State Univ, University Pk, PA 16802 USA. [Wilkinson, Krista M.; Mitchell, Teresa] Univ Massachusetts, EK Shriver Ctr, Sch Med, Waltham, MA USA. RP Wilkinson, KM (reprint author), Penn State Univ, 308 Ford Hall, University Pk, PA 16802 USA. EM kmw22@psu.edu FU NIH [P01 HD25995]; Hintz Family Endowed Chair in Children's Communicative Competence at the Pennsylvania State University; National Institute on Disability and Rehabilitation Research [H133E030018] FX Many people have contributed to the authors' ever-growing knowledge of eye tracking, including William Dube and Wilkie Wong. The eye tracking research activities of both authors have been supported by NIH P01 HD25995. Support for the first author has also been supplied by the Rehabilitation Engineering Research Center on Communication Enhancement, a virtual research center that is funded by the National Institute on Disability and Rehabilitation Research under Grant H133E030018 and from the Hintz Family Endowed Chair in Children's Communicative Competence at the Pennsylvania State University. 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M., 2004, NATURE REV NEUROSCIE, V5, P1, DOI DOI 10.1038/NM1411 NR 52 TC 5 Z9 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0743-4618 EI 1477-3848 J9 AUGMENT ALTERN COMM JI Augment. Altern. Commun. PD JUN PY 2014 VL 30 IS 2 BP 106 EP 119 DI 10.3109/07434618.2014.904435 PG 14 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA AI6XL UT WOS:000337020600002 PM 24758526 ER PT J AU Wilkinson, KM Light, J AF Wilkinson, Krista M. Light, Janice TI Preliminary Study of Gaze Toward Humans in Photographs by Individuals with Autism, Down Syndrome, or Other Intellectual Disabilities: Implications for Design of Visual Scene Displays SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Eye-tracking; Intellectual disability; Display design; Gaze patterns; AAC; Visual scene displays ID PERVASIVE DEVELOPMENTAL DISORDER; EYE TRACKING RESEARCH; SPECTRUM DISORDERS; WILLIAMS-SYNDROME; COMMUNICATION DEVELOPMENT; AAC TECHNOLOGIES; UNITED-STATES; HUMAN-FIGURES; CHILDREN; ATTENTION AB Visual scene displays (VSDs) are a form of augmentative and alternative communication display in which language concepts are embedded into an image of a naturalistic event. VSDs are based on the theory that language learning occurs through interactions with other people, and recommendations for VSD design have emphasized using images of these events that include humans. However, many VSDs also include other items that could potentially be distracting. We examined gaze fixation in 18 school-aged participants with and without severe intellectual/developmental disabilities (i.e., individuals with typical development, autism, Down syndrome and other intellectual disabilities) while they viewed photographs with human figures of various sizes and locations in the image, appearing alongside other interesting, and potentially distracting items. In all groups, the human figures attracted attention rapidly (within 1.5 seconds). The proportions of each participant's own fixation time spent on the human figures were similar across all groups, as were the proportions of total fixations made to the human figures. Although the findings are preliminary, this initial evidence supports the inclusion of humans in VSD images. C1 [Wilkinson, Krista M.; Light, Janice] Penn State Univ, University Pk, PA 16802 USA. 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M., 2004, AUGMENTATIVE ALTERNA, V20, P123, DOI 10.1080/07434610410001699717 Wilkinson KM, 2011, J SPEECH LANG HEAR R, V54, P1644, DOI 10.1044/1092-4388(2011/10-0098) Wilkinson KM, 2012, AUGMENT ALTERN COMM, V28, P137, DOI 10.3109/07434618.2012.704522 Wilkinson KM, 2014, AUGMENT ALTERN COMM, V30, P106, DOI 10.3109/07434618.2014.904435 Woodhouse J. M., 2005, SYNDROME NEWS UPDATE, V4, P87 NR 67 TC 4 Z9 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0743-4618 EI 1477-3848 J9 AUGMENT ALTERN COMM JI Augment. Altern. Commun. PD JUN PY 2014 VL 30 IS 2 BP 130 EP 146 DI 10.3109/07434618.2014.904434 PG 17 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA AI6XL UT WOS:000337020600004 PM 24773517 ER PT J AU Brady, NC Anderson, CJ Hahn, LJ Obermeier, SM Kapa, LL AF Brady, Nancy C. Anderson, Christa J. Hahn, Laura J. Obermeier, Sara M. Kapa, Leah L. TI Eye Tracking as a Measure of Receptive Vocabulary in Children with Autism Spectrum Disorders SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Speech comprehension; Receptive language; Autism spectrum disorders; Eye tracking ID COMMUNICATIVE DEVELOPMENT INVENTORY; YOUNG-CHILDREN; PRELINGUISTIC PREDICTORS; PREFERENTIAL LOOKING; EXPRESSIVE LANGUAGE; DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; WILLIAMS-SYNDROME; DOWNS-SYNDROME; COMPREHENSION AB This study examined the utility of eye tracking research technology to measure speech comprehension in 14 young boys with autism spectrum disorders (ASD) and 15 developmentally matched boys with typical development. Using eye tracking research technology, children were tested on individualized sets of known and unknown words, identified based on their performance on the Peabody Picture Vocabulary Test. Children in both groups spent a significantly longer amount of time looking at the target picture when previous testing indicated the word was known (known condition). Children with ASD spent similar amounts of time looking at the target and non-target pictures when previous testing indicated the word was unknown (unknown condition). However, children with typical development looked longer at the target pictures in the unknown condition as well, potentially suggesting emergent vocabulary knowledge. C1 [Brady, Nancy C.] Univ Kansas, Lawrence, KS 66045 USA. [Anderson, Christa J.; Hahn, Laura J.; Obermeier, Sara M.; Kapa, Leah L.] Univ Kansas, Life Span Inst, Lawrence, KS 66045 USA. RP Brady, NC (reprint author), Univ Kansas, 1000 Sunnyside Ave,Room 3008, Lawrence, KS 66045 USA. 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Koenigs, Michael TI Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition SO BRAIN LA English DT Article DE attention; emotion; prefrontal cortex; social cognition; lesion studies; eye tracking ID FRONTAL-LOBE DAMAGE; AMYGDALA DAMAGE; ORBITOFRONTAL CORTEX; BILATERAL DAMAGE; DECISION-MAKING; EXPRESSIONS; LESIONS; AUTISM; FACE; CONNECTIONS AB The ventromedial prefrontal cortex plays a crucial role in regulating emotion and social behavior, yet the precise mechanisms underlying this function remain unclear. Using eye-tracking in patients with brain lesions, Wolf et al. show that ventromedial prefrontal cortex is critical for directing visual attention during facial emotion recognition.The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. C1 [Wolf, Richard C.; Philippi, Carissa L.; Motzkin, Julian C.; Koenigs, Michael] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA. [Wolf, Richard C.; Motzkin, Julian C.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Motzkin, Julian C.] Univ Wisconsin, Med Scientist Training Program, Madison, WI 53705 USA. [Baskaya, Mustafa K.] Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. RP Koenigs, M (reprint author), Univ Wisconsin, Dept Psychiat, 6001 Res Pk Blvd, Madison, WI 53719 USA. EM mrkoenigs@wisc.edu FU NIMH [MH086787]; NIH [T32GM008692, T32GM007507, T32MH018931]; NSF [DGE-1256259] FX This work was funded by a grant from NIMH (MH086787), with additional support from NIH grants T32GM008692, T32GM007507, T32MH018931, as well as a fellowship from the NSF (DGE-1256259). 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Using a 3-week online program targeting holistic face processing, DeGutis et al. reveal perceptual improvements in 24 subjects. Those who reached more difficult levels of training showed the greatest improvements in holistic processing.Prosopagnosia has largely been regarded as an untreatable disorder. However, recent case studies using cognitive training have shown that it is possible to enhance face recognition abilities in individuals with developmental prosopagnosia. Our goal was to determine if this approach could be effective in a larger population of developmental prosopagnosics. We trained 24 developmental prosopagnosics using a 3-week online face-training program targeting holistic face processing. Twelve subjects with developmental prosopagnosia were assessed before and after training, and the other 12 were assessed before and after a waiting period, they then performed the training, and were then assessed again. The assessments included measures of front-view face discrimination, face discrimination with view-point changes, measures of holistic face processing, and a 5-day diary to quantify potential real-world improvements. Compared with the waiting period, developmental prosopagnosics showed moderate but significant overall training-related improvements on measures of front-view face discrimination. Those who reached the more difficult levels of training ('better' trainees) showed the strongest improvements in front-view face discrimination and showed significantly increased holistic face processing to the point of being similar to that of unimpaired control subjects. Despite challenges in characterizing developmental prosopagnosics' everyday face recognition and potential biases in self-report, results also showed modest but consistent self-reported diary improvements. In summary, we demonstrate that by using cognitive training that targets holistic processing, it is possible to enhance face perception across a group of developmental prosopagnosics and further suggest that those who improved the most on the training task received the greatest benefits. C1 [DeGutis, Joseph] Boston Div VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Jamaica Plain, MA USA. [DeGutis, Joseph; Cohan, Sarah; Nakayama, Ken] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. RP DeGutis, J (reprint author), Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA 02130 USA. EM degutis@wjh.harvard.edu FU National Institutes of Health [5R01EY013602-07] FX We would like to acknowledge funding support from the National Institutes of Health 5R01EY013602-07 awarded to KN and JD's Veterans Affairs Career Development Award. 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Prigge, Molly B. D. Nielsen, Jared A. Froehlich, Alyson L. Abildskov, Tracy J. Anderson, Jeffrey S. Fletcher, P. Thomas Zygmunt, Kristen M. Travers, Brittany G. Lange, Nicholas Alexander, Andrew L. Bigler, Erin D. Lainhart, Janet E. TI Longitudinal changes in cortical thickness in autism and typical development SO BRAIN LA English DT Article DE autism; brain development; developmental neuroimaging; human brain mapping; MRI ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; AGE 2 YEARS; HEAD CIRCUMFERENCE; BRAIN VOLUME; INTELLECTUAL ABILITY; SPECTRUM DISORDERS; SURFACE-AREA; MRI; CHILDREN AB The natural history of brain growth in autism spectrum disorders (ASD) remains unclear. Zielinski et al. examine longitudinal changes in cortical thickness in individuals with autism and typically-developing controls. Cortical development in ASD appears to undergo three phases, and developmental abnormalities are region-specific, age-dependent, and remain dynamic well into adulthood.The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood. C1 [Zielinski, Brandon A.; Prigge, Molly B. D.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Zielinski, Brandon A.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Zielinski, Brandon A.] PCMC, Salt Lake City, UT 84113 USA. [Prigge, Molly B. D.; Nielsen, Jared A.; Anderson, Jeffrey S.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Froehlich, Alyson L.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Abildskov, Tracy J.; Bigler, Erin D.] Brigham Young Univ, Neurosci Ctr, Provo, UT 84602 USA. [Anderson, Jeffrey S.] Univ Utah, Interdept Program Neurosci, Salt Lake City, UT USA. [Fletcher, P. Thomas; Zygmunt, Kristen M.] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA. [Fletcher, P. Thomas] Univ Utah, Sch Comp, Salt Lake City, UT USA. [Travers, Brittany G.; Alexander, Andrew L.; Lainhart, Janet E.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Lange, Nicholas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lange, Nicholas] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. [Lange, Nicholas] McLean Hosp, Neurostat Lab, Belmont, MA 02178 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Alexander, Andrew L.; Lainhart, Janet E.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Bigler, Erin D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. RP Zielinski, BA (reprint author), PCMC, 100 N Mario Capecchi Dr,3rd Floor Div Neurol, Salt Lake City, UT 84113 USA. EM brandon.zielinski@hsc.utah.edu FU National Institute Of Mental Health [RO1 MH080826, RO1 MH084795, RO1 MH097464, KO8 MH100609, KO8 MH092697]; Eunice Kennedy Shriver NICHD [T32 HD07489, P30 HD003352-45, CHRCDA K12HD001410]; Hartwell Foundation; Primary Children's Medical Center Foundation FX The project described was supported by Grant Numbers RO1 MH080826 (JEL, EDB, ALA, NL), RO1 MH084795 (JEL, PTF, NL), RO1 MH097464 (JEL, NL), KO8 MH100609 (BAZ), and KO8 MH092697 (JSA) from the National Institute Of Mental Health; Grant Numbers T32 HD07489 (BGT), P30 HD003352-45 (Waisman Center Core Grant), and CHRCDA K12HD001410 (BAZ) from the Eunice Kennedy Shriver NICHD; The Hartwell Foundation (BGT); and the Primary Children's Medical Center Foundation Early Career Development Award (BAZ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institute of Child Health & Development, or the National Institutes of Health. 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Corsello, Christina Kennedy, Daniel P. Adolphs, Ralph TI Agenesis of the corpus callosum and autism: a comprehensive comparison SO BRAIN LA English DT Article DE autism; corpus callosum; developmental neuropathology; connectivity; social cognition ID HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; SPECTRUM DISORDERS; ASPERGER-SYNDROME; SYSTEMATIZING QUOTIENT; SENTENCE COMPREHENSION; SOCIAL COGNITION; EMPATHY QUOTIENT; WHITE-MATTER; MR ANALYSIS AB Isolated congenital absence of the corpus callosum may result in significant social impairments despite intact general intelligence. Paul et al. report that approximately one-third of acallosal adults exhibit an autistic behaviour profile, while another third display social and communication impairments. Findings support a role for the corpus callosum in autism.The corpus callosum, with its similar to 200 million axons, remains enigmatic in its contribution to cognition and behaviour. Agenesis of the corpus callosum is a congenital condition in which the corpus callosum fails to develop; such individuals exhibit localized deficits in non-literal language comprehension, humour, theory of mind and social reasoning. These findings together with parent reports suggest that behavioural and cognitive impairments in subjects with callosal agenesis may overlap with the profile of autism spectrum disorders, particularly with respect to impairments in social interaction and communication. To provide a comprehensive test of this hypothesis, we directly compared a group of 26 adults with callosal agenesis to a group of 28 adults with a diagnosis of autism spectrum disorder but no neurological abnormality. All participants had full-scale intelligence quotient scores > 78 and groups were matched on age, handedness, and gender ratio. Using the Autism Diagnostic Observation Schedule together with current clinical presentation to assess autistic symptomatology, we found that 8/26 (about a third) of agenesis subjects presented with autism. However, more formal diagnosis additionally involving recollective parent-report measures regarding childhood behaviour showed that only 3/22 met complete formal criteria for an autism spectrum disorder (parent reports were unavailable for four subjects). We found no relationship between intelligence quotient and autism symptomatology in callosal agenesis, nor evidence that the presence of any residual corpus callosum differentiated those who exhibited current autism spectrum symptoms from those who did not. Relative to the autism spectrum comparison group, parent ratings of childhood behaviour indicated children with agenesis were less likely to meet diagnostic criteria for autism, even for those who met autism spectrum criteria as adults, and even though there was no group difference in parent report of current behaviours. The findings suggest two broad conclusions. First, they support the hypothesis that congenital disruption of the corpus callosum constitutes a major risk factor for developing autism. Second, they quantify specific features that distinguish autistic behaviour associated with callosal agenesis from autism more generally. Taken together, these two findings also leverage specific questions for future investigation: what are the distal causes (genetic and environmental) determining both callosal agenesis and its autistic features, and what are the proximal mechanisms by which absence of the callosum might generate autistic symptomatology?. C1 [Paul, Lynn K.; Kennedy, Daniel P.; Adolphs, Ralph] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. [Corsello, Christina] Rady Childrens Hosp, San Diego, CA USA. [Kennedy, Daniel P.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Adolphs, Ralph] CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Paul, LK (reprint author), CALTECH, Baxter MC 228-77,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM lkpaul@hss.caltech.edu FU National Institutes of Mental Health [R01MH080721, K99/R00MH094409]; Simons Foundation Autism Research Initiative; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; Brain and Behavior Research Foundation FX This work is supported in part by grants from the National Institutes of Mental Health (R01MH080721) and the Simons Foundation Autism Research Initiative to R.A., a National Alliance for Research on Schizophrenia and Depression Young Investigator Award presented to L.K.P, and a grant from the National Institutes of Mental Health (K99/R00MH094409) and a Brain and Behavior Research Foundation Young Investigator Award to D.P.K. 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Nur Kalay, Ersan Yildirim, Cem Dincer, Tuba Olmez, Akgun Toraman, Bayram Kocyigit, Ali Bulgu, Yunus Okur, Volkan Satiroglu-Tufan, Lale Akarsu, Nurten A. TI Novel splice-site and missense mutations in the ALDH1A3 gene underlying autosomal recessive anophthalmia/microphthalmia SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINOIC ACID; ALDEHYDE DEHYDROGENASE; STRA6 MUTATIONS; MICROPHTHALMIA; ANOPHTHALMIA; SPECTRUM; AUTISM; HYPOPLASIA; DYSPLASIA; COLOBOMA AB Aim This study aimed to identify the underlying genetic defect responsible for anophthalmia/microphthalmia. Methods In total, two Turkish families with a total of nine affected individuals were included in the study. Affymetrix 250 K single nucleotide polymorphism genotyping and homozygosity mapping were used to identify the localisation of the genetic defect in question. Coding region of the ALDH1A3 gene was screened via direct sequencing. cDNA samples were generated from primary fibroblast cell cultures for expression analysis. Reverse transcriptase PCR (RT-PCR) analysis was performed using direct sequencing of the obtained fragments. Results The causative genetic defect was mapped to chromosome 15q26.3. A homozygous G>A substitution (c. 666G>A) at the last nucleotide of exon 6 in the ALDH1A3 gene was identified in the first family. Further cDNA sequencing of ALDH1A3 showed that the c. 666G>A mutation caused skipping of exon 6, which predicted in-frame loss of 43 amino acids (p. Trp180_Glu222del). A novel missense c. 1398C>A mutation in exon 12 of ALDH1A3 that causes the substitution of a conserved asparagine by lysine at amino acid position 466 (p.Asn466Lys) was observed in the second family. No extraocular findings-except for nevus flammeus in one affected individual and a variant of Dandy-Walker malformation in another affected individual-were observed. Autistic-like behaviour and mental retardation were observed in three cases. Conclusions In conclusion, novel ALDH1A3 mutations identified in the present study confirm the pivotal role of ALDH1A3 in human eye development. Autistic features, previously reported as an associated finding, were considered to be the result of social deprivation and inadequate parenting during early infancy in the presented families. C1 [Semerci, C. Nur; Okur, Volkan; Satiroglu-Tufan, Lale] Pamukkale Univ, Sch Med, Dept Med Genet, TR-20020 Kinikli, Denizli, Turkey. [Kalay, Ersan; Dincer, Tuba; Toraman, Bayram] Karadeniz Tech Univ, Sch Med, Dept Med Biol, Trabzon, Turkey. [Yildirim, Cem] Pamukkale Univ, Sch Med, Dept Ophthalmol, TR-20020 Kinikli, Denizli, Turkey. [Olmez, Akgun] Denizli State Hosp, Minist Hlth, Dept Pediat Neurol, Denizli, Turkey. [Kocyigit, Ali] Pamukkale Univ, Sch Med, Dept Radiol, TR-20020 Kinikli, Denizli, Turkey. [Bulgu, Yunus] State Hosp, Dept Ophthalmol, Suhut Afyonkarahisar, Afyon, Turkey. [Akarsu, Nurten A.] Hacettepe Univ, Sch Med, Dept Med Genet, Gene Mapping Lab, Ankara, Turkey. RP Semerci, CN (reprint author), Pamukkale Univ, Sch Med, Dept Med Genet, TR-20020 Kinikli, Denizli, Turkey. EM nsemerci1@yahoo.com FU Pamukkale University Scientific Research Grants Fund [2012ARS001] FX This study was supported by the Pamukkale University Scientific Research Grants Fund, grant number 2012ARS001. 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A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy. C1 [Majewska, Maria Dorota; Bienkowski, Przemyslaw; Mierzejewski, Pawel] Inst Psychiat & Neurol, Dept Pharmacol & Physiol Nervous Syst, PL-02957 Warsaw, Poland. [Hill, Martin] Inst Endocrinol, Prague, Czech Republic. [Urbanowicz, Ewa; Rok-Bujko, Paulina; Namyslowska, Irena] Inst Psychiat & Neurol, Dept Child & Adolescent Psychiat, PL-02957 Warsaw, Poland. RP Majewska, MD (reprint author), Inst Psychiat & Neurol, Dept Pharmacol & Physiol Nervous Syst, Sobieskiego 9, PL-02957 Warsaw, Poland. EM mdmajewska@gmail.com FU European Commission [MEXC-CT 2006-042371]; Ministry of Science and Higher Education of Poland FX We are grateful to the psychologists, M. S. Agnieszka Lucjanek and M. S. Justyna Szczechowicz-Konciala for help in diagnosis of autistic children; to Dr. Michal Wroniszewski, Dr. Joanna Grochowska and Ms. Ursula Rusilowicz from the Synapsis Foundation, and Dr. Anna Szymanska from the Navicula Foundation for aid in recruitment of autistic patients. This study was a part of ASTER project funded by the European Commission grant (MEXC-CT 2006-042371) and by the supplementary grant from the Ministry of Science and Higher Education of Poland, both to Maria Dorota Majewska. 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Child Adolesc. Psych. PD JUN PY 2014 VL 23 IS 6 BP 485 EP 498 DI 10.1007/s00787-013-0472-0 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI7HX UT WOS:000337058200011 PM 24043498 ER PT J AU Gabriele, S Sacco, R Persico, AM AF Gabriele, Stefano Sacco, Roberto Persico, Antonio M. TI Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 5-HT; Autism; Biomarker; Endophenotype; Meta-analysis ID POOR PLASMA SEROTONIN; 1ST-DEGREE RELATIVES; PLATELET SEROTONIN; BRAIN-SEROTONIN; RETARDED-CHILDREN; INFANTILE-AUTISM; RECEPTOR-BINDING; 5-HT2A RECEPTOR; TRANSPORTER; ADULTS AB Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0 x 10(-12)], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7 x 10(-7)]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multimarker diagnostic panels for clinical use. (C) 2014 Elsevier B.V. and ECNP. All rights reserved. C1 [Gabriele, Stefano; Sacco, Roberto; Persico, Antonio M.] Univ Campus Biomed, Lab Mol Psychiat & Neurogenet, Unit Child & Adolescent NeuroPsychiat, I-00128 Rome, Italy. [Gabriele, Stefano; Sacco, Roberto; Persico, Antonio M.] IRCCS Fdn Santa Lucia, Dept Expt Neurosci, Rome, Italy. [Persico, Antonio M.] Mafalda Luce Ctr Pervas Dev Disorders, Milan, Italy. RP Persico, AM (reprint author), Univ Campus Biomed, Lab Mol Psychiat & Neurogenet, Unit Child & Adolescent NeuroPsychiat, Via Alvaro del Portillo 21, I-00128 Rome, Italy. EM a.persico@unicampus.it FU Italian Ministry for University, Scientific Research and Technology [2006058195, 2008BACT54_002]; Italian Ministry of Health [RFPS-2007-5-640174, RF-2011-02350537]; Fondazione Gaetano e Mafalda Luce (Milan, Italy); Autism Aid ONLUS (Naples, Italy); Autism Speaks (Princeton, NJ); Autism Research Institute (San Diego, CA); Innovative Medicines Initiative Joint Undertaking (EU-AIMS) [115300] FX This work was supported by the Italian Ministry for University, Scientific Research and Technology (PRIN n.2006058195 and n.2008BACT54_002), the Italian Ministry of Health (RFPS-2007-5-640174 and RF-2011-02350537), the Fondazione Gaetano e Mafalda Luce (Milan, Italy), Autism Aid ONLUS (Naples, Italy), Autism Speaks (Princeton, NJ), the Autism Research Institute (San Diego, CA), and the Innovative Medicines Initiative Joint Undertaking (EU-AIMS, n.115300). The authors declare that these funding sources had no role in study design, in the collection, analysis and interpretation of the data, in the writing of this report and in the decision to submit this paper for publication. 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Neuropsychopharmacol. PD JUN PY 2014 VL 24 IS 6 BP 919 EP 929 DI 10.1016/j.euroneuro.2014.02.004 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AI4YF UT WOS:000336871900010 PM 24613076 ER PT J AU Molenhuis, RT de Visser, L Bruining, H Kas, MJ AF Molenhuis, Remco T. de Visser, Leonie Bruining, Hilgo Kas, Martien J. TI Enhancing the value of psychiatric mouse models; differential expression of developmental behavioral and cognitive profiles in four inbred strains of mice SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Developmental trajectories; Mouse models; Cognitive flexibility; Repetitive behavior; BTBR ID T PLUS TF/J; AUTISM SPECTRUM DISORDER; REPETITIVE BEHAVIOR; ANIMAL-MODELS; CHILDREN; TRAJECTORIES; RELEVANT; ANXIETY; MOTOR; SCHIZOPHRENIA AB The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10-12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long-term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders. (C) 2014 Elsevier B.V. and ECNP. All rights reserved. C1 [Molenhuis, Remco T.; de Visser, Leonie; Bruining, Hilgo; Kas, Martien J.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands. [Bruining, Hilgo] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands. RP Kas, MJ (reprint author), Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, Univ Sweg 100, NL-3584 CG Utrecht, Netherlands. EM m.j.h.kas@umcutrecht.nl FU ZonMW VIDI - Netherlands Organization for Scientific Research (NWO) [91786327]; EU-AIMS; Innovative Medicines Initiative Joint [115300]; European Union [FP7/2007-2013]; EFPIA companies; Autism Speaks FX This research was supported by a ZonMW VIDI Grant (91786327) from The Netherlands Organization for Scientific Research (NWO) to Dr. Martien Kas and by EU-AIMS. The research of EU-AIMS receives support from the Innovative Medicines Initiative Joint Undertaking under Grant agreement no. 115300, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013), from the EFPIA companies in kind contribution and from Autism Speaks. 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Neuropsychopharmacol. PD JUN PY 2014 VL 24 IS 6 BP 945 EP 954 DI 10.1016/j.euroneuro.2014.01.013 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AI4YF UT WOS:000336871900013 PM 24491952 ER PT J AU Hodgson, NW Waly, MI Al-Farsi, YM Al-Sharbati, MM Al-Farsi, O Ali, A Ouhtit, A Zang, TZ Zhou, ZS Deth, RC AF Hodgson, Nathaniel W. Waly, Mostafa I. Al-Farsi, Yahya M. Al-Sharbati, Marwan M. Al-Farsi, Omar Ali, Amanat Ouhtit, Allal Zang, Tianzhu Zhou, Zhaohui Sunny Deth, Richard C. TI Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE Cobalamin; epigenetic; folic acid; homocysteine thiolactone; methionine synthase; neurodevelopment ID ONE-CARBON METABOLISM; OXIDATIVE STRESS; SPECTRUM DISORDERS; DNA METHYLATION; GASTROINTESTINAL SYMPTOMS; HOMOCYSTEINE THIOLACTONE; PERIPHERAL-BLOOD; NERVOUS-SYSTEM; HEAVY-METALS; CHILDREN AB Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B-12. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury. C1 [Hodgson, Nathaniel W.; Deth, Richard C.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Waly, Mostafa I.; Ali, Amanat] Sultan Qaboos Univ, Dept Food Sci & Nutr, Muscat 123, Oman. [Waly, Mostafa I.] Univ Alexandria, High Inst Publ Hlth, Dept Nutr, Alexandria 165, Egypt. [Al-Farsi, Yahya M.; Al-Farsi, Omar] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Family Med & Publ Hlth, Muscat 123, Oman. [Al-Farsi, Yahya M.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Al-Sharbati, Marwan M.] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Behav Med, Muscat 123, Oman. [Ouhtit, Allal] Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Genet, Muscat 123, Oman. [Zang, Tianzhu; Zhou, Zhaohui Sunny] Northeastern Univ, Coll Sci, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. RP Deth, RC (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. EM r.deth@neu.edu FU Internal Grant Fund [IG/AGR/FOOD/10/01]; Strategic Research Fund [SR/MED/FMCO/11/01]; College of Medicine and Health Sciences; Sultan Qaboos University; NIH NIGMS [1R01GM101396]; American Heart Association [09PRE2300071]; Autism Research Institute; College of Agricultural and Marine Sciences FX This study was supported by the Internal Grant Fund (IG/AGR/FOOD/10/01), College of Agricultural and Marine Sciences, Sultan Qaboos University (to MIW), the Strategic Research Fund offered by His Majesty Sultan of Oman (SR/MED/FMCO/11/01), College of Medicine and Health Sciences, Sultan Qaboos University (to YMA), and grants from the NIH NIGMS (1R01GM101396 to ZSZ), American Heart Association (09PRE2300071 to T.Z.) and the Autism Research Institute (to RCD). 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Biol. Med. PD JUN PY 2014 VL 239 IS 6 BP 697 EP 706 DI 10.1177/1535370214527900 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI6GU UT WOS:000336970900006 PM 24676906 ER PT J AU Goh, S Dong, ZC Zhang, YD DiMauro, S Peterson, BS AF Goh, Suzanne Dong, Zhengchao Zhang, Yudong DiMauro, Salvatore Peterson, Bradley S. TI Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder Evidence From Brain Imaging SO JAMA PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; CHILDREN; NEURODEGENERATION; INDIVIDUALS; INTERVIEW; SCHEDULE; HISTORY; DISEASE; VERSION AB IMPORTANCE Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD. OBJECTIVES To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability. DESIGN, SETTING, AND PARTICIPANTS Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with ASD and 96 age-and sex-matched, typically developing controls. MAIN OUTCOMES AND MEASURES Lactate doublets (present or absent) on brain magnetic resonance spectroscopic imaging. RESULTS Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than controls (1%) (P = .001). In the ASD group, the presence of lactate doublets correlated significantly with age (P = .004) and was detected more often in adults (20%) than in children (6%), though it did not correlate with sex, ASD subtype, intellectual ability, or the Autism Diagnostic Observation Schedule total score or subscores. In those with ASD, lactate was detected most frequently within the cingulate gyrus but it was also present in the subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri. CONCLUSIONS AND RELEVANCE In vivo brain findings provide evidence for a possible neurobiological subtype of mitochondrial dysfunction in ASD. C1 [Goh, Suzanne; Dong, Zhengchao; Zhang, Yudong; Peterson, Bradley S.] Columbia Univ Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Dong, Zhengchao; Zhang, Yudong] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [DiMauro, Salvatore] Columbia Univ Med Ctr, Dept Neurol, New York, NY 10032 USA. RP Peterson, BS (reprint author), Columbia Univ Med Ctr, Dept Psychiat, 1051 Riverside Dr,Unit 74, New York, NY 10032 USA. EM bp2014@columbia.edu RI Zhang, Yudong/I-7633-2013 OI Zhang, Yudong/0000-0002-4870-1493 FU National Institutes of Health [NIMH R01 MH089582]; Tom Klingenstein and Nancy Perlman Family Fund; Suzanne Crosby Murphy Endowment at Columbia University FX This study was made possible by funding from the National Institutes of Health (grant NIMH R01 MH089582), the Tom Klingenstein and Nancy Perlman Family Fund, and the Suzanne Crosby Murphy Endowment at Columbia University. 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Kassel, Rachel Khanna, Geetika Liang, Shannon Ngwube, Alexander Baszis, Kevin W. Hunstad, David A. White, Andrew J. TI Scurvy Revealed by Difficulty Walking Three Cases in Young Children SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE scurvy; osteomyelitis; oral aversion ID CHILD AB Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. 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This article provides a critical review of the key aspects of the transition process and identifies recommendations for policy and practice. The review highlights the literature and explores recommendations across the manifold elements of this transition, including social and psychological development, high school curriculum, work, and college. Five policy recommendations are outlined in the areas of school curriculum, employment development, postsecondary education, inclusion with nondisabled peers, and systematic instruction. Finally, the authors offer recommendations for further research in the areas of social interaction, increased academic and vocational rigor, employment, technology, independence, and postsecondary education. C1 [Wehman, Paul; Schall, Carol; Carr, Staci; Targett, Pam; West, Michael; Cifu, Gabriella] Virginia Commonwealth Univ, Richmond, VA 23284 USA. 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PD JUN PY 2014 VL 25 IS 1 SI SI BP 30 EP 40 DI 10.1177/1044207313518071 PG 11 WC Rehabilitation SC Rehabilitation GA AI3VA UT WOS:000336791900004 ER PT J AU Chevallier, C Parish-Morris, J Tonge, N Le, L Miller, J Schultz, RT AF Chevallier, Coralie Parish-Morris, Julia Tonge, Natasha Le, Lori Miller, Judith Schultz, Robert T. TI Susceptibility to the Audience Effect Explains Performance Gap Between Children With and Without Autism in a Theory of Mind Task SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article DE audience effect; autism spectrum disorders; motivation; reputation; theory of mind ID SOCIAL FACILITATION; SPECTRUM DISORDERS; INTELLIGENCE; LANGUAGE; OTHERS; GAME; FACE; COMMUNICATION; IMPAIRMENTS; COMPETENCE AB Diminished social motivation constitutes one of the core impairments of autism spectrum disorder (ASD) and is thought to have a strong impact on the way individuals with autism respond to the presence of others. In this study, we hypothesized that experimental contexts involving direct interaction with an experimenter might elicit different reactions in children with ASD and thus act as a potential confound in the interpretation of group differences during social cognitive tests. Following classic work in social psychology on the audience effect-wherein individuals act differently when they are being watched in a more or less conscious attempt to enhance their reputation in the eyes of others-we reasoned that social contexts are indeed likely to produce an increase in performance in typically developing (TD) individuals but that children with ASD would be less susceptible to such audience effects. More specifically, we were interested in testing the idea that susceptibility to the audience effect might explain part of the performance gap between children with autism (ASDs) and children without autism in theory of mind (ToM) tasks, which are typically administered by a human experimenter. We tested this hypothesis by comparing performance on a ToM task administered in a social versus a nonsocial setting. We found that ASDs and controls performed similarly when the task was administered using a nonsocial medium. However, control participants outperformed ASDs when an experimenter administered the task. Thus, TD controls demonstrated a relative improvement in performance when in the presence of an experimenter that children with ASD did not. The implications of this diminished audience effect in ASD are discussed. C1 [Chevallier, Coralie; Parish-Morris, Julia; Tonge, Natasha; Le, Lori; Miller, Judith; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Parish-Morris, Julia; Schultz, Robert T.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Parish-Morris, Julia; Schultz, Robert T.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Chevallier, C (reprint author), Ctr Autism Res, Suite 860,3535 Market St, Philadelphia, PA 19104 USA. 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PD JUN PY 2014 VL 143 IS 3 BP 972 EP 979 DI 10.1037/a0035483 PG 8 WC Psychology, Experimental SC Psychology GA AI3TK UT WOS:000336786300004 PM 24392710 ER PT J AU Ehashi, T Suzuki, N Ando, S Sumida, K Saito, K AF Ehashi, Tomo Suzuki, Noriyuki Ando, Satoshi Sumida, Kayo Saito, Koichi TI Effects of valproic acid on gene expression during human embryonic stem cell differentiation into neurons SO JOURNAL OF TOXICOLOGICAL SCIENCES LA English DT Article DE Embryotoxicity; Embryonic stem cell test; Human embryonic stem cells; Neural differentiation; Valproic acid; Gene expression ID IN-UTERO EXPOSURE; DEVELOPMENTAL TOXICITY; ES CELLS; DOPAMINERGIC-NEURONS; ANTIEPILEPTIC DRUGS; MOLECULAR MARKERS; BIRTH-DEFECTS; AUTISM; VITRO; PROLIFERATION AB The widely used antiepileptic drug valproic acid (VPA) is known to exhibit teratogenicity in the form of a failure of the neural tube in humans. Embryonic stem cells (ESCs) are reported to be a promising cell source for evaluating chemical teratogenicity, because they are capable of reproducing embryonic developmental model and enable reduction in the number of experimental animals used. We previously investigated 22 genes for which expressions are altered by teratogens, specifically focusing on neural differentiation of mouse ESCs. In the present study, expressions of the investigated genes were evaluated by quantitative real-time PCR and compared during differentiation of human ESCs into neurons with or without VPA. Under the conditions, almost all gene expressions significantly changed in VPA-containing culture. Specifically, in neural development-related genes such as DCX, ARX, MAP2, and NNAT, more than 2-fold expression was observed. 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Here we provide a protocol for breakpoint resolution with sequence-level precision. Massively parallel sequencing is performed on libraries generated from haplotype-resolved chromosomes, genomic DNA or molecular inversion probe (MIP)-captured breakpoint-informative regions harboring paralog-distinguishing variants. Quantification of sequencing depth over informative sites enables breakpoint localization, typically within several kilobases to tens of kilobases. Depending on the approach used, the sequencing platform, and the accuracy and completeness of the reference genome sequence, this protocol takes from a few days to several months to complete. Once established for a specific genomic disorder, it is possible to process thousands of DNA samples within as little as 3-4 weeks. C1 [Nuttle, Xander; Itsara, Andy; Shendure, Jay; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Sch Med, Seattle, WA 98195 USA. [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Sch Med, Seattle, WA 98195 USA. RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, Sch Med, Seattle, WA 98195 USA. EM eee@gs.washington.edu FU National Science Foundation Graduate Research Fellowship [DGE-1256082]; US National Institutes of Health [HG004120, HG002385] FX We thank J. Huddleston for assistance in testing analysis software and preparing it for public access; P. Sudmant for analyzing the number of SUNKs in windows across the reference genome; and T. Brown for assistance with manuscript preparation. X. N. is supported by a National Science Foundation Graduate Research Fellowship under grant no. DGE- 1256082. This work was supported by US National Institutes of Health grants HG004120 and HG002385 to E. E. E. E. E. E. is an investigator of the Howard Hughes Medical Institute. 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However, genetic influences on habituation in ASD have not been examined. We hypothesized that serotonin transporter-linked promoter region (5-HTTLPR) genotype affects change in amygdala response to repeated sad faces differently in individuals with ASD vs healthy controls. Forty-four youth with ASD and 65 controls aged 8-19 years were genotyped and underwent an event-related functional magnetic resonance imaging scan where they identified the gender of emotional faces presented for 250 ms. The first half of the run was compared with the second half to assess habituation. 5-HTTLPR genotype influences amygdala habituation to sad faces differently for individuals with ASD vs controls. The genotype-by-diagnosis-by-run half interaction was driven by individuals with ASD and low expressing genotypes (S/S, S/L-G and L-G/L-G), who trended toward sensitization (increase in amygdala activation) and whose habituation scores significantly differed from individuals with ASD and higher expressing genotypes (L-A/L-A, S/L-A and L-A/L-G) as well as controls with low expressing genotypes. Our results show that amygdala response to social stimuli in ASD, which may contribute to social symptoms, is genetically influenced. C1 [Wiggins, Jillian Lee; Swartz, Johnna R.; Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Martin, Donna M.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Martin, Donna M.; Monk, Christopher S.] Univ Michigan, Neurosci Program, Ann Arbor, MI 48109 USA. [Martin, Donna M.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Lord, Catherine] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Monk, Christopher S.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Monk, Christopher S.] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. RP Wiggins, JL (reprint author), 530 Church St, Ann Arbor, MI 48109 USA. EM leejilli@umich.edu RI Monk, Christopher/J-1805-2014 FU Autism Speaks Predoctoral Fellowship [4773, 2573]; Michigan Institute for Clinical Health Research Predoctoral Fellowship [UL1RR024986]; National Institutes of Health [R01NS54784, R01DC009410, U19HD35482, MH066496] FX We thank our research assistants and are grateful to the families for participating. This work was supported by an Autism Speaks Predoctoral Fellowship (4773 to J.L.W.) and grant (2573 to C.S.M.); Michigan Institute for Clinical Health Research Predoctoral Fellowship (UL1RR024986 to J.L.W.) and National Institutes of Health grants (R01NS54784 and R01DC009410 to D.M.M. and U19HD35482 and MH066496 to C.L.). C.L. receives royalties from the publisher of diagnostic instruments used on participants. All profits are given to charity. Other authors declare no conflict of interest. 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Cogn. Affect. Neurosci. PD JUN PY 2014 VL 9 IS 6 BP 832 EP 838 DI 10.1093/scan/nst039 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AI7MU UT WOS:000337076600013 PM 23526151 ER PT J AU Li, XL Qu, FQ Xie, WJ Wang, FL Liu, HM Song, SH Chen, TT Zhang, Y Zhu, S Wang, Y Guo, CX Tang, TS AF Li, Xiaoling Qu, Fengqin Xie, Wenjuan Wang, Fengli Liu, Hongmei Song, Shuhui Chen, Tingting Zhang, Yang Zhu, Shu Wang, Yun Guo, Caixia Tang, Tie-Shan TI Transcriptomic Analyses of Neurotoxic Effects in Mouse Brain After Intermittent Neonatal Administration of Thimerosal SO TOXICOLOGICAL SCIENCES LA English DT Article DE thimerosal; transcriptomic analyses; anterior pituitary; hormone; neurotoxicity; autistic disorder ID AUTISM SPECTRUM DISORDERS; LONG-TERM POTENTIATION; PERVASIVE DEVELOPMENTAL DISORDERS; NEURODEVELOPMENTAL DISORDERS; CONTAINING VACCINES; PREFRONTAL CORTEX; CHILDHOOD VACCINES; UNITED-STATES; MERCURY; CHILDREN AB Thimerosal is a vaccine antimicrobial preservative which has long been suspected an iatrogenic factor possibly contributing to neurodevelopmental disorders including autism. The association between infant vaccine thimerosal exposure and autism remains an open question. Although thimerosal has been removed from mandatory childhood vaccines in the United States, thimerosal-preserved vaccines are still widely used outside of the United States especially in developing countries. Notably, thimerosal-containing vaccines are being given to the newborns within the first 12-24 h after birth in some countries. To examine the possible neurotoxic effects of early neonatal exposure to a higher level of thimerosal, FVB mice were subcutaneously injected with thimerosal-mercury at a dose which is 20x higher than that used for regular Chinese infant immunization during the first 4 months of life. Thimerosal-treated mice exhibited neural development delay, social interaction deficiency, and inclination of depression. Apparent neuropathological changes were also observed in adult mice neonatally treated with thimerosal. High-throughput RNA sequencing of autistic-behaved mice brains revealed the alternation of a number of canonical pathways involving neuronal development, neuronal synaptic function, and the dysregulation of endocrine system. Intriguingly, the elevation of anterior pituitary secreting hormones occurred exclusively in male but not in female thimerosal-treated mice, demonstrating for the first time the gender bias of thimerosal-mercury toxicity with regard to endocrine system. Our results indicate that higher dose of neonatal thimerosal-mercury (20x higher than that used in human) is capable of inducing long-lasting substantial dysregulation of neurodevelopment, synaptic function, and endocrine system, which could be the causal involvements of autistic-like behavior in mice. C1 [Li, Xiaoling; Qu, Fengqin; Xie, Wenjuan; Wang, Fengli; Liu, Hongmei; Zhang, Yang; Zhu, Shu; Wang, Yun; Tang, Tie-Shan] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China. [Song, Shuhui; Chen, Tingting; Guo, Caixia] Chinese Acad Sci, Beijing Inst Genom, Ctr Genome Variat & Precis Biomed, Beijing 100029, Peoples R China. RP Tang, TS (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, 1 Beichen West Rd, Beijing 100101, Peoples R China. EM tangtsh@ioz.ac.cn FU National Basic Research Program of China [2011CB965003, 2012CB944702, 2011CB944302]; National Natural Science Foundation of China [81371415, 81300982, 31170730]; CAS/SAFEA; CAS FX National Basic Research Program of China (2011CB965003, 2012CB944702, 2011CB944302); National Natural Science Foundation of China (81371415, 81300982, 31170730); CAS/SAFEA International Partnership Program for Creative Research Teams; One-Hundred-Talent Program of CAS (to C.G.). 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Sci. PD JUN PY 2014 VL 139 IS 2 BP 452 EP 465 DI 10.1093/toxsci/kfu049 PG 14 WC Toxicology SC Toxicology GA AI7MO UT WOS:000337075900016 PM 24675092 ER PT J AU Garg, N Silverberg, JI AF Garg, Nitin Silverberg, Jonathan I. TI Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; INCREASED RISK; DEFICIT/HYPERACTIVITY DISORDER; UNINTENTIONAL INJURY; ATOPIC-DERMATITIS; CHILDREN; ASTHMA; SLEEP; ADOLESCENTS; BEHAVIOR AB Background: Children with allergic disease have multiple risk factors for accidental injuries. Objective: To determine the prevalence of injuries requiring medical treatment in US children with allergic disease. Methods: The authors analyzed data from the 2007 to 2008 National Survey of Children's Health, including a nationally representative sample of 27,556 children 0 to 5 years old. Results: The prevalence (95% confidence interval [CI]) of at least 1 allergic disease was 29.4% (28.0-30.8); 6.6% (5.8-7.4) were diagnosed with asthma, 15.0% (14.0-16.0) with eczema, 11.6% (10.6-12.6) with hay fever, and 6.1% (5.4-6.9) with food allergy. Children with allergic disorders had higher odds of at least 1 comorbid psychiatric and behavioral disorder (PBD; survey logistic regression; odds ratio 2.93, 95% CI 2.13 -4.03), including attention-deficit/hyperactivity disorder (4.75, 2.89-7.80), depression (6.03, 1.29-28.27), anxiety (5.54, 2.70-11.37), conduct/oppositional defiant disorder (2.97, 1.88-4.70), and learning delay (2.49, 1.70-3.66), but not autism/ Asperger disorder (1.89, 0.98-3.64). The prevalence of injury in the past year requiring medical attention was 10.5% (95% CI 9.5-11.4). The association between allergic disease and injury requiring medical attention was mediated in part by a PBD (Sobel test 0.0021, 95% CI 0.0014-0.0029, P < .0001; bootstrapping approach, indirect effects, odds ratio 1.005, 95% CI 1.003-1.007; Baron-Kenny beta(yx, m) 0.04, P < .0001, R-2 = 0.002). However, children with at least 1 allergic disorder (1.74, 1.23-2.46), including eczema (1.59, 1.01-2.50), asthma (1.91, 1.10-3.31), hay fever (2.05, 1.24-3.39), and food allergies (2.00, 1.10-3.67), had higher odds of sustaining injuries even after controlling for comorbid PBDs and medical disorders. Conclusion: The results suggest that the association between allergic disease and injury is multifactorial, including being secondary to PBD. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Garg, Nitin; Silverberg, Jonathan I.] Northwestern Univ, Dept Dermatol, Chicago, IL 60611 USA. 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Allergy Asthma Immunol. PD JUN PY 2014 VL 112 IS 6 BP 525 EP 532 DI 10.1016/j.anai.2014.03.006 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA AH9XJ UT WOS:000336498400009 PM 24713577 ER PT J AU von dem Hagen, EAH Stoyanova, RS Rowe, JB Baron-Cohen, S Calder, AJ AF von dem Hagen, Elisabeth A. H. Stoyanova, Raliza S. Rowe, James B. Baron-Cohen, Simon Calder, Andrew J. TI Direct Gaze Elicits Atypical Activation of the Theory-of-Mind Network in Autism Spectrum Conditions SO CEREBRAL CORTEX LA English DT Article DE autism; connectivity; eye gaze; theory-of-mind ID EYE-GAZE; BRAIN MECHANISMS; SOCIAL-INTERACTION; AVERTED GAZE; NEURAL BASIS; HEAD MOTION; CHILDREN; INDIVIDUALS; EMOTION; OTHERS AB Eye contact plays a key role in social interaction and is frequently reported to be atypical in individuals with autism spectrum conditions (ASCs). Despite the importance of direct gaze, previous functional magnetic resonance imaging in ASC has generally focused on paradigms using averted gaze. The current study sought to determine the neural processing of faces displaying direct and averted gaze in 18 males with ASC and 23 matched controls. Controls showed an increased response to direct gaze in brain areas implicated in theory-of-mind and gaze perception, including medial prefrontal cortex, temporoparietal junction, posterior superior temporal sulcus region, and amygdala. In contrast, the same regions showed an increased response to averted gaze in individuals with an ASC. This difference was confirmed by a significant gaze direction x group interaction. Relative to controls, participants with ASC also showed reduced functional connectivity between these regions. We suggest that, in the typical brain, perceiving another person gazing directly at you triggers spontaneous attributions of mental states (e.g. he is "interested" in me), and that such mental state attributions to direct gaze may be reduced or absent in the autistic brain. C1 [von dem Hagen, Elisabeth A. H.; Stoyanova, Raliza S.; Rowe, James B.; Calder, Andrew J.] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England. [Rowe, James B.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. RP von dem Hagen, EAH (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England. EM elisabeth.vondemhagen@mrc-cbu.cam.ac.uk FU UK Medical Research Council [MC_US_A060_5PQ50]; Wellcome Trust [088324]; UK Medical Research Council FX This work was funded by the UK Medical Research Council (MC_US_A060_5PQ50 to A.J.C. and a program grant to S. B. C.). J.B.R. is supported by the Wellcome Trust (088324). Funding to pay the Open Access publication charges for this article was provided by the UK Medical Research Council. 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Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors. We have performed targeted high-throughput sequencing of 220 genes, including MAOA, in patients with undiagnosed ID. We identified ac. 797_798delinsTT (p.C266F) missense mutation in MAOA in a boy with autism spectrum disorder, attention deficit and autoaggressive behavior. Two maternal uncles carry the mutation and have severe ID, with a history of maltreatment in early childhood. This novel missense mutation decreases MAOA enzymatic activity, leading to abnormal levels of urinary monoamines. The identification of this new point mutation confirms, for the first time since 1993, the monogenic implication of the MAOA gene in ID of various degrees, autism and behavioral disturbances. The variable expressivity of the mutation observed in male patients of this family may involve gene-environment interactions, and the identification of a perturbation in monoamine metabolism should be taken into account when prescribing psychoactive drugs in such patients. C1 [Piton, Amelie; Redin, Claire; Muller, Jean; Mandel, Jean-Louis] Univ Strasbourg, CNRS, UMR 7104, IGBMC,INSERM,U964, Illkirch Graffenstaden, France. [Piton, Amelie; Redin, Claire; Mandel, Jean-Louis] Coll France, Chaire Genet Humaine, F-75231 Paris, France. [Poquet, Helene; Masurel, Alice; Thevenon, Julien; Chancenotte, Sophie; Huet, Frederic; Thauvin-Robinet, Christel; Faivre, Laurence] Hop Enfants, Ctr Genet, Dijon, France. [Poquet, Helene; Masurel, Alice; Thevenon, Julien; Chancenotte, Sophie; Huet, Frederic; Thauvin-Robinet, Christel; Faivre, Laurence] Hop Enfants, Ctr Reference Anomalies Dev & Syndromes Malformat, Dijon, France. [Poquet, Helene; Pinoit, Jean-Michel] Hop Enfants, Serv Pedopsychiat, Dijon, France. [Lauer, Julia; Muller, Jean; Herenger, Yvan; Jaeger, Anne-Sophie; Gerard, Benedicte; Mandel, Jean-Louis] Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France. [Thevenon, Julien; Thauvin-Robinet, Christel; Faivre, Laurence] Univ Bourgogne, Fac Med, EA GAD 4271, Dijon, France. [Chancenotte, Sophie; Bonnet, Marlene] Hop Enfants, Ctr Referent Troubles Langage & Apprentissages, Dijon, France. [Le Gras, Stephanie; Jost, Bernard] IGBMC, Illkirch Graffenstaden, France. [Peoc'h, Katell; Launay, Jean-Marie] Grp Hosp Univ St Louis Lariboisiere Fernand Widal, AP HP, Serv Biochim & Biol Mol, Paris, France. RP Piton, A (reprint author), Univ Strasbourg, CNRS, UMR 7104, Dept Translat Med & Neurogenet,IGBMC,INSERM,U964, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France. EM piton@igbmc.fr; jlmandel@igbmc.fr FU Agence de BioMedecine; Fondation Jerome Lejeune; Fondation pour la Recherche Medicale; Fondation APLM; 7th European Union Framework [241995] FX We thank Nadege Calmels, Nadine Kempf, Valerie Biancalana and all the other members of the Genetic Diagnostic Laboratory of Nouvel Hopital Civil (Strasbourg) for their help with patient DNA samples selection and preparation. We thank Serge Vicaire and Muriel Phillips for their help and technical assistance with HTS. We would also like to thank Veronique Geoffroy and Cecile Pizot for the development of VaRank. We are very grateful to Pr Han Brunner for providing us DNA for one member of the initial Brunner-syndrome family. This work was supported by Agence de BioMedecine, Fondation Jerome Lejeune, Fondation pour la Recherche Medicale and Fondation APLM. This project also benefitiated from 7th European Union Framework (grant no. 241995; GENCODYS). 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One of the critical determinants of a child's behavioral outcome with autism and cognitive dysfunction is the age of onset of seizures. In order to examine whether seizures during postnatal days 7-11 result in learning and memory deficits and behavioral features of autism we administered the inhalant flurothyl to induce seizures in C57BL/6J mice. Mice received three seizures per day for five days starting on postnatal day 7. Parallel control groups consisted of similarly handled animals that were not exposed to flurothyl and naive mice. Subjects were then processed through a battery of behavioral tests in adulthood: elevated-plus maze, nose-poke assay, marble burying, social partition, social chamber, fear conditioning, and Morris water maze. Mice with early-life seizures had learning and memory deficits in the training portion of the Morris water maze (p < 0.05) and probe trial (p < 0.01). Mice with seizures showed no differences in marble burying, the nose-poke assay, or elevated plus-maze testing compared to controls. However, they showed a significant difference in the social chamber and social partition tests. Mice with seizures during postnatal days 7-11 showed a significant decrease in social interaction in the social chamber test and had a significant impairment in social behavior in the social partition test. Together, these results indicate that early life seizures result in deficits in hippocampal-dependent memory tasks and produce long-term disruptions in social behavior. (C) 2014 Elsevier Inc All rights reserved. C1 [Lugo, Joaquin N.] Baylor Univ, Dept Psychol & Neurosci, Waco, TX 76798 USA. [Lugo, Joaquin N.; Swann, John W.; Anderson, Anne E.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Cain Fdn Labs, Houston, TX 77030 USA. [Lugo, Joaquin N.; Swann, John W.; Anderson, Anne E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Swann, John W.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Anderson, Anne E.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Lugo, JN (reprint author), Baylor Univ, Dept Psychol & Neurosci, One Bear Pl 97334, Waco, TX 76706 USA. EM joaquin_lugo@baylor.edu FU Epilepsy Foundation [221523]; NIH from the Eunice Kennedy Shriver Institute of Child Health and Human Development [NS056664, P30HD 024064]; NIH NINDS [NS049427, NS039943, NS018309] FX This research was funded by the Epilepsy Foundation (221523) and NIH NS056664 Postdoctoral Fellowships to JNL, NIH NINDS grants NS049427 and NS039943 to AEA, and NIH NINDS grant NS018309 to JWS. The work was completed at the Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (IDDRC) Mouse Neurobehavior Core, which receives funding from the NIH P30HD 024064 from the Eunice Kennedy Shriver Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the NIH. 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PD JUN PY 2014 VL 256 BP 74 EP 80 DI 10.1016/j.expneurol.2014.03.014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AI1VZ UT WOS:000336644600010 PM 24685665 ER PT J AU Kasari, C Kaiser, A Goods, K Nietfeld, J Mathy, P Landa, R Murphy, S Almirall, D AF Kasari, Connie Kaiser, Ann Goods, Kelly Nietfeld, Jennifer Mathy, Pamela Landa, Rebecca Murphy, Susan Almirall, Daniel TI Communication Interventions for Minimally Verbal Children With Autism: A Sequential Multiple Assignment Randomized Trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism spectrum disorders; minimally verbal; school-aged; communication intervention; SMART design ID ADAPTIVE TREATMENT STRATEGY; SPECTRUM DISORDERS; FOLLOW-UP; JOINT ATTENTION; PRESCHOOLERS; PLAY AB Objective: This study tested the effect of beginning treatment with a speech-generating device (SGD) in the context of a blended, adaptive treatment design for improving spontaneous, communicative utterances in school-aged, minimally verbal children with autism. Method: A total of 61 minimally verbal children with autism, aged 5 to 8 years, were randomized to a blended developmental/behavioral intervention (JASP+EMT) with or without the augmentation of a SGD for 6 months with a 3-month follow-up. The intervention consisted of 2 stages. In stage 1, all children received 2 sessions per week for 3 months. Stage 2 intervention was adapted (by increased sessions or adding the SGD) based on the child's early response. The primary outcome was the total number of spontaneous communicative utterances; secondary measures were the total number of novel words and total comments from a natural language sample. Results: Primary aim results found improvements in spontaneous communicative utterances, novel words, and comments that all favored the blended behavioral intervention that began by including an SGD (JASP+EMT+SGD) as opposed to spoken words alone (JASP+EMT). Secondary aim results suggest that the adaptive intervention beginning with JASP+EMT+SGD and intensifying JASP+EMT+SGD for children who were slow responders led to better posttreatment outcomes. Conclusion: Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel, blended intervention that focuses on joint engagement and play skills and incorporates an SGD. Future studies should further explore the tailoring design used in this study to better understand children's response to treatment. Clinical trial registration information Developmental and Augmented Intervention for Facilitating Expressive Language (CCNIA); http://clinicaltrials.gov/; NCT01013545. C1 [Kasari, Connie] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Kasari, Connie; Nietfeld, Jennifer] Vanderbilt Univ, Nashville, TN USA. [Goods, Kelly] First Five Los Angeles, Los Angeles, CA USA. [Mathy, Pamela] Univ Utah, Speech Language & Hearing Clin, Salt Lake City, UT 84112 USA. [Landa, Rebecca] Kennedy Krieger Inst, Baltimore, MD USA. [Murphy, Susan; Almirall, Daniel] Univ Michigan, Ann Arbor, MI 48109 USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, Semel Inst 68 268, Los Angeles, CA 90024 USA. EM kasari@gseis.ucla.edu FU National Institute of Child Health and Human Development (NICHD) [R01HD073975-02, R01HD073975-03]; National Institute of Mental Health (NIMH) [R03MH097954-02, RC4MH092722-01]; National Institute on Drug Abuse [NIDA] [P50DA10075] FX This study was funded by Autism Speaks #5666, Characterizing Cognition in Nonverbal Individuals with Autism, oh initiative begun by Ms. Portia Iverson and Cure Autism Now. Grant support was also provided by the National Institute of Child Health and Human Development (NICHD) R01HD073975-02 (C.K., A.K., S.M., D.A.), and R01HD073975-03 (C.K., R.L.), R03MH097954-02 (D.A), and RC4MH092722-01 (D.A) from the National Institute of Mental Health (NIMH), and P50DA10075 (National Institute on Drug Abuse [NIDA], S.M., D.A.). 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Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2014 VL 53 IS 6 BP 635 EP 646 DI 10.1016/j.jaac.2014.01.019 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI0SO UT WOS:000336560400007 PM 24839882 ER PT J AU Bent, S Hendren, RL Zandi, T Law, K Choi, JE Widjaja, F Kalb, L Nestle, J Law, P AF Bent, Stephen Hendren, Robert L. Zandi, Tara Law, Kiely Choi, Jae-Eun Widjaja, Felicia Kalb, Luther Nestle, Jay Law, Paul TI Internet-Based, Randomized, Controlled Trial of Omega-3 Fatty Acids for Hyperactivity in Autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; nutritional supplement; alternative medicine; hyperactivity ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED-TRIAL; SPECTRUM DISORDERS; PARENT REPORT; CHILDREN; METHYLPHENIDATE; SUPPLEMENTATION; IRRITABILITY; ARIPIPRAZOLE; RISPERIDONE AB Objective: Preliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder (ASD). We sought to examine the feasibility of a novel, Internet-based clinical trial design to evaluate the efficacy of this supplement. Method: E-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network. All study procedures, including screening, informed consent, and collection of outcome measures took place over the Internet. The primary Outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist (ABC-H). Results: During the 6-week recruitment period, 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks. Outcome assessments were obtained from all 57 participants and 57 teachers, and the study was completed in 3 months. Children in the omega-3 fatty acid group had a greater reduction in hyperactivity (-5.3 points) compared to the placebo group (-2.6 points), but the difference was not statistically significant (1.9-point greater improvement in the omega-3 group, 95% CI = -2.2 to 5.2). Adverse events were rare and not associated with omega-3 fatty acids. Participant feedback was positive. Conclusion: Internet-based, randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials. A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids. Clinical trial registration information-Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder; http://clinicaltrials.gov; NCT 01694667. C1 [Bent, Stephen; Hendren, Robert L.; Choi, Jae-Eun; Widjaja, Felicia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zandi, Tara; Law, Kiely; Kalb, Luther; Nestle, Jay; Law, Paul] Kennedy Krieger Inst, Baltimore, MD USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu FU Simons Foundation [SFARI 206484]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131] FX This work was supported by a grant from the Simons Foundation (SFARI 206484, S.B.) and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. 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PD JUN PY 2014 VL 53 IS 6 BP 658 EP 666 DI 10.1016/j.jaac.2014.01.018 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI0SO UT WOS:000336560400009 PM 24839884 ER PT J AU Field, SS AF Field, Scott S. TI Interaction of genes and nutritional factors in the etiology of autism and attention deficit/hyperactivity disorders: A case control study SO MEDICAL HYPOTHESES LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ESSENTIAL FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; SPECTRUM DISORDERS; DOCOSAHEXAENOIC ACID; DOUBLE-BLIND; RISK-FACTORS; YOUNG-CHILDREN; BIRTH-WEIGHT; PATERNAL AGE AB Objective: To compare risk factors of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) to age/sex-matched controls with particular attention to family history, parental age and nutrition. Method: 31 ASD and 81 ADHD patients were compared to 612 age/sex-matched controls by reviewing charts for parental age, sibling order, gestational age, and early feeding, and by parental interview for early feeding and family history of psychopathology on affected patients and 139 of those controls. Findings: Parental age affected ASD and ADHD females but not males. First-born males were at increased risk for both disorders even though their siblings had older parents and their parents were not more likely to stop having children. Breastfeeding in the absence of parental psychopathology reduced ADHD risk, but breastfeeding of first-born males by older mothers with psychopathology was a risk for ASD. Breastfeeding was only a risk for ADHD if the mother had psychopathology. Parent emigration from a place of high fish consumption was a significant ASD risk factor. Resulting hypotheses: ADHD and ASD share risk factors due to shared genetic and nutritional interactions, likely revolving around deficiencies of omega-3 fatty acids (n3FAs) during brain development. Fatty acid metabolism genes are important in that process. The 4:1 male to female ratio for both disorders results from hormonally driven fat metabolism differences. Risk factors for both disorders including maternal smoking, prematurity, and gestational diabetes may also be attributed to their effect on n3FA supplies. Breastfeeding can be a risk factor when the mother's genes and/or age affect her milk quality. Parental age and gene defects may affect female more than male offspring. Childbirth with adequate spacing and breastfeeding can override maternal age and protect subsequent offspring. Genetic variations in fat metabolism can be influenced by cultural/geographic diet, causing deficiencies in offspring with migration-influenced diet changes. Interaction of n3FA deficient diets, delayed child-bearing, and breastfeeding by mothers with psychopathology may be important factors in the rising incidence of ASD and ADHD in recent decades. Partial prevention through diet and supplements may be possible. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Field, Scott S.] Univ Alabama Birmingham, Huntsville Hosp, Birmingham, AL USA. RP Field, SS (reprint author), Field Pediat PC, 1106 Gleneagles Dr, Huntsville, AL 35801 USA. 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Hypotheses PD JUN PY 2014 VL 82 IS 6 BP 654 EP 661 DI 10.1016/j.mehy.2014.02.021 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI2QX UT WOS:000336704200004 PM 24685108 ER PT J AU Gialloreti, LE Benvenuto, A Benassi, F Curatolo, P AF Gialloreti, Leonardo Emberti Benvenuto, Arianna Benassi, Francesca Curatolo, Paolo TI Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders? SO MEDICAL HYPOTHESES LA English DT Article ID PERINATAL RISK-FACTORS; DEVELOPING-COUNTRIES; DRAMATIC INCREASE; SOCIAL-BEHAVIOR; RATES; PREVALENCE; CONSEQUENCES; VASOPRESSIN; HEALTH; CHINA AB The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While ASDs have been shown to be heritable, several environmental co-factors, such as, e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of the disorder as well. Prevalence of ASDs appears to have increased in the last three decades, but the causes of this surge are not fully understood. As perinatal adverse events have increased as well, they have been regarded as logical contributors to the risen prevalence of ASDs. Over the last three decades there has been also a considerable increase in the rates of induced labor and caesarean sections (CS). However, even if a causal association between CS and ASDs increase has been suggested, it has not yet been proven. Nevertheless, we hypothesize here that such an association is actual and that it might help to explain a part of the increase in ASD diagnoses. Our assumption is based on the wider epidemiological picture of ASDs and CS, as well as on the possible biological plausibility of this correlation, by postulating potential epigenetic and neurobiological mechanisms underpinning this relationship. Today, several observations point toward the existence of epigenetic dysregulation in ASDs and this raises the issue of the role of environmental factors in bringing about epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide systems could play a role in the behavioral dysfunctions of ASDs. Particularly, some evidence suggests a dysregulation of the oxytocinergic system in autistic brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting effects on the development of social behaviors. Within the perinatal period, various processes, like pitocin infusion or CS, can alter the OT balance in the newborn; OT dysregulation could then interact with genetic factors, leading ultimately to the development of ASDs. Large long-term prospective studies are needed to identify causal pathways for ASDs and examine whether and how (epi-)genetic susceptibility interacts with obstetric risk factors in the development of ASDs. A better understanding of such a potential interplay could become paradigmatic for a wide range of genetic-environmental interactions in ASDs. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Gialloreti, Leonardo Emberti] Univ Roma Tor Vergata, Dept Biomed & Prevent, I-00133 Rome, Italy. [Gialloreti, Leonardo Emberti; Benassi, Francesca] Ctr Commun & Neurorehabil Res CNAPP, Rome, Italy. [Benvenuto, Arianna; Curatolo, Paolo] Univ Roma Tor Vergata, Dept Neurosci, Pediat Neurol Unit, I-00133 Rome, Italy. RP Gialloreti, LE (reprint author), Univ Roma Tor Vergata, Dept Biomed & Prevent, Via Montpellier 1, I-00133 Rome, Italy. 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Hypotheses PD JUN PY 2014 VL 82 IS 6 BP 713 EP 718 DI 10.1016/j.mehy.2014.03.011 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI2QX UT WOS:000336704200018 PM 24685110 ER PT J AU Xu, XJ Xiong, ZM Zhang, LS Liu, YL Lu, LN Peng, Y Guo, H Zhao, JP Xia, K Hu, ZM AF Xu, Xiaojuan Xiong, Zhimin Zhang, Lusi Liu, Yalan Lu, Lina Peng, Yu Guo, Hui Zhao, Jingping Xia, Kun Hu, Zhengmao TI Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE Autism; Neuroligin; NLGN; Variation ID MENTAL-RETARDATION; NEUROLIGINS; MUTATION; BINDING; DISORDER AB Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were "Probably Damaging". The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case-control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95 % CI 2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population. C1 [Xu, Xiaojuan; Xiong, Zhimin; Zhang, Lusi; Liu, Yalan; Lu, Lina; Peng, Yu; Guo, Hui; Zhao, Jingping; Xia, Kun; Hu, Zhengmao] Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China. [Xu, Xiaojuan] Lanzhon Univ, Hosp 1, Reprod Med Hosp, Lanzhou, Gansu, Peoples R China. [Xiong, Zhimin; Xia, Kun; Hu, Zhengmao] Cent S Univ, Sch Biol Sci & Technol, Changsha, Hunan, Peoples R China. [Zhao, Jingping] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China. RP Xia, K (reprint author), Cent S Univ, Sch Biol Sci & Technol, Changsha, Hunan, Peoples R China. EM xiakun@sklmg.edu.cn; huzhengmao@sklmg.edu.cn FU National Basic Research Program 973 of China [2012CB 517902, 2010 CB 529601]; National Natural Science Foundation of China [81330027, 81161120544, 31301023] FX We thank the patients and their families for agreeing to participate in this study and special teachers whose participation made this project possible. We also thank Cong Wang and Haoying Hao for sequencing, Jiada Li for manuscript revision. We were appreciated for the help and advices of our colleagues. This study was supported by the National Basic Research Program 973 of China (Grant No. 2012CB 517902, 2010 CB 529601) and the National Natural Science Foundation of China (Grant No. 81330027, 81161120544, 31301023). 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TI De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability SO MOLECULAR PSYCHIATRY LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; L1 RETROTRANSPOSITION; SPECTRUM DISORDERS; SEQUENCING DATA; HUMAN BRAIN; RISK LOCI; DISEASE; VARIANTS AB Schizophrenia is a serious psychiatric disorder with a broadly undiscovered genetic etiology. Recent studies of de novo mutations (DNMs) in schizophrenia and autism have reinforced the hypothesis that rare genetic variation contributes to risk. We carried out exome sequencing on 57 trios with sporadic or familial schizophrenia. In sporadic trios, we observed a similar to 3.5-fold increase in the proportion of nonsense DNMs (0.101 vs 0.031, empirical P= 0.01, Benjamini-Hochberg-corrected P= 0.044). These mutations were significantly more likely to occur in genes with highly ranked probabilities of haploinsufficiency (P= 0.0029, corrected P= 0.006). DNMs of potential functional consequence were also found to occur in genes predicted to be less tolerant to rare variation (P= 2.01 x 10(-5), corrected P = 2.1 x 10(-3)). Genes with DNMs overlapped with genes implicated in autism (for example, AUTS2, CHD8 and MECP2) and intellectual disability (for example, HUWE1 and TRAPPC9), supporting a shared genetic etiology between these disorders. Functionally CHD8, MECP2 and HUWE1 converge on epigenetic regulation of transcription suggesting that this may be an important risk mechanism. Our results were consistent in an analysis of additional exome-based sequencing studies of other neurodevelopmental disorders. These findings suggest that perturbations in genes, which function in the epigenetic regulation of brain development and cognition, could have a central role in the susceptibility to, pathogenesis and treatment of mental disorders. C1 [McCarthy, S. E.; Gillis, J.; Kramer, M.; Lihm, J.; Yoon, S.; Berstein, Y.; Solomon, R.; Ghiban, E.; Antoniou, E.; McCombie, W. R.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 11724 USA. [Mistry, M.; Pavlidis, P.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Mistry, M.; Pavlidis, P.] Univ British Columbia, Ctr High Throughput Biol, Vancouver, BC, Canada. [Kelleher, E.; O'Brien, C.; Donohoe, G.; Gill, M.; Morris, D. W.; Corvin, A.] Univ Dublin Trinity Coll, Inst Mol Med, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [McCombie, W. R.] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. RP McCarthy, SE (reprint author), Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA. EM mccarthy@cshl.edu; mccombie@cshl.edu; acorvin@tcd.ie FU Science Foundation Ireland [08/IN.1/B1916]; NIH [GM076990]; Michael Smith Foundation for Health Research; Canadian Institutes for Health Research FX We would like to thank Stephanie Muller, Gloria Cheang, Senem Mavruk, Manasa Kolli, Nabil Azamy, Anthony DeSantis and Patricia Mocombe for contributing their expertise and help to perform exome capture, sequencing, validations and genotyping. We are grateful to Elodie Portales-Casamar for assistance with Neurocarta. We thank Jianchao Yao for helpful discussion and feedback. Funding for this study was provided by grants from T and V Stanley to SEM, JG, MK, JL, SY, YB, RS, EG, EA and WRM and from Science Foundation Ireland (08/IN.1/B1916) to AC, MG and DWM. PP was supported by NIH Grant GM076990 and salary awards from the Michael Smith Foundation for Health Research and the Canadian Institutes for Health Research. We thank James Watson for his constant support and encouragement. 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Psychiatr. PD JUN PY 2014 VL 19 IS 6 BP 652 EP 658 DI 10.1038/mp.2014.29 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AI2BZ UT WOS:000336663100006 PM 24776741 ER PT J AU Di Martino, A Yan, CG Li, Q Denio, E Castellanos, FX Alaerts, K Anderson, JS Assaf, M Bookheimer, SY Dapretto, M Deen, B Delmonte, S Dinstein, I Ertl-Wagner, B Fair, DA Gallagher, L Kennedy, DP Keown, CL Keysers, C Lainhart, JE Lord, C Luna, B Menon, V Minshew, NJ Monk, CS Mueller, S Muller, RA Nebel, MB Nigg, JT O'Hearn, K Pelphrey, KA Peltier, SJ Rudie, JD Sunaert, S Thioux, M Tyszka, JM Uddin, LQ Verhoeven, JS Wenderoth, N Wiggins, JL Mostofsky, SH Milham, MP AF Di Martino, A. Yan, C-G Li, Q. Denio, E. Castellanos, F. X. Alaerts, K. Anderson, J. S. Assaf, M. Bookheimer, S. Y. Dapretto, M. Deen, B. Delmonte, S. Dinstein, I. Ertl-Wagner, B. Fair, D. A. Gallagher, L. Kennedy, D. P. Keown, C. L. Keysers, C. Lainhart, J. E. Lord, C. Luna, B. Menon, V. Minshew, N. J. Monk, C. S. Mueller, S. Mueller, R. A. Nebel, M. B. Nigg, J. T. O'Hearn, K. Pelphrey, K. A. Peltier, S. J. Rudie, J. D. Sunaert, S. Thioux, M. Tyszka, J. M. Uddin, L. Q. Verhoeven, J. S. Wenderoth, N. Wiggins, J. L. Mostofsky, S. H. Milham, M. P. TI The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism SO MOLECULAR PSYCHIATRY LA English DT Article DE data sharing; default network; interhemispheric connectivity; intrinsic functional connectivity; resting-state fMRI; thalamus ID FUNCTIONAL CONNECTIVITY MRI; SPECTRUM DISORDERS; CORPUS-CALLOSUM; REGIONAL-VARIATION; DEFAULT NETWORK; HEAD MOTION; ABNORMALITIES; CHILDREN; SYSTEMS; UNDERCONNECTIVITY AB Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_ 1000. projects. nitrc. org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo-and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid-and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies. C1 [Di Martino, A.; Denio, E.; Castellanos, F. X.; Alaerts, K.] NYU, Langone Med Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, NYU Child Study Ctr, New York, NY 10016 USA. [Yan, C-G; Castellanos, F. X.; Milham, M. P.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Li, Q.; Milham, M. P.] Ctr Developing Brain, Child Mind Inst, New York, NY USA. [Alaerts, K.; Wenderoth, N.] Katholieke Univ Leuven, Louvain, Belgium. [Anderson, J. S.] Univ Utah, Div Neuroradiol, Salt Lake City, UT USA. [Anderson, J. S.] Univ Utah, Interdept Program Neurosci, Salt Lake City, UT USA. [Anderson, J. S.] Univ Utah, Inst Brain, Salt Lake City, UT USA. [Anderson, J. S.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. [Assaf, M.] Hartford Hosp, Inst Living, Olin Neuropsychiatry Res Ctr, Hartford, CT 06115 USA. [Assaf, M.; Deen, B.; Pelphrey, K. A.] Yale Univ, Sch Med, New Haven, CT USA. [Bookheimer, S. Y.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Los Angeles, CA USA. [Bookheimer, S. Y.; Dapretto, M.; Rudie, J. D.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bookheimer, S. Y.; Dapretto, M.; Rudie, J. D.] Univ Calif Los Angeles, Interdept Neurosci Program, Los Angeles, CA USA. [Bookheimer, S. Y.; Rudie, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dapretto, M.; Rudie, J. D.] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA USA. [Deen, B.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Delmonte, S.; Gallagher, L.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland. [Delmonte, S.; Gallagher, L.] Trinity Coll Dublin, Trinity Coll, Inst Neurosci, Dublin, Ireland. [Dinstein, I.] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Dinstein, I.] Ben Gurion Univ Negev, Beer Sheva, Israel. [Ertl-Wagner, B.; Mueller, S.] Univ Munich, Inst Clin Radiol, Munich, Germany. [Fair, D. A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Fair, D. A.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Fair, D. A.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA. [Kennedy, D. P.] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. [Kennedy, D. P.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Keown, C. L.; Mueller, R. A.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Keysers, C.; Thioux, M.] Royal Dutch Acad Sci KNAW, Netherlands Inst Neurosci, Amsterdam, Netherlands. [Keysers, C.; Thioux, M.] Univ Groningen, Univ Med Ctr Groningen, BCN NeuroImaging Ctr, NL-9713 AV Groningen, Netherlands. [Lainhart, J. E.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Lainhart, J. E.] Univ Wisconsin, Dept Psychiat, Div Child & Adolescent Psychiat, Madison, WI 53706 USA. [Lord, C.] Weill Cornell Med Coll, New York, NY USA. [Luna, B.; O'Hearn, K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Menon, V.; Uddin, L. Q.] Stanford Univ, Stanford, CA 94305 USA. [Minshew, N. J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Minshew, N. J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Monk, C. S.; Peltier, S. J.; Wiggins, J. L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nebel, M. B.; Mostofsky, S. H.] Kennedy Krieger Inst, Lab Neurocognit & Imaging Res, Baltimore, MD USA. [Nigg, J. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sunaert, S.; Verhoeven, J. S.] Katholieke Univ Leuven, Univ Leuven, Translat MRI, Louvain, Belgium. [Tyszka, J. M.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Mostofsky, S. H.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mostofsky, S. H.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Di Martino, A (reprint author), NYU, Langone Med Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, NYU Child Study Ctr, One Pk Ave,8th Floor, New York, NY 10016 USA. EM dimara01@nyumc.org; michael.milham@childmind.org RI Monk, Christopher/J-1805-2014; Milham, Michael/K-9501-2014; Di Martino, Adriana/L-2497-2014; Tyszka, Julian/O-3498-2014; Yan, Chao-Gan/D-1713-2015; Nebel, Mary Beth/D-3305-2015; Wenderoth, Nicole/D-7262-2015 OI Tyszka, Julian/0000-0001-9342-9014; Yan, Chao-Gan/0000-0003-3413-5977; Nebel, Mary Beth/0000-0003-0185-3382; Wenderoth, Nicole/0000-0002-3246-9386 FU NIMH [K23MH087770, R03MH09632, BRAINSRO1MH094639-01]; Leon Levy Foundation; Joseph P Healey and the Stavros Niarchos Foundation; NIH [DC011095, MH084164, K01MH092288-Stanford, HD55748, KO1MH081191, MH67924-Pitt, K08MH092697, P50MH60450, R01NS34783, R01MH080826, T32DC008553-USM, R01HD065282, R21MH084126-NYU, MH066496, R21MH079871, U19HD035482-UM1&UM2, R00MH091238, R01MH086654, R01MH096773-OHSU, R01MH081023-SDSU;, 1R01HD06528001-UCLA1 and -UCLA2;, K01MH071284-Yale, R01MH080721, K99/R00MH094409-Caltech]; NINDS [R01NS048527]; NICHD (Yale) [P50 HD055784, UCLA1 and 2]; NICHD/NIDCD [P01/U19]; the Simons Foundation (OHSU, Yale, Caltech, CMU); the Belgian Interuniversity Attraction Poles [P6/29, Leuven 1 and 2]; Ben B and Iris M Margolis Foundation; European Commission; Marie Curie Excellence [MEXT-CT-2005-023253]; Flanders Fund for Scientific Research [Leuven 1 and 2, 1841313N, G.0354.06, G.0758.10, post-doc grant]; Hartford Hospital (Olin); John Merck Scholars Fund (Yale); Kyulan Family Foundation (Trinity); Michigan Institute for Clinical and Health Research (MICHR) Predoctoral Fellowship [UM1 and 2]; The Meath Foundation, Adelaide & Meath Hospital (AMNCH; Trinity); National Initiative for Brain and Cognition NIHC HCMI [056-13-014, 056-13-017]; NWO [051.07.003, 452-04-305, 400-08-089]; Netherlands Brain Foundation [KS 2010(1)-29]; NRSA Pre-doctoral Fellowship [F31DC010143]; Research Research Council of the University of Leuven [Leuven 1 and 2]; Singer Foundation and Stanford Institute for Neuro-Innovations and Translational Neurosciences (Stanford); Leon Levy Foundation (NYU); Stavros Niarchos Foundation (NYU); UCLA Autism Center of Excellence [UCLA1 and 2]; Autism Science Foundation (Yale); University of Utah Multidisciplinary Research Seed Grant (USM); [R01MH081218] FX We thank the numerous contributors at each site (see Supplementary Table 2 and http://fcon_1000.projects.nitrc.org/indi/abide/), particularly Drs Marlene Behrmann and Leonardo Cerliani for their efforts in the collection, organization and sharing of their data sets; the NITRC (http://www.nitrc.org) for providing the data sharing platform for the ABIDE initiative as well as the other informatics databases for providing additional platforms (see http://fcon_1000.projects.nitrc.org/indi/abide). We also thank Ranjit Khanuja and Sharad Sikka for programming support; Dr R Cameron Craddock for invaluable suggestions regarding data analysis, as well as oversight of the development of the Configurable Pipeline for the Analysis of Connectomes, and Drs Zhen Yang and Clare Kelly for suggestions on earlier versions of this manuscript. Support for ABIDE coordination and data aggregation was partially provided by NIMH (K23MH087770, R03MH09632 and BRAINSRO1MH094639-01), the Leon Levy Foundation and by gifts from Joseph P Healey and the Stavros Niarchos Foundation. Support for data collection at each site was provided by NIH (DC011095, MH084164, K01MH092288-Stanford; HD55748, KO1MH081191, MH67924-Pitt; K08MH092697, P50MH60450, R01NS34783, R01MH080826, T32DC008553-USM; K23MH087770, R01HD065282, R01MH081218, R21MH084126-NYU; MH066496, R21MH079871, U19HD035482-UM1 & UM2; R00MH091238, R01MH086654, R01MH096773-OHSU; R01MH081023-SDSU; 1R01HD06528001-UCLA1 and -UCLA2; K01MH071284-Yale; R01MH080721; K99/R00MH094409-Caltech), Autism Speaks (KKI, NYU, Olin, UM1and 2, Pitt, USM, Yale), NINDS (R01NS048527; KKI), NICHD (Yale) NICHD (P50 HD055784; UCLA1 and 2), NICHD/NIDCD (P01/U19; CMU) the Simons Foundation (OHSU, Yale, Caltech, CMU), the Belgian Interuniversity Attraction Poles Grant (P6/29; Leuven 1 and 2), Ben B and Iris M Margolis Foundation (USM), European Commission, Marie Curie Excellence Grant (MEXT-CT-2005-023253; SBL), Flanders Fund for Scientific Research (1841313N, G.0354.06, G.0758.10; and post-doc grant; Leuven 1 and 2), Hartford Hospital (Olin), John Merck Scholars Fund (Yale), Kyulan Family Foundation (Trinity), Michigan Institute for Clinical and Health Research (MICHR) Predoctoral Fellowship (UM1 and 2), The Meath Foundation, Adelaide & Meath Hospital, Dublin Incorporating the National Children's Hospital (AMNCH; Trinity), National Initiative for Brain and Cognition NIHC HCMI (056-13-014, 056-13-017; SBL), NWO (051.07.003, 452-04-305, 400-08-089; SBL) and Netherlands Brain Foundation (KS2010(1)-29; SBL), NRSA Pre-doctoral Fellowship (F31DC010143; USM), Research Council of the University of Leuven (Leuven 1 and 2), Singer Foundation and Stanford Institute for Neuro-Innovations and Translational Neurosciences (Stanford), Leon Levy fOundation (NYU), Stavros Niarchos Foundation (NYU), UCLA Autism Center of Excellence (UCLA1 and 2), Autism Science Foundation (Yale) and University of Utah Multidisciplinary Research Seed Grant (USM). 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Psychiatr. PD JUN PY 2014 VL 19 IS 6 BP 659 EP 667 DI 10.1038/mp.2013.78 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AI2BZ UT WOS:000336663100007 PM 23774715 ER PT J AU McCarro, SA Feng, GP Hyman, SE AF McCarro, Steven A. Feng, Guoping Hyman, Steven E. TI Genome-scale neurogenetics: methodology and meaning SO NATURE NEUROSCIENCE LA English DT Article ID DE-NOVO MUTATIONS; ALZHEIMERS-DISEASE; GENETIC-VARIATION; PSYCHIATRIC-DISORDERS; POPULATION-SCALE; RISK LOCI; AUTISM; SCHIZOPHRENIA; ASSOCIATION; COMMON AB Genetic analysis is currently offering glimpses into molecular mechanisms underlying such neuropsychiatric disorders as schizophrenia, bipolar disorder and autism. 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[Dadayan, Aleksander; Zolotarev, Yurii] RAS, Inst Mol Genet, Moscow 117901, Russia. [Grachev, Sergei] RAS, Inst Bioorgan Chem, Moscow 117901, Russia. [Varlamov, Oleg] Oregon Natl Primate Res Ctr, Beaverton, OR USA. RP Sokolov, O (reprint author), Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia. EM oleg-sokolov@yandex.ru FU Russian Fund of Fundamental Research [06-04-08257, 10-04-01781-a] FX This work was supported by the grant of Russian Fund of Fundamental Research 06-04-08257 and 10-04-01781-a. 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TI Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders SO PHARMACOGENOMICS JOURNAL LA English DT Article DE autism spectrum disorders; dopamine; genetics; hyperactivity; methylphenidate ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DOPAMINE TRANSPORTER GENOTYPE; ABERRANT BEHAVIOR CHECKLIST; ADHD CHILDREN; DOSE-RESPONSE; RECEPTOR GENE; SCHIZOPHRENIC CHILDREN; GENOME BROWSER; ASSOCIATION AB Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P< 0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability. C1 [McCracken, J. T.; Badashova, K. K.; Whelan, F.; Shah, B.; Nurmi, E. L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci, Los Angeles, CA 90024 USA. [Posey, D. J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychiat, Columbus, OH 43210 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychol, Columbus, OH 43210 USA. [Scahill, L.] Yale Univ, Child Study Ctr, New Haven, CT USA. [Tierney, E.] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA. [Chuang, S. Z.; Davies, M.] Columbia Univ, Dept Psychiat, New York, NY USA. [McDougle, C. J.] Massachusetts Gen Hosp, Lurie Autism Ctr, Dept Psychiat, Boston, MA 02114 USA. RP McCracken, JT (reprint author), UCLA NPI Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jmccracken@mednet.ucla.edu RI Nurmi, Erika/P-4627-2014 OI Nurmi, Erika/0000-0003-4893-8957 FU NIMH [N01 MH-70070, N01 MH-70009, N01 MH-70001, N01 MH 80011, MH-01805, MH094613, T32MH073517, MH-68627]; NIH Division of Research Resources General Clinical Research Center [M01 RR-00750, M01 RR-00052, M01 RR-00034, M01 RR-06022]; Korczak Foundation FX The RUPP Autism Network comprises the following investigators listed by role and study site: Ohio State University: principal investigator Michael G Amen, PhD, co-investigators L Eugene Arnold, MEd, MD, Yaser Ramadan, MD, Andrea Witwer, MA, Ronald Lindsay, MD and Patricia Nash, MD; University of California at Los Angeles: principal investigator James T McCracken, MD, co-investigators Bhavik Shah, MD, James Mc Gough, MD, Pegeen Cronin, PhD, Lisa Lee, BA; Indiana University: principal investigator Christopher J McDougle, MD, co-investigators David Posey, MD, Naomi Swiezy, PhD, Arlene Kohn, BA; Yale University: principal investigator Lawrence Scahill, MSN, PhD, co-investigators Andres Martin, MD, Kathleen Koenig, MSN, Fred Volkmar, MD, Deirdre Carroll, MSN, Allison Lancor, BS; Kennedy Krieger Institute: principal investigator Elaine Tierney, MD, co-investigators Jaswinder Ghuman, MD, Nilda Gonzalez, MD, Marco Grados, MD; National Institute of Mental Health: principal investigator Benedetto Vitiello, MD, co-investigator Louise Ritz, MBA; statisticians: Shirley Z Chuang, MS, Mark Davies, MPH, of Columbia University; data management: James Robinson, MEd, Don McMahon, MS, Nathan Kline Institute. Research supported by NIMH contracts N01 MH-70070 (principal investigator: Dr McCracken), N01 MH-70009 (principal investigator: Dr Scahill), N01 MH-70001 (principal investigator: Dr McDougle), and N01 MH 80011 (principal investigator: Dr Amen); by NIH Division of Research Resources General Clinical Research Center grants M01 RR-00750 (to Indiana University), M01 RR-00052 (to John Hopkins University), M01 RR-00034 (to Ohio University) and M01 RR-06022 (to Yale University); by NIMH grants MH-01805 (to Dr McCracken) NIMH grants MH094613 and T32MH073517 (Dr Nurmi) and MH-68627 (to Dr Posey); and by funding from the Korczak Foundation (to Dr Scahill). The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services. 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Richling, Sarah M. Carroll, Regina A. TI Preliminary Effects of Conditioned Establishing Operations on Stereotypy SO PSYCHOLOGICAL RECORD LA English DT Article DE Autism; Automatic reinforcement; Establishing operation; Conditioned motivating operation; Stereotypy ID BEHAVIOR-ANALYSIS; MULTIPLE FORMS; INTERVENTION; STIMULATION; SKILLS AB We repeatedly paired preferred stimuli with known establishing properties and poster boards (i.e., neutral stimuli) to examine whether these poster boards would acquire the effects of a conditioned establishing operation in five children with autism. Following pairing, the poster boards, which had been previously shown to be neutral, increased immediate or subsequent engagement in stereotypy for three of five participants. The results suggest that it is possible to condition establishing operations for stereotypy and that this process may occur inadvertently. 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PD JUN PY 2014 VL 64 IS 2 BP 209 EP 216 DI 10.1007/s40732-014-0027-x PG 8 WC Psychology, Multidisciplinary SC Psychology GA AI2ZX UT WOS:000336729000007 ER PT J AU Moran, L Stewart, I McElwee, J Ming, S AF Moran, Laura Stewart, Ian McElwee, John Ming, Siri TI Relational Ability and Language Performance in Children With Autism Spectrum Disorders and Typically Developing Children: A Further Test of the TARPA Protocol SO PSYCHOLOGICAL RECORD LA English DT Article DE TARPA; Autism spectrum disorder; PLS-4; Language; Relational frame theory ID FRAME-THEORY; TRANSPOSITION; EQUIVALENCE; INFANT AB The Training and Assessment of Relational Precursors and Abilities (TARPA) protocol was developed to assess the emergence of derived relational responding, which has been argued by relational frame theory (RFT) to be the key process underlying language. Previous research showed a correlation between the TARPA and the Vineland Adaptive Behavior Scales (VABS) in several children with autism spectrum disorder (ASD). The current study advanced this work by correlating a more comprehensive and systematic TARPA protocol with the Preschool Language Scale, Fourth Edition (PLS-4), a mainstream performance-based language assessment, in 10 additional children with ASD (Experiment 1) and 13 typically developing children (Experiment 2). This study also involved a hierarchical analysis of the TARPA. Results showed (a) a strong and significant correlation between the TARPA and PLS-4 full scale and subscales, and (b) evidence to support the hierarchical structure of the TARPA. The implications of these and other findings are discussed. C1 [Moran, Laura; Stewart, Ian] Natl Univ Ireland Galway, Sch Psychol, Galway City, Ireland. RP Stewart, I (reprint author), Natl Univ Ireland Galway, Sch Psychol, Galway City, Ireland. 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PD JUN PY 2014 VL 64 IS 2 BP 233 EP 251 DI 10.1007/s40732-014-0032-0 PG 19 WC Psychology, Multidisciplinary SC Psychology GA AI2ZX UT WOS:000336729000009 ER PT J AU Mirzaa, GM Millen, KJ Barkovich, AJ Dobyns, WB Paciorkowski, AR AF Mirzaa, Ghayda M. Millen, Kathleen J. Barkovich, A. James Dobyns, William B. Paciorkowski, Alex R. TI The Developmental Brain Disorders Database (DBDB): A curated neurogenetics knowledge base with clinical and research applications SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE developmental brain disorders; database; bioinformatics; levels of evidence ID DE-NOVO MUTATIONS; GENETIC CLASSIFICATION; CORTICAL DEVELOPMENT; DELAY; MALFORMATIONS; SPECTRUM; AUTISM AB The number of single genes associated with neurodevelopmental disorders has increased dramatically over the past decade. The identification of causative genes for these disorders is important to clinical outcome as it allows for accurate assessment of prognosis, genetic counseling, delineation of natural history, inclusion in clinical trials, and in some cases determines therapy. Clinicians face the challenge of correctly identifying neurodevelopmental phenotypes, recognizing syndromes, and prioritizing the best candidate genes for testing. However, there is no central repository of definitions for many phenotypes, leading to errors of diagnosis. Additionally, there is no system of levels of evidence linking genes to phenotypes, making it difficult for clinicians to know which genes are most strongly associated with a given condition. We have developed the Developmental Brain Disorders Database (DBDB: https://www.dbdb.urmc.rochester.edu/home), a publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders. DBDB contains the first referenced ontology of developmental brain phenotypes, and uses a novel system of levels of evidence for gene-phenotype associations. It is intended to assist clinicians in arriving at the correct diagnosis, select the most appropriate genetic test for that phenotype, and improve the care of patients with developmental brain disorders. For researchers interested in the discovery of novel genes for developmental brain disorders, DBDB provides a well-curated source of important genes against which research sequencing results can be compared. Finally, DBDB allows novel observations about the landscape of the neurogenetics knowledge base. (c) 2014 Wiley Periodicals, Inc. C1 [Mirzaa, Ghayda M.; Millen, Kathleen J.; Dobyns, William B.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA. [Mirzaa, Ghayda M.; Millen, Kathleen J.; Dobyns, William B.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Ctr Neural Dev & Dis, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Neurol Pediat & Biomed Genet, Rochester, NY 14642 USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, 610 Elmwood Ave, Rochester, NY 14642 USA. EM alex_paciorkowski@urmc.rochester.edu FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health [R01NS046616, R01NS050375, R01NS058721, K08NS078054] FX Grant sponsor: National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health; Grant numbers: R01NS046616, R01NS050375, R01NS058721, K08NS078054. 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PD JUN PY 2014 VL 8 IS 2 BP 65 EP 70 DI 10.1111/cdep.12064 PG 6 WC Psychology, Developmental SC Psychology GA AH6ZU UT WOS:000336282300002 ER PT J AU Treur, J AF Treur, Jan TI Displaying and Regulating Different Social Response Patterns: A Computational Agent Model SO COGNITIVE COMPUTATION LA English DT Article DE Social response; ASD; Regulation; Computational agent model ID AUTISM SPECTRUM DISORDERS; MIRROR NEURON SYSTEM; EMOTION REGULATION; FRONTAL-CORTEX; COMMUNICATION; CONSEQUENCES; IMITATION; GAZE; DYSFUNCTION; EXPRESSION AB Differences in social responses of individuals can often be related to differences in functioning of certain neurological mechanisms. This paper presents a computational agent model capable of showing different types of social response patterns based on such mechanisms, adopted from theories on mirror neuron systems, emotion integration, emotion regulation, and empathy. 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Comput. PD JUN PY 2014 VL 6 IS 2 BP 182 EP 199 DI 10.1007/s12559-013-9233-0 PG 18 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA AH7LD UT WOS:000336313700005 ER PT J AU Ganz, JB Rispoli, MJ Mason, RA Hong, ER AF Ganz, Jennifer B. Rispoli, Mandy J. Mason, Rose Ann Hong, Ee Rea TI Moderation of effects of AAC based on setting and types of aided AAC on outcome variables: An aggregate study of single-case research with individuals with ASD SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE AAC; augmentative and alternative communication; meta-analysis; autism; setting; PECS; SGD ID EXCHANGE COMMUNICATION-SYSTEM; AUTISM SPECTRUM DISORDERS; SPEECH-GENERATING DEVICES; DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; FUNCTIONAL COMMUNICATION; SUBJECT RESEARCH; YOUNG-CHILDREN; PARTICIPANT CHARACTERISTICS; QUANTITATIVE SYNTHESIS AB Objective: The purpose of this meta-analysis was to evaluate the potential moderating effects of intervention setting and type of aided augmentative and alternative communication (AAC) on outcome variables for students with autism spectrum disorders. Methods: Improvement rate difference, an effect size measure, was used to calculate aggregate effects across 35 single-case research studies. Results: Results indicated that the largest effects for aided AAC were observed in general education settings. With respect to communication outcomes, both speech generating devices (SGDs) and the Picture Exchange Communication System (PECS) were associated with larger effects than other picture-based systems. With respect to challenging behaviour outcomes, SGDs produced larger effects than PECS. Conclusion: This aggregate study highlights the importance of considering intervention setting, choice of AAC system and target outcomes when designing and planning an aided AAC intervention. C1 [Ganz, Jennifer B.; Rispoli, Mandy J.; Mason, Rose Ann; Hong, Ee Rea] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. [Mason, Rose Ann] Univ Kansas, Juniper Gardens Childrens Project, Kansas City, KS 66101 USA. RP Ganz, JB (reprint author), Texas A&M Univ, Dept Educ Psychol, 4225 TAMU, College Stn, TX 77843 USA. 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Kleinboeck, Tina Poustka, Fritz Boelte, Sven Schmoetzer, Gabriele Voran, Anette Huy, Ellen Meyer, Jobst Bourgeron, Thomas Klauck, Sabine M. Freitag, Christine M. Chiocchetti, Andreas G. TI Common variants in genes of the postsynaptic FMRP signalling pathway are risk factors for autism spectrum disorders SO HUMAN GENETICS LA English DT Article ID FRAGILE-X-SYNDROME; PROTEIN-KINASE-IV; METABOTROPIC GLUTAMATE RECEPTORS; MENTAL-RETARDATION PROTEIN; GENOME-WIDE ASSOCIATION; DIAGNOSTIC INTERVIEW; MESSENGER-RNA; GERMAN FORM; EXPRESSION; TRANSLATION AB Autism spectrum disorders (ASD) are heterogeneous disorders with a high heritability and complex genetic architecture. Due to the central role of the fragile X mental retardation gene 1 protein (FMRP) pathway in ASD we investigated common functional variants of ASD risk genes regulating FMRP. We genotyped ten SNPs in two German patient sets (N = 192 and N = 254 families, respectively) and report association for rs7170637 (CYFIP1; set 1 and combined sets), rs6923492 (GRM1; combined sets), and rs25925 (CAMK4; combined sets). An additional risk score based on variants with an odds ratio (OR) > 1.25 in set 1 and weighted by their respective log transmitted/untransmitted ratio revealed a significant effect (OR 1.30, 95 % CI 1.11-1.53; P = 0.0013) in the combined German sample. A subsequent meta-analysis including the two German samples, the "Strict/European" ASD subsample of the Autism Genome Project (1,466 families) and a French case/control (541/366) cohort showed again association of rs7170637-A (OR 0.85, 95 % CI 0.75-0.96; P = 0.007) and rs25925-G (OR 1.31, 95 % CI 1.04-1.64; P = 0.021) with ASD. Functional analyses revealed that these minor alleles predicted to alter splicing factor binding sites significantly increase levels of an alternative mRNA isoform of the respective gene while keeping the overall expression of the gene constant. These findings underpin the role of ASD candidate genes in postsynaptic FMRP regulation suggesting that an imbalance of specific isoforms of CYFIP1, an FMRP interaction partner, and CAMK4, a transcriptional regulator of the FMRP gene, modulates ASD risk. Both gene products are related to neuronal regulation of synaptic plasticity, a pathomechanism underlying ASD and may thus present future targets for pharmacological therapies in ASD. C1 [Waltes, Regina; Duketis, Eftichia; Schlitt, Sabine; Jarczok, Tomasz A.; Sachse, Michael; Kaempfer, Laura M.; Kleinboeck, Tina; Poustka, Fritz; Boelte, Sven; Schmoetzer, Gabriele; Freitag, Christine M.; Chiocchetti, Andreas G.] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Knapp, Michael] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53105 Bonn, Germany. [Anney, Richard J. L.] Trinity Coll Dublin, Dept Psychiat, Sch Med, Autism Genet Grp, Dublin 8, Ireland. [Huguet, Guillaume; Bourgeron, Thomas] Inst Pasteur, F-75015 Paris, France. [Huguet, Guillaume; Bourgeron, Thomas] Univ Paris Diderot Paris 7, Fdn FondaMental, CNRS, URA 2182, F-75015 Paris, France. [Boelte, Sven] Karolinska Inst, Ctr Neurodev Disorders KIND, Dept Womens & Childrens Hlth, S-11330 Stockholm, Sweden. [Boelte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, S-11895 Stockholm, Sweden. [Voran, Anette; Huy, Ellen] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, D-66421 Homburg, Germany. [Meyer, Jobst] Univ Trier, Inst Psychobiol, Dept Neurobehav Genet, D-54290 Trier, Germany. [Klauck, Sabine M.] German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany. RP Chiocchetti, AG (reprint author), Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Deutschordenstr 50, D-60528 Frankfurt, Germany. EM andreas.chiocchetti@kgu.de FU Saarland University [T6 03 10 00-45]; Deutsche Forschungsgemeinschaft DFG [Po 255/17-4]; European Commission; German Bundesministerium fur Bildung und Forschung BMBF (ERA-NET NEURON project: EUHFAUTISM) [EUHFAUTISM-01EW1105]; Landes-Offensive zur Entwicklung wissenschaftlich-okonomischer Exzellenz (LOEWE): Neuronal Coordination Research Focus Frankfurt (NeFF) FX We thank all patients and their families for taking part in this study. In addition, we thoroughly thank Veronika Delcheva, Silvia Lindlar, Marnie Kopp, Hiacynta Jelen and Cornelia Wirth for excellent technical assistance and Heiko Zerlaut and Rusico Weber for database management. This work was supported by the Saarland University (T6 03 10 00-45 to C. M. F.); the Deutsche Forschungsgemeinschaft DFG (Po 255/17-4 to F. P.); the European Commission and the German Bundesministerium fur Bildung und Forschung BMBF (ERA-NET NEURON project: EUHFAUTISM) (EUHFAUTISM-01EW1105 to C. M. F.); and the Landes-Offensive zur Entwicklung wissenschaftlich-okonomischer Exzellenz (LOEWE): Neuronal Coordination Research Focus Frankfurt (NeFF). Furthermore, we gratefully acknowledge the families participating in the Autism Genome Project (AGP) and the main funders: Autism Speaks (USA), the Health Research Board (HRB; Ireland), the Medical Research Council (MRC; UK), Genome Canada/Ontario Genomics Institute and the Hilibrand Foundation (USA). 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Genet. PD JUN PY 2014 VL 133 IS 6 BP 781 EP 792 DI 10.1007/s00439-013-1416-y PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AH7MI UT WOS:000336317000010 PM 24442360 ER PT J AU Cridland, EK Jones, SC Caputi, P Magee, CA AF Cridland, Elizabeth K. Jones, Sandra C. Caputi, Peter Magee, Christopher A. TI Being a Girl in a Boys' World: Investigating the Experiences of Girls with Autism Spectrum Disorders During Adolescence SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Female; Girl; Adolescence; Qualitative; Family systems ID HIGH-FUNCTIONING CHILDREN; PERVASIVE DEVELOPMENTAL DISORDERS; QUALITY-OF-LIFE; ASPERGER-SYNDROME; SEX-DIFFERENCES; PARENTAL PERSPECTIVE; SEXUALITY EDUCATION; SOCIAL STORIES; AMBIGUOUS LOSS; PERCEPTIONS AB This study investigates the experiences of adolescent girls with autism spectrum disorders (ASD) during adolescence. Semi-structured interviews were conducted with three mother-daughter dyads and two additional mothers. A range of issues were highlighted covering physical, emotional, social and sexual domains. Some of these issues were similar to those experienced by boys with ASD during adolescence, such as negative implications of late diagnosis, challenges of transitioning to and coping with high school, 'hands-on' role of parents into adolescence, difficulties adjusting to the increased demands of adolescent hygiene routines, and the importance of learning personal boundaries in interactions with others. Other issues discussed were of particular relevance to adolescent girls with ASD, such as difficulties socialising with neurotypically developing girls, sex-specific puberty issues, and sexual vulnerabilities. This study highlights an important research area and is a preliminary step towards understanding the experiences of adolescent girls with ASD and their families. C1 [Cridland, Elizabeth K.; Caputi, Peter] Univ Wollongong, Sch Psychol, Wollongong, NSW, Australia. [Cridland, Elizabeth K.; Jones, Sandra C.; Caputi, Peter; Magee, Christopher A.] Univ Wollongong, Ctr Hlth Initiat, Wollongong, NSW, Australia. RP Cridland, EK (reprint author), Univ Wollongong, Sch Psychol, Wollongong, NSW, Australia. 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Albert, Chantel TI Evaluating Autism Diagnostic and Screening Tools for Cultural and Linguistic Responsiveness SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Diagnostic assessment; Screening; Diverse populations ID SPECTRUM DISORDERS; CHILDREN; IDENTIFICATION; AGE; CHECKLIST; TODDLERS; ISSUES; MODEL AB While clear guidelines and best practices exist for the assessment of autism spectrum disorders (ASD), little information is available about assessing for ASD in culturally and linguistically diverse (CLD) populations. CLD populations might be misidentified and under-identified with ASD due to the assessment practices that we employ. Four autism diagnostic tools and six autism screeners were selected and evaluated for their cultural and linguistic responsiveness. Although the evaluation of ASD within CLD populations is highly complex, this study identified the need for improved autism assessment tools and practices. 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TI Effect of Augmented Sensorimotor Input on Learning Verbal and Nonverbal Tasks Among Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Sensorimotor; Tactile-kinesthetic; PROMPT; Verbal/nonverbal learning ID OBJECT RECOGNITION; ABNORMALITIES; INTERVENTIONS; DISABILITIES; EXPLORATION; HAPTICS; MEMORY AB Thirty-four children, with autism spectrum disorders, ages 4-14 years, were matched and randomly assigned to one of two conditions for learning a novel juice-making task and producing two novel words about the event. Seventeen sighted children were manually guided to perform the task and tactually prompted during imitated productions of novel words for the event. Their matched controls heard the novel words and watched the juice-making task being performed. 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PD JUN PY 2014 VL 44 IS 6 BP 1288 EP 1302 DI 10.1007/s10803-013-1990-9 PG 15 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400003 PM 24234676 ER PT J AU El Zein, F Solis, M Vaughn, S McCulley, L AF El Zein, Farah Solis, Michael Vaughn, Sharon McCulley, Lisa TI Reading Comprehension Interventions for Students with Autism Spectrum Disorders: A Synthesis of Research SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Reading comprehension; Reading intervention; Synthesis ID HIGH-FUNCTIONING AUTISM; INTEGRATION STRATEGY; ASPERGER-SYNDROME; SCHOOL STUDENTS; SIMPLE VIEW; CHILDREN; INDIVIDUALS; INSTRUCTION; HYPERLEXIA; LANGUAGE AB The authors synthesized reading intervention studies conducted between 1980 and 2012 with K-12 students identified with autism spectrum disorders (ASD). Nine single-subject design studies, one quasi-experimental study, and two single-group design studies met the criteria for inclusion. Findings from the studies indicate that modifying instructional interventions associated with improved comprehension for students with reading difficulties may improve reading comprehension in students with ASD. Four studies implemented strategy instruction that included (a) question generation; (b) graphic organizers; and (c) making predictions. Two studies utilized anaphoric cueing instruction, three implemented explicit instruction, and three examined student grouping practices. Among the reviewed studies, the majority (n = 9) measured reading comprehension through researcher-developed probes, and two studies reported results from standardized measures. C1 [El Zein, Farah; Solis, Michael; Vaughn, Sharon; McCulley, Lisa] Univ Texas Austin, Coll Educ, Meadows Ctr Preventing Educ Risk, Austin, TX 78712 USA. RP El Zein, F (reprint author), Univ Texas Austin, Coll Educ, Meadows Ctr Preventing Educ Risk, SZB 308 A,1 Univ Stn D4900, Austin, TX 78712 USA. 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PD JUN PY 2014 VL 44 IS 6 BP 1303 EP 1322 DI 10.1007/s10803-013-1989-2 PG 20 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400004 PM 24218240 ER PT J AU Fujiwara, T AF Fujiwara, Takeo TI Socioeconomic Status and the Risk of Suspected Autism Spectrum Disorders Among 18-Month-Old Toddlers in Japan: A Population-Based Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Autism spectrum disorders; Epidemiology; Health care system; Socioeconomic status ID PERVASIVE DEVELOPMENTAL DISORDERS; SOCIAL-CLASS; MODIFIED CHECKLIST; INFANTILE-AUTISM; BIRTH COHORT; CHILDREN; CALIFORNIA; STRESS; NEURODEVELOPMENT; DIAGNOSIS AB The association between family socioeconomic status (SES) and the suspected autism spectrum disorder (ASD) status of 18-month-old toddlers was investigated using a population-based sample in Japan, which has a universal healthcare system and a mandatory health checkup system for toddlers. Questionnaires including SES measurements and modified checklist for autism in toddlers were mailed to all families with 18-month-old toddlers in Chiba, a city near Tokyo (N = 6,061; response rate: 64 %). The results of logistic regression analysis (which were adjusted for potential confounders) indicated that low maternal education, but not paternal education or family income, were associated with having suspected ASD offspring. Lower maternal education was associated with an increased risk of autistic traits in Japan. C1 Natl Res Inst Child Hlth & Dev, Dept Social Med, Setagaya Ku, Tokyo 1578535, Japan. RP Fujiwara, T (reprint author), Natl Res Inst Child Hlth & Dev, Dept Social Med, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535, Japan. 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1323 EP 1331 DI 10.1007/s10803-013-1988-3 PG 9 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400005 PM 24202730 ER PT J AU Tseng, A Bansal, R Liu, J Gerber, AJ Goh, S Posner, J Colibazzi, T Algermissen, M Chiang, IC Russell, JA Peterson, BS AF Tseng, Angela Bansal, Ravi Liu, Jun Gerber, Andrew J. Goh, Suzanne Posner, Jonathan Colibazzi, Tiziano Algermissen, Molly Chiang, I-Chin Russell, James A. Peterson, Bradley S. TI Using the Circumplex Model of Affect to Study Valence and Arousal Ratings of Emotional Faces by Children and Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Circumplex model of affect; Valence; Arousal; Autism spectrum disorders; Facial emotion ID HIGH-FUNCTIONING AUTISM; DIAGNOSTIC OBSERVATION SCHEDULE; SYSTEMS SUBSERVING VALENCE; FACIAL EXPRESSIONS; BASIC EMOTIONS; AFFECTIVE NEUROSCIENCE; ASPERGER-SYNDROME; SOCIAL-BEHAVIOR; RECOGNITION; PERCEPTION AB The Affective Circumplex Model holds that emotions can be described as linear combinations of two underlying, independent neurophysiological systems (arousal, valence). Given research suggesting individuals with autism spectrum disorders (ASD) have difficulty processing emotions, we used the circumplex model to compare how individuals with ASD and typically-developing (TD) individuals respond to facial emotions. Participants (51 ASD, 80 TD) rated facial expressions along arousal and valence dimensions; we fitted closed, smooth, 2-dimensional curves to their ratings to examine overall circumplex contours. We modeled individual and group influences on parameters describing curve contours to identify differences in dimensional effects across groups. Significant main effects of diagnosis indicated the ASD-group's ratings were constricted for the entire circumplex, suggesting range constriction across all emotions. Findings did not change when covarying for overall intelligence. C1 [Tseng, Angela; Bansal, Ravi; Liu, Jun; Gerber, Andrew J.; Goh, Suzanne; Posner, Jonathan; Colibazzi, Tiziano; Algermissen, Molly; Chiang, I-Chin; Peterson, Bradley S.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Russell, James A.] Boston Coll, Dept Psychol, Boston, MA USA. RP Tseng, A (reprint author), Columbia Univ Coll Phys & Surg, Unit 78,1051 Riverside Dr, New York, NY 10032 USA. 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1332 EP 1346 DI 10.1007/s10803-013-1993-6 PG 15 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400006 PM 24234677 ER PT J AU Wilson, BJ Manangan, CN Dauterman, HA Davis, HN AF Wilson, Beverly J. Manangan, Christen N. Dauterman, Hayley A. Davis, Heather N. TI ADHD Symptoms Moderate the Relation Between ASD Status and Internalizing Symptoms in 3-6-Year-Old Children SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Autism; ADHD; Internalizing problems; Depression; Somatization ID AUTISM SPECTRUM DISORDER; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; DEPRESSIVE SYMPTOMS; BEHAVIOR CHECKLIST; ANXIETY DISORDERS; ADOLESCENTS; CHILDHOOD; PREVALENCE; PATTERNS AB The current study sought to understand the relation between diagnostic status (autism spectrum disorders [ASD] versus typically developing) and internalizing problems in children with and without co-occurring attention deficit hyperactivity disorder (ADHD) symptoms. Participants were 88 children, ages 3:0-6:11, their parents and teachers. Findings indicated that ADHD symptoms moderated the relation between diagnostic status and depressive and somatic symptoms. 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1347 EP 1356 DI 10.1007/s10803-013-1995-4 PG 10 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400007 PM 24242972 ER PT J AU Towle, PO Vacanti-Shova, K Shah, S Higgins-D'alessandro, A AF Towle, Patricia O. Vacanti-Shova, Karyn Shah, Shristi Higgins-D'alessandro, Ann TI School-Aged Functioning of Children Diagnosed with Autism Spectrum Disorder Before Age Three: Parent-Reported Diagnostic, Adaptive, Medication, and School Placement Outcomes SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Early diagnosis; Longitudinal; School-age; School placement; Adaptive behavior; Medication use ID PERVASIVE DEVELOPMENTAL DISORDERS; FOLLOW-UP; INTERRATER RELIABILITY; EARLY INTERVENTION; YOUNG-CHILDREN; EARLY IDENTIFICATION; PRESCHOOL YEARS; DRUG-USE; STABILITY; SURVEILLANCE AB Eighty children with early autism spectrum disorder (ASD) diagnoses (under 36 months) were identified using a chart abstraction protocol applied to early intervention charts. Parents filled out questionnaires by mail when the children were school-aged (ages 6-16 years). 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1357 EP 1372 DI 10.1007/s10803-013-1997-2 PG 16 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400008 PM 24346492 ER PT J AU Sawyer, ACP Williamson, P Young, R AF Sawyer, Alyssa C. P. Williamson, Paul Young, Robyn TI Metacognitive Processes in Emotion Recognition: Are They Different in Adults with Asperger's Disorder? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger's Disorder; Emotion recognition; Metacognitive monitoring; Social skill ID AUTISM SPECTRUM DISORDERS; CHILDREN; MIND; INDIVIDUALS; METAMEMORY; MEMORY; EXPRESSIONS; COMPETENCE; ACCURACY; DEFICITS AB Deficits in emotion recognition and social interaction characterize individuals with Asperger's Disorder (AS). Moreover they also appear to be less able to accurately use confidence to gauge their emotion recognition accuracy (i.e., metacognitive monitoring). 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1373 EP 1382 DI 10.1007/s10803-013-1999-0 PG 10 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400009 PM 24272525 ER PT J AU Huang, CY Yen, HC Tseng, MH Tung, LC Chen, YD Chen, KL AF Huang, Chien-Yu Yen, Hsui-Chen Tseng, Mei-Hui Tung, Li-Chen Chen, Ying-Dar Chen, Kuan-Lin TI Impacts of Autistic Behaviors, Emotional and Behavioral Problems on Parenting Stress in Caregivers of Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic behaviors; Emotional and behavioral problems; Parenting stress; Autism ID RATING-SCALE CARS; SPECTRUM DISORDERS; CHILDHOOD AUTISM; PRESCHOOL-CHILDREN; MOTHERS; FATHERS; ASSOCIATIONS; TODDLERS AB This study examined the effects of autistic behaviors and individual emotional and behavioral problems on parenting stress in caregivers of children with autism. Caregivers were interviewed with the Childhood Autism Rating Scale and completed the Strength and Difficulties Questionnaire and the Parenting Stress Index Short Form. Results revealed that caregivers of children with mild/moderate autistic behavior problems perceived lower parenting stress than did those of children with no or severe problems. In addition, prosocial behaviors and conduct problems respectively predicted stress in the parent-child relationship and child-related stress. The findings can provide guidance in evaluations and interventions with a focus on mitigating parenting stress in caregivers of children with autism. C1 [Huang, Chien-Yu; Tseng, Mei-Hui] Natl Taiwan Univ, Coll Med, Sch Occupat Therapy, Taipei 100, Taiwan. [Yen, Hsui-Chen; Tung, Li-Chen] Chi Mei Med Ctr, Dept Phys Med & Rehabil, Tainan 710, Taiwan. [Tseng, Mei-Hui; Chen, Kuan-Lin] Natl Taiwan Univ Hosp, Dept Phys Med & Rehabil, Taipei, Taiwan. [Chen, Ying-Dar] Country Hosp, Dept Phys Med & Rehabil, Taipei 106, Taiwan. [Chen, Kuan-Lin] Natl Cheng Kung Univ, Coll Med, Sch Occupat Therapy, Tainan 701, Taiwan. RP Chen, KL (reprint author), Natl Cheng Kung Univ, Coll Med, Sch Occupat Therapy, 1 Univ Rd, Tainan 701, Taiwan. EM klchen@mail.ncku.edu.tw CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Chlebowski C, 2010, J AUTISM DEV DISORD, V40, P787, DOI 10.1007/s10803-009-0926-x Davis NO, 2008, J AUTISM DEV DISORD, V38, P1278, DOI 10.1007/s10803-007-0512-z DILALLA DL, 1994, J AUTISM DEV DISORD, V24, P115, DOI 10.1007/BF02172092 Du Yasong, 2008, Child Adolesc Psychiatry Ment Health, V2, P8, DOI 10.1186/1753-2000-2-8 Dumas J. 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PD JUN PY 2014 VL 44 IS 6 BP 1383 EP 1390 DI 10.1007/s10803-013-2000-y PG 8 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400010 PM 24287878 ER PT J AU Boulter, C Freeston, M South, M Rodgers, J AF Boulter, Christina Freeston, Mark South, Mikle Rodgers, Jacqui TI Intolerance of Uncertainty as a Framework for Understanding Anxiety in Children and Adolescents with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorders; Anxiety; Intolerance of Uncertainty; Children; Adolescents ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; GENERALIZED ANXIETY; PSYCHOMETRIC PROPERTIES; EXPERIMENTAL MANIPULATION; PSYCHOLOGICAL-RESEARCH; REPETITIVE BEHAVIOR; PROBLEM ORIENTATION; SOCIAL-ANXIETY; WORRY AB Anxiety is a problem for many children diagnosed with Autism Spectrum Disorders (ASDs). There is a paucity of models of the cognitive processes underlying this. Intolerance of Uncertainty (IU) has utility in explaining anxiety in neurotypical populations but has only recently received attention in ASD. We modelled the relationship between anxiety and IU in ASD and a typically developing comparison group, using parent and child self-report measures. Results confirmed significant relationships between IU and anxiety in children with ASD which appears to function similarly in children with and without ASD. Results were consistent with a causal model suggesting that IU mediates the relationship between ASD and anxiety. The findings confirm IU as a relevant construct in ASD. C1 [Boulter, Christina] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Boulter, Christina; Freeston, Mark] Northumberland Tyne & Wear NHS Trust, Newcastle Upon Tyne NE3 3XT, Tyne & Wear, England. [Freeston, Mark; Rodgers, Jacqui] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [South, Mikle] Brigham Young Univ, Dept Psychol & Neurosci, Provo, UT 84602 USA. RP Rodgers, J (reprint author), Newcastle Univ, Inst Neurosci, Ridley Bldg, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. 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SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Behavior rating scales; Early childhood ID DIAGNOSTIC INTERVIEW; SPECTRUM DISORDERS; CHILDREN; IDENTIFICATION; CBCL; PRESCHOOLERS; CHECKLIST; SCORES AB In order to start providing important early intervention services to preschoolers and toddlers with autism, those children first need to be identified. Despite the availability of specialized autism assessment instruments, there is a need for effective screeners at the early childhood level. Three broadband behavior rating scales were evaluated in this study to determine if any of the scales on the instruments could adequately distinguish between children with autism from other clinically referred children. There were four scales from two instruments that resulted in mean scores outside the average range and had statistically significant differences. 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PD JUN PY 2014 VL 44 IS 6 BP 1403 EP 1413 DI 10.1007/s10803-013-2004-7 PG 11 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400012 PM 24287879 ER PT J AU Gangi, DN Ibanez, LV Messinger, DS AF Gangi, Devon N. Ibanez, Lisa V. Messinger, Daniel S. TI Joint Attention Initiation With and Without Positive Affect: Risk Group Differences and Associations with ASD Symptoms SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Anticipatory smiling; High-risk siblings; Autism spectrum disorders; Initiating joint attention ID AUTISM SPECTRUM DISORDERS; NONVERBAL-COMMUNICATION; LANGUAGE-DEVELOPMENT; UNAFFECTED SIBLINGS; INFANT INTERACTION; SMILE PRODUCTION; MOTHER-INFANT; DOWN-SYNDROME; CHILDREN; ENGAGEMENT AB Infants at risk for autism spectrum disorders (ASD) may have difficulty integrating smiles into initiating joint attention (IJA) bids. A specific IJA pattern, anticipatory smiling, may communicate preexisting positive affect when an infant smiles at an object and then turns the smile toward the social partner. We compared the development of anticipatory smiling at 8, 10, and 12 months in infant siblings of children with ASD (high-risk siblings) and without ASD (low-risk siblings). High-risk siblings produced less anticipatory smiling than low-risk siblings, suggesting early differences in communicating preexisting positive affect. While early anticipatory smiling distinguished the risk groups, IJA not accompanied by smiling best predicted later severity of ASD-related behavioral characteristics among high-risk siblings. High-risk infants appear to show lower levels of motivation to share positive affect with others. However, facility with initiating joint attention in the absence of a clear index of positive affective motivation appears to be central to the prediction of ASD symptoms. C1 [Gangi, Devon N.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Ibanez, Lisa V.] Univ Washington, Dept Psychol, Autism Ctr, Seattle, WA 98195 USA. [Messinger, Daniel S.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Messinger, Daniel S.] Univ Miami, Dept Pediat, Coral Gables, FL 33146 USA. [Messinger, Daniel S.] Univ Miami, Dept Elect & Comp Engn, Coral Gables, FL 33146 USA. RP Gangi, DN (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA. 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Gorrindo, Phillip Rosenberg, Daniel Lee, Evon Batey Levitt, Pat Veenstra-VanderWeele, Jeremy TI Rigid-Compulsive Behaviors are Associated with Mixed Bowel Symptoms in Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Repetitive behavior; Constipation; Encopresis ID FUNCTIONAL GASTROINTESTINAL DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; SEROTONIN TRANSPORTER; UNITED-STATES; CHILDREN; PREVALENCE; FAMILIES; INSIGHTS; FEATURES AB Based on clinical experience, we hypothesized that rigid-compulsive behaviors are associated with severe constipation and co-occurring diarrhea or underwear staining in children with autism spectrum disorder. Using data from the Autism Treatment Network, we evaluated the association between these gastrointestinal symptoms and measures of rigid compulsive behavior in children ages 2-17. 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1433 EP 1446 DI 10.1007/s10803-013-2008-3 PG 14 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400015 PM 24305776 ER PT J AU Taylor, JL Smith, LE Mailick, MR AF Taylor, Julie Lounds Smith, Leann E. Mailick, Marsha R. TI Engagement in Vocational Activities Promotes Behavioral Development for Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Adult; Vocation; Autism symptoms; Behavior problems; Activities of daily living ID RECEPTIVE LANGUAGE DISORDER; FAMILY-LIFE-STYLES; YOUNG-ADULTS; FOLLOW-UP; HOME-ENVIRONMENT; MENTAL-HEALTH; DIAGNOSTIC INTERVIEW; EARLY-CHILDHOOD; ADOLESCENTS; CHILDREN AB This study examined the bidirectional relations over time between behavioral functioning (autism symptoms, maladaptive behaviors, activities of daily living) and vocational/educational activities of adults with autism spectrum disorders (ASD). Participants were 153 adults with ASD (M age = 30.2 years) who were part of a larger longitudinal study. Data were collected at two time points separated by 5.5 years. Cross-lag models were used, which accounted for stability over time while testing both directions of cross-lagged effects. Results suggested that greater vocational independence and engagement was related to subsequent reductions in autism symptoms and maladaptive behaviors, and improvements in activities of daily living. Relations between earlier behavioral variables (symptoms, behaviors, and activities of daily living) and later vocational independence were not statistically significant. C1 [Taylor, Julie Lounds] Vanderbilt Kennedy Ctr, Nashville, TN 37203 USA. [Taylor, Julie Lounds] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Taylor, Julie Lounds] Monroe Carell Jr Childrens Hosp Vanderbilt, Nashville, TN USA. 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PD JUN PY 2014 VL 44 IS 6 BP 1447 EP 1460 DI 10.1007/s10803-013-2010-9 PG 14 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400016 PM 24287880 ER PT J AU Horder, J Wilson, CE Mendez, MA Murphy, DG AF Horder, Jamie Wilson, C. Ellie Mendez, M. Andreina Murphy, Declan G. TI Autistic Traits and Abnormal Sensory Experiences in Adults SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Adults; Anxiety; Autism; Comorbidities; Sensory ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; ASPERGER-SYNDROME; CHILDREN; SYMPTOMS; TODDLERS; PATTERNS; ANXIETY; PROFILE; AQ AB Sensory processing abnormalities are common in autism spectrum disorders (ASD), and now form part of the Diagnostic and Statistical Manual 5th Edition (DSM-5) diagnostic criteria, but it is unclear whether they characterize the 'broader phenotype' of the disorder. We recruited adults (n = 772) with and without an ASD and administered the Autism Quotient (AQ) along with the Adult/Adolescent Sensory Profile (AASP), the Cardiff Anomalous Perceptions Scale (CAPS), and the Glasgow Sensory Questionnaire (GSQ), all questionnaire measures of abnormal sensory responsivity. Autism traits were significantly correlated with scores on all three sensory scales (AQ/GSQ r = 0.478; AQ/AASP r = 0.344; AQ/CAPS r = 0.333; all p < 0.001). This relationship was linear across the whole range of AQ scores and was true both in those with, and without, an ASD diagnosis. It survived correction for anxiety trait scores, and other potential confounds such as mental illness and migraine. C1 [Horder, Jamie; Wilson, C. Ellie; Mendez, M. Andreina; Murphy, Declan G.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London SE5 8AF, England. [Murphy, Declan G.] Kings Coll London, Inst Psychiat, Sackler Ctr Translat Neurodev, London SE5 8AF, England. RP Horder, J (reprint author), Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, De Crespigny Pk,POB 50, London SE5 8AF, England. EM jamie.horder@kcl.ac.uk CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Baker AEZ, 2008, J AUTISM DEV DISORD, V38, P867, DOI 10.1007/s10803-007-0459-0 Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 Bell V, 2006, SCHIZOPHRENIA BULL, V32, P366, DOI 10.1093/schbul/sbj014 Ben-Sasson A, 2007, AM J OCCUP THER, V61, P584 Ben-Sasson A, 2008, J CHILD PSYCHOL PSYC, V49, P817, DOI 10.1111/j.1469-7610.2008.01899.x Blakemore SJ, 2006, BRAIN COGNITION, V61, P5, DOI 10.1016/j.bandc.2005.12.013 Boyd BA, 2009, RES AUTISM SPECT DIS, V3, P959, DOI 10.1016/j.rasd.2009.05.003 Chamak B, 2008, PSYCHOTHER PSYCHOSOM, V77, P271, DOI 10.1159/000140086 Brock ME, 2012, J AUTISM DEV DISORD, V42, P2271, DOI 10.1007/s10803-012-1472-5 Brugha TS, 2011, ARCH GEN PSYCHIAT, V68, P459, DOI 10.1001/archgenpsychiatry.2011.38 Buse D. 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TI Brief Report: Arrested Development of Audiovisual Speech Perception in Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Sensory processing; Multisensory integration; Speech perception; Audiovisual; McGurk effect ID AUDITORY SPEECH; VISUAL INFLUENCES; CHILDHOOD AUTISM; SOCIAL BRAIN; CHILDREN; INTEGRATION; LANGUAGE; COMMUNICATION; RECOGNITION; ACQUISITION AB Atypical communicative abilities are a core marker of Autism Spectrum Disorders (ASD). A number of studies have shown that, in addition to auditory comprehension differences, individuals with autism frequently show atypical responses to audiovisual speech, suggesting a multisensory contribution to these communicative differences from their typically developing peers. To shed light on possible differences in the maturation of audiovisual speech integration, we tested younger (ages 6-12) and older (ages 13-18) children with and without ASD on a task indexing such multisensory integration. To do this, we used the McGurk effect, in which the pairing of incongruent auditory and visual speech tokens typically results in the perception of a fused percept distinct from the auditory and visual signals, indicative of active integration of the two channels conveying speech information. Whereas little difference was seen in audiovisual speech processing (i.e., reports of McGurk fusion) between the younger ASD and TD groups, there was a significant difference at the older ages. While TD controls exhibited an increased rate of fusion (i.e., integration) with age, children with ASD failed to show this increase. These data suggest arrested development of audiovisual speech integration in ASD. The results are discussed in light of the extant literature and necessary next steps in research. C1 [Stevenson, Ryan A.] Vanderbilt Univ, Med Ctr, Vanderbilt Brain Inst, Vanderbilt Kennedy Ctr,Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [Stevenson, Ryan A.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Siemann, Justin K.] Vanderbilt Univ, Neurosci Grad Program, Nashville, TN 37232 USA. [Woynaroski, Tiffany G.; Camarata, Stephen M.] Vanderbilt Univ, Med Ctr, Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [Schneider, Brittany C.; Eberly, Haley E.] Vanderbilt Univ, Program Neurosci, Nashville, TN 37232 USA. [Wallace, Mark T.] Vanderbilt Univ, Med Ctr, Dept Hearing & Speech Sci Psychol & Psychiat, Vanderbilt Brain Inst,Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA. RP Stevenson, RA (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Brain Inst, Vanderbilt Kennedy Ctr,Dept Hearing & Speech Sci, 7110 MRB 3 BioSci Bldg,465 21st Ave South, Nashville, TN 37232 USA. 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Autism Dev. Disord. PD JUN PY 2014 VL 44 IS 6 BP 1470 EP 1477 DI 10.1007/s10803-013-1992-7 PG 8 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400018 PM 24218241 ER PT J AU Jing, W Fang, JM AF Jing, Wei Fang, Junming TI Brief Report: Do Children with Autism Gather Information from Social Contexts to Aid Their Word Learning? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism disorder; Social contexts; Word learning; Late childhood ID ALTERNATIVE ACCOUNT; LANGUAGE; INFANTS; ABILITY AB Typically developing (TD) infants could capitalize on social eye gaze and social contexts to aid word learning. Although children with autism disorder (AD) are known to exhibit atypicality in word learning via social eye gaze, their ability to utilize social contexts for word learning is not well understood. We investigated whether verbal AD children exhibit word learning ability via social contextual cues by late childhood. 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PD JUN PY 2014 VL 44 IS 6 BP 1478 EP 1482 DI 10.1007/s10803-013-1994-5 PG 5 WC Psychology, Developmental SC Psychology GA AH7RN UT WOS:000336331400019 PM 24234720 ER PT J AU Shrestha, M Shrestha, R AF Shrestha, Merina Shrestha, Rena TI Symptom Recognition to Diagnosis of Autism in Nepal SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Early intervention; Health seeking AB Awareness and knowledge about autism is almost non-existent in Nepal. Children who eventually get the diagnosis often miss their opportunity for early intervention. The current study shows that medical help was seeked at mean age of 27.9 + 14.5 months and most of them were for delayed language and the first preference for parents were pediatricians. The mean age of diagnosis of autism was 55.6 months. The time length between help seeking to diagnosis was 29.4 months with longest time lag of 13 years. 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Hughes, Amber TI Career Development for College Students With Asperger's Syndrome SO JOURNAL OF CAREER DEVELOPMENT LA English DT Article DE Asperger's syndrome; college students; social cognitive career theory ID AUTISM SPECTRUM DISORDERS; SELF-EFFICACY BELIEFS; HIGH-SCHOOL-STUDENTS; DISABILITIES; INDIVIDUALS; CHILDREN; LIFE; ADOLESCENTS; PERSPECTIVE; PERFORMANCE AB An increasing number of students with Asperger's syndrome are entering college today. Students with Asperger's syndrome face complex symptomology such as difficulty with social skills, narrowed interests, sensory issues, and lack of self-awareness that may affect their ability to complete college and successfully enter the workforce. Career counselors could apply social cognitive career theory as an effective intervention when working with college students diagnosed with Asperger's syndrome. A case illustration is presented as an example. C1 [Mynatt, Blair Sumner; Gibbons, Melinda M.; Hughes, Amber] Univ Tennessee, Dept Educ Psychol & Counseling, Knoxville, TN 37996 USA. RP Mynatt, BS (reprint author), Univ Tennessee, Dept Educ Psychol & Counseling, 432 Claxton Complex,1122 Volunteer Blvd, Knoxville, TN 37996 USA. EM bmynatt@utk.edu CR American Psychiatric Association, 2004, DIAGN STAT MAN MENT Anderson SL, 2001, J VOCAT BEHAV, V58, P98, DOI 10.1006/jvbe.2000.1753 Bandura A., 1986, SOCIAL FDN THOUGHT A Barnhill G. 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Katusic, Slavica K. Weaver, Amy L. Matern, Dietrich Mellon, Bryan Jensen, Craig L. Barbaresi, William J. TI Dietary Docosahexaenoic Acid Supplementation in Children With Autism SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE autism; complementary and alternative therapy; dietary supplements; docosahexaenoic acid; fish oil; -3 fatty acids; pervasive developmental disorders ID ESSENTIAL FATTY-ACIDS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; GROUP RANDOMIZED-TRIALS; DOUBLE-BLIND; PSYCHOACTIVE MEDICINES; CEREBROSPINAL-FLUID; UPDATED GUIDELINES; BRAIN; SEROTONIN AB Objective:The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism.Methods:A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months.Results:A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P=0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P=0.02).Conclusions:Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size. C1 [Voigt, Robert G.; Mellon, Bryan] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA. [Mellon, Michael W.] Mayo Clin, Dept Psychol & Psychiat, Rochester, MN USA. [Katusic, Slavica K.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Weaver, Amy L.; Matern, Dietrich] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Jensen, Craig L.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Barbaresi, William J.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Voigt, RG (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Meyer Ctr Dev Pediat, 8080 North Stadium Dr,Suite 180, Houston, TX 77054 USA. EM rgvoigt@bcm.edu FU Mayo Foundation; Mead Johnson Nutritional FX The study was supported by funding from the Mayo Foundation. The DHA supplements and placebos used in this study were provided by Martek Biosciences Corporation (Columbia, MD).C.L.J. has been a consultant and has received payment for lectures and for development of educational presentations from Mead Johnson Nutritional. The other authors report no conflicts of interest. 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Pediatr. Gastroenterol. Nutr. PD JUN PY 2014 VL 58 IS 6 BP 715 EP 722 DI 10.1097/MPG.0000000000000260 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AH6SS UT WOS:000336261600016 PM 24345834 ER PT J AU Billingslea, EN Tatard-Leitman, VM Anguiano, J Jutzeler, CR Suh, J Saunders, JA Morita, S Featherstone, RE Ortinski, PI Gandal, MJ Lin, R Liang, YL Gur, RE Carlson, GC Hahn, CG Siegel, SJ AF Billingslea, Eddie N. Tatard-Leitman, Valerie M. Anguiano, Jaynie Jutzeler, Catherine R. Suh, Jimmy Saunders, John A. Morita, Susumu Featherstone, Robert E. Ortinski, Pavel I. Gandal, Michael J. Lin, Robert Liang, Yuling Gur, Raquel E. Carlson, Gregory C. Hahn, Chang-Gyu Siegel, Steven J. TI Parvalbumin Cell Ablation of NMDA-RI Causes Increased Resting Network Excitability with Associated Social and Self-Care Deficits SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID INBRED MOUSE STRAINS; SPECTRUM DISORDERS; GAMMA OSCILLATIONS; SCHIZOPHRENIA; MICE; KETAMINE; AUTISM; ANTAGONIST; RESPONSES; MODEL AB NMDA-receptor (NMDAR) hypofunction is strongly implicated in the pathophysiology of schizophrenia. Several convergent lines of evidence suggest that net excitation propagated by impaired NMDAR signaling on GABAergic intemeurons may be of particular interest in mediating several aspects of schizophrenia. However, it is unclear which behavioral domains are govrned by a net increase of excitation and whether modulating downstream GABAergic signaling can reverse neural and thus behavioral deficits. The current study determines the selective contributions of NMDAR dysfunction on PV-containing intemeurons to electrophysiological, cognitive, and negative-symptom-related behavioral phenotypes of schizophrenia using mice with a PVcre-NRI flox-driven ablation of NRI on PV-containing intemeurons. In addition, we assessed the efficacy of one agent that directly modulates GABAergic signaling (baclofen) and one agent that indirectly modifies NMDAR-mediated signaling through antagonism of mGluR5 receptors (2-methyl-6-(phenylethynyl) pyridine (MPEP)). The data indicate that loss of NMDAR function on PV intemeurons impairs self-care and sociability while increasing NI latency and baseline gamma power, and reducing induction and maintenance of long-term potentiation. Baclofen normalized baseline gamma power without corresponding effects on behavior. MPEP further increased NI latency and reduced social behavior in PVcre/ NRI +1+ mice. These two indices were negatively correlated before and following MPEP such that as NI latency increases, sociability decreases. This finding suggests a predictive role for NI latency with respect to social function. Although previous data suggest that MPEP may be beneficial for core features of autism spectrum disorders, current data suggest that such effects require intact function of NMDAR on PV interneurons. C1 [Billingslea, Eddie N.; Tatard-Leitman, Valerie M.; Anguiano, Jaynie; Jutzeler, Catherine R.; Suh, Jimmy; Saunders, John A.; Morita, Susumu; Featherstone, Robert E.; Ortinski, Pavel I.; Gandal, Michael J.; Lin, Robert; Liang, Yuling; Gur, Raquel E.; Carlson, Gregory C.; Hahn, Chang-Gyu; Siegel, Steven J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Siegel, SJ (reprint author), Univ Penn, Translat Res Labs, Room 2202,125 S 31st St, Philadelphia, PA 19104 USA. EM siegels@upenn.edu FU Developmental funds from the University of Pennsylvania; [5R01DA023210-04]; [5R01MH074672 -04]; [1P50MH096891-01]; [T32MH019112] FX Funding was provided by 5R01DA023210-04 (Siegel), 5R01MH074672 -04 (SJ Siegel), 1P50MH096891-01 (RE Gur), T32MH019112 to RE (Gur), as well as Developmental funds from the University of Pennsylvania (SJ Siegel). 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Maske, Anna R. Lynch, Gary Gall, Christine M. TI Long-Term Memory Deficits are Associated with Elevated Synaptic ERK1/2 Activation and Reversed by mGluR5 Antagonism in an Animal Model of Autism SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE BTBR; Fmrl KO; object location memory; cAMP response element binding protein (CREB); positive AMPA receptor modulator (ampakine); MPEP ID T PLUS TF/J; FRAGILE-X-SYNDROME; BTBR MOUSE MODEL; SPECTRUM DISORDERS; SOCIAL BEHAVIORS; T+TF/J MICE; PLASTICITY; ADULT; PREVALENCE; CORTEX AB A significant proportion of patients with autism exhibit some degree of intellectual disability. The BTBR T+ Itpr3(tf/)J mouse strain exhibits behaviors that align with the major diagnostic criteria of autism. To further evaluate the BTBR strain's cognitive impairments, we quantified hippocampus-dependent object location memory (OLM) and found that one-third of the BTBR mice exhibited robust memory, whereas the remainder did not Fluorescence deconvolution tomography was used to test whether synaptic levels of activated extracellular signal-regulated kinase 1/2 (ERK1/2), a protein that contributes importantly to plasticity, correlate with OLM scores in individual mice. In hippocampal field CA1, the BTBRs had fewer post-synaptic densities associated with high levels of phosphorylated (p-) ERK1/2 as compared with C57BL/6 mice. Although counts of p-ERK1/2 immunoreactive synapses did not correlate with OLM performance, the intensity of synaptic p-ERK1/2 immunolabeling was negatively correlated with OLM scores across BTBRs. Metabotropic glutamate receptor (mGluR) 5 signaling activates ERK1/2. Therefore, we tested whether treatment with the mGluR5 antagonist MPEP normalizes synaptic and learning measures in BTBR mice: MPEP facilitated OLM and decreased synaptic p-ERK1/2 immunolabeling intensity without affecting numbers of p-ERK1/2 synapses. In contrast, semi-chronic ampakine treatment, which facilitates memory in other models of cognitive impairment, had no effect on OLM in BTBRs. These results suggest that intellectual disabilities associated with different neurodevelopmental disorders on the autism spectrum require distinct therapeutic strategies based on underlying synaptic pathology. C1 [Seese, Ronald R.; Maske, Anna R.; Lynch, Gary; Gall, Christine M.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Lynch, Gary] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. [Gall, Christine M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. RP Gall, CM (reprint author), Univ Calif Irvine, Sch Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. EM cmgall@uci.edu FU National Institutes of Health [MH082042, NS04260]; UC Irvine Center for Autism Research and Treatment; NIMH predoctoral fellowship [FMH095432A]; [T32-GM0862] FX This work was supported by National Institutes of Health grants MH082042 and NS04260 and the UC Irvine Center for Autism Research and Treatment. R.R.S. was supported by grant T32-GM0862 and NIMH predoctoral fellowship FMH095432A. Drs Lynch and Gall are coauthors on patents, owned by the University of California, for the use of ampakines to support cognitive function (Lynch) and increase endogenous BDNF expression (Lynch, Gall). 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SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Theory of mind; Development; Autism spectrum disorder; Asperger's syndrome; Pervasive developmental disorder not otherwise specified; DSM ID HIGH-FUNCTIONING AUTISM; NONSPECIFIC INTELLECTUAL DISABILITIES; ASPERGER-SYNDROME; TASK-PERFORMANCE; DIAGNOSTIC-CRITERIA; NORMAL-CHILDREN; VERBAL-ABILITY; ADULTS; INDIVIDUALS; RECOGNITION AB It is unclear how theory of mind (TOM; understanding mental states and their influence on behaviour) develops in autism spectrum disorders (ASD). At least two possibilities exist: development is delayed or developmental patterns deviate from normal. We used a cross-sectional design to examine ToM skills in 4-16 year-old children. First, participants were classified in terms of the DSM-IV categories low-functioning autism (n = 21), high-functioning autism (n = 24), Asperger's syndrome (n = 21), and pervasive developmental disorder not otherwise specified (PDD-NOS; n = 20). The high-functioning autism, Asperger's syndrome and PDD-NOS groups displayed delayed ToM onset compared to a typically developing group (n = 30), but normal ToM developmental rates and sequences; supporting delayed development. ToM in low-functioning ASD fit the deviant development model: Age did not predict ToM. A second ToM model using DSM-5 ASD and verbal IQ. supported ToM development differences: Greater verbal ability was associated with increased ToM in ASD but not in typical development. As a single explanation for ToM development in ASD is insufficient, it is imperative to report specifiers such as intellectual functioning when using DSM-5 classification. DSM-IV classification contributed little to the prediction of ToM development beyond the influence of intellectual functioning. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hoogenhout, Michelle; Malcolm-Smith, Susan] Univ Cape Town, Dept Psychol, ZA-7701 Rondebosch, South Africa. 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Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 597 EP 607 DI 10.1016/j.rasd.2014.02.005 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200001 ER PT J AU Roberts, AL Koenen, KC Lyall, K Ascherio, A Weisskopf, MG AF Roberts, Andrea L. Koenen, Karestan C. Lyall, Kristen Ascherio, Alberto Weisskopf, Marc G. TI Women's posttraumatic stress symptoms and autism spectrum disorder in their children SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Posttraumatic stress disorder; Gestational effects ID CHILDHOOD GENDER NONCONFORMITY; ANTENATAL MATERNAL ANXIETY; MALE VIETNAM VETERANS; PSYCHIATRIC-DISORDERS; PARENTING STRESS; GENERAL-POPULATION; PRENATAL EXPOSURE; SOCIAL SUPPORT; ELEVATED RISK; MOTHERS AB Maternal posttraumatic stress disorder (PTSD) may be associated with autism spectrum disorder (ASD) in offspring through multiple pathways: maternal stress may affect the fetus; ASD in children may increase risk of PTSD in mothers; and the two disorders may share genetic risk. Understanding whether maternal PTSD is associated with child's ASD is important for clinicians treating children with ASD, as PTSD in parents is associated with poorer family functioning. We examined the association of maternal PTSD with offspring ASD in a large US cohort (N ASD cases = 413, N controls = 42,868). Mother's PTSD symptoms were strongly associated with child's ASD (RR 4-5 PTSD symptoms = 1.98, 95% CI = 1.39, 2.81; RR 6-7 symptoms = 2.89, 95% CI = 2.00, 4.18). Clinicians treating persons with ASD should be aware of elevated risk of PTSD in the mother. Genetic studies should investigate PTSD risk alleles in relation to ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Roberts, Andrea L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Lyall, Kristen; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lyall, Kristen] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Ascherio, Alberto; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. 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PD JUN PY 2014 VL 8 IS 6 BP 608 EP 616 DI 10.1016/j.rasd.2014.02.004 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200002 ER PT J AU Conner, CM White, SW AF Conner, Caitlin M. White, Susan W. TI Stress in mothers of children with autism: Trait mindfulness as a protective factor SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Mindfulness; Parenting; Stress ID PARENTING STRESS; PSYCHOMETRIC PROPERTIES; SPECTRUM DISORDER; PERCEIVED STRESS; SELF-REGULATION; BEHAVIOR; HEALTH; SCALE AB Mindfulness-based interventions may reduce parents' stress and improve parent-child relationships. Given the chronic nature of autism spectrum disorder (ASD) and its influence on parents' stress, interventions to promote mindfulness may be especially helpful for parents of children with ASD. Prior to undertaking intervention development, it is first necessary to establish the relationship between mindfulness and stress, as other factors like child behavioral difficulties may overshadow the mother's regulation strategies. In a sample of mothers of children with ASD (n = 67) and a comparison sample of mothers without ASD (n = 87), mindfulness was significantly associated with the level of maternal stress above and beyond child behavior problems (non-ASD: beta = -.232; F(1, 64) = 15.749, p < .000; ASD: beta = -.206; F(1, 84) = 15.576, p < .000). Results suggest that interventions to promote mindfulness may be helpful in reducing parenting stress among mothers of children with ASD, as well as mothers of typically developing children. Due to the chronic nature of ASD, such interventions may be particularly applicable. Published by Elsevier Ltd. C1 [Conner, Caitlin M.; White, Susan W.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24060 USA. 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PD JUN PY 2014 VL 8 IS 6 BP 617 EP 624 DI 10.1016/j.rasd.2014.02.001 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200003 ER PT J AU Chen, MH Su, TP Chen, YS Hsu, JW Huang, KL Chang, WH Chen, TJ Bai, YM AF Chen, Mu-Hong Su, Tung-Ping Chen, Ying-Sheue Hsu, Ju-Wei Huang, Kai-Lin Chang, Wen-Han Chen, Tzeng-Ji Bai, Ya-Mei TI Is neonatal jaundice associated with autism spectrum disorder, attention deficit hyperactivity disorder, and other psychological development? A nationwide prospective study SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Neonatal jaundice; ASD; ADHD; Developmental delay ID DEVELOPMENT CLINICAL-TRIAL; BRAIN-STEM RESPONSES; LOW-BIRTH-WEIGHT; FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; INFANTILE-AUTISM; CHILD-HEALTH; HYPERBILIRUBINEMIA; RISK; BILIRUBIN AB Neonatal jaundice may cause the lifelong sequelae of central nerve system developmental disorders. However, the results are inconsistent. 2016 newborns with neonatal jaundice and 8064 age-/gender-matched (1:4) controls were enrolled during 1999-2000. Participants of autistic spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and other developmental disorders that occurred during the follow-up were identified. Newborns with neonatal jaundice had increased risks of developing ASD (hazard ratio [HR]: 1.75,95% confidence interval [CI]: 1.05-2.90), any developmental delay (HR: 1.27,95% Cl: 1.02-1.58), and developmental speech or language disorder (HR: 1.41, 95% Cl: 1.11-1.79). Newborn exposure to hyperbilirubinemia was related to the increased risk of developing ASD, any developmental delay, and developmental speech or language disorder in later life. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Bai, Ya-Mei] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan. [Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Bai, Ya-Mei] Natl Yang Ming Univ, Coll Med, Dept Psychiat, Taipei 112, Taiwan. [Chen, Tzeng-Ji] Taipei Vet Gen Hosp, Dept Family Med, Taipei, Taiwan. [Su, Tung-Ping] Natl Yang Ming Univ, Inst Brain Sci, Taipei 112, Taiwan. 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Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 625 EP 632 DI 10.1016/j.rasd.2014.03.006 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200004 ER PT J AU Reszka, SS Hume, KA Sperry, L Boyd, BA McBee, MT AF Reszka, Stephanie S. Hume, Kara A. Sperry, Laurie Boyd, Brian A. McBee, Matthew T. TI The Classroom Practice Inventory: Psychometric evaluation of a rating scale of intervention practices for children with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Classroom practices; Psychometric evaluation; Eclectic; Autism; Intervention ID COMPREHENSIVE TREATMENT MODELS; YOUNG-CHILDREN; ASD; IMPLEMENTATION; RELIABILITY; PROGRAMS; FIDELITY; OUTCOMES; SCHOOL; LEAP AB The Classroom Practice Inventory (CPI) was developed as a tool to provide descriptive information about the practices used in classrooms to address the developmental needs of children with autism spectrum disorder (ASD). Data from a multi-site study examining the outcomes for preschool students with ASD served in three types of classroom models indicate that the CPI produces reliable and valid assessments of practices used in classrooms. Items on the CPI can be used to discriminate among classroom models and can be used to provide descriptive information about classrooms following a prescribed comprehensive treatment model as well as those providing an eclectic model of services. Implications for the future use of the CPI are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Reszka, Stephanie S.; Hume, Kara A.; Boyd, Brian A.] Univ N Carolina, Chapel Hill, NC USA. [Sperry, Laurie] Regis Univ, Denver, CO USA. [McBee, Matthew T.] E Tennessee State Univ, Johnson City, TN 37614 USA. RP Reszka, SS (reprint author), UNC CH Allied Hlth Sci, 321 S Columbia St,Bondurant Hall CB 7122, Chapel Hill, NC 27599 USA. 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PD JUN PY 2014 VL 8 IS 6 BP 633 EP 643 DI 10.1016/j.rasd.2014.02.003 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200005 ER PT J AU Erstenyuk, V Swanson, MR Siller, M AF Erstenyuk, Valentyna Swanson, Meghan R. Siller, Michael TI Pupillary responses during a joint attention task are associated with nonverbal cognitive abilities and sub-clinical symptoms of autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorder; Pupil; Joint attention; Gaze following; Intelligence; Broad autism phenotype ID TYPICALLY DEVELOPING-CHILDREN; EYE-TRACKING MEASURE; INDIVIDUAL-DIFFERENCES; 6-MONTH-OLDS; INTELLIGENCE; PERFORMANCE; SENTENCES; LANGUAGE; BEHAVIOR; INFANTS AB Measures of pupillary dilation provide a temporally sensitive, quantitative indicator of cognitive resource allocation. The current study included 39 typically developing children between 3 and 9 years of age. Children completed a free-viewing task designed to elicit gaze following, a core deficit of Autism Spectrum Disorders (ASD). Results revealed a negative association between children's pupil dilation and a standardized measure of nonverbal intelligence, suggesting that children with lower intelligence allocated more cognitive resources than children with higher intelligence. In addition, the results revealed a negative association between pupil dilation and a parent-report measure of sub-clinical symptoms of ASD, suggesting that children with fewer ASD-related symptoms allocated more cognitive resources than children who showed more sub-clinical symptoms of ASD. Both associations were independent of each other and could not be explained by variation in chronological age. These findings extend previous research demonstrating associations between basic aspects of visual processing and intelligence. 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Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 644 EP 653 DI 10.1016/j.rasd.2014.03.003 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200006 ER PT J AU Yi, L Fan, YB Joseph, L Huang, D Wang, XQ Li, J Zou, XB AF Yi, Li Fan, Yuebo Joseph, Lisa Huang, Dan Wang, Xueqin Li, Jiao Zou, Xiaobing TI Event-based prospective memory in children with autism spectrum disorder: The role of executive function SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Prospective memory; Autism spectrum disorder; Executive function; Working memory; Inhibitory control; Event-based prospective memory ID INTELLIGENCE; PERFORMANCE; VERSION; TASKS AB The present study investigated event-based prospective memory (PM) and its cognitive correlates in children with autism spectrum disorder (ASD) compared to age- and ability-matched typically developing (TD) peers. Participants included 25 children with ASD, 25 age-matched TO peers, and 28 ability-matched TO peers. Participants completed one PM task, and several executive functioning tasks assessing working memory (Block Recall Task), inhibitory control (Stroop Task), and cognitive flexibility (Dimensional Change Card Sorting Task). Results indicated that children with ASD had significantly lower scores on the PM task than children in the TD groups. Additionally, PM performance of children with ASD was significantly predicted by their nonverbal IQ, whereas PM performance of TO children was significantly predicted by their inhibitory control. These results provide evidence for the PM deficit in children with ASD and the effect of cognitive functioning, rather than a specific aspect of executive function, on the development of PM. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Yi, Li; Joseph, Lisa; Li, Jiao] Sun Yat Sen Univ, Dept Psychol, Guangzhou 510275, Guangdong, Peoples R China. [Fan, Yuebo; Huang, Dan] Guangzhou Cana Sch, Guangzhou, Guangdong, Peoples R China. [Fan, Yuebo; Huang, Dan] Guangzhou Rehabil & Res Ctr Children ASD, Guangzhou, Guangdong, Peoples R China. [Wang, Xueqin] Sun Yat Sen Univ, Sch Math & Computat Sci, Dept Stat Sci, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Xueqin] Sun Yat Sen Univ, Southern China Res Ctr Stat Sci, Guangzhou 510275, Guangdong, Peoples R China. [Zou, Xiaobing] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China. RP Yi, L (reprint author), Sun Yat Sen Univ, Dept Psychol, 135 Xingang West Rd, Guangzhou 510275, Guangdong, Peoples R China. 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PD JUN PY 2014 VL 8 IS 6 BP 654 EP 660 DI 10.1016/j.rasd.2014.03.005 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200007 ER PT J AU Salomone, E Kutlu, B Derbyshire, K McCloy, C Hastings, RP Howlin, P Charman, T AF Salomone, Erica Kutlu, Besterah Derbyshire, Kayleigh McCloy, Carlye Hastings, Richard P. Howlin, Patricia Charman, Tony TI Emotional and behavioural problems in children and young people with autism spectrum disorder in specialist autism schools SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Mental health; Emotional and behavioural problems; CAMHS; Service use ID MENTAL-HEALTH PROBLEMS; DIFFICULTIES QUESTIONNAIRE; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; AGE-CHILDREN; PDD-NOS; ADOLESCENTS; STRENGTHS; IMPACT AB We investigated emotional and behavioural problems in a sample (N = 615) of children and young people with autism spectrum disorders (ASD), most of whom also had intellectual disability (ID), attending specialist autism schools. High rates of parent- and teacher-reported problems were recorded. Teacher-reported levels of hyperactivity were higher in younger children. Teacher- but not parent-reported levels of conduct problems and hyperactivity were highest in children without phrase speech. 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Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 661 EP 668 DI 10.1016/j.rasd.2014.03.004 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200008 ER PT J AU Radley, KC O'Handley, RD Ness, EJ Ford, WB Battaglia, AA McHugh, MB McLemore, CE AF Radley, Keith C. O'Handley, Roderick D. Ness, Emily J. Ford, W. Blake Battaglia, Allison A. McHugh, Melissa B. McLemore, Chandler E. TI Promoting social skill use and generalization in children with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Social skills; Generalization; Intervention ID INTERVENTIONS; BEHAVIOR; METAANALYSIS; SCHOOL AB Social skills training is a frequently utilized intervention for addressing social deficits of children with autism spectrum disorder (ASD). The current study investigated the effects of the Superheroes Social Skills program, a social skills training program consisting of multiple evidence-based practices, in promoting accurate demonstration of target social skills in both a training and generalized setting. Three children with ASD between the ages of 10 and 14 attended 10 social skills training sessions over five weeks, with social skills lessons targeting participation, conversation, perspective taking, and problem solving skills. A multiple probe design across behaviors and replicated across participants was utilized to evaluate accurate demonstration of target social skills. Results suggest improvement in skill accuracy in both the training and generalization settings. Indirect secondary measures of participant social functioning and parental stress were also collected and suggest improvements associated with social skills training. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Radley, Keith C.; O'Handley, Roderick D.; Ness, Emily J.; Ford, W. Blake; Battaglia, Allison A.; McHugh, Melissa B.; McLemore, Chandler E.] Univ So Mississippi, Dept Psychol, Hattiesburg, MS 39406 USA. RP Radley, KC (reprint author), Univ So Mississippi, Dept Psychol, 118 Coll Dr 5025, Hattiesburg, MS 39406 USA. 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Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 669 EP 680 DI 10.1016/j.rasd.2014.03.012 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200009 ER PT J AU Chan, AS Sze, SL Han, YMY AF Chan, Agnes S. Sze, Sophia L. Han, Yvonne M. Y. TI An intranasal herbal medicine improves executive functions and activates the underlying neural network in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Herbal medicine; Executive functions; EEG; Prefrontal; Anterior cingulate ID INFERIOR FRONTAL-CORTEX; SPECTRUM DISORDERS; RESPONSE-INHIBITION; ANTERIOR CINGULATE; RECTAL DIAZEPAM; OXYTOCIN; ATTENTION; BORNEOL; BRAIN; INTERVENTIONS AB Our animal and human studies have provided empirical evidence that a patented intranasal herbal medicine alters brain functions and neurophysiology. In particular, it reduces clinical symptoms and immunological anomalies in children with autism spectrum disorders (ASD). The present study explored whether the herbal formula can improve executive functions and the associated neuroelectrophysiological activity in ASD. Thirty children with ASD were evenly assigned to receive a daily intranasal administration of the herbal formula or no treatment. Their executive functions, behavioral problems, and electroencephalographic activity during an executive control task were measured before and after six months of treatment with the herbal formula. After treatment, the experimental group showed significantly improved inhibitory control, mental flexibility, and planning, which coincided with an event-related elevation in the activity of their prefrontal and anterior cingulate cortices (regions that are critical for executive control of behaviors) as well as reduced daily dysexecutive behaviors. In contrast, the control group showed no significant changes in executive functions or neural system activity. These findings support the administration of the intranasal herbal medicine as a possible intervention for improving executive functions in ASD. 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). C1 [Chan, Agnes S.; Sze, Sophia L.] Chinese Univ Hong Kong, Dept Psychol, Neuropsychol Lab, Shatin, Hong Kong, Peoples R China. [Chan, Agnes S.; Sze, Sophia L.] Chinese Univ Hong Kong, Chanwuyi Res Ctr Neuropsychol Well Being, Shatin, Hong Kong, Peoples R China. [Chan, Agnes S.] Henan Songshan Res Inst Chanwuyi, Chanwuyi 452470, Henan, Peoples R China. [Han, Yvonne M. Y.] Hong Kong Inst Educ, Dept Special Educ & Counselling, Tai Po, Hong Kong, Peoples R China. RP Chan, AS (reprint author), Chinese Univ Hong Kong, Dept Psychol, Shatin, Hong Kong, Peoples R China. 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H., 2014, CLIN INTERV IN PRESS NR 73 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 681 EP 691 DI 10.1016/j.rasd.2014.03.007 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200010 ER PT J AU Lin, JD Lin, LP Su, SF Hsu, SW Chou, YC Lin, FG Loh, CH Wu, JL Chu, CM AF Lin, Jin-Ding Lin, Lan-Ping Su, Sheng-Fang Hsu, Shang-Wei Chou, Yu-Ching Lin, Fu-Gong Loh, Ching-Hui Wu, Jia-Ling Chu, Cordia M. TI The interference of low back pain on everyday functions of life in care workers for persons with intellectual, autistic, and associated multiple disabilities: The Brief Pain Inventory short form (BPI-SF) survey SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Intellectual disability; Autism; Low back pain; Life interference; FACES pain rating scale; BPI-SF ID QUALITY-OF-LIFE; NECK PAIN; INSTITUTIONAL CAREGIVERS; SLEEP DISTURBANCE; STAFF WORKING; HEALTH; PEOPLE; ADULTS; PREVALENCE; RISK AB Low back pain is a critical public health problem; this condition significantly affects the quality of life and has a major socioeconomic impact. The present study aimed to investigate the interference of low back pain with everyday functions of life in disability care workers, and to examine the influencing factors of the interference, such as workers' demographic, lifestyle habits, self-reported health status, working conditions and previous pain experience. The Wong-Baker FACES Pain Rating Scale and Brief Pain Inventory Short Form were used to identify the pain severity and life interference of 677 participants who had experienced low back pain conditions in the previous year. The results indicated that the mean score of the pain severity was 3.78 +/- 1.82, 78.9% subjects experienced mild pain (score 2-4), 13.7% subjects experienced moderate pain, and 5.3% subjects experienced severe pain. More than twenty percent of the respondents reported that low back pain moderately or severely interfered with their daily functions. Many working conditions and pain experienced significantly correlated with the score of pain interference in the care workers after controlling for factors of healthy lifestyle and health status (R-2 = 41.7%). These findings may garner attention from health welfare authorities and lead to improvements in health promotion initiatives to prevent low back pain from interfering with the daily activities of care workers for people with intellectual, autistic and associated disabilities. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lin, Jin-Ding; Lin, Lan-Ping; Su, Sheng-Fang; Chou, Yu-Ching; Lin, Fu-Gong; Chu, Cordia M.] Natl Def Med Ctr, Sch Publ Hlth, Taipei 114, Taiwan. [Lin, Jin-Ding; Wu, Jia-Ling] Chung Hua Fdn Persons Intellectual Disabil, New Taipei City, Taiwan. [Lin, Jin-Ding; Chu, Cordia M.] Griffith Univ, Ctr Environm & Populat Hlth, Brisbane, Qld 4111, Australia. [Hsu, Shang-Wei] Asia Univ, Dept Healthcare Adm, Taichung, Taiwan. [Hsu, Shang-Wei] China Med Univ, Dept Publ Hlth, Taichung, Taiwan. [Loh, Ching-Hui] Taichung Armed Forces Gen Hosp, Taichung, Taiwan. RP Lin, JD (reprint author), Natl Def Med Ctr, Sch Publ Hlth, 161,Minquan E Rd,Sect 6, Taipei 114, Taiwan. 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Maljaars, Jarymke Le Couteur, Ann Gould, Judith Wing, Lorna Noens, Ilse Van Berckelaer-Onnes, Ina Leekam, Susan R. TI DSM-5 Autism Spectrum Disorder: In search of essential behaviours for diagnosis SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; DSM-5; Abbreviated; Diagnosis; DISCO ID PERVASIVE DEVELOPMENTAL DISORDERS; COMMUNICATION DISORDERS; IV-TR; SHORT-FORM; CRITERIA; INTERVIEW; CHILDREN; SPECIFICITY; SENSITIVITY; VALIDATION AB The objective of this study was to identify a set of 'essential' behaviours sufficient for diagnosis of DSM-5 Autism Spectrum Disorder (ASD). Highly discriminating, 'essential' behaviours were identified from the published DSM-5 algorithm developed for the Diagnostic Interview for Social and Communication Disorders (DISCO). Study 1 identified a reduced item set (48 items) with good predictive validity (as measured using receiver operating characteristic curves) that represented all symptom sub-domains described in the DSM-5 ASD criteria but lacked sensitivity for individuals with higher ability. An adjusted essential item set (54 items; Study 2) had good sensitivity when applied to individuals with higher ability and performance was comparable to the published full DISCO DSM-5 algorithm. Investigation at the item level revealed that the most highly discriminating items predominantly measured social-communication behaviours. This work represents a first attempt to derive a reduced set of behaviours for DSM-5 directly from an existing standardised ASD developmental history interview and has implications for the use of DSM-5 criteria for clinical and research practice. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). C1 [Carrington, Sarah J.; Kent, Rachel G.; Leekam, Susan R.] Cardiff Univ, Sch Psychol, Wales Autism Res Ctr, Cardiff CF10 3AX, S Glam, Wales. [Maljaars, Jarymke; Noens, Ilse] Univ Leuven KU Leuven, Louvain, Belgium. [Maljaars, Jarymke; Van Berckelaer-Onnes, Ina] Leiden Univ, NL-2300 RA Leiden, Netherlands. [Le Couteur, Ann] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Gould, Judith; Wing, Lorna] Natl Autist Soc, Lorna Wing Ctr, Bromley, England. RP Carrington, SJ (reprint author), Sch Psychol, Wales Autism Res Ctr, Tower Bldg,Pk Pl, Cardiff CF10 3AT, S Glam, Wales. 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PD JUN PY 2014 VL 8 IS 6 BP 701 EP 715 DI 10.1016/j.rasd.2014.03.017 PG 15 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200012 ER PT J AU Boonen, H Maljaars, J Lambrechts, G Zink, I Van Leeuwen, K Noens, I AF Boonen, Hannah Maljaars, Jarymke Lambrechts, Greet Zink, Inge Van Leeuwen, Karla Noens, Ilse TI Behavior problems among school-aged children with autism spectrum disorder: Associations with children's communication difficulties and parenting behaviors SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Externalizing behavior problems; Internalizing behavior problems; Communication difficulties; Parenting behaviors ID EMOTIONAL-PROBLEMS; PSYCHOMETRIC PROPERTIES; CONDUCT PROBLEMS; EARLY-CHILDHOOD; MENTAL-HEALTH; STRESS; QUESTIONNAIRE; STRENGTHS; LANGUAGE; ADOLESCENTS AB Research has clearly demonstrated that behavior problems are common among children with ASD. These co-occurring behavior problems place children with ASD and their families at risk for a range of negative outcomes. This questionnaire study aimed to investigate whether and how age, gender, and communication difficulties at the child level and parenting behaviors at the family level are associated with externalizing and internalizing problems among children with ASD (n = 206) and without ASD (n = 187) aged 6-12 years. Results indicated that pragmatic language difficulties of the child and negative controlling parenting behaviors both made a significant and unique contribution to externalizing behavior problems for the ASD group. In the control group, chronological age and pragmatic language difficulties were the most robust concurrent predictors of externalizing problems. With regard to internalizing problems, pragmatic language difficulties and ASD adapted parenting behaviors were significant predictors for both the ASD and control group. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Boonen, Hannah; Maljaars, Jarymke; Lambrechts, Greet; Van Leeuwen, Karla; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, B-3000 Louvain, Belgium. [Boonen, Hannah; Maljaars, Jarymke; Lambrechts, Greet; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res, B-3000 Louvain, Belgium. [Zink, Inge] Katholieke Univ Leuven, Dept Neurosci, ExpORL, B-3000 Louvain, Belgium. RP Boonen, H (reprint author), Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leopold Vanderkelesntr 32,Box 3765, B-3000 Louvain, Belgium. EM Hannah.Boonen@ppw.kuleuven.be CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Barber Brian K, 2005, Monogr Soc Res Child Dev, V70, P1 Bauminger N, 2010, AUTISM RES, V3, P101, DOI 10.1002/aur.131 Bishop D. V. 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C., 1999, FUNCTIONAL ANAL PROB Sikora D, 2013, RES AUTISM SPECT DIS, V7, P307, DOI 10.1016/j.rasd.2012.09.006 Smith CL, 2004, DEV PSYCHOL, V40, P29, DOI 10.1037/0012-1649.40.1.29 Taylor JL, 2011, J AUTISM DEV DISORD, V41, P566, DOI 10.1007/s10803-010-1070-3 Tomanik S, 2004, J INTELLECT DEV DIS, V29, P16, DOI 10.1080/13668250410001662892 Tremblay RE, 2000, INT J BEHAV DEV, V24, P129 Van Leeuwen KG, 2004, EUR J PSYCHOL ASSESS, V20, P283, DOI 10.1027/1015-5759.20.4.283 Vermulst A., 2010, HANDLEIDING BI UNPUB Wood JJ, 2003, J CHILD PSYCHOL PSYC, V44, P134, DOI 10.1111/1469-7610.00106 NR 60 TC 2 Z9 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUN PY 2014 VL 8 IS 6 BP 716 EP 725 DI 10.1016/j.rasd.2014.03.008 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200013 ER PT J AU Tzanakaki, P Grindle, CF Dungait, S Hulson-Jones, A Saville, M Hughes, JC Hastings, RP AF Tzanakaki, Pagona Grindle, Corinna F. Dungait, Sarah Hulson-Jones, Amy Saville, Maria Hughes, J. Carl Hastings, Richard P. TI Use of a tactile prompt to increase social initiations in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Social interaction; Initiations ID INTERVENTION; PRESCHOOLERS; TEENAGERS; STUDENTS; SKILLS; PEERS AB Making appropriate verbal initiations to others is an aspect of social interaction that can be problematic for individuals with autism. A variety of teaching and prompting methods have been developed to address the issue including the use of a tactile prompt, a small device that can fit in the participant's pocket and can be programmed to vibrate at regular intervals. Our aim was to extend the existing research on the use of the tactile prompt by incorporating reinforcement during intervention and attempting a systematic fading of the prompt. Three children with autism participated in Study 1 and two children in Study 2. In both studies, the intervention was conducted during free-play activities with mainstream peers. Results indicated that the participants' verbal initiations to their peers increased in comparison to baseline. Additionally in Study 2, the use of both the tactile prompt and the prosthetic reinforcement were successfully faded. Implications regarding the use of covert prompting methods to help individuals with autism in the area of social interactions are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tzanakaki, Pagona; Grindle, Corinna F.; Dungait, Sarah; Hulson-Jones, Amy; Saville, Maria; Hughes, J. Carl; Hastings, Richard P.] Bangor Univ, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales. RP Tzanakaki, P (reprint author), 11 Nafpliou Str, Athens 13461, Greece. EM pagonatzanakaki@hotmail.com RI Hastings, Richard/D-9657-2013 OI Hastings, Richard/0000-0002-0495-8270 CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT, V5 Anglesea MM, 2008, J APPL BEHAV ANAL, V41, P107, DOI 10.1901/jaba.2008.41-107 Anson HM, 2008, BEHAV RES METHODS, V40, P1106, DOI 10.3758/BRM.40.4.1106 Cooper J. O., 2007, APPL BEHAV ANAL GREENWOOD C R, 1981, Journal of Pediatric Psychology, V6, P343, DOI 10.1093/jpepsy/6.4.343 Grindle C. 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PD JUN PY 2014 VL 8 IS 6 BP 726 EP 736 DI 10.1016/j.rasd.2014.03.016 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AH4PT UT WOS:000336111200014 ER PT J AU Malakar, S Bhattacharya, S AF Malakar, S. Bhattacharya, S. TI MINDING THE GREENS: ROLE OF DIETARY SALICYLATES IN COMMON BEHAVIOURAL HEALTH CONDITIONS SO ACTA ALIMENTARIA LA English DT Article DE naturally occurring salicylates; diet; ADHD; autism; depression; schizophrenia ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; DOUBLE-BLIND; CLINICAL PHARMACOKINETICS; FEINGOLD HYPOTHESIS; CONTROLLED-TRIAL; FOOD-ADDITIVES; FATTY-ACIDS; CHILDREN; SCHIZOPHRENIA AB The role of artificial food additives and food chemicals in abetting certain behavioural conditions has been the subject of behavioural nutrition research over several decades. However, a few studies have also raised questions regarding a similar role possibly played by naturally occurring phytochemicals in general and salicylates in particular. Such studies have, however, been rather few and far between. More importantly, till date, there has been no attempt to collate the findings from the few studies that have been carried out at different points in time by different researchers across different countries and cultures. This gap in the extant body of knowledge is made especially prominent by the fact that naturally occurring salicylates abound in many green vegetables and fruit, which are common constituents of a healthy diet. The aim of this review article is two-fold - firstly, to collate and present the related researches on the effects of salicylates in general and natural salicylates in particular on mental health; and secondly, to identify promising research directions for the future. 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TI Post-transcriptional regulation of the creatine transporter gene: Functional relevance of alternative splicing SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Na+ /Cl- cotransporter; Creatine transporter; Alternative splicing; Creatine uptake upregulation; Intellectual disability ID UBIQUITIN LIGASE NEDD4-2; EPITHELIAL NA+ CHANNEL; NEUROTRANSMITTER TRANSPORTERS; MESSENGER-RNA; INBORN ERROR; KINASES SGK1; SERUM; RAT; SUPPLEMENTATION; DEFICIENCY AB Background: Aberrations in about 10-15% of X-chromosome genes account for intellectual disability (ID); with a prevalence of 1-3% (Gecz et al., 2009 [1]). The SLC6A8 gene, mapped to Xq28, encodes the creatine transporter (CTR1). Mutations in SLC6A8, and the ensuing decrease in brain creatine, lead to co-occurrence of speech/language delay, autism-like behaviors and epilepsy with ID. A splice variant of SLC6A8-SLC6A8C, containing intron 4 and exons 5-13, was identified. Herein, we report the identification of a novel variant SLC6A8D, and functional relevance of these isoforms. Methods: Via (quantitative) RT-PCR, uptake assays, and confocal microscopy, we investigated their expression and function vis-a-vis creatine transport. Results: SLC6A8D is homologous to SLC6A8C except for a deletion of exon 9 (without occurrence of a frame shift). Both contain an open reading frame encoding a truncated protein but otherwise identical to CTR1. Like SLC6A8, both variants are predominantly expressed in tissues with high energy requirement. Our experiments reveal that these truncated isoforms do not transport creatine. However, in SLC6A8 (CTR1)-overexpressing cells, a subsequent infection (transduction) with viral constructs encoding either the SLC6A8C (CTR4) or SLC6A8D (CfR5) isoform resulted in a significant increase in creatine accumulation compared to C1'R1 cells re-infected with viral constructs containing the empty vector. Moreover, transient transfection of CTR4 or C1'R5 into HEK293 cells resulted in significantly higher creatine uptake. Conclusions: CTR4 and CTR5 are possible regulators of the creatine transporter since their overexpression results in upregulated CTR1 protein and creatine uptake. General significance: Provides added insight into the mechanism(s) of creatine transport regulation. (c) 2014 Elsevier B.V. All rights reserved. C1 [Ndika, Joseph D. T.; Martinez-Munoz, Cristina; Anand, Nandaja; van Dooren, Silvy J. M.; Kanhai, Warsha; Smith, Desiree E. C.; Jakobs, Cornelis; Salomons, Gajja S.] Vrije Univ Amsterdam, Med Ctr, Metab Unit, Dept Clin Chem, Amsterdam, Netherlands. [Ndika, Joseph D. T.; Salomons, Gajja S.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Salomons, Gajja S.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. RP Salomons, GS (reprint author), Metabool Lab, PK 1X 009,Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. 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Biophys. Acta-Gen. Subj. PD JUN PY 2014 VL 1840 IS 6 BP 2070 EP 2079 DI 10.1016/j.bbagen.2014.02.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AH3GW UT WOS:000336012700048 PM 24561156 ER PT J AU Schwarzkopf, S Schilbach, L Vogeley, K Timmermans, B AF Schwarzkopf, Sarah Schilbach, Leonhard Vogeley, Kai Timmermans, Bert TI "Making it explicit" makes a difference: Evidence for a dissociation of spontaneous and intentional level 1 perspective taking in high-functioning autism SO COGNITION LA English DT Article DE Visuospatial level 1 perspective taking; High-functioning autism; Asperger syndrome; Attention shift; Implicit processing ID ASPERGER-SYNDROME; SPECTRUM DISORDER; VISUAL-PERCEPTION; FALSE BELIEF; ATTENTION; ADULTS; CHILDREN; OTHERS; SELF; REPRESENTATION AB The ability of perspective taking is a fundamental aspect of social cognition. The ability to decide, what another person can or cannot see is referred to as "level 1 perspective taking." This is thought to be a process that we can make use of intentionally, but which also takes place spontaneously. Autism is characterized by impairments of social interaction, which are thought to be related to deficits in implicit rather than explicit perspective taking. In order to assess both levels of processing with regard to perspective taking, we employed an established task in patients and controls. Our results demonstrate that both groups engage in spontaneous level 1 perspective taking. In contrast to controls, however, patients reacted more slowly if they had to verify the other's as compared to their own perspective, which shows that participants with high-functioning autism have selective difficulties in explicit, but not implicit, level 1 perspective taking. 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However, whether this confirmed finding has an equivalent in the auditory modality is still unknown. To fill this gap, 18 autistics and 18 typical participants completed a melodic decision task where global and local level information can be congruent or incongruent. While focusing either on the global (melody) or local level (group of notes) of hierarchical auditory stimuli, participants have to decide whether the focused level is rising or falling. Autistics showed intact global processing, a superior performance when processing local elements and a reduced global-to-local interference compared to typical participants. These results are the first to demonstrate that autistic processing of auditory hierarchical stimuli closely parallels processing of visual hierarchical stimuli. When analyzing complex auditory information, autistic participants present a local bias and a more autonomous local processing, but not to the detriment of global processing. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bouvet, Lucie; Paignon, Adeline; Donnadieu, Sophie] CNRS, Lab Psychol & Neurocognit, UMR 5105, Grenoble, France. [Bouvet, Lucie] Univ Lille 3, Lab Neurosci Fonct & Pathol, UFR Psychol, Villeneuve Dascq, France. [Simard-Meilleur, Andree-Anne; Mottron, Laurent] Hop Riviere des Prairies, CETEDUM, Montreal, PQ, Canada. [Simard-Meilleur, Andree-Anne; Mottron, Laurent] Dept Psychiat, Montreal, PQ, Canada. [Paignon, Adeline; Donnadieu, Sophie] Univ Savoie, Chambery, France. RP Bouvet, L (reprint author), Univ Lille Nord France, Lab Neurosci Fonct & Pathol, Lille, France. 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T., 1983, STOCHASTIC MODELLING Wang LX, 2007, COGN NEUROPSYCHOL, V24, P550, DOI 10.1080/13546800701417096 White SJ, 2011, J AUTISM DEV DISORD, V41, P1565, DOI 10.1007/s10803-011-1182-4 NR 45 TC 3 Z9 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 EI 1873-7838 J9 COGNITION JI Cognition PD JUN PY 2014 VL 131 IS 3 BP 367 EP 372 DI 10.1016/j.cognition.2014.02.006 PG 6 WC Psychology, Experimental SC Psychology GA AH3FG UT WOS:000336008500005 PM 24637103 ER PT J AU Cote, DL Jones, VL Barnett, C Pavelek, K Nguyen, H Sparks, SL AF Cote, Debra L. Jones, Vita L. Barnett, Crystal Pavelek, Karin Nguyen, Hoang Sparks, Shannon L. TI Teaching Problem Solving Skills to Elementary Age Students with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SELF-DETERMINATION; DEVELOPMENTAL-DISABILITIES; GENERAL CURRICULUM; LEARNING-MODEL; MODERATE; INSTRUCTION AB Students with disabilities need problem-solving skills to promote their success in solving the problems of daily life. The research into problem-solving instruction has been limited for students with autism. Using a problem-solving intervention and the Self Determined Learning Model of Instruction, three elementary age students with autism were taught to set personal goals related to their academic achievement, identify problems, and self-evaluate their problems-solving skills. A multiple-probe design was used, and data suggested that all students achieved and maintained their self-set goals. C1 [Cote, Debra L.; Jones, Vita L.; Barnett, Crystal; Pavelek, Karin; Nguyen, Hoang] Calif State Univ Fullerton, Fullerton, CA 92834 USA. [Sparks, Shannon L.] Univ Nevada, Las Vegas, NV 89154 USA. RP Cote, DL (reprint author), Calif State Univ Fullerton, Dept Special Educ, Coll Pk 570,POB 6868, Fullerton, CA 92834 USA. EM dcote@fullerton.edu CR Agran M, 2006, RES PRACT PERS SEV D, V31, P230 Agran M, 2002, REM SPEC EDUC, V23, P279, DOI 10.1177/07419325020230050301 Agran M., 2005, MENTAL RETARDATION I, P255 Agran M, 2001, RES DEV DISABIL, V22, P319, DOI 10.1016/S0891-4222(01)00075-0 Alderson-Day B., 2010, J AUTISM DEV DISORD, V41, P555 Bicard S. C., 2010, MEASURING BEHAV Cole B., 1986, PRINCESS SMARTYPANTS Cote D, 2010, EDUC TRAIN AUTISM DE, V45, P512 Cote D. L., 2009, THESIS U NEVADA LAS Cote DL, 2011, INTERV SCH CLIN, V46, P259, DOI 10.1177/1053451210395387 Friend M., 2011, SPECIAL ED CONTEMPOR Glago K, 2009, REM SPEC EDUC, V30, P372, DOI 10.1177/0741932508324394 Glago K. 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PD JUN PY 2014 VL 49 IS 2 BP 189 EP 199 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3IA UT WOS:000336015700002 ER PT J AU Ergenekon, Y Tekin-Iftar, E Kapan, A Akmanoglu, N AF Ergenekon, Yasemin Tekin-Iftar, Elif Kapan, Alper Akmanoglu, Nurgul TI Comparison of Video and Live Modeling in Teaching Response Chains to Children with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID PERSPECTIVE-TAKING; IN-VIVO; PLAY; PRESCHOOLERS; REINFORCEMENT; INTERVENTIONS; INDIVIDUALS; SEQUENCES; PROMPTS; PICTURE AB Research has shown that video and live modeling are both effective in teaching new skills to children with autism. An adapted alternating treatments design was used to compare the effectiveness and efficiency of video and live modeling in. teaching response chains to three children with autism. Each child was taught two chained skills; one skill was planned to be taught by video modeling and the other was planned to be taught by live modeling. Results showed that two children were able to acquire the response chains assigned to them successfully with both procedures. For the third child, live modeling was found to be more effective than video modeling. When the efficiency of two procedures is considered, no dramatic differences were observed in favor of either modeling across participants. C1 [Ergenekon, Yasemin; Tekin-Iftar, Elif; Kapan, Alper; Akmanoglu, Nurgul] Anadolu Univ, TR-26470 Eskisehir, Turkey. RP Ergenekon, Y (reprint author), Anadolu Univ, Engelliler Arastirma Enstitusu, TR-26470 Eskisehir, Turkey. 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PD JUN PY 2014 VL 49 IS 2 BP 200 EP 213 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3IA UT WOS:000336015700003 ER PT J AU Reilly, C Hughes, C Harvey, M Brigham, N Cosgriff, J Kaplan, L Bernstein, R AF Reilly, Caitlin Hughes, Carolyn Harvey, Michelle Brigham, Nicolette Cosgriff, Joseph Kaplan, Lauren Bernstein, Rebekah TI "Let's Talk!": Increasing Novel Peer-Directed Questions by High School Students with Autism to Their General Education Peers SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID HIGH-FUNCTIONING CHILDREN; SOCIAL-SKILLS; SPECTRUM DISORDERS; INTELLECTUAL DISABILITIES; ASPERGER SYNDROME; ADOLESCENTS; INTERVENTION; RECIPROCITY; VALIDITY; BEHAVIOR AB We taught three high school students with high-functioning autism to increase their novel peer-directed questions when using a communication book to converse with general education partners at school. Novel question training was associated with participants asking peer-directed questions not displayed in communication books across a variety of conversational partners. Partners systematically responded to questions participants asked throughout the study, whether questions asked were displayed in participants' books or not. In addition, partners' initiations to participants increased when participants asked more peer-directed questions not displayed in their books. Social validation data gathered from participants and partners generally confirmed the importance of the study's goals and outcomes; normative data indicated that participants engaged in conversation in a fashion similar to their general education peers. Findings are discussed with respect to future research and practice. C1 [Reilly, Caitlin; Harvey, Michelle; Brigham, Nicolette; Cosgriff, Joseph; Kaplan, Lauren; Bernstein, Rebekah] Vanderbilt Univ, Nashville, TN USA. 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Train. Autism Dev. Disabil. PD JUN PY 2014 VL 49 IS 2 BP 214 EP 231 PG 18 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3IA UT WOS:000336015700004 ER PT J AU Ardic, A Cavkaytar, A AF Ardic, Avsar Cavkaytar, Atilla TI Effectiveness of the Modified Intensive Toilet Training Method on Teaching Toilet Skills to Children with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article AB The purpose of this study was to determine effectiveness of a modified version of Azrin and Foxx's (1971) intensive toilet training method on teaching of toilet skills to children with autism. This method consists of administering extra fluids and a time schedule, but does not use overcorrection procedures. Implementation requires a study of six hours per day. The study was conducted with three children with autism in an educational setting and used a multiple probe design. Both inter-observer and procedural reliability data were collected. Graphical analysis was used to determine effectiveness of a modified version of Azrin and Foxx's method for teaching toilet skills to children with autism. Results of the study indicate that the modified Azrin and Foxx method was effective in teaching dryness and urinating into the toilet at acquisition level to children with autism. Parents of the research subjects were very satisfied with the results. C1 [Ardic, Avsar] Ege Univ, TR-35040 Izmir, Turkey. [Cavkaytar, Atilla] Anadolu Univ, Eskisehir, Turkey. RP Ardic, A (reprint author), Ege Univ, Fac Educ, Dept Special Educ, TR-35040 Izmir, Turkey. 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J., 2009, RES DEV DISABIL, V30, P1388 Post AR, 2004, BEHAV INTERVENT, V19, P45, DOI 10.1002/bin.149 Ricciardi JN, 2003, CHILD FAM BEHAV THER, V25, P53, DOI 10.1300/J019v25n04_04 Richards S. B., 1998, SINGLE SUBJECT RES A Snell M. E., 1993, SELF CARE SKILLS INS Tarbox RSE, 2004, J APPL BEHAV ANAL, V37, P97, DOI 10.1901/jaba.2004.37-97 Tekin-Iftar E., 2006, OZEL EGITIMDE YANLIS, V2nd Turnbull A, 2007, EXCEPTIONAL LIVES SP Williams G, 2003, J DEV PHYS DISABIL, V15, P335, DOI 10.1023/A:1026310216069 NR 21 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2014 VL 49 IS 2 BP 263 EP 276 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3IA UT WOS:000336015700007 ER PT J AU West, EA Pirtle, JM AF West, Elizabeth A. Pirtle, Jody M. TI Mothers' and Fathers' Perspectives on Quality Special Educators and the Attributes that Influence Effective Inclusive Practices SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SEVERE DISABILITIES; PARENTS PERCEPTIONS; CHILDREN; SATISFACTION; MODERATE; STIGMA; AUTISM; VIEWS AB Research over the last decade or so has made it clear that quality teachers matter to student achievement. What is less clear is the ways in which they matter and how we can prepare such high-quality teachers for a variety of contexts. The research question guiding this project was what do important stakeholder groups perceive to be the skills and knowledge that high quality, beginning special educators need when they start teaching? In the field of special education, there is no clear consensus on this matter; voices of key players-parents of children with moderate to severe disabilities-have not been adequately heard. This study fills this gap in our understanding as focus group interviews were conducted with parents of children with moderate to severe disabilities. Analysis of these interviews revealed that participants' responses fell under five major themes: Understanding, Teacher Training, Effective Communication, System, and Teacher Disposition. Inclusive practices are highlighted as parents identified these across all themes. Teacher education developers can play a major role in transforming programs to better align with what parents perceive to be the skills and knowledge that a high quality beginning special educator needs when he/she starts teaching. This information can be used to revise and renew programs to better prepare special educators. C1 [West, Elizabeth A.] Univ Washington, Seattle, WA 98195 USA. [Pirtle, Jody M.] Univ Arizona, Tucson, AZ 85721 USA. RP West, EA (reprint author), Univ Washington, Area Special Educ, Box 353600, Seattle, WA 98195 USA. 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Autism Dev. Disabil. PD JUN PY 2014 VL 49 IS 2 BP 290 EP 300 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AH3IA UT WOS:000336015700009 ER PT J AU Camacho, J Jones, K Miller, E Ariza, J Noctor, S Van de Water, J Martinez-Cerdeno, V AF Camacho, Jasmin Jones, Karen Miller, Elaine Ariza, Jeanelle Noctor, Stephen Van de Water, Judy Martinez-Cerdeno, Veronica TI Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism spectrum disorders; Maternal antibodies; In utero exposure; Immune; Mouse behavior ID ENVIRONMENTAL-FACTORS; ANTIBRAIN ANTIBODIES; IGG ANTIBODIES; BRAIN; PREGNANCY; CHILDREN; MOTHERS; PROTEINS AB Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior. (C) 2014 Elsevier B.V. All rights reserved. C1 [Camacho, Jasmin; Miller, Elaine; Ariza, Jeanelle; Martinez-Cerdeno, Veronica] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [Camacho, Jasmin; Miller, Elaine; Ariza, Jeanelle; Martinez-Cerdeno, Veronica] Inst Pediat Regenerat Med, Sacramento, CA 95817 USA. [Camacho, Jasmin; Miller, Elaine; Ariza, Jeanelle; Martinez-Cerdeno, Veronica] Shriners Hosp Children Northern Calif, Sacramento, CA 95817 USA. [Jones, Karen; Noctor, Stephen; Van de Water, Judy; Martinez-Cerdeno, Veronica] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Jones, Karen; Van de Water, Judy] Univ Calif Davis, Dept Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Noctor, Stephen] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. RP Martinez-Cerdeno, V (reprint author), 2425 Stockton Blvd, Sacramento, CA 95817 USA. EM vmartinezcerdeno@ucdavis.edu FU NIMH [R01-MH094681]; NIEHS [1 P01 ES11269-01, 1 R01-ES015359]; U.S. Environmental Protection Agency (U.S.EPA) through the Science to Achieve Results (STAR) program [R829388]; Shriners Hospitals FX Funding for this project was obtained from the NIMH (R01-MH094681), NIEHS 1 P01 ES11269-01, the U.S. Environmental Protection Agency (U.S.EPA) through the Science to Achieve Results (STAR) program (Grant R829388), NIEHS 1 R01-ES015359, and Shriners Hospitals. 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Brain Res. PD JUN 1 PY 2014 VL 266 BP 46 EP 51 DI 10.1016/j.bbr.2014.02.045 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH0JN UT WOS:000335805300006 PM 24613242 ER PT J AU McKimm, E Corkill, B Goldowitz, D Albritton, LM Homayouni, R Blaha, CD Mittleman, G AF McKimm, Eric Corkill, Beau Goldowitz, Dan Albritton, Lorraine M. Homayouni, Ramin Blaha, Charles D. Mittleman, Guy TI Glutamate Dysfunction Associated with Developmental Cerebellar Damage: Relevance to Autism Spectrum Disorders SO CEREBELLUM LA English DT Article DE Autism; Cerebellum; Dopamine; Glutamate; Fmr1 mice ID LURCHER MUTANT MICE; QUANTITATIVE MORPHOLOGICAL ANALYSIS; PURKINJE-CELL LOSS; PREFRONTAL CORTEX; NEUROANATOMICAL ABNORMALITIES; STEREOLOGICAL EXPERIMENT; CHOLINERGIC NEURONS; ANTERIOR CINGULATE; DOPAMINE; RAT AB Neural abnormalities commonly associated with autism spectrum disorders include prefrontal cortex (PFC) dysfunction and cerebellar pathology in the form of Purkinje cell loss and cerebellar hypoplasia. It has been reported that loss of cerebellar Purkinje cells results in aberrant dopamine neurotransmission in the PFC which occurs via dysregulation of multisynaptic efferents from the cerebellum to the PFC. Using a mouse model, we investigated the possibility that developmental cerebellar Purkinje cell loss could disrupt glutamatergic cerebellar projections to the PFC that ultimately modulate DA release. We measured glutamate release evoked by local electrical stimulation using fixed-potential amperometry in combination with glutamate selective enzyme-based recording probes in urethane-anesthetized Lurcher mutant and wildtype mice. Target sites included the mediodorsal and ventrolateral thalamic nuclei, reticulotegmental nuclei, pedunculopontine nuclei, and ventral tegmental area. With the exception of the ventral tegmental area, the results indicated that in comparison to wildtype mice, evoked glutamate release was reduced in Lurcher mutants by between 9 and 72 % at all stimulated sites. These results are consistent with the notion that developmental loss of cerebellar Purkinje cells drives reductions in evoked glutamate release in cerebellar efferent pathways that ultimately influence PFC dopamine release. Possible mechanisms whereby reductions in glutamate release could occur are discussed. C1 [McKimm, Eric; Corkill, Beau; Blaha, Charles D.; Mittleman, Guy] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Goldowitz, Dan] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. [Albritton, Lorraine M.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Homayouni, Ramin] Univ Memphis, Bioinformat Program, Memphis, TN 38152 USA. [Homayouni, Ramin] Univ Memphis, Ctr Translat Informat, Dept Biol, Memphis, TN 38152 USA. RP Mittleman, G (reprint author), Univ Memphis, Dept Psychol, 400 Innovat Dr, Memphis, TN 38152 USA. EM gmittlmn@memphis.edu FU NINDS [1R01NS063009] FX This project was made possible by NINDS grant 1R01NS063009. 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Huber, Heartley B. Carter, Erik W. Juarez, A. Pablo Warren, Zachary E. TI Statewide Assessment of Professional Development Needs Related to Educating Students With Autism Spectrum Disorder SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorder; training needs; professional development; training methods ID IMPLEMENTATION SCIENCE; SCHOOL; TEACHERS; STRATEGIES; CHILDREN; YOUTH AB Preparing teachers to implement evidence-based practices for students with autism spectrum disorder (ASD) is a pressing need. We surveyed 456 teachers and administrators in a southern state about professional development related to educating students with ASD. Specifically, we were interested in confidence in implementation of evidence-based practices, interest in accessing training on these topics, perceived benefit of different avenues of professional development, and interest in accessing these avenues. Overall, teachers were not very confident in their ability to implement evidence-based practices and address important issues for students with ASD. Surprisingly, lower confidence was not related to increased interest in training. In addition, teachers and administrators perceived workshops to be a more beneficial and attractive avenue of professional development compared with coaching, despite empirical evidence to the contrary. We offer possible explanations for these findings and share implications for administrators, technical assistance providers, and policy makers who make decisions about professional development opportunities. C1 [Brock, Matthew E.; Huber, Heartley B.; Carter, Erik W.; Juarez, A. Pablo; Warren, Zachary E.] Vanderbilt Univ, Nashville, TN 37203 USA. RP Brock, ME (reprint author), Vanderbilt Univ, Dept Special Educ, 230 Appleton Pl,PMB 228, Nashville, TN 37203 USA. 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TI Special Education Complaints Filed by Parents of Students With Autism Spectrum Disorders in the Midwestern United States SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE legal cases; special education; autism spectrum disorders; complaint investigations ID YOUNG-CHILDREN; PROGRAMS; HEARINGS; QUALITY; SUPPORT AB The number of students with autism spectrum disorders (ASD) receiving services in public schools is increasing steadily. However, the findings of previous research and recent litigation trends suggest that a notable disconnect persists between school-based services and parental satisfaction. As a means to better understand parental dissatisfaction with educational services, I analyzed presenting issues and outcomes of complaint investigations filed by parents of children with ASD in a midwestern U.S. state. A total of 97 electronic summaries of complaint investigations filed from January 2004 to January 2009 were examined using content analysis to identify the most frequently cited complaint issues, as well as the findings of fact leading to decisions in favor of schools. Common complaint issues included problems with Individualized Education Program content and implementation, parental participation, evaluation and case conference committee procedures, staff qualifications, and behavior/disciplinary procedures. Implications of the findings for educators, parents, and future research are discussed. C1 [White, Stacy E.] Indiana Univ, Bloomington, IN 47405 USA. RP White, SE (reprint author), Indiana Univ, WW Wright Sch Educ, 201 N Rose Ave, Bloomington, IN 47405 USA. EM stacwhit@indiana.edu CR Baird M. M., 1999, P 20 NAT I LEG ISS E Chambers J. G., 2003, SPECIAL ED EXPENDITU Etscheidt S, 2003, RES PRACT PERS SEV D, V28, P51, DOI 10.2511/rpsd.28.2.51 Fish W. 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PD JUN PY 2014 VL 29 IS 2 BP 80 EP 87 DI 10.1177/1088357613478830 PG 8 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AG6ZZ UT WOS:000335569000002 ER PT J AU Chiang, HM AF Chiang, Hsu-Min TI A Parent Education Program for Parents of Chinese American Children With Autism Spectrum Disorders (ASDs) A Pilot Study SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE multicultural issues; evidence-based practices; intervention; parent; autism ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; HISPANIC ADOLESCENTS; INTERACTION THERAPY; CENTERED APPROACH; YOUNG-CHILDREN; MENTAL-HEALTH; HONG-KONG; FAMILIES; MOTHERS AB This study was conducted to examine the effectiveness of a parent education program on decreasing parenting stress and increasing parental confidence and quality of life in parents of Chinese American children with autism spectrum disorders (ASDs). A pre-, posttest group design was used in this study. A total of nine families of Chinese American children with ASDs participated in a 10-week parent education program (including 10-weekly 120-min group sessions). The findings of this study revealed that after receiving the program, parents of Chinese American children with ASDs showed significant reduction in parenting stress, improvement in parental confidence, and improvement in quality of life in physical health and environment domains. C1 [Chiang, Hsu-Min] Columbia Univ, New York, NY 10027 USA. RP Chiang, HM (reprint author), Columbia Univ, Teachers Coll, Special Educ Program, Box 223, New York, NY 10027 USA. EM hchiang@tc.edu CR Abidin R. R., 1995, PSYCHOL ASSESSMENT R Anan RM, 2008, BEHAV INTERVENT, V23, P165, DOI 10.1002/bin.262 Blackledge JT, 2006, CHILD FAM BEHAV THER, V28, P1, DOI 10.1300/J019v28n01_01 Brookman-Frazee L, 2004, J POSIT BEHAV INTERV, V6, P195, DOI 10.1177/10983007040060040201 Callicott K. 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Disabil. PD JUN PY 2014 VL 29 IS 2 BP 88 EP 94 DI 10.1177/1088357613504990 PG 7 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AG6ZZ UT WOS:000335569000003 ER PT J AU Meadan, H Angell, ME Stoner, JB Daczewitz, ME AF Meadan, Hedda Angell, Maureen E. Stoner, Julia B. Daczewitz, Marcus E. TI Parent-Implemented Social-Pragmatic Communication Intervention A Pilot Study SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE visual teaching strategies; young children with Down syndrome; parent interventionists; naturalistic teaching strategies ID AUTISM SPECTRUM DISORDERS; EDUCATION-PROGRAMS; TRAINING-PROGRAM; CHILDREN; LANGUAGE; ACQUISITION; TEACHERS; PLAY AB This pilot study investigated the feasibility and effectiveness of a home-based parent training and coaching program on the use of naturalistic and visual teaching strategies by parents of children (aged 2-5 years) with Down syndrome to promote and enhance these children's social-pragmatic communication skills. Five parent interventionist-child dyads participated. A single-case multiple-baseline design demonstrated the feasibility and effectiveness of the parent training and coaching program on parents' correct use of naturalistic and visual teaching strategies. Findings suggest that parents and children benefited from the intervention. Parents learned the new teaching strategies, implemented them with high fidelity, and were satisfied with intervention procedures and outcomes. In addition, parents reported improvement in their children's social-pragmatic communication skills. Implications for practice and future research are described. C1 [Meadan, Hedda] Univ Illinois, Champaign, IL 61820 USA. [Angell, Maureen E.; Stoner, Julia B.; Daczewitz, Marcus E.] Illinois State Univ, Normal, IL 61761 USA. RP Meadan, H (reprint author), Univ Illinois, Dept Special Educ, 1310 S Sixth St, Champaign, IL 61820 USA. 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PD JUN PY 2014 VL 29 IS 2 BP 95 EP 110 DI 10.1177/1088357613517504 PG 16 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AG6ZZ UT WOS:000335569000004 ER PT J AU Hebert, EB AF Hebert, Elizabeth Baltus TI Factors Affecting Parental Decision-Making Regarding Interventions for Their Child With Autism SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE choice; autism spectrum disorders; parent ID SPECTRUM DISORDERS; ALTERNATIVE MEDICINE; DOWN-SYNDROME; COMPLEMENTARY; FAMILIES; CARE; DISABILITY; PRESCHOOL; PATTERNS; MOTHERS AB Due to the numerous interventions available for children with autism, parents are faced with challenging decisions regarding treatments from the time of diagnosis and throughout their child's life. This exploratory qualitative study investigated the reasons behind parents' decisions about interventions for their child with autism. In-depth interviews were conducted with 23 parents from 18 families making decisions for 19 young children to understand their perspectives on deciding a philosophical approach, choosing a preschool program, and/or deciding on alternative treatments. Children had a diagnosis of pervasive developmental disorder not otherwise specified or autistic disorder and were below the age of 7 years. Parents' considerations were categorized into the themes of parental, child, and program attributes. Recommendations were made regarding areas to explore with families to provide support as they weigh the numerous options available. Recommendations for policy changes that could improve diagnostic and treatment services for children with autism and their families were discussed. C1 [Hebert, Elizabeth Baltus] Nazareth Coll, Rochester, NY 14618 USA. RP Hebert, EB (reprint author), Nazareth Coll, Occupat Therapy Dept, 4245 East Ave, Rochester, NY 14618 USA. 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Disabil. PD JUN PY 2014 VL 29 IS 2 BP 111 EP 124 DI 10.1177/1088357614522291 PG 14 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AG6ZZ UT WOS:000335569000005 ER PT J AU Mammarella, IC Giofre, D Caviola, S Cornoldi, C Hamilton, C AF Mammarella, Irene C. Giofre, David Caviola, Sara Cornoldi, Cesare Hamilton, Colin TI Visuospatial working memory in children with autism: The effect of a semantic global organization SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism Spectrum Disorder (ASD); Visuospatial working memory (VSWM); Central coherence theory; Semantic organization ID SHORT-TERM-MEMORY; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; INDIVIDUALS; CONSOLIDATION; ADOLESCENTS; CONTRIBUTES; INFORMATION; PERFORMANCE; PERCEPTION AB It has been reported that individuals with Autism Spectrum Disorders (ASD) perceive visual scenes as a sparse set of details rather than as a congruent and meaningful unit, failing in the extraction of the global configuration of the scene. In the present study, children with ASD were compared with typically developing (TD) children, in a visuospatial working memory task, the Visual Patterns Test (VPT). The VPT array was manipulated to vary the semantic affordance of the pattern, high semantic (global) vs. low semantic; temporal parameters were also manipulated within the change detection protocol. Overall, there was no main effect associated with Group, however there was a significant effect associated with Semantics, which was further qualified by an interaction between the Group and Semantic factors; there was only a significant effect of semantics in the TD group. The findings are discussed in light of the weak central coherence theory where the ASD group are unable to make use of long term memory semantics in order to construct global representations of the array. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mammarella, Irene C.; Caviola, Sara] Univ Padua, Dept Dev & Social Psychol, I-35131 Padua, Italy. [Giofre, David; Cornoldi, Cesare] Univ Padua, Dept Gen Psychol, I-35131 Padua, Italy. 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Dev. Disabil. PD JUN PY 2014 VL 35 IS 6 BP 1349 EP 1356 DI 10.1016/j.ridd.2014.03.030 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AG7YQ UT WOS:000335635100017 PM 24705488 ER PT J AU Harrington, C Foster, M Rodger, S Ashburner, J AF Harrington, Caitlin Foster, Michele Rodger, Sylvia Ashburner, Jill TI Engaging young people with Autism Spectrum Disorder in research interviews SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE methodology; Asperger Syndrome; young people; qualitative; interviews; autism ID ASPERGER-SYNDROME; CHILDREN; EXPERIENCE; LANGUAGE; MEMORY; CHALLENGES; DIFFERENCE; VIEWS AB Accessible summary Listening to young people with autism spectrum disorder is important. Researchers can help support young people to have their say. Each young person is different. The supports used need to match their needs. This study draws on the first author's doctoral research on the mainstream schooling experiences of young people with autism spectrum disorder (ASD) and their parents in Queensland, Australia. The aims are to share some of the practical strategies that were adapted and developed to engage the young people in the research and to critically reflect on what this means for future inclusive methodological approaches in this area. The key message is that diagnostic-related assumptions about impairments can lead researchers to develop strategies which exclude or restrict rather than maximise participation of disabled people in research. To enable young people with ASD to provide rich and meaningful insights researchers need to acknowledge and plan creatively and flexibly for the interactive dynamic that is unique to each individual as well as for needs which might be shared. C1 [Harrington, Caitlin; Foster, Michele] Univ Queensland, Social Work Serv, St Lucia, Qld 4072, Australia. [Harrington, Caitlin; Foster, Michele] Univ Queensland, Human Serv, St Lucia, Qld 4072, Australia. [Rodger, Sylvia; Ashburner, Jill] Univ Queensland, Sch Hlth & Rehabil Sci, St Lucia, Qld 4072, Australia. RP Harrington, C (reprint author), Univ Queensland, Social Work Serv, St Lucia, Qld 4072, Australia. 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J. Learn. Disabil. PD JUN PY 2014 VL 42 IS 2 BP 153 EP 161 DI 10.1111/bld.12037 PG 9 WC Education, Special SC Education & Educational Research GA AF9AS UT WOS:000335007900008 ER PT J AU Pritchard, D Hoerger, M Dyer, T Graham, N Penney, H Mace, FC AF Pritchard, Duncan Hoerger, Marguerite Dyer, Tim Graham, Nicola Penney, Heather Mace, F. Charles TI Sodium valproate withdrawal correlates with reduced aggression SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE bipolar disorder; Aggression; sodium valproate; learning disability ID INTELLECTUAL DISABILITIES; COGNITIVE THERAPY; PSYCHOTROPIC MEDICATION; RESIDENTIAL FACILITIES; LEARNING-DISABILITIES; BEHAVIOR; PEOPLE; POPULATION; ADULTS; INDIVIDUALS AB Accessible A 16-year-old boy diagnosed with a mild learning disability, atypical autism, attention-deficit hyperactivity disorder, bipolar disorder, conduct disorder and epilepsy was admitted to a residential special school for treatment of severe aggression. Prior to admission, he had been prescribed various psychotropic medications, including sodium valproate, to treat his aggressive behaviour, bipolar disorder and epilepsy. His behaviour improved when his medication was stopped. People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or epilepsy were observed over the course of this 135-week case study. No aggression was observed during the last 20weeks of the study. Aggressive behaviour as a possible side effect of sodium valproate should be considered in people with learning disabilities. C1 [Pritchard, Duncan; Dyer, Tim; Graham, Nicola; Penney, Heather] Aran Hall Sch, Dolgellau LL40 2AR, Gwynedd, Wales. [Pritchard, Duncan] Bangor Univ, Dolgellau LL40 2AR, Gwynedd, Wales. [Hoerger, Marguerite] Bangor Univ, Bangor, Gwynedd, Wales. [Mace, F. Charles] Nova SE Univ, Ft Lauderdale, FL 33314 USA. RP Pritchard, D (reprint author), Aran Hall Sch, Dolgellau LL40 2AR, Gwynedd, Wales. EM duncanpritchard@aranhall.com CR Brosnan J, 2011, RES DEV DISABIL, V32, P437, DOI 10.1016/j.ridd.2010.12.023 Chowdhury M, 2011, RES DEV DISABIL, V32, P383, DOI 10.1016/j.ridd.2010.11.015 COCCARO EF, 1989, ARCH GEN PSYCHIAT, V46, P587 Cooper SA, 1997, J APPL RES INTELLECT, V10, P303 Deb S, 2001, J INTELL DISABIL RES, V45, P506 Donley M, 2012, BRIT J LEARN DISABIL, V40, P286, DOI 10.1111/j.1468-3156.2011.00707.x Fisher WW, 1996, AM J MENT RETARD, V101, P15 Hagopian LP, 2002, BEHAV THER, V33, P65, DOI 10.1016/S0005-7894(02)80006-5 HARRIS P, 1993, J INTELL DISABIL RES, V37, P221 HILL BK, 1984, AM J MENT DEF, V88, P380 Johnson J., 2007, INT J BEHAV CONSULTA, V3, P512 Kazdin A. 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PD JUN PY 2014 VL 42 IS 2 BP 162 EP 167 DI 10.1111/bld.12019 PG 6 WC Education, Special SC Education & Educational Research GA AF9AS UT WOS:000335007900009 ER PT J AU Li, XJ Sjostedt, C Sundquist, K Zoller, B Sundquist, J AF Li, Xinjun Sjostedt, Cecilia Sundquist, Kristina Zoller, Bengt Sundquist, Jan TI Neighborhood deprivation and childhood autism: A nationwide study from Sweden SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Childhood autism; Incidence; Multilevel modeling; Neighborhood-level deprivation; Sociodemographic factors ID CORONARY-HEART-DISEASE; SPECTRUM DISORDERS; MULTILEVEL ANALYSIS; RISK-FACTORS; SOCIOECONOMIC-STATUS; DEVELOPMENTAL-DISABILITIES; SOCIAL-PARTICIPATION; VIOLENT CRIME; HEALTH; COMMUNITY AB Objective: To examine whether there is an association between neighborhood deprivation and childhood autism, after accounting for family- and individual-level sociodemographic characteristics. Methods: An open cohort of all children aged 2-11 years was followed between January 1, 2000 and December 31, 2010. Childhood residential locations were geocoded and classified according to neighborhood deprivation (an index of low education, low income, unemployment, and receipt of welfare assistance). Data were analyzed by multilevel logistic regression, with family- and individual-level characteristics at the first level and level of neighborhood deprivation at the second level. Results: During the study period, among a total of 643,456 children, 1699 (0.3%) were diagnosed with childhood autism. Age-standardized cumulative incidence, defined as first registration for childhood autism during the study period, increased with increasing level of neighborhood deprivation. In the study population, 22 per 1000 and 3.6 per 1000 children in the least and most deprived neighborhoods, respectively, were diagnosed with childhood autism. Incidence of childhood autism increased with increasing neighborhood-level deprivation across all family and individual-level sociodemographic categories. The odds ratio (OR) for childhood autism for those living in high-deprivation neighborhoods versus those living in low-deprivation neighborhoods was 1.59 (95% confidence interval = 1.35-1.88). High neighborhood deprivation remained significantly associated with odds of childhood autism after adjustment for family- and individual-level sociodemographic characteristics (OR = 1.28, 95% confidence. interval = 1.07-1.53, P = 0.007). Conclusions: This study is the largest so far on potential neighborhood influences on childhood autism. Our results show that neighborhood deprivation is associated with childhood autism, independently of family- and individual-level sociodemographic characteristics. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Li, Xinjun; Sjostedt, Cecilia; Sundquist, Kristina; Zoller, Bengt; Sundquist, Jan] Lund Univ Reg Skane, Ctr Primary Hlth Care Res, Lund, Sweden. [Sundquist, Kristina; Sundquist, Jan] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Li, XJ (reprint author), Skane Univ Hosp, CRC, Ctr Primary Hlth Care Res, Bldg 28,Floor 11,Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden. EM xinjun.li@med.lu.se FU National Institute of Drug Abuse [R01 DA030005]; Region Skane; Swedish Research Council FX This work was supported by the National Institute of Drug Abuse (R01 DA030005), ALF funding from Region Skane awarded to Jan and Kristina Sundquist, and grants from the Swedish Research Council (awarded to Jan Sundquist and Kristina Sundquist). The registers used in the present study are maintained by Statistics Sweden and the National Board of Health and Welfare. 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Psychiatr. Res. PD JUN PY 2014 VL 53 BP 187 EP 192 DI 10.1016/j.jpsychires.2014.02.011 PG 6 WC Psychiatry SC Psychiatry GA AG0KK UT WOS:000335104200027 PM 24613033 ER PT J AU Lamb, JC Boffetta, P Foster, WG Goodman, JE Hentz, KL Rhomberg, LR Staveley, J Swaen, G Van Der Kraak, G Williams, AL AF Lamb, James C. Boffetta, Paolo Foster, Warren G. Goodman, Julie E. Hentz, Karyn L. Rhomberg, Lorenz R. Staveley, Jane Swaen, Gerard Van Der Kraak, Glen Williams, Amy L. TI Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals-2012 SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Endocrine-disrupting chemicals (EDCs); Weight of evidence; Causation; State of the science; Disease trends; Low-dose effects; Non-monotonic dose response (NMDR) ID AUTISM SPECTRUM DISORDERS; SPRAGUE-DAWLEY RATS; DIETARY BISPHENOL-A; NONMONOTONIC DOSE-RESPONSES; SERUM THYROXINE LEVEL; PROSTATE-CANCER RISK; FROGS RANA-PIPIENS; DIBENZO-P-DIOXINS; SEMEN QUALITY; POLYCHLORINATED-BIPHENYLS AB Early in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a stateof-the-science review and does not follow the 2002 WHO recommended weight-of-evidence approach. Second, endocrine disruption is often presumed to occur based on exposure or a potential mechanism despite a lack of evidence to show that chemicals are causally established as endocrine disruptors. Additionally, causation is often inferred by the presentation of a series of unrelated facts, which collectively do not demonstrate causation. Third, trends in disease incidence or prevalence are discussed without regard to known causes or risk factors; endocrine disruption is implicated as the reason for such trends in the absence of evidence. Fourth, dose and potency are ignored for most chemicals discussed. Finally, controversial topics (i.e., low dose effects, non-monotonic dose response) are presented in a one-sided manner and these topics are important to understanding endocrine disruption. Overall, the 2012 report does not provide a balanced perspective, nor does it accurately reflect the state of the science on endocrine disruption. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Lamb, James C.; Hentz, Karyn L.; Staveley, Jane; Williams, Amy L.] Exponent, Alexandria, VA 22314 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Foster, Warren G.] McMaster Univ, Dept Obstet & Gynecol, Hamilton, ON L8S 4K1, Canada. [Goodman, Julie E.; Rhomberg, Lorenz R.] Gradient, Cambridge, MA 02138 USA. [Swaen, Gerard] Lenz, Exponent, Harrogate HG2 8RE, England. [Van Der Kraak, Glen] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada. RP Lamb, JC (reprint author), Exponent, 1800 Diagonal Rd,Suite 500, Alexandria, VA 22314 USA. 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Toxicol. Pharmacol. PD JUN PY 2014 VL 69 IS 1 BP 22 EP 40 DI 10.1016/j.yrtph.2014.02.002 PG 19 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA AG0SL UT WOS:000335125800003 PM 24530840 ER PT J AU Tincani, M Cucchiarra, MB Thurman, SK Snyder, MR McCarthy, CM AF Tincani, Matt Cucchiarra, Maia Bloomfield Thurman, S. Kenneth Snyder, Mark R. McCarthy, Catherine M. TI Evaluating NRC's Recommendations for Educating Children with Autism a Decade Later SO CHILD & YOUTH CARE FORUM LA English DT Article DE Autism spectrum disorder; Autism; National Research Council; Policy; Parent advocacy ID SPECTRUM DISORDERS; SCHOOLS; PARENTS AB Over a decade ago, the National Research Council (NRC) published the influential book, Educating Children with Autism. To survey parents and state-level special education administrators to evaluate how NRC's recommendations, as published in Educating Children with Autism, have impacted educational practices for children with autism in the US. 149 parents of children with autism and 35 state-level special education administrators from 35 states were surveyed on the degree to which they agreed with NRC's recommendations and the degree to which they believed NRC's recommendations have been implemented. Parents and administrators agreed with most NRC recommendations; however, disagreements between parents and administrators were evident regarding labeling of students with autism, intensity of services, and training of staff. Conversely, parents and administrators concurred that the recommendations had been poorly to modestly implemented, overall. Lowest levels of implementation were found for training of qualified staff, research-based curricula, and mental health supports for families. Qualitative analysis of parents' comments highlighted that vigorous advocacy was necessary for their children to receive appropriate services consistent with NRC's recommendations. Over a decade following publication of Educating Children with Autism, most of NRC's recommendations have not been fully implemented. Policy makers should focus particular attention on improving professional training, disseminating research-based practices, and providing mental health supports for families. C1 [Tincani, Matt; Thurman, S. Kenneth; Snyder, Mark R.; McCarthy, Catherine M.] Temple Univ, Dept Psychol Org & Leadership Studies, Philadelphia, PA 19122 USA. [Cucchiarra, Maia Bloomfield] Temple Univ, Dept Teaching & Learning, Philadelphia, PA 19122 USA. RP Thurman, SK (reprint author), Temple Univ, Dept Psychol Org & Leadership Studies, Ritter Annex 283 1301 CB Moore Ave, Philadelphia, PA 19122 USA. 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Nineteen children with SLI (mean age 6; 1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI. C1 [Makinen, Leena; Loukusa, Soile; Laukkanen, Paivi; Kunnari, Sari] Univ Oulu, Child Language Res Ctr, Fac Humanities, FI-90014 Oulu, Finland. [Leinonen, Eeva] Univ Wollongong, Dept Psychol, Wollongong, NSW 2500, Australia. RP Makinen, L (reprint author), Univ Oulu, Child Language Res Ctr, Fac Humanities, POB 1000, FI-90014 Oulu, Finland. EM leena.makinen@oulu.fi FU Finnish Brain Foundation; Finnish Cultural Foundation; Oulu University Scholarship Foundation; University of Oulu Faculty of Humanities; Academy of Finland FX The authors report no declarations of interest. This research was supported by grants from the Finnish Brain Foundation, the Finnish Cultural Foundation, the Oulu University Scholarship Foundation, University of Oulu Faculty of Humanities and the Academy of Finland. 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Linguist. Phon. PD JUN PY 2014 VL 28 IS 6 BP 413 EP 427 DI 10.3109/02699206.2013.875592 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AF8AX UT WOS:000334938500003 PM 24446795 ER PT J AU Roche, L Sigafoos, J Lancioni, GE O'Reilly, MF van der Meer, L Achmadi, D Green, VA Kagohara, D Sutherland, D Rayner, C Marschik, PB AF Roche, Laura Sigafoos, Jeff Lancioni, Giulio E. O'Reilly, Mark F. van der Meer, Larah Achmadi, Donna Green, Vanessa A. Kagohara, Debora Sutherland, Dean Rayner, Christopher Marschik, Peter B. TI Comparing Tangible Symbols, Picture Exchange, and a Direct Selection Response for Enabling Two Boys with Developmental Disabilities to Access Preferred Stimuli SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Augmentative and alternative communication; Autism spectrum disorders; Developmental disability; Direct selection; Picture exchange; Tangible symbols ID AUTISM SPECTRUM DISORDERS; COMMUNICATION-SYSTEM PECS; MULTIPLE DISABILITIES; COMPARATIVE EFFICACY; REQUESTING SKILLS; VISUAL IMPAIRMENT; CHILDREN; MODES AB We compared how quickly two boys with developmental disabilities learned to use tangible symbols, picture exchange, and a direct selection response to access cartoon videos. Intervention, aimed at teaching the boys to use each option, was evaluated in a multiple-baseline across participants and alternating treatments design. Following intervention, the boys were allowed to choose among the three options. Both participants learned to access six cartoon videos using the three options at comparable rates. Following acquisition, both boys most often chose to use tangible symbols. These findings are consistent with previous studies reporting comparable acquisition rates and a preference among communication options. The present study extends the literature by including a comparison of tangible symbols and a direct selection response. Our results provide additional support for the use of tangible symbols as a communication option for children with developmental disabilities. C1 [Roche, Laura; Sigafoos, Jeff; van der Meer, Larah; Achmadi, Donna; Green, Vanessa A.; Kagohara, Debora] Victoria Univ Wellington, Sch Educ Psychol, Wellington 6147, New Zealand. [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, Bari, Italy. [O'Reilly, Mark F.] Univ Texas Austin, Meadows Ctr Preventing Educ Risk, Austin, TX 78712 USA. [Sutherland, Dean] Univ Canterbury, Sch Hlth Sci, Coll Educ, Christchurch 1, New Zealand. [Rayner, Christopher] Univ Tasmania, Sch Educ, Hobart, Tas, Australia. [Marschik, Peter B.] Med Univ Graz, Inst Physiol, Graz, Austria. RP Sigafoos, J (reprint author), Victoria Univ Wellington, Sch Educ Psychol, POB 17-310, Wellington 6147, New Zealand. EM jeff.sigafoos@vuw.ac.nz CR Ali E, 2011, EDUC TRAIN AUTISM DE, V46, P425 Boesch MC, 2013, RES AUTISM SPECT DIS, V7, P480, DOI 10.1016/j.rasd.2012.12.002 Boesch MC, 2013, AUGMENT ALTERN COMM, V29, P197, DOI 10.3109/07434618.2013.818059 Duker P. C., 2004, ONE TO ONE TRAINING Flores M, 2012, AUGMENT ALTERN COMM, V28, P74, DOI 10.3109/07434618.2011.644579 Kennedy C, 2005, SINGLE CASE DESIGNS Lorah ER, 2013, J DEV PHYS DISABIL, V25, P637, DOI 10.1007/s10882-013-9337-1 Lund SK, 2008, J AUTISM DEV DISORD, V38, P719, DOI 10.1007/s10803-007-0439-4 Wilkins J, 2007, INT REV RES MENT RET, V34, P321, DOI 10.1016/S0074-7750(07)34010-X Parker A. T., 2010, AER J RES PRACTICE V, V3, P2 Roche L., 2013, TANGIBLE SYMBO UNPUB Schlosser R. W., 2002, AUGMENTATIVE ALTERNA, V18, P102, DOI 10.1080/07434610212331281201 Schlosser R. W., 2003, EFFICACY AUGMENTATIV ROWLAND C, 1989, AAC (Augmentative and Alternative Communication), V5, P226, DOI 10.1080/07434618912331275276 Schweigert P., 2000, AUGMENTATIVE ALTERNA, V16, P61, DOI DOI 10.1080/07434610012331278914 Sigafoos J., 2005, TECHNOLOGY DISABILIT, V17, P143 Son Seung-Hyun, 2006, Pediatr Rehabil, V9, P389, DOI 10.1080/13638490500519984 Sparrow SS, 2005, VINELAND ADAPTIVE BE Trief E, 2013, J VISUAL IMPAIR BLIN, V107, P180 Trief E, 2007, J VISUAL IMPAIR BLIN, V101, P613 Turnell Ruth, 1994, Australia and New Zealand Journal of Developmental Disabilities, V19, P193 van der Meer L., 2013, CLIN CASE STUDIES van der Meer L, 2013, AUGMENT ALTERN COMM, V29, P222, DOI 10.3109/07434618.2013.815801 van der Meer L, 2012, J DEV PHYS DISABIL, V24, P451, DOI 10.1007/s10882-012-9283-3 van der Meer L, 2012, RES AUTISM SPECT DIS, V6, P1247, DOI 10.1016/j.rasd.2012.04.005 NR 25 TC 1 Z9 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1056-263X EI 1573-3580 J9 J DEV PHYS DISABIL JI J. Dev. Phys. Disabil. PD JUN PY 2014 VL 26 IS 3 BP 249 EP 261 DI 10.1007/s10882-013-9361-1 PG 13 WC Rehabilitation SC Rehabilitation GA AF4LV UT WOS:000334685100001 ER PT J AU Davis, TN Fuentes, L Durand, S AF Davis, Tonya N. Fuentes, Lisa Durand, Shannon TI Examination of Systematic Durations of Presession Reinforcer Access on Functional Communication Training SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Functional communication training; Motivating operation; Autism; Challenging behavior ID PROBLEM BEHAVIOR; DISABILITIES; OPERATION; ATTENTION; STIMULI AB In this study, we identified the latency to satiation with an activity that maintained problem behavior for a boy with autism. Next, functional communication training (FCT) was implemented. Prior to FCT sessions, the participant was exposed one of to two conditions of presession exposure to stimuli that served as the reinforcer during subsequent FCT sessions. Latency to satiation was used to systematically identify the two durations of stimulus access: (a) 25 % of the mean latency to satiation and (b) 50 % of the mean latency to satiation. Results indicate that while both durations of presession access to the preferred activity resulted in decreased problem behavior, independent manding during FCT was higher in the shorter duration of presession access. The implications of this research are that the presession exposure to stimuli can be systematically individualized to optimize its effect as a motivating operation. C1 [Davis, Tonya N.; Fuentes, Lisa; Durand, Shannon] Baylor Univ, Waco, TX 76798 USA. RP Davis, TN (reprint author), Baylor Univ, Waco, TX 76798 USA. EM Tonya_Davis@baylor.edu CR AYLLON T, 1968, J APPL BEHAV ANAL, V1, P13, DOI 10.1901/jaba.1968.1-13 CARR EG, 1985, J APPL BEHAV ANAL, V18, P111, DOI 10.1901/jaba.1985.18-111 Davis TN, 2009, J DEV PHYS DISABIL, V21, P515, DOI 10.1007/s10882-009-9158-4 FISHER W, 1992, J APPL BEHAV ANAL, V25, P491, DOI 10.1901/jaba.1992.25-491 IWATA BA, 1994, J APPL BEHAV ANAL, V27, P197, DOI 10.1901/jaba.1994.27-197 McComas JJ, 2003, J APPL BEHAV ANAL, V36, P297, DOI 10.1901/jaba.2003.36-297 MICHAEL J, 1982, J EXP ANAL BEHAV, V37, P149, DOI 10.1901/jeab.1982.37-149 O'Reilly M, 2009, J APPL BEHAV ANAL, V42, P773, DOI 10.1901/jaba.2009.42-773 O'Reilly MF, 2008, RES DEV DISABIL, V29, P333, DOI 10.1016/j.ridd.2007.06.004 Rispoli M, 2011, J APPL BEHAV ANAL, V44, P187, DOI 10.1901/jaba.2011.44-187 Roantree CF, 2006, J APPL BEHAV ANAL, V39, P381, DOI 10.1901/jaba.2006.97-05 Skinner B. F., 1957, VERBAL BEHAV NR 12 TC 2 Z9 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1056-263X EI 1573-3580 J9 J DEV PHYS DISABIL JI J. Dev. Phys. Disabil. PD JUN PY 2014 VL 26 IS 3 BP 263 EP 270 DI 10.1007/s10882-013-9360-2 PG 8 WC Rehabilitation SC Rehabilitation GA AF4LV UT WOS:000334685100002 ER PT J AU Falcomata, TS Gainey, S AF Falcomata, Terry S. Gainey, Summer TI An Evaluation of Noncontingent Reinforcement for the Treatment of Challenging Behavior with Multiple Functions SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Challenging behavior; Multiple functions; Noncontingent reinforcement ID INTERVENTION; AUTISM AB The purpose of this study was to evaluate the relative treatment effects of different forms of noncontingent reinforcement (NCR) on challenging behavior with multiple functions. We first conducted a functional analysis of challenging behavior exhibited by a child with autism. The results of the functional analysis suggested that challenging behavior served multiple functions. Next, we conducted a treatment evaluation in which we (a) compared the effects of NCR with attention to NCR with attention and preferred activities in the absence of work activities and (b) compared the effects of NCR with attention and NCR with attention and preferred activities during work activities. The results of the treatment evaluation showed that NCR with attention and preferred activities was more effective at decreasing challenging behavior than NCR with attention both when work was not implemented and during work situations. The current results provide support for the use of noncontingent multiple functional reinforcers to treat multiply-maintained challenging behavior. C1 [Falcomata, Terry S.; Gainey, Summer] Univ Texas Austin, Austin, TX 78712 USA. RP Falcomata, TS (reprint author), Univ Texas Austin, Austin, TX 78712 USA. EM falcomata@austin.utexas.edu CR Bachmeyer MH, 2009, J APPL BEHAV ANAL, V42, P641, DOI 10.1901/jaba.2009.42-641 Borrero CSW, 2006, J APPL BEHAV ANAL, V39, P375, DOI 10.1901/jaba.2006.170-04 Call NA, 2005, J APPL BEHAV ANAL, V38, P385, DOI 10.1901/jaba.2005.51-04 CARR EG, 1985, J APPL BEHAV ANAL, V18, P111, DOI 10.1901/jaba.1985.18-111 DAY HM, 1994, J APPL BEHAV ANAL, V27, P279, DOI 10.1901/jaba.1994.27-279 Falcomata T. S., 2012, J DEV PHYS DISABIL, V6, P529 Falcomata TS, 2013, BEHAV MODIF, V37, P723, DOI 10.1177/0145445513500785 Hagopian LP, 2001, J APPL BEHAV ANAL, V34, P229, DOI 10.1901/jaba.2001.34-229 Ingvarsson ET, 2008, J APPL BEHAV ANAL, V41, P435, DOI 10.1901/jaba.2008.41-435 IWATA BA, 1994, J APPL BEHAV ANAL, V27, P197, DOI 10.1901/jaba.1994.27-197 Kazdin A. E., 1982, SINGLE CASE RES DESI Love JR, 2009, J AUTISM DEV DISORD, V39, P363, DOI 10.1007/s10803-008-0633-z Neidert P. L., 2005, EXCEPTIONALITY, V13, P45, DOI 10.1207/s15327035ex1301_6 O'Reilly M, 2010, RES AUTISM SPECT DIS, V4, P1, DOI 10.1016/j.rasd.2009.07.001 Reese R. M., 2003, FOCUS AUTISM OTHER D, V18, P87 Rispoli M, 2013, J DEV PHYS DISABIL, V25, P135, DOI 10.1007/s10882-012-9315-z Roane HS, 1998, J APPL BEHAV ANAL, V31, P605, DOI 10.1901/jaba.1998.31-605 Sigafoos J, 1996, BEHAV MODIF, V20, P60, DOI 10.1177/01454455960201003 Vollmer TR, 1997, J APPL BEHAV ANAL, V30, P161, DOI 10.1901/jaba.1997.30-161 NR 19 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1056-263X EI 1573-3580 J9 J DEV PHYS DISABIL JI J. Dev. Phys. Disabil. PD JUN PY 2014 VL 26 IS 3 BP 317 EP 324 DI 10.1007/s10882-014-9366-4 PG 8 WC Rehabilitation SC Rehabilitation GA AF4LV UT WOS:000334685100006 ER PT J AU Schroeder, SR Richman, DM Abby, L Courtemanche, AB Oyama-Ganiko, R AF Schroeder, Stephen R. Richman, David M. Abby, Layla Courtemanche, Andrea B. Oyama-Ganiko, Rosa TI Functional Analysis Outcomes and Comparison of Direct Observations and Informant Rating Scales in the Assessment of Severe Behavior Problems of Infants and Toddlers At-Risk for Developmental Delays SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Functional analysis; Informant ratings; Infants; Toddlers; Developmental delays ID INVENTORY-SHORT FORM; INTELLECTUAL DISABILITIES; YOUNG-CHILDREN; SELF-INJURY; INDIVIDUALS; VALIDITY; RELIABILITY; AUTISM; ADULTS AB Severe problem behaviors, like aggression, self-injury, and repetitive behaviors, in people with intellectual and developmental disabilities often appear during early development and may persist without early intervention. The frequencies of self-injurious behavior, aggression, tantrums, property destruction and stereotyped behavior among 17 infants and toddlers at risk for developmental delays and severe behavior problems were assessed using two methods: 1) direct observation of responses during 10 s partial interval recording during analogue functional analysis and 2) the Behavior Problem Inventory-01 (BPI-01; Rojahn et al. Journal of Autism and Developmental Disorders, 31, 577-588, 2001), an informant rating scale. Analogue functional analysis results suggested that the most common function for problem behavior was automatic reinforcement, followed by negative reinforcement in the form of escape from demands. Agreement across the two types of measurement systems as to occurrence of the behaviors reported on the BPI-01 and direct observations during analogue functional analyses was greater than 75 % across aggression, self-injury, and stereotyped behavior. Agreement at a more molecular level of the ranking of the most commonly occurring specific behaviors was considerably lower. Results are discussed in terms of future research on identifying conditions that set the occasion for high levels of agreement between indirect and direct measurement systems for severe behavior problems. C1 [Schroeder, Stephen R.] Univ Kansas, Lawrence, KS 66045 USA. [Richman, David M.; Abby, Layla] Texas Tech Univ, Lubbock, TX 79409 USA. [Oyama-Ganiko, Rosa] Ctr Ann Sullivan Peru, Lima, Peru. [Courtemanche, Andrea B.] Univ Kansas, Med Ctr, Kansas City, MO USA. RP Schroeder, SR (reprint author), Univ Kansas, Lawrence, KS 66045 USA. EM srs@ku.edu CR Barlow D. H., 2008, SINGLE CASE EXPT DES Bayley N., 2006, MANUAL BAYLEY SCALES, V3rd Beavers GA, 2013, J APPL BEHAV ANAL, V46, P1, DOI 10.1002/jaba.30 Berkson G, 2001, AM J MENT RETARD, V106, P539, DOI 10.1352/0895-8017(2001)106<0539:EDOSAS>2.0.CO;2 Gonzalez ML, 2009, J APPL RES INTELLECT, V22, P223, DOI 10.1111/j.1468-3148.2008.00429.x Guilford J. 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R., 2014, AM J INTELL IN PRESS Schroeder SR, 2014, J DEV PHYS DISABIL, V26, P237, DOI 10.1007/s10882-013-9359-8 Sturmey P., 1993, J DEV PHYS DISABIL, V5, P327, DOI 10.1007/BF01046389 THOMPSON T, 1986, J EXP ANAL BEHAV, V46, P219, DOI 10.1901/jeab.1986.46-219 Wacker DP, 1998, J DEV BEHAV PEDIATR, V19, P260, DOI 10.1097/00004703-199808000-00004 Wetherby AM, 2002, COMMUNICATION SYMBOL NR 28 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1056-263X EI 1573-3580 J9 J DEV PHYS DISABIL JI J. Dev. Phys. Disabil. PD JUN PY 2014 VL 26 IS 3 BP 325 EP 334 DI 10.1007/s10882-014-9368-2 PG 10 WC Rehabilitation SC Rehabilitation GA AF4LV UT WOS:000334685100007 ER PT J AU Lorah, ER Crouser, J Gilroy, SP Tincani, M Hantula, D AF Lorah, Elizabeth R. Crouser, Julie Gilroy, Shawn P. Tincani, Matt Hantula, Donald TI Within Stimulus Prompting to Teach Symbol Discrimination Using an iPadA (R) Speech Generating Device SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Mand; Speech-generating device; Voice output communication aid; Autism; Stimulus discrimination ID DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; CHILDREN; AUTISM; INDIVIDUALS; PREFERENCES; MODES AB This study evaluated the effects of within stimulus prompting and prompt fading to teach four preschool children with autism picture symbol discrimination using an iPadA (R) and the Proloqu2Go application as a speech-generating device. Participants were taught to discriminate between a progressively more complex field of picture-symbols depicted on the screen of an iPad with a five-phased training procedure. All participants acquired discrimination between picture-symbols while using the iPad to mand for preferred items in a field of four picture-symbols. The results provide tentative support for a procedure to teach children with autism to discriminate between picture symbols while manding using a handheld speech-generating device. C1 [Lorah, Elizabeth R.] Univ Arkansas, Fayetteville, AR 72701 USA. [Crouser, Julie; Gilroy, Shawn P.; Tincani, Matt; Hantula, Donald] Temple Univ, Philadelphia, PA 19122 USA. RP Lorah, ER (reprint author), Univ Arkansas, Fayetteville, AR 72701 USA. EM lorah@uark.edu CR Andermeier K., 2008, RES AUTISM SPECT DIS, V2, P430 Bondy A. S., 1994, FOCUS AUTISTIC BEHAV, V9, P1, DOI DOI 10.1177/108835769400900301 Cooper J. O., 2007, APPL BEHAV ANAL DeLeon IG, 1996, J APPL BEHAV ANAL, V29, P519, DOI 10.1901/jaba.1996.29-519 Gast D. L., 2010, SINGLE SUBJECT RES M Kagohara DM, 2013, RES DEV DISABIL, V34, P147, DOI 10.1016/j.ridd.2012.07.027 Lindsley OR, 1964, J EDUC, V147, P62 Lorah ER, 2013, J DEV PHYS DISABIL, V25, P637, DOI 10.1007/s10882-013-9337-1 MacDuff G. 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PD JUN PY 2014 VL 26 IS 3 BP 335 EP 346 DI 10.1007/s10882-014-9369-1 PG 12 WC Rehabilitation SC Rehabilitation GA AF4LV UT WOS:000334685100008 ER PT J AU Lancioni, GE Singh, NN O'Reilly, MF Sigafoos, J Boccasini, A Alberti, G Lang, R AF Lancioni, Giulio E. Singh, Nirbhay N. O'Reilly, Mark F. Sigafoos, Jeff Boccasini, Adele Alberti, Gloria Lang, Russell TI People with Multiple Disabilities Use Basic Reminding Technology to Engage in Daily Activities at the Appropriate Times SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Technology; Smartphone; Daily activities; Multiple disabilities ID TRAUMATIC BRAIN-INJURY; MODERATE ALZHEIMERS-DISEASE; PERSONAL DIGITAL ASSISTANT; MILD COGNITIVE IMPAIRMENT; AUTISM SPECTRUM DISORDERS; PICTURE ACTIVITY SCHEDULE; DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITIES; SOCIAL VALIDATION; INDIVIDUALS AB We assessed whether three adults with multiple disabilities could use simple reminding technology to carry out daily activities at the appropriate times. The technology consisted of a Galaxy S-3 mini smartphone (by Samsung) with the application of (a) the talking alarm program for providing verbal instructions about the single activities scheduled (for two participants) or (b) the photo alarm program for providing vibration alerting combined with pictorial instructions about the activities (for the third participant). For each participant, the study involved an ABAB sequence, in which A represented baseline phases (without technology) and B intervention phases (with technology). All three participants were successful in using the technology to independently perform the activities scheduled (i.e., between seven and 10 per day) at the appropriate times. The practical implications of the findings and the importance of technology resources in programs for people with multiple disabilities are discussed. C1 [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, I-70100 Bari, Italy. [Singh, Nirbhay N.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [O'Reilly, Mark F.] Univ Texas Austin, Austin, TX 78712 USA. [Sigafoos, Jeff] Victoria Univ Wellington, Wellington, New Zealand. [Boccasini, Adele; Alberti, Gloria] Lega F DOro Res Ctr, Osimo, Italy. [Lang, Russell] SW Texas State Univ, San Marcos, TX 78666 USA. RP Lancioni, GE (reprint author), Univ Bari, Dept Neurosci & Sense Organs, Via Quintino Sella 268, I-70100 Bari, Italy. 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PD JUN PY 2014 VL 122 BP 1 EP 20 DI 10.1016/j.jecp.2013.11.017 PG 20 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA AF7NB UT WOS:000334900700001 PM 24508666 ER PT J AU Li, J Ji, HF Cao, L Zang, D Gu, R Xia, B Wu, Q AF Li, Jie Ji, Hongfei Cao, Lei Zang, Di Gu, Rong Xia, Bin Wu, Qiang TI EVALUATION AND APPLICATION OF A HYBRID BRAIN COMPUTER INTERFACE FOR REAL WHEELCHAIR PARALLEL CONTROL WITH MULTI-DEGREE OF FREEDOM SO INTERNATIONAL JOURNAL OF NEURAL SYSTEMS LA English DT Article DE Electroencephalogram; hybrid brain-computer interface; wheelchair; parallel control; multi-degree of freedom ID SINGLE-TRIAL EEG; FUZZY SYNCHRONIZATION LIKELIHOOD; WAVELET-CHAOS METHODOLOGY; MILD COGNITIVE IMPAIRMENT; AUTISM SPECTRUM DISORDER; ALZHEIMERS-DISEASE; COMPONENT ANALYSIS; ASYNCHRONOUS BCI; NEURAL-NETWORK; MOTOR IMAGERY AB There have been many attempts to design brain-computer interfaces (BCIs) for wheelchair control based on steady state visual evoked potential (SSVEP), event-related desynchronization/synchronization (ERD/ERS) during motor imagery (MI) tasks, P300 evoked potential, and some hybrid signals. However, those BCI systems cannot implement the wheelchair navigation flexibly and effectively. In this paper, we propose a hybrid BCI scheme based on two-class MI and four-class SSVEP tasks. It cannot only provide multi- degree control for its user, but also allow the user implement the different types of commands in parallel. In order for the subject to learn the hybrid mental strategies effectively, we design a visual and auditory cues and feedback-based training paradigm. Furthermore, an algorithm based on entropy of classification probabilities is proposed to detect intentional control (IC) state for hybrid tasks, and ensure that multi-degree control commands are accurately and quickly generated. The experiment results attest to the efficiency and flexibility of the hybrid BCI for wheelchair control in the real- world. C1 [Li, Jie; Ji, Hongfei; Cao, Lei; Zang, Di] Tongji Univ, Dept Comp Sci & Technol, Shanghai 200092, Peoples R China. [Gu, Rong] Tongji Univ, Dept Elect Sci & Technol, Shanghai 200092, Peoples R China. [Xia, Bin] Shanghai Maritime Univ, Inst Informat Engn, Shanghai 201306, Peoples R China. [Xia, Bin] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany. [Wu, Qiang] Shandong Univ, Sch Informat Sci & Engn, Jinan 250100, Peoples R China. RP Ji, HF (reprint author), Tongji Univ, Dept Comp Sci & Technol, 4800 Cao An Highway, Shanghai 200092, Peoples R China. EM nijanice@gmail.com; jh410@duke.edu; scallray@163.com; zangdi@tongji.edu.cn; gurong2001@163.com; bin.xia@uni-tuebingen.de; wuqiang@sdu.edu.cn FU Fundamental Research Funds for the Central Universities [0800219202]; National Natural Science Foundation of China [61105122, 61103071, 61272271, 61305060]; Excellent Youth and Middle Age Scientists Fund of Shandong Province [BS2012DX020]; Natural Science Foundation Program of Shanghai [11ZR1440200, 12ZR1434000]; Specialized Research Fund for the Doctoral Program of Higher Education [20110072120065, 20130131120025] FX The work was supported by the Fundamental Research Funds for the Central Universities (Grant No. 0800219202), the National Natural Science Foundation of China (Grant Nos. 61105122, 61103071, 61272271 and 61305060), the Excellent Youth and Middle Age Scientists Fund of Shandong Province (Grant No. BS2012DX020), Natural Science Foundation Program of Shanghai (Grant Nos. 11ZR1440200 and 12ZR1434000) and Specialized Research Fund for the Doctoral Program of Higher Education (Grant Nos. 20110072120065 and 20130131120025). 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At first, the raw EEG epochs are preprocessed via Gaussian low pass filtering and differential operation. Then, in the scheme of sparse representation based classification (SRC), a test EEG sample is sparsely represented on the training set by solving l(1)-minimization problem, and the represented residuals associated with ictal and interictal training samples are computed. The test EEG sample is categorized as the class that yields the minimum represented residual. So unlike the conventional EEG classification methods, the choice and calculation of EEG features are avoided in the proposed framework. Moreover, the kernel trick is employed to generate a kernel version of the SRC method for improving the separability between ictal and interictal classes. The satisfactory recognition accuracy of 98.63% for ictal and interictal EEG classification and for ictal and normal EEG classification has been achieved by the kernel SRC. In addition, the fast speed makes the kernel SRC suit for the real-time seizure monitoring application in the near future. C1 [Yuan, Qi; Zhou, Weidong; Yuan, Shasha; Li, Xueli] Shandong Univ, Sch Informat Sci & Engn, Jinan 250100, Peoples R China. [Yuan, Qi; Zhou, Weidong; Yuan, Shasha; Li, Xueli] Shandong Univ, Suzhou Inst, Suzhou 215123, Peoples R China. [Wang, Jiwen; Jia, Guijuan] Shandong Univ, Qilu Hosp, Jinan 250100, Peoples R China. RP Zhou, WD (reprint author), Shandong Univ, Sch Informat Sci & Engn, Jinan 250100, Peoples R China. EM wdzhou@sdu.edu.cn FU Natural Science Foundation of Shandong Province [ZR2013FZ002]; Program of Science and Technology of Suzhou [ZXY2013030]; Independent Innovation Foundation of Shandong University, China [2012DX008] FX The support of the Key Program of Natural Science Foundation of Shandong Province (No. ZR2013FZ002), the Program of Science and Technology of Suzhou (No. ZXY2013030), and the Independent Innovation Foundation of Shandong University (No. 2012DX008), China is gratefully acknowledged. 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We present the first case of an ALS patient carrying a de novo nonsense mutation in exon 14 of the FUS gene (c.1483c>t; p.R495X) with an apparently familial ALS. This mutation causes a phenotype characterized by a young age at onset, a rapid course (<24 months), and a bulbar onset with early respiratory involvement with a predominant lower motor neuron disease. De novo mutations could account for a sizable number of apparently sporadic ALS patients carrying mutations of ALS-related genes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, I-10126 Turin, Italy. [Brunetti, Maura; Barberis, Marco; Restagno, Gabriella] Azienda Osped Citta Salute & Sci, Mol Genet Lab, Turin, Italy. [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Carrara, Giovanna; Valentini, Consuelo] Dept Neuroradiol, Azienda Osped Citta Salute & Sci, Dept Neuroradiol, Turin, Italy. [Chio, Adriano] Neurosci Inst Torino, Turin, Italy. RP Calvo, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net FU Fondazione Vialli e Mauro for ALS Research Onlus; Federazione Italiana Giuoco Calcio; Ministero della Salute [RF-PIE-2007-635695, RF-2010-2309849]; Joint Programmed-Neurodegenerative Disease Research (Strength Project); European Community [259867]; Intramural Research Program of the National Institutes of Health and the National Institute on Aging [Z01 AG000949-02] FX Adriano Chio had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank the patient and her family for having collaborated to this study. This work was funded by grants of Fondazione Vialli e Mauro for ALS Research Onlus, Federazione Italiana Giuoco Calcio, Ministero della Salute (Ricerca Sanitaria Finalizzata 2007, grant RF-PIE-2007-635695, and 2010, grant RF-2010-2309849), and Joint Programmed-Neurodegenerative Disease Research (Strength Project). The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) (grant agreement no. 259867). This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging (project Z01 AG000949-02). Funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. 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Van Daalen, Emma Van Engeland, Herman TI Parental Reaction to Early Diagnosis of Their Children's Autism Spectrum Disorder: An Exploratory Study SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Autism spectrum disorder; Parenting; Resolution; Early diagnosis; Young children ID COMMUNICATIVE DEVELOPMENT INVENTORY; ABERRANT BEHAVIOR CHECKLIST; PRESCHOOL-CHILDREN; QUOTIENT AQ; MENTAL-RETARDATION; MOTHERS RESOLUTION; COPING STRATEGIES; ASPERGER-SYNDROME; EARLY-CHILDHOOD; CEREBRAL-PALSY AB This study explores parental reactions subsequent to receiving their child's autism spectrum disorder (ASD)-diagnosis. Seventy seven parents of recently diagnosed children participated in the Reaction to Diagnosis Interview. Within this group, associations between parental reaction to diagnosis, parental and child characteristics and prediagnostic circumstances were analysed. In a sub-sample, the stability of reaction to diagnosis was examined. The majority of parents were classified as 'resolved' regarding their child's diagnosis. Conversely, parents of children with more severe ASD symptoms or non-Dutch parents were more likely to be classified as 'unresolved'. Sub-sample analysis revealed stability of reaction to ASD-diagnosis. The majority of parents adapted well to the circumstances and the care for their child. Autism severity and parental nationality were significant factors affecting parental reactions. Thus, early identification of parental reaction to children's ASD-diagnosis may aid in providing more tailored parental support programs. C1 [Poslawsky, Irina E.; Van Daalen, Emma; Van Engeland, Herman] Univ Med Ctr Utrecht, Div Neurosci, Brain Ctr Rudolf Magnus, NL-3508 GA Utrecht, Netherlands. [Naber, Fabienne B. A.] Leiden Univ, Ctr Child & Family Studies, NL-2300 RA Leiden, Netherlands. [Naber, Fabienne B. A.] Erasmus Univ, Sch Pedag & Educ Sci, NL-3000 DR Rotterdam, Netherlands. RP Poslawsky, IE (reprint author), Univ Med Ctr Utrecht, Div Neurosci, Brain Ctr Rudolf Magnus, A01-468,POB 85500, NL-3508 GA Utrecht, Netherlands. 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PD JUN PY 2014 VL 45 IS 3 BP 294 EP 305 DI 10.1007/s10578-013-0400-z PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AE5TE UT WOS:000334051400004 PM 23959534 ER PT J AU Nuske, HJ Vivanti, G Dissanayake, C AF Nuske, Heather J. Vivanti, Giacomo Dissanayake, Cheryl TI Reactivity to fearful expressions of familiar and unfamiliar people in children with autism: an eye-tracking pupillometry study SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Emotion; Familiarity; Physiological reactivity; Pupillometry; Eye-tracking; Response latency ID FACIAL-EMOTION RECOGNITION; SPECTRUM DISORDER; YOUNG-CHILDREN; ASPERGER-SYNDROME; FACE RECOGNITION; IMPAIRED RECOGNITION; PUPILLARY RESPONSES; 6-MONTH-OLD INFANTS; PERSON FAMILIARITY; NEURAL CIRCUITRY AB Background: Individuals with autism are often reported to have difficulty with emotion processing. However, clinical and experimental data show that they are sensitive to familiarity; for example, they show normative attachment to familiar people, and have normative brain activity in response to familiar faces. To date, no study has measured their reactivity to the emotions of familiar vs. unfamiliar people. Thus, our aim was to determine whether individuals with autism would show normative reactivity to emotion in familiar people. Methods: Participants were 21 children with autism and 21 children with typical development, aged two to five years, matched on age and gender. The children observed videos of familiar people (their child-care teachers) and unfamiliar people expressing fear, whilst their visual attention and pupillary reactions were recorded (the latter as an index of emotional reactivity), using eye tracking technology. Results: The children with autism showed normative pupillary reactions (peak magnitude) to fear expressed by familiar people, but a reduced response to fear expressed by unfamiliar people. However, across familiarity conditions, the children with autism had longer latency peak responses than the typically developing children. This pattern of findings was independent of cognitive factors or visual attention as visual attention by group was not related to familiarity condition. The children with autism had reduced visual attention to neutral faces; however, on fearful faces there were no group differences. Abnormalities in pupillary reactivity in the autism group were related to less prosocial behaviour and more severe play and communication deficits. Conclusions: Children with autism were less atypical in their responses to fearful expressions of people they know, arguing against a pervasive emotional impairment in autism, but rather one that may be mediated by familiarity. 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W., 1963, PROGRESS BRAIN RESEA, V3, P50, DOI 10.1016/S0079-6123(08)60566-X NR 119 TC 2 Z9 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1866-1947 EI 1866-1955 J9 J NEURODEV DISORD JI J. Neurodev. Disord. PD MAY 31 PY 2014 VL 6 AR 14 DI 10.1186/1866-1955-6-14 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AK5MO UT WOS:000338469000001 PM 24982695 ER PT J AU Caulfield, F Ewing, L Burton, N Avard, E Rhodes, G AF Caulfield, Frances Ewing, Louise Burton, Nichola Avard, Eleni Rhodes, Gillian TI Facial Trustworthiness Judgments in Children with ASD Are Modulated by Happy and Angry Emotional Cues SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; ASPERGER-SYNDROME; SOCIAL COGNITION; FACES; EXPRESSIONS; BEHAVIOR; IMPRESSIONS; AMYGDALA; BRAIN; ATTRACTIVENESS AB Appearance-based trustworthiness inferences may reflect the misinterpretation of emotional expression cues. Children and adults typically perceive faces that look happy to be relatively trustworthy and those that look angry to be relatively untrustworthy. Given reports of atypical expression perception in children with Autism Spectrum Disorder (ASD), the current study aimed to determine whether the modulation of trustworthiness judgments by emotional expression cues in children with ASD is also atypical. Cognitively-able children with and without ASD, aged 6-12 years, rated the trustworthiness of faces showing happy, angry and neutral expressions. Trust judgments in children with ASD were significantly modulated by overt happy and angry expressions, like those of typically-developing children. Furthermore, subtle emotion cues in neutral faces also influenced trust ratings of the children in both groups. These findings support a powerful influence of emotion cues on perceived trustworthiness, which even extends to children with social cognitive impairments. C1 [Caulfield, Frances; Ewing, Louise; Burton, Nichola; Avard, Eleni; Rhodes, Gillian] Univ Western Australia, Sch Psychol, Australian Res Council, Ctr Excellence Cognit & Its Disorders, Perth, WA 6009, Australia. RP Ewing, L (reprint author), Univ Western Australia, Sch Psychol, Australian Res Council, Ctr Excellence Cognit & Its Disorders, Perth, WA 6009, Australia. EM louise.ewing@uwa.edu.au RI Ewing, Louise/H-9158-2014 FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; ARC Professional Fellowship [DP0877379]; ARC Discovery Outstanding Researcher Award [DP130102300] FX This research was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Professional Fellowship to Rhodes (DP0877379) and an ARC Discovery Outstanding Researcher Award to Rhodes (DP130102300). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Thirty-nine U.S. caregivers completed in-depth interviews, PWB Scales, and Family Time and Routines Index (FTRI). We used a multi-step analysis. Interview data was coded and vignettes created without knowledge of PWB and FTRI ratings. Next, the relationship of quantitative measures was analyzed. Four groups were created using FTRI-extent and PWB means: (1) low routine-low PWB, (2) low routine-high PWB, (3) high routine-low PWB, and (4) high routine-high PWB. We examined qualitative differences in key features between groups. Findings: Total PWB and FTRI scores were not significantly correlated, PWB Purpose in Life and FTRI-extent scores were moderately positively correlated, and PWB Environmental Mastery and FTRI-extent correlation approached significance. Qualitative findings describe caregivers' structuring of routines, intensity of oversight, support in routines, management of dinner, paid work, and needs for respite. The four groups differed in paid work, household support, degree the child could self-occupy, Environmental Mastery, and opportunities to recuperate. Caregivers with higher levels of well-being and more regular routines did paid work, had supportive spouses, had children who more often could follow routines, had higher Environmental Mastery, could orchestrate a family meal, and had breaks from care in either work or leisure. All Native American caregivers and Mexican American caregivers with spouses were in the high routine-high PWB group. Insight into this complex negotiation between family members within daily routines may provide practitioners a better understanding of how to work within family circles to foster therapeutic alliances, identify focused intervention targets, and promote positive family wide outcomes. C1 [Larson, Elizabeth; Miller-Bishoff, Thomas] Univ Wisconsin, Dept Kinesiol, Occupat Therapy Program, Madison, WI 53706 USA. 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PD MAY 30 PY 2014 VL 5 AR 495 DI 10.3389/fpsyg.2014.00495 PG 14 WC Psychology, Multidisciplinary SC Psychology GA AJ3CD UT WOS:000337541800001 PM 24910625 ER PT J AU Dvash, J Ben-Zeev, A Noga, A Shamay-Tsoory, S AF Dvash, Jonathan Ben-Zeev, Aaron Noga, Adler Shamay-Tsoory, Simone TI The road not taken: Social vs. private comparisons in Asperger's syndrome and high functioning autism SO PSYCHIATRY RESEARCH LA English DT Article DE Social comparison; Autism; Counterfactual thinking; Emotion; Reward processing ID COUNTERFACTUAL THINKING; SPECTRUM DISORDERS; JOINT ATTENTION; YOUNG-CHILDREN; EMOTIONS; OTHERS; BRAIN; MIND; DYSFUNCTION; IMPAIRMENT AB Evaluation of the outcomes of our decisions may instigate comparisons of our actual outcome with those of others (social comparisons) or comparisons with alternative outcomes of choices not made (private comparisons). Previous research has suggested a deficit in attention to social information among individuals with autism spectrum disorders. As social comparison involves the processing of social information, here we investigated the orientation towards and sensitivity to social vs. private comparisons in individuals with autism spectrum disorders. We compared the sensitivity to social vs. private comparisons among individuals diagnosed with Asperger's Syndrome (AS) or High Functioning Autism, using a task that entailed monetary rewards. Results showed that while individuals with AS generally demonstrate comparable sensitivity to absolute and relative rewards, they show less sensitivity to social comparison as compared to controls. Furthermore, they are characterized by a higher sensitivity to private rather than social comparison. These results suggest that low sensitivity to social comparisons is an important factor to consider in autism spectrum disorders. (C) 2014 Elsevier Ireland Ltd. All rights reserved. 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TI AUDITORY-CUED SENSORIMOTOR TASK REVEALS DISENGAGEMENT DEFICITS IN RATS EXPOSED TO THE AUTISM-ASSOCIATED TERATOGEN VALPROIC ACID SO NEUROSCIENCE LA English DT Article DE autism; disengagement; temporal lobe; valproic acid; attention; savant ID TEMPORAL CORTEX; SPECTRUM DISORDERS; NEURAL MECHANISMS; VISUAL-ATTENTION; ANIMAL-MODEL; MEMORY; CHILDREN; PROJECTIONS; MODULATION; THALAMUS AB Autism Spectrum Disorder (ASD) is often found to co-exist with non-core behavioral manifestations that include difficulties in disengagement of attention to sensory cues. Here we examined whether this behavioral abnormality can be induced in rats prenatally exposed to valproic acid (VPA), a well-established teratogen associated with ASD animal models. We tested rats using an auditory-cued sensorimotor task (ACST) based on the premise that ACST will be more sensitive to developmental changes in temporal association cortex (TeA) of the posterior attention system. We show that VPA rats learned the ACST markedly faster than control animals, but they exhibited a profound preoccupation with cues associated with the expectancy at the reward location such that disengagement was disrupted. Control rats on the other hand were able to disengage and utilize auditory cues for re-engagement. However, both control and VPA-treated rats performed similarly when tested on novel object recognition (NOR) and novel context mismatch (NOCM) behavioral tasks that are known to be sensitive to normal perirhinal and prefrontal network functioning respectively. Consistent with disrupted posterior rather than frontal networks, we also report that VPA can selectively act on deep-layer TeA cortical neurons by showing that VPA increased dendritic density in isolated deep-layer TeA but not frontal neurons. These results describe a useful approach to examine the role of cue-dependent control of attention systems in rodent models of autism and suggest that disengagement impairments may arise from an inability to modify behavior through the appropriate use of sensory cue associations. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Chomiak, T.; Hung, J.; Cihal, A.; Dhaliwal, J.; Baghdadwala, M. I.; Dzwonek, A.; Podgorny, P.; Hu, B.] Univ Calgary, Fac Med, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada. RP Chomiak, T (reprint author), 3280 Hosp Dr NW, Calgary, AB, Canada. EM tgchomia@ucalgary.ca; hub@ucalgary.ca FU Canadian Institutes of Health Research, Canada; CIHR Regenerative Medicine Initiative, Canada; NSERC, Canada; Killam Trusts; Sinneave Family Foundation FX This study was supported by grants to B. H. from Canadian Institutes of Health Research, Canada; CIHR Regenerative Medicine Initiative, Canada; and training grants from NSERC, Canada; and Killam Trusts. TC was previously supported by a fellowship from Sinneave Family Foundation. We would also like to thank Dr. Minh Dang Nguyen's lab and Dr. Laura Craig for technical assistance. 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Genetic factors are strongly implicated in IS, however, the exact genetic defects remain unknown in the majority of cases. Rare mutations in a single gene or in copy number variants (CNVs) have been implicated in IS of children in Western countries. The objective of this study was to dissect the role of copy number variations in Chinese children with infantile spasms. Methods: We used the Agilent Human Genome CGH microarray 180 K for genome-wide detection of CNVs. Real-time qPCR was used to validate the CNVs. We performed genomic and medical annotations for individual CNVs to determine the pathogenicity of CNVs related to IS. Results: We report herein the first genome-wide CNV analysis in children with IS, detecting a total of 14 CNVs in a cohort of 47 Chinese children with IS. Four CNVs (4/47 = 8.5%) (1q21.1 gain; 1q44, 2q31.1, and 17p13 loss) are considered to be pathogenic. The CNV loss at 17p13.3 contains PAFAH1B1 (LIS1), a causative gene for lissencephaly. Although the CNVs at 1q21.1, 1q44, and 2q23.1 have been previously implicated in a wide spectrum of clinical features including autism spectrum disorders (ASD) and generalized seizure, our study is the first report identifying them in individuals with a primary diagnosis of IS. The CNV loss in the 1q44 region contains HNRNPU, a strong candidate gene recently suggested in IS by the whole exome sequencing of children with IS. The CNV loss at 2q23.1 includes MBD5, a methyl-DNA binding protein that is a causative gene of ASD and a candidate gene for epileptic encephalopathy. We also report a distinct clinical presentation of IS, microcephaly, intellectual disability, and absent hallux in a case with the 2q23.1 deletion. Conclusion: Our findings strongly support the role of CNVs in infantile spasms and expand the clinical spectrum associate with 2q23.1 deletion. In particular, our study implicates the HNRNPU and MBD5 genes in Chinese children with IS. Our study also supports that the molecular mechanisms of infantile spasms appear conserved among different ethnic backgrounds. C1 [Du, Xiaonan; Yu, Lifei; Guo, Xiaohong; Sun, Daokan; Zhou, Shuizhen; Wang, Yi] Fudan Univ, Childrens Hosp, Div Neurol, Shanghai 201102, Peoples R China. [An, Yu; Liu, Renchao; Qin, Yanrong; Wu, Bailin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [An, Yu; Liu, Renchao; Qin, Yanrong; Wu, Bailin] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200032, Peoples R China. [Wu, Bailin] Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA USA. [Jiang, Yong-hui] Duke Univ, Sch Med, Dept Pediat & Neurobiol, Div Med Genet, Durham, NC 27710 USA. RP Jiang, YH (reprint author), Duke Univ, Sch Med, Dept Pediat & Neurobiol, Div Med Genet, 905 S LaSalle ST, Durham, NC 27710 USA. EM yong-hui.jiang@duke.edu; yiwang@shmu.edu.cn FU National Natural Science Foundation of China (NSCF) [81071116]; Shanghai Committee of Science and Technology (STCSM) [12XD1401100]; 973 National Basic Research Program of China [2010CB529601]; NIH [5R01MH098114-03] FX We would like to thank all of families who participated in this project. This study was supported by a grant from the National Natural Science Foundation of China (NSCF, 81071116) and the Shanghai Committee of Science and Technology (STCSM, 12XD1401100). YA is supported by the 973 National Basic Research Program of China (2010CB529601). YHJ is supported by NIH 5R01MH098114-03. 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To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmrl knockout (KO) mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild-type and Fmrl KO mice seen as shortened latency to enter the center area in the open field test. In Fmrl KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced brain-derived neurotrophic factor (BDNF) and increased TrkB receptor expression levels in the hippocampus of Fmrl KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmrl KO mice when compared with wild-type controls. The postnatal mRNA expression of serotonin transporter (SERT) was reduced in the thalamic nuclei of Fmrl KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild-type and Fmrl mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD. C1 [Uutela, Marko; Hunter, Kerri; Castren, Maija L.] Univ Helsinki, Inst Biomed Physiol, FIN-00014 Helsinki, Finland. [Lindholm, Jesse; Rantamaki, Tomi; Umemori, Juzoh; Voikar, Vootele] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. [Castren, Maija L.] Univ Helsinki Hosp, Hosp Children & Adolescents, Dept Child Neurol, Helsinki, Finland. RP Castren, ML (reprint author), Univ Helsinki, Inst Biomed Physiol, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland. 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Cell. Neurosci. PD MAY 28 PY 2014 VL 8 AR 150 DI 10.3389/fncel.2014.00150 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AI1XR UT WOS:000336649000002 PM 24904293 ER PT J AU Sylvester, J Donnell, N Gray, S Higgins, K Stalker, K AF Sylvester, Janet Donnell, Nigel Gray, Shelley Higgins, Kate Stalker, Kirsten TI A survey of disabled children and young people's views about their quality of life SO DISABILITY & SOCIETY LA English DT Article DE children's views; disabled children and young people; survey; quality of life; social relational understanding of disability ID DISABILITY; CAREGIVERS; FAMILIES; AUTISM AB This study aimed to explore disabled children and young people's perspectives about their quality of life, in terms of physical, mental and social well-being. Ninety-one disabled children, recruited through voluntary organisations in Scotland, completed KIDSCREEN-27, a validated measure of health-related quality of life for children. Findings were compared with those from a European study of predominantly non-disabled children. The children gave largely positive reports about school, family relationships and their physical health. However, one in three reported often feeling 'sad' and many were excluded from social activities with their peers. Expectations of achieving academic qualifications, and moving into further or higher education, were generally low. The children's perceived quality of life was lower than their European counterparts, less so in relation to school but particularly for friendships and peer support. The findings are discussed in the light of the social relational understanding of disability. Policy and practice implications are identified. C1 [Sylvester, Janet; Donnell, Nigel] Scot Inform Ltd, Edinburgh, Midlothian, Scotland. [Gray, Shelley] Hlth & Social Care Alliance, Glasgow, Lanark, Scotland. [Higgins, Kate] Children 1st, Edinburgh, Midlothian, Scotland. 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PD MAY 28 PY 2014 VL 29 IS 5 BP 763 EP 777 DI 10.1080/09687599.2013.848782 PG 15 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA AH1MD UT WOS:000335884000008 ER PT J AU Isomura, T Ogawa, S Yamada, S Shibasaki, M Masataka, N AF Isomura, Tomoko Ogawa, Shino Yamada, Satoko Shibasaki, Masahiro Masataka, Nobuo TI Preliminary evidence that different mechanisms underlie the anger superiority effect in children with and without Autism Spectrum Disorders SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE Autism Spectrum Disorders; anger superiority effect; children; face-in-the-crowd effect; visual search; emotion; facial expressions; attention ID EMOTIONAL FACIAL EXPRESSIONS; VISUAL-SEARCH; CAPTURE ATTENTION; REAL FACES; CROWD; THREAT; RESPONSES; STIMULI; PARTS AB Previous studies have demonstrated that angry faces capture humans' attention more rapidly than emotionally positive faces. This phenomenon is referred to as the anger superiority effect (ASE). Despite atypical emotional processing, adults and children with Autism Spectrum Disorders (ASD) have been reported to show ASE as well as typically developed (TD) individuals. So far, however, few studies have clarified whether or not the mechanisms underlying ASE are the same for both TD and ASD individuals. Here, we tested how TD and ASD children process schematic emotional faces during detection by employing a recognition task in combination with a face-in-the-crowd task. Results of the face-in-the-crowd task revealed the prevalence of ASE both in TD and ASD children. However, the results of the recognition task revealed group differences: In TD children, detection of angry faces required more configural face processing and disrupted the processing of local features. In ASD children, on the other hand, it required more feature-based processing rather than configural processing. Despite the small sample sizes, these findings provide preliminary evidence that children with ASD, in contrast to TD children, show quick detection of angry faces by extracting local features in faces. C1 [Isomura, Tomoko; Ogawa, Shino; Yamada, Satoko; Shibasaki, Masahiro; Masataka, Nobuo] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan. RP Isomura, T (reprint author), Kyoto Univ, Primate Res Inst, 41-2 Kanrin, Inuyama, Aichi 484, Japan. 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Psychol. PD MAY 27 PY 2014 VL 5 AR 461 DI 10.3389/fpsyg.2014.00461 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AI6JR UT WOS:000336980400001 PM 24904477 ER PT J AU Tenenbaum, EJ Amso, D Abar, B Sheinkopf, SJ AF Tenenbaum, Elena J. Amso, Dima Abar, Beau Sheinkopf, Stephen J. TI Attention and word learning in autistic, language delayed, and typically developing children SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE autism spectrum disorders; eye tracking; word learning; attention to faces; language development ID DIAGNOSTIC OBSERVATION SCHEDULE; JOINT ATTENTION; SPECTRUM DISORDERS; MUTUAL EXCLUSIVITY; VOCABULARY GROWTH; YOUNG-CHILDREN; GAZE BEHAVIOR; SOCIAL SCENES; 2ND YEAR; INFANTS AB Previous work has demonstrated that patterns of social attention hold predictive value for language development in typically developing infants. The goal of this research was to explore how patterns of attention in autistic, language delayed, and typically developing children relate to early word learning and language abilities. We tracked patterns of eye movements to faces and objects while children watched videos of a woman teaching them a series of new words. Subsequent test trials measured participants' recognition of these novel word-object pairings. Results indicated that greater attention to the speaker's mouth was related to higher scores on standardized measures of language development for autistic and typically developing children (but not for language delayed children). This effect was mediated by age for typically developing, but not autistic children. When effects of age were controlled for, attention to the mouth among language delayed participants was negatively correlated with standardized measures of language learning. Attention to the speaker's mouth and eyes while she was teaching the new words was also predictive of faster recognition of those words among autistic children. These results suggest that language delays among children with autism may be driven in part by aberrant social attention, and that the mechanisms underlying these delays may differ from those in language delayed participants without autism. C1 [Tenenbaum, Elena J.; Sheinkopf, Stephen J.] Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Providence, RI 02905 USA. [Amso, Dima] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02905 USA. [Abar, Beau] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Sheinkopf, Stephen J.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Tenenbaum, EJ (reprint author), Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. 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TI A 1.5 Mb terminal deletion of 12p associated with autism spectrum disorder SO GENE LA English DT Article DE Autism spectrum disorder; 12p13.33 microdeletion; Array comparative genomic hybridization; ERC1; Neurodevelopmental delay ID SUBTELOMERIC DELETION; MICRODELETION; RELEASE; ELKS AB We report a patient with a terminal 12p deletion associated with autism spectrum disorder (ASD). This 12p13.33 deletion is 1.5 Mb in size and encompasses 13 genes (B4GALNT3, CCDC77, ERC1, FBXL14, IQSEC3, KDM5A, LINC00942, L00574538, NINJ2, RAD52, SLC6Al2, SLC6A13 and WNK1). All previous cases reported with partial monosomy of 12p13.33 are associated with neurodevelopmental delay, and we suggest that ERC1, which encodes a regulator of neurotransmitter release, is the best gene candidate contributing to this phenotype as well as to the ASD of our patient. (C) 2014 Elsevier B.V. All rights reserved. C1 [Silva, Isabela M. W.] Pontificia Univ Catolica Parana, Sch Hlth & Biosci, Grp Adv Mol Invest NIMA, BR-11558021 Curitiba, Parana, Brazil. [Rosenfeld, Jill] PerkinElmer Inc, Signature Genom, Spokane, WA USA. [Antoniuk, Sergio A.] Univ Fed Parana, Dept Pediat, BR-80060000 Curitiba, Parana, Brazil. [Raskin, Salmo] GENETIKA Ctr Aconselhamento & Lab Genet, Curitiba, Parana, Brazil. [Raskin, Salmo; Sotomaior, Vanessa S.] Pontificia Univ Catolica Parana, Sch Med, Grad Program Hlth Sci, Grp Adv Mol Invest NIMA, BR-11558021 Curitiba, Parana, Brazil. RP Sotomaior, VS (reprint author), Pontificia Univ Catolica Parana, Escola Med, Programs Posgrad Ciencias Saude, Rua Imaculada Conceicao 1155, BR-11558021 Curitiba, Parana, Brazil. 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Belkin, Mikhail Dennis, Simon TI Robust features for the automatic identification of autism spectrum disorder in children SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Event-related potential; EEG; Classification ID DIAGNOSTIC OBSERVATION SCHEDULE; RATING-SCALE; BLINK RATE; COHERENCE; VALIDITY; CONNECTIVITY; POTENTIALS; ARTIFACTS; BEHAVIOR; SUBTYPES AB Background: It is commonly reported that children with autism spectrum disorder (ASD) exhibit hyper-reactivity or hypo-reactivity to sensory stimuli. Electroencephalography (EEG) is commonly used to study neural sensory reactivity, suggesting that statistical analysis of EEG recordings is a potential means of automatic classification of the disorder. EEG recordings taken from children, however, are frequently contaminated with large amounts of noise, making analysis difficult. In this paper, we present a method for the automatic extraction of noise-robust EEG features, which serve to quantify neural sensory reactivity. We show the efficacy of a system for the classification of ASD using these features. Methods: An oddball paradigm was used to elicit event-related potentials from a group of 19 ASD children and 30 typically developing children. EEG recordings were taken and robust features were extracted. A support vector machine, logistic regression, and a naive Bayes classifier were used to classify the children as having ASD or being typically developing. Results: A classification accuracy of 79% was achieved, making our method competitive with other automatic diagnosis methods based on EEG. Additionally, we found that classification performance is reduced if eye blink artifacts are removed during preprocessing. Conclusions: This study shows that robust EEG features that quantify neural sensory reactivity are useful for the classification of ASD. We showed that noise-robust features are crucial for our analysis, and observe that traditional preprocessing methods may lead to poor classification performance in the face of a large amount of noise. Further exploration of alternative preprocessing methods is warranted. C1 [Eldridge, Justin; Belkin, Mikhail] Ohio State Univ, Dept Comp Sci & Engn, Columbus, OH 43210 USA. [Lane, Alison E.] Univ Newcastle, Sch Hlth Sci, Callaghan, NSW 2308, Australia. [Dennis, Simon] Univ Newcastle, Sch Psychol, Callaghan, NSW 2308, Australia. RP Eldridge, J (reprint author), Ohio State Univ, Dept Comp Sci & Engn, 395 Dreese Labs,2015 Neil Ave, Columbus, OH 43210 USA. EM eldridge@cse.ohio-state.edu FU Ohio State University Center for Clinical and Translational Science [UL1RR025755]; National Center for Research Resources; National Center for Advancing Translational Sciences [8KL2TR000112-05, 8UL1TR000090-05, 8TL1TR000091-05]; Center for Cognitive Science at the Ohio State University FX We would like to thank Karen Harpster and Brittany Hand. This project was partially supported by grants to AEL from the Ohio State University Center for Clinical and Translational Science (Award Number UL1RR025755) and from the National Center for Research Resources and the National Center for Advancing Translational Sciences (8KL2TR000112-05, 8UL1TR000090-05, and 8TL1TR000091-05). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. JE's work was partially funded by a fellowship from the Center for Cognitive Science at the Ohio State University. 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PD MAY 23 PY 2014 VL 6 AR 12 DI 10.1186/1866-1955-6-12 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AK5MJ UT WOS:000338468500001 PM 24936212 ER PT J AU Chong, WWS Lo, IFM Lam, STS Wang, CC Luk, HM Leung, TY Choy, KW AF Chong, Wilson Wai Sing Lo, Ivan Fai Man Lam, Stephen Tak Sum Wang, Chi Chiu Luk, Ho Ming Leung, Tak Yeung Choy, Kwong Wai TI Performance of chromosomal microarray for patients with intellectual disabilities/developmental delay, autism, and multiple congenital anomalies in a Chinese cohort SO MOLECULAR CYTOGENETICS LA English DT Article DE Chromosomal microarray; Array CGH; Developmental delay; Intellectual disabilities; Multiple congenital anomalies ID COMPARATIVE GENOMIC HYBRIDIZATION; COPY-NUMBER VARIANTS; MENTAL-RETARDATION; DEVELOPMENTAL DELAY; ARRAY-CGH; SUBTELOMERIC REGIONS; DYSMORPHIC FEATURES; AMERICAN-COLLEGE; DISABILITY; DISORDERS AB Background: Chromosomal microarray (CMA) is currently the first-tier genetic test for patients with idiopathic neuropsychiatric diseases in many countries. Its improved diagnostic yield over karyotyping and other molecular testing facilitates the identification of the underlying causes of neuropsychiatric diseases. In this study, we applied oligonucleotide array comparative genomic hybridization as the molecular genetic test in a Chinese cohort of children with DD/ID, autism or MCA. Results: CMA identified 7 clinically significant microduplications and 17 microdeletions in 19.0% (20/105) patients, with size of aberrant regions ranging from 11 kb to 10.7 Mb. Fourteen of the pathogenic copy number variant (CNV) detected corresponded to well known microdeletion or microduplication syndromes. Four overlapped with critical regions of recently identified genomic syndromes. We also identified a rare de novo 2.3 Mb deletion at 8p21.3-21.2 as a pathogenic submicroscopic CNV. We also identified two novel CNVs, one at Xq28 and the other at 12q21.31-q21.33, in two patients (1.9%) with unclear clinical significance. 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In this study, university participants from the social sciences, physical sciences, and humanities completed a battery of measures that assessed face, object and emotion recognition abilities, general perceptual-cognitive style, and sub-clinical autistic traits (the Autism Quotient (AQ)). We employed separate hierarchical multiple regression analyses to evaluate which factors could predict face recognition scores and AQ scores. Gender, object recognition performance, and AQ scores predicted face recognition behaviour. Specifically, males, individuals with more autistic traits, and those with lower object recognition scores performed more poorly on the face recognition test. Conversely, university major, gender and face recognition performance reliably predicted AQ scores. Science majors, males, and individuals with poor face recognition skills showed more autistic-like traits. These results suggest that the broader autism phenotype is associated with lower face recognition abilities, even among typically developing individuals. C1 [Halliday, Drew W. R.; MacDonald, Stuart W. S.; Tanaka, James W.] Univ Victoria, Victoria, BC, Canada. [Sherf, Suzanne K.] Penn State Univ, State Coll, PA USA. [Halliday, Drew W. R.; Tanaka, James W.] Ctr Autism Res Technol & Educ, Victoria, BC, Canada. RP Tanaka, JW (reprint author), Univ Victoria, Victoria, BC, Canada. EM jtanaka@uvic.ca FU Temporal Dynamics of Learning Center (NSF) [SBE-0542013]; National Institute of Child Health and Human Development (NIH) [HD-46526]; Natural Sciences and Engineering Research FX The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported by grants from the Temporal Dynamics of Learning Center (NSF Grant #SBE-0542013), National Institute of Child Health and Human Development (NIH Grant HD-46526) and the Natural Sciences and Engineering Research. 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Jansen, Wilma Raat, Hein TI Screening for Autism Spectrum Disorders with the Brief Infant-Toddler Social and Emotional Assessment SO PLOS ONE LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; TRAITS QUESTIONNAIRE ESAT; PRESCHOOL-CHILDREN; ASSESSMENT BITSEA; ASSESSMENT ITSEA; EARLY-CHILDHOOD; DIAGNOSIS; PREVALENCE; RELIABILITY; COMPETENCE AB Objective: Using parent-completed questionnaires in (preventive) child health care can facilitate the early detection of psychosocial problems and psychopathology, including autism spectrum disorders (ASD). A promising questionnaire for this purpose is the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). The screening accuracy with regard to ASD of the BITSEA Problem and Competence scales and a newly calculated Autism score were evaluated. Method: Data, that was collected between April 2010 and April 2011, from a community sample of 2-year-olds (N = 3127), was combined with a sample of preschool children diagnosed with ASD (N = 159). For the total population and for subgroups by child's gender, area under the Receiver Operating Characteristic (ROC) curve was examined, and across a range of BITSEA Problem, Competence and Autism scores, sensitivity, specificity, positive and negative likelihood ratio's, diagnostic odds ratio and Youden's index were reported. Results: The area under the ROC curve (95% confidence interval, [95%CI]) of the Problem scale was 0.90(0.87-0.92), of the Competence scale 0.93(0.91-0.95), and of the Autism score 0.95(0.93-0.97). For the total population, the screening accuracy of the Autism score was significantly better, compared to the Problem scale. The screening accuracy of the Competence scale was significantly better for girls (AUC = 0.97; 95%CI = 0.95-0.98) than for boys (AUC = 0.91; 95%CI = 0.88-0.94). Conclusion: The results indicate that the BITSEA scales and newly calculated Autism score have good discriminative power to differentiate children with and without ASD. Therefore, the BITSEA may be helpful in the early detection of ASD, which could have beneficial effects on the child's development. C1 [Kruizinga, Ingrid; Raat, Hein] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. [Visser, Janne C.] Karakter Univ, Ctr Nijmegen, Nijmegen, Netherlands. [van Batenburg-Eddes, Tamara] Vrije Univ Amsterdam, Dept Psychol & Educ, Amsterdam, Netherlands. [Carter, Alice S.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Jansen, Wilma] Rotterdam Municipal Hlth Serv GGD Rotterdam Rijnm, Dept Youth Policy, Rotterdam, Netherlands. RP Raat, H (reprint author), Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. EM h.raat@erasmusmc.nl FU ZonMw, The Netherlands Organization for Health Research and Development [80-82435-98-8058] FX This study is funded by a grant from the funding body ZonMw, The Netherlands Organization for Health Research and Development (www.zonmw.nl), project number: 80-82435-98-8058. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI CBRAIN: a web-based, distributed computing platform for collaborative neuroimaging research SO FRONTIERS IN NEUROINFORMATICS LA English DT Article DE eScience; distributed computing; meta-scheduler; collaborative platform; interoperability; cloud computing; neuroimaging; visualization ID IMAGE-ANALYSIS AB The Canadian Brain Imaging Research Platform (CBRAIN) is a web-based collaborative research platform developed in response to the challenges raised by data-heavy, compute-intensive neuroimaging research. CBRAIN offers transparent access to remote data sources, distributed computing sites, and an array of processing and visualization tools within a controlled, secure environment. Its web interface is accessible through any modern browser and uses graphical interface idioms to reduce the technical expertise required to perform large-scale computational analyses. CBRAIN's flexible meta-scheduling has allowed the incorporation of a wide range of heterogeneous computing sites, currently including nine national research High Performance Computing (HPC) centers in Canada, one in Korea, one in Germany, and several local research servers. CBRAIN leverages remote computing cycles and facilitates resource-interoperability in a transparent manner for the end-user. Compared with typical grid solutions available, our architecture was designed to be easily extendable and deployed on existing remote computing sites with no tool modification, administrative intervention, or special software/hardware configuration. As October 2013, CBRAIN serves over 200 users spread across 53 cities in 17 countries. The platform is built as a generic framework that can accept data and analysis tools from any discipline. However, its current focus is primarily on neuroimaging research and studies of neurological diseases such as Autism, Parkinson's and Alzheimer's diseases, Multiple Sclerosis as well as on normal brain structure and development. This technical report presents the CBRAIN Platform, its current deployment and usage and future direction. C1 [Sherif, Tarek; Rioux, Pierre; Rousseau, Marc-Etienne; Kassis, Nicolas; Beck, Natacha; Adalat, Reza; Das, Samir; Glatard, Tristan; Evans, Alan C.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, ACElab, Montreal, PQ H3A 2B4, Canada. [Glatard, Tristan] Univ Lyon, CNRS, INSERM, CREATIS, Lyon, France. RP Evans, AC (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, ACElab, 3801 Univ St,Webster 2B 208, Montreal, PQ H3A 2B4, Canada. EM alan.evans@mcgill.ca RI Glatard, Tristan/H-3656-2014 FU CANARIE; Canada's Advanced Research and Innovation Network; McGill University; Compute Canada FX This work has been funded by CANARIE, Canada's Advanced Research and Innovation Network (http://www.canarie.ca) and McGill University. We are grateful for the computing cycles, storage, and support obtained from Compute Canada (https:// computecanada.ca) and our collaborators at KISTI (Korea) and at the Julich Supercomputing Centre (Germany). In addition to the authors, we would like to thank Mathieu Desrosiers for contributing sustained development efforts and site project coordination. 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Here, we perform a systematic investigation of the role of both de novo and inherited LOF variants in schizophrenia using exome sequencing data from 231 case and 34 control trios. We identify two de novo LOF variants in the SETD1A gene, which encodes a subunit of histone methyltransferase, a finding unlikely to have occurred by chance, and provide evidence for a more general role of chromatin regulators in schizophrenia risk. Transmission pattern analyses reveal that LOF variants are more likely to be transmitted to affected individuals than controls. This is especially true for private LOF variants in genes intolerant to functional genetic variation. These findings highlight the contribution of LOF mutations to the genetic architecture of schizophrenia and provide important insights into disease pathogenesis. C1 [Takata, Atsushi; Xu, Bin; Karayiorgou, Maria] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Ionita-Laza, Iuliana] Columbia Univ, Med Ctr, Dept Biostat, New York, NY 10032 USA. [Roos, J. Louw] Univ Pretoria, Dept Psychiat, Weskoppies Hosp, ZA-0001 Pretoria, South Africa. [Gogos, Joseph A.] Columbia Univ, Med Ctr, Dept Neurosci, New York, NY 10032 USA. [Gogos, Joseph A.] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Karayiorgou, Maria] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Gogos, JA (reprint author), Columbia Univ, Med Ctr, Dept Neurosci, New York, NY 10032 USA. EM jag90@columbia.edu; mk2758@columbia.edu FU National Institute of Mental Health (NIMH) [MH061399, MH097879]; Lieber Center for Schizophrenia Research at Columbia University; JSPS; National Alliance for Research in Schizophrenia and Depression (NARSAD) FX We are grateful to all the families who participated in this research. We thank S. L. Lundy for valuable assistance with clinical database maintenance. We also thank S. Levy and the HudsonAlpha Genomics Services Laboratory for sequencing. This work was partially supported by National Institute of Mental Health (NIMH) grants MH061399 (to M. K.) and MH097879 (to J.A.G.) and the Lieber Center for Schizophrenia Research at Columbia University. A. T. was supported by the JSPS Postdoctoral Fellowship for Research Abroad. B. X. was partially supported by a National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award. 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Vieland, Veronica Gallagher, Louise TI The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses SO MOLECULAR AUTISM LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIATION; SPECTRUM DISORDERS; COMMUNICATION CHECKLIST; GENOME; INDIVIDUALS; SCALE; RISK; IDENTIFICATION; VALIDATION AB Background: There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. Methods: In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year programto collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center. Results: Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI). Conclusions: TASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples. C1 [Buxbaum, Joseph D.; Brownfeld, Jessica M.; Pinto, Dalila] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. [Bolshakova, Nadia; Anney, Richard J. L.; Gallagher, Louise] Autism Genet Grp, Sch Med, Dept Psychiat, Trin Coll, Dublin 8, Ireland. [Bender, Patrick] NIMH, Bethesda, MD 20892 USA. [Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL 60608 USA. [Coon, Hilary] Univ Utah, Dept Psychiat, Sch Med, Salt Lake City, UT 84108 USA. [Cuccaro, Michael] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33101 USA. [Freitag, Christine M.; Poustka, Fritz] JW Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Hallmayer, Joachim] Stanford Sch Med, Dept Psychiat & Behav Sci Child & Adolescent Psyc, Stanford, CA USA. [Geschwind, Daniel] Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA. [Klauck, Sabine M.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Nurnberger, John I.] Indiana Univ, Dept Psychiat, Sch Med, Indianapolis, IN 46202 USA. [Oliveira, Guiomar] Ctr Hosp, Unidade Neurodesenvolvimento & Autismo, Serv Ctr Desenvolvimento Crianca, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Ctr Hosp, Ctr Invest & Form Clin, Pediat Hosp, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Coimbra, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Clin Pediat, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Coimbra, Inst Biomed Imaging & Life Sci, Fac Med, P-3000602 Coimbra, Portugal. [Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Dept Mol Genet, Toronto, ON M5G 1X8, Canada. [Scherer, Stephen W.] McLaughlin Ctr, Toronto, ON M5G 1X8, Canada. [Scherer, Stephen W.] Univ Toronto, Toronto, ON M5G 1X8, Canada. [Shih, Andy] Autism Speaks, New York, NY 10016 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Ctr Human Genet Res & Mol Neurosci, Nashville, TN 37232 USA. [Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. [Vicente, Astrid M.] Inst Nacl Saude Dr Ricardo Jorge, P-1649016 Lisbon, Portugal. [Vicente, Astrid M.] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal. [Vicente, Astrid M.] BioFIG Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal. [Vieland, Veronica] Ohio State Univ, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43210 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu; lgallagh@tcd.ie RI Scherer, Stephen /B-3785-2013; Sutcliffe, James/C-1348-2012 OI Scherer, Stephen /0000-0002-8326-1999; Sutcliffe, James/0000-0001-5200-6007 FU National Institutes of Health [MH094303, MH100233] FX The TASC consortium collection and genotyping was supported by Autism Speaks. Funding for the sequencing and distribution of TASC samples was provided by the National Institutes of Health (MH094303 and MH100233). 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Autism PD MAY 20 PY 2014 VL 5 AR 34 DI 10.1186/2040-2392-5-34 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6BL UT WOS:000350449400001 PM 25392729 ER PT J AU Ahtola, E Stjerna, S Yrttiaho, S Nelson, CA Leppanen, JM Vanhatalo, S AF Ahtola, Eero Stjerna, Susanna Yrttiaho, Santeri Nelson, Charles A. Leppanen, Jukka M. Vanhatalo, Sampsa TI Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; 7-MONTH-OLD INFANTS; VISUAL-ATTENTION; FEARFUL FACES; COGNITIVE-DEVELOPMENT; DISENGAGEMENT; CHILDREN; DURATION; BEHAVIOR; LOOKING AB Objective: To develop new standardized eye tracking based measures and metrics for infants' gaze dynamics in the face-distractor competition paradigm. Method: Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants' initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus). Results: The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants. Conclusion: The results suggest that eye tracking based assessments of infants' cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals. Significance: Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development. C1 [Ahtola, Eero; Stjerna, Susanna; Vanhatalo, Sampsa] Univ Helsinki, Cent Hosp, Dept Childrens Clin Neurophysiol, Helsinki, Finland. [Ahtola, Eero] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Yrttiaho, Santeri; Leppanen, Jukka M.] Univ Tampere, Infant Cognit Lab, Tampere Ctr Child Hlth Res, FIN-33101 Tampere, Finland. [Nelson, Charles A.] Childrens Hosp, Labs Cognit Neurosci, Boston, MA 02115 USA. [Nelson, Charles A.] Harvard Univ, Sch Med, Boston, MA USA. [Vanhatalo, Sampsa] Univ Helsinki, Dept Neurol Sci, Helsinki, Finland. RP Ahtola, E (reprint author), Univ Helsinki, Cent Hosp, Dept Childrens Clin Neurophysiol, Helsinki, Finland. EM eero.ahtola@hus.fi FU Helsinki University Hospital; Juselius Foundation; Paivi and Sakari Sohlberg Foundation; Academy of Finland [218284]; European Community [FP7-PEOPLE-2009-IOF, 254235, 283763] FX This work was supported by Helsinki University Hospital, Juselius Foundation, Paivi and Sakari Sohlberg Foundation, Academy of Finland (#218284 and 218284), as well as the European Community's Seventh Framework Programme (FP7-PEOPLE-2009-IOF, grant agreements #254235 and #283763). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, there have been few large-scale studies reporting on the association between Conduct Disorder (CD) and motor/perception functions. The aim of the present study was to investigate how motor function and perception relate to measures of ADHD, ASD, and CD. Methods: Parents of 16,994 Swedish twins (ages nine and twelve years) were interviewed using the Autism-Tics, ADHD and other Comorbidities inventory (A-TAC), which has been validated as a screening instrument for early onset child psychiatric disorders and symptoms. Associations between categorical variables of scoring above previously validated cut-off values for diagnosing ADHD, ASD, and CD on the one hand and motor and/or perception problems on the other hand were analysed using cross-tabulations, and the Fisher exact test. Associations between the continuous scores for ADHD, ASD, CD, and the subdomains Concentration/Attention, Impulsiveness/Activity, Flexibility, Social Interaction and Language, and the categorical factors age and gender, on the one hand, and the dependent dichotomic variables Motor control and Perception problems, on the other hand, were analysed using binary logistic regression in general estimated equation models. Results: Male gender was associated with increased risk of Motor control and/or Perception problems. Children scoring above the cut-off for ADHD, ASD, and/or CD, but not those who were `CD positive' but `ADHD/ASD negative', hadmore Motor control and/or Perception problems, compared with children who were screen-negative for all three diagnoses. In the multivariable model, CD and Impulsiveness/Activity had no positive associations with Motor control and/or Perception problems. Conclusions: CD symptoms or problems with Impulsiveness/Activity were associated with Motor control or Perception problems only in the presence of ASD symptoms and/or symptoms of inattention. Our results indicate that children with CD but without ASD or inattention do not show a deviant development of motor and perceptual functions. Therefore, all children with CD should be examined concerning motor control and perception. If problems are present, a suspicion of ADHD and/or ASD should be raised. C1 [Gustafsson, Peik; Rastam, Maria] Lund Univ, Dept Clin Sci, SE-22240 Lund, Sweden. [Kerekes, Nora; Anckarsater, Henrik] Univ Gothenburg, CELAM Ctr Eth Law & Mental Hlth, Gothenburg, Sweden. [Kerekes, Nora] Swedish Prison & Probat Serv, R&D Gothenburg, Gothenburg, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. 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Neurodev. Disord. PD MAY 20 PY 2014 VL 6 AR 11 DI 10.1186/1866-1955-6-11 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AK5MG UT WOS:000338468100001 PM 24872861 ER PT J AU Engineer, CT Centanni, TM Im, KW Rahebi, KC Buell, EP Kilgard, MP AF Engineer, Crystal T. Centanni, Tracy M. Im, Kula W. Rahebi, Kimiya C. Buell, Elizabeth P. Kilgard, Michael P. TI Degraded speech sound processing in a rat model of fragile X syndrome SO BRAIN RESEARCH LA English DT Article DE Fragile X syndrome; Speech; Auditory cortex ID CORTICAL ACTIVITY PATTERNS; AUTISM SPECTRUM DISORDERS; PRIMARY AUDITORY-CORTEX; MENTAL-RETARDATION PROTEIN; CRITICAL PERIOD PLASTICITY; WORKING-MEMORY; MOUSE MODEL; DISCRIMINATION ABILITY; INSULAR CORTEX; ENVIRONMENTAL ENRICHMENT AB Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies. (C) 2014 Elsevier B.V. All rights reserved. C1 [Engineer, Crystal T.; Centanni, Tracy M.; Im, Kula W.; Rahebi, Kimiya C.; Buell, Elizabeth P.; Kilgard, Michael P.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA. RP Engineer, CT (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, 800 West Campbell Rd GR41, Richardson, TX 75080 USA. EM novitski@utdallas.edu FU National Institutes of Health [5R01DC010433] FX The authors would like to thank Akbar Afsar, Stephanie Barata, Laura Baxter, Ian Heimbuch, Ashley Ramdeen, Ryan Russell, Amreen Sitabkhan, Jacob VanNattan, and Nujeen Zubari for running behavior training sessions. This work was supported by a grant from the National Institutes of Health (Grant # 5R01DC010433 to M.P.K.). 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PD MAY 20 PY 2014 VL 1564 BP 72 EP 84 DI 10.1016/j.brainres.2014.03.049 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AI2QU UT WOS:000336703900008 PM 24713347 ER PT J AU Tan, ES Yong, MH Lim, ECP Li, ZH Brett, MSY Tan, EC AF Tan, Ee-Shien Yong, Min-Hwee Lim, Eileen C. P. Li, Zhi-hui Brett, Maggie S. Y. Tan, Ene-Choo TI Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern SO MOLECULAR CYTOGENETICS LA English DT Article DE 15q duplication syndrome; Array comparative genomic hybridization (aCGH); Copy number gain; Autism; Developmental delay; Fluorescence in situ hybridization (FISH); Marker chromosome ID AUTISM-SPECTRUM DISORDERS; PRADER-WILLI-SYNDROME; INTERSTITIAL DUPLICATION; HIGH-RESOLUTION; SCHIZOPHRENIA; REGION; REARRANGEMENTS; ABNORMALITIES; PHENOTYPE; 15Q AB Background: The 15q11-q13 region contains many low copy repeats and is well known for its genomic instability. Several syndromes are associated with genomic imbalance or copy-number-neutral uniparental disomy. We report on two patients: Patient 1 is a boy with developmental delay and autism; and Patient 2 is a girl with developmental delay, hypotonia and dysmorphism. We performed analyses to delineate their dosage in the 15q region, determine whether the patients' dosage correlates with phenotypic severity, and whether genes in the amplified regions are significantly associated with identified functional networks. Results: For the proximal region of 15q, molecular cytogenetic analysis with Agilent oligonucleotide array showed a copy number of 3 for Patient 1 and a copy number of 4 for Patient 2. Fluorescent in situ hybridization analysis of Patient 2 showed two different populations of cells with different marker chromosomes. Methylation analysis of the amplified region showed that the extra copies of small nuclear ribonucleoprotein polypeptide N gene were of maternal origin. Phenotypic severity did not correlate with the size and dosage of 15q, or whether the amplification is interstitial or in the form of a supernumerary marker. Pathway analysis showed that in Patient 2, the main functional networks that are affected by the genes from the duplicated/triplicated regions are developmental disorder, neurological disease and hereditary disease. Conclusions: The 15q11-q13 gains that were found in both patients could explain their phenotypic presentations. This report expands the cohort of patients for which 15q11-q13 duplications are molecularly characterized. C1 [Tan, Ee-Shien] KK Womens & Childrens Hosp, Genet Serv, Singapore 229899, Singapore. [Yong, Min-Hwee] KK Womens & Childrens Hosp, Cytogenet Lab, Singapore 229899, Singapore. [Lim, Eileen C. P.; Brett, Maggie S. Y.; Tan, Ene-Choo] KK Womens & Childrens Hosp, KK Res Lab, Singapore 229899, Singapore. [Li, Zhi-hui] Genomax Technol Pte Ltd, Singapore 117586, Singapore. [Tan, Ene-Choo] Duke NUS Grad Med Sch, Off Clin Sci, Singapore 169857, Singapore. RP Tan, EC (reprint author), KK Womens & Childrens Hosp, KK Res Lab, 100 Bukit Timah Rd, Singapore 229899, Singapore. EM tanec@bigfoot.com FU Agency for Science and Technology and Research [BMRC 06/1/50/19/485]; National Medical Research Council, Ministry of Health, Republic of Singapore [NMRC/PPG/KKH12010-Theme3] FX This work was supported by BMRC 06/1/50/19/485 (Agency for Science and Technology and Research) and NMRC/PPG/KKH12010-Theme3 (National Medical Research Council, Ministry of Health, Republic of Singapore). The authors appreciate the medical editing assistance of Jon Kilner, MS, MA (Pittsburgh, Pennsylvania, USA). 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In contrast, depletion of the Cdk5 activity renders neurons vulnerable to stresses. Recent reports suggest the involvement of Cdk5 in mental disorders. We hypothesized that perturbation of Cdk5 activity is related to mental conditions. To verify this hypothesis, we investigated the effect of valproic acid (VPA), which is a drug of choice for psychiatric disorders, on Cdk5 activity. VPA decreased the expression of p35 at both the protein and mRNA levels in cultured neurons, resulting in a decrease of Cdk5 activity. VPA decreased the p35 mRNA via histone deacetylase inhibition. The chronic administration of VPA also downregulated p35 in mouse brains. These results indicate that VPA regulates Cdk5 activity in neurons via p35 transcription mediated by HDAC inhibition. (C) 2014 Elsevier Inc. All rights reserved. C1 [Takahashi, Miyuki; Ishida, Manami; Saito, Taro; Hisanaga, Shin-ichi] Tokyo Metropolitan Univ, Dept Biol Sci, Hachioji, Tokyo 1920397, Japan. 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Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g., through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar pheno-typical consequences. Ambra1, strongly expressed in cortex, hippocampus, and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1(+/-) females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups, which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1(+/-) mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1(+/-) females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation. C1 [Dere, Ekrem; Dahm, Liane; Lu, Derek; Ju, Anes; Tantra, Martesa; Kaestner, Anne; Ehrenreich, Hannelore] Max Planck Inst Expt Med, D-37075 Gottingen, Germany. [Dere, Ekrem; Ehrenreich, Hannelore] DFG Ctr Nanoscale Microscopy & Mol Physiol Brain, Gottingen, Germany. [Hammerschmidt, Kurt] German Primate Ctr, Gottingen, Germany. [Chowdhury, Kamal] Max Planck Inst Biophys Chem, Dept Mol Cell Biol, Gottingen, Germany. RP Ehrenreich, H (reprint author), Max Planck Inst Expt Med, Hermann Rein St 3, D-37075 Gottingen, Germany. EM ehrenreich@em.mpg.de FU Max Planck Society; Max Planck Forderstiftung; DFG (CNMPB); EU-AIMS; Innovative Medicines Initiative [115300] FX This work was supported by the Max Planck Society, the Max Planck Forderstiftung, the DFG (CNMPB) as well as by EU-AIMS. The research of EU-AIMS receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013), from the EFPIA companies, and from Autism Speaks. 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Behav. Neurosci. PD MAY 16 PY 2014 VL 8 AR 181 DI 10.3389/fnbeh.2014.00181 PG 19 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH2MW UT WOS:000335956600002 PM 24904333 ER PT J AU Jones, MA Amr, S Ferebee, A Huynh, P Rosenfeld, JA Miles, MF Davies, AG Korey, CA Warrick, JM Shiang, R Elsea, SH Girirajan, S Grotewiel, M AF Jones, Melanie A. Amr, Sami Ferebee, Aerial Huynh, Phung Rosenfeld, Jill A. Miles, Michael F. Davies, Andrew G. Korey, Christopher A. Warrick, John M. Shiang, Rita Elsea, Sarah H. Girirajan, Santhosh Grotewiel, Mike TI Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease SO BIOLOGY OPEN LA English DT Article DE RNA interference; Neurodegeneration; Genetic modifiers; Wolfram syndrome; Copy number variants; Lysosomal storage disease; Gene network ID DE-NOVO MUTATIONS; NEURONAL CEROID-LIPOFUSCINOSIS; AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIATION; INTELLECTUAL DISABILITY; MICRODELETION SYNDROME; ENDOPLASMIC-RETICULUM; DEVELOPMENTAL DELAY; NETWORK INTEGRATION; DIABETES-MELLITUS AB Wolframsyndrome (WFS) is a progressive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. WFS1 and WFS2 are caused by recessive mutations in the genes Wolfram Syndrome 1 (WFS1) and CDGSH iron sulfur domain 2 (CISD2), respectively. To explore the function of CISD2, we performed genetic studies in flies with altered expression of its Drosophila orthologue, cisd2. Surprisingly, flies with strong ubiquitous RNAi-mediated knockdown of cisd2 had no obvious signs of altered life span, stress resistance, locomotor behavior or several other phenotypes. We subsequently found in a targeted genetic screen, however, that altered function of cisd2 modified the effects of overexpressing the fly orthologues of two lysosomal storage disease genes, palmitoyl-protein thioesterase 1 (PPT1 in humans, Ppt1 in flies) and ceroid-lipofuscinosis, neuronal 3 (CLN3 in humans, cln3 in flies), on eye morphology in flies. We also found that cln3 modified the effects of overexpressing Ppt1 in the eye and that overexpression of cln3 interacted with a loss of function mutation in cisd2 to disrupt locomotor ability in flies. Follow-up multi-species bioinformatic analyses suggested that a gene network centered on CISD2, PPT1 and CLN3 might impact disease through altered carbohydrate metabolism, protein folding and endopeptidase activity. Human genetic studies indicated that copy number variants (duplications and deletions) including CLN3, and possibly another gene in the CISD2/PPT1/CLN3 network, are over-represented in individuals with developmental delay. Our studies indicate that cisd2, Ppt1 and cln3 function in concert in flies, suggesting that CISD2, PPT1 and CLN3 might also function coordinately in humans. Further, our studies raise the possibility that WFS2 and some lysosomal storage disorders might be influenced by common mechanisms and that the underlying genes might have previously unappreciated effects on developmental delay. C1 [Jones, Melanie A.; Amr, Sami; Ferebee, Aerial; Huynh, Phung; Shiang, Rita; Grotewiel, Mike] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Amr, Sami; Grotewiel, Mike] Virginia Commonwealth Univ, Mol Biol & Genet Program, Richmond, VA 23298 USA. [Rosenfeld, Jill A.] Signature Genom Labs, Spokane, WA 99207 USA. [Miles, Michael F.; Davies, Andrew G.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Korey, Christopher A.] Coll Charleston, Dept Biol, Charleston, SC 29401 USA. [Warrick, John M.] Univ Richmond, Dept Biol, Richmond, VA 23173 USA. [Elsea, Sarah H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Girirajan, Santhosh] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Girirajan, Santhosh] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. RP Grotewiel, M (reprint author), Virginia Commonwealth Univ, Dept Human & Mol Genet, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM msgrotewiel@vcu.edu FU A. D. Williams Foundation (Virginia Commonwealth University); National Institutes of Health/National Institute on Aging [AG030376] FX This work was supported by research grants from the A. D. Williams Foundation (Virginia Commonwealth University) and the National Institutes of Health/National Institute on Aging [AG030376] to M. G. 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Open PD MAY 15 PY 2014 VL 3 IS 5 BP 342 EP 352 DI 10.1242/bio.20147559 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AZ2MQ UT WOS:000348068100005 PM 24705017 ER PT J AU Duffy, FH Shankardass, A McAnulty, GB Eksioglu, YZ Coulter, D Rotenberg, A Als, H AF Duffy, Frank H. Shankardass, Aditi McAnulty, Gloria B. Eksioglu, Yaman Z. Coulter, David Rotenberg, Alexander Als, Heidelise TI Corticosteroid therapy in regressive autism: a retrospective study of effects on the Frequency Modulated Auditory Evoked Response (FMAER), language, and behavior SO BMC NEUROLOGY LA English DT Article DE Autism; Behavior; Corticosteroids; Distortion; EEG; Electroencephalogram; Evoked potential; EP; Frequency modulated auditory evoked response; FMAER; Language; Regression; Spectral; Steroids; STG; Superior temporal gyrus; Treatment ID LANDAU-KLEFFNER-SYNDROME; SPECTRUM DISORDERS; DEVELOPMENTAL-DISABILITIES; EPILEPTIFORM ACTIVITY; INFANTILE SPASMS; CONTINUOUS SPIKE; CHILDREN; APHASIA; SLEEP; ANOMALIES AB Background: Up to a third of children with Autism Spectrum Disorder (ASD) manifest regressive autism (R-ASD). They show normal early development followed by loss of language and social skills. Absent evidence-based therapies, anecdotal evidence suggests improvement following use of corticosteroids. This study examined the effects of corticosteroids for R-ASD children upon the 4 Hz frequency modulated evoked response (FMAER) arising from language cortex of the superior temporal gyrus (STG) and upon EEG background activity, language, and behavior. An untreated clinical convenience sample of ASD children served as control sample. Methods: Twenty steroid-treated R-ASD (STAR) and 24 not-treated ASD patients (NSA), aged 3 - 5 years, were retrospectively identified from a large database. All study participants had two sequential FMAER and EEG studies; Landau-Kleffner syndrome diagnosis was excluded. All subjects' records contained clinical receptive and expressive language ratings based upon a priori developed metrics. The STAR group additionally was scored behaviorally regarding symptom severity as based on the Diagnostic and Statistical Manual IV (DSM-IV) ASD criteria list. EEGs were visually scored for abnormalities. FMAER responses were assessed quantitatively by spectral analysis. Treated and untreated group means and standard deviations for the FMAER, EEG, language, and behavior, were compared by paired t-test and Fisher's exact tests. Results: The STAR group showed a significant increase in the 4 Hz FMAER spectral response and a significant reduction in response distortion compared to the NSA group. Star group subjects' language ratings were significantly improved and more STAR than NSA group subjects showed significant language improvement. Most STAR group children showed significant behavioral improvement after treatment. STAR group language and behavior improvement was retained one year after treatment. Groups did not differ in terms of minor EEG abnormalities. Steroid treatment produced no lasting morbidity. Conclusions: Steroid treatment was associated with a significantly increased FMAER response magnitude, reduction of FMAER response distortion, and improvement in language and behavior scores. This was not observed in the non-treated group. These pilot findings warrant a prospective randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG, and standardized ASD, language and behavior measures, and a longer follow-up period. C1 [Duffy, Frank H.; Coulter, David; Rotenberg, Alexander] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Duffy, Frank H.; Shankardass, Aditi; McAnulty, Gloria B.; Coulter, David; Rotenberg, Alexander; Als, Heidelise] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shankardass, Aditi; McAnulty, Gloria B.; Als, Heidelise] Boston Childrens Hosp, Dept Psychiat Psychol, Boston, MA 02115 USA. [Eksioglu, Yaman Z.] Golisano Childrens Hosp, Syracuse, NY 13292 USA. [Eksioglu, Yaman Z.] SUNY Upstate Med Univ, Syracuse, NY 13292 USA. RP Duffy, FH (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM fhd@sover.net FU National Institutes of Health/National Institute of Child Health and Human Development [R01HD047730]; Harris Foundation; Buehler Family Fund; Intellectual and Developmental Disabilities Research Center (IDDRC) [P30HD018655]; Boston Children's Hospital; Tommy Fuss Fund; Harvard Medical School FX The authors thank EEG technologists Herman Edwards, R. EEG T. and Sheryl Manganaro, R. EEG T., for the quality of their data acquisition and for their consistent efforts over the years. The authors also thank Jack Connolly, BSIT, R. EEG T., Director of Electroneurodiagnostic Training Program, for both his supervisory and technical assistance and frequent more direct support. The professionals acknowledged performed their roles as part of their regular clinical and research obligations and were not additionally compensated for their contribution. This work was supported in part by National Institutes of Health/National Institute of Child Health and Human Development grant R01HD047730 to Heidelise Als, PhD, the Harris Foundation (to Dr Als), the Buehler Family Fund (to DrAls), and the Intellectual and Developmental Disabilities Research Center (IDDRC) grant P30HD018655 to Scott Pomeroy, MD, PhD, Boston Children's Hospital and Harvard Medical School. The authors furthermore acknowledge support from the Tommy Fuss Fund to Joseph Gonzalez-Heydrich, MD, and thank the Chairmen of Neurology (Dr. Pomeroy) and Psychiatry (David R. DeMaso, MD) for their continuing support of these research efforts. The funding bodies indicated above had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. 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PD MAY 15 PY 2014 VL 14 AR 70 DI 10.1186/1471-2377-14-70 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA AH1EQ UT WOS:000335863000001 PM 24885033 ER PT J AU Lionel, AC Tammimies, K Vaags, AK Rosenfeld, JA Ahn, JW Merico, D Noor, A Runke, CK Pillalamarri, VK Carter, MT Gazzellone, MJ Thiruvahindrapuram, B Fagerberg, C Laulund, LW Pellecchia, G Lamoureux, S Deshpande, C Clayton-Smith, J White, AC Leather, S Trounce, J Bedford, HM Hatchwell, E Eis, PS Yuen, RKC Walker, S Uddin, M Geraghty, MT Nikkel, SM Tomiak, EM Fernandez, BA Soreni, N Crosbie, J Arnold, PD Schachar, RJ Roberts, W Paterson, AD So, J Szatmari, P Chrysler, C Woodbury-Smith, M Lowry, RB Zwaigenbaum, L Mandyam, D Wei, J MacDonald, JR Howe, JL Nalpathamkalam, T Wang, ZZ Tolson, D Cobb, DS Wilks, TM Sorensen, MJ Bader, PI An, Y Wu, BL Musumeci, SA Romano, C Postorivo, D Nardone, AM Della Monica, M Scarano, G Zoccante, L Novara, F Zuffardi, O Ciccone, R Antona, V Carella, M Zelante, L Cavalli, P Poggiani, C Cavallari, U Argiropoulos, B Chernos, J Brasch-Andersen, C Speevak, M Fichera, M Ogilvie, CM Shen, YP Hodge, JC Talkowski, ME Stavropoulos, DJ Marshall, CR Scherer, SW AF Lionel, Anath C. Tammimies, Kristiina Vaags, Andrea K. Rosenfeld, Jill A. Ahn, Joo Wook Merico, Daniele Noor, Abdul Runke, Cassandra K. Pillalamarri, Vamsee K. Carter, Melissa T. Gazzellone, Matthew J. Thiruvahindrapuram, Bhooma Fagerberg, Christina Laulund, Lone W. Pellecchia, Giovanna Lamoureux, Sylvia Deshpande, Charu Clayton-Smith, Jill White, Ann C. Leather, Susan Trounce, John Bedford, H. Melanie Hatchwell, Eli Eis, Peggy S. Yuen, Ryan K. C. Walker, Susan Uddin, Mohammed Geraghty, Michael T. Nikkel, Sarah M. Tomiak, Eva M. Fernandez, Bridget A. Soreni, Noam Crosbie, Jennifer Arnold, Paul D. Schachar, Russell J. Roberts, Wendy Paterson, Andrew D. So, Joyce Szatmari, Peter Chrysler, Christina Woodbury-Smith, Marc Lowry, R. Brian Zwaigenbaum, Lonnie Mandyam, Divya Wei, John MacDonald, Jeffrey R. Howe, Jennifer L. Nalpathamkalam, Thomas Wang, Zhuozhi Tolson, Daniel Cobb, David S. Wilks, Timothy M. Sorensen, Mark J. Bader, Patricia I. An, Yu Wu, Bai-Lin Musumeci, Sebastiano Antonino Romano, Corrado Postorivo, Diana Nardone, Anna M. Della Monica, Matteo Scarano, Gioacchino Zoccante, Leonardo Novara, Francesca Zuffardi, Orsetta Ciccone, Roberto Antona, Vincenzo Carella, Massimo Zelante, Leopoldo Cavalli, Pietro Poggiani, Carlo Cavallari, Ugo Argiropoulos, Bob Chernos, Judy Brasch-Andersen, Charlotte Speevak, Marsha Fichera, Marco Ogilvie, Caroline Mackie Shen, Yiping Hodge, Jennelle C. Talkowski, Michael E. Stavropoulos, Dimitri J. Marshall, Christian R. Scherer, Stephen W. TI Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes SO HUMAN MOLECULAR GENETICS LA English DT Article ID COPY-NUMBER VARIATIONS; DE-NOVO MUTATIONS; GENOME-WIDE ASSOCIATION; E3 UBIQUITIN LIGASE; NEURONAL MIGRATION; MENTAL-RETARDATION; INTELLECTUAL DISABILITY; BIPOLAR-DISORDER; EXONIC DELETIONS; RARE DELETIONS AB Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronalmigration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. C1 [Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Merico, Daniele; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Pellecchia, Giovanna; Lamoureux, Sylvia; Yuen, Ryan K. C.; Walker, Susan; Uddin, Mohammed; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Merico, Daniele; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Pellecchia, Giovanna; Lamoureux, Sylvia; Yuen, Ryan K. C.; Walker, Susan; Uddin, Mohammed; Arnold, Paul D.; Paterson, Andrew D.; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Carter, Melissa T.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Lionel, Anath C.; Gazzellone, Matthew J.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A8, Canada. [Tammimies, Kristiina] Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders, S-11330 Stockholm, Sweden. [Vaags, Andrea K.; Argiropoulos, Bob; Chernos, Judy] Alberta Childrens Prov Gen Hosp, Cytogenet Lab, GLS South, Alberta Hlth Serv, Calgary, AB T3B 6A8, Canada. [Lowry, R. Brian] Alberta Childrens Prov Gen Hosp, Dept Med Genet, Calgary, AB T3B 6A8, Canada. [Lowry, R. Brian] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB T3B 6A8, Canada. [Argiropoulos, Bob; Chernos, Judy] Univ Calgary, Alberta Childrens Hosp Res Inst Child & Maternal, Calgary, AB T3B 6A8, Canada. [Vaags, Andrea K.] Calgary Lab Serv, Dept Anat Pathol & Cytopathol, Calgary, AB T2L 2K8, Canada. [Rosenfeld, Jill A.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA. [Ahn, Joo Wook; Deshpande, Charu; Ogilvie, Caroline Mackie] Guys & St Thomas NHS Fdn Trust, Cytogenet Dept & Clin Genet, London SE1 9RT, England. [Noor, Abdul; Stavropoulos, Dimitri J.] Hosp Sick Children, Cytogenet Lab, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. [Noor, Abdul; So, Joyce; Speevak, Marsha; Stavropoulos, Dimitri J.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5T 1R8, Canada. [Crosbie, Jennifer; Arnold, Paul D.; Schachar, Russell J.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Runke, Cassandra K.; Hodge, Jennelle C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Runke, Cassandra K.; Hodge, Jennelle C.] Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. [Pillalamarri, Vamsee K.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pillalamarri, Vamsee K.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Fagerberg, Christina; Brasch-Andersen, Charlotte] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Laulund, Lone W.; Brasch-Andersen, Charlotte] Odense Univ Hosp, Dept Paediat, DK-5000 Odense, Denmark. [Clayton-Smith, Jill] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester Ctr Genom Med, Manchester M13 9WL, Lancs, England. [White, Ann C.] Brighton Gen Hosp, Sussex Community NHS Trust, Brighton BN2 3EW, E Sussex, England. [Leather, Susan] Lewisham Healthcare NHS Trust, Community Paediat, London SE13 6LH, England. [Trounce, John] Brighton & Sussex Univ Hosp NHS Trust, Brighton BN2 5BE, E Sussex, England. [Bedford, H. Melanie] North York Gen Hosp, Genet Program, Toronto, ON M2K 1E1, Canada. [Hatchwell, Eli; Eis, Peggy S.] Populat Diagnost Inc, Melville, NY 11747 USA. [Geraghty, Michael T.; Nikkel, Sarah M.] Univ Ottawa, Dept Pediat, Ottawa, ON K1H 8L1, Canada. [Geraghty, Michael T.; Nikkel, Sarah M.; Tomiak, Eva M.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada. [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Med, St John, NF A1B 3V6, Canada. [Soreni, Noam] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON L8P 3B6, Canada. [Roberts, Wendy; Szatmari, Peter] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada. [Roberts, Wendy] Univ Toronto, Bloorview Res Inst, Toronto, ON M4G 1R8, Canada. [So, Joyce; Szatmari, Peter] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Chrysler, Christina; Woodbury-Smith, Marc] McMaster Univ, Offord Ctr Child Studies, Dept Psychiat & Behav Neurosci, Hamilton, ON L8S 4K1, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB T5G 0B7, Canada. [Tolson, Daniel; Cobb, David S.; Wilks, Timothy M.] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Sorensen, Mark J.] Kalispell Reg Med Ctr, Kalispell, MT 59901 USA. [Bader, Patricia I.] Northeast Indiana Genet Counseling Ctr, Ft Wayne, IN 46845 USA. [An, Yu; Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Inst Biomed Sci, Shanghai 200032, Peoples R China. [An, Yu; Wu, Bai-Lin] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200032, Peoples R China. [Wu, Bai-Lin; Shen, Yiping] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wu, Bai-Lin; Shen, Yiping] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Musumeci, Sebastiano Antonino] IRCCS Oasi Maria SS, Neurol Unit, I-94018 Troina, Italy. [Romano, Corrado] IRCCS Oasi Maria SS, Unit Pediat & Med Genet, I-94018 Troina, Italy. [Fichera, Marco] IRCCS Oasi Maria SS, Med Genet Lab, I-94018 Troina, Italy. [Postorivo, Diana; Nardone, Anna M.] Univ Roma Tor Vergata, Dept Med Genet, I-00133 Rome, Italy. [Della Monica, Matteo; Scarano, Gioacchino] Gaetano Rummo Gen Hosp, Dept Med Genet, I-82100 Benevento, Italy. [Zoccante, Leonardo] Univ Verona, GB Rossi Hosp, Dept Life Sci & Reprod, Child Neuropsychiat Unit, I-37126 Verona, Italy. [Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy. [Zuffardi, Orsetta] IRCCS C Mondino Natl Inst Neurol Fdn, I-27100 Pavia, Italy. [Antona, Vincenzo] Univ Palermo, Dept Sci Hlth Promot & Mother & Child Care, I-90127 Palermo, Italy. [Carella, Massimo; Zelante, Leopoldo] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, I-71013 San Giovanni Rotondo, FG, Italy. [Cavalli, Pietro; Cavallari, Ugo] AO Ist Ospitalieri Cremona, Genet Unit, I-26100 Cremona, Italy. [Poggiani, Carlo] AO Ist Ospitalieri Cremona, Neonatal Intens Care Unit, I-26100 Cremona, Italy. [Argiropoulos, Bob; Chernos, Judy] Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada. [Speevak, Marsha] Credit Valley Hosp Site, Trillium Hlth Partners, Dept Genet, Mississauga, ON L5M 2N1, Canada. [Fichera, Marco] Univ Catania, I-95123 Catania, Italy. [Shen, Yiping] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China. [Crosbie, Jennifer; Schachar, Russell J.] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. RP Scherer, SW (reprint author), Hosp Sick Children, Ctr Appl Genom, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM stephen.scherer@sickkids.ca RI Romano, Corrado/B-9695-2008; Scherer, Stephen /B-3785-2013; Yuen, Ryan/J-4876-2012 OI Romano, Corrado/0000-0003-1049-0683; Scherer, Stephen /0000-0002-8326-1999; FU University of Toronto McLaughlin Centre; NeuroDevNet; Genome Canada; Ontario Genomics Institute; Canadian Institutes for Health Research (CIHR); National Institutes of Health [MH095867]; Canadian Institute for Advanced Research; Canada Foundation for Innovation; Government of Ontario; Autism Speaks; The Hospital for Sick Children Foundation; NeuroDevNet doctoral fellowship; Swedish Research Council; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK Central Repositories; NIH Genes, Environment and Health Initiative [GEI] [U01HG004399]; National Institutes of Health (NIH) [CA87969, CA55075, DK58845]; NIH GEI [U01HG004424]; Division of Aging Biology, National Institute on Aging; Division of Geriatrics and Clinical Gerontology, National Institute on Aging; National Eye Institute; Center for Inherited Disease Research (CIDR) [1 X01 HG005274-01]; Gene Environment Association Studies (GENEVA) Coordinating Center [U01HG004446]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; University of Wisconsin Transdisciplinary Tobacco Use Research Center [P50 DA019706, P50 CA084724]; National Institute of Diabetes; Endocrinology and Metabolic Diseases of the NIDDK; NIH FX This work was supported by grants from the University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada and the Ontario Genomics Institute, the Canadian Institutes for Health Research (CIHR), National Institutes of Health (MH095867), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the Government of Ontario, Autism Speaks and The Hospital for Sick Children Foundation. A. C. L. was supported by a NeuroDevNet doctoral fellowship. K. T. holds a post-doctoral fellowship from the Swedish Research Council. S. W. S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. D. T., D. S. C. and T. M. W. are US military service members and this work was prepared as part of their official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of the Navy, Department of Defense, nor the US Government. Title 17, USC 105 provides that 'Copyright protection under this title is not available for any work of the U.S. Government.' Title 17, USC 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties. Control datasets were obtained, along with permission for use, from the database of Genotypes and Phenotypes (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through accession numbers phs000143.v1.p1 (Starr County Health Studies' Genetics of Diabetes Study), phs000091.v2.p1 (GENEVA NHS/HPFS Diabetes study), phs000169.v1.p1 (Whole Genome Association Study of Visceral Adiposity in the HABC Study), phs000303.v1.p1 (Genetic Epidemiology of Refractive Error in the KORA Study), phs000404.v1.p1 (COGEND; The Genetic Architecture of Smoking and Smoking Cessation) and phs000086.v2.p1 (DCCT-EDIC Clinical Trial and Follow-up of Persons with Type 1 Diabetes). The Starr County Health Studies Genetics of Diabetes Study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NIDDK Central Repositories. Support for the GWAS of Gene and Environment Initiatives in Type 2 Diabetes was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01HG004399). The human subjects participating in the GWAS derive from The Nurses' Health Study and Health Professionals' Follow-up Study and these studies are supported by National Institutes of Health (NIH) grants CA87969, CA55075 and DK58845. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, GENEVA Coordinating Center (U01 HG004446) and the National Center for Biotechnology Information. Support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the NIH GEI (U01HG004424). Support for the 'CIDR Visceral Adiposity Study' was provided through the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, National Institute on Aging. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Health ABC Study HABC) Investigators. The KORA dataset was obtained from the NEI Refractive Error Collaboration (NEIREC) Database, support for which was provided by the National Eye Institute.Support for genotyping of the COGEND samples, which was performed at the Center for Inherited Disease Research (CIDR), was provided by 1 X01 HG005274-01. Assistance with genotype cleaning of the COGEND samples, as well as with general study coordination, was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (U01HG004446). Support for the collection of COGEND datasets and samples was provided by the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the University of Wisconsin Transdisciplinary Tobacco Use Research Center (P50 DA019706, P50 CA084724). The DCCT-EDIC Research Group is sponsored through research contracts from the National Institute of Diabetes, Endocrinology and Metabolic Diseases of the NIDDK and the NIH. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIDDK or the NIH. 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1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2014 VL 23 IS 10 BP 2752 EP 2768 DI 10.1093/hmg/ddt669 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AF4PB UT WOS:000334694800020 PM 24381304 ER PT J AU Lawson, RP Rees, G Friston, KJ AF Lawson, Rebecca P. Rees, Geraint Friston, Karl J. TI An aberrant precision account of autism SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism spectrum disorder (ASD); predictive coding; precision; sensory attenuation; learning; perception and action; sensory sensitivity; social interaction ID FIGURES TASK-PERFORMANCE; SUPERIOR VISUAL-SEARCH; SPECTRUM DISORDERS; REPETITION SUPPRESSION; BINOCULAR-RIVALRY; BASAL FOREBRAIN; FREE-ENERGY; MISMATCH NEGATIVITY; ACTIVE INFERENCE; COGNITIVE-STYLE AB Autism is a neurodevelopmental disorder characterized by problems with social-communication, restricted interests and repetitive behavior. A recent and thoughtprovoking article presented a normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation namely, predictive coding many features of autistic perception can be attributed to aberrant precision (or beliefs about precision) within the context of hierarchical message passing in the brain (Friston et al., 2013). Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings that speak directly or indirectly to neurobiological mechanisms are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs. C1 [Lawson, Rebecca P.; Rees, Geraint; Friston, Karl J.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England. 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Hum. Neurosci. PD MAY 14 PY 2014 VL 8 AR 302 DI 10.3389/fnhum.2014.00302 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AL9WI UT WOS:000339493700001 PM 24860482 ER PT J AU Simpson, EA Sclafani, V Paukner, A Hamel, AF Novak, MA Meyer, JS Suomi, SJ Ferrari, PF AF Simpson, Elizabeth A. Sclafani, Valentina Paukner, Annika Hamel, Amanda F. Novak, Melinda A. Meyer, Jerrold S. Suomi, Stephen J. Ferrari, Pier Francesco TI Inhaled oxytocin increases positive social behaviors in newborn macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE imitation recognition; neonatal imitation; individual differences ID AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; PLASMA OXYTOCIN; RHESUS MACAQUES; DOSE-RESPONSE; NEURAL BASIS; AFFILIATION; BRAIN; ATTENTION; MONKEYS AB Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults-including expression recognition and affiliation-it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors-lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver-suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder. C1 [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. [Simpson, Elizabeth A.; Sclafani, Valentina; Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. [Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. EM simpsonea@mail.nih.gov FU Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NICHD [P01HD064653]; National Institutes of Health [RR11122] FX We thank Ruth Woodward and Angela Ruggiero for technical assistance administering oxytocin and collecting saliva. We thank Lydia Martin, Grace Maloney, and Chris Catalfamo for behavioral reliability coding. Thanks to Nathan Fox for feedback on an earlier version of this paper. The Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NICHD Grant P01HD064653 (to P.F.F.), and National Institutes of Health Grant RR11122 (to M.A.N.) supported this research. CR Ainsworth M. 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Natl. Acad. Sci. U. S. A. PD MAY 13 PY 2014 VL 111 IS 19 BP 6922 EP 6927 DI 10.1073/pnas.1402471111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH0GS UT WOS:000335798000049 PM 24778211 ER PT J AU Siniscalco, D AF Siniscalco, Dario TI The searching for autism biomarkers: a commentary on: a new methodology of viewing extra-axial fluid and cortical abnormalities in children with autism via transcranial ultrasonography SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; transcranial ultrasonography; biomarkers; brain lesions and behavior disturbances; neurotransmitter agents C1 [Siniscalco, Dario] Univ Naples 2, Dept Expt Med, Naples, Italy. [Siniscalco, Dario] Ctr Autism La Forza Silenzio, Caserta, Italy. [Siniscalco, Dario] Cancellautismo, Florence, Italy. RP Siniscalco, D (reprint author), Univ Naples 2, Dept Expt Med, Naples, Italy. EM dariosin@uab.edu CR Baio J., 2014, MMWR SURVEILL SUM S2, V63, P1 Bradstreet JJ, 2014, FRONT HUM NEUROSCI, V7, DOI 10.3389/fnhum.2013.00934 Siniscalco D, 2012, J AUTISM DEV DISORD, V42, P1403, DOI 10.1007/s10803-011-1373-z Siniscalco D., 2013, AUTISM S, VS2, pe001, DOI DOI 10.4172/2165-7890.S2-E001 Siniscalco D., 2013, AUTISM, V3, pe119, DOI [10.4172/2165-7890.1000e119, DOI 10.4172/2165-7890.1000E119] NR 5 TC 0 Z9 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY 12 PY 2014 VL 8 AR 240 DI 10.3389/fnhum.2014.00240 PG 2 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AH4XP UT WOS:000336132600001 PM 24860465 ER PT J AU de Rezende, VB Rosa, DV Comim, CM Magno, LAV Rodrigues, ALS Vidigal, P Jeromin, A Quevedo, J Romano-Silva, MA AF de Rezende, Vitor Bortolo Rosa, Daniela Valadao Comim, Clarissa Martinelli Viana Magno, Luiz Alexandre Severo Rodrigues, Ana Lucia Vidigal, Paula Jeromin, Andreas Quevedo, Joao Romano-Silva, Marco Aurelio TI NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE NCS-1; Knockout; Behavior; Anxiety; Depression; Memory ID NEURONAL CALCIUM SENSOR-1; INHIBITORY AVOIDANCE TASK; GENE; FREQUENIN; PROTEIN; FACILITATION; EXPRESSION; PLASTICITY; DROSOPHILA; RECEPTOR AB Sensing and regulating intracellular levels of calcium are essential for proper cellular function. In neurons, calcium sensing plays important roles in neuronal plasticity, neurotransmitter release, long-term synapse modification and ion channel activity. Neuronal calcium sensor-1 (NCS-1) is a member of the highly conserved neuronal calcium sensor family. Although NCS-1 has been associated with psychiatric conditions including autism, bipolar disorder and schizophrenia, it is unclear which role NCS-1 plays in behavior. To understand the involvement of NCS-1 in psychiatric conditions, we provided a comprehensive behavioral characterization of NCS-1 knockout (KO) mice. These mice grow and develop normally without apparent abnormalities in comparison to wild type littermates. However, open field showed that NCS-1 deficiency impairs novelty-induced exploratory activity in both KO and heterozygote (HT) mice. Moreover, NCS-1-deficiency also resulted in anxiety- and depressive-like behaviors as demonstrated by elevated plus maze, large open field, forced swim and tail suspension tasks. Furthermore, based on spontaneous object recognition test, non-aversive long-term memory was impaired in NCS-1 KO mice. In contrast, neither social behavior nor a kind of aversive memory was affected under NCS-1 deficiency. These data implicate NCS-1 in exploratory activity, memory and mood-related behaviors, suggesting that NCS-1 gene ablation may result in phenotypic abnormalities associated with neuropsychiatric disorders. (C) 2014 Elsevier Inc. All rights reserved. C1 [de Rezende, Vitor Bortolo; Rosa, Daniela Valadao; Viana Magno, Luiz Alexandre; Romano-Silva, Marco Aurelio] Univ Fed Minas Gerais, Fac Med, Dept Saude Mental, Lab Neurociencia,INCT Med Mol, BR-30130100 Belo Horizonte, MG, Brazil. [Vidigal, Paula] Univ Fed Minas Gerais, Fac Med, Dept Anat Patol & Med Legal, Lab Patol Mol, BR-30130100 Belo Horizonte, MG, Brazil. [Comim, Clarissa Martinelli; Quevedo, Joao] Univ Extremo Sul Catarinense, Unidade Acad Ciencias Saude, Programa Posgrad Ciencias Saude, Lab Neurociencias,INCT Translac Med, BR-88806000 Criciuma, SC, Brazil. [Severo Rodrigues, Ana Lucia] Univ Fed Santa Catarina, Dept Bioquim, Ctr Ciencias Biol, Lab Neurobiol Depressao, BR-88040900 Florianopolis, SC, Brazil. [Jeromin, Andreas] Banyan Biomarkers Inc, Alachua, FL 32615 USA. RP Romano-Silva, MA (reprint author), Univ Fed Minas Gerais, Fac Med, Dept Saude Mental, Inst Nacl Ciencia & Tecnol,Lab Neurociencia, Av Alfredo Balena,190 Room 114, Belo Horizonte, MG, Brazil. EM romano-silva@ufmg.br RI Quevedo, Joao/E-5491-2013; Magno, Luiz Alexandre/B-1552-2010 OI Quevedo, Joao/0000-0003-3114-6611; Magno, Luiz Alexandre/0000-0003-3693-1897 FU INCT-MM (FAPEMIG) [CBB-APQ-00075-09/CNPq 573646/2008-2] FX Grant INCT-MM (FAPEMIG: CBB-APQ-00075-09/CNPq 573646/2008-2) supported this work. We thank to Dr. Karen Torres, Dr. Bruno Sousa, M.Sc. Amy Kowalski and Dr. Juliana Carten for critical review of the manuscript. We also thank Dr. Maicon Albuquerque for providing statistical assistance during our data analysis, and to Dr. Andreas Mullemann and Dr. Horst Bluethmann (Hoffmann-La-Roche-Switzerland) for generating NCS-1 knockout mouse. Dr. Andreas Jeromin is an employee of Banyan Biomarkers, Inc. The other authors declare no conflict of interest in all terms of editorial policy section. 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Behav. PD MAY 10 PY 2014 VL 130 BP 91 EP 98 DI 10.1016/j.physbeh.2014.03.005 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA AI4XM UT WOS:000336869900013 PM 24631552 ER PT J AU Iwata, K Matsuzaki, H Tachibana, T Ohno, K Yoshimura, S Takamura, H Yamada, K Matsuzaki, S Nakamura, K Tsuchiya, KJ Matsumoto, K Tsujii, M Sugiyama, T Katayama, T Mori, N AF Iwata, Keiko Matsuzaki, Hideo Tachibana, Taro Ohno, Koji Yoshimura, Saori Takamura, Hironori Yamada, Kohei Matsuzaki, Shinsuke Nakamura, Kazuhiko Tsuchiya, Kenji J. Matsumoto, Kaori Tsujii, Masatsugu Sugiyama, Toshirou Katayama, Taiichi Mori, Norio TI N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism SO MOLECULAR AUTISM LA English DT Article DE Serotonin transporter; NSF; Interaction; Membrane trafficking; Autism; Post-mortem brain; Lymphocyte ID PROTEIN-KINASE-C; BIOGENIC-AMINE TRANSPORTERS; HIGH-FUNCTIONING AUTISM; DOPAMINE TRANSPORTER; SPECTRUM DISORDERS; GABA(A) RECEPTORS; SYNTAXIN 1A; 1ST-DEGREE RELATIVES; EPILEPTIC SEIZURES; RETARDED-CHILDREN AB Background: Changes in serotonin transporter (SERT) function have been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated whether the expression of one such protein was affected in subjects with autism. Methods: Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains. Alterations in the mRNA expression of SERT (SLC6A4) and the SERT-binding protein in the post-mortem brains and the lymphocytes of autism patients were compared to nonclinical controls. Results: N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF was co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and decreased SERT uptake function. NSF was endogenously co-localized with SERT and interacted with SERT. While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, and was significantly reduced in lymphocytes of autistic subjects, which correlated with the severity of the clinical symptoms. Conclusions: These data clearly show that NSF interacts with SERT under physiological conditions and is required for SERT membrane trafficking and uptake function. A possible role for NSF in the pathophysiology of autism through modulation of SERT trafficking, is suggested. C1 [Iwata, Keiko; Matsuzaki, Hideo] Univ Fukui, Res Ctr Child Mental Dev, Fukui 910, Japan. [Iwata, Keiko; Matsuzaki, Hideo] Osaka Univ, United Grad Sch Child Dev, Dept Dev Funct Brain Act, Fukui, Japan. [Iwata, Keiko; Matsuzaki, Hideo] Kanazawa Univ, Fukui, Japan. [Iwata, Keiko; Matsuzaki, Hideo] Hamamatsu Univ, Sch Med, Fukui, Japan. [Iwata, Keiko; Matsuzaki, Hideo] Chiba Univ, Fukui, Japan. [Iwata, Keiko; Matsuzaki, Hideo] Univ Fukui, Fukui 910, Japan. [Matsuzaki, Hideo; Tsuchiya, Kenji J.; Matsumoto, Kaori; Tsujii, Masatsugu; Mori, Norio] Hamamatsu Univ, Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka, Japan. [Tachibana, Taro; Yoshimura, Saori] Osaka City Univ, Grad Sch Engn, Dept Bioengn, Osaka 558, Japan. [Ohno, Koji] Hamamatsu Univ, Sch Med, Dept Anat, Hamamatsu, Shizuoka, Japan. [Takamura, Hironori; Yamada, Kohei; Matsuzaki, Shinsuke; Katayama, Taiichi] Osaka Univ, United Grad Sch Child Dev, Dept Mol Brain Sci, Suita, Osaka, Japan. [Takamura, Hironori; Yamada, Kohei; Matsuzaki, Shinsuke; Katayama, Taiichi] Kanazawa Univ, Suita, Osaka, Japan. [Takamura, Hironori; Yamada, Kohei; Matsuzaki, Shinsuke; Katayama, Taiichi] Hamamatsu Univ, Sch Med, Suita, Osaka, Japan. [Takamura, Hironori; Yamada, Kohei; Matsuzaki, Shinsuke; Katayama, Taiichi] Chiba Univ, Suita, Osaka, Japan. [Takamura, Hironori; Yamada, Kohei; Matsuzaki, Shinsuke; Katayama, Taiichi] Univ Fukui, Suita, Osaka, Japan. [Takamura, Hironori; Yamada, Kohei] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Suita, Osaka, Japan. [Nakamura, Kazuhiko; Mori, Norio] Hamamatsu Univ, Sch Med, Dept Psychiat, Hamamatsu, Shizuoka, Japan. [Tsujii, Masatsugu] Chukyo Univ, Fac Contemporary Sociol, Toyota, Japan. [Sugiyama, Toshirou] Hamamatsu Univ, Sch Med, Dept Child & Adolescent Psychiat, Hamamatsu, Shizuoka, Japan. RP Matsuzaki, H (reprint author), Univ Fukui, Res Ctr Child Mental Dev, Fukui 910, Japan. EM matsuzah@u-fukui.ac.jp; katayama@ugscd.osaka-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan FX We thank Dr Jane Pickett, Director of Brain Resources and Data, Autism Tissue Program, for facilitating brain tissue collection. Human tissue was obtained from the National Institute of Child Health and Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. Tissue samples were also provided by the Harvard Brain Tissue Resource Center. Written informed consent was obtained from the participants or their families for publication of this manuscript and accompanying figures. We would like to thank all the participants and families for their time and effort. We thank Heinrich Betz for the generous supply of full-length rat SERT cDNA. We also thank Masako Suzuki (Research Equipment Center, Hamamatsu University School of Medicine) for the technical support of the mass spectrometry analysis. This study was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to KI and a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to HM. A part of this study is the result of integrated research on neuropsychiatric disorders carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. 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Autism PD MAY 10 PY 2014 VL 5 AR 33 DI 10.1186/2040-2392-5-33 PG 18 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AH3YE UT WOS:000336061400001 PM 24834316 ER PT J AU Eden, KE de Vries, PJ Moss, J Richards, C Oliver, C AF Eden, Kate E. de Vries, Petrus J. Moss, Jo Richards, Caroline Oliver, Chris TI Self-injury and aggression in tuberous sclerosis complex: cross syndrome comparison and associated risk markers SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Aggression; ASD; Impulsivity; Pain; Repetitive/stereotyped behaviour; Self-injury; Tuberous sclerosis complex ID AUTISM SPECTRUM DISORDERS; DE-LANGE-SYNDROME; INTELLECTUAL DISABILITIES; PROBLEM BEHAVIOR; DEVELOPMENTAL-DISABILITIES; CHALLENGING BEHAVIOR; FUNCTIONAL-ANALYSIS; PSYCHOMETRIC PROPERTIES; COGNITIVE IMPAIRMENTS; EARLY-CHILDHOOD AB Background: Research reporting prevalence rates of self-injurious and aggressive behaviour in people with tuberous sclerosis complex (TSC) is limited. No studies have compared rates of these behaviours in TSC with those in other syndrome groups matched for degree of disability or investigated risk markers for these behaviours in TSC. Methods: Data from the Challenging Behaviour Questionnaire were collected for 37 children, aged 4 to 15 years, with TSC. Odds ratios were used to compare rates of self-injury and aggression in children with TSC with children with idiopathic autism spectrum disorder (ASD), fragile X, Cornelia de Lange and Down syndromes. Characteristics were measured using the Mood Interest and Pleasure Questionnaire, the Activity Questionnaire, the Social Communication Questionnaire, the Repetitive Behaviour Questionnaire, the Wessex Behaviour Schedule and the revised Non-communicating Children Pain Checklist. Mann-Whitney U analyses were used to compare characteristics between individuals with self-injury and aggression and those not showing these behaviours. Results: Rates of self-injury and aggression in TSC were 27% and 50%, respectively. These are high but not significantly different from rates in children with Down syndrome or other syndrome groups. Both self-injury and aggression were associated with stereotyped and pain-related behaviours, low mood, hyperactivity, impulsivity and repetitive use of language. Children who engaged in self-injury also had lower levels of interest and pleasure and showed a greater degree of `insistence on sameness' than children who did not self-injure. Aggression was associated with repetitive behaviour. The majority of these associations remained significant when the association with level of adaptive functioning was controlled for. Conclusions: Behavioural profiles can be used to identify those most at risk of developing self-injury and aggression. Further research is warranted to understand the influence of such internal factors as mood, ASD symptomatology and pain on challenging behaviour in people with intellectual disability. C1 [Eden, Kate E.; Moss, Jo; Richards, Caroline; Oliver, Chris] Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Birmingham B15 2TT, W Midlands, England. [de Vries, Petrus J.] Univ Cape Town, Div Child & Adolescent Psychiat, ZA-7700 Rondebosch, South Africa. [Moss, Jo] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. RP Eden, KE (reprint author), Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Birmingham B15 2TT, W Midlands, England. EM kate.eden1@gmail.com RI Moss, Jo/C-8812-2009 FU Cerebra FX Cerebra funded this project. The Tuberous Sclerosis Association helped to recruit families of children with tuberous sclerosis complex. Many members of the Cerebra Centre for Neurodevelopmental Disorders also helped to collect and enter data for the comparison groups, including Michelle Hooker and Sarah Duffay. 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Neurodev. Disord. PD MAY 10 PY 2014 VL 6 AR 10 DI 10.1186/1866-1955-6-10 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH1FU UT WOS:000335866000001 PM 24822087 ER PT J AU deCastro, BR AF deCastro, B. Rey TI Acrolein and Asthma Attack Prevalence in a Representative Sample of the United States Adult Population 2000-2009 SO PLOS ONE LA English DT Article ID HAZARDOUS AIR-POLLUTANTS; AUTISM SPECTRUM DISORDERS; HEALTH INTERVIEW SURVEY; TOXICS CONCENTRATIONS; OXIDATIVE STRESS; INHALED ACROLEIN; RISK-ASSESSMENT; LUNG-FUNCTION; MAIN ROAD; POLLUTION AB Background: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 mu g/m(3). Objectives: Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. Methods: NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (>= 18 years old) in the NHIS (National Health Interview Survey) 2000 - 2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. Results: In the highest quintile of outdoor acrolein exposure (0.05 - 0.46 mu g/m(3)), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI] = 1.08 [0.98: 1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98: 1.29]) in a model limited to never smokers (n = 153,820). Conclusions: Chronic exposure to outdoor acrolein of 0.05 - 0.46 mg/m(3) appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population. 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Brancazio, Lawrence TI Seeing to hear? Patterns of gaze to speaking faces in children with autism spectrum disorders SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE autism spectrum disorders; audiovisual speech perception; eyetracking; communication development; speech in noise; lipreading ID AUDIOVISUAL SPEECH-PERCEPTION; VISUAL INFLUENCES; EYE-TRACKING; EFFECT SIZE; INFORMATION; INTEGRATION; INDIVIDUALS; STATISTICS; DESIGNS; COMPETENCE AB Using eye-tracking methodology, gaze to a speaking face was compared in a group of children with autism spectrum disorders (ASD) and a group with typical development (TD). Patterns of gaze were observed under three conditions: audiovisual (AV) speech in auditory noise, visual only speech and an AV non-face, non-speech control. Children with ASD looked less to the face of the speaker and fixated less on the speakers' mouth than TD controls. No differences in gaze were reported for the non-face, non-speech control task. 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TI Differential role of temporoparietal junction and medial prefrontal cortex in causal inference in autism: An independent component analysis SO NEUROSCIENCE LETTERS LA English DT Article DE Autism; Independent component analysis; fMRI; Functional connectivity; Theory of Mind ID TEMPORO-PARIETAL JUNCTION; ASPERGER-SYNDROME; MIND; BRAIN; ATTRIBUTION; PERFORMANCE; ACTIVATION; SPECTRUM; TASKS; FMRI AB Neuroimaging studies have consistently identified a network of brain regions responsible for making inferences of others' mental states. This network includes the medial prefrontal cortex (MPFC), posterior superior temporal sulcus (pSTS) at the temporoparietal junction (TPJ), and temporal poles. Although TPJ and MPFC are key nodes of the Theory of Mind (ToM) network, their relative functional roles are still debated. This study sought to examine the contribution of these regions in causal attribution and to explore the nature of the ToM network in people with autism spectrum disorders (ASD). Participants watched a series of comic strip vignettes in the MRI scanner, and identified the most logical ending to each vignette, which sometimes required intentional causal attribution. Independent component analysis was done to isolate temporally correlated brain networks. The functional networks for intentional causality included the TPJ and MPFC, with an increased contribution of TPJ. There was also a significant group difference in the TPJ, with reduced response in participants with ASD. These results suggest an increased role of TPJ in intentional causality. In addition, the reduced response in ASD in TPJ may reflect their difficulties in social cognition. (c) 2014 Elsevier Ireland Ltd. All rights reserved. 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Hence, changes in an array of behaviors, including behavioral flexibility, consistent with altered functioning of cortico-limbic circuits have been reported in rodent models of MIA. Surprisingly, previous studies have not examined the effect of MIA on the extinction of fear conditioning which depends on cortico-limbic circuits. Thus, we tested the effects of treating pregnant Long Evans rats with the viral mimetic polyl:C (gestational day 15; 4 mg/kg; i.v.) on fear conditioning and extinction in the male offspring using two different tasks. In the first experiment, we observed no effect of polyl:C treatment on the acquisition or extinction of a classically conditioned fear memory in a non-discriminative auditory cue paradigm. However, polyl:C-treated offspring did increase contextual freezing during the recall of fear extinction in this non-discriminative paradigm. The second experiment utilized a recently developed task to explicitly test the ability of rats to discriminate among cues signifying fear, reward, and safety; a task that requires behavioral flexibility. To our surprise, polyl:C-treated rats acquired the task in a manner similar to saline-treated rats. However, upon subsequent extinction training, they showed significantly faster extinction of the freezing response to the fear cue. In contrast, during the extinction recall test, polyl:C-treated offspring showed enhanced freezing behavior before and after presentation of the fear cue, suggesting an impairment in their ability to regulate fear behavior. These behavioral results are integrated into the literature suggesting impairments in cortico-limbic brain function in the offspring of rats treated with polyl:C during pregnancy. C1 [Sangha, Susan; Greba, Quentin; Robinson, Paul D.; Ballendine, Stephanie A.; Howland, John G.] Univ Saskatchewan, Dept Physiol, Saskatoon, SK S7N 5E5, Canada. RP Sangha, S (reprint author), Univ Saskatchewan, Dept Physiol, GB33,Hlth Sci Bldg,107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada. EM sangha@purdue.edu; john.howland@usask.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes for Health Research (CIHR); NSERC; CIHR FX This work was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Operating Grant from the Canadian Institutes for Health Research (CIHR) to John G. Howland. Paul D. Robinson was supported by an NSERC Undergraduate Student Research Award. Stephanie A. Ballendine received support from a CIHR Master's scholarship. John G. Howland is a CIHR New Investigator. The authors thank Don A. Davies for contributing to video scoring. 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Behav. Neurosci. PD MAY 7 PY 2014 VL 8 AR 168 DI 10.3389/fnbeh.2014.00168 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AH2LR UT WOS:000335953500001 PM 24847231 ER PT J AU Sandin, S Lichtenstein, P Kuja-Halkola, R Larsson, H Hultman, CM Reichenberg, A AF Sandin, Sven Lichtenstein, Paul Kuja-Halkola, Ralf Larsson, Henrik Hultman, Christina M. Reichenberg, Abraham TI The Familial Risk of Autism SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDER; SPECTRUM DISORDERS; ENVIRONMENTAL-FACTORS; EPIDEMIOLOGIC SURVEY; RECURRENCE RISK; TWIN; REGISTER; SCHIZOPHRENIA; HERITABILITY; GENETICS AB IMPORTANCE Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains OBJECTIVE To provide estimates of familial aggregation and heritability of ASD. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort including 2 049 973 Swedish children born 1982 through 2006. We identified 37 570 twin pairs, 2 642 064 full sibling pairs, 432 281 maternal and 445 531 paternal half sibling pairs, and 5 799 875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained. MAIN OUTCOMES AND MEASURES The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors. RESULTS In the sample, 14 516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100 000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude. We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64). CONCLUSIONS AND RELEVANCE Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children. C1 [Sandin, Sven; Lichtenstein, Paul; Kuja-Halkola, Ralf; Larsson, Henrik; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Sandin, Sven] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England. [Reichenberg, Abraham] Ichan Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Reichenberg, Abraham] Ichan Sch Med Mt Sinai, Dept Prevent Med, New York, NY USA. [Reichenberg, Abraham] Ichan Sch Med Mt Sinai, Seaver Autism Ctr, New York, NY USA. [Reichenberg, Abraham] Ichan Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. RP Sandin, S (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden. EM sven.sandin@ki.se FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences [HD073978]; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health [MH097849]; Beatrice and Samuel A. Seaver Foundation FX This study was supported, in part, by grants from the National Institutes of Health; grant HD073978 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, and National Institute of Neurological Disorders and Stroke; grant MH097849 from the National Institute of Mental Health; and by the Beatrice and Samuel A. Seaver Foundation. 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Am. Med. Assoc. PD MAY 7 PY 2014 VL 311 IS 17 BP 1770 EP 1777 DI 10.1001/jama.2014.4144 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AG4IG UT WOS:000335382300022 PM 24794370 ER PT J AU Baron-Cohen, S Murphy, L Chakrabarti, B Craig, I Mallya, U Lakatosova, S Rehnstrom, K Peltonen, L Wheelwright, S Allison, C Fisher, SE Warrier, V AF Baron-Cohen, Simon Murphy, Laura Chakrabarti, Bhismadev Craig, Ian Mallya, Uma Lakatosova, Silvia Rehnstrom, Karola Peltonen, Leena Wheelwright, Sally Allison, Carrie Fisher, Simon E. Warrier, Varun TI A Genome Wide Association Study of Mathematical Ability Reveals an Association at Chromosome 3q29, a Locus Associated with Autism and Learning Difficulties: A Preliminary Study SO PLOS ONE LA English DT Article ID COGNITIVE-ABILITY; LOW PERFORMANCE; MICRODELETION; ACHIEVEMENT; MICROARRAYS; DISABILITY; LINKAGE; DESIGN AB Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U. K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p, P<1.5 x 10(-5), 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 x 10(-6)). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 x 10(-4)). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study. C1 [Baron-Cohen, Simon; Murphy, Laura; Chakrabarti, Bhismadev; Mallya, Uma; Lakatosova, Silvia; Wheelwright, Sally; Allison, Carrie; Warrier, Varun] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 1TN, Cambs, England. [Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust CPFT, CLASS Clin, Cambridge, Cambs, England. [Chakrabarti, Bhismadev] Univ Reading, Ctr Integrat Neurosci & Neurodynam, Sch Psychol & Clin Language Sci, Reading, Berks, England. [Craig, Ian] Kings Coll London, Inst Psychiat, MRC, Ctr Social Genet & Dev Psychiat, London, England. [Rehnstrom, Karola; Peltonen, Leena] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Fisher, Simon E.] Max Planck Inst Psycholinguist, NL-6500 AH Nijmegen, Netherlands. [Fisher, Simon E.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Baron-Cohen, S (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 1TN, Cambs, England. EM sb205@cam.ac.uk; vw260@medschl.cam.ac.uk RI Fisher, Simon/E-9130-2012 OI Fisher, Simon/0000-0002-3132-1996 FU Nancy Lurie Marks Family Foundation; Medical Research Council (MRC) UK; Autism Research Trust (ART); Max Planck Society FX This work was funded by grants to SBC from the Nancy Lurie Marks Family Foundation, the Medical Research Council (MRC) UK, and the Autism Research Trust (ART). LM and SEF were supported by the Max Planck Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Vallender, Eric J. TI Evolutionary conservation in genes underlying human psychiatric disorders SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE schizophrenia; autism; Homo sapiens; adaptation ID GENOME-WIDE ASSOCIATION; HUMAN BRAIN-SIZE; AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIATION; ADAPTIVE EVOLUTION; MOLECULAR EVOLUTION; LIFETIME PREVALENCE; MAJOR DETERMINANT; BIPOLAR DISORDER; ANIMAL-MODELS AB Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of the protein-coding regions of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago) and 34 non-primate mammalian species. Evolutionary parameters, including d(N)/d(S), are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals, and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant) compared to their small-brained sister species. Evidence of differential selection in humans to the exclusion of non-human primates was absent, however elevated d(N)/d(S) was detected in catarrhines as a whole, as well as in cetaceans, possibly as part of a more general trend. Although this may suggest that protein changes associated with schizophrenia and autism are not a cost of the higher brain function found in humans, it may also point to insufficiencies in the study of these diseases including incomplete or inaccurate gene association lists and/or a greater role of regulatory changes or copy number variation. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained. C1 [Ogawa, Lisa M.; Vallender, Eric J.] Harvard Univ, Sch Med, Div Neurosci, New England Primate Res Ctr, Southborough, MA 01772 USA. RP Vallender, EJ (reprint author), Harvard Univ, Sch Med, Div Neurosci, New England Primate Res Ctr, One Pine Hill Dr, Southborough, MA 01772 USA. 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Hum. Neurosci. PD MAY 6 PY 2014 VL 8 AR 283 DI 10.3389/fnhum.2014.00283 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AH4UB UT WOS:000336122900001 PM 24834046 ER PT J AU Schilbach, L AF Schilbach, Leonhard TI On the relationship of online and offline social cognition SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE social interaction; social neuroscience; social cognition from an observer's point of view; social cognition from an interactor's point of view; developmental psychology ID MIRROR NEURONS; EYE-MOVEMENTS; 2ND-PERSON NEUROSCIENCE; BRAIN; MIND; SELF; SIMULATION; IMITATION; AUTISM; GAZE AB Social neuroscience studies the neurobiological underpinnings of people making sense of people. Due to both conceptual and methodological constraints, the majority of studies in this field of research, however, has employed experimental paradigms that focus on social cognition from an observer's rather than from an interactor's point of view (offline vs. online social cognition). This calls for an increased effort to systematically investigate the neural bases of participation in real-time social interaction. In light of the ontogenetic primacy of social interaction over observation and the idea that neural networks established during social interaction may be "re-used" during observation, other important objectives of the field will be to relate new findings into the neural bases of social interaction to previous work investigating the neural bases of social observation as well as to find ways to directly compare the two. C1 Univ Hosp Cologne, Dept Psychiat, D-50924 Cologne, Germany. RP Schilbach, L (reprint author), Univ Hosp Cologne, Dept Psychiat, Kerpener Str 62, D-50924 Cologne, Germany. 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PD MAY 6 PY 2014 VL 8 AR 278 DI 10.3389/fnhum.2014.00278 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AH4TY UT WOS:000336122600001 PM 24834045 ER PT J AU Ozkubat, U Ozdemir, S AF Ozkubat, Ufuk Ozdemir, Selda TI A comparison of social skills in Turkish children with visual impairments, children with intellectual impairments and typically developing children SO INTERNATIONAL JOURNAL OF INCLUSIVE EDUCATION LA English DT Article DE visual impairments; intellectual impairments; inclusive education; social skills ID ELEMENTARY-SCHOOL CLASSROOMS; AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION; BEHAVIOR PROBLEMS; PARENTING STRESS; INCLUSION; DISABILITIES; ADOLESCENTS; INTEGRATION; ACCEPTANCE AB The purpose of this study was to compare the social skills of five groups of children: children with visual impairments attending inclusive education schools, children with visual impairments attending schools for the blind, children with intellectual impairments attending inclusive education schools, children with intellectual impairments attending segregated special education schools, and typically developing children. A hundred and sixty-nine children aged from 7 to 12 participated in the study. The children's social skills were rated by their teachers on the Social Skills Rating System (SSRS) - Turkish Form. The results suggested significant group differences between children attending inclusive education schools and children attending special education schools. Analysis of the findings indicated that children with visual impairments and children with intellectual impairments had poorer social skills than typically developing children; however children with visual impairments and children with intellectual impairments attending inclusive education schools had higher social skills than children attending segregated special education schools. The findings of the study were discussed and suggestions for future research were provided. C1 [Ozkubat, Ufuk; Ozdemir, Selda] Gazi Univ, Dept Special Educ, TR-06500 Ankara, Turkey. 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PD MAY 4 PY 2014 VL 18 IS 5 BP 500 EP 514 DI 10.1080/13603116.2013.789088 PG 15 WC Education & Educational Research SC Education & Educational Research GA AH0XL UT WOS:000335844000005 ER PT J AU Kuzmanovic, B Schilbach, L Georgescu, AL Kockler, H Santos, NS Shah, NJ Bente, G Fink, GR Vogeley, K AF Kuzmanovic, Bojana Schilbach, Leonhard Georgescu, Alexandra L. Kockler, Hanna Santos, Natacha S. Shah, N. Jon Bente, Gary Fink, Gereon R. Vogeley, Kai TI Dissociating animacy processing in high-functioning autism: Neural correlates of stimulus properties and subjective ratings SO SOCIAL NEUROSCIENCE LA English DT Article DE Animacy; High-functioning autism; Amygdala; dmPFC; Social cognition ID ASPERGER-SYNDROME; SPECTRUM DISORDERS; SOCIAL COGNITION; PREFRONTAL CORTEX; 1ST IMPRESSIONS; MENTAL STATES; MIND; BRAIN; ATTRIBUTION; PERCEPTION AB When movements indicate meaningful actions, even nonbiological objects induce the impression of having a mind or animacy. This basic social ability was investigated in adults with high-functioning autism (HFA, n=13, and matched controls, n=13) by systematically varying motion properties of simple geometric shapes. Critically, trial-by-trial variations of (1) motion complexity of stimuli, and of (2) participants' individual animacy ratings were separately correlated with neural activity to dissociate cognitive strategies relying more closely on stimulus analysis vs. subjective experience. Increasing motion complexity did not yield any significant group differences, and in both groups, it correlated with neural activity in regions involved in perceptual and evaluative processing, including the ventral medial prefrontal cortex (mPFC), superior temporal gyrus (STG) and posterior cingulate cortex (PCC). In contrast, although there were no significant behavioral differences between the groups, increasing animacy ratings correlated with neural activity in the insula, STG, amygdala, dorsal mPFC and PCC more strongly in controls than in HFA. These results indicate that in HFA the evaluation of stimulus properties cuing for animacy is intact, while increasing subjective ratings do not seem to be robustly related to social processing, including spontaneous mental state inferences and experience of salience. C1 [Kuzmanovic, Bojana] Res Ctr Juelich, Inst Neurosci & Med Eth Neurosci INM 8, Julich, Germany. [Kuzmanovic, Bojana; Schilbach, Leonhard; Georgescu, Alexandra L.; Kockler, Hanna; Santos, Natacha S.; Vogeley, Kai] Univ Hosp Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany. [Shah, N. Jon] Res Ctr Juelich, Inst Neurosci & Med Med Imaging Phys INM 4, Julich, Germany. [Bente, Gary] Univ Cologne, Dept Social Psychol & Media Psychol, D-50931 Cologne, Germany. [Fink, Gereon R.; Vogeley, Kai] Res Ctr Juelich, Inst Neurosci & Med Cognit Neurosci INM 3, Julich, Germany. [Fink, Gereon R.] Univ Hosp Cologne, Dept Neurol, Cologne, Germany. RP Kuzmanovic, B (reprint author), Forschungszentrum Julich, INM 8, D-52425 Julich, Germany. EM b.kuzmanovic@fz-juelich.de RI Fink, Gereon/E-1616-2012 OI Fink, Gereon/0000-0002-8230-1856 FU Federal Ministry of Education and Research, Germany [01GP0802] FX This work was supported by the Federal Ministry of Education and Research, Germany [01GP0802; KV]. 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Neurosci. PD MAY 4 PY 2014 VL 9 IS 3 BP 309 EP 325 DI 10.1080/17470919.2014.886618 PG 17 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AE5ZE UT WOS:000334067000011 PM 24512520 ER PT J AU Beck, DE Maranto, R Lo, WJ AF Beck, Dennis E. Maranto, Robert Lo, Wen-Juo TI Determinants of Student and Parent Satisfaction at a Cyber Charter School SO JOURNAL OF EDUCATIONAL RESEARCH LA English DT Article DE special education; parent satisfaction; cyber schools; student satisfaction ID COMPARING RESPONSE RATES; DOWN-SYNDROME; AUTISM; CHILDREN; EDUCATION; METAANALYSIS; ADOLESCENCE; SUPPORT; HEALTH; LIFE AB Research indicates that in traditional public schools the subjective well-being of students and parents varies by gender, race, and special education status. Prior studies suggest that general education students are more satisfied with their schooling than special education students, that female students have greater satisfaction with their schooling than male students, and that Caucasian and Latino students report greater school satisfaction than African American students. No prior research has studied parental and student subjective well-being in a cyber environment. The authors investigate parental and student subjective well-being in a cyber charter school, using a student (n = 269; 53.7% response rate) and parent (n = 232; 48.7% response rate) survey. They find statistically significant differences in subjective well-being across demographic groups of students, and also significantly higher satisfaction among special education students in the cyber school environment. Implications are discussed. C1 [Beck, Dennis E.] Univ Arkansas, Fayetteville, AR 72701 USA. 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TI Romantic Attachment, Empathy, and the Broader Autism Phenotype among College Students SO JOURNAL OF GENETIC PSYCHOLOGY LA English DT Article DE broader autism phenotype; empathy; romantic attachment ID SPECTRUM QUOTIENT AQ; ADULT ATTACHMENT; RELATIONSHIP SATISFACTION; FUNCTIONING AUTISM; NONCLINICAL SAMPLE; GENERAL-POPULATION; PATTERNS; CHILDREN; TRAITS; STYLES AB Recent research suggests that mild autistic-like characteristics can be measured among relatives of individuals with autism and in the general population. These characteristics have been referred to as the broader autism phenotype (BAP), and include pragmatic language difficulties, aloofness, and rigidity. Evidence is growing to suggest that individuals with BAP encounter difficulties in their social interactions. Recent work demonstrates that college students scoring high on the BAP report more loneliness (Jobe & Williams White, 2007) and more interpersonal problems (Wainer, Ingersoll, & Hopwood, 2012). 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Genet. Psychol. PD MAY 4 PY 2014 VL 175 IS 3 BP 202 EP 213 DI 10.1080/00221325.2013.856838 PG 12 WC Psychology, Developmental; Psychology; Psychology, Multidisciplinary SC Psychology GA AG3EG UT WOS:000335298000002 PM 25175527 ER PT J AU Michel, C Hoehl, S Striano, T AF Michel, Christine Hoehl, Stefanie Striano, Tricia TI The influence of familiarity on explicit eye gaze judgement in preschoolers SO EUROPEAN JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE Familiarity; Preschoolers; Explicit eye gaze judgement ID AUTISM SPECTRUM DISORDER; 6-MONTH-OLD INFANTS; VISUAL-ATTENTION; YOUNG-CHILDREN; RECOGNITION; FACE; MOTHERS; STRANGERS; LOOKING; AGE AB The current study explores the influence of familiarity on explicit eye gaze judgement in preschoolers. We introduce reaction times for touches as a new measure for children studies. Children aged four-six years saw either their caregiver's face or a stranger's face looking at an object or away from it. Children were asked to touch the face that was looking at the object and reaction times to correct touches were measured. Children reacted faster to strangers' faces than to their caregivers' faces. This may indicate that preschoolers used the face of a stranger more effectively as a source of information about the environment and for this reason detected the eye gaze-object relationship faster. In addition, children's reactions were faster in a nonsocial shape-matching task than in the social eye gaze-judgement task. The applied paradigm is appropriate to further investigate the development and influencing factors of explicit eye gaze judgements in preschoolers. C1 [Michel, Christine; Hoehl, Stefanie] Heidelberg Univ, Inst Psychol, D-69117 Heidelberg, Germany. [Striano, Tricia] CUNY Hunter Coll, New York, NY 10021 USA. [Striano, Tricia] Inst Educ Hlth & Res, Milton, MA USA. RP Michel, C (reprint author), Heidelberg Univ, Inst Psychol, Hauptstr 47-51, D-69117 Heidelberg, Germany. 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J. Dev. Psychol. PD MAY 4 PY 2014 VL 11 IS 3 BP 344 EP 355 DI 10.1080/17405629.2013.832670 PG 12 WC Psychology, Developmental SC Psychology GA AE4WW UT WOS:000333988000006 ER PT J AU Prevost, M Carrier, ME Chowne, G Zelkowitz, P Joseph, L Gold, I AF Prevost, Marie Carrier, Marie-Eve Chowne, Gabrielle Zelkowitz, Phyllis Joseph, Lawrence Gold, Ian TI The Reading the Mind in the Eyes test: validation of a French version and exploration of cultural variations in a multi-ethnic city SO COGNITIVE NEUROPSYCHIATRY LA English DT Article DE theory of mind; empathy; translation; Francophone; culture; language ID UNAFFECTED 1ST-DEGREE RELATIVES; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; SCHIZOPHRENIA-PATIENTS; SOCIAL COGNITION; IMPAIRED THEORY; POPULATION; EMPATHY; ADULTS; FACE AB IntroductionThe first aim of our study was to validate the French version of the Reading the Mind in the Eyes test, a theory of mind test. The second aim was to test whether cultural differences modulate performance on this test.MethodsA total of 109 participants completed the original English version and 97 participants completed the French version. Another group of 30 participants completed the French version twice, one week apart.ResultsWe report a similar overall distribution of scores in both versions and no differences in the mean scores between them. However, 2 items in the French version did not collect a majority of responses, which differed from the results of the English version. Test-retest showed good stability of the French version. As expected, participants who do not speak French or English at home, and those born in Asia, performed worse than North American participants, and those who speak English or French at home.ConclusionsWe report a French version with acceptable validity and good stability. The cultural differences observed support the idea that Asian culture does not use theory of mind to explain people's behaviours as much as North American people do. C1 [Prevost, Marie; Chowne, Gabrielle; Gold, Ian] McGill Univ, Dept Philosophy, Montreal, PQ H3A 2T7, Canada. [Prevost, Marie; Chowne, Gabrielle; Gold, Ian] McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T7, Canada. [Carrier, Marie-Eve; Zelkowitz, Phyllis] McGill Univ, Jewish Gen Hosp, Dept Psychiat, Montreal, PQ H3T 1E2, Canada. [Carrier, Marie-Eve; Zelkowitz, Phyllis] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Joseph, Lawrence] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. RP Prevost, M (reprint author), McGill Univ, Dept Philosophy, Leacock Bldg,Room 908,855 Sherbrooke West, Montreal, PQ H3A 2T7, Canada. EM marie.prevost@mail.mcgill.ca FU CIHR Team in Perinatal Mental Health FX This work was supported by the CIHR Team in Perinatal Mental Health. CR Adams RB, 2010, J COGNITIVE NEUROSCI, V22, P97, DOI 10.1162/jocn.2009.21187 Ahmed FS, 2011, J AUTISM DEV DISORD, V41, P667, DOI 10.1007/s10803-010-1087-7 Alaerts K, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0020989 Baron-Cohen S, 2001, J CHILD PSYCHOL PSYC, V42, P241, DOI 10.1017/S0021963001006643 BaronCohen S, 1997, J CHILD PSYCHOL PSYC, V38, P813, DOI 10.1111/j.1469-7610.1997.tb01599.x Boisseau E., 2010, THESIS U QUEBEC MONT Carroll JM, 2006, J AUTISM DEV DISORD, V36, P949, DOI 10.1007/s10803-006-0127-9 Chapman E, 2006, SOC NEUROSCI, V1, P135, DOI 10.1080/17470910600992239 Chatel-Goldman J, 2013, FRONT HUM NEUROSCI, V7, DOI 10.3389/fnhum.2013.00107 Choi I, 2003, J PERS SOC PSYCHOL, V84, P46, DOI 10.1037/0022-3514.84.1.46 Cook CM, 2010, PERS INDIV DIFFER, V49, P712, DOI 10.1016/j.paid.2010.06.010 de Achaval D, 2010, NEUROPSYCHOLOGIA, V48, P1209, DOI 10.1016/j.neuropsychologia.2009.12.019 Dehning S, 2012, BMC MED EDUC, V12, DOI 10.1186/1472-6920-12-34 Dziobek I, 2006, J AUTISM DEV DISORD, V36, P623, DOI 10.1007/s10803-006-0107-0 Golan O, 2006, DEV PSYCHOPATHOL, V18, P591, DOI 10.1017/S0954579406060305 Hallerbäck Maria Unenge, 2009, Cogn Neuropsychiatry, V14, P127, DOI 10.1080/13546800902901518 Harkness KL, 2010, COGNITION EMOTION, V24, P497, DOI 10.1080/02699930902750249 Hirao K, 2008, SCHIZOPHR RES, V105, P165, DOI 10.1016/j.schres.2008.07.021 Irani F, 2006, SCHIZOPHR RES, V88, P151, DOI 10.1016/j.schres.2006.07.016 Johnston L, 2008, AUST J PSYCHOL, V60, P135, DOI 10.1080/00049530701449521 Kelemen O, 2004, ACTA PSYCHIAT SCAND, V110, P146, DOI 10.1111/j.1600-0047.2004.00357.x Kelemen O, 2005, NEUROPSYCHOLOGY, V19, P494, DOI 10.1037/0894-4105.19.4.494 Kenyon M, 2012, INT J EAT DISORDER, V45, P377, DOI 10.1002/eat.20967 Kettle JWL, 2008, SCHIZOPHR RES, V99, P96, DOI 10.1016/j.schres.2007.11.011 Kucera H., 1967, COMPUTATIONAL ANAL P Kunihira Y, 2006, J AUTISM DEV DISORD, V36, P553, DOI 10.1007/s10803-006-0094-1 Lillard A, 1998, PSYCHOL BULL, V123, P3, DOI 10.1037/0033-2909.123.1.3 Lillard A, 1999, CURR DIR PSYCHOL SCI, V8, P57, DOI 10.1111/1467-8721.00014 Mason MF, 2010, SOC COGN AFFECT NEUR, V5, P292, DOI 10.1093/scan/nsq034 Masuda T, 2008, J PERS SOC PSYCHOL, V94, P365, DOI 10.1037/0022-3514.94.3.365 Masuda T, 2001, J PERS SOC PSYCHOL, V81, P922, DOI 10.1037//0022-3514.81.5.922 McGlade N, 2008, BRIT J PSYCHIAT, V193, P77, DOI 10.1192/bjp.bp.107.044198 MORRIS MW, 1994, J PERS SOC PSYCHOL, V67, P949, DOI 10.1037/0022-3514.67.6.949 Murphy David, 2006, Cogn Neuropsychiatry, V11, P99, DOI 10.1080/13546800444000182 New B, 2001, ANN PSYCHOL, V101, P447 PREMACK D, 1978, BEHAV BRAIN SCI, V1, P515 Rule NO, 2010, J PERS SOC PSYCHOL, V98, P1, DOI 10.1037/a0017673 Russell TA, 2000, AM J PSYCHIAT, V157, P2040, DOI 10.1176/appi.ajp.157.12.2040 Serafin M, 2004, GIORNALE ITALIANO PS, V4, P839 Shahaeian A, 2011, DEV PSYCHOL, V47, P1239, DOI 10.1037/a0023899 Smeets T, 2009, HORM BEHAV, V55, P507, DOI 10.1016/j.yhbeh.2009.01.011 Stanford AD, 2011, SCHIZOPHR RES, V131, P11, DOI 10.1016/j.schres.2011.06.005 Valla JM, 2010, AUTISM RES, V3, P174, DOI 10.1002/aur.143 Voracek M, 2006, PERS INDIV DIFFER, V41, P1481, DOI 10.1016/j.paid.2006.06.009 Yildirim EA, 2011, TURK PSIKIYATR DERG, V22, P177, DOI 10.5080/u6500 NR 45 TC 1 Z9 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-6805 EI 1464-0619 J9 COGN NEUROPSYCHIATRY JI Cogn. Neuropsychiatry PD MAY 4 PY 2014 VL 19 IS 3 BP 189 EP 204 DI 10.1080/13546805.2013.823859 PG 16 WC Psychiatry SC Psychiatry GA AA3YS UT WOS:000331031700001 PM 23937473 ER PT J AU Bellebaum, C Brodmann, K Thoma, P AF Bellebaum, Christian Brodmann, Katja Thoma, Patrizia TI Active and observational reward learning in adults with autism spectrum disorder: relationship with empathy in an atypical sample SO COGNITIVE NEUROPSYCHIATRY LA English DT Article DE autism; empathy; reward; FRN; observational learning ID MAJOR DEPRESSIVE DISORDER; EVENT-RELATED POTENTIALS; ERROR-RELATED NEGATIVITY; HIGH-FUNCTIONING AUTISM; TIME-ESTIMATION TASK; NEURAL SYSTEM; DOPAMINERGIC INNERVATION; PSYCHIATRIC-DISORDERS; PERSPECTIVE-TAKING; BRAIN POTENTIALS AB IntroductionAutism spectrum disorders (ASDs) are characterised by disturbances in social behaviour. A prevailing hypothesis suggests that these problems are related to deficits in assigning rewarding value to social stimuli. The present study aimed to examine monetary reward processing in adults with ASDs by means of event-related potentials (ERPs).MethodsTen individuals with mild ASDs (Asperger's syndrome and high-functioning autism) and 12 healthy control subjects performed an active and an observational probabilistic reward-learning task.ResultsBoth groups showed similar overall learning performance. With respect to reward processing, subjects with ASDs exhibited a general reduction in feedback-related negativity (FRN) amplitude, irrespective of feedback valence and type of learning (active or observational). Individuals with ASDs showed lower scores for cognitive empathy, while affective empathy did not differ between groups. Correlation analyses revealed that higher empathy (both cognitive and affective) negatively affected performance in observational learning in controls and in active learning in ASDs (only cognitive empathy). No relationships were seen between empathy and ERPs.ConclusionsReduced FRN amplitudes are discussed in terms of a deficit in fast reward processing in ASDs, which may indicate altered reward system functioning. C1 [Bellebaum, Christian; Brodmann, Katja; Thoma, Patrizia] Ruhr Univ Bochum, Fac Psychol, Dept Neuropsychol, Inst Cognit Neurosci, Bochum, Germany. RP Thoma, P (reprint author), Ruhr Univ Bochum, Fac Psychol, Dept Neuropsychol, Inst Cognit Neurosci, Bochum, Germany. EM Patrizia.Thoma@rub.de FU Ministry of Innovation, Science and Research of the federal state of Nordrhein-Westfalen, Germany (Ministerium fur Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen [334-4]; DFG (German Research Foundation) FX We thank the Ministry of Innovation, Science and Research of the federal state of Nordrhein-Westfalen, Germany (Ministerium fur Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen [grant number 334-4]) for supporting this research. This study was also partly funded by a scheme to reward the successful first attainment of DFG (German Research Foundation) projects ("Novice Premium''), awarded to P. T. by the Ruhr University Bochum. 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The findings lead to the formalization of two hypotheses: (i) color obsessions and phobias in individuals with ASD are related to an unusually strong ability to associate colors with entities; (ii) color obsessions are related to hyposensitivity, and color phobias to hypersensitivity, in the affected regions of color space. C1 [Ludlow, Amanda K.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. [Heaton, Pamela; Hill, Elisabeth] Univ London Goldsmiths Coll, Dept Psychol, London SE14 6NW, England. [Franklin, Anna] Univ Sussex, Sch Psychol, Brighton, E Sussex, England. RP Ludlow, AK (reprint author), Univ Birmingham, Birmingham B15 2TT, W Midlands, England. EM a.k.ludlow@bham.ac.uk FU EU [12984]; FRSF grant from the University of Surrey FX We would like to thank all the children for taking part in the study and also their parents and teachers for their co-operation in our research. This work was supported by EU grant (12984) Stages in the Evolution and Development of Sign Use (SEDSU), and a FRSF grant from the University of Surrey to AF. 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We simulated the potential effects of both measurement error (ME) in exposures and misclassification of ASD-related phenotype (assessed as Autism Observation Scale for Infants (AOSI) scores) on measures of association generated under this study design. We investigated the impact on the power to detect true associations with exposure and the false positive rate (FPR) for a non-causal correlate of exposure (X-2, r= 0.7) for continuous AOSI score (linear model) versus dichotomised AOSI (logistic regression) when the sample size (n), degree of ME in exposure, and strength of the expected (true) OR (eOR)) between exposure and AOSI varied. Exposure was a continuous variable in all linear models and dichotomised at one SD above the mean in logistic models. Simulations reveal complex patterns and suggest that: (1) There was attenuation of associations that increased with eOR and ME; (2) The FPR was considerable under many scenarios; and (3) The FPR has a complex dependence on the eOR, ME and model choice, but was greater for logistic models. The findings will stimulate work examining cost-effective strategies to reduce the impact of ME in realistic sample sizes and affirm the importance for EARLI of investment in biological samples that help precisely quantify a wide range of environmental exposures. C1 [Heavner, Karyn] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Newschaffer, Craig; Burstyn, Igor] Drexel Univ, Sch Publ Hlth, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. [Hertz-Picciotto, Irva; Bennett, Deborah] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Burstyn, Igor] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. 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Epidemiol. Community Health PD MAY PY 2014 VL 68 IS 5 BP 438 EP 445 DI 10.1136/jech-2013-202982 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CB0CY UT WOS:000349294000004 PM 24470431 ER PT J AU Deriziotis, P Graham, SA Estruch, SB Fisher, SE AF Deriziotis, Pelagia Graham, Sarah A. Estruch, Sara B. Fisher, Simon E. TI Investigating Protein-protein Interactions in Live Cells Using Bioluminescence Resonance Energy Transfer SO Jove-Journal of Visualized Experiments LA English DT Article DE Cellular Biology; Issue 87; Protein-protein interactions; Bioluminescence Resonance Energy Transfer; Live cell; Transfection; Luciferase; Yellow Fluorescent Protein; Mutations ID DE-NOVO MUTATIONS; LANGUAGE DEFICITS; LIVING CELLS; SPEECH; BRET; IDENTIFICATION; DISORDERS; AUTISM; DOMAIN; FOXP1 AB Assays based on Bioluminescence Resonance Energy Transfer (BRET) provide a sensitive and reliable means to monitor protein-protein interactions in live cells. BRET is the non-radiative transfer of energy from a 'donor' luciferase enzyme to an 'acceptor' fluorescent protein. In the most common configuration of this assay, the donor is Renilla reniformis luciferase and the acceptor is Yellow Fluorescent Protein (YFP). Because the efficiency of energy transfer is strongly distance-dependent, observation of the BRET phenomenon requires that the donor and acceptor be in close proximity. To test for an interaction between two proteins of interest in cultured mammalian cells, one protein is expressed as a fusion with luciferase and the second as a fusion with YFP. An interaction between the two proteins of interest may bring the donor and acceptor sufficiently close for energy transfer to occur. Compared to other techniques for investigating protein-protein interactions, the BRET assay is sensitive, requires little hands-on time and few reagents, and is able to detect interactions which are weak, transient, or dependent on the biochemical environment found within a live cell. It is therefore an ideal approach for confirming putative interactions suggested by yeast two-hybrid or mass spectrometry proteomics studies, and in addition it is well-suited for mapping interacting regions, assessing the effect of post-translational modifications on protein-protein interactions, and evaluating the impact of mutations identified in patient DNA. C1 [Deriziotis, Pelagia; Graham, Sarah A.; Estruch, Sara B.; Fisher, Simon E.] Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands. [Fisher, Simon E.] Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. RP Fisher, SE (reprint author), Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands. EM simon.fisher@mpi.nl RI Derizioti, Pelagia/C-3857-2015; Fisher, Simon/E-9130-2012 OI Derizioti, Pelagia/0000-0001-5544-8345; Fisher, Simon/0000-0002-3132-1996 FU Max Planck Society FX This work was supported by the Max Planck Society. 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Vis. Exp. PD MAY PY 2014 IS 87 AR e51438 DI 10.3791/51438 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA4VV UT WOS:000348905400050 ER PT J AU Hahn, LJ Zimmer, BJ Brady, NC Romine, RES Fleming, KK AF Hahn, Laura J. Zimmer, B. Jean Brady, Nancy C. Romine, Rebecca E. Swinburne Fleming, Kandace K. TI Role of Maternal Gesture Use in Speech Use by Children With Fragile X Syndrome SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE fragile X syndrome; gesture; language development; speech ID AUTISM SPECTRUM DISORDER; LANGUAGE-DEVELOPMENT; YOUNG-CHILDREN; DOWN-SYNDROME; JOINT ATTENTION; DEVELOPMENTAL DELAYS; PRESCHOOL-CHILDREN; SPOKEN LANGUAGE; VERBAL LABELS; COMMUNICATION AB Purpose: The purpose of this study was to investigate how maternal gesture relates to speech production by children with fragile X syndrome (FXS). Method: Participants were 27 young children with FXS (23 boys, 4 girls) and their mothers. Videotaped home observations were conducted between the ages of 25 and 37 months (toddler period) and again between the ages of 60 and 71 months (child period). The videos were later coded for types of maternal utterances and maternal gestures that preceded child speech productions. Children were also assessed with the Mullen Scales of Early Learning at both ages. Results: Maternal gesture use in the toddler period was positively related to expressive language scores at both age periods and was related to receptive language scores in the child period. Maternal proximal pointing, in comparison to other gestures, evoked more speech responses from children during the mother-child interactions, particularly when combined with wh-questions. Conclusion: This study adds to the growing body of research on the importance of contextual variables, such as maternal gestures, in child language development. 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PD MAY PY 2014 VL 23 IS 2 BP 146 EP 159 DI 10.1044/2013_AJSLP-13-0046 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AU5ZP UT WOS:000345682200005 PM 24686460 ER PT J AU Ronald, A Larsson, H Anckarsater, H Lichtenstein, P AF Ronald, Angelica Larsson, Henrik Anckarsater, Henrik Lichtenstein, Paul TI Symptoms of Autism and ADHD: A Swedish Twin Study Examining Their Overlap SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism; ADHD; twins; comorbidity; genetics ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SUBSTANTIAL GENETIC OVERLAP; SPECTRUM DISORDERS; DSM-IV; PSYCHIATRIC-DISORDERS; SOCIAL-COMMUNICATION; GENERAL-POPULATION; COMMUNITY TWIN; TRAITS AB Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) show high comorbidity. The following questions were addressed regarding their specific symptoms: What is the factor structure of ASD and ADHD symptoms, to what degree do different symptom domains cluster together, to what extent are these domains caused by the same genetic and environmental influences, and what is the best model of their co-occurrence? A population-based twin cohort of over 17,000 9- and 12-year-olds were assessed using the Autism-Tics, AD/HD, and other Comorbidities parental interview inventory. Principal component analyses were conducted, and symptom domain clustering was assessed. Four multivariate twin models were compared. Factors split into three ASD (social impairments, communication impairments, and restricted repetitive behaviors and interests), and three ADHD (inattention, hyperactivity, and impulsivity) symptom domains. Some ASD-ADHD symptom domain combinations clustered together often, although others not at all. A two-factor common pathway model fit the data, suggesting that ASD and ADHD symptom domains tap into separate "ASD" and "ADHD" latent factors that showed high genetic overlap. All subdomains also showed significant specific genetic and environmental influences, reflecting the etiological heterogeneity both within and between ASD and ADHD. These findings support the conceptual distinction of ASD and ADHD, and demonstrate the considerable natural co-occurrence of particular ASD/ADHD symptom domains. The results imply that more children with 1 condition show features of the other condition than show complete comorbidity. Emphasis on symptom co-occurrence, rather than complete comorbidity between disorders, may help focus clinical approaches and advance molecular genetic research. C1 [Ronald, Angelica] Univ London, Ctr Brain & Cognit Dev, London WC1E 7HX, England. [Larsson, Henrik; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Larsson, Henrik] Karolinska Inst, Ctr Neurodev Disorders, Stockholm, Sweden. [Anckarsater, Henrik] Gothenburg Univ, Inst Neurosci & Physiol, Sahlgrens Acad, S-41124 Gothenburg, Sweden. RP Ronald, A (reprint author), Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, Malet St, London WC1E 7HX, England. 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Abnorm. Psychol. PD MAY PY 2014 VL 123 IS 2 BP 440 EP 451 DI 10.1037/a0036088 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA AS1AF UT WOS:000344007600016 PM 24731073 ER PT J AU Pearn, J AF Pearn, John TI Professor Tyndale John Rendle-Short (1919-2010), British and Australian paediatrician: A life in two domains SO JOURNAL OF MEDICAL BIOGRAPHY LA English DT Article DE Paediatrics; medical history; Rendle-Short kindred; theology; medical education ID INFANTILE AUTISM AB Professor Tyndale John Rendle-Short (1919-2010), a British and Australian paediatrician, lived a professional life of considerable influence in two domains - academic paediatrics and fundamentalist theology. A Cambridge medical graduate (1943) and doctor-soldier, he was appointed as the Foundation Professor of Child Health at the University of Queensland (1961). In Australia, he was a pioneer in three paediatric developments ('rooming-in' for mothers in hospitals, autism research and cystic fibrosis). His A Synopsis of Children's Diseases was published in six editions, was translated into three languages and was used as a standard paediatric textbook on four Continents. Distinct from this clinical domain, as a passionate anti-Darwinist his fundamentalist theology was that variously self-described as 'theistic evolution' (believing in 'progressive Creationism') and later that of 'six-literal day young-earth Creation'. He established and was the Foundation Chairman of the Creation Science Foundation (UK) and was World Chairman of the US-based Creation Ministries International. This biography is a record of this perhaps paradoxical and unique life. C1 Royal Childrens Hosp, Dept Paediat & Child Hlth, Brisbane, Qld 4029, Australia. RP Pearn, J (reprint author), Royal Childrens Hosp, Dept Paediat & Child Hlth, Brisbane, Qld 4029, Australia. 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Med. Biogr. PD MAY PY 2014 VL 22 IS 2 BP 63 EP 70 DI 10.1177/0967772013479508 PG 8 WC History & Philosophy Of Science SC History & Philosophy of Science GA AQ1XA UT WOS:000342576400002 ER PT J AU Ranft, P AF Ranft, Patricia TI Ruminations on Hildegard of Bingen (1098-1179) and autism SO JOURNAL OF MEDICAL BIOGRAPHY LA English DT Article DE Hildegard of Bingen; autism; Asperger; monasticism ID DIAGNOSIS AB The article brings together contemporary research on autism spectrum disorder and historical sources concerning the medical condition of a 12th century nun, Hildegard of Bingen, to test two hypotheses: first, that Hildegard manifested disabilities that meet the criteria for autism spectrum disorder and, second, that medieval monasticism was unwittingly well-suited to treat Hildegard's condition. Abundant Hildegardian sources document traces of autism spectrum disorder behaviour in Hildegard's unusual childhood and the composite picture that emerges, when these individual traits are gathered together, is consistent with an autism spectrum disorder diagnosis. The role monasticism played in helping Hildegard overcome these behaviours is documented and aspects that monasticism shares with modern autism spectrum disorder treatment programs are identified. By recognizing the presence of autism spectrum disorder traits in a major cultural leader of another era and by identifying the type of life she lived while those traits were minimized, we gain insight into the history of autism, medieval monastic life and effective elements of autism spectrum disorder treatment. C1 [Ranft, Patricia] Cent Michigan Univ, Mt Pleasant, MI USA. RP Ranft, P (reprint author), 133 Hampton Rd Ave, Hampton, VA 23661 USA. 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Med. Biogr. PD MAY PY 2014 VL 22 IS 2 BP 107 EP 115 DI 10.1177/0967772013479283 PG 10 WC History & Philosophy Of Science SC History & Philosophy of Science GA AQ1XA UT WOS:000342576400009 ER PT J AU Chok, JT Koesler, B AF Chok, James T. Koesler, Bryan TI Distinguishing Obsessive-Compulsive Behavior From Stereotypy: A Preliminary Investigation SO BEHAVIOR MODIFICATION LA English DT Article DE stereotypy; ritualistic and repetitive behavior; physiology; Obsessive-Compulsive Disorder ID REPETITIVE BEHAVIORS; FUNCTIONAL-ANALYSIS; INTERESTS DOMAIN; DISORDER; AUTISM; INDIVIDUALS; DISABILITIES; PARENTS AB The current project was an initial attempt to develop assessment procedures for distinguishing between obsessive-compulsive (OC) and stereotypic behavior and evaluate the impact of different treatments for these behaviors. Two individuals with autism, one with repetitive behavior characteristic of OC behavior and one with repetitive behavior not characteristic of OC behavior, participated in the study. In Experiment 1, given that individuals with Obsessive-Compulsive Disorder (OCD) report experiencing unpleasant urges that are relieved when they perform compulsive actions, an attempt was made to identify these experiences by measuring heart rate and affect when access to repetitive behavior was restricted and allowed. In Experiment 2, a multiple schedules treatment was conducted with each participant, and in Experiment 3, the participant with autism and OC behavior completed exposure and response prevention (ERP) treatment. The overall results across studies suggest that one potential way to discriminate between OC behavior and stereotypy in nonvocal children with autism is to consider the topography of repetitive behavior along with changes in physiology and affect. 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PD MAY PY 2014 VL 38 IS 3 SI SI BP 344 EP 373 DI 10.1177/0145445513509475 PG 30 WC Psychology, Clinical SC Psychology GA AQ3GW UT WOS:000342680400002 ER PT J AU Enloe, KA Rapp, JT AF Enloe, Kimberley A. Rapp, John T. TI Effects of Noncontingent Social Interaction on Immediate and Subsequent Engagement in Vocal and Motor Stereotypy in Children With Autism SO BEHAVIOR MODIFICATION LA English DT Article DE motor stereotypy; noncontingent reinforcement; subsequent effects; vocal stereotypy ID MATCHED STIMULATION; RESPONSE INTERRUPTION; FUNCTIONAL-ANALYSIS; SPECTRUM DISORDERS; BEHAVIOR; INDIVIDUALS; REDIRECTION; MUSIC; FORMS AB This study evaluated the effects of noncontingent social interaction (SI) on immediate and subsequent engagement in vocal and motor stereotypy in three children with autism. During SI, a therapist delivered continuous interaction in the form of reading aloud from a Kindle T e-reader. Results showed that when compared with a no-interaction baseline sequence, SI decreased immediate engagement vocal stereotypy for all three participants without increasing subsequent engagement for any participant. Furthermore, SI also increased immediate engagement in motor stereotypy for one participant, decreased immediate engagement in motor stereotypy for two participants, but did not increase subsequent engagement in motor stereotypy for any participant. Some clinical implications and limitations of the findings are discussed. C1 [Enloe, Kimberley A.] St Cloud State Univ, St Cloud, MN USA. [Rapp, John T.] Auburn Univ, Behav Anal Program, Auburn, AL 36849 USA. RP Rapp, JT (reprint author), Auburn Univ, Dept Psychol, 226 Thach, Auburn, AL 36849 USA. EM jtr0014@auburn.edu CR Athens ES, 2008, J APPL BEHAV ANAL, V41, P291, DOI 10.1901/jaba.2008.41-291 DiGennaro-Reed F. 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Modificat. PD MAY PY 2014 VL 38 IS 3 SI SI BP 374 EP 391 DI 10.1177/0145445513514081 PG 18 WC Psychology, Clinical SC Psychology GA AQ3GW UT WOS:000342680400003 ER PT J AU Rispoli, M Camargo, SH Neely, L Gerow, S Lang, R Goodwyn, F Ninci, J AF Rispoli, Mandy Camargo, Siglia Hoher Neely, Leslie Gerow, Stephanie Lang, Russell Goodwyn, Fara Ninci, Jennifer TI Pre-Session Satiation as a Treatment for Stereotypy During Group Activities SO BEHAVIOR MODIFICATION LA English DT Article DE abolishing operation; stereotypy; automatically maintained behavior; autism ID CHALLENGING BEHAVIOR; DEVELOPMENTAL-DISABILITIES; AUTOMATIC REINFORCEMENT; MOTIVATING OPERATIONS; VOCAL STEREOTYPY; STIMULI; INTERVENTION; IMMEDIATE; CHILDREN; AUTISM AB Individuals with developmental disabilities may engage in automatically reinforced behaviors that may interfere with learning opportunities. Manipulation of motivating operations has been shown to reduce automatically maintained behavior in some individuals. Considering behavioral indicators of satiation may assist in identifying the point at which an abolishing operation has begun to effect behavior. The purpose of this study was to evaluate the effects of pre-session satiation of automatic reinforcement on subsequent levels of stereotypy and activity engagement during group activities for three males ages 5 to 13 years with developmental disabilities. Following functional analyses with analogue conditions, an alternating treatment design compared a pre-session access to stereotypy condition with a no-presession access condition prior to group activity sessions. Results indicated that pre-session satiation of the putative reinforcer produced by stereotypy was effective in decreasing stereotypy and increasing activity engagement during subsequent group activities for all participants. These findings add to the literature supporting the effectiveness of abolishing operations to decrease automatically maintained stereotypy. C1 [Rispoli, Mandy; Neely, Leslie; Gerow, Stephanie; Goodwyn, Fara] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. [Camargo, Siglia Hoher] Texas A&M Univ, College Stn, TX 77843 USA. [Ninci, Jennifer] Texas A&M Univ, Dept Educ Psychol, Special Educ Program, College Stn, TX 77843 USA. [Lang, Russell] Texas State Univ, Dept Curriculum & Instruct, San Marcos, TX USA. [Lang, Russell] Texas State Univ, Clin Autism Res Evaluat & Support, San Marcos, TX USA. RP Rispoli, M (reprint author), Texas A&M Univ, 4225 TAMU, College Stn, TX 77843 USA. EM mrispoli@tamu.edu CR Chung YC, 2010, BEHAV MODIF, V34, P479, DOI 10.1177/0145445510378380 IWATA BA, 1994, J APPL BEHAV ANAL, V27, P197, DOI 10.1901/jaba.1994.27-197 Lang R, 2009, J APPL BEHAV ANAL, V42, P889, DOI 10.1901/jaba.2009.42-889 Lang R, 2010, BEHAV MODIF, V34, P267, DOI 10.1177/0145445510370713 Lanovaz MJ, 2009, BEHAV MODIF, V33, P682, DOI 10.1177/0145445509344972 Lanovaz MJ, 2013, RES AUTISM SPECT DIS, V7, P1234, DOI 10.1016/j.rasd.2013.07.009 Laraway S, 2003, J APPL BEHAV ANAL, V36, P407, DOI 10.1901/jaba.2003.36-407 MacDonald R, 2007, RES DEV DISABIL, V28, P266, DOI 10.1016/j.ridd.2006.01.004 O'Reilly M, 2009, J APPL BEHAV ANAL, V42, P773, DOI 10.1901/jaba.2009.42-773 Piazza CC, 2000, J APPL BEHAV ANAL, V33, P13, DOI 10.1901/jaba.2000.33-13 Rapp JT, 2013, BEHAV MODIF, V37, P543, DOI 10.1177/0145445512461650 Rapp JT, 2005, RES DEV DISABIL, V26, P527, DOI 10.1016/j.ridd.2004.11.005 Rapp JT, 2004, BEHAV INTERVENT, V19, P287, DOI 10.1002/bin.166 Rispoli M, 2011, J APPL BEHAV ANAL, V44, P187, DOI 10.1901/jaba.2011.44-187 Rispoli MJ, 2011, EDUC TRAIN AUTISM DE, V46, P607 Roantree CF, 2006, J APPL BEHAV ANAL, V39, P381, DOI 10.1901/jaba.2006.97-05 Simmons JN, 2003, J APPL BEHAV ANAL, V36, P541, DOI 10.1901/jaba.2003.36-541 VOLLMER TR, 1994, RES DEV DISABIL, V15, P187, DOI 10.1016/0891-4222(94)90011-6 NR 18 TC 2 Z9 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD MAY PY 2014 VL 38 IS 3 SI SI BP 392 EP 411 DI 10.1177/0145445513511631 PG 20 WC Psychology, Clinical SC Psychology GA AQ3GW UT WOS:000342680400004 ER PT J AU Watkins, N Sparling, E AF Watkins, Nicholas Sparling, Elizabeth TI The Effectiveness of the Snug Vest on Stereotypic Behaviors in Children Diagnosed With an Autism Spectrum Disorder SO BEHAVIOR MODIFICATION LA English DT Article DE autism; stereotypy; sensory integration; deep pressure; Snug Vest; QABF ID SENSORY INTEGRATION THERAPY; SELF-INJURIOUS-BEHAVIOR; VOCAL STEREOTYPY; FUNCTIONAL-ANALYSIS; WEIGHTED VESTS; NONCONTINGENT REINFORCEMENT; DIFFERENTIAL REINFORCEMENT; AUTOMATIC REINFORCEMENT; DEVELOPMENTAL DISORDERS; OCCUPATIONAL-THERAPY AB Various reviews of the effects of sensory integration therapy (SIT) have concluded that such interventions fail to reduce stereotypy. However, a new, and as yet untested, SIT iteration, an inflatable wearable vest known as the Snug Vest purports to decrease such repetitive behavior. In the current study, three children who emitted different forms of stereotypy participated in an alternating treatments design in which each participant wore a fully inflated vest and either a fully deflated vest or no vest. The results of the study show that the Snug Vest failed to reduce any participants' stereotypy. We highlight our findings in the context of professional practice and discuss several potential limitations. C1 [Watkins, Nicholas] Douglas Coll, Dept Disabil & Community Studies, New Westminster, BC V3L 5B2, Canada. [Sparling, Elizabeth] Pivot Point Family Growth Ctr, Surrey, BC, Canada. RP Watkins, N (reprint author), Douglas Coll, POB 2503, New Westminster, BC V3L 5B2, Canada. EM watkinsn@douglascollege.ca CR Ahearn WH, 2005, J APPL BEHAV ANAL, V38, P247, DOI 10.1901/jaba.2005.36-04 Ahearn WH, 2007, J APPL BEHAV ANAL, V40, P263, DOI 10.1901/jaba.2007.30-06 Ahrens EN, 2011, J APPL BEHAV ANAL, V44, P95, DOI 10.1901/jaba.2011.44-95 [Anonymous], 2013, CLIN SUPPORT [Anonymous], INSTR MAN [Anonymous], 2009, NAT STAND PROJ ADDR Athens ES, 2008, J APPL BEHAV ANAL, V41, P291, DOI 10.1901/jaba.2008.41-291 Ayres A. J., 1974, DEV SENSORY INTEGRAT, P96 Ayres A. J., 1972, SENSORY INTEGRATION Ayres AJ, 1979, SENSORY INTEGRATION Bahrami F, 2012, RES DEV DISABIL, V33, P1183, DOI 10.1016/j.ridd.2012.01.018 Barlow D., 2009, SINGLE CASE EXPT DES Beavers GA, 2011, J APPL BEHAV ANAL, V44, P593, DOI 10.1901/jaba.2011.44-593 Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Britton LN, 2002, BEHAV INTERVENT, V17, P93, DOI 10.1002/bin.110 Bulkeley K, 2013, RES AUTISM SPECT DIS, V7, P1257, DOI 10.1016/j.rasd.2013.07.014 Carter S. 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G., 1997, ZERO 3, V17, P29 NR 69 TC 1 Z9 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD MAY PY 2014 VL 38 IS 3 SI SI BP 412 EP 427 DI 10.1177/0145445514532128 PG 16 WC Psychology, Clinical SC Psychology GA AQ3GW UT WOS:000342680400005 ER PT J AU Petrova, EG Hyman, M Estrella, MRP Inglehart, MR AF Petrova, Elena G. Hyman, Michael Estrella, Maria Regina Padilla Inglehart, Marita R. TI Children with Special Health Care Needs: Exploring the Relationships between Patients' Level of Functioning, Their Oral Health, and Caregivers' Oral Health-related Responses SO PEDIATRIC DENTISTRY LA English DT Article DE CHILDREN WITH DISABILITIES; ORAL HEALTH; HEALTH EDUCATION; PARENTS; CHILDREN WITH SPECIAL HEALTH CARE NEEDS ID SPECIAL OLYMPICS; BEHAVIOR; PERCEPTIONS; ATTITUDES; AUTISM AB Purpose: The purposes of this study were to increase dentists' understanding of how to best engage parents and their children with special health care needs (SHCN) in oral health promotion efforts and explore the relationships between these patients' level of functioning. and oral health and their parents' comfort concerning oral health promotion. Methods: Survey data were collected from 154 caregivers of SHCN children. Children's oral health data were obtained from their clinical charts. Results: The patients' level of functioning ranged from the lowest to the highest regarding their ability to listen/understand, talk, relate to others, care for themselves, play with others, and participate in physical activities. Children's gingival health was correlated with their ability to talk (r=-.12; P<.05). Their oral hygiene score correlated with their ability to talk (r=.18; P<.05) and their skills in social play interactions (r=.21; P<.05). The parents' comfort level concerning oral health promotion correlated positively with their child's level of functioning. Parents' interest in receiving oral health instruction correlated positively with their child's level of functioning. Conclusions: Understanding patient's level of functioning might predict the degree to which parents actually engage in oral health promotion efforts and are interested in oral health-related education. C1 [Petrova, Elena G.] Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA. [Hyman, Michael] Wayne State Univ, Masters Program Biomed Sci, Detroit, MI USA. [Inglehart, Marita R.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA. [Inglehart, Marita R.] Univ Michigan, Dept Psychol, Coll Literature Sci & Arts, Ann Arbor, MI USA. [Estrella, Maria Regina Padilla] Univ Adelaide, Adelaide, SA, Australia. [Estrella, Maria Regina Padilla] Womens & Childrens Hosp, Adelaide, SA, Australia. RP Inglehart, MR (reprint author), Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA. EM mri@umich.edu CR Alhammad Nouf S, 2010, Odontostomatol Trop, V33, P5 American Academy of Pediatric Dentistry, 2013, PEDIAT DENT, V35, P157 [Anonymous], 2010, STAT PACK SOC SCI SP Bakry NS, 2012, J CLIN PEDIATR DENT, V36, P319 Bissar AR, 2010, INT J PAEDIATR DENT, V20, P451, DOI 10.1111/j.1365-263X.2010.01065.x Brown BR, 2011, ANGLE ORTHOD, V81, P1090, DOI 10.2319/013111-64.1 Dao Loan P, 2005, J Dent Educ, V69, P1107 Edelstein BL, 2009, ACAD PEDIATR, V9, P415, DOI 10.1016/j.acap.2009.09.010 Garfinkle AJ, 2010, J PERIODONTOL, V81, P1 Kenney MK, 2008, AMBUL PEDIATR, V8, P312, DOI 10.1016/j.ambp.2008.04.005 Kerins C, 2011, PEDIATR DENT, V33, P107 Kewallal A, PEDIAT DENT UNPUB Leroy R, 2012, COMMUNITY DENT HLTH, V29, P68, DOI 10.1922/CDH_2704Leroy06 Mouradian W E, 2001, J Dent Educ, V65, P821 Nahar Sultana Gul, 2010, Bangladesh Med Res Counc Bull, V36, P61 National Maternal and Child Oral Health Resource Center, 2005, OR HLTH SERV CHILDR Nelson LP, 2011, PEDIATR DENT, V33, P29 Oredugba Folakemi A, 2010, Spec Care Dentist, V30, P211, DOI 10.1111/j.1754-4505.2010.00155.x Purohit Bharathi M, 2010, Spec Care Dentist, V30, P235, DOI 10.1111/j.1754-4505.2010.00160.x Rich John P 3rd, 2006, J Dent Educ, V70, P1308 Sparrow SS, 2005, VINELAND ADAPTIVE BE Thikkurissy S, 2009, Dent Clin North Am, V53, P351, DOI 10.1016/j.cden.2008.12.004 U.S. Department of Health and Human Services, HIPAA ADM SIMPL STAT US Department of Health and Human Services, 2000, NIH PUBL, V00-4713, P7 US Department of Health and Human Services Health Resources and Services Administration Maternal and Child Health Bureau, 2005, NAT SURV CHILDR HLTH Van Dyck P, 2003, ARCH PEDIAT ADOLESC, V158, P884 Weil TN, 2010, J DENT EDUC, V74, P1294 Weil TN, 2012, PEDIATR DENT, V34, P473 NR 28 TC 0 Z9 0 PU AMER ACAD PEDIATRIC DENTISTRY PI CHICAGO PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA SN 0164-1263 EI 1942-5473 J9 PEDIATR DENT JI Pediatr. Dent. PD MAY-JUN PY 2014 VL 36 IS 3 BP 233 EP 239 PG 7 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA AP8NW UT WOS:000342336700011 PM 24960391 ER PT J AU Papineau, SD Wilson, S AF Papineau, Scott D. Wilson, Stephen TI Dentition Abnormalities in a Timothy Syndrome Patient With a Novel Genetic Mutation: A Case Report SO PEDIATRIC DENTISTRY LA English DT Article DE TIMOTHY SYNDROME; ENAMEL HYPOPLASIA; GENETICS ID LONG QT SYNDROME; ARRHYTHMIA AB The purpose of this paper was to present the case of a two-year-old male diagnosed with Timothy syndrome who presented with generalized enamel defects in the primary dentition. Timothy syndrome is an autosomal dominant condition characterized by a de novo missense mutation in the Ca(v)1.2 L-type calcium channel CACNA1C. Timothy syndrome patients present with multiple clinical manifestations, including: cardiac arrhythmias; syndactyly; immune deficiency; intermittent hypoglycemia; and neurologic issues, including seizures, mental retardation, hypotonia, and autism. Craniofacial abnormalities reported include: low-set ears; flat nasal bridge; small upper jaw; thin upper lip; round face; and baldness at birth. Abnormalities in the dentition have been reported, including small, misplaced teeth with poor enamel and severe caries. At present, there is no thorough description of the dental abnormalities seen in a patient with Timothy syndrome. C1 [Wilson, Stephen] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Dent, Cincinnati, OH 45229 USA. 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PD MAY-JUN PY 2014 VL 36 IS 3 BP 245 EP 249 PG 5 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA AP8NW UT WOS:000342336700013 PM 24960393 ER PT J AU Kaurani, L Vishal, M Kumar, D Sharma, A Mehani, B Sharma, C Chakraborty, S Jha, P Ray, J Sen, A Dash, D Ray, K Mukhopadhyay, A AF Kaurani, Lalit Vishal, Mansi Kumar, Dhirendra Sharma, Anchal Mehani, Bharati Sharma, Charu Chakraborty, Subhadip Jha, Pankaj Ray, Jharna Sen, Abhijit Dash, Debasis Ray, Kunal Mukhopadhyay, Arijit TI Gene-Rich Large Deletions Are Overrepresented in POAG Patients of Indian and Caucasian Origins SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE glaucoma; POAG; genomics; CNV; CNTN4 ID COPY-NUMBER VARIATION; OPEN-ANGLE GLAUCOMA; CHROMOSOME 3Q; REVEALS; SUSCEPTIBILITY; DUPLICATIONS; POPULATIONS; PHENOTYPES; VARIANTS; SPECTRUM AB PURPOSE. Large copy number variations (CNV) can contribute to increased burden for neurodegenerative diseases. In this study, we analyzed the genome-wide burden of large CNVs > 100 kb in primary open angle glaucoma (POAG), a neurodegenerative disease of the eye that is the largest cause of irreversible blindness. METHODS. Genome-wide analysis of CNVs > 100 kb were analyzed in a total of 1720 individuals, including an Indian cohort (347 POAG cases and 345 controls) and a Caucasian cohort (624 cases and 404 controls). All the CNV data were obtained from experiments performed on Illumina 660W-Quad (infinium) arrays. RESULTS. We observed that for both the populations CNVs > 1 Mb was significantly enriched for gene-rich regions unique to the POAG cases (P < 10 (11)). In the Indian cohort CNVs > 1 Mb (39 calls) in patients influenced 125 genes while in controls 31 such CNVs influenced only 5 genes with no overlap. In both cohorts we observed 1.9-fold gene enrichment in patients for deletions compared to duplications, while such a bias was not observed in controls (0.3-fold). Overall duplications > 1 Mb were more than deletions (Del/Dup = 0.82) confirming that the enrichment of gene-rich deletions in patients was associated with the disease. Of the 39 CNVs > 1 Mb from Indian patients, 28 (72%) also were implicated in other neurodegenerative disorders, like autism, schizophrenia, sensorineural hearing loss, and so forth. We found one large duplication encompassing CNTN4 gene in Indian and Caucasian POAG patients that was absent in the controls. CONCLUSIONS. To our knowledge, our study is the first report on large CNV bias for gene-rich regions in glaucomatous neurodegeneration, implicating its impact across populations of contrasting ethnicities. We identified CNTN4 as a novel candidate gene for POAG. C1 [Kaurani, Lalit; Vishal, Mansi; Sharma, Anchal; Mehani, Bharati; Jha, Pankaj; Mukhopadhyay, Arijit] CSIR Inst Genom & Integrat Biol, Delhi, India. [Vishal, Mansi; Chakraborty, Subhadip; Ray, Kunal] CSIR Indian Inst Chem Biol, Mol & Human Genet Div, Kolkata, India. [Kumar, Dhirendra; Dash, Debasis] CSIR Inst Genom & Integrat Biol, GN Ramachandran Knowledge Ctr Genome Informat, Delhi, India. [Sharma, Anchal; Ray, Kunal; Mukhopadhyay, Arijit] Acad Sci & Innovat Res AcSIR, New Delhi, India. [Sharma, Charu] Shiv Nadar Univ, Dept Math, Gautam Buddha Nagar, Uttar Pradesh, India. [Chakraborty, Subhadip; Ray, Jharna] Univ Calcutta, SN Pradhan Ctr Neurosci, Kolkata, India. [Sen, Abhijit] Dristi Pradip, Kolkata, India. RP Mukhopadhyay, A (reprint author), CSIR Cent Rd Res Inst, Acad Sci & Innovat Res, CSIR Inst Genom & Integrat Biol IGIB, Mathura Rd Near Sukhdev Vihar, New Delhi 110025, India. EM kunalray@gmail.com; arijit@igib.res.in FU Council of Scientific and Industrial Research (CSIR), India [MLP-0016, BSC-0123]; CSIR-India; National Institutes of Health (NIH) Genes, Environment and Health Initiative [GEI] [U01HG004728]; Gene Environment Association Studies (GENEVA) under GEI; NIH GEI [U01 HG04424] FX Supported by the Council of Scientific and Industrial Research (CSIR), India (Grants MLP-0016 and BSC-0123), and a senior research fellowship from CSIR-India (LK). The GLAUGEN study was supported by the National Institutes of Health (NIH) Genes, Environment and Health Initiative ([GEI], U01HG004728). The GLAUGEN study is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Genotyping, which was performed at the Broad Institute of the Massachusetts Institute of technology (MIT; Cambridge, MA, USA) and Harvard University (Cambridge, MA, USA), was supported by the NIH GEI (U01 HG04424). 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Ophthalmol. Vis. Sci. PD MAY PY 2014 VL 55 IS 5 BP 3258 EP 3264 DI 10.1167/iovs.14-14339 PG 7 WC Ophthalmology SC Ophthalmology GA AL9TP UT WOS:000339484800058 PM 24764060 ER PT J AU Dodd, JL Hagge, DK AF Dodd, Janet L. Hagge, Darla K. TI AAC Camp as an Alternative School-Based Service Delivery Model: A Retrospective Survey SO COMMUNICATION DISORDERS QUARTERLY LA English DT Article DE AAC intervention; progress monitoring; complex communication needs; alternative service delivery model ID COMPLEX COMMUNICATION NEEDS; AIDED LANGUAGE STIMULATION; DEVELOPMENTAL-DISABILITIES; SPEECH PRODUCTION; CHILDREN; INTERVENTIONS; ADULTS; INDIVIDUALS; AUTISM; IMPACT AB School-based speech-language pathologists are obligated to apply evidence-based practice and document progress of their students' response to intervention in compliance with federal law. The purpose of this preliminary study was to explore the effects of an augmentative and alternative communication (AAC)-based intervention provided in a camp format and begin the exploration of examining strategies to monitor and document progress. Through the use of a survey, data were also collected regarding the demographics of camp attendees and their response to the camp-based intervention model. Results indicated children with autism and intellectual disability comprised a significant portion of the children referred for this type of intervention, and positive gains were documented both in the areas of communicative behaviors and pragmatic use. C1 [Dodd, Janet L.] Chapman Univ, Orange, CA 92866 USA. [Hagge, Darla K.] Calif State Univ Sacramento, Sacramento, CA 95819 USA. RP Dodd, JL (reprint author), Chapman Univ, 1 Univ, Orange, CA 92866 USA. 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PD MAY PY 2014 VL 35 IS 3 BP 123 EP 132 DI 10.1177/1525740113512670 PG 10 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA AL7SP UT WOS:000339335800001 ER PT J AU DeVeney, SL Cress, CJ Reid, R AF DeVeney, Shari L. Cress, Cynthia J. Reid, Robert TI Comparison of Two Word Learning Techniques and the Effect of Neighborhood Density for Late Talkers SO COMMUNICATION DISORDERS QUARTERLY LA English DT Article DE birth to 3 years; age; intervention strategies; language/linguistics; delays/disorders; research; single subject; methodology; research ID LATE-TALKING TODDLERS; LANGUAGE IMPAIRMENT; PHONOTACTIC PROBABILITY; READING OUTCOMES; VOCABULARY; ACTIVATION; AUTISM; DELAYS AB The investigators compared two techniques for teaching expressive vocabulary to late talkers: modeling with an expectant pause and modeling with an evoked child production. They also explored the influence of neighborhood density on children's real word learning. Three late talkers (ages 25-33 months) received two alternating vocabulary treatments (expectant pause and evoked production) in the home. Two participants were identified as having an expressive language delay, and one participant was identified as having an expressive and receptive language delay. During the expectant pause treatment, the clinician paused several seconds after each target word model, looking at the child expectantly. In the evoked production condition, after each target word model, a child was prompted to say the word using a cloze procedure of the modeled phrase. Both treatments were effective for all participants; no consistent advantage of one treatment technique over the other was noted. Two participants produced denser words than sparse words, one in early sessions and one in later experimental sessions, but a consistent pattern was not present across all participants. This study provided support for focused vocabulary intervention with late talking toddlers. 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Minnis, Helen Thompson, Lucy Wilson, Philip Gillberg, Christopher TI Neurodevelopmental and psychosocial risk factors in serial killers and mass murderers SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE Autistic Spectrum Disorder; Serial killer; Mass murder; Brain injury; Psychosocial stressors ID ASPERGERS-SYNDROME; SEXUAL HOMICIDE; ANTISOCIAL-BEHAVIOR; CRIMINAL BEHAVIOR; UNITED-STATES; HEAD-INJURY; VIOLENCE; AGGRESSION; DAHMER,JEFFREY; PSYCHOPATHY AB Multiple and serial murders are rare events that have a very profound societal impact. We have conducted a systematic review, following PRISMA guidelines, of both the peer reviewed literature and of journalistic and legal sources regarding mass and serial killings. Our findings tentatively indicate that these extreme forms of violence may be a result of a highly complex interaction of biological, psychological and sociological factors and that, potentially, a significant proportion of mass or serial killers may have had neurodevelopmental disorders such as autism spectrum disorder or head injury. Research into multiple and serial murders is in its infancy: there is a lack of rigorous studies and most of the literature is anecdotal and speculative. Specific future study of the potential role of neurodevelopmental disorders in multiple and serial murders is warranted and, due to the rarity of these events, innovative research techniques may be required. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Allely, Clare S.; Minnis, Helen; Thompson, Lucy] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G3 8SJ, Lanark, Scotland. [Wilson, Philip] Univ Aberdeen, Ctr Rural Hlth, Ctr Hlth Sci, Inverness IV2 3JH, Scotland. 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TI Eyes and IQ: A meta-analysis of the relationship between intelligence and "Reading the Mind in the Eyes" SO INTELLIGENCE LA English DT Article DE Mental state; Mentalizing; RMET; Social cognition; Theory of mind ID HIGH-FUNCTIONING AUTISM; VOXEL-BASED MORPHOMETRY; SOCIAL COGNITION; ASPERGER-SYNDROME; FALSE-BELIEF; EMOTIONAL INTELLIGENCE; ANOREXIA-NERVOSA; MULTIPLE-SCLEROSIS; DOMAIN-SPECIFICITY; LOBE CONTRIBUTIONS AB Although the Reading the Mind in the Eyes Test (RMET; Baron-Cohen et al. 1997, 2001) has been used as a measure of mental state understanding in over 250 studies, the extent to which it correlates with intelligence is seldom considered. We conducted a meta-analysis to investigate whether or not a relationship exists between intelligence and performance on the RMET. The analysis of 77 effects sizes with 3583 participants revealed a small positive correlation (r = .24) with no difference between verbal and performance abilities. We conclude that intelligence does play a significant role in performance on the RMET and that verbal and performance abilities contribute to this relationship equally. We discuss these findings in the context of the theory of mind and domain-general resources literature. (C) 2014 Elsevier Inc. All rights reserved. C1 [Baker, Crystal A.; Peterson, Eric; Pulos, Steven; Kirkland, Rena A.] Univ No Colorado, Sch Psychol Sci, Greeley, CO 80639 USA. RP Baker, CA (reprint author), Univ No Colorado, Sch Psychol Sci, 501 20th St, Greeley, CO 80639 USA. 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Whillock, Katherine M. Kim, Seo Hyun Greenberg, Julia R. Jones, Katherine B. Patel, Anushka R. Steefel-Moore, David L. Shaw, Allyson J. Rupert, Deborah D. Gauer, Jacqueline L. Kudura, Aisha G. TI Gestalt Principle Use in College Students, Children With Autism, Toddlers (Homo sapiens), and Cotton Top Tamarins (Saguinus oedipus) SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article DE tamarin; primate; perception; Gestalt; autism ID MONKEYS CEBUS-APELLA; CHIMPANZEES PAN-TROGLODYTES; HIERARCHICAL VISUAL-STIMULI; PIGEONS COLUMBA-LIVIA; BRAIN EVOLUTION; CORPUS-CALLOSUM; MACACA-MULATTA; HUMANS; PERCEPTION; ATTENTION AB The use of Gestalt principles of proximity, similarity, and closure to recognize objects by configural superiority was examined in college students, low- and high-functioning children with autism, toddlers, and adult cotton top tamarin monkeys. At issue was whether the monkeys showed differences from humans in perceptual processing and whether they showed any similarities with clinical or developmental groups. The method required a pointing response to discriminate an odd item in a 4-item visual display. All subjects were trained to a high accuracy to point to the odd item before being tested with graphic stimuli that differentiated feature changes based on configural superiority. The results were that college students and high-functioning children with autism responded faster and more accurately to trials in which the odd item was easily noticed by the use of Gestalt principles and configural superiority. Toddlers also responded more accurately to the Gestalt trials, but without being faster at making the response. Low-functioning children with autism and tamarins showed no advantage to Gestalt trials but exhibited different processing styles. The implications of these findings to track the evolution of human perception and to develop a primate model for the perceptual deficits of autism are discussed. C1 [Neiworth, Julie J.] Carleton Coll, Dept Psychol, Northfield, MN 55057 USA. [Whillock, Katherine M.] Penn State Univ, University Pk, PA 16802 USA. [Kim, Seo Hyun] Columbia Univ, Dept Psychol & Educ, New York, NY 10027 USA. [Greenberg, Julia R.] Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. [Jones, Katherine B.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. [Patel, Anushka R.] Harvard Univ, Cambridge, MA 02138 USA. [Steefel-Moore, David L.] MATCH Publ Charter Sch, Plymouth, MN USA. [Shaw, Allyson J.] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Rupert, Deborah D.] Columbia Univ, New York, NY 10027 USA. [Gauer, Jacqueline L.] Univ Texas Dallas, Dallas, TX 75230 USA. [Kudura, Aisha G.] New Mexico State Univ, Las Cruces, NM 88003 USA. RP Neiworth, JJ (reprint author), Carleton Coll, Dept Psychol, One North Coll St, Northfield, MN 55057 USA. EM jneiwort@carleton.edu FU NIMH AREA [1-R15MH071232-01A2] FX This research was funded by NIMH AREA 1-R15MH071232-01A2 to Julie Neiworth, principal investigator. We acknowledge the support of Julia Strand and Sarah Meerts of Carleton College, for editing advice on earlier versions of this article; Kristen A. Miller for help in collecting data from the toddlers; and Shaun M. Sawtell for help in collecting data from college students and tamarins. CR Bolte S, 2007, J AUTISM DEV DISORD, V37, P1493, DOI 10.1007/s10803-006-0231-x Boring E. 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Comp. Psychol. PD MAY PY 2014 VL 128 IS 2 SI SI BP 188 EP 198 DI 10.1037/a0034840 PG 11 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA AJ7TB UT WOS:000337899000014 PM 24491175 ER PT J AU Braun, JM Kalkbrenner, AE Just, AC Yolton, K Calafat, AM Sjodin, A Hauser, R Webster, GM Chen, AM Lanphear, BP AF Braun, Joseph M. Kalkbrenner, Amy E. Just, Allan C. Yolton, Kimberly Calafat, Antonia M. Sjodin, Andreas Hauser, Russ Webster, Glenys M. Chen, Aimin Lanphear, Bruce P. TI Gestational Exposure to Endocrine-Disrupting Chemicals and Reciprocal Social, Repetitive, and Stereotypic Behaviors in 4-and 5-Year-Old Children: The HOME Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID ATTENTION DEFICIT/HYPERACTIVITY DISORDER; POLYBROMINATED DIPHENYL ETHERS; PERSISTENT ORGANIC POLLUTANTS; AUTISM SPECTRUM DISORDERS; BISPHENOL-A EXPOSURE; POLYFLUOROALKYL CHEMICALS; HIERARCHICAL REGRESSION; ORGANOCHLORINE EXPOSURE; CHILDHOOD BEHAVIOR; PERINATAL EXPOSURE AB Background: Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult. Objective: Our goal was to identify gestational EDC exposures associated with autistic behaviors. Methods: We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs. Results: Most of the EDCs were associated with negligible absolute differences in SRS scores (<= 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (beta = 2.5; 95% CI: -0.6, 5.6) or trans-nonachlor (beta = 4.1; 95% CI: 0.8-7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (beta = -3.0; 95% CI: -6.3, 0.2), beta-hexachlorocyclohexane (beta = -3.3; 95% CI: -6.1, -0.5), or PBDE-85 (beta = -3.2; 95% CI: -5.9, -0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (beta = -2.0; 95% CI: -4.4, 0.4). Conclusions: Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, beta-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors. C1 [Braun, Joseph M.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Kalkbrenner, Amy E.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA. 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Health Perspect. PD MAY PY 2014 VL 122 IS 5 BP 513 EP 520 DI 10.1289/ehp.1307261 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AJ3ZC UT WOS:000337606300022 PM 24622245 ER PT J AU Atkin, K Tozer, R AF Atkin, Karl Tozer, Rosemary TI Personalisation, family relationships and autism: Conceptualising the role of adult siblings SO JOURNAL OF SOCIAL WORK LA English DT Article DE Social work; autism; carers; European; family support; learning disability; social support ID EXPERIENCE AB .Summary: Current policy discourses demonstrate a weak connection to broader theoretical debates about family obligation and in particular how family responsibilities become negotiated over time and across the life course. How policy imagines family care can, therefore, be different to the actual experiences of families. This qualitative paper, using semi-structured interviews, explores the experience of a particularly neglected group, adult siblings, who have a brother or sister with autism (plus learning disability). We spoke to 21 adult siblings, met with 12 of their siblings with autism and talked to 12 health and social care professionals. Findings: Our analysis suggests that connectedness and commitment, which remained subject to continuous redefinition by all family members, informed sibling relationships Practitioners, however, struggle to engage with this complexity, thereby undermining the extent siblings' relationships can be realised. Application: The paper concludes that policy initiatives are at risk of becoming an uneasy compromise, in which the need to offer choice occurs alongside the 'problem' of managing family care. Sibling relationships are more than simply 'being of' or 'belonging to' a family. They are dynamic, subject to contingency and negotiation. 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Work PD MAY PY 2014 VL 14 IS 3 BP 225 EP 242 DI 10.1177/1468017313476453 PG 18 WC Social Work SC Social Work GA AJ4EH UT WOS:000337624000001 ER PT J AU Zeidan-Chulia, F de Oliveira, BHN Salmina, AB Casanova, MF Gelain, DP Noda, M Verkhratsky, A Moreira, JCF AF Zeidan-Chulia, F. de Oliveira, B-H N. Salmina, A. B. Casanova, M. F. Gelain, D. P. Noda, M. Verkhratsky, A. Moreira, J. C. F. TI Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy SO CELL DEATH & DISEASE LA English DT Article DE proliferation; mitochondria; APP; magnesium; rapamycin ID AMYLOID-PRECURSOR-PROTEIN; REGULATED PROTEOLYSIS; SPECTRUM DISORDERS; COGNITIVE DEFICITS; RNA INTERFERENCE; GAMMA-SECRETASE; NMDA RECEPTORS; CELL-SURVIVAL; MOUSE MODEL; SAPP-ALPHA AB Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-beta precursor protein-alpha has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria- related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of alpha-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg2+) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed. C1 [Zeidan-Chulia, F.; de Oliveira, B-H N.; Gelain, D. P.; Moreira, J. C. F.] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Ctr Estudos Estresse Oxidat, BR-90035003 Porto Alegre, RS, Brazil. [Salmina, A. B.] Krasnoyarsk State Med Univ, Dept Biochem Med Pharmaceut & Toxicol Chem, Krasnoyarsk, Russia. [Casanova, M. F.] Univ Louisville, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. [Noda, M.] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Pathophysiol, Fukuoka 812, Japan. [Verkhratsky, A.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Verkhratsky, A.] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain. [Verkhratsky, A.] Univ Basque Country UPV EHU, Dept Neurosci, Leioa, Spain. RP Zeidan-Chulia, F (reprint author), Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Ctr Estudos Estresse Oxidat, Rua Ramiro Barcelos 2600 ANEXO, BR-90035003 Porto Alegre, RS, Brazil. EM fzchulia.biomed@gmail.com RI Verkhratsky, Alexei/J-4527-2013; Zeidan Chulia, Fares/E-5605-2015 OI Verkhratsky, Alexei/0000-0003-2592-9898; FU FAPERGS [PqG 1008860, PqG 1008857, ARD11/1893-7, PRONEX 1000274]; CAPES [PROCAD 066/2007]; CNPq [558289/2008-8, 302330/2009-7]; PROPESQ-UFRGS FX First of all, our sincere apologies to the authors whose work have not been cited in the present study because of space considerations. We thank Brazilian research funding agencies FAPERGS (PqG 1008860, PqG 1008857, ARD11/1893-7, and PRONEX 1000274), CAPES (PROCAD 066/2007), CNPq (558289/2008-8 and 302330/2009-7), as well as PROPESQ-UFRGS for supporting this work. 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PD MAY PY 2014 VL 5 SI SI AR e1250 DI 10.1038/cddis.2014.227 PG 13 WC Cell Biology SC Cell Biology GA AI9DN UT WOS:000337229300050 PM 24853428 ER PT J AU Bink, M van Nieuwenhuizen, C Popma, A Bongers, IL van Boxtel, GJM AF Bink, Marleen van Nieuwenhuizen, Chijs Popma, Arne Bongers, Ilja L. van Boxtel, Geert J. M. TI Neurocognitive Effects of Neurofeedback in Adolescents With ADHD: A Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY-DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDERS; CONTROLLED CLINICAL-TRIAL; DSM-IV; CHILDREN; EEG; PREVALENCE AB Objective: Neurofeedback aims to reduce symptoms of attention-deficit/hyperactivity disorder (ADHD), mainly attention problems. However, the additional influence of neurofeedback over treatment as usual (TAU) on neurocognitive functioning for adolescents with ADHD remains unclear. Method: By using a multicenter parallel randomized controlled trial (RCT) design, male adolescents with a DSM-IV-TR diagnosis of ADHD (mean age = 16.1 years; range, 12-24) were randomized to receive either a combination of TAU and neurofeedback (n = 45) or TAU (n = 26). Randomization was computer generated and stratified by age group (ages 12 through 15, 16 through 20, and 21 through 24 years). The neurofeedback intervention consisted of approximately 37 sessions over a period of 25 weeks of theta/sensorimotor rhythm training on the vertex (Cz). Primary neurocognitive outcomes included performance parameters derived from the D2 Test of Attention, the Digit Span backward, the Stroop Color-Word Test and the Tower of London, all assessed preintervention and postintervention. Data were collected between December 2009 and July 2012. Results: At postintervention, outcomes of attention and/or motor speed were improved, with faster processing times for both intervention conditions and with medium to large effect sizes (range,.p 2 =.08-. 54; P values <.023). In both groups, no improvements for higher executive functions were observed. Results might partly resemble practice effects. Conclusions: Although neurocognitive outcomes improved in all adolescents receiving treatment for ADHD, no additional value for neurofeedback over TAU was observed. Hence, this study does not provide evidence for using theta/sensorimotor rhythm neurofeedback to enhance neurocognitive performance as additional intervention to TAU for adolescents with ADHD symptoms. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Bink, Marleen; van Nieuwenhuizen, Chijs] Tilburg Univ, Sci Ctr Care & Welf Tranzo, NL-5000 LE Tilburg, Netherlands. [van Boxtel, Geert J. M.] Tilburg Univ, Dept Psychol, NL-5000 LE Tilburg, Netherlands. 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Clin. Psychiatry PD MAY PY 2014 VL 75 IS 5 BP 535 EP U279 DI 10.4088/JCP.13m08590 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI9LZ UT WOS:000337255400019 PM 24922488 ER PT J AU Sisskin, V Wasilus, S AF Sisskin, Vivian Wasilus, Samantha TI Lost in the Literature, but Not the Caseload: Working with Atypical Disfluency from Theory to Practice SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Stuttering; atypical disfluency; word-final repetition; autism ID WORD-FINAL DISFLUENCIES; FUNCTIONING AUTISM; BRAIN-DAMAGE; REPETITIONS; CHILDREN AB Atypical disfluency is a frustrating but little addressed clinical problem. The purpose of this article and case study was to summarize what is known about atypical fluency profiles and to describe the presenting behaviors and successful treatment of an unusual fluency profile (numerous word-final syllable repetitions) in a school-aged child. To this end, we describe the speech fluency and associated communication characteristics of a young boy diagnosed with Asperger disorder who was between 7; 2 and 8; 0 when seen for evaluation and treatment. We describe a therapy protocol that was successful in nearly eliminating these atypical disfluencies. The protocol emphasized self-monitoring and was integrated with other goals to improve the child's communication, which had features consistent with mild autism spectrum disorder (ASD). Following an 8-week treatment, the child significantly reduced his percent stuttered syllables of atypical disfluencies (word-final repetition and phrase-final repetition), resulting in significant qualitative improvements to his speech. This case study demonstrates that traditional stuttering modification treatment can be successful in reducing atypical and typical disfluencies in a child with concomitant social language impairment consistent with ASD. The therapy approach reported here may be useful in treatment of other cases having symptoms similar to the child we treated. C1 [Sisskin, Vivian; Wasilus, Samantha] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. RP Wasilus, S (reprint author), Univ Maryland, Dept Hearing & Speech Sci, 0100 LeFrak Hall, College Pk, MD 20742 USA. 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Speech Lang. PD MAY PY 2014 VL 35 IS 2 DI 10.1055/s-0034-1371757 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AI9XW UT WOS:000337301600005 PM 24782276 ER PT J AU Lewis, JD Evans, AC Pruett, JR Botteron, K Zwaigenbaum, L Estes, A Gerig, G Collins, L Kostopoulos, P McKinstry, R Dager, S Paterson, S Schultz, RT Styner, M Hazlett, H Piven, J AF Lewis, J. D. Evans, A. C. Pruett, J. R. Botteron, K. Zwaigenbaum, L. Estes, A. Gerig, G. Collins, L. Kostopoulos, P. McKinstry, R. Dager, S. Paterson, S. Schultz, R. T. Styner, M. Hazlett, H. Piven, J. CA IBIS Network TI Network inefficiencies in autism spectrum disorder at 24 months SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID HIGH-FUNCTIONING AUTISM; CEREBRAL-BLOOD-FLOW; FUSIFORM FACE AREA; CHILDHOOD AUTISM; CORPUS-CALLOSUM; TEMPORAL-LOBE; WHITE-MATTER; SMALL-WORLD; FRONTAL-CORTEX; BRAIN NETWORK AB Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral symptoms that emerge during the first years of life. Associated with these symptoms are differences in the structure of a wide array of brain regions, and in the connectivity between these regions. However, the use of cohorts with large age variability and participants past the generally recognized age of onset of the defining behaviors means that many of the reported abnormalities may be a result of cascade effects of developmentally earlier deviations. This study assessed differences in connectivity in ASD at the age at which the defining behaviors first become clear. There were 113 24-month-old participants at high risk for ASD, 31 of whom were classified as ASD, and 23 typically developing 24-month-old participants at low risk for ASD. Utilizing diffusion data to obtain measures of the length and strength of connections between anatomical regions, we performed an analysis of network efficiency. Our results showed significantly decreased local and global efficiency over temporal, parietal and occipital lobes in high-risk infants classified as ASD, relative to both low-and high-risk infants not classified as ASD. The frontal lobes showed only a reduction in global efficiency in Broca's area. In addition, these same regions showed an inverse relation between efficiency and symptom severity across the high-risk infants. The results suggest delay or deficits in infants with ASD in the optimization of both local and global aspects of network structure in regions involved in processing auditory and visual stimuli, language and nonlinguistic social stimuli. C1 [Lewis, J. D.; Evans, A. C.; Collins, L.; Kostopoulos, P.] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. [Pruett, J. R.; Botteron, K.; McKinstry, R.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Zwaigenbaum, L.] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. [Estes, A.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Gerig, G.] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA. [Dager, S.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Paterson, S.; Schultz, R. T.] Univ Penn, Ctr Autism Res, Philadelphia, PA 19104 USA. [Styner, M.] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA. [Styner, M.; Hazlett, H.; Piven, J.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA. RP Lewis, JD (reprint author), McGill Univ, Montreal Neurol Inst, 3801 Univ,WB208, Montreal, PQ H3A 2B4, Canada. EM jlewis@bic.mni.mcgill.ca FU NIH Autism Center of Excellence grant [HD055741]; Autism Speaks; Simons Foundation; Canada Foundation for Innovation (CFI); Government of Quebec; National Science and Engineering Research Council (NSERC); Fonds Quebecois de Recherche sur la Nature et les Technologies (FQRNT) FX This work was supported by an NIH Autism Center of Excellence grant (a longitudinal MRI study of infants at risk for autism, NIH, R01 Supplement, 2009-2013, NIMH and NICHD #HD055741 to Principal Investigator JP) and funding from Autism Speaks, the Simons Foundation, the Canada Foundation for Innovation (CFI), the Government of Quebec, the National Science and Engineering Research Council (NSERC) and the Fonds Quebecois de Recherche sur la Nature et les Technologies (FQRNT). 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Psychiatr. PD MAY PY 2014 VL 4 AR e388 DI 10.1038/tp.2014.24 PG 11 WC Psychiatry SC Psychiatry GA AJ2RX UT WOS:000337509500001 PM 24802306 ER PT J AU Rakap, S Snyder, P Pasia, C AF Rakap, Salih Snyder, Patricia Pasia, Cathleen TI Comparison of Nonoverlap Methods for Identifying Treatment Effect in Single-Subject Experimental Research SO BEHAVIORAL DISORDERS LA English DT Article ID EFFECT SIZES; QUANTITATIVE SYNTHESIS; CHALLENGING BEHAVIOR; VISUAL INSPECTION; DESIGNS; METAANALYSIS; CHILDREN; AUTISM; INSTRUCTION; PERCENTAGE AB Debate is occurring about which result interpretation aides focused on examining the experimental effect should be used in single-subject experimental research. In this study, we examined seven nonoverlap methods and compared results using each method to judgments of two visual analysts. The data sources for the present study were 36 studies focused on naturalistic instruction interventions for young children with disabilities and 222 A-B graphs available in these studies. Two visual analysts made judgments about whether a functional relationship was evident in 222 A-B graphs. A graphing program was used to derive data for calculating each of the nonoverlap methods. Results showed that (a) estimates of experimental effect varied across the seven nonoverlap methods and (b) nonoverlap methods corresponding most closely with visual analysts' judgments of a change in data patterns differed from the nonoverlap methods that corresponded most closely with visual analysts' judgments of no change in data patterns. Based on findings from this study, we discuss considerations for selection and use of nonoverlap methods as result interpretation aides in single-subject experimental research and offer directions for future research. 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Folks, Nathan Hardy, Jordan TI On the dynamics of stimulus control during guided skill learning in nonhumans SO BEHAVIOURAL PROCESSES LA English DT Article DE Autonomy; Expertise; Motor skill; Prompt dependence; Skill learning; Stimulus control ID REINFORCEMENT CONTINGENCIES; GUIDING CUES; DISCRIMINATION; EXPERTISE; BEHAVIOR; AUTISM; MEMORY; DOGS; RATS AB This study measured skill acquisition in the presence and absence of guiding cues in pigeons. It asked whether the speed of development of autonomy for the motor skill is influenced by the difficulty level of two guiding-cue conditions requiring the same left-right response sequence. The Follow-Red condition required a simple go, no-go discrimination (red = S+, green = S-), whereas the Red-Green condition was a more difficult simultaneous chain requiring sensitivity to the serial order of key colors (red = S+, green = S- for the first peck, but red = S-, green = S+ for the second peck). Pigeons exposed to the difficult Red-Green condition displayed significantly higher accuracy levels during no-cues conditions earlier in training than those exposed to the easier Follow-Red condition. A modified Power Law of Practice was used to evaluate the null hypothesis that autonomy develops equally in explicit guiding-cues conditions and no-cues conditions. This hypothesis was retained in the Follow-Red condition but rejected in the Red-Green condition. Practice completing the response sequence in the Follow-Red and no-cues conditions both contributed equally to autonomy. Autonomy developed faster in the Red,Green group in both conditions, and it developed unexpectedly rapidly during the second guiding-cues condition, implying the involvement of a second process for the Red-Green condition. We discuss the implications of these results to prompt dependence in children with learning disabilities, the transfer of stimulus control, and potential behavioral interventions. 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Processes PD MAY PY 2014 VL 104 SI SI BP 72 EP 83 DI 10.1016/j.beproc.2014.01.017 PG 12 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA AI4HK UT WOS:000336826100010 PM 24468214 ER PT J AU Suraev, AS Bowen, MT Ali, SO Hicks, C Ramos, L McGregor, LS AF Suraev, Anastasia S. Bowen, Michael T. Ali, Sinan O. Hicks, Callum Ramos, Linnet McGregor, Lain S. TI Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood SO HORMONES AND BEHAVIOR LA English DT Article DE Oxytocin; TGOT; Social behavior; Social play; Anxiety; EIA ID AUTISM SPECTRUM DISORDERS; V1A VASOPRESSIN RECEPTOR; ANXIETY-RELATED BEHAVIOR; MALE-RATS; INTRANASAL OXYTOCIN; ENZYME-IMMUNOASSAY; FOS EXPRESSION; BRAIN; MICE; SYSTEM AB There are indications that exposing adolescent rodents to oxytocin (OT) may have positive "trait-changing" effects resulting in increased sociability and decreased anxiety that last well beyond acute drug exposure and into adulthood. Such findings may have relevance to the utility of OT in producing sustained beneficial effects in human psychiatric conditions. The present study further examined these effects using an intermittent regime of OT exposure in adolescence, and using Long Evans rats, that are generally more sensitive to the acute prosocial effects of OT. As OT has substantial affinity for the vasopressin Via receptor (V1aR) in addition to the oxytocin receptor (OTR), we examined whether a more selective peptidergic OTR agonist - [Thr4, Gly7]-oxytocin (TGOT) - would have similar lasting effects on behavior. Male Long Evans rats received OT or TGOT (0.5-1 mg/kg, intraperitoneal), once every three days, for a total of 10 doses during adolescence (postnatal day (PND) 28-55). Social and anxiety-related behaviors were assessed during acute administration as well as later in adulthood (from PND 70 onwards). OT produced greater acute behavioral effects than TGOT, including an inhibition of social play and reduced rearing, most likely reflecting primary sedative effects. In adulthood, OT but not TGOT pretreated rats displayed lasting increases in social interaction, accompanied by an enduring increase in plasma OT. These findings confirm lasting behavioral and neuroendocrine effects of adolescent OT exposure. However, the absence of such effects with TGOT suggests possible involvement of the V1aR as well as the OTR in this example of developmental neuroplasticity. (C) 2014 Elsevier Inc. All rights reserved. C1 [Suraev, Anastasia S.; Bowen, Michael T.; Ali, Sinan O.; Hicks, Callum; Ramos, Linnet; McGregor, Lain S.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. RP McGregor, LS (reprint author), Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. EM iain.mcgregor@sydney.edu.au FU National Health and Medical Research Council (NHMRC); Australian Research Council (ARC) FX This study was supported by research funding to Professor lain McGregor from the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC). Professor McGregor is an ARC Australian Professorial Fellow and NHMRC Principal Research Fellow. 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Behav. PD MAY PY 2014 VL 65 IS 5 BP 488 EP 496 DI 10.1016/j.yhbeh.2014.03.002 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AI5DG UT WOS:000336885000007 PM 24631584 ER PT J AU Gabis, LV Pomeroy, J AF Gabis, Lidia V. Pomeroy, John TI An Etiologic Classification of Autism Spectrum Disorders SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE pervasive developmental disorders; autism spectrum disorders (ASD); regression; classification; children; epidemiology ID RISK-FACTORS; CHILDREN; POPULATION; SUBTYPES; COMPLEX AB Background: Autism spectrum disorders (AS) represent a common phenotype related to Multiple etiologies, such as genetic, brain injury (e.g., prematurity), environmental (e.g., viral, toxic), multiple or unknown causes. Objectives: To devise a clinical classification of children diagnosed with ASP according to etiologic workup. Methods: Children diagnosed with ASD (n=436) from two databases were divided into groups of symptomatic, cryptogenic or idiopathic, and variables within each database and diagnostic category were compared. Results: By analyzing the two separate databases, 5.4% of the children were classified as symptomatic, 27% as cryptogenic and 67.75% as idiopathic. Among other findings, the entire symptomatic group demonstrated language delays, but almost none showed evidence for regression. Our results indicate similarities between the idiopathic and cryptogenic subgroups in most of the examined variables, and mutual differences from the symptomatic subgroup. The similarities between the first two subgroups Support prior evidence that most perinatal factors and minor physical anomalies do not contribute to the development of core symptoms of autism. Conclusions: Differences in gender and clinical and diagnostic features were found when etiology was used to create Subtypes of ASD. This classification could have heuristic importance in the search for an autism gene(s). C1 [Gabis, Lidia V.] Chaim Sheba Med Ctr, Weinberg Dev Ctr, IL-52621 Tel Hashomer, Israel. [Gabis, Lidia V.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Gabis, Lidia V.] Ono Acad Coll, Kiryat Ono, Israel. [Pomeroy, John] Cody Ctr Autism, Stony Brook, NY USA. RP Gabis, LV (reprint author), Chaim Sheba Med Ctr, Weinberg Dev Ctr, IL-52621 Tel Hashomer, Israel. 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Med. Assoc. J. PD MAY PY 2014 VL 16 IS 5 BP 295 EP 298 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AI5CZ UT WOS:000336884300008 PM 24979834 ER PT J AU Berko, ER Suzuki, M Beren, F Lemetre, C Alaimo, CM Calder, RB Ballaban-Gil, K Gounder, B Kampf, K Kirschen, J Maqbool, SB Momin, Z Reynolds, DM Russo, N Shulman, L Stasiek, E Tozour, J Valicenti-McDermott, M Wang, SL Abrahams, BS Hargitai, J Inbar, D Zhang, ZD Buxbaum, JD Molholm, S Foxe, JJ Marion, RW Auton, A Greally, JM AF Berko, Esther R. Suzuki, Masako Beren, Faygel Lemetre, Christophe Alaimo, Christine M. Calder, R. Brent Ballaban-Gil, Karen Gounder, Batya Kampf, Kaylee Kirschen, Jill Maqbool, Shahina B. Momin, Zeineen Reynolds, David M. Russo, Natalie Shulman, Lisa Stasiek, Edyta Tozour, Jessica Valicenti-McDermott, Maria Wang, Shenglong Abrahams, Brett S. Hargitai, Joseph Inbar, Dov Zhang, Zhengdong Buxbaum, Joseph D. Molholm, Sophie Foxe, John J. Marion, Robert W. Auton, Adam Greally, John M. TI Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder SO PLOS GENETICS LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIATION; DNA METHYLATION; GENE PRIORITIZATION; MATERNAL AGE; R PACKAGE; NETWORK; PATTERNS; BRAIN; PHENOTYPE AB DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of >= 35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder. C1 [Berko, Esther R.; Suzuki, Masako; Lemetre, Christophe; Calder, R. Brent; Kirschen, Jill; Maqbool, Shahina B.; Momin, Zeineen; Reynolds, David M.; Stasiek, Edyta; Tozour, Jessica; Abrahams, Brett S.; Hargitai, Joseph; Zhang, Zhengdong; Auton, Adam; Greally, John M.] Albert Einstein Coll Med, Ctr Epigenom, Bronx, NY 10467 USA. [Berko, Esther R.; Suzuki, Masako; Lemetre, Christophe; Calder, R. Brent; Kirschen, Jill; Maqbool, Shahina B.; Momin, Zeineen; Reynolds, David M.; Stasiek, Edyta; Tozour, Jessica; Abrahams, Brett S.; Hargitai, Joseph; Zhang, Zhengdong; Auton, Adam; Greally, John M.] Albert Einstein Coll Med, Dept Genet, Div Computat Genet, Bronx, NY 10467 USA. [Beren, Faygel; Gounder, Batya] Yeshiva Univ, Stern Coll Women, New York, NY 10033 USA. [Alaimo, Christine M.; Russo, Natalie; Molholm, Sophie; Foxe, John J.] Albert Einstein Coll Med, Childrens Evaluat & Rehabil Ctr, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, Bronx, NY 10467 USA. [Alaimo, Christine M.; Russo, Natalie; Molholm, Sophie; Foxe, John J.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Alaimo, Christine M.; Russo, Natalie; Abrahams, Brett S.; Molholm, Sophie; Foxe, John J.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. [Ballaban-Gil, Karen] Childrens Hosp Montefiore, Dept Neurol, Bronx, NY USA. [Russo, Natalie] Syracuse Univ, Dept Psychol, Coll Arts & Sci, Syracuse, NY USA. [Shulman, Lisa; Valicenti-McDermott, Maria; Marion, Robert W.] Albert Einstein Coll Med, Dept Pediat, Childrens Evaluat & Rehabil Ctr, Bronx, NY 10467 USA. [Wang, Shenglong] NYU, Informat Technol Serv, New York, NY USA. [Inbar, Dov] Schneider Childrens Med Ctr, Child Dev & Rehabil Inst, Petah Tiqwa, Israel. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, Dept Genet & Genom Sci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. RP Berko, ER (reprint author), Albert Einstein Coll Med, Ctr Epigenom, Bronx, NY 10467 USA. EM john.greally@einstein.yu.edu FU Jonas Ehrlich Charitable Foundation; Dennis Weatherstone Pre-Doctoral Fellowship from Autism Speaks; Einstein's Medical Student Training Program award [NIH NIGMS T32 GM007288]; Einstein's Center for Epigenomics; Eunice Kennedy Shriver National Institute of Child Health & Human Development [NICHD P30 HD071593]; Sheryl and Daniel R. Tishman Charitable Foundation; Seaver Foundation FX Support for this project was provided by the Jonas Ehrlich Charitable Foundation, and a Dennis Weatherstone Pre-Doctoral Fellowship from Autism Speaks to ERB. Support was also provided by Einstein's Medical Student Training Program award (NIH NIGMS T32 GM007288), and Einstein's Center for Epigenomics. The Human Clinical Phenotyping Core is a facility of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) which is funded through a center grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD P30 HD071593). Ongoing support of The Cognitive Neurophysiology Laboratory is provided through a grant from the Sheryl and Daniel R. Tishman Charitable Foundation. JDB receives support from the Seaver Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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PD MAY PY 2014 VL 10 IS 5 AR e1004402 DI 10.1371/journal.pgen.1004402 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AI8FP UT WOS:000337145100073 PM 24875834 ER PT J AU Portmann, T Yang, M Mao, R Panagiotakos, G Ellegood, J Dolen, G Bader, PL Grueter, BA Goold, C Fisher, E Clifford, K Rengarajan, P Kalikhman, D Loureiro, D Saw, NL Zhou, ZQ Miller, MA Lerch, JP Henkelman, RM Shamloo, M Malenka, RC Crawley, JN Dolmetsch, RE AF Portmann, Thomas Yang, Mu Mao, Rong Panagiotakos, Georgia Ellegood, Jacob Dolen, Gul Bader, Patrick L. Grueter, Brad A. Goold, Carleton Fisher, Elaine Clifford, Katherine Rengarajan, Pavitra Kalikhman, David Loureiro, Darren Saw, Nay L. Zhou Zhengqui Miller, Michael A. Lerch, Jason P. Henkelman, R. Mark Shamloo, Mehrdad Malenka, Robert C. Crawley, Jacqueline N. Dolmetsch, Ricardo E. TI Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome SO CELL REPORTS LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; AUTISM SPECTRUM DISORDERS; SUBTYPE-SPECIFIC GENES; PROJECTION NEURONS; MOLECULAR SPECIFICATION; NUCLEUS-ACCUMBENS; PYRAMIDAL NEURONS; TIMOTHY SYNDROME; CORPUS-CALLOSUM; PHENOTYPES AB A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. C1 [Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Dolmetsch, Ricardo E.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. [Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Shamloo, Mehrdad; Malenka, Robert C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Yang, Mu; Kalikhman, David; Loureiro, Darren; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. Stanford Univ, Neurosci Program, Stanford, CA 94305 USA. [Ellegood, Jacob; Lerch, Jason P.; Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr MICe, Toronto, ON M5T 3H7, Canada. [Dolen, Gul] Johns Hopkins Univ, Brain Sci Inst, Dept Neurosci, Baltimore, MD 21205 USA. [Bader, Patrick L.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Grueter, Brad A.; Malenka, Robert C.] Stanford Univ, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA. [Saw, Nay L.; Zhou Zhengqui; Miller, Michael A.; Shamloo, Mehrdad] Stanford Behav & Funct Neurosci Lab, Stanford, CA 94305 USA. [Lerch, Jason P.; Henkelman, R. Mark] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Shamloo, Mehrdad] Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA. [Dolmetsch, Ricardo E.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Dolmetsch, RE (reprint author), Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. EM ricardo.dolmetsch@novartis.com RI Henkelman, Mark/F-3662-2011 FU Simons foundation SFARI grant [204340]; Nina Jauw; Swiss National Science Foundation [PBSKP3-123434, PA00P3_134196]; NIMH Intramural Research Program; University of California Davis MIND Institute; NIMH [MH09064802]; NIH/NIMH [MH091160]; Institute of Neurological Disorders and Stroke P30 center core grant [NS06937501A1] FX We would like to thank Ulrich Elling and Josef Penninger (IMBA Vienna, Austria) for help and advice on mouse ESC targeting, Marty Bigos of the Stanford shared FACS facility for assistance with clone sorting, Renee Reijo-Pera for generously providing the Biomark Instruments, Kristin L. Sainani for advice in statistical analysis of mouse behavioral data, and Yishan Sun for validating and providing primer pairs for the single-cell gene expression analysis. This research was funded by the Simons foundation SFARI grant no. 204340 (R.E.D. and J.N.C.), Nina Jauw (R.E.D.), the Swiss National Science Foundation (nos. PBSKP3-123434 and PA00P3_134196, T. P.), the NIMH Intramural Research Program and the University of California Davis MIND Institute (M.Y., D.K., D.L., and J.N.C.), an F31 NRSA from the NIMH (no. MH09064802, G.P.), a K99 from the NIH/NIMH (no. MH091160, R.M.), and the Institute of Neurological Disorders and Stroke P30 center core grant no. NS06937501A1 (M.S.). 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Alzheimer's disease; Behavioural variant frontotemporal dementia; Paired associates learning; Social cognition; Theory of Mind ID MILD COGNITIVE IMPAIRMENT; LOBAR DEGENERATION; EPISODIC MEMORY; DIFFERENTIAL-DIAGNOSIS; NETWORK CONNECTIVITY; ASPERGER-SYNDROME; REVISED VERSION; MIND DEFICITS; ATROPHY; DYSFUNCTION AB Introduction: Most of our learning activity takes place in a social context. I examined how social interactions influence associative learning in neurodegenerative diseases and atypical neurodevelopmental conditions primarily characterised by social cognitive and memory dysfunctions. Methods: Participants were individuals with high-functioning autism (HFA, n = 18), earlystage behavioural variant frontotemporal dementia (bvFTD, n = 16) and Alzheimer's disease (AD, n = 20). The leading symptoms in HFA and bvFTD were social and behavioural dysfunctions, whereas AD was characterised by memory deficits. Participants received three versions of a paired associates learning task. In the game with boxes test, objects were hidden in six candy boxes placed in different locations on the computer screen. In the game with faces, each box was labelled by a photo of a person. In the real-life version of the game, participants played with real persons. Results: Individuals with HFA and bvFTD performed well in the computer games, but failed on the task including real persons. In contrast, in patients with early-stage AD, social interactions boosted paired associates learning up to the level of healthy control volunteers. Worse performance in the real life game was associated with less successful recognition of complex emotions and mental states in the Reading the Mind in the Eyes Test. Spatial span did not affect the results. Conclusions: When social cognition is impaired, but memory systems are less compromised (HFA and bvFTD), real-life interactions disrupt associative learning; when disease process impairs memory systems but social cognition is relatively intact (early-stage AD), social interactions have a beneficial effect on learning and memory. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Keri, Szabolcs] Univ Szeged, Dept Physiol, Fac Med, H-6720 Szeged, Hungary. [Keri, Szabolcs] Nyiro Gyula Hosp, Natl Inst Psychiat & Addict, Budapest, Hungary. [Keri, Szabolcs] Budapest Univ Technol & Econ, Dept Cognit Sci, Budapest, Hungary. RP Keri, S (reprint author), Univ Szeged, Dept Physiol, Dom Sq 10, H-6720 Szeged, Hungary. EM keri.szabolcs.gyula@med.u-szeged.hu FU European Union; European Social Fund; National Brain Research Program FX I am grateful to Ibolya Halasz, Katalin Kiss, Zoltan Fekete, Oguz Kelemen and Henrik Vougt for their assistance in the recruitment and assessment of the patients and neuro-imaging analysis. This research was realized in the frames of TAMOP 4.2.4. A/2-11-1-2012-0001 "National Excellence Program - elaborating and operating an inland student and researcher personal support system". The project was subsidized by the European Union and co-financed by the European Social Fund and the National Brain Research Program. 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Eda Haliloglu, Goknur Volkan-Salanci, Bilge Cetinkaya, Arda Kiper, Pelin O. Alanay, Yasemin Aktas, Dilek Anlar, Banu Topcu, Meral Boduroglu, Koray Alikasifoglu, Mehmet TI Etiological yield of SNP microarrays in idiopathic intellectual disability SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE SNP microarray; Intellectual disability; NRXN1; FOXP2; UBE2A; Uniparental disomy; Subtelomeric rearrangements ID GLOBAL DEVELOPMENTAL DELAY; MENTAL-RETARDATION SYNDROME; AUTISM SPECTRUM DISORDER; CLINICAL DIAGNOSTIC-TEST; CHROMOSOMAL MICROARRAY; DYSMORPHIC FEATURES; CA2+ CHANNELS; SPEECH DELAY; ARRAY CGH; DELETION AB Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix (R) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism. (C) 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Utine, G. Eda; Haliloglu, Goknur; Volkan-Salanci, Bilge; Kiper, Pelin O.; Alanay, Yasemin; Anlar, Banu; Topcu, Meral; Boduroglu, Koray] Hacettepe Univ, Dept Pediat, Ankara, Turkey. [Utine, G. Eda; Volkan-Salanci, Bilge; Cetinkaya, Arda; Kiper, Pelin O.; Alanay, Yasemin; Aktas, Dilek; Boduroglu, Koray; Alikasifoglu, Mehmet] Hacettepe Univ, Dept Pediat Genet, Ankara, Turkey. [Haliloglu, Goknur; Anlar, Banu; Topcu, Meral] Hacettepe Univ, Dept Pediat Neurol, Ankara, Turkey. [Cetinkaya, Arda; Aktas, Dilek; Alikasifoglu, Mehmet] Hacettepe Univ, Dept Med Genet, Ankara, Turkey. RP Utine, GE (reprint author), Hacettepe Univ, Dept Pediat, Dept Pediat Genet, Ankara, Turkey. 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J. Paediatr. Neurol. PD MAY PY 2014 VL 18 IS 3 BP 327 EP 337 DI 10.1016/j.ejpn.2014.01.004 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AI2NQ UT WOS:000336695500012 PM 24508361 ER PT J AU Goddard, E Carral-Fernandez, L Denneny, E Campbell, IC Treasure, J AF Goddard, Elizabeth Carral-Fernandez, Laura Denneny, Emma Campbell, Iain C. Treasure, Janet TI Cognitive flexibility, central coherence and social emotional processing in males with an eating disorder SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE Anorexia nervosa; Eating disorders; Gender; Neuropsychology; Cognitive flexibility ID AUTISM SPECTRUM DISORDERS; ANOREXIA-NERVOSA PATIENTS; BULIMIA-NERVOSA; ASPERGER-SYNDROME; GENDER-DIFFERENCES; EMBEDDED FIGURES; WEAK COHERENCE; RECOGNITION; MIND; PERFECTIONISM AB Objectives. Females are more likely to develop an eating disorder (ED) than males. Studies of affected men may therefore inform models of risk and resilience to EDs. The aim of this study was to examine putative neurocognitive intermediate phenotypes of EDs in affected males. Methods. Cognitive flexibility, central coherence (global/detail processing), complex emotion recognition and social-threat sensitivity were investigated in men with EDs and healthy men. Measures of distress, perfectionism, and obsessive compulsivity were collected. Results. Men with EDs were more cognitively inflexible across tasks and had more difficulty integrating global information than healthy men. Unexpectedly, there were no group differences on a visuospatial task of detail processing or on social-emotional processing tasks. Men with EDs had higher scores on measures of distress, perfectionism and obsessive compulsivity than healthy men. Conclusions. Men with EDs share some of the intermediate cognitive phenotype present in women with EDs. Like their female counterparts, males with EDs show an inflexible, fragmented cognitive style. However, relative to healthy men, men with EDs do not have superior detail processing abilities, poor emotion recognition or increased sensitivity to social-threat. It is possible that gender differences in social-threat processing contribute to the female preponderance of EDs. C1 [Goddard, Elizabeth; Campbell, Iain C.; Treasure, Janet] Kings Coll London, Dept Psychol Med, Sect Eating Disorders, Inst Psychiat, London WC2R 2LS, England. [Carral-Fernandez, Laura] Univ Hosp Marques de Valdecilla, Eating Disorders Unit, Santander, Spain. [Denneny, Emma] Guys Kings & St Thomas Sch Med, London, England. RP Goddard, E (reprint author), Sect Eating Disorders, P059,103 Denmark Hill, London SE5 8AF, England. EM Elizabeth.Goddard@kcl.ac.uk FU National Institute for Health Research (NIHR) [RP-PG-0606-1043]; NIHR [PB-PG-0609-19025]; Marques de Valdecilla Public Foundation-Research Institute (FMV-IFIMAV, Santander, Spain); Institute of Health Carlos III (Spain) FX This article discusses independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0606-1043). EG was supported by research funded by NIHR under its Research for Patient Benefit programme (PB-PG-0609-19025). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Laura Carral-Fernandez was supported by a jointly funded research training fellowship from the Marques de Valdecilla Public Foundation-Research Institute (FMV-IFIMAV, Santander, Spain) and the Institute of Health Carlos III (Spain). 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TI Prenatal stress and limbic-prefrontal white matter microstructure in children aged 6-9 years: a preliminary diffusion tensor imaging study SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE DT-MRI; prenatal stress; neuroimaging; uncinate fasciculus; white matter ID MATERNAL ANTENATAL ANXIETY; BEHAVIOURAL/EMOTIONAL PROBLEMS; ADHD SYMPTOMS; HUMAN BRAIN; PREGNANCY; CHILDHOOD; EXPOSURE; AUTISM; TEMPERAMENT; FEARFULNESS AB Objectives. Maternal prenatal stress is associated with elevated risk of adverse behavioural outcomes in offspring. This association may involve developmental disruption to limbic-prefrontal white matter circuitry, of which the uncinate fasciculus is the major tract. One potential candidate for modulating brain development is maternal prenatal stress. We provide the first prospective study of prenatal stress and white matter microstructure in children. Methods. A total of 22 healthy children (mean age 7 years) of mothers recruited in pregnancy underwent diffusion tensor magnetic resonance imaging. We examined correlations between prenatal stressful life events and white matter microstructural organisation indices (fractional anisotropy (FA) and perpendicular diffusivity (D-perp)) of the uncinate fasciculus and a "control" tract. Results. Maternal prenatal stressful life events were correlated positively with right uncinate fasciculus FA, and negatively with right uncinate fasciculus D-perp in their child, with a similar trend with left uncinate fasciculus D-perp. Prenatal stress was not associated with control tract properties; sociodemographic/obstetric variables were not associated with FA/D-perp of either tract. Conclusions. Variation in maternal prenatal stress may be associated with differences in the development of white matter within brain networks underlying child social behaviour. C1 [Sarkar, Sagari; Craig, Michael C.; Dell'Acqua, Flavio; Catani, Marco; Deeley, Quinton; Murphy, Declan G. M.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London WC2R 2LS, England. [Craig, Michael C.; Dell'Acqua, Flavio; Catani, Marco] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, Natbrainlab, London WC2R 2LS, England. [Craig, Michael C.; Dell'Acqua, Flavio; Catani, Marco; Deeley, Quinton; Murphy, Declan G. M.] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, South London & Maudsley NHS Fdn Trust, London WC2R 2LS, England. [Craig, Michael C.; Dell'Acqua, Flavio; Catani, Marco; Deeley, Quinton; Murphy, Declan G. M.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [O'Connor, Thomas G.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Glover, Vivette] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England. [Sarkar, Sagari] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Craig, Michael C.] South London & Maudsley NHS Fdn Trust, Bethlem Royal Hosp, Natl Autism Unit, London, England. RP Craig, MC (reprint author), Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London WC2R 2LS, England. EM michael.c.craig@kcl.ac.uk FU March of Dimes foundation; Baily Thomas Charitable Fund; Academy of Medical Sciences; NIHR Biomedical Research Centre for Mental Health at King's College London; Institute of Psychiatry; South London & Maudsley NHS Foundation Trust FX This work was funded by the March of Dimes foundation, Baily Thomas Charitable Fund, The Academy of Medical Sciences, the NIHR Biomedical Research Centre for Mental Health at King's College London, Institute of Psychiatry and South London & Maudsley NHS Foundation Trust, and a generous donation from a private individual. We would also like to thank all the children and their parents for taking part. We would like to acknowledge Fiona Rose-Clarke for her assistance with recruitment and data collection. 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Biol. Psychiatry PD MAY PY 2014 VL 15 IS 4 BP 346 EP 352 DI 10.3109/15622975.2014.903336 PG 7 WC Psychiatry SC Psychiatry GA AI1AH UT WOS:000336581500010 PM 24815522 ER PT J AU Mendez, MF Fong, SS Shapira, JS Jimenez, EE Kaiser, NC Kremen, SA Tsai, PH AF Mendez, Mario F. Fong, Sylvia S. Shapira, Jill S. Jimenez, Elvira E. Kaiser, Natalie C. Kremen, Sarah A. Tsai, Po-Heng TI Observation of Social Behavior in Frontotemporal Dementia SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE dementia; frontotemporal lobar degeneration; Alzheimer's disease; social behavior; autism ID LOBAR DEGENERATION; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; MIND DEFICITS; RATING-SCALE; VARIANT; COGNITION; CONSENSUS AB Background: The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. Methods: Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. Results: Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of you comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. Conclusions: The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias. C1 [Mendez, Mario F.; Fong, Sylvia S.; Shapira, Jill S.; Jimenez, Elvira E.; Kaiser, Natalie C.; Kremen, Sarah A.; Tsai, Po-Heng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Fong, Sylvia S.; Shapira, Jill S.; Jimenez, Elvira E.; Kaiser, Natalie C.; Tsai, Po-Heng] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIH [R01AG034499-03] FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by NIH grant #R01AG034499-03. 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PD MAY PY 2014 VL 85 IS 3 BP 941 EP 955 DI 10.1111/cdev.12187 PG 15 WC Psychology, Educational; Psychology, Developmental SC Psychology GA AH0CL UT WOS:000335786600008 PM 24266591 ER PT J AU Winstone, N Huntington, C Goldsack, L Kyrou, E Millward, L AF Winstone, Naomi Huntington, Corinne Goldsack, Lisa Kyrou, Elli Millward, Lynne TI Eliciting rich dialogue through the use of activity-oriented interviews Exploring self-identity in autistic young people SO CHILDHOOD-A GLOBAL JOURNAL OF CHILD RESEARCH LA English DT Article DE child-centred research methods; self-identity; interview; qualitative; Autism ID CHILDREN; MIND; IMPAIRMENTS; LANGUAGE; GENDER; ADULTS; LINKS; POWER; FUN AB The ability of children and young people to form and express their perspectives through qualitative research studies can be constrained by difficulties that they can face in typical interview situations. This article describes and evaluates an interview method using concrete and engaging activities designed to enable autistic young people to voice their abilities and perspectives. Participants' sense of self-identity was explored using traditional semi-structured interviews and novel activity-oriented interviews. The latter method provided a context within which autistic young people were better able to voice their perspectives. The efficacy of this method and considerations for its use are discussed. C1 [Winstone, Naomi; Goldsack, Lisa; Kyrou, Elli; Millward, Lynne] Univ Surrey, Guildford GU2 7XH, Surrey, England. [Huntington, Corinne] Kings Coll Hosp London, London SE5 8RX, England. RP Winstone, N (reprint author), Univ Surrey, Sch Psychol, Guildford GU2 7XH, Surrey, England. 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J. Child Res. PD MAY PY 2014 VL 21 IS 2 BP 190 EP 206 DI 10.1177/0907568213491771 PG 17 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA AH0RN UT WOS:000335828000004 ER PT J AU Juneja, M Mishra, D Russell, PSS Gulati, S Deshmukh, V Tudu, P Sagar, R Silberberg, D Bhutani, VK Pinto, JM Durkin, M Pandey, RM Nair, MKC Arora, NK AF Juneja, Monica Mishra, Devendra Russell, Paul S. S. Gulati, Sheffali Deshmukh, Vaishali Tudu, Poma Sagar, Rajesh Silberberg, Donald Bhutani, Vinod K. Pinto, Jennifer M. Durkin, Maureen Pandey, Ravindra M. Nair, M. K. C. Arora, Narendra K. CA INCLEN Study Grp TI INCLEN diagnostic tool for autism spectrum disorder (INDT-ASD): Development and validation SO INDIAN PEDIATRICS LA English DT Article DE Childhood; Neuro developmental disorders; Resource limited settings; Childhood austism rating scale; Pervasive developmental disorders ID SYMPTOM MODEL; FIELD TRIAL; DSM-IV; CRITERIA; CLASSIFICATION; COMPONENTS; INTERVIEW; VALIDITY; CHILDREN; SCALE AB To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD). Diagnostic test evaluation by cross sectional design Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India. Children aged 2-9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard). Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. 154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P < 0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for' ASD group' was 82.52% [Cohen's kappa=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = -0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance. INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder. C1 [Juneja, Monica; Mishra, Devendra; Russell, Paul S. S.; Gulati, Sheffali; Deshmukh, Vaishali; Tudu, Poma; Sagar, Rajesh; Silberberg, Donald; Bhutani, Vinod K.; Pinto, Jennifer M.; Durkin, Maureen; Pandey, Ravindra M.; Nair, M. K. C.; Arora, Narendra K.; INCLEN Study Grp] INCLEN TRUST Int, New Delhi, India. RP Arora, NK (reprint author), INCLEN TRUST Int, F1-5 Okhla Ind Area,Phase 1, New Delhi, India. EM nkarora@inclentrust.org RI Durkin, Maureen/B-7834-2015; Karande, Sunil/F-1835-2013 OI Karande, Sunil/0000-0002-1170-325X FU Ministry of Social Justice and Empowerment (National Trust); National Institute of Health (NIH-USA); Fogarty International Center (FIH); Autism Speaks (USA) FX Ministry of Social Justice and Empowerment (National Trust), National Institute of Health (NIH-USA), Fogarty International Center (FIH), and Autism Speaks (USA). 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This study examines infant-directed speech of mothers of infants later diagnosed with autism (LDA; n = 12) or of typically developing infants (TD; n = 11) as well as infants' productions (13 LDA, 13 TD). Since LDA infants appear to behave differently in the first months of life, it can affect the functioning of dyadic interactions, especially the first vocal productions, sensitive to expressiveness and emotions sharing. We assumed that in the first 6 months of life, prosodic characteristics (mean duration, mean pitch, and intonative contour types) will be different in dyads with autism. We extracted infants' and mothers' vocal productions from family home movies and analyzed the mean duration and pitch as well as the pitch contours in interactive episodes. Results show that mothers of LDA infants use relatively shorter productions as compared to mothers talking to TD infants. LDA infants' productions are not different in duration or pitch, but they use less complex modulated productions (i.e., those with more than two melodic modulations) than do TD. Further studies should focus on developmental profiles in the first year, analyzing prosody monthly. RESUMEN La investigacion sobre las tempranas senales de autismo en interacciones sociales a menudo se enfoca en la conducta motora de los infantes; pocos estudios se han enfocado en las caracteristicas del habla. Este estudio examina el habla dirigida a los infantes de madres cuyos infantes son diagnosticados con autismo posteriormente (LDA, n = 12) o de infantes que se desarrollan tipicamente (TD, n = 11), asi como las producciones de los infantes (13 LDA y 13 TD). El hecho de que los infantes LDA parecen comportarse diferentemente en su primer mes de vida puede afectar el funcionamiento de las interacciones diadicas, especialmente las primeras producciones vocales, sensibles a la expresividad y a compartir emociones. Asumimos que en los primeros seis meses de vida, las caracteristicas prosodicas (promedio de duracion, promedio de entonacion y tipos de curvas de entonacion) seran diferentes en diadas con autismo. Obtuvimos producciones vocales de los infantes y madres en videos caseros y analizamos el promedio de duracion y entonacion, asi como las curvas de entonacion en episodios interactivos. Los resultados muestran que las madres de infantes LDA usan producciones relativamente mas cortas comparadas con las madres que le hablan a infantes del grupo TD. Las producciones de los infantes LDA no son diferentes en duracion o entonacion, pero ellos usan producciones moduladas (las que tienen mas de dos modulaciones melodicas) menos complejas que las de los infantes con desarrollo tipico. Estudios posteriores deben enfocarse en perfiles de desarrollo en el primer ano, analizando cada mes la prosodia. RESUME La recherche sur les signes precoces d'autisme dans les interactions sociales met souvent l'accent sur les comportements moteurs des nourrissons. Peu d'etudes mettent l'accent sur les caracteristiques vocales. Cette etude examine les paroles dirigees vers le nourrisson des meres de bebes plus tard diagnostiques avec un autisme (abreges selon l'anglais LDA, n = 12) ou d'un bebe se developpant de maniere typique (abreges selon l'anglais TD, n = 11), ainsi que les productions des nourrissons (13 LDA et 13 TD). Puisque les bebes LDA semblent se comporter differemment dans les premiers mois de leur vie, cela peut affecter le fonctionnement d'interactions dyadiques, surtout les premieres productions vocales, la partage d'emotions et la sensibilite a l'expression. Nous supposons que dans les six premiers mois de la vie les caracteristiques prosodiques (duree moyenne, hauteur moyenne de la voix, types de contour de l'intonation) sont differentes chez les dyades avec un autisme. Nous avons extrait les productions vocales de bebes et de meres dans des videos familiales et analyse la duree moyenne et la voix moyenne, ainsi que les contours de voix dans des episodes d'interaction. Les resultats montrent que les meres de bebes LDA utilisent des productions relativement plus courtes que ne le font les meres parlant a des bebes TD. Les productions de bebes LDA n'etaient differentes ni en duree ni en voix mais utilisaient des productions modulees moins complexes (pour ce qui concerne ceux qui faisaient etat de plus de deux modulations melodiques) que les bebes se developpant de maniere typique. Plus d'etudes devraient se pencher sur les profils de developpement dans la premiere annee, en analysant la prosodie mensuellement. ZUSAMMENFASSUNG Forschung uber fruhe Anzeichen von Autismus in sozialen Interaktionen fokussiert oft auf motorische Verhaltensweisen von Sauglingen, nur wenige Studien legten den Fokus auf Sprachmerkmale. Diese Studie untersucht die an den Saugling gerichtete Sprache der Mutter von Sauglingen mit spater diagnostiziertem Autismus (LDA (later diagnosed with autism), n = 12) oder von normal entwickelten Sauglingen (TD (typically developing), n = 11) sowie die stimmlichen Produktionen der Sauglinge (13 LDA und 13 TD). LDA-Sauglinge scheinen sich im ersten Lebensmonat anders zu verhalten. Dieses Verhalten kann dyadische Interaktionen beeinflussen, vor allem die ersten stimmlichen Produktionen, die mit Ausdrucksfahigkeit und geteilten Emotionen zusammenhangen. Wir gehen davon aus, dass in den ersten sechs Lebensmonaten prosodische Merkmale (mittlere Dauer, mittlere Tonhohe und Tonhohenkonturen) in Dyaden mit Autismus anders sein werden. Wir extrahierten stimmliche Produktionen von Sauglingen und Muttern aus Familienvideos und analysierten die mittlere Dauer, Tonhohe und die Tonhohenkonturen anhand interaktiver Episoden. Die Ergebnisse zeigen, dass Mutter von LDA-Sauglingen vergleichsweise kurzere Produktionen verwenden als Mutter die zu ihren TD-Sauglingen sprechen. Produktionen von LDA-Sauglingen unterscheiden sich nicht in Dauer oder Tonhohe, aber sie verwenden weniger komplex modulierte Produktionen (mit mehr als zwei melodischen Modulationen) als normal entwickelte Sauglingen. Weitere Studien sollten auf die Entwicklungsprofile im ersten Jahr fokussieren und dabei die Prosodie monatlich analysieren. ABSTRACT Research on early signs of autism in social interactions often focuses on infants' motor behaviors; few studies focused on speech characteristics. This study examines infant-directed speech of mothers of infants later diagnosed with autism (LDA, n = 12) or of typically developing infant (TD, n = 11), as well as infants' productions (13 LDA and 13 TD). ?????????????????????????????????????????????????????????????????????????????????????????????(LDA, n = 12)???????????????(TD, n = 11)??????????????????????????(13 LDA and 13 TD)??????LAD?????????1????????????????????????????????????????????????????????????????????6????????????prosodic characteristics(??????????????????????????????)?????????????????????????????????????????????????????????????????????????????????????????????????LDA???????TD?????????????????????????????????????????LDA????????????????????????????????????????????????????(?????????????????)?????????????????????prosody???????????1?????????????????????? C1 [Brisson, Julie; Serres, Josette; Adrien, Jean-Louis] Univ Paris Descartes Sorbonne Cite, Paris, France. 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Health J. PD MAY PY 2014 VL 35 IS 3 BP 285 EP 295 DI 10.1002/imhj.21442 PG 11 WC Psychology, Developmental SC Psychology GA AF4IB UT WOS:000334674100008 PM 25798482 ER PT J AU Goch, CJ Stieltjes, B Henze, R Hering, J Poustka, L Meinzer, HP Maier-Hein, KH AF Goch, Caspar J. Stieltjes, Bram Henze, Romy Hering, Jan Poustka, Luise Meinzer, Hans-Peter Maier-Hein, Klaus H. TI Quantification of changes in language-related brain areas in autism spectrum disorders using large-scale network analysis SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Connectomics; Network analysis; Diffusion imaging; Autism spectrum disorder; Open-source ID HIGH-FUNCTIONING AUTISM; HUMAN CEREBRAL-CORTEX; WHITE-MATTER; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; CHILDREN; LATERALIZATION; CLASSIFICATION; CONNECTOMICS; ORGANIZATION AB Diagnosis of autism spectrum disorders (ASD) is difficult, as symptoms vary greatly and are difficult to quantify objectively. Recent work has focused on the assessment of non-invasive diffusion tensor imaging-based biomarkers that reflect the microstructural characteristics of neuronal pathways in the brain. While tractography-based approaches typically analyze specific structures of interest, a graph-based large-scale network analysis of the connectome can yield comprehensive measures of larger-scale architectural patterns in the brain. Commonly applied global network indices, however, do not provide any specificity with respect to functional areas or anatomical structures. Aim of this work was to assess the concept of network centrality as a tool to perform locally specific analysis without disregarding the global network architecture and compare it to other popular network indices. We create connectome networks from fiber tractographies and parcellations of the human brain and compute global network indices as well as local indices for Wernicke's Area, Broca's Area and the Motor Cortex. Our approach was evaluated on 18 children suffering from ASD and 18 typically developed controls using magnetic resonance imaging-based cortical parcellations in combination with diffusion tensor imaging tractography. We show that the network centrality of Wernicke's area is significantly (p 0.001) reduced in ASD, while the motor cortex, which was used as a control region, did not show significant alterations. This could reflect the reduced capacity for comprehension of language in ASD. The betweenness centrality could potentially be an important metric in the development of future diagnostic tools in the clinical context of ASD diagnosis. Our results further demonstrate the applicability of large-scale network analysis tools in the domain of region-specific analysis with a potential application in many different psychological disorders. C1 [Goch, Caspar J.; Stieltjes, Bram; Hering, Jan; Meinzer, Hans-Peter; Maier-Hein, Klaus H.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Henze, Romy] Univ Heidelberg Hosp, D-69115 Heidelberg, Germany. [Poustka, Luise] Heidelberg Univ, Cent Inst Mental Hlth, Clin Fac Mannheim, Dept Child & Adolescent Psychiat & Psychotherapy, D-68159 Mannheim, Germany. RP Goch, CJ (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM c.goch@dkfz.de; k.maier-hein@dkfz.de FU Helmholtz International Graduate School for Cancer Research; German Research Foundation (DFG) [ME 833/15-1] FX This study was in part financed by the Helmholtz International Graduate School for Cancer Research. Dr. Maier-Hein (ne Fritzsche) received support from the German Research Foundation (DFG), Grant ME 833/15-1. 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PD MAY PY 2014 VL 9 IS 3 SI SI BP 357 EP 365 DI 10.1007/s11548-014-0977-0 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA AH8KP UT WOS:000336387000003 PM 24459035 ER PT J AU Nishiyama, T Suzuki, M Adachi, K Sumi, S Okada, K Kishino, H Sakai, S Kamio, Y Kojima, M Suzuki, S Kanne, SM AF Nishiyama, Takeshi Suzuki, Masako Adachi, Katsunori Sumi, Satoshi Okada, Kensuke Kishino, Hirohisa Sakai, Saeko Kamio, Yoko Kojima, Masayo Suzuki, Sadao Kanne, Stephen M. TI Comprehensive Comparison of Self-administered Questionnaires for Measuring Quantitative Autistic Traits in Adults SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Quantitative autistic traits (QAT); Broader autism phenotype (BAP); Autism spectrum disorder (ASD); Reliability; Validity ID SPECTRUM QUOTIENT AQ; PERVASIVE DEVELOPMENTAL DISORDERS; EPWORTH SLEEPINESS SCALE; BRIEF SYMPTOM INVENTORY; JAPANESE VERSION; FAMILY-HISTORY; HEALTH SURVEY; SOCIAL IMPAIRMENT; PATIENT GROUPS; DATA QUALITY AB We comprehensively compared all available questionnaires for measuring quantitative autistic traits (QATs) in terms of reliability and construct validity in 3,147 non-clinical and 60 clinical subjects with normal intelligence. We examined four full-length forms, the Subthreshold Autism Trait Questionnaire (SATQ), the Broader Autism Phenotype Questionnaire, the Social Responsiveness Scale2-Adult Self report (SRS2-AS), and the Autism-Spectrum Quotient (AQ). 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[Sakai, Saeko] Osaka Univ, United Grad Sch Child Dev, Dept Child Dev, Osaka, Japan. [Kamio, Yoko] Natl Ctr Neurol & Psychiat, Dept Child & Adolescent Mental Hlth, Tokyo, Japan. [Kojima, Masayo; Suzuki, Sadao] Nagoya City Univ, Dept Publ Hlth, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Kanne, Stephen M.] Univ Missouri, Dept Hlth Psychol, Thompson Ctr Autism & Neurodev Disorder, Columbia, MO USA. RP Nishiyama, T (reprint author), Aichi Med Univ, Dept Publ Hlth, 1-1 Yazako, Nagakute, Aichi 4801195, Japan. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 993 EP 1007 DI 10.1007/s10803-013-2020-7 PG 15 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200001 PM 24342972 ER PT J AU Gardiner, E Iarocci, G AF Gardiner, Emily Iarocci, Grace TI Students with Autism Spectrum Disorder in the University Context: Peer Acceptance Predicts Intention to Volunteer SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Acceptance; Post-secondary education; Behavioral intent; Peers ID POSTSECONDARY EDUCATION; INTELLECTUAL DISABILITIES; CHILDRENS ATTITUDES; COMMUNITY-SERVICE; COLLEGE-STUDENTS; PERCEPTIONS; SCHIZOPHRENIA; ADULTS; TRANSITION; YOUTH AB With growing numbers of individuals with autism spectrum disorder (ASD) entering post-secondary institutions, strategies are needed to facilitate the social integration of these students. The goal of this study was to examine the role of various factors in university students' acceptance of, and intention to volunteer with, a peer with ASD. Both contact quantity and quality emerged as significant predictors of acceptance; however, for those who had experienced direct contact with individuals with ASD, only perceived quality emerged as significant. Moreover, acceptance played a significant role in participants' likelihood of signing up to volunteer. These findings point to the central role that positive experiences play in attitude formation for this population. C1 [Gardiner, Emily; Iarocci, Grace] Simon Fraser Univ, Dept Psychol, Burnaby, BC V5A 1S6, Canada. RP Gardiner, E (reprint author), Simon Fraser Univ, Dept Psychol, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. 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Rutherford, M. D. TI Strategies for Perceiving Facial Expressions in Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Face perception; Emotion perception; Perceptual strategies ID CHILDREN; PERCEPTION; EMOTIONS; DEFICITS; FACES AB Rutherford and McIntosh (J Autism Dev Disord 37: 187-196, 2007) demonstrated that individuals with autism spectrum disorder (ASD) are more tolerant than controls of exaggerated schematic facial expressions, suggesting that they may use an alternative strategy when processing emotional expressions. The current study was designed to test this finding using photographs of real people. In addition, two control tasks were added to eliminate alternative explanations. We replicated the findings of Rutherford and McIntosh (J Autism Dev Disord 37: 187-196, 2007) and also demonstrated that adults with ASD do not show this tolerance when evaluating how realistic the expressions are. These results suggest adults with ASD employ a rule-based strategy to a greater extent than typical adults when processing facial expressions but not when processing other aspects of faces. C1 [Walsh, Jennifer A.; Vida, Mark D.; Rutherford, M. D.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada. RP Rutherford, MD (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM rutherm@mcmaster.ca CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Behrmann M, 2006, NEUROPSYCHOLOGIA, V44, P110, DOI 10.1016/j.neuropsychologia.2005.04.002 Blalock H. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1018 EP 1026 DI 10.1007/s10803-013-1953-1 PG 9 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200003 PM 24077783 ER PT J AU Duff, CK Flattery, JJ AF Duff, Christine K. Flattery, J. J., Jr. TI Developing Mirror Self Awareness in Students with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Joint attention; Mirror self-awareness; Pronoun development; Self permanence; Video modeling ID JOINT ATTENTION; CHILDREN; RECOGNITION; AMYGDALA; 6-MONTH-OLDS; EMERGENCE; LANGUAGE; GAZE AB A teaching methodology and curriculum was designed to develop and increase positive self-awareness in students diagnosed with autism spectrum disorders (ASD). Joint attention (JA) strategies were first utilized to directly teach students about reflected mirror images, and then subsequently, to indirectly teach students about their reflected image. Not only were Mirror Self Awareness Development (MSAD) JA activities initiated and preferred by students over non MSAD JA activities, they yielded a four step framework with which to measure increases in student self-awareness. While the focus of this study was to increase positive self-awareness in students with ASD, it may contribute to understanding the developmental stages of 'Self'. RP Duff, CK (reprint author), 291 Torpoint Gate, Longwood, FL 32779 USA. 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PD MAY PY 2014 VL 44 IS 5 BP 1027 EP 1038 DI 10.1007/s10803-013-1954-0 PG 12 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200004 PM 24077784 ER PT J AU Pallett, PM Cohen, SJ Dobkins, KR AF Pallett, Pamela M. Cohen, Shereen J. Dobkins, Karen R. TI Face and Object Discrimination in Autism, and Relationship to IQ and Age SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorders; Face processing; Object processing; Inversion effects; Adolescents; Development ID EMBEDDED FIGURES TASK; ASPERGER-SYNDROME; SPECTRUM DISORDERS; CONFIGURAL INFORMATION; IDENTITY RECOGNITION; EXTRASTRIATE CORTEX; SPATIAL-FREQUENCY; WILLIAMS-SYNDROME; INVERSION LEADS; FUNCTIONAL MRI AB The current study tested fine discrimination of upright and inverted faces and objects in adolescents with Autism Spectrum Disorder (ASD) as compared to age- and IQ-matched controls. Discrimination sensitivity was tested using morphed faces and morphed objects, and all stimuli were equated in low-level visual characteristics (luminance, contrast, spatial frequency make-up). Participants with ASD exhibited slight, non-significant impairments in discrimination sensitivity for faces, yet significantly enhanced discrimination sensitivity for objects. The ASD group also showed a protracted development of face and object inversion effects. Finally, for ASD participants, face sensitivity improved with increasing IQ while object sensitivity improved with age. By contrast, for controls, face sensitivity improved with age, but neither face nor object sensitivity was influenced by IQ. These findings suggest that individuals with ASD follow a qualitatively different path in the development of face and object processing abilities. C1 [Pallett, Pamela M.; Cohen, Shereen J.; Dobkins, Karen R.] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Dobkins, KR (reprint author), Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. 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TI Using Self-Management to Improve the Reciprocal Social Conversation of Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Communication; Conversation; Self-management; Intervention ID TEACHING-CHILDREN; QUESTION-ASKING; SCHOOL-STUDENTS; SKILLS; INTERVENTIONS; SOCIALIZATION; COMMUNICATION; DISABILITIES; INDIVIDUALS; SETTINGS AB Individuals with autism spectrum disorders often exhibit difficulties with reciprocal social conversation, engaging in limited verbal exchanges, even when language structures are intact. This study employed a multiple baseline design to examine the effectiveness of a self-management intervention targeting (1) on-topic responsiveness to a conversational partner; (2) expansion of the conversational topic; and (3) on-topic question asking. Results demonstrated improved reciprocal social conversation through elaborated responses and on-topic question asking, which generalized and maintained. Social validity measures by naive observers indicated that the intervention led to meaningful improvements during conversation, including interest, naturalness, and desirability as a conversational partner. C1 [Koegel, Lynn Kern] Univ Calif Santa Barbara, Koegel Autism Ctr, Santa Barbara, CA 93106 USA. [Park, Mi N.] Univ Calif Santa Barbara, Gevirtz Grad Sch Educ, Counseling Clin & Sch Psychol Dept, Santa Barbara, CA 93106 USA. [Koegel, Robert L.] Univ Calif Santa Barbara, Gevirtz Grad Sch Educ, Koegel Autism Ctr, Counseling Clin & Sch Psychol Dept, Santa Barbara, CA 93106 USA. RP Koegel, RL (reprint author), Univ Calif Santa Barbara, Gevirtz Grad Sch Educ, Koegel Autism Ctr, Counseling Clin & Sch Psychol Dept, Santa Barbara, CA 93106 USA. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1055 EP 1063 DI 10.1007/s10803-013-1956-y PG 9 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200006 PM 24127164 ER PT J AU van Steijn, DJ Oerlemans, AM van Aken, MAG Buitelaar, JK Rommelse, NNJ AF van Steijn, Daphne J. Oerlemans, Anoek M. van Aken, Marcel A. G. Buitelaar, Jan K. Rommelse, Nanda N. J. TI The Reciprocal Relationship of ASD, ADHD, Depressive Symptoms and Stress in Parents of Children with ASD and/or ADHD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Attention-deficit/hyperactivity disorder; Parenting stress; Depressive symptoms; Parental symptoms; Child pathology ID AUTISM SPECTRUM DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIOR PROBLEMS; INTELLECTUAL DISABILITY; SYNDROME SPECIFICITY; PRESCHOOL-CHILDREN; FAMILY RESILIENCE; MENTAL-HEALTH; QUOTIENT AQ AB This study investigated the role of parental Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and depressive symptoms on parenting stress in 174 families with children with ASD and/or ADHD, using generalized linear models and structural equation models. 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A One Year Follow-up of Autistic, Attention and Anxiety Symptoms in High-Functioning Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Gender; Autism spectrum disorder; Attention; Anxiety; Girls ID PERVASIVE DEVELOPMENTAL DISORDERS; SEX-DIFFERENCES; PSYCHOPATHOLOGY; INDIVIDUALS; ADOLESCENCE; COMORBIDITY; CHILDHOOD; PEOPLE; SAMPLE AB Gender differences in autism spectrum disorder (ASD) symptoms and associated problem behaviours over development may provide clues regarding why more males than females are diagnosed with ASD. Fifty-six high-functioning children with ASD, and 44 typically developing controls, half of the participants female, were assessed at baseline (aged 7-12 years) and one-year later, collecting measures of autism, attention and anxiety symptoms, school placement and support information. Findings indicated no gender differences in autistic symptoms. Males were more hyperactive and received more integration-aide support in mainstream schools, and females were more socially anxious. Overall, similar gender profiles were present across two time points. Lower hyperactivity levels in females might contribute to their under-identification. Implications are discussed using a biopsychosocial model of gender difference. C1 [May, Tamara; Cornish, Kim; Rinehart, Nicole] Monash Univ, Sch Psychol & Psychiat, Melbourne, Vic 3800, Australia. RP May, T (reprint author), Monash Univ, Sch Psychol & Psychiat, Wellington Rd, Melbourne, Vic 3800, Australia. EM Tamara.May@monash.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baron-Cohen S, 2002, TRENDS COGN SCI, V6, P248, DOI 10.1016/S1364-6613(02)01904-6 Biederman J, 2000, AM J PSYCHIAT, V157, P816, DOI 10.1176/appi.ajp.157.5.816 Billstedt E, 2005, J AUTISM DEV DISORD, V35, P351, DOI 10.1007/s10803-005-3302-5 Bishop D. V. 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TI Hospitalizations of Children with Autism Increased from 1999 to 2009 SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Mental health; Hospitalization; Adolescence ID HEALTH-CARE EXPENDITURES; SPECTRUM DISORDERS; PSYCHIATRIC-HOSPITALIZATION; MEDICAID; COSTS AB We performed a retrospective analysis of hospital discharges for children with autism, in comparison to children with cerebral palsy, Down syndrome, mental retardation/intellectual disability, and the general population. Hospitalizations for autism increased nearly threefold over 10 years, especially at the oldest ages, while hospitalizations for the other groups did not change. Leading discharge diagnoses for each age group in children with autism included mental health and nervous system disorders. Older age, Caucasian ethnicity, and living in a region with a high number of pediatric beds predicted hospitalizations associated with mental health diagnoses. These findings underscore the need for comprehensive clinical services that address the complex needs of children with autism to prevent costly hospitalizations. C1 [Nayfack, Aaron M.; Huffman, Lynne C.; Feldman, Heidi M.; Chan, Jia; Saynina, Olga; Wise, Paul H.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Nayfack, Aaron M.] Santa Clara Valley Med Ctr, Dept Pediat, San Jose, CA 95128 USA. [Huffman, Lynne C.; Feldman, Heidi M.; Chan, Jia; Saynina, Olga; Wise, Paul H.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. RP Nayfack, AM (reprint author), 828 S Bascom Ave,Suite 100, San Jose, CA 95128 USA. EM aaron.nayfack@hhs.sccgov.org CR Amendah D., 2011, AUTISM SPECTRUM DISO, P1347 American Psychiatric Association, 2013, DIAGN STAT MAN MENT CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Centet on budget and policy priorities, 2007, COMP PUBLIC PRIVATE Chamber J., 2004, WHAT ARE WE SPENDING Chamberlain LJ, 2010, PEDIATRICS, V125, P1190, DOI 10.1542/peds.2009-1109 Cidav Z, 2013, J AUTISM DEV DISORD, V43, P924, DOI 10.1007/s10803-012-1637-2 Croen LA, 2006, PEDIATRICS, V118, pE1203, DOI 10.1542/peds.2006-0127 Department of Health Care Services, 2010, SPEC CAR CTR DIR Ganz ML, 2007, ARCH PEDIAT ADOL MED, V161, P343, DOI 10.1001/archpedi.161.4.343 Government Accountability Office, 2005, REP CHAIRM RANK MIN Health Care Financing Administration, 2002, DRGS DIAGN REL GROUP Knapp M, 2009, AUTISM, V13, P317, DOI 10.1177/1362361309104246 Liptak GS, 2006, J AUTISM DEV DISORD, V36, P871, DOI 10.1007/s10803-006-0119-9 Lokhandwala T, 2012, J AUTISM DEV DISORD, V42, P95, DOI 10.1007/s10803-011-1217-x Mandell DS, 2008, J AUTISM DEV DISORD, V38, P1059, DOI 10.1007/s10803-007-0481-2 Mandell DS, 2006, J AUTISM DEV DISORD, V36, P475, DOI 10.1007/s10803-006-0088-z Mandell DS, 2012, ARCH PEDIAT ADOL MED, V166, P68, DOI 10.1001/archpediatrics.2011.714 Peacock G, 2012, J DEV BEHAV PEDIATR, V33, P2, DOI 10.1097/DBP.0b013e31823969de Peng CZ, 2009, J CHILD NEUROL, V24, P140, DOI 10.1177/0883073808321059 Pineda N, 2011, ARTHRIT CARE RES, V63, P998, DOI 10.1002/acr.20458 Pineda N., J PEDIAT HE IN PRESS Shimabukuro TT, 2008, J AUTISM DEV DISORD, V38, P546, DOI 10.1007/s10803-007-0424-y Wang L, 2010, J AM ACAD CHILD PSY, V49, P1165, DOI 10.1016/j.jaac.2010.08.003 NR 24 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1087 EP 1094 DI 10.1007/s10803-013-1965-x PG 8 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200009 PM 24122446 ER PT J AU Dammeyer, J AF Dammeyer, Jesper TI Symptoms of Autism Among Children with Congenital Deafblindness SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Blind; Deaf; Deafblindness; Differential diagnostics; Dual sensory impairment ID PERVASIVE DEVELOPMENTAL DISORDERS; INTELLECTUAL DISABILITY; BEHAVIOR CHECKLIST; SPECTRUM DISORDERS; INFANTILE-AUTISM; BLIND-CHILDREN; DEAF-CHILDREN; PEOPLE; MIND; COOCCURRENCE AB Associations between congenital deafness or blindness and autism have been found. The main consequences of congenital sensory impairment, being barriers for communication, language and social interaction development, may lead to symptoms of autism. To date only few studies have been reported concerning individuals with congenital deafblindness. 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TI Validity of the Aberrant Behavior Checklist in Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Aberrant Behavior Checklist; Factor analysis; Irritability; Rating scales; Assessment ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; FRAGILE-X-SYNDROME; MENTAL-RETARDATION; ADOLESCENTS; ARIPIPRAZOLE; IRRITABILITY; RISPERIDONE; COMMUNITY; SAMPLE AB The Aberrant Behavior Checklist (ABC) is a widely used measure in autism spectrum disorder (ASD) treatment studies. We conducted confirmatory and exploratory factor analyses of the ABC in 1,893 children evaluated as part of the Autism Treatment Network. The root mean square error of approximation was .086 for the standard item assignment, and in exploratory factor analysis, the large majority of items continued to load on the originally assigned factors. 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Hertz-Picciotto, Irva TI Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Gastrointestinal problems; Autism; Developmental delays; Maladaptive behaviors ID SPECTRUM DISORDERS; SYMPTOMS; ASSOCIATION; PREVALENCE; DISEASE; ASDS AB To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children with high versus low frequency GI symptoms. Compared to TD children, those with ASD [aOR 7.92 (4.89-12.85)] and DD [aOR 4.55 (2.51-8.24)] were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on irritability, social withdrawal, stereotypy, and hyperactivity compared with children having no frequent GI symptoms. Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention. C1 [Chaidez, Virginia] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95618 USA. [Hansen, Robin L.] Univ Calif Davis, Sch Med, Dept Pediat, Davis, CA 95616 USA. [Hansen, Robin L.; Hertz-Picciotto, Irva] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Davis, CA 95616 USA. [Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Div Environm & Occupat Hlth, Davis, CA 95616 USA. RP Chaidez, V (reprint author), Univ Calif Davis, UC CalFresh Nutr Educ Program, State Off, 1103 Meyer Hall, Davis, CA 95616 USA. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1117 EP 1127 DI 10.1007/s10803-013-1973-x PG 11 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200012 PM 24193577 ER PT J AU Lecavalier, L Wood, JJ Halladay, AK Jones, NE Aman, MG Cook, EH Handen, BL King, BH Pearson, DA Hallett, V Sullivan, KA Grondhuis, S Bishop, SL Horrigan, JP Dawson, G Scahill, L AF Lecavalier, Luc Wood, Jeffrey J. Halladay, Alycia K. Jones, Nancy E. Aman, Michael G. Cook, Edwin H. Handen, Benjamin L. King, Bryan H. Pearson, Deborah A. Hallett, Victoria Sullivan, Katherine Anne Grondhuis, Sabrina Bishop, Somer L. Horrigan, Joseph P. Dawson, Geraldine Scahill, Lawrence TI Measuring Anxiety as a Treatment Endpoint in Youth with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Anxiety; Instrument; Measure; Assessment; Treatment; Intervention ID PERVASIVE DEVELOPMENTAL DISORDERS; COGNITIVE-BEHAVIORAL THERAPY; DRUG-ADMINISTRATION PERSPECTIVE; MULTIPLE INFORMANT AGREEMENT; REVISED CHILD ANXIETY; CONTROLLED-TRIAL; INTERVIEW SCHEDULE; RATING-SCALE; DSM-IV; PSYCHOMETRIC PROPERTIES AB Despite the high rate of anxiety in individuals with autism spectrum disorder (ASD), measuring anxiety in ASD is fraught with uncertainty. This is due, in part, to incomplete consensus on the manifestations of anxiety in this population. Autism Speaks assembled a panel of experts to conduct a systematic review of available measures for anxiety in youth with ASD. To complete the review, the panel held monthly conference calls and two face-to-face meetings over a fourteen-month period. Thirty eight published studies were reviewed and ten assessment measures were examined: four were deemed appropriate for use in clinical trials, although with conditions; three were judged to be potentially appropriate, while three were considered not useful for clinical trials assessing anxiety. Despite recent advances, additional relevant, reliable and valid outcome measures are needed to evaluate treatments for anxiety in ASD. C1 [Lecavalier, Luc; Aman, Michael G.; Grondhuis, Sabrina] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Lecavalier, Luc; Aman, Michael G.; Grondhuis, Sabrina] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Wood, Jeffrey J.] Univ Calif Los Angeles, Dept Educ, Los Angeles, CA USA. [Wood, Jeffrey J.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Halladay, Alycia K.; Jones, Nancy E.; Horrigan, Joseph P.; Dawson, Geraldine] Autism Speaks, New York, NY USA. [Jones, Nancy E.; Horrigan, Joseph P.] Neuren Pharmaceut Ltd, Durham, NC USA. [Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Handen, Benjamin L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [King, Bryan H.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [King, Bryan H.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA. [King, Bryan H.] Seattle Childrens Hosp, Seattle, WA USA. [Pearson, Deborah A.] Univ Texas Med Sch, Dept Psychiat, Houston, TX USA. [Pearson, Deborah A.] Univ Texas Med Sch, Dept Behav Sci, Houston, TX USA. [Hallett, Victoria] Kings Coll London, London WC2R 2LS, England. [Sullivan, Katherine Anne] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Bishop, Somer L.] Weill Cornell Med Coll, Dept Psychiat & Psychol, New York, NY USA. 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PD MAY PY 2014 VL 44 IS 5 BP 1128 EP 1143 DI 10.1007/s10803-013-1974-9 PG 16 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200013 PM 24158679 ER PT J AU Miller, L McGonigle-Chalmers, M AF Miller, Louisa McGonigle-Chalmers, Maggie TI Exploring Perceptual Skills in Children with Autism Spectrum Disorders: From Target Detection to Dynamic Perceptual Discrimination SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Attention switching; Perception; Target discrimination ID HIGH-FUNCTIONING AUTISM; VISUAL-SEARCH; ATTENTION; DEFICIT; ADULTS; IMPAIRMENT; TASK; DISSOCIATION; ADHD AB Perceptual processing in autism is associated with both 'strengths' and 'weaknesses' but within a literature that varies widely in terms of the assessments used. We report data from 12 children with autism spectrum disorders (ASD) and 12 age and IQ matched neurotypical controls tested on a set of tasks using the same stimuli throughout but systematically changing in difficulty. These tasks ranged through simple detection of stimulus onset to pairwise size discrimination across two approaching targets. Children with ASD were slower than controls even in simple detection tasks, but this did not explain further group differences found in the size discrimination of approaching targets. The results are discussed in terms of impairments in speed of responding in ASD under certain conditions of visuomotor coupling, stimulus presentation and increased information processing demands. C1 [Miller, Louisa; McGonigle-Chalmers, Maggie] Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, Edinburgh EH8 9JZ, Midlothian, Scotland. 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TI Postsecondary Pathways and Persistence for STEM Versus Non-STEM Majors: Among College Students with an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; 2-Year community colleges; 4-Year universities; College pathway; College persistence; Science, technology, engineering and mathematics (STEM) ID PREVALENCE; CHILDREN AB Little is known about postsecondary pathways and persistence among college students with an autism spectrum disorder (ASD). This study analyzed data from the National Longitudinal Transition Study-2, 2001-2009, a nationally representative sample of students in special education with an ASD who progressed from high school to postsecondary education. Findings suggest that most college students with an ASD enrolled in a 2-year community college at some point in the postsecondary careers (81 %). 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PD MAY PY 2014 VL 44 IS 5 BP 1159 EP 1167 DI 10.1007/s10803-013-1978-5 PG 9 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200015 PM 24158680 ER PT J AU Cholemkery, H Mojica, L Rohrmann, S Gensthaler, A Freitag, CM AF Cholemkery, Hannah Mojica, Laura Rohrmann, Sonja Gensthaler, Angelika Freitag, Christine M. TI Can Autism Spectrum Disorders and Social Anxiety Disorders be Differentiated by the Social Responsiveness Scale in Children and Adolescents? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Psychometric assessment; Differential diagnosis; Child psychiatric disorder; Autism spectrum disorder; Social anxiety disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; CROSS-CULTURAL VALIDATION; SELECTIVE MUTISM; ASPERGER-SYNDROME; TRAITS; SYMPTOMS; FAMILY; MOOD; SRS AB Autism spectrum disorder (ASD) as well as social phobia (SP), and selective mutism (SM) are characterised by impaired social interaction. We assessed the validity of the Social Responsiveness Scale (SRS) to differentiate between ASD, and SP/SM. Raw scores were compared in 6-18 year old individuals with ASD (N = 60), SP (N = 38), SM (N = 43), and typically developed (N = 42). Sensitivity and specificity were examined. The three disorders showed overlapping SRS scores. Especially in boys with SM (ROC-AUC = .81), presence of ASD was overestimated by the SRS. A combination of three disorder specific questionnaires resulted in marginally improved diagnostic accuracy. For the clinically very relevant differential diagnosis of SP/SM, SRS results must be interpreted with caution. C1 [Cholemkery, Hannah; Mojica, Laura; Gensthaler, Angelika; Freitag, Christine M.] JW Goethe Univ Hosp, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Rohrmann, Sonja] Goethe Univ Frankfurt, Dept Psychol, D-60054 Frankfurt, Germany. RP Cholemkery, H (reprint author), JW Goethe Univ Hosp, Dept Child & Adolescent Psychiat Psychosomat & Ps, Deutschordenstr 50, D-60528 Frankfurt, Germany. EM Hannah.Cholemkery@kgu.de; L.Mojica@stud.uni-heidelberg.de; Rohrmann@psych.uni-frankfurt.de; Angelika.Gensthaler@kgu.de; C.Freitag@em.uni-frankfurt.de CR Achenbach T. 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PD MAY PY 2014 VL 44 IS 5 BP 1168 EP 1182 DI 10.1007/s10803-013-1979-4 PG 15 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200016 PM 24682652 ER PT J AU Brezis, RS Galili, T Wong, T Piggot, JI AF Brezis, Rachel S. Galili, Tal Wong, Tiffany Piggot, Judith I. TI Impaired Social Processing in Autism and its Reflections in Memory: A Deeper View of Encoding and Retrieval Processes SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social memory; Autism; Encoding; Retrieval; Levels of processing ID ASPERGERS-SYNDROME; INDIVIDUALS; SELF; DISORDERS; COGNITION; CHILDREN; ABILITY; RATINGS; ADULTS; WORDS AB Previous studies of memory in autism spectrum conditions (ASC) have consistently shown that persons with ASC have reduced memories for social information, relative to a spared memory for non-social facts. The current study aims to reproduce these findings, while examining the possible causes leading to this difference. Participants' memory for trait-words was tested after they had viewed the words in three study contexts: visuo-motor, letter-detection, and social judgment. While participants with ASC showed a levels-of-processing effect, such that their memory for words viewed in the social judgment context was greater than their memory for words viewed in the letter-detection context, their memory for socially-processed words was reduced relative to comparison participants. This interaction effect could not be explained by a speed/accuracy trade-off, nor could it be explained solely by differences in encoding. These results suggest that social memory deficits in ASC arise from difficulties both in orienting towards and encoding social content, as well as retaining and retrieving it. Implications for theory and clinical practice are discussed. C1 [Brezis, Rachel S.] Univ Chicago, Dept Comparat Human Dev, Chicago, IL 60637 USA. [Brezis, Rachel S.] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90024 USA. [Galili, Tal] Tel Aviv Univ, Dept Stat & Operat Res, IL-69978 Tel Aviv, Israel. [Wong, Tiffany; Piggot, Judith I.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Brezis, RS (reprint author), Univ Calif Los Angeles, Ctr Culture & Hlth, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Box 62,Room B7-435, Los Angeles, CA 90024 USA. EM rsbrezis@ucla.edu CR ANDERSON NH, 1968, J PERS SOC PSYCHOL, V9, P272, DOI 10.1037/h0025907 Baron-Cohen S., 1999, UNDERSTANDING OTHER Ben Shalom D, 2003, CORTEX, V39, P1129 Blair RJR, 1996, J AUTISM DEV DISORD, V26, P571 Boucher J, 2012, AUTISM, V16, P603, DOI 10.1177/1362361311417738 Boucher J, 2008, MEMORY AUTISM THEORY Bowler DM, 2004, J AUTISM DEV DISORD, V34, P533, DOI 10.1007/s10803-004-2548-7 Brezis R. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1183 EP 1192 DI 10.1007/s10803-013-1980-y PG 10 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200017 PM 24214241 ER PT J AU Grainger, C Williams, DM Lind, SE AF Grainger, Catherine Williams, David M. Lind, Sophie E. TI Online Action Monitoring and Memory for Self-Performed Actions in Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Action monitoring; Enactment effect; Source memory; Self-referencing; Agency ID ASPERGER-SYNDROME; AUTOBIOGRAPHICAL MEMORY; FUNCTIONING AUTISM; CHILDRENS MEMORY; EPISODIC MEMORY; ADULTS; EVENTS; MIND; INDIVIDUALS; RECOGNITION AB This study explored whether individuals with autism spectrum disorder (ASD) experience difficulties with action monitoring. Two experimental tasks examined whether adults with ASD are able to monitor their own actions online, and whether they also show a typical enactment effects in memory (enhanced memory for actions they have performed compared to actions they have observed being performed). Individuals with ASD and comparison participants showed a similar pattern of performance on both tasks. In a task which required individuals to distinguish person-caused from computer-caused changes in phenomenology both groups found it easier to monitor their own actions compared to those of an experimenter. Both groups also showed typical enactment effects. Despite recent suggestions to the contrary, these results support suggestions that action monitoring is unimpaired in ASD. C1 [Grainger, Catherine; Williams, David M.] Univ Kent, Sch Psychol, Keynes Coll, Canterbury CT2 7NP, Kent, England. [Lind, Sophie E.] City Univ London, Dept Psychol, Autism Res Grp, London EC1R 0JD, England. RP Grainger, C (reprint author), Univ Kent, Sch Psychol, Keynes Coll, Canterbury CT2 7NP, Kent, England. EM cg341@kent.ac.uk; D.M.Williams@kent.ac.uk; Sophie.Lind.2@city.ac.uk3 CR American Psychiatric Association, 2000, DIAGNOSTIC AND STATI American Psychiatric Association, 2013, DIAGNOSTIC AND STATI BAKERWARD L, 1990, COGNITIVE DEV, V5, P55, DOI 10.1016/0885-2014(90)90012-I Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Ben Shalom D, 2006, J AUTISM DEV DISORD, V36, P395, DOI 10.1007/s10803-006-0077-2 Blakemore SJ, 2006, BRAIN COGNITION, V61, P5, DOI 10.1016/j.bandc.2005.12.013 COLTHEART M, 1981, Q J EXP PSYCHOL-A, V33, P497 Crane L, 2012, J AUTISM DEV DISORD, V42, P2100, DOI 10.1007/s10803-012-1459-2 Crane L, 2008, J AUTISM DEV DISORD, V38, P498, DOI 10.1007/s10803-007-0420-2 d Health Organization, 1993, INTERNATIONAL CLASSI David N, 2008, J AUTISM DEV DISORD, V38, P593, DOI 10.1007/s10803-007-0425-x ENGELKAMP J, 1989, PSYCHOL RES-PSYCH FO, V51, P153, DOI 10.1007/BF00309142 Engelkamp J., 1998, MEMORY FOR ACTIONS Farrant A, 1998, J AUTISM DEV DISORD, V28, P43, DOI 10.1023/A:1026010919219 FERRARI M, 1983, J AUTISM DEV DISORD, V13, P317, DOI 10.1007/BF01531569 FRITH CD, 1989, PSYCHOL MED, V19, P359 FRITH U, 1969, J CHILD PSYCHOL PSYC, V10, P153, DOI 10.1111/j.1469-7610.1969.tb02077.x Hala S, 2005, J AUTISM DEV DISORD, V35, P75, DOI 10.1007/s10803-004-1036-4 Hamilton AFD, 2007, NEUROPSYCHOLOGIA, V45, P1859, DOI 10.1016/j.neuropsychologia.2006.11.022 Hare DJ, 2007, RES DEV DISABIL, V28, P317, DOI 10.1016/j.ridd.2006.03.003 Hill E, 2004, J AUTISM DEV DISORD, V34, P229, DOI 10.1023/B:JADD.0000022613.41399.14 Hill EL, 2002, INFANT CHILD DEV, V11, P159, DOI 10.1002/icd.303 Hobson R. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1193 EP 1206 DI 10.1007/s10803-013-1987-4 PG 14 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200018 PM 24193578 ER PT J AU Harrop, C McConachie, H Emsley, R Leadbitter, K Green, J AF Harrop, Clare McConachie, Helen Emsley, Richard Leadbitter, Kathy Green, Jonathan CA PACT Consortium TI Restricted and Repetitive Behaviors in Autism Spectrum Disorders and Typical Development: Cross-Sectional and Longitudinal Comparisons SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Repetitive behaviors; Measurement longitudinal ID YOUNG-CHILDREN; DIAGNOSTIC INTERVIEW; COMMUNICATION DISORDERS; ASPERGER-SYNDROME; FOLLOW-UP; INTERESTS; STEREOTYPIES; INFANTS; TIME; PLAY AB Restricted and repetitive behaviors (RRBs) are characteristic of autism spectrum disorders (ASD). However, compared to social and communicative impairments, less is known about their development, trajectory and etiology. This study explored RRBs in young children with ASD matched to typically developing (TD) children on non-verbal development. RRBs were coded from direct observation at three time points within 13 months of development. Children with ASD displayed higher frequency and greater diversity of RRBs at all time points, however RRBs were not unique to ASD and evident in the TD control group albeit at a reduced frequency. RRBs did not correlate with social and communicative impairments in the ASD group, suggesting dissociation between these domains. C1 [Harrop, Clare] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Autism Res & Treatment, Los Angeles, CA 90024 USA. [McConachie, Helen] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1207 EP 1219 DI 10.1007/s10803-013-1986-5 PG 13 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200019 PM 24234675 ER PT J AU Riby, DM Hanley, M Kirk, H Clark, F Little, K Fleck, R Janes, E Kelso, L O'Kane, F Cole-Fletcher, R Allday, MH Hocking, D Cornish, K Rodgers, J AF Riby, Deborah M. Hanley, Mary Kirk, Hannah Clark, Fiona Little, Katie Fleck, Ruth Janes, Emily Kelso, Linzi O'Kane, Fionnuala Cole-Fletcher, Rachel Allday, Marianne Hvistendahl Hocking, Darren Cornish, Kim Rodgers, Jacqui TI The Interplay Between Anxiety and Social Functioning in Williams Syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Williams syndrome; Social; Anxiety ID ASPERGER-SYNDROME; AUTISM SPECTRUM; BEHAVIORAL-CHARACTERISTICS; PSYCHOMETRIC PROPERTIES; CHILDRENS ANXIETY; CONTROLLED-TRIAL; YOUNG-CHILDREN; MENTAL-HEALTH; DISORDERS; ADULTS AB The developmental disorder Williams syndrome (WS) has been associated with an atypical social profile of hyper-sociability and heightened social sensitivity across the developmental spectrum. In addition, previous research suggests that both children and adults with WS have a predisposition towards anxiety. The current research aimed to explore the profiles of social behaviour and anxiety across a broad age range of individuals with the disorder (n = 59, ages 6-36 years). We used insights from parental reports on two frequently used measures, the Spence Children's Anxiety Scale (SCAS-P) and the Social Responsiveness Scale (SRS). Severity of anxiety was correlated with a greater degree of social dysfunction as measured by the SRS in this group. We split the group according to high or low anxiety as measured by the SCAS-P and explored the profile of social skills for the two groups. Individuals high and low in anxiety differed in their social abilities. The results emphasise the need to address anxiety issues in this disorder and to consider how components of anxiety might relate to other features of the disorder. C1 [Riby, Deborah M.; Hanley, Mary] Univ Durham, Dept Psychol, Sci Labs, Durham DH1 3LE, England. [Riby, Deborah M.; Kirk, Hannah; Hocking, Darren; Cornish, Kim] Monash Univ, Sch Psychol & Psychiat, Melbourne, Vic 3004, Australia. [Hanley, Mary; Kelso, Linzi; O'Kane, Fionnuala] Queens Univ, Sch Psychol, Belfast, Antrim, North Ireland. [Clark, Fiona; Little, Katie; Fleck, Ruth; Allday, Marianne Hvistendahl] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Janes, Emily; Cole-Fletcher, Rachel; Rodgers, Jacqui] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Janes, Emily] Northumberland Tyne & Wear NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England. RP Riby, DM (reprint author), Univ Durham, Dept Psychol, Sci Labs, South Rd, Durham DH1 3LE, England. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1220 EP 1229 DI 10.1007/s10803-013-1984-7 PG 10 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200020 PM 24197115 ER PT J AU Griffith, GM Hastings, RP Petalas, MA AF Griffith, Gemma M. Hastings, Richard P. Petalas, Michael A. TI Brief Report: Fathers' and Mothers' Ratings of Behavioral and Emotional Problems in Siblings of Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Sibling; SDQ; Mother; Father; Behavior ID MATERNAL MENTAL-HEALTH; INTELLECTUAL DISABILITY; DIFFICULTIES QUESTIONNAIRE; ADJUSTMENT; PARENT; STRENGTHS; SYMPTOMS; PSYCHOPATHOLOGY; PERCEPTIONS; PROGRAMS AB Debate is ongoing about whether typically developing siblings of children with autism spectrum disorder (ASD) are at greater risk of behavioral or emotional problems than siblings of children without ASD. Most data on behavior is provided by mothers, and we do not know whether fathers' reports differ. The strengths and difficulties questionnaire (Goodman in J Child Psychol Psychiatry 38(5):581-586, 1997) was completed by 168 mothers and 130 fathers. Parents were more likely to rate siblings as having 'abnormal' behavior when compared to a normative population. We found moderate correlations between mother-father ratings. More research may be needed to understand any clinical benefits of gathering data about sibling adjustment from more than one parent in the family. Implications for clinical practice and future research are discussed. C1 [Griffith, Gemma M.] Bangor Univ, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales. [Hastings, Richard P.] Univ Warwick, Ctr Educ Dev Appraisal & Res, Coventry CV4 7AL, W Midlands, England. [Petalas, Michael A.] Plas Coch Independent Hosp, St Asaph LL17 0HU, Denbigh, Wales. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1230 EP 1235 DI 10.1007/s10803-013-1969-6 PG 6 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200021 PM 24141746 ER PT J AU Russell-Smith, SN Comerford, BJE Maybery, MT Whitehouse, AJO AF Russell-Smith, Suzanna N. Comerford, Bronwynn J. E. Maybery, Murray T. Whitehouse, Andrew J. O. TI Brief Report: Further Evidence for a Link Between Inner Speech Limitations and Executive Function in High-Functioning Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Autism spectrum disorder; Executive function; Cognitive flexibility; Inner speech; Wisconsin card sorting test; Articulatory suppression ID CARD SORTING TEST; PRIVATE SPEECH; PERFORMANCE; DYSFUNCTION; MEMORY; TASKS AB This study investigated the involvement of inner speech limitations in the executive dysfunction associated with autism spectrum disorders (ASDs). Seventeen children with ASD and 18 controls, statistically-matched in age and IQ, performed a computer-based card sorting test (CST) to assess cognitive flexibility under four conditions: baseline, with articulatory suppression, with a concurrent mouthing task, and while verbalizing their strategies aloud. Articulatory suppression adversely affected CST performance for the control group but not the ASD group. The results additionally showed that overtly verbalizing strategies did not benefit the ASD children as it did the typically developing children. The findings thus provide further evidence that ASD children do not use inner speech to the same extent, or with the same effectiveness, as typically developing children when performing executive tasks. C1 [Russell-Smith, Suzanna N.; Comerford, Bronwynn J. E.; Maybery, Murray T.; Whitehouse, Andrew J. O.] Univ Western Australia, Sch Psychol, Neurocognit Dev Unit, Perth, WA 6009, Australia. [Whitehouse, Andrew J. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1236 EP 1243 DI 10.1007/s10803-013-1975-8 PG 8 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200022 PM 24197114 ER PT J AU Schreibman, L Stahmer, AC AF Schreibman, Laura Stahmer, Aubyn C. TI A Randomized Trial Comparison of the Effects of Verbal and Pictorial Naturalistic Communication Strategies on Spoken Language for Young Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Behavioral intervention; Functional communication; Vocal language intervention; Pictorial communication intervention; Augmentative communication ID INTERVENTIONS; SPECTRUM; SPEECH; PRESCHOOLERS; ACQUISITION; DISORDERS; PARADIGM; BEHAVIOR; PARENTS AB Presently there is no consensus on the specific behavioral treatment of choice for targeting language in young nonverbal children with autism. This randomized clinical trial compared the effectiveness of a verbally-based intervention, Pivotal Response Training (PRT) to a pictorially-based behavioral intervention, the Picture Exchange Communication System (PECS) on the acquisition of spoken language by young (2-4 years), nonverbal or minimally verbal (<= 9 words) children with autism. Thirty-nine children were randomly assigned to either the PRT or PECS condition. Participants received on average 247 h of intervention across 23 weeks. Dependent measures included overall communication, expressive vocabulary, pictorial communication and parent satisfaction. Children in both intervention groups demonstrated increases in spoken language skills, with no significant difference between the two conditions. Seventy-eight percent of all children exited the program with more than 10 functional words. Parents were very satisfied with both programs but indicated PECS was more difficult to implement. C1 [Schreibman, Laura] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. [Stahmer, Aubyn C.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stahmer, Aubyn C.] Rady Childrens Hosp, San Diego, CA USA. RP Schreibman, L (reprint author), Univ Calif San Diego, Dept Psychol, 9500 Gilman Dr MC 0109, La Jolla, CA 92093 USA. EM lschreibman@ucsd.edu; astahmer@ucsd.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bondy A, 2001, BEHAV MODIF, V25, P725, DOI 10.1177/0145445501255004 Charlop-Christy MH, 2002, J APPL BEHAV ANAL, V35, P213, DOI 10.1901/jaba.2002.35-213 Dawson G, 2008, DEV PSYCHOPATHOL, V20, P775, DOI 10.1017/S0954579408000370 Fenson L., 2006, MACARTHUR BATES COMM Frost L., 2002, PICTURE EXCHANGE COM, V2nd Ganz J. B., 2007, RES AUTISM SPECT DIS, V2, P167 Gardner MF, 1990, EXPRESSIVE ONE WORD Koegel R. 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Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1244 EP 1251 DI 10.1007/s10803-013-1972-y PG 8 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200023 PM 24272416 ER PT J AU McGonigle, JJ Migyanka, JM Glor-Scheib, SJ Cramer, R Fratangeli, JJ Hegde, GG Shang, J Venkat, A AF McGonigle, John J. Migyanka, Joann M. Glor-Scheib, Susan J. Cramer, Ryan Fratangeli, Jeffrey J. Hegde, Gajanan G. Shang, Jennifer Venkat, Arvind TI Development and Evaluation of Educational Materials for Pre-hospital and Emergency Department Personnel on the Care of Patients with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Emergency medical services; Emergency nurse; Emergency department; Autism spectrum disorder; Education ID CHILDREN; HEALTH AB With the rising prevalence of patients with autism spectrum disorder (ASD), there has been an increase in the acute presentation of these individuals to the general health care system. Emergency medical services and emergency department personnel commonly address the health care needs of patients with ASD at times of crisis. Unfortunately, there is little education provided to front-line emergency medical technicians, paramedics and emergency nurses on the characteristics of ASD and how these characteristics can create challenges for individuals with ASD and their health care providers in the pre-hospital and emergency department settings. This paper describes the development of educational materials on ASD and the results of training of emergency medical services and emergency department personnel. C1 [McGonigle, John J.; Cramer, Ryan] Univ Pittsburgh, Western Psychiat Inst & Clin, Western Reg ASERT, Med Ctr, Pittsburgh, PA 15213 USA. [Migyanka, Joann M.; Glor-Scheib, Susan J.] Indiana Univ Penn, Indiana, PA USA. [Fratangeli, Jeffrey J.] Indiana Univ Penn, Coll Educ & Educ Technol, Indiana, PA USA. [Hegde, Gajanan G.; Shang, Jennifer] Univ Pittsburgh, Katz Grad Sch Business, Pittsburgh, PA 15260 USA. [Venkat, Arvind] Allegheny Gen Hosp, Dept Emergency Med, Allegheny Hlth Network, Pittsburgh, PA 15212 USA. RP Venkat, A (reprint author), Allegheny Gen Hosp, Dept Emergency Med, Allegheny Hlth Network, 320 East North Ave, Pittsburgh, PA 15212 USA. EM avenkat@wpahs.org CR Autism society, 2013, AUT FACTS STAT Autism society, 2013, SAF SOUND CAMP Autism society, 2013, AB AUT Centers for Disease Control and Prevention, 2010, NAT HOSP AMB MED SUR Gurney JG, 2006, ARCH PEDIAT ADOL MED, V160, P825, DOI 10.1001/archpedi.160.8.825 Kogan MD, 2008, PEDIATRICS, V122, pE1149, DOI 10.1542/peds.2008-1057 National Center for Health Care Statistics, 2013, HLTH US 2012 SPEC FE Pennsylvania Department of Public Welfare Office of Developmental Programs Bureau of Autism Services and Autism Services Education Resources Training Collaboratives, 2011, 4 PENNS DEP PUBL WEL Scarpinato N, 2010, J SPEC PEDIATR NURS, V15, P244, DOI 10.1111/j.1744-6155.2010.00244.x Shellenbarger Teresa, 2004, J Emerg Nurs, V30, P278, DOI 10.1016/j.jen.2004.02.002 van Olejnik L., 2004, J EMERGENCY MED SERV, V29, P56 Venkat A, 2012, POSTGRAD MED J, V88, P472, DOI 10.1136/postgradmedj-2011-130727 NR 12 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2014 VL 44 IS 5 BP 1252 EP 1259 DI 10.1007/s10803-013-1962-0 PG 8 WC Psychology, Developmental SC Psychology GA AH7RD UT WOS:000336330200024 PM 24091472 ER PT J AU Norbury, CF Gemmell, T Paul, R AF Norbury, Courtenay Frazier Gemmell, Tracey Paul, Rhea TI Pragmatics abilities in narrative production: a cross-disorder comparison SO JOURNAL OF CHILD LANGUAGE LA English DT Article ID AUTISTIC-SPECTRUM DISORDERS; HIGH-FUNCTIONING CHILDREN; LANGUAGE IMPAIRMENT; ASPERGER-SYNDROME; STORY; COHERENCE; ADULTS; SKILLS; MIND AB We aimed to disentangle contributions of socio-pragmatic and structural language deficits to narrative competence by comparing the narratives of children with autism spectrum disorder (ASD; n=25), non-autistic children with language impairments (LI; n=23), and children with typical development (TD; n=27). Groups were matched for age (61/2 to 15 years; mean: 10;6) and non-verbal ability; ASD and TD groups were matched on standardized language scores. Despite distinct clinical presentation, children with ASD and LI produced similarly simple narratives that lacked semantic richness and omitted important story elements, when compared to TD peers. Pragmatic errors were common across groups. Within the LI group, pragmatic errors were negatively correlated with story macrostructure scores and with an index of semantic-pragmatic relevance. For the group with ASD, pragmatic errors consisted of comments that, though extraneous, did not detract from the gist of the narrative. These findings underline the importance of both language and socio-pragmatic skill for producing coherent, appropriate narratives. C1 [Norbury, Courtenay Frazier] Univ London, Dept Psychol, Egham TW20 0EX, Surrey, England. [Gemmell, Tracey] Winnebago Cty Special Educ Cooperat, Rockton, IL USA. [Paul, Rhea] Univ Cattolica Sacro Cuore, I-20123 Milan, Italy. RP Norbury, CF (reprint author), Univ London, Dept Psychol, Egham TW20 0EX, Surrey, England. EM courtenay.norbury@rhul.ac.uk CR American Psychiatric and Association, 2012, DIAGN STAT MAN MENT American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Beaumont R, 2006, AUTISM, V10, P365, DOI 10.1177/1362361306064416 Berman R. A., 2009, CAMBRIDGE HDB CHILD, P354, DOI DOI 10.1017/CB09780511576164CB09780511576164 Bishop D. V. 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Helt, Molly Troyb, Eva Tyson, Katherine E. Barton, Marianne L. Eigsti, Inge-Marie Naigles, Letitia Fein, Deborah A. TI Intervention for Optimal Outcome in Children and Adolescents with a History of Autism SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism spectrum disorder; optimal outcomes; intervention history; medication ID INTENSIVE BEHAVIORAL TREATMENT; ALTERNATIVE MEDICINE TREATMENTS; SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; YOUNG-CHILDREN; COMMUNICATION; COMPLEMENTARY; INDIVIDUALS; PREDICTORS AB Objective:Autism spectrum disorders (ASDs) were once considered lifelong disorders, but recent findings indicate that some children with ASDs no longer meet diagnostic criteria for any ASD and reach normal cognitive function. These children are considered to have achieved optimal outcomes (OO). The present study aimed to retrospectively examine group differences in the intervention history of children and adolescents with OO and those with high-functioning autism (HFA).Method:The current study examined intervention histories in 25 individuals with OO and 34 individuals with HFA (current age, 8-21 years), who did not differ on age, sex, nonverbal intelligence, or family income. Intervention history was collected through detailed parent questionnaires.Results:Children in the OO group had earlier parental concern, received earlier referrals to specialists, and had earlier and more intensive intervention than those in the HFA group. Substantially more children with OO than HFA received applied behavior analysis (ABA) therapy, although for children who received ABA, the intensity did not differ between the groups. Children in the HFA group were more likely to have received medication, especially antipsychotics and antidepressants. There were no group differences in the percent of children receiving special diets or supplements.Conclusion:These data suggest that OO individuals generally receive earlier, more intense interventions, and more ABA, whereas HFA individuals receive more pharmacologic treatments. Although the use of retrospective data is a clear limitation to the current study, the substantial differences in the reported provision of early intervention, and ABA in particular, is highly suggestive and should be replicated in prospective studies. C1 [Orinstein, Alyssa J.; Helt, Molly; Troyb, Eva; Tyson, Katherine E.; Barton, Marianne L.; Eigsti, Inge-Marie; Naigles, Letitia; Fein, Deborah A.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. RP Orinstein, AJ (reprint author), Univ Connecticut, Dept Psychol, 406 Babbidge Rd,Unit 1020, Storrs, CT 06269 USA. EM alyssa.orinstein@uconn.edu FU National Institutes of Mental Health [R01MH076189] FX Supported by the National Institutes of Mental Health grant (R01MH076189). 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Dev. Behav. Pediatr. PD MAY PY 2014 VL 35 IS 4 BP 247 EP 256 DI 10.1097/DBP.0000000000000037 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AH3AZ UT WOS:000335994900002 PM 24799263 ER PT J AU Gillette, MLD Stough, CO Beck, AR Maliszewski, G Best, CM Gerling, JK Summar, S AF Gillette, Meredith L. Dreyer Stough, Cathleen Odar Beck, Amy R. Maliszewski, Genevieve Best, Cora M. Gerling, Janelle K. Summar, Shelly TI Outcomes of a Weight Management Clinic for Children with Special Needs SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE childhood obesity; eating behaviors; autism spectrum disorders; Down syndrome; intervention ID RANDOMIZED CONTROLLED-TRIAL; DEVELOPMENTAL-DISABILITIES; PEDIATRIC OBESITY; DOWN-SYNDROME; AUTISM; OVERWEIGHT; PREVALENCE; INTERVENTION; ADOLESCENTS; BEHAVIORS AB Objective:Rates of obesity are elevated among children with special needs (e.g., autism spectrum disorder, Down syndrome, or developmental disabilities). The objective of this study was to evaluate the effectiveness of a multidisciplinary tailored intervention to treat obesity among youth with special needs.Method:Seventy-six children aged 2 to 19 years participated in a multidisciplinary weight management clinic adapted for children with special needs. A description of the patients presenting for specialized clinical services is provided, and the impact of the intervention on child body mass index (BMI) and food variety was examined for a subset (n = 30) of children. Descriptive statistics of the patient population at baseline were calculated and a series of t tests, correlations, and analysis of variance models examined change in BMI z-scores (BMIz) and diet variety. Factors related to treatment outcomes were also explored.Results:BMIz decreased significantly by the 6-month follow-up (M = 2.43 to M = 2.36, p < .01). There were significant increases in the variety of fruits, vegetables, and grains that children ate (t(16) = 3.18, p < .01; t(16) = 2.63, p = .02; t(16) = 2.37, p = .03, respectively).Conclusion:A multidisciplinary clinic-based intervention was effective in reducing BMIz over a 6-month period and increasing the variety of foods that children were eating. These results have implications for providing tailored weight management interventions for youth with obesity and special needs. C1 [Gillette, Meredith L. Dreyer; Beck, Amy R.] Childrens Mercy Hosp, Dept Pediat Dev & Behav Sci, Kansas City, MO 64108 USA. [Gillette, Meredith L. Dreyer; Beck, Amy R.; Best, Cora M.; Gerling, Janelle K.; Summar, Shelly] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Gillette, Meredith L. Dreyer; Stough, Cathleen Odar; Beck, Amy R.] Ctr Childrens Healthy Lifestyles & Nutr, Kansas City, MO USA. [Stough, Cathleen Odar] Univ Kansas, Clin Child Psychol Program, Lawrence, KS 66045 USA. [Maliszewski, Genevieve] Univ Missouri, Dept Counseling & Educ Psychol, Kansas City, MO 64110 USA. [Gerling, Janelle K.] Childrens Mercy Hosp, Dept Allied Hlth Profess Phys & Occupat Therapy, Kansas City, MO 64108 USA. RP Gillette, MLD (reprint author), Childrens Mercy Hosp, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM mldreyer@cmh.edu FU Healthcare Foundation of Greater Kansas City; Kenneth and Eva S. Smith Scholar in Pediatric Obesity Award FX The study was supported by funding from the Healthcare Foundation of Greater Kansas City and the Kenneth and Eva S. Smith Scholar in Pediatric Obesity Award. The authors declare no conflict of interest. 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Dev. Behav. Pediatr. PD MAY PY 2014 VL 35 IS 4 BP 266 EP 273 DI 10.1097/DBP.0000000000000055 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AH3AZ UT WOS:000335994900004 PM 24799265 ER PT J AU Rumsey, RK Rudser, K Delaney, K Potegal, M Whitley, CB Shapiro, E AF Rumsey, Robin K. Rudser, Kyle Delaney, Kathleen Potegal, Michael Whitley, Chester B. Shapiro, Elsa TI Acquired Autistic Behaviors in Children with Mucopolysaccharidosis Type IIIA SO JOURNAL OF PEDIATRICS LA English DT Article ID SANFILIPPO SYNDROME; PREVALENCE; DISORDERS AB Objectives To assess autism spectrum disorder (ASD) behaviors in children with mucopolysaccharidosis type IIIA (MPS IIIA) using a standard measure, understand the behavioral evolution of the disease, and provide specific guidelines for diagnosis. Study design Children (n = 21) with documented enzyme deficiency and SGSH gene mutations, cognitive age-equivalent >12 months, and early onset were administered the Autism Diagnostic Observation Schedule (ADOS) (module 1) and Bayley Scales of Infant Development-Third Edition. ADOS Social Affect and Restricted Repetitive Behavior total scores, as well as Bayley Scales of Infant Development-Third Edition cognitive age-equivalent scores, are reported using descriptive statistics and graphic presentations. Results Thirteen of the 21 children evaluated met the ADOS criteria for ASD/autism. ADOS score was strongly associated with age; all 11 children aged >46 months met the criteria, compared with only 2 of 10 aged <46 months. Social and affective abnormalities were most frequent; restricted interests and repetitive behaviors were largely absent. Lack of cognitive growth paralleled ADOS score. Conclusion An increased incidence of ASD-like social behaviors was seen at age 3-4 years in children with early-onset MPS IIIA. Although more frequent in the severely impaired children, ASD-like behaviors were observed across the entire range of cognitive impairment. Clinicians must be aware that when a child acquires ASD-like behaviors, MPS IIIA should be included in the differential diagnosis. C1 [Rumsey, Robin K.; Delaney, Kathleen; Potegal, Michael; Whitley, Chester B.; Shapiro, Elsa] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Rudser, Kyle] Univ Minnesota, Div Biostat, Minneapolis, MN USA. RP Rumsey, RK (reprint author), Autism Spectrum & Neurodev Disorders Clin, 717 Delaware St SE,Suite 340, Minneapolis, MN 55414 USA. EM rumse002@umn.edu FU National Institute of Neurological Disorders and Stroke [U54NS065768] FX We would like to acknowledge the University of Minnesota Autism Spectrum and Neurodevelopmental Disorders Clinic; the Center for Neurobehavioral Development; Amy Esler, PhD (University of Minnesota Autism Spectrum and Neurodevelopmental Disorders Clinic), who conducted several of the ADOS assessments; Brianna Yund (funded by National Institute of Neurological Disorders and Stroke [U54NS065768]), who entered the data; and the families who helped advance research by participating in this study. We thank Patrick Haslett, MD (employee of Shire Pharmaceuticals) for his role in designing the overall trial and assistance in reviewing the initial manuscript. 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Pediatr. PD MAY PY 2014 VL 164 IS 5 BP 1147 EP + DI 10.1016/j.jpeds.2014.01.007 PG 6 WC Pediatrics SC Pediatrics GA AG6GB UT WOS:000335516000041 PM 24582005 ER PT J AU Semino, E AF Semino, Elena TI Pragmatic failure, mind style and characterisation in fiction about autism SO LANGUAGE AND LITERATURE LA English DT Article DE Autism; Theory of Mind; Grice; fiction; pragmatic failure; figurative language; impoliteness; mind style; metaphor; characterisation ID LANGUAGE; CHILDREN AB This article presents an analysis of different types of pragmatic failure in the interactional behaviour of the 'autistic' protagonists of three recent novels. Three main types of pragmatic failure occur across all three novels: problems with informativeness and relevance in conversational contributions; problems with face management resulting in unintentional impolite behaviours; and problems with the interpretation of figurative language. These problems are salient and frequent enough to contribute to the projection of distinctive mind styles, and more generally to the characterisation of the protagonists as individuals with communication and socialisation difficulties that are likely to both reflect and reinforce general perceptions of autism-spectrum disorders. It is also argued that pragmatic failure contributes to the potential defamiliarisation of 'normal' communication, which is presented as being fraught with obscurity, ambiguity and insincerity. C1 [Semino, Elena] Univ Lancaster, Lancaster LA1 4YL, England. RP Semino, E (reprint author), Univ Lancaster, Dept Linguist & English Language, Lancaster LA1 4YL, England. 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Lit. PD MAY PY 2014 VL 23 IS 2 BP 141 EP 158 DI 10.1177/0963947014526312 PG 18 WC Linguistics; Language & Linguistics SC Linguistics GA AG9UR UT WOS:000335765900003 ER PT J AU Naviaux, RK AF Naviaux, Robert K. TI Metabolic features of the cell danger response SO MITOCHONDRION LA English DT Article DE Oxidative stress; Oxidative shielding; Innate immunity; Inflammation; Purinergic signaling; Mitochondria ID INNATE IMMUNE-RESPONSES; CYSTINE/GLUTAMATE ANTIPORTER; PYRIMIDINE METABOLISM; AUTOIMMUNE-DISEASE; IMPROVES RECOVERY; OXIDATIVE-STRESS; ATP RELEASE; LUNG INJURY; KAPPA-B; RECEPTOR AB The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatoty and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TB!), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis. (C) 2013 The Author. Published by Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Naviaux, Robert K.] Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, Dept Med, San Diego, CA 92103 USA. [Naviaux, Robert K.] Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, Dept Pediat, San Diego, CA 92103 USA. [Naviaux, Robert K.] Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, Dept Pathol, San Diego, CA 92103 USA. [Naviaux, Robert K.] Vet Affairs Ctr Excellence Stress & Mental Hlth C, La Jolla, CA USA. RP Naviaux, RK (reprint author), Univ Calif San Diego, Sch Med, Mitochondrial & Metab Dis Ctr, 214 Dickinson St,Bldg CTF,Rm C102, San Diego, CA 92103 USA. EM Naviaux@ucsd.edu FU UCSD Christini Fund; Jane Botsford Johnson Foundation; Wright Foundation; Lennox Foundation; Takes Guts Foundation; UCSD Mitochondrial Disease Research Foundation; Hailey's Wish Foundation FX RKN thanks Jane Naviaux, Will Alaynick, Jim Adams, Steve Edelson, Kate Crowley, and Vicki Kobliner for helpful comments on the manuscript. This work was made possible by support from the UCSD Christini Fund, the Jane Botsford Johnson Foundation, the Wright Foundation, the Lennox Foundation, the It Takes Guts Foundation, the UCSD Mitochondrial Disease Research Foundation, and the Hailey's Wish Foundation. 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Lee, Li-Ching Crum, Rosa M. Zimmerman, Andrew W. Hertz-Picciotto, Irva TI Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay SO PEDIATRICS LA English DT Article DE selective serotonin reuptake inhibitors; autism; developmental delay; pregnancy; epidemiology ID SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT MEDICATIONS; MATERNAL DEPRESSION; PLATELET SEROTONIN; BRAIN-DEVELOPMENT; PREGNANCY; EXPOSURE; POPULATION; RISK; TRANSPORTER AB OBJECTIVE:To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).METHODS:A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information.RESULTS:Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98-11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62). Findings were similar among mothers with an anxiety or mood disorder history.CONCLUSIONS:In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms. C1 [Harrington, Rebecca A.; Lee, Li-Ching] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Crum, Rosa M.] Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. [Crum, Rosa M.] Johns Hopkins Med Inst, Dept Psychiat, Baltimore, MD 21205 USA. [Crum, Rosa M.] Johns Hopkins Med Inst, Dept Mental Hlth, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Hertz-Picciotto, Irva] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. 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Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of 7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing 1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network. C1 [Napoli, Eleonora; Wong, Sarah; Giulivi, Cecilia] Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA. [Hertz-Picciotto, Irva] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Hertz-Picciotto, Irva; Giulivi, Cecilia] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Davis, CA 95616 USA. RP Giulivi, C (reprint author), Univ Calif Davis, Dept Mol Biosci, 1089 Vet Med Dr,VetMed 3B, Davis, CA 95616 USA. EM cgiulivi@ucdavis.edu FU Simons Foundation [SFARI 271406]; NIEHS [R01-ES011269, R01-ES015359, R01-ES020392]; National Institutes of Health (NIH) FX This study was performed with funding from the Simons Foundation (SFARI 271406 to Dr Giulivi) and NIEHS R01-ES011269, R01-ES015359, and R01-ES020392. Funded by the National Institutes of Health (NIH). 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Hirtz, D Lie, KK Lipkin, WI Magnus, P Reichborn-Kjennerud, T Schjolberg, S Susser, E Oyen, AS Smith, GD Stoltenberg, C AF Suren, Pal Gunnes, Nina Roth, Christine Bresnahan, Michaeline Hornig, Mady Hirtz, Deborah Lie, Kari Kveim Lipkin, W. Ian Magnus, Per Reichborn-Kjennerud, Ted Schjolberg, Synnve Susser, Ezra Oyen, Anne-Siri Smith, George Davey Stoltenberg, Camilla TI Parental Obesity and Risk of Autism Spectrum Disorder SO PEDIATRICS LA English DT Article DE autism spectrum disorder; autistic disorder; Asperger disorder; PDD-NOS; parental obesity; parental BMI; child cohort study ID BODY-MASS INDEX; BIRTH COHORT; BIAS; PREGNANCY; DELETIONS; ORIGIN; ADHD AB OBJECTIVES:The objective of the study was to investigate the associations among maternal prepregnancy BMI, paternal BMI, and the risk of autism spectrum disorders (ASDs) in children.METHODS:The study sample of 92909 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The age range was 4.0 through 13.1 (mean 7.4) years. Relative risks of ASDs were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models.RESULTS:At the end of follow-up on December 31, 2012, 419 children in the study sample had been diagnosed with ASDs: 162 with autistic disorder, 103 with Asperger disorder, and 154 with pervasive developmental disorder not otherwise specified. Maternal obesity (BMI 30) was only weakly associated with ASD risk, whereas paternal obesity was associated with an increased risk of autistic disorder and Asperger disorder. The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07-2.82). For Asperger disorder, analyses were limited to children aged 7 years (n = 50116). The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13-3.57). No associations were found for pervasive developmental disorder not otherwise specified.CONCLUSIONS:Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies. C1 [Suren, Pal; Gunnes, Nina; Roth, Christine; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway. [Suren, Pal] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Gunnes, Nina; Roth, Christine; Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway. [Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway. [Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Stoltenberg, Camilla] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. RP Suren, P (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway. 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Sasaki, Akihiro T. Shimada, Koji Kakigi, Ryusuke Sadato, Norihiro TI The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE anterior cingulate cortex; anterior insular cortex; embarrassment; functional magnetic resonance imaging; self-evaluation of the face ID EVENT-RELATED FMRI; AUTISM SPECTRUM DISORDERS; MEDIAL PREFRONTAL CORTEX; AUTOBIOGRAPHICAL MEMORY; FUNCTIONAL NEUROANATOMY; SOCIAL COGNITION; NEURAL BASIS; OWN FACE; ACTIVATION; TIME AB Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. 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TI Neural evidence for an association between social proficiency and sensitivity to social reward SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE NAcc; social interest; empathy; social reward; autism ID EVENT-RELATED FMRI; AUTISM SPECTRUM DISORDERS; INFANT JOINT ATTENTION; EMPATHY QUOTIENT; IDENTITY RECOGNITION; FUNCTIONING AUTISM; ASPERGER-SYNDROME; MONETARY REWARD; SKILLS BATTERY; ANTICIPATION AB Data from developmental psychology suggests a link between the growth of socio-emotional competences and the infant's sensitivity to the salience of social stimuli. The aim of the present study was to find evidence for this relationship in healthy adults. Thirty-five participants were recruited based on their score above the 85th or below the 15th percentile of the empathy quotient questionnaire (EQ, Baron-Cohen and Wheelwright, 2004). Functional magnetic resonance imaging (fMRI) was used to compare neural responses to cues of social and non-social (monetary) reward. When compared to the high-EQ group, the low-EQ group showed reduced activity of the brain s reward system, specifically the right nucleus accumbens, in response to cues predictive of social reward (videos showing gestures of approval)-but increased activation in this area for monetary incentives. Our data provide evidence for a link between self-reported deficits in social proficiency and reduced sensitivity to the motivational salience of positive social stimuli. C1 [Gossen, Anna; Groppe, Sarah E.; Winkler, Lina; Gruender, Gerhard; Spreckelmeyer, Katja N.] Rhein Westfal TH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Fac Med, D-52074 Aachen, Germany. [Gossen, Anna; Groppe, Sarah E.; Winkler, Lina; Gruender, Gerhard; Spreckelmeyer, Katja N.] JARA Translat Brain Med, Aachen, Nordrhein Westf, Germany. [Gossen, Anna; Groppe, Sarah E.; Winkler, Lina; Gruender, Gerhard; Spreckelmeyer, Katja N.] JARA Translat Brain Med, Julich, Nordrhein Westf, Germany. [Kohls, Gregor; Herrington, John; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Spreckelmeyer, Katja N.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Gossen, A (reprint author), Rhein Westfal TH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Pauwelsstr 30, D-52074 Aachen, Germany. EM angossen@ukaachen.de FU German Research Foundation (Deutsche Forschungsgemeinschaft) [IRTG 1328]; RWTH Aachen medical faculty funding program START; National Institutes of Health [P30HD026979]; Robert Wood Johnson Foundation [66727] FX This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, IRTG 1328), RWTH Aachen medical faculty funding program START (K.N.S., L. W., S. G.), the National Institutes of Health (P30HD026979) ( R. T. S., G. K.) and the Robert Wood Johnson Foundation #66727 (R.T.S.). 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Cogn. Affect. Neurosci. PD MAY PY 2014 VL 9 IS 5 BP 661 EP 670 DI 10.1093/scan/nst033 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AH9UK UT WOS:000336489000013 PM 23512930 ER PT J AU Thomas, GM AF Thomas, Gareth M. TI Cooling the Mother Out: Revisiting and Revising Goffman's Account SO SYMBOLIC INTERACTION LA English DT Article DE mothers; cooling the mark out; stigma; Goffman; disability ID DOWN-SYNDROME; CHILDREN; STIGMA; DISABILITIES; FAMILIES; IDENTITY; FAILURE; PARENTS; AUTISM AB This article revisits Erving Goffman's important yet neglected metaphor of "cooling the mark out." Drawing on a study of mothers whose child has Down's syndrome, I explore the value of Goffman's work for capturing how mothers interpret their child's diagnosis as a loss and rectify this breach by constructing an acceptance of their new situation. 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Interact. PD MAY PY 2014 VL 37 IS 2 BP 283 EP 299 DI 10.1002/symb.91 PG 17 WC Sociology SC Sociology GA AG8CX UT WOS:000335647500008 ER PT J AU Hu, X Gan, SQ Xie, GE Li, L Chen, C Ding, XF Han, M Xiang, SL Zhang, J AF Hu, Xiang Gan, Shiquan Xie, Guie Li, Li Chen, Cheng Ding, Xiaofeng Han, Mei Xiang, Shuanglin Zhang, Jian TI KCTD10 is critical for heart and blood vessel development of zebrafish SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Article DE KCTD10; PDIP1; heart; blood vessel; zebrafish ID CELL NUCLEAR ANTIGEN; PROTEIN; GENES; EXPRESSION; TETRAMERIZATION; PROLIFERATION; HEMATOPOIESIS; EVOLUTION; INTERACTS; DOMAIN AB KCTD10 is a member of the PDIP1 family, which is highly conserved during evolution, sharing a lot of similarities among human, mouse, and zebrafish. Recently, zebrafish KCTD13 has been identified to play an important role in the early development of brain and autism. However, the specific function of KCTD10 remains to be elucidated. In this study, experiments were carried out to determine the expression pattern of zebrafish KCTD10 mRNA during embryonic development. It was found that KCTD10 is a maternal gene and KCTD10 is of great importance in the shaping of heart and blood vessels. Our data provide direct clues that knockdown of KCTD10 resulted in severe pericardial edema and loss of heart formation indicated by morphological observation and crucial heart markers like amhc, vmhc, and cmlc2. The heart defect caused by KCTD10 is linked to RhoA and PCNA. Flk-1 staining revealed that intersomitic vessels were lost in the trunk, although angioblasts could migrate to the midline. These findings could be helpful to better understand the determinants responsible for the heart and blood vessel defects. C1 [Hu, Xiang; Gan, Shiquan; Xie, Guie; Li, Li; Chen, Cheng; Ding, Xiaofeng; Han, Mei; Xiang, Shuanglin; Zhang, Jian] Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Changsha 410081, Hunan, Peoples R China. [Zhang, Jian] Shanghai Jiao Tong Univ, E Inst Shanghai Univ, Model Organism Div, Shanghai 200240, Peoples R China. RP Xiang, SL (reprint author), Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, State Educ Minist China, Changsha 410081, Hunan, Peoples R China. EM xshlin@hunnu.edu.cn; zhangjian@hunnu.edu.cn FU Ministry of Science and Technique of China [2010CB529900]; E-Institutes of Shanghai Municipal Education Commission [E03003]; Science & Technology Department of Hunan Province [13JJ6037]; Hunan Postdoctoral Science Foundation [2012RS4016] FX This study was supported by the grants from the Ministry of Science and Technique of China (No. 2010CB529900), the E-Institutes of Shanghai Municipal Education Commission (No. E03003), the Science & Technology Department of Hunan Province (13JJ6037), and the Hunan Postdoctoral Science Foundation (2012RS4016). 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Bijttebier, Patricia Roeyers, Herbert TI Effortful control and executive attention in typical and atypical development: An event-related potential study SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Executive attention; Flanker task; ERP; ERN; Effortful control; ADHD; Autism spectrum disorder ID DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDER; ANTERIOR CINGULATE CORTEX; ERROR-RELATED-NEGATIVITY; DEFICIT/HYPERACTIVITY DISORDER; RESPONSE-INHIBITION; INDIVIDUAL-DIFFERENCES; SOURCE LOCALIZATION; SELF-REGULATION; FUNCTIONAL-SIGNIFICANCE AB Executive attention and its relationship with effortful control (EC) were investigated in children with ADHD (n = 24), autism spectrum disorder (ASD; n = 20), and controls (n = 21). Executive attention measures included flanker-performance and event-related potentials (N2, P3, and ERN). EC was assessed using questionnaires. Only the ERN was found to be robustly related to EC across groups. N2 did not differ between groups and only children with ADHD + ODD showed diminished executive attention as expressed in RT and P3. In ADHD, monitoring of incorrect (ERN) and correct (CRN) responses was diminished. Overall, the link between EC and executive attention was less strong as expected and varied depending on group and measure considered. All groups were able to detect conflict (N2) and all but ADHD + ODD were able to allocate extra attention in order to respond correctly (P3). Findings indicate a general reduced response monitoring in ADHD. (C) 2014 Elsevier B.V. All rights reserved. C1 [Samyn, Vicky; Wiersema, Jan R.; Roeyers, Herbert] Univ Ghent, B-9000 Ghent, Belgium. [Bijttebier, Patricia] Univ Louvain, B-3000 Louvain, Belgium. RP Wiersema, JR (reprint author), Univ Ghent, Henri Dunantlaan 2, B-9000 Ghent, Belgium. EM vicky_samyn@hotmail.com; Roeljan.Wiersema@UGent.be; Patricia.Bijttebier@ppw.kuleuven.be; Herbert.Roeyers@UGent.be FU faculty of Psychology and Educational Sciences of the Ghent University FX The first author received funding from the research fund of the faculty of Psychology and Educational Sciences of the Ghent University. The funding source had no further involvement. 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J. van Steijn, Daphne J. de Ruiter, Saskia W. de Bruijn, Yvette G. E. de Sonneville, Leo M. J. Buitelaar, Jan K. Rommelse, Nanda N. J. TI Recognition of facial emotion and affective prosody in children with ASD ( plus ADHD) and their unaffected siblings SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Autism spectrum disorders (ASD); Attention-deficit/hyperactivity disorder (ADHD); Emotion recognition; Endophenotype; Sibling ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; ENDOPHENOTYPE APPROACH; PROCESSING STRATEGIES; SCHIZOPHRENIA; INFORMATION; SYMPTOMS; QUESTIONNAIRE; HERITABILITY AB Autism is a highly heritable and clinically heterogeneous neuropsychiatric disorder that frequently co-occurs with other psychopathologies, such as attention-deficit/hyperactivity disorder (ADHD). An approach to parse heterogeneity is by forming more homogeneous subgroups of autism spectrum disorder (ASD) patients based on their underlying, heritable cognitive vulnerabilities (endophenotypes). Emotion recognition is a likely endophenotypic candidate for ASD and possibly for ADHD. Therefore, this study aimed to examine whether emotion recognition is a viable endophenotypic candidate for ASD and to assess the impact of comorbid ADHD in this context. A total of 90 children with ASD (43 with and 47 without ADHD), 79 ASD unaffected siblings, and 139 controls aged 6-13 years, were included to test recognition of facial emotion and affective prosody. Our results revealed that the recognition of both facial emotion and affective prosody was impaired in children with ASD and aggravated by the presence of ADHD. The latter could only be partly explained by typical ADHD cognitive deficits, such as inhibitory and attentional problems. The performance of unaffected siblings could overall be considered at an intermediate level, performing somewhat worse than the controls and better than the ASD probands. Our findings suggest that emotion recognition might be a viable endophenotype in ASD and a fruitful target in future family studies of the genetic contribution to ASD and comorbid ADHD. Furthermore, our results suggest that children with comorbid ASD and ADHD are at highest risk for emotion recognition problems. C1 [Oerlemans, Anoek M.; de Ruiter, Saskia W.; Rommelse, Nanda N. J.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Oerlemans, Anoek M.; van der Meer, Jolanda M. J.; van Steijn, Daphne J.; de Ruiter, Saskia W.; de Bruijn, Yvette G. E.; Buitelaar, Jan K.; Rommelse, Nanda N. J.] Univ Ctr, NL-6525 GC Nijmegen, Netherlands. [van der Meer, Jolanda M. J.; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [de Sonneville, Leo M. J.] Leiden Univ, Leiden Inst Brain & Cognit, Dept Clin Child & Adolescent Studies, Leiden, Netherlands. RP Oerlemans, AM (reprint author), Univ Ctr, Reinier Postlaan 12, NL-6525 GC Nijmegen, Netherlands. EM am.oerlemans@psy.umcn.nl FU Netherlands Organisation for Scientific Research (NWO) [91610024] FX This study was partly funded by a grant assigned to Dr. Rommelse by The Netherlands Organisation for Scientific Research (NWO grant # 91610024). The authors would like to thank all the parents, teachers, and children who kindly participated. 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To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication. C1 [Wentz, Elisabet; Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, SE-41119 Gothenburg, Sweden. [Vujic, Mihailo; Karrstedt, Ewa-Lotta; Erlandsson, Anna] Sahlgrens Univ Hosp, Dept Clin Genet, Gothenburg, Sweden. [Gillberg, Christopher] Univ Glasgow, Yorkhill Hosp, Dept Child & Adolescent Psychiat, Glasgow, Lanark, Scotland. [Gillberg, Christopher] UCL, Inst Child Hlth, London, England. RP Wentz, E (reprint author), Univ Gothenburg, Gillberg Neuropsychiat Ctr, Kungsgatan 12, SE-41119 Gothenburg, Sweden. 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Child Adolesc. Psych. PD MAY PY 2014 VL 23 IS 5 BP 329 EP 336 DI 10.1007/s00787-013-0455-1 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AH2MU UT WOS:000335956400009 PM 23974867 ER PT J AU Palmqvist, M Edman, G Bolte, S AF Palmqvist, Margita Edman, Gunnar Bolte, Sven TI Screening for substance use disorders in neurodevelopmental disorders: a clinical routine? SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Psychiatry; Assessment; Toxicology; Questionnaire; Best practice; Guidelines; Autism; ADHD; Asperger syndrome; Drugs ID AUTISM SPECTRUM DISORDERS; PREVALENCE; CHILDREN; COHORT; ADHD AB Evidence suggests that substance use disorders (SUD) tend to be underdiagnosed in psychiatry. The objective of this study was to investigate whether drug and alcohol screening is a clinical routine in the assessment of two prominent neurodevelopmental disorders, namely ADHD and autism spectrum disorder (ASD). We surveyed drug and alcohol screening routines in 34 general child and adolescent (only practice for adolescents, not children, was assessed) and 29 adult psychiatric outpatient departments in Stockholm County, Sweden. Structured telephone interviews mapping SUD screening procedures were conducted with department representatives in charge. Only a minority of child and adolescent departments regularly used SUD screening questionnaires (6 %) in ADHD and ASD assessment, while this was more common in adult psychiatry (55 %). Urine/blood-based toxicology tests were always used in 28 % and sometimes or in case of clinical suspicion in 38 % of the adult units. Such tests were used sometimes or in case of clinical suspicion in 15 % of the child psychiatric departments, but never routinely. Findings reveal that screening for SUD in ADHD and ASD is not an integral part of routine clinical assessments in psychiatry, although increasingly an integral part of many clinical guidelines. Thus, SUD might be underdiagnosed in neurodevelopmental disorders, which could be particularly true for child and adolescent psychiatry settings. C1 [Palmqvist, Margita; Edman, Gunnar] Tiohundra AB, Dept Psychiat, Neuropsychiat Unit, Norrtalje, Sweden. [Bolte, Sven] Karolinska Inst, CAP Res Ctr, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth,Neuropsychiat Unit, S-11330 Stockholm, Sweden. [Bolte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. RP Bolte, S (reprint author), Karolinska Inst, CAP Res Ctr, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth,Neuropsychiat Unit, Gavlegatan 22, S-11330 Stockholm, Sweden. EM sven.bolte@ki.se FU Swedish Research Council [523-2009-7054] FX We sincerely thank all clinical units in Stockholm County which participated in this study. Sven Bolte was supported by the Swedish Research Council (Grant nr. 523-2009-7054). 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Child Adolesc. Psych. PD MAY PY 2014 VL 23 IS 5 BP 365 EP 368 DI 10.1007/s00787-013-0459-x PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AH2MU UT WOS:000335956400013 PM 23949101 ER PT J AU Wang, XS Peng, CZ Cai, WJ Xia, J Jin, DZ Dai, YQ Luo, XG Klyachko, VA Deng, PY AF Wang, Xiao-Sheng Peng, Chun-Zi Cai, Wei-Jun Xia, Jian Jin, Daozhong Dai, Yuqiao Luo, Xue-Gang Klyachko, Vitaly A. Deng, Pan-Yue TI Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE excitatory postsynaptic current; release probability; short-term plasticity; mouse; hippocampus; fragile X syndrome ID SHORT-TERM PLASTICITY; SYNAPTIC INFORMATION-TRANSMISSION; RAT ENTORHINAL CORTEX; FMR1 KNOCKOUT MICE; MOUSE MODEL; GLUTAMATE RELEASE; SOMATOSENSORY CORTEX; PRESYNAPTIC FMR1; NMDA RECEPTORS; IN-VITRO AB Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak-scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS. C1 [Wang, Xiao-Sheng; Cai, Wei-Jun; Luo, Xue-Gang; Deng, Pan-Yue] Cent S Univ, Dept Histol & Embryol, Dept Anat & Neurobiol, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China. [Peng, Chun-Zi] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Xia, Jian] Cent S Univ, Inst Neurol, Xiangya Hosp, Changsha 410013, Hunan, Peoples R China. [Jin, Daozhong] Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. [Dai, Yuqiao] Univ Missouri, Sch Pharm, Div Pharmacol & Toxicol, Kansas City, MO 64110 USA. [Klyachko, Vitaly A.; Deng, Pan-Yue] Washington Univ, Sch Med, Dept Cell Biol & Physiol, Dept Biomed Engn, St Louis, MO 63110 USA. RP Deng, PY (reprint author), Cent S Univ, Dept Histol & Embryol, Dept Anat & Neurobiol, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China. EM klyachko@wustl.edu; pydeng@yahoo.com FU Shenghua Scholar Program of Central South University; National Natural Science Foundation of China [81370248, 81271299]; NINDS [R01 NS081972]; FRAXA Foundation; McDonnell Center for Systems Neuroscience, USA FX This work was partly supported by the Shenghua Scholar Program of Central South University and grants from the National Natural Science Foundation of China (81370248 and 81271299), NINDS R01 NS081972, FRAXA Foundation, and McDonnell Center for Systems Neuroscience, USA. 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J. Neurosci. PD MAY PY 2014 VL 39 IS 10 BP 1602 EP 1612 DI 10.1111/ejn.12546 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AH2JO UT WOS:000335947500005 PM 24646437 ER PT J AU Sparks, SE Wassif, CA Goodwin, H Conley, SK Lanham, DC Kratz, LE Hyland, K Gropman, A Tierney, E Porter, FD AF Sparks, S. E. Wassif, C. A. Goodwin, H. Conley, S. K. Lanham, D. C. Kratz, L. E. Hyland, K. Gropman, A. Tierney, E. Porter, F. D. TI Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID HUMAN SEROTONIN(1A) RECEPTOR; CEREBROSPINAL-FLUID; CHOLESTEROL-BIOSYNTHESIS; LIGAND-BINDING; OPTIZ-SYNDROME; MOUSE MODEL; 7-DEHYDROCHOLESTEROL; BEHAVIOR; AUTISM; METABOLITES AB Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3 beta-hydroxysterol Delta(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials. C1 [Sparks, S. E.] Carolinas Med Ctr, Dept Pediat, Charlotte, NC 28203 USA. [Wassif, C. A.; Goodwin, H.; Conley, S. K.; Porter, F. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Lanham, D. C.; Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Kratz, L. E.] Kennedy Krieger Inst, Biochem Genet Lab, Baltimore, MD USA. [Hyland, K.] Med Neurogenet, Atlanta, GA USA. [Gropman, A.] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. RP Porter, FD (reprint author), 10 CRC,Rm 5-2571,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov FU National Institute of Child Health and Human Development; Office of Rare Diseases; NIH Clinical Center; National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) [UL1 TR 000424-06]; NIH Roadmap for Medical Research FX This work was supported by the intramural program of the National Institute of Child Health and Human Development and a Bench-to-Bedside award from the Office of Rare Diseases and the NIH Clinical Center. Autism Speaks, the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 000424-06 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. We would like to thank Richard Kelly for critical review of this manuscript. We would like to express our appreciation to the patients and families that participated in this study. 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Inherit. Metab. Dis. PD MAY PY 2014 VL 37 IS 3 BP 415 EP 420 DI 10.1007/s10545-013-9672-5 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA AG9NH UT WOS:000335745700011 PM 24500076 ER PT J AU Ben-Sasson, A Habib, S Tirosh, E AF Ben-Sasson, Ayelet Habib, Sonia Tirosh, Emanuel TI Feasibility and Validity of Early Screening for Identifying Infants With Poor Social-Communication Development in a Well-Baby Clinic System SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Article DE Autism; ASD; Social development; Community screening; Infants; Feasibility; Validity ID AUTISM SPECTRUM DISORDERS; EARLY IDENTIFICATION; PRETERM INFANTS; PRIMARY-CARE; CHILDREN; AGE; PREVALENCE; INSTRUMENT; TODDLERS; RISK AB Objective: This study examined the feasibility and validity of implementing an autism spectrum disorders (ASD) screening for 12-month-old infants. Method: Parents of 583 infants, 12 months of age attending well baby clinics (WBCs), completed the First Year Inventory-Lite (FYI-L). Ten infants who failed the FYI-L and a subset of 12 infants who passed the identified FYI-L were evaluated using the Autism Observation Scale for Infants (AOSI) and the Mullen Scales of Early Learning. Information regarding social-communication development >= 24 months of age was extracted from medical records of 153 of the 583 infants. Results: Mean response rate across clinics was 26.63%. Infants at risk compared to controls showed significantly higher scores on the AOSI, lower composite scores on the MSEL, and a higher rate of referral for a developmental evaluation. At 24 months, 95% of infants who were negatively screened had no social-communication problems on their medical records; 60% of those who were screened positive had documented problems on medical records. Conclusion: ASD screening using the FYI-L at 12 months in a healthcare setting identifies infants with poor social-communication development, yet parents had low compliance with screening. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ben-Sasson, Ayelet] Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-31999 Haifa, Israel. [Habib, Sonia] Minist Hlth, Haifa, Israel. [Tirosh, Emanuel] Technion Israel Inst Technol, Bnai Zion Med Ctr, Hannah Khousy Child Dev Ctr, Haifa, Israel. [Tirosh, Emanuel] Technion Israel Inst Technol, Rappoport Fac Med, Haifa, Israel. RP Ben-Sasson, A (reprint author), Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-31999 Haifa, Israel. EM asasson@univ.haifa.ac.il FU Israeli Ministry of Health; European International Reintegration Grant (IRG) [203715] FX This work was supported by a feasibility grant from the Israeli Ministry of Health and a European International Reintegration Grant (IRG: No. 203715). We are grateful to Profs. Grace Baranek, Alice Carter, David Oppenheim, Nurit Yirmiya, and Lonnie Zwaigenbaum for their insightful feedback regarding the design of this study. CR Al- Qabandi M., 2011, PEDIATRICS, V128, P1098 Arain M, 2010, BMC MED RES METHODOL, V10, P1 Baird G, 2000, J AM ACAD CHILD PSY, V39, P694, DOI 10.1097/00004583-200006000-00007 Baranek G. T., 2009, 1 YEAR INVENTO UNPUB Baranek GT, 2003, 1 YEAR INVENTORY FYI Barbaro J, 2011, J PEDIATR NURS, V26, P334, DOI 10.1016/j.pedn.2010.04.007 Ben-Sasson A, 2013, RES AUTISM SPECT DIS, V7, P879, DOI 10.1016/j.rasd.2013.03.006 Ben-Sasson A, 2012, J AUTISM DEV DISORD, V42, P1906, DOI 10.1007/s10803-011-1436-1 Bryson S. 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M., 2012, AUTISM, V17, P527 Veness C, 2012, AUTISM, V16, P163, DOI 10.1177/1362361311399936 Webb P. L., 2011, JNP-J NURSE PRACT, V7, P229, DOI 10.1016/j.nurpra.2010.07.008 Wetherby AM, 2008, AUTISM, V12, P487, DOI 10.1177/1362361308094501 Zwaigenbaum L, 2005, INT J DEV NEUROSCI, V23, P143, DOI 10.1016/j.ijdevneu.2004.05.001 NR 34 TC 1 Z9 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0882-5963 J9 J PEDIATR NURS JI J. Pediatr. Nurs. PD MAY-JUN PY 2014 VL 29 IS 3 BP 238 EP 247 DI 10.1016/j.pedn.2013.11.001 PG 10 WC Nursing; Pediatrics SC Nursing; Pediatrics GA AG9JF UT WOS:000335734700009 PM 24333238 ER PT J AU Vulto-van Silfhout, AT Rajamanickam, S Jensik, PJ Vergult, S de Rocker, N Newhall, KJ Raghavan, R Reardon, SN Jarrett, K McIntyre, T Bulinski, J Ownby, SL Huggenvik, JI McKnight, GS Rose, GM Cai, X Willaert, A Zweier, C Endele, S De Ligt, J Van Bon, BWM Lugtenberg, D de Vries, PF Veltman, JA van Bokhoven, H Brunner, HG Rauch, A De Brouwer, APM Carvill, GL Hoischen, A Mefford, HC Eichler, EE Vissers, LELM Menten, B Collard, MW de Vries, BBA AF Vulto-van Silfhout, Anneke T. Rajamanickam, Shivakumar Jensik, Philip J. Vergult, Sarah de Rocker, Nina Newhall, Kathryn J. Raghavan, Ramya Reardon, Sara N. Jarrett, Kelsey McIntyre, Tara Bulinski, Joseph Ownby, Stacy L. Huggenvik, Jodi I. McKnight, G. Stanley Rose, Gregory M. Cai, Xiang Willaert, Andy Zweier, Christiane Endele, Sabine de Ligt, Joep van Bon, Bregje W. M. Lugtenberg, Dorien de Vries, Petra F. Veltman, Joris A. van Bokhoven, Hans Brunner, Han G. Rauch, Anita de Brouwer, Arjan P. M. Carvill, Gemma L. Hoischen, Alexander Mefford, Heather C. Eichler, Evan E. Vissers, Lisenka E. L. M. Menten, Bjorn Collard, Michael W. de Vries, Bert B. A. TI Mutations Affecting the SAND Domain of DEAF1 Cause Intellectual Disability with Severe Speech Impairment and Behavioral Problems SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DE-NOVO MUTATIONS; CELL-CYCLE ENTRY; FACTOR-I DEAF-1; RECEPTOR GENE; PROTEIN; EXPRESSION; DISEASE; AUTISM; NUDR; TRANSCRIPTION AB Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. C1 [Vulto-van Silfhout, Anneke T.; de Ligt, Joep; van Bon, Bregje W. M.; Lugtenberg, Dorien; de Vries, Petra F.; Veltman, Joris A.; van Bokhoven, Hans; Brunner, Han G.; de Brouwer, Arjan P. M.; Hoischen, Alexander; Vissers, Lisenka E. L. M.; de Vries, Bert B. A.] Radford Univ, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Rajamanickam, Shivakumar; Jensik, Philip J.; Raghavan, Ramya; Reardon, Sara N.; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L.; Huggenvik, Jodi I.; Rose, Gregory M.; Cai, Xiang; Collard, Michael W.] So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. [Rajamanickam, Shivakumar; Jensik, Philip J.; Raghavan, Ramya; Reardon, Sara N.; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L.; Huggenvik, Jodi I.; Rose, Gregory M.; Cai, Xiang; Collard, Michael W.] So Illinois Univ, Sch Med, Ctr Integrated Res Cognit & Neural Sci, Carbondale, IL 62901 USA. [Vergult, Sarah; de Rocker, Nina; Willaert, Andy; Menten, Bjorn] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Newhall, Kathryn J.; McKnight, G. Stanley] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Rose, Gregory M.] So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. [Zweier, Christiane; Endele, Sabine] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany. [van Bokhoven, Hans; de Brouwer, Arjan P. M.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands. [Rauch, Anita] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland. [Rauch, Anita] Univ Zurich, Neurosci Ctr Zurich, CH-8603 Schwerzenbach, Switzerland. [Rauch, Anita] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8603 Schwerzenbach, Switzerland. [Carvill, Gemma L.; Mefford, Heather C.] Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98195 USA. [Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA. RP de Vries, BBA (reprint author), Radford Univ, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. EM bert.devries@radboudumc.nl RI Rauch, Anita/C-5568-2014; Brunner, Han/C-9928-2013; Vissers, Lisenka/A-2598-2015; Veltman, Joris/F-5128-2010; Zweier, Christiane/F-2202-2015 OI Rauch, Anita/0000-0003-2930-3163; FU European Commission GENCODYS [241995]; Netherlands Organisation for Health Research and Development [917-86-319, 912-12-109, 916-12-095]; NIH [CA89438, CA137556, HD060122]; Southern Illinois University School of Medicine; Fraternal Order of Eagles in Carbondale FX We are grateful to the individuals involved and their parents for their participation. We would like to thank Hanka Venselaar for the in silico modeling of the DEAF1 mutations. This work was supported by European Commission GENCODYS grant 241995 under the Seventh Framework Programme (to A.T.V.v.S. and B.B.A.d.V.), Netherlands Organisation for Health Research and Development grants 917-86-319 (to B.B.A.d.V.), 912-12-109 (to B.B.A.d.V. and J.A.V.), and 916-12-095 (to A.H.), NIH grants CA89438, CA137556, and HD060122 (to J.I.H. and M.W.C.), funds from the Southern Illinois University School of Medicine (to J.I.H. and M.W.C.), and funds from the Fraternal Order of Eagles in Carbondale (to J.I.H. and M.W.C.). 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PD MAY 1 PY 2014 VL 94 IS 5 BP 649 EP 661 DI 10.1016/j.ajhg.2014.03.013 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AG5VB UT WOS:000335485700001 PM 24726472 ER PT J AU Pinto, D Delaby, E Merico, D Barbosa, M Merikangas, A Klei, L Thiruvahindrapuram, B Xu, X Ziman, R Wang, ZZ Vorstman, JAS Thompson, A Regan, R Pilorge, M Pellecchia, G Pagnamenta, AT Oliveira, B Marshall, CR Magalhaes, TR Lowe, JK Howe, JL Griswold, AJ Gilbert, J Duketis, E Dombroski, BA De Jonge, MV Cuccaro, M Crawford, EL Correia, CT Conroy, J Conceicao, IC Chiocchetti, AG Casey, JP Cai, G Cabrol, C Bolshakova, N Bacchelli, E Anney, R Gallinger, S Cotterchio, M Casey, G Zwaigenbaum, L Wittemeyer, K Wing, K Wallace, S van Engeland, H Tryfon, A Thomson, S Soorya, L Roge, B Roberts, W Poustka, F Mouga, S Minshew, N McInnes, LA McGrew, SG Lord, C Leboyer, M Le Couteur, AS Kolevzon, A Gonzalez, PJ Jacob, S Holt, R Guter, S Green, J Green, A Gillberg, C Fernandez, BA Duque, F Delorme, R Dawson, G Chaste, P Cafe, C Brennan, S Bourgeron, T Bolton, PF Bolte, S Bernier, R Baird, G Bailey, AJ Anagnostou, E Almeida, J Wijsman, EM Vieland, VJ Vicente, AM Schellenberg, GD Pericak-Vance, M Paterson, AD Parr, JR Oliveira, G Nurnberger, JI Monaco, AP Maestrini, E Klauck, SM Hakonarson, H Haines, JL Geschwind, DH Freitag, CM Folstein, SE Ennis, S Coon, H Battaglia, A Szatmari, P Sutcliffe, JS Hallmayer, J Gill, M Cook, EH Buxbaum, JD Devlin, B Gallagher, L Betancur, C Scherer, SW AF Pinto, Dalila Delaby, Elsa Merico, Daniele Barbosa, Mafalda Merikangas, Alison Klei, Lambertus Thiruvahindrapuram, Bhooma Xu, Xiao Ziman, Robert Wang, Zhuozhi Vorstman, Jacob A. S. Thompson, Ann Regan, Regina Pilorge, Marion Pellecchia, Giovanna Pagnamenta, Alistair T. Oliveira, Barbara Marshall, Christian R. Magalhaes, Tiago R. Lowe, Jennifer K. Howe, Jennifer L. Griswold, Anthony J. Gilbert, John Duketis, Eftichia Dombroski, Beth A. De Jonge, Maretha V. Cuccaro, Michael Crawford, Emily L. Correia, Catarina T. Conroy, Judith Conceicao, Ines C. Chiocchetti, Andreas G. Casey, Jillian P. Cai, Guiqing Cabrol, Christelle Bolshakova, Nadia Bacchelli, Elena Anney, Richard Gallinger, Steven Cotterchio, Michelle Casey, Graham Zwaigenbaum, Lonnie Wittemeyer, Kerstin Wing, Kirsty Wallace, Simon van Engeland, Herman Tryfon, Ana Thomson, Susanne Soorya, Latha Roge, Bernadette Roberts, Wendy Poustka, Fritz Mouga, Susana Minshew, Nancy McInnes, L. Alison McGrew, Susan G. Lord, Catherine Leboyer, Marion Le Couteur, Ann S. Kolevzon, Alexander Gonzalez, Patricia Jimenez Jacob, Suma Holt, Richard Guter, Stephen Green, Jonathan Green, Andrew Gillberg, Christopher Fernandez, Bridget A. Duque, Frederico Delorme, Richard Dawson, Geraldine Chaste, Pauline Cafe, Catia Brennan, Sean Bourgeron, Thomas Bolton, Patrick F. Boelte, Sven Bernier, Raphael Baird, Gillian Bailey, Anthony J. Anagnostou, Evdokia Almeida, Joana Wijsman, Ellen M. Vieland, Veronica J. Vicente, Astrid M. Schellenberg, Gerard D. Pericak-Vance, Margaret Paterson, Andrew D. Parr, Jeremy R. Oliveira, Guiomar Nurnberger, John I. Monaco, Anthony P. Maestrini, Elena Klauck, Sabine M. Hakonarson, Hakon Haines, Jonathan L. Geschwind, Daniel H. Freitag, Christine M. Folstein, Susan E. Ennis, Sean Coon, Hilary Battaglia, Agatino Szatmari, Peter Sutcliffe, James S. Hallmayer, Joachim Gill, Michael Cook, Edwin H. Buxbaum, Joseph D. Devlin, Bernie Gallagher, Louise Betancur, Catalina Scherer, Stephen W. TI Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIANTS; GENOME-WIDE ASSOCIATION; FRAGILE-X-SYNDROME; INTELLECTUAL DISABILITY; STRUCTURAL VARIATION; PHENOTYPE ONTOLOGY; DELETIONS; DUPLICATIONS; RISK AB Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 x 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 x 10(-15), similar to 3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation. C1 [Pinto, Dalila; Barbosa, Mafalda; Cai, Guiqing; Tryfon, Ana; Soorya, Latha; McInnes, L. Alison; Kolevzon, Alexander; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Pinto, Dalila; Barbosa, Mafalda; Xu, Xiao; Cai, Guiqing; Tryfon, Ana; Soorya, Latha; McInnes, L. Alison; Kolevzon, Alexander; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Pinto, Dalila; Barbosa, Mafalda; Cai, Guiqing; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Pinto, Dalila; Barbosa, Mafalda; Xu, Xiao; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Pinto, Dalila; Xu, Xiao] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Pinto, Dalila; Kolevzon, Alexander; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Delaby, Elsa; Pilorge, Marion; Cabrol, Christelle; Betancur, Catalina] Inst Natl Sante & Rech Med U1130, F-75005 Paris, France. [Delaby, Elsa; Pilorge, Marion; Cabrol, Christelle; Betancur, Catalina] CNRS, UMR 8246, F-75005 Paris, France. [Delaby, Elsa; Pilorge, Marion; Cabrol, Christelle; Betancur, Catalina] Univ Paris 04, Univ Paris 06, Neurosci Paris Seine, F-75005 Paris, France. [Merico, Daniele; Thiruvahindrapuram, Bhooma; Ziman, Robert; Wang, Zhuozhi; Pellecchia, Giovanna; Marshall, Christian R.; Howe, Jennifer L.; Paterson, Andrew D.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Gen, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada. [Merikangas, Alison; Bolshakova, Nadia; Anney, Richard; Brennan, Sean; Gill, Michael; Gallagher, Louise] Univ Dublin Trinity Coll, Sch Med, Discipline Psychiat, Dublin 8, Ireland. [Klei, Lambertus; Minshew, Nancy; Chaste, Pauline; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Vorstman, Jacob A. S.; De Jonge, Maretha V.; van Engeland, Herman] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CX Utrecht, Netherlands. [Thompson, Ann; Szatmari, Peter] McMaster Univ, Offord Ctr Child Studies, Dept Psychiat & Behav Neurosci, Hamilton, ON L8S 4K1, Canada. [Regan, Regina; Magalhaes, Tiago R.; Casey, Jillian P.] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin 12, Ireland. [Regan, Regina; Magalhaes, Tiago R.; Conroy, Judith; Casey, Jillian P.; Green, Andrew; Ennis, Sean] Univ Coll Dublin, Sch Med & Med Sci, Acad Ctr Rare Dis, Dublin 4, Ireland. [Pagnamenta, Alistair T.; Wing, Kirsty; Holt, Richard; Monaco, Anthony P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Oliveira, Barbara; Correia, Catarina T.; Conceicao, Ines C.; Vicente, Astrid M.] Inst Nacl Saude Doutor Ricardo Jorge, P-1649016 Lisbon, Portugal. [Oliveira, Barbara; Correia, Catarina T.; Conceicao, Ines C.; Vicente, Astrid M.] Univ Lisbon, Fac Sci, Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal. [Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Semel Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Griswold, Anthony J.; Gilbert, John; Cuccaro, Michael; Pericak-Vance, Margaret] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Griswold, Anthony J.; Gilbert, John; Cuccaro, Michael; Pericak-Vance, Margaret] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miller Sch Med, Miami, FL 33136 USA. [Duketis, Eftichia; Chiocchetti, Andreas G.; Poustka, Fritz; Freitag, Christine M.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Dombroski, Beth A.; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Crawford, Emily L.; Thomson, Susanne; Haines, Jonathan L.; Sutcliffe, James S.] Vanderbilt Univ, Ctr Human Genet Res, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Crawford, Emily L.; Thomson, Susanne; Haines, Jonathan L.; Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Conroy, Judith] Childrens Univ Hosp Temple St, Dublin 1, Ireland. [Bacchelli, Elena; Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON M5G 2L7, Canada. [Casey, Graham] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB T6B 2H3, Canada. [Wittemeyer, Kerstin] Univ Birmingham, Sch Educ, Birmingham B15 2TT, W Midlands, England. [Wallace, Simon; Bailey, Anthony J.] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England. [Wallace, Simon; Bailey, Anthony J.] Warneford Hosp, Oxford OX3 7JX, England. [Roge, Bernadette] Univ Toulouse 2, Unite Rech Interdisciplinaire Octogone, Ctr Etud & Rech Psychopathol, F-31058 Toulouse, France. [Roberts, Wendy] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada. [Mouga, Susana; Duque, Frederico; Cafe, Catia; Almeida, Joana; Oliveira, Guiomar] Ctr Hosp Coimbra, Pediat Hosp, Unidade Neurodesenvolvimento & Autismo Serv, Ctr Desenvolvimento Crianca, P-3000602 Coimbra, Portugal. [Mouga, Susana; Duque, Frederico; Cafe, Catia; Almeida, Joana; Oliveira, Guiomar] Ctr Hosp Coimbra, Ctr Invest & Formacao Clin, Pediat Hosp, P-3000602 Coimbra, Portugal. [Mouga, Susana; Duque, Frederico; Cafe, Catia; Almeida, Joana; Oliveira, Guiomar] Univ Coimbra, P-3000602 Coimbra, Portugal. [Mouga, Susana; Duque, Frederico; Cafe, Catia; Almeida, Joana; Oliveira, Guiomar] Univ Coimbra, P-3000354 Coimbra, Portugal. [Mouga, Susana; Duque, Frederico; Oliveira, Guiomar] Univ Coimbra, Univ Clin Pediat, P-3000354 Coimbra, Portugal. [Mouga, Susana; Duque, Frederico; Oliveira, Guiomar] Univ Coimbra, Inst Biomed Imaging & Life Sci, Fac Med, P-3000354 Coimbra, Portugal. [McGrew, Susan G.] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. [Lord, Catherine] NewYorkPresbyterian Weill Cornell Med Ctr, New York, NY 10065 USA. [Leboyer, Marion; Delorme, Richard; Chaste, Pauline; Bourgeron, Thomas] FondaMental Fdn, F-94010 Creteil, France. [Leboyer, Marion] Inst Natl Sante & Rech U955, F-94010 Creteil, France. [Leboyer, Marion] Univ Paris Est, Fac Med, F-94010 Creteil, France. [Leboyer, Marion] Henri Mondor Albert Chenevier Hosp, AP HP, Dept Psychiat, F-94010 Creteil, France. [Le Couteur, Ann S.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Gonzalez, Patricia Jimenez] Hosp Nacl Ninos Dr Carlos Saenz Herrera, Child Dev & Behav Unit, Caja Costarricense Seguro Social, San Jose, Costa Rica. [Jacob, Suma; Guter, Stephen; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. [Jacob, Suma] Univ Minnesota, Inst Translat Neurosci, Minneapolis, MN 55455 USA. [Jacob, Suma] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Green, Jonathan] Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester M13 9PL, Lancs, England. [Green, Jonathan] Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, England. [Green, Andrew; Ennis, Sean] Our Ladys Childrens Hosp, Natl Ctr Med Genet, Dublin 12, Ireland. [Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, S-41119 Gothenburg, Sweden. [Fernandez, Bridget A.] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada. [Delorme, Richard; Bourgeron, Thomas] Inst Pasteur, Human Genet & Cognit Funct Unit, F-75015 Paris, France. [Delorme, Richard; Bourgeron, Thomas] Inst Pasteur, CNRS, URA Genes Synapses & Cognit 2182, F-75015 Paris, France. [Delorme, Richard] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. [Dawson, Geraldine] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Bourgeron, Thomas] Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France. [Bolton, Patrick F.] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Bolton, Patrick F.] South London & Maudsley Biomed Res Ctr Mental Hlt, London SES 8AF, England. [Boelte, Sven] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baird, Gillian] Kings Coll London, Kings Hlth Partners, London WC2R 2L5, England. [Anagnostou, Evdokia] Univ Toronto, Bloorview Res Inst, Toronto, ON M4G 1R8, Canada. [Wijsman, Ellen M.] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Vieland, Veronica J.] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH 43205 USA. [Paterson, Andrew D.] Dalla Lana Sch Publ Hlth, Toronto, ON MST 3M7, Canada. [Parr, Jeremy R.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Nurnberger, John I.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. [Nurnberger, John I.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Nurnberger, John I.] Indiana Univ Sch Med, Program Med Neurosci, Indianapolis, IN 46202 USA. [Monaco, Anthony P.] Tufts Univ, Off President, Medford, MA 02155 USA. [Klauck, Sabine M.] Deutsch Krebsforschungszentrum, German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Folstein, Susan E.] Univ Miami, Dept Psychiat, Miller Sch Med, Div Child & Adolescent Psychiat, Miami, FL 33136 USA. [Coon, Hilary] Univ Utah, Sch Med, Dept Psychiat, Utah Autism Res Program, Salt Lake City, UT 84108 USA. [Battaglia, Agatino] Stella Maris Clin Res Inst Child & Adolescent Neu, I-56128 Pisa, Italy. [Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Betancur, C (reprint author), Inst Natl Sante & Rech Med U1130, F-75005 Paris, France. EM catalina.betancur@inserm.fr; stephen.scherer@sickkids.ca RI Gallinger, Steven/E-4575-2013; Scherer, Stephen /B-3785-2013; Duque, Frederico/H-3692-2014; Bailey, Anthony/J-2860-2014; Jacob, Suma/J-7941-2013; Bolton, Patrick/E-8501-2010; Monaco, Anthony/A-4495-2010; Sutcliffe, James/C-1348-2012 OI Scherer, Stephen /0000-0002-8326-1999; Duque, Frederico/0000-0001-5684-1472; Bailey, Anthony/0000-0003-4257-972X; Jacob, Suma/0000-0001-7434-7398; Bolton, Patrick/0000-0002-5270-6262; Monaco, Anthony/0000-0001-7480-3197; Sutcliffe, James/0000-0001-5200-6007 FU Autism Speaks (USA); Health Research Board (Ireland) [AUT/2006/1, AUT/2006/2, PD/2006/48]; Medical Research Council (UK); Hilibrand Foundation (USA); Genome Canada; Canadian Institutes of Health Research (CIHR); Brain & Behavior Research Foundation; Ontario Genomics Institute FX The authors thank the main funders of the Autism Genome Project: Autism Speaks (USA), the Health Research Board (Ireland; AUT/2006/1, AUT/2006/2, PD/2006/48), the Medical Research Council (UK), the Hilibrand Foundation (USA), Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR). Additional support for individual groups is shown in the Supplemental Acknowledgments. D.P. is the Abraham & Mildred Goldstein Seaver Center Faculty Fellow, J.D.B. holds the G. Harold and Leila Y. Mathers Professorship, C.B. is the recipient of a NARSAD Independent Investigator Grant from the Brain & Behavior Research Foundation, and S.W.S. holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. E.H.C. is an advisor of Seaside Therapeutics, G.D. is a member of the Scientific Advisory Board at Integragen Inc., and S.W.S. is an advisor to Population Diagnostics and advisor and founder of YouNique Genomics. D.P., P.S J.S.S., J.H., M.G., E.H.C., J.D.B., B.D., L.G., C.B., and S.W.S were leading contributors to the design and analysis of this study, and D.P., E. Delaby, D.M., M.B., J.D.B., B.D., L.G., C.B., and S.W.S wrote the manuscript. 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PD MAY 1 PY 2014 VL 94 IS 5 BP 677 EP 694 DI 10.1016/j.ajhg.2014.03.018 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA AG5VB UT WOS:000335485700003 PM 24768552 ER PT J AU Sanz-Cortes, M Egana-Ugrinovic, G Zupan, R Figueras, F Gratacos, E AF Sanz-Cortes, Magdalena Egana-Ugrinovic, Gabriela Zupan, Rudolf Figueras, Francesc Gratacos, Eduard TI Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE brain stem; cerebellum; fetal MRI; intrauterine growth restriction (IUGR); small-for-gestational-age (SGA) ID INTRAUTERINE GROWTH-RESTRICTION; BEHAVIORAL-ASSESSMENT SCALE; AUTISM SPECTRUM DISORDER; PRETERM INFANTS; CHILDREN; BIRTH; HIPPOCAMPUS; SIZE; NEUROSONOGRAPHY; INTERVENTIONS AB OBJECTIVE: We tested the hypothesis whether small-for-gestational-age (SGA) fetuses have different brain stem and cerebellar morphometry when compared with appropriate-for-gestational-age (AGA) fetuses and whether the differences in these structures were associated with their neonatal neurobehavior. STUDY DESIGN: Magnetic resonance imaging was performed on 51 SGA fetuses and 47 AGA fetuses at 37 weeks' gestation. Pontine width, medullar width, vermian width and height, cerebellar primary fissure's depth, and cerebellar volume were measured and corrected by biparietal diameter and cerebellar volume by total intracranial volume. Ratios were compared between cases and control subjects. The association between morphometric differences and neuro-behavioral outcome in SGAs was tested. RESULTS: Brainstem and cerebellar ratios were significantly larger in SGA fetuses: pontine width, SGA 0.143 +/- 0.01 vs AGA 0.135 +/- 0.01 (P < .01); medullar width, SGA 0.088 +/- 0.01 vs AGA 0.083 +/- 0.01 (P = .03); vermian width, SGA 0.181 +/- 0.03 vs AGA 0.162 +/- 0.02 (P < .01); vermian height, SGA 0.235 +/- 0.03 vs AGA 0.222 +/- 0.01 (P < .01); cerebellar volume, SGA 0.042 +/- 0.01 vs AGA 0.038 +/- 0.00 (P = .04); with deeper cerebellar primary fissure in SGAs, SGA 0.041 +/- 0.01 vs AGA 0.035 +/- 0.01 (P = .01). Medullar, cerebellar biometries, and volumetry were significantly associated with different Neonatal Behavioral Assessment Scale cluster scores in SGA infants. CONCLUSION: Brain stem and cerebellar morphometric measurements are significantly different in term SGA fetuses, which are associated significantly with their neurobehavioral outcome. This finding supports the existence of brain microstructural changes in SGA fetuses and lays the basis for potential image biomarkers to detect fetuses who are at risk. C1 [Sanz-Cortes, Magdalena] Univ Barcelona, Hosp Clin, ICGON, Dept Maternal Fetal Med, Barcelona, Spain. Inst Invest Biomed August Pi I Sunyer IDIBAPS, Fetal & Perinatal Med Res Grp, Barcelona, Spain. Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain. RP Sanz-Cortes, M (reprint author), Univ Barcelona, Hosp Clin, ICGON, Dept Maternal Fetal Med, Barcelona, Spain. FU Cerebra Foundation for the Brain-Injured Child, Carmarthen, Wales, UK; Obra Social "La Caixa"; Fundacion Dexeus, Barcelona, Spain; Rio Hortega postdoctoral fellowship (Spain) [CM10/00222]; CONICYT [72120071] FX Supported by grants from the Cerebra Foundation for the Brain-Injured Child, Carmarthen, Wales, UK, and Obra Social "La Caixa" and Fundacion Dexeus, Barcelona, Spain; a Rio Hortega postdoctoral fellowship (Spain; CM10/00222; M. S.-C.); and grant no. 72120071 from CONICYT (Chile; PFCHA/Doctorado al Extranjero 4a Convocatoria; G.E.-U.). 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Mutations of these exchangers cause autism-spectrum disorders and neurodegeneration. NHE6, NHE7, and NHE9 are hypothesized to exchange cytosolic K+ for H+ and alkalinize vesicles, but this notion has remained untested in K+ because their intracellular localization prevents functional measurements. Using protonkilling techniques, we selected a cell line that expresses wild-type NHE7 at the plasma membrane, enabling measurement of the exchanger's transport parameters. We found that NHE7 transports Li+ and Na+, but not K+, is nonreversible in physiological conditions and is constitutively activated by cytosolic H+. Therefore, NHE7 acts as a proton-loading transporter rather than a proton leak. NHE7 mediates an acidification of intracellular vesicles that is additive to that of V-ATPases and that accelerates endocytosis. This study reveals an unexpected function for vesicular Na+/H+ exchangers and provides clues for understanding NHE-linked neurological disorders. C1 [Milosavljevic, Nina; Monet, Michael; Lena, Isabelle; Counillon, Laurent; Poet, Mallorie] Univ Nice Sophia Antipolis, LP2M, CNRS UMR 7370, Fac Med, F-06107 Nice, France. [Brau, Frederic; Feliciangeli, Sylvain] Univ Nice Sophia Antipolis, IPMC, CNRS UMR 7275, F-06560 Valbonne, France. [Lacas-Gervais, Sandra] Univ Nice Sophia Antipolis, CCMA, Fac Sci, F-06108 Nice, France. RP Counillon, L (reprint author), Univ Nice Sophia Antipolis, LP2M, CNRS UMR 7370, Fac Med, 28 Ave Valombrose, F-06107 Nice, France. EM laurent.counillon@unice.fr FU University of Nice-Sophia Antipolis; ANR (JCJC SVSE1 NHEint); Basileus EMECW FX This work was supported by the University of Nice-Sophia Antipolis, the ANR (JCJC SVSE1 NHEint), and the CNRS. N.M. was funded by the Basileus EMECW project. We thank Drs. Jacques Barhanin (LP2M CNRS-UMR 7370), Bruno Antonny (IPMC, CNRS-UMR 7275), and Mireille Cormont (C3M INSERM-U 1065) for fruitful discussions, Dr. Ellen Van Obberghen-Schilling (IBV CNRS-UMR 7277) for critical reading of the manuscript, and Fabien Labbal (LP2M CNRS-UMR 7370) for assistance in cell culture. 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Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2(-/-) mice to investigate their phenotypes of synaptic function and social behaviors. Methods: The creation of Dlgap2(-/-) mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident-intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2(-/-) mice. Results: Dlgap2(-/-) mice displayed exacerbated aggressive behaviors in the resident-intruder task, and elevated social dominance in the tube test. In addition, Dlgap2(-/-) mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2(-/-) mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC. Conclusions: Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism. C1 [Jiang-Xie, Li-Feng; Liao, Hsiao-Mei; Chen, Chia-Hsiang; Gau, Susan Shur-Fen] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10002, Taiwan. [Jiang-Xie, Li-Feng; Chen, Yuh-Tarng; Lee, Li-Jen; Liou, Horng-Huei; Fu, Wen-Mei; Gau, Susan Shur-Fen] Natl Taiwan Univ, Grad Inst Brain & Mind Sci, Taipei, Taiwan. [Chen, Chia-Hsiang] Chang Gung Mem Hosp Linkou, Dept Psychiat, Taoyuan, Taiwan. [Chen, Chia-Hsiang] Chang Gung Univ, Dept & Grad Inst Biomed Sci, Taoyuan, Taiwan. [Ho, Shih-Yin; Lu, Dai-Hua; Liou, Horng-Huei; Fu, Wen-Mei] Natl Taiwan Univ, Coll Med, Sch Med, Dept Pharmacol, Taipei 10051, Taiwan. [Lee, Li-Jen] Natl Taiwan Univ, Coll Med, Dept Anat & Cell Biol, Taipei, Taiwan. RP Fu, WM (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan South Rd, Taipei 10002, Taiwan. EM wenmei@ntu.edu.tw; gaushufe@ntu.edu.tw FU National Science Council, Taiwan [NSC 97-3112-B-002-009, NSC 98-3112-B-002-004, NSC 99-3112-B-002-036, NSC 101-2314-B-002-136-MY3]; National Taiwan University Hospital [NTUH 100-S1525]; National Taiwan University (AIM for Top University Excellent Research Project) [10R81918-03101R892103, 102R892103] FX This work was supported by National Science Council, Taiwan (NSC 97-3112-B-002-009, NSC 98-3112-B-002-004, NSC 99-3112-B-002-036 and NSC 101-2314-B-002-136-MY3 to SSG), National Taiwan University Hospital (NTUH 100-S1525 to SSG) and National Taiwan University (AIM for Top University Excellent Research Project: 10R81918-03101R892103, 102R892103 to SSG). We thank the technical services provided by the Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, the National Science Council and the Gene Knockout Mouse Core Laboratory of the National Taiwan University Center of Genomic Medicine. We would like to express our thanks to Su-Mei Lai for assisting in creating ultrathin sections for the electron microscopy experiments. 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Rhodes, Gillian TI Face identity aftereffects increase monotonically with adaptor extremity over, but not beyond, the range of natural faces SO VISION RESEARCH LA English DT Article DE Face perception; Face identification; Face adaptation; Face aftereffects ID VISUAL REPRESENTATION; FACIAL IDENTITY; ADAPTATION; PERCEPTION; CHILDREN; SIZE; DISTINCTIVENESS; RECOGNITION; MECHANISMS; AUTISM AB Face identity aftereffects have been used to test theories of the neural coding underlying expert face recognition. Previous studies reported larger aftereffects for adaptors that are morphed further from the average face than for adaptors closer to the average, which appeared to support opponent coding along face-identity dimensions. However, only two levels were tested and it is not clear where they were located relative to the range of naturally occurring faces. This range is of interest given the functional need of the visual system both to produce good discrimination of real everyday faces and to process novel kinds of faces that we may encounter. Here, Experiment 1 establishes the boundary of faces judged as being able to occur in everyday life. Experiment 2 then shows that aftereffects increase with adaptor extremity up to this natural-range boundary, drop significantly immediately outside the boundary, and then remain stable with no drop towards zero even for highly distorted adaptors far beyond the boundary. Computational modelling shows that this unexpected pattern cannot be explained either by a simple opponent or by a classic multichannel model. However, its qualitative features can be captured either by a combination of opponent and multichannel coding (raising the possibility that not all identity-related face dimensions are opponent coded), or by a 3-pool model containing two S-shaped-response channels and a central bell-shaped channel around the average face (raising the possibility of unexpected similarities with coding of eye and head direction). (C) 2014 Elsevier Ltd. All rights reserved. C1 [McKone, Elinor] Australian Natl Univ, Res Sch Psychol, Canberra, ACT 0200, Australia. [Jeffery, Linda; Boeing, Alexandra; Rhodes, Gillian] Univ Western Australia, ARC Ctr Excellence Cognit & Its Disorders, Sch Psychol, Nedlands, WA 6009, Australia. [Clifford, Colin W. G.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. RP McKone, E (reprint author), Australian Natl Univ, Sch Psychol, GPO Box 4, Canberra, ACT 0200, Australia. EM elinor.mckone@anu.edu.au FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; ARC Professorial Fellowship [DP0877379]; ARC Queen Elizabeth II Fellowship [DP0984558]; Australian Research Council Future Fellowship [FT110100150] FX This research was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Professorial Fellowship to Rhodes (DP0877379), an ARC Queen Elizabeth II Fellowship to McKone (DP0984558), and Australian Research Council Future Fellowship to Clifford (FT110100150). We thank Eleni Avard and Stephen Pond for assistance with testing, Stephen Pond for preparing the figures and Mayu Nishimura and Daphne Maurer for co-creating the "Robbers Task". Ethical approval was granted by the Human Research Ethics Committee of the University of Western Australia. 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PD MAY PY 2014 VL 98 BP 1 EP 13 DI 10.1016/j.visres.2014.01.007 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AG7UJ UT WOS:000335624000001 PM 24582798 ER PT J AU Zuckerman, KE Sinche, B Mejia, A Cobian, M Becker, T Nicolaidis, C AF Zuckerman, Katharine E. Sinche, Brianna Mejia, Angie Cobian, Martiza Becker, Thomas Nicolaidis, Christina TI Latino Parents' Perspectives on Barriers to Autism Diagnosis SO ACADEMIC PEDIATRICS LA English DT Article DE autism spectrum disorder; delayed diagnosis; health services accessibility; Hispanic Americans; qualitative research ID SPECTRUM DISORDERS; ETHNIC DISPARITIES; EARLY INTERVENTION; HEALTH-CARE; SERVICE USE; CHILDREN; ACCESS; AGE; IDENTIFICATION; INFORMATION AB OBJECTIVE: Latino children are diagnosed with autism spectrum disorders (ASDs) at older ages and at the point of more severe symptoms. We sought to qualitatively describe community, family, and health care system barriers to ASD diagnosis in Latino children. METHODS: Five focus groups and 4 qualitative interviews were conducted with 33 parents of Latino children previously diagnosed with an ASD. Participants described Latino community perceptions of autism and barriers they experienced during the diagnostic process. Sessions were audiorecorded and transcribed. Transcripts were coded by 2 researchers, and data were analyzed using thematic, analysis. RESULTS: Parents reported low levels of ASD information and high levels of mental health and disability stigma in the Latino community. Parents had poor access to care as a result of poverty, limited English proficiency, and lack of empowerment to take advantage of services. Providers sometimes dismissed parents' concerns. The ASD diagnostic process itself was slow, inconvenient, confusing, and uncomfortable for the child. These factors led many parents to normalize their child's early behaviors, deny that a problem existed, and lose trust in the medical system. CONCLUSIONS: Additional educational outreach to Latino families, destigmatization of ASD, streamlining the ASD diagnostic process, and providing additional support to Latino parents of at-risk children may decrease delays in ASD diagnosis among Latino, children. C1 [Zuckerman, Katharine E.; Sinche, Brianna; Mejia, Angie; Cobian, Martiza] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Div Gen Pediat, Portland, OR 97239 USA. [Mejia, Angie] Syracuse Univ, Dept Sociol, Syracuse, NY USA. [Cobian, Martiza] Univ Pacific, Dept Psychol, Hillsboro, OR USA. [Becker, Thomas; Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Internal Med & Geriatr, Portland, OR 97239 USA. [Nicolaidis, Christina] Portland State Univ, Sch Social Work, Portland, OR 97207 USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, 707 SW Gaines Rd,Mail Code,CDRC P, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU National Institute of Mental Health [1K23MH095828]; Academic Pediatric Association/Commonwealth Fund Young Investigator Award FX The authors would like to acknowledge Drs Ellen Lipstein and Somnath Saha for their guidance regarding qualitative methods; Dr Christina Bethell for material support; Teresa Gomez and the OHSU Autism Clinic staff for help in recruitment; and Susie Larios and Erendira Valdivia for their helpful perspectives and assistance with data analysis. Funded by grant 1K23MH095828 from the National Institute of Mental Health (PI=Zuckerman); partially funded by an Academic Pediatric Association/Commonwealth Fund Young Investigator Award (PI=Zuckerman). 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Method: Sixteen medicated schizophrenia patients and 16 healthy comparison subjects performed an action imitation/observation task during functional MRI. Participants saw a video of a moving,hand or spatial cue and were instructed to either execute finger movements associated with the stimulus or simply observe. Activation in the mirror neuron system was measured during imitative versus nonimitative actions and observation of a moving hand versus a moving spatial cue. These contrasts were compared across groubs. Results: Activation in the mirror neuron system was less specific for imitation in schizophrenia. Relative to healthy subjects, patients had reduced activity in the posterior superior temporal sulcus during imitation and greater activity in the posterior superior temporal sulcus and inferior parietal lobe during nonimitative action. Patients also showed reduced activity in these regions during action observation. Mirror neuron system activation was related to symptom severity and social functioning in patients and to schizotypal syndrome in comparison subjects. Conclusions: Given the role of the inferior parietal lobe and posterior superior temporal sulcus in imitation and social cognition, impaired imitative ability in schizophrenia may stem from faulty perception of biological. motion and transformations from perception to action. These findings extend our understanding of social dysfunction in schizophrenia. C1 [Thakkar, Katharine N.; Peterman, Joel S.; Park, Sohee] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. RP Park, S (reprint author), Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. 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J. Psychiat. PD MAY PY 2014 VL 171 IS 5 BP 539 EP 548 DI 10.1176/appi.ajp.2013.13040498 PG 10 WC Psychiatry SC Psychiatry GA AG0SI UT WOS:000335125500012 PM 24626638 ER PT J AU Miniscalco, C Rudling, M Rastam, M Gillberg, C Johnels, JA AF Miniscalco, Carmela Rudling, Maja Rastam, Maria Gillberg, Christopher Johnels, Jakob Asberg TI Imitation (rather than core language) predicts pragmatic development in young children with ASD: a preliminary longitudinal study using CDI parental reports SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE imitation; pre-linguistic skills; autism; development; CDI; pragmatic ID AUTISM SPECTRUM DISORDERS; COMMUNICATIVE DEVELOPMENT INVENTORY; JOINT ATTENTION; IMPAIRMENT; ENGAGEMENT; SKILLS; PLAY AB Background Research in the last decades has clearly pointed to the important role of language and communicative level when trying to understand developmental trajectories in children with autism spectrum disorders (ASD). Aims The purpose of this longitudinal study was to investigate whether (1) core language skills, measured as expressive vocabulary and grammar, and/or (2) pre-linguistic social-communicative skills, including gestures and imitation abilities, drive pragmatic language development in young children with ASD. Methods & Procedures We examined correlates and longitudinal predictors of pragmatic growth in a sample of 34 children with Autism spectrum disorder (ASD), whose parents were given parts of two MacArthur Communicative Developmental Inventories (CDI: Words & Gestures and CDI: Words & Sentences) for completion at two time points (at time 1 the mean child age was 41 months, and at time 2 it was 54 months). A novel feature in this study is that the relevant parts from both CDI forms were included at both time points, allowing us to examine whether pre-linguistic social-communication skills (e.g. imitation and gesturing) and/or core language skills (i.e. grammar and vocabulary) predict pragmatic language growth. Outcomes & Results The results show that basically all pre-linguistic, linguistic and pragmatic skills were associated concurrently. When controlling for possible confounders and for the autoregressive effect, imitation skills predicted pragmatic growth over time, whereas core language did not. This could only have been shown by the use of both CDI forms. Conclusions & Implications This preliminary study may be of both conceptual and methodological importance for research in the field of language and communication development in ASD. Imitation may play a pivotal role in the development of subsequent conversational pragmatic abilities in young children with ASD. Future research should be directed at unravelling the mechanisms underlying this association. C1 [Miniscalco, Carmela; Gillberg, Christopher; Johnels, Jakob Asberg] Univ Gothenburg, Inst Neurosci & Physiol, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Miniscalco, Carmela; Johnels, Jakob Asberg] Univ Gothenburg, Inst Neurosci & Physiol, Div Speech & Language Pathol, Gothenburg, Sweden. [Rudling, Maja; Rastam, Maria] Lund Univ, Dept Clin Sci Lund Child & Adolescent Psychiat, S-22100 Lund, Sweden. [Johnels, Jakob Asberg] Univ Gothenburg, Dept Psychol, Gothenburg, Sweden. RP Miniscalco, C (reprint author), Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. 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PD MAY PY 2014 VL 49 IS 3 BP 369 EP 375 DI 10.1111/1460-6984.12085 PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AG0AZ UT WOS:000335078200009 PM 24684579 ER PT J AU Siu, AFY Zhou, Y AF Siu, Angela F. Y. Zhou, Ya TI Behavioral Assessment of the Dysexecutive Syndrome for Children An Examination of Clinical Utility for Children With Attention-Deficit Hyperactivity Disorder (ADHD) SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE executive function; ecological validity; Hong Kong; assessment; ADHD ID LATENT-VARIABLE ANALYSIS; PERFORMANCE-BASED MEASURES; AUTISM SPECTRUM DISORDERS; EXECUTIVE FUNCTION; RATING INVENTORY; DEFICIT/HYPERACTIVITY DISORDER; ECOLOGICAL VALIDITY; CONSTRUCT-VALIDITY; INTERFERENCE; SUBTYPES AB The present study evaluated the utility of the Behavioral Assessment of Dysexecutive Syndrome for Children for discerning differences in executive functioning between attention-deficit hyperactivity disorder (ADHD) children and normal controls and examined its associations with real-life executive function as rated by parent reports on the Dysexecutive Questionnaire for Children. Sixty-three children diagnosed with ADHD and 60 normal healthy peers were recruited for this study. All participants completed the Behavioral Assessment of Dysexecutive Syndrome for Children, while their parents completed the Dysexecutive Questionnaire for Children. Results revealed that the ADHD group exhibited significantly poorer performance than the controls on 3 subtests of the Behavioral Assessment of Dysexecutive Syndrome for Children (ie, Playing Cards Test, Water Test, and Zoo Map Test 2), as well as on the total Dysexecutive Questionnaire for Children. Significant correlation was found between the total Dysexecutive Questionnaire for Children and the 6-Part Test. Findings suggested that some subtests of the Behavioral Assessment of Dysexecutive Syndrome for Children were particularly useful for detecting real-life executive dysfunction in ADHD. Yet, further studies are needed to provide extended validity data. C1 [Siu, Angela F. 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Child Neurol. PD MAY PY 2014 VL 29 IS 5 BP 608 EP 616 DI 10.1177/0883073813516191 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AG0FJ UT WOS:000335090400006 PM 24453147 ER PT J AU Marques, F Brito, MJ Conde, M Pinto, M Moreira, A AF Marques, Filipa Brito, Maria Joao Conde, Marta Pinto, Monica Moreira, Ana TI Autism Spectrum Disorder Secondary to Enterovirus Encephalitis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE children; enterovirus; autism spectrum disorder; encephalitis ID HERPES-SIMPLEX ENCEPHALITIS; CENTRAL-NERVOUS-SYSTEM; PCR ASSAY; INFECTIONS; CHILDHOOD; MENINGITIS; DIAGNOSIS; SYMPTOMS; CHILDREN; COHORT AB Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder. C1 [Marques, Filipa; Brito, Maria Joao; Conde, Marta] Ctr Hosp Lisboa Cent EPE, Hosp Dona Estefania, Infect Dis Unit, P-1169045 Lisbon, Portugal. 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Child Neurol. PD MAY PY 2014 VL 29 IS 5 BP 708 EP 714 DI 10.1177/0883073813508314 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AG0FJ UT WOS:000335090400022 PM 24782421 ER PT J AU Puts, NAJ Wodka, EL Tommerdahl, M Mostofsky, SH Edden, RAE AF Puts, Nicolaas A. J. Wodka, Ericka L. Tommerdahl, Mark Mostofsky, Stewart H. Edden, Richard A. E. TI Impaired tactile processing in children with autism spectrum disorder SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE autism; inhibition; tactile; somatosensory; psychophysics ID GABA CONCENTRATION; CANDIDATE GENE; SENSITIVITY; ADAPTATION; DISRUPTION; GABRB3; ADULTS; DISCRIMINATION; INDIVIDUALS; PERCEPTION AB Impaired responses to tactile stimulation are a commonly reported symptom among children with autism spectrum disorder (ASD). Furthermore, impairments in filtering or habituation to tactile input have been described in ASD. This study measured different aspects of tactile processing to investigate atypical touch sensitivity in children with ASD, methodology that has not been previously used in this population. Sixty-seven typically developing children (TDC) and 32 children with ASD (ages 8-12) completed vibrotactile tasks assessing: reaction time (RT); static and dynamic detection threshold (DT); amplitude discrimination with and without single-site adaptation; frequency discrimination; and temporal order judgment (TOJ) with and without concurrent stimulation. Children with ASD showed raised static detection thresholds and an absence of the effect of a dynamically increasing subthreshold stimulus on static detection threshold. Children with ASD also showed poorer amplitude discrimination than TDC, as well as decreased adaptation. There were no significant differences in frequency discrimination or TOJ performance between the groups. Differences in the effect of dynamic stimulation on detection threshold suggest impaired feed-forward inhibition in autism, which may be linked to poor sensory filtering. Increased baseline amplitude discrimination thresholds in ASD suggest that lateral inhibitory connections are weaker in ASD, and an absence of the effect of adaptation suggests impaired modulation of lateral inhibitory connections in ASD, which may relate to aberrant habituation. These results suggest a functional deficit in the somatosensory inhibitory system in autism. Understanding the specific mechanisms underlying sensory symptoms in autism may allow for more specific therapeutic or drug targeting in the near future. C1 [Puts, Nicolaas A. J.; Edden, Richard A. E.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Puts, Nicolaas A. J.; Edden, Richard A. E.] Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD USA. [Wodka, Ericka L.; Mostofsky, Stewart H.] Kennedy Krieger Inst, Lab Neurocognit & Imaging Res, Baltimore, MD USA. [Wodka, Ericka L.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA. [Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Wodka, Ericka L.; Mostofsky, Stewart H.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. RP Puts, NAJ (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St, Baltimore, MD 21287 USA. EM nputs1@jhmi.edu FU Autism Speaks Translational Postdoctoral Fellowship; Organization for Autism Research; National Institutes of Health [P41-EB-015909, R21-MH-098228, 2-R01-NS-048527-08, 2-R01-MH-078160-06A1]; Johns Hopkins University School of Medicine Institute for Clinical and Translational Research National Institutes of Health/ National Center for Research Resources Clinical and Translational Science Award Program [UL1-RR-025005] FX N. A. Puts is funded by an Autism Speaks Translational Postdoctoral Fellowship. E. L. Wodka is supported by the Organization for Autism Research. This work was further supported by National Institutes of Health Grants P41-EB-015909, R21-MH-098228, 2-R01-NS-048527-08, and 2-R01-MH-078160-06A1 and Johns Hopkins University School of Medicine Institute for Clinical and Translational Research National Institutes of Health/ National Center for Research Resources Clinical and Translational Science Award Program UL1-RR-025005. None of the funding bodies had influence on the acquisition or analysis of the data nor on the writing and submission of this article. CR Blakemore SJ, 2006, BRAIN COGNITION, V61, P5, DOI 10.1016/j.bandc.2005.12.013 Blankenburg F, 2003, SCIENCE, V299, P1864, DOI 10.1126/science.1080806 Casanova MF, 2002, NEUROLOGY, V58, P428 Casanova MF, 2004, ANN NEUROL, V56, P54 Casanova MF, 2003, NEUROSCIENTIST, V9, P496, DOI 10.1177/1073858403253552 Cascio C, 2008, J AUTISM DEV DISORD, V38, P127, DOI 10.1007/s10803-007-0370-8 DeLorey TM, 2011, BEHAV BRAIN RES, V216, P36, DOI 10.1016/j.bbr.2010.06.032 Delorey TM, 2005, INT REV NEUROBIOL, V71, P359, DOI 10.1016/S0074-7742(05)71015-1 Dinstein I, 2012, NEURON, V75, P981, DOI 10.1016/j.neuron.2012.07.026 Favorov OV, 2011, J NEUROPHYSIOL, V105, P1342, DOI 10.1152/jn.00708.2010 Gaetz W, 2014, NEUROIMAGE, V86, P1, DOI 10.1016/j.neuroimage.2013.05.068 Guclu B, 2007, SOMATOSENS MOT RES, V24, P21, DOI 10.1080/08990220601179418 Holden JK, 2012, J NEUROSCI METH, V204, P215, DOI 10.1016/j.jneumeth.2011.11.007 Kohn A, 2007, J NEUROPHYSIOL, V97, P3155, DOI 10.1152/jn.00086.2007 Kohn A, 2002, BEHAV BRAIN RES, V135, P119, DOI 10.1016/S0166-4328(02)00139-0 LORD C, 1994, J AUTISM DEV DISORD, V24, P659, DOI 10.1007/BF02172145 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 McLaughlin DF, 2005, CEREB CORTEX, V15, P1791, DOI 10.1093/cercor/bhi056 Milne E, 2011, FRONT PSYCHOL, V2, DOI 10.3389/fpsyg.2011.00051 OLDFIELD RC, 1971, NEUROPSYCHOLOGIA, V9, P97, DOI 10.1016/0028-3932(71)90067-4 O'Riordan M, 2006, J AUTISM DEV DISORD, V36, P665, DOI 10.1007/s10803-006-0106-1 Puts NAJ, 2013, J NEUROSCI METH, V218, P39, DOI 10.1016/j.jneumeth.2013.04.012 Puts NAJ, 2011, J NEUROSCI, V31, P16556, DOI 10.1523/JNEUROSCI.4489-11.2011 Rogers SJ, 2005, J CHILD PSYCHOL PSYC, V46, P1255, DOI 10.1111/j.1469-7610.2005.01431.x Rojas DC, 2014, NEUROIMAGE, V86, P28, DOI 10.1016/j.neuroimage.2013.01.045 Rojas DC, 2011, MOL AUTISM, V2, DOI 10.1186/2040-2392-2-11 Tannan V, 2007, BRAIN RES, V1186, P164, DOI 10.1016/j.brainres.2007.10.024 Tannan V, 2008, AUTISM RES, V1, P223, DOI 10.1002/aur.34 Tavassoli T, 2012, MOL AUTISM, V3, DOI 10.1186/2040-2392-3-6 Tommerdahl M, 2010, NEUROSCI BIOBEHAV R, V34, P160, DOI 10.1016/j.neubiorev.2009.08.009 Tommerdahl M, 2007, BRAIN RES, V1154, P116, DOI 10.1016/j.brainres.2007.04.032 Tommerdahl M, 2008, BEHAV BRAIN FUNCT, V4, DOI 10.1186/1744-9081-4-19 Wechsler D., 2003, WECHSLER INTELLIGENC Whitsel BL, 2003, SOMATOSENS MOT RES, V20, P45, DOI 10.1080/0899022031000083834 Whitsel BL, 1989, SENSORY PROCESSING M, P84 Zhang Z, 2011, FRONT AGING NEUROSCI, V3, DOI 10.3389/fnagi.2011.00018 NR 36 TC 6 Z9 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2014 VL 111 IS 9 BP 1803 EP 1811 DI 10.1152/jn.00890.2013 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AG9ZR UT WOS:000335779300009 PM 24523518 ER PT J AU Kim, YS Fombonne, E Koh, YJ Kim, SJ Cheon, KA Leventhal, BL AF Kim, Young Shin Fombonne, Eric Koh, Yun-Joo Kim, Soo-Jeong Cheon, Keun-Ah Leventhal, Bennett L. TI A Comparison of DSM-IV Pervasive Developmental Disorder and DSM-5 Autism Spectrum Disorder Prevalence in an Epidemiologic Sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ASD; SCD; DSM-IV; DSM-5; prevalence ID CRITERIA; CHILDREN AB Objective: Changes in autism diagnostic criteria found in DSM-5 may affect autism spectrum disorder (ASD) prevalence, research findings, diagnostic processes, and eligibility for clinical and other services. Using our published, total-population Korean prevalence data, we compute DSM-5 ASD and social communication disorder (SCD) prevalence and compare them with DSM-IV pervasive developmental disorder (PDD) prevalence estimates. We also describe individuals previously diagnosed with DSM-IV PDD when diagnoses change with DSM-5 criteria. Method: The target population was all children from 7 to 12 years of age in a South Korean community (N = 55,266), those in regular and special education schools, and a disability registry. We used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of screen-positive children were offered comprehensive assessments using standardized diagnostic procedures, including the Autism Diagnostic Interview Revised and Autism Diagnostic Observation Schedule. Best-estimate clinical diagnoses were made using DSM-IV PDD and DSM-5 ASD and SCD criteria. Results: DSM-5 ASD estimated prevalence was 2.20% (95% confidence interval = 1.77-3.64). Combined DSM-5 ASD and SCD prevalence was virtually the same as DSM-IV PDD prevalence (2.64%). Most children with autistic disorder (99%), Asperger disorder (92%), and PDD-NOS (63%) met DSM-5 ASD criteria, whereas 1%, 8%, and 32%, respectively, met SCD criteria. All remaining children (2%) had other psychopathology, principally attention-deficit/hyperactivity disorder and anxiety disorder. Conclusion:. Our findings suggest that most individuals with a prior DSM-IV PDD meet DSM-5 diagnostic criteria for ASD and SCD. PDD, ASD or SCD; extant diagnostic criteria identify a large, clinically meaningful group of individuals and families who require evidence-based services. C1 [Kim, Young Shin] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Kim, Young Shin; Leventhal, Bennett L.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Kim, Young Shin; Cheon, Keun-Ah; Leventhal, Bennett L.] Yonsei Univ, Seoul 120749, South Korea. [Fombonne, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Koh, Yun-Joo] Korea Inst Childrens Social Dev Rudolph, Seoul, South Korea. [Kim, Soo-Jeong] Univ Washington, Seattle, WA 98195 USA. [Leventhal, Bennett L.] Univ Illinois, Chicago, IL USA. RP Leventhal, BL (reprint author), Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd,Bldg 35, Orangeburg, NY 10962 USA. FU Autism Speaks Pilot Research Grant; Brain Research Foundation; Simons Foundation [137032 M134793]; National Institute for Mental Health (NIMH) [5K01MH079317-02, K23MH082883]; National Institute of Environmental Health Sciences (NIEHS) [R01 ES021462-01]; Korean Health Technology Research and Development Project, Ministry of Health and Welfare [HI12C0021, HI12C0245-A120029]; Jean Young and Walden W. Shaw Foundation; Daniel X. and Mary Freedman Foundation; Dukyoung Foundation; [7996] FX This research was funded by an Autism Speaks Pilot Research Grant, and a Supplement Grant (7996), a Brain Research Foundation Research Grant, a Simons Foundation Autism Research Initiative Pilot Grant (137032 M134793), the National Institute for Mental Health (NIMH) Career Awards (5K01MH079317-02 [Y.S.K.] and K23MH082883 [S.J.K.]), the National Institute of Environmental Health Sciences (NIEHS) R01 Award (R01 ES021462-01), and the Korean Health Technology Research and Development Project, Ministry of Health and Welfare (HI 12C0021; HI12C0245-A120029).Additional funding was provided by the Jean Young and Walden W. Shaw Foundation, the Daniel X. and Mary Freedman Foundation, and the Dukyoung Foundation. CR American Psychiatric Association, 2013, DSM5 AM PSYCH ASS American Psychiatric Association, 2013, A05 SOC COMM [Anonymous], 2012, NY TIMES Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Fombonne E, 1999, PSYCHOL MED, V29, P769, DOI 10.1017/S0033291799008508 Fombonne E, 2009, PEDIATR RES, V65, P591 Frazier TW, 2012, J AM ACAD CHILD PSY, V51, P28, DOI 10.1016/j.jaac.2011.09.021 Gibbs V, 2012, J AUTISM DEV DISORD, V42, P1750, DOI 10.1007/s10803-012-1560-6 Huerta M, 2012, AM J PSYCHIAT, V169, P1056, DOI 10.1176/appi.ajp.2012.12020276 Kelsey J. L., 1996, METHODS OBSERVATIONA Kim YS, 2011, AM J PSYCHIAT, V168, P904, DOI 10.1176/appi.ajp.2011.10101532 Mattila ML, 2011, J AM ACAD CHILD PSY, V50, P583, DOI 10.1016/j.jaac.2011.04.001 McPartland JC, 2012, J AM ACAD CHILD PSY, V51, P368, DOI 10.1016/j.jaac.2012.01.007 Taheri A, 2012, J AUTISM DEV DISORD, V42, P1810, DOI 10.1007/s10803-012-1599-4 NR 14 TC 2 Z9 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2014 VL 53 IS 5 BP 500 EP 508 DI 10.1016/j.jaac.2013.12.021 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AG0HJ UT WOS:000335096200004 PM 24745950 ER PT J AU Strickland, AD AF Strickland, Alan D. TI Prevention of cerebral palsy, autism spectrum disorder, and attention deficit - Hyperactivity disorder SO MEDICAL HYPOTHESES LA English DT Article ID FETAL HYPOXIA-ISCHEMIA; FATTY-ACID COMPOSITION; WHITE-MATTER; DEFICIT/HYPERACTIVITY DISORDER; DOCOSAHEXAENOIC ACID; NEONATAL-RATS; BRAIN; INFLAMMATION; MICROGLIA; DAMAGE AB This hypothesis states that cerebral palsy (CP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) are all caused by an exaggerated central nervous system inflammatory response to a prenatal insult. This prenatal insult may be one or more episodes of ischemia-reperfusion, an infectious disease of the mother or the fetus, or other causes of maternal inflammation such as allergy or autoimmune disease. The resultant fetal inflammatory hyper-response injures susceptible neurons in the developing white matter of the brain in specific areas at specific gestational ages. The exaggerated neuroinflammatory response is theorized to occur between about 19 and 34 post-conception weeks for CP, about 32 and 40 weeks for ADHD, and about 36 and 48 weeks (i.e. 2 months after delivery) for ASD. The exaggerated inflammatory response is hypothesized to occur because present diets limit intake of effective antioxidants and omega-3 polyunsaturated fatty acids while increasing intake of omega-6 polyunsaturated fatty acids. Oxidation products of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) limit neuroinflammation while oxidation products of the omega-6 fatty acid arachidonic acid exacerbate inflammation. Preventative treatment should begin in all pregnant women during the first trimester and should include both DHA and an effective antioxidant for prevention of neuroinflammation. The suggested antioxidant would be N-acetylcysteine, though melatonin could be chosen instead. Combined DHA and NAC therapy is theorized to decrease the incidence of the three disorders by more than 75%. (C) 2014 Elsevier Ltd. All rights reserved. RP Strickland, AD (reprint author), 101 Waterlily, Lake Jackson, TX 77566 USA. 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Hypotheses PD MAY PY 2014 VL 82 IS 5 BP 522 EP 528 DI 10.1016/j.mehy.2014.02.003 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG0KT UT WOS:000335105100004 PM 24581674 ER PT J AU Wen, W Wen, SW AF Wen, Wendy Wen, Shi Wu TI Expanding upon the 'extreme male brain' theory of autism as a common link between other major risk factors: A hypothesis SO MEDICAL HYPOTHESES LA English DT Article ID SEX-DIFFERENCES; EMPATHY QUOTIENT; AGGRESSION; MECHANISMS AB On average, males have a stronger preference for physical systems and machines over interpersonal interactions; they have lower average levels of cognitive empathy or social cognition than females; and they have higher rates of 'extreme' intelligence when it comes to abstract concepts such as those found in mathematics and sciences. All three traits are also commonly associated with individuals with an autism spectrum disorder or ASD; clearly, it is not coincidental that incidence rates of autism are reportedly four times higher in males than in females. The common link between the majority of risk factors assessed in this review (including technological advancements, advanced parental age, socioeconomic status, and genetic predispositions towards ASDs in families of scientists and engineers) can be traced to a specific hormone, testosterone. It was established that traits which are typically associated with males are also typically associated with ASDs as well as individuals with antisocial personality disorder, or APD. The key distinction between individuals who are considered to be 'autistic' as opposed to those who are considered 'sociopathic' lies in the difference between their empathy deficits: whereas those who are 'autistic' are said to lack cognitive empathy (the ability to identify and understand the thoughts and feelings of others and to respond to these with appropriate emotions), those who are 'sociopathic' are said to lack emotional empathy (which is responsible for inhibiting acts of physical aggression or violence). This would explain why autistic individuals can have elevated testosterone levels without becoming physically aggressive. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Wen, Wendy] Univ Ottawa, Dept Math & Stat, Fac Sci, Ottawa, ON K1H 8L6, Canada. [Wen, Shi Wu] Univ Ottawa, Dept Obstet & Gynecol, OMNI Res Grp, Ottawa, ON K1H 8L6, Canada. [Wen, Shi Wu] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. 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Hypotheses PD MAY PY 2014 VL 82 IS 5 BP 615 EP 618 DI 10.1016/j.mehy.2014.02.020 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG0KT UT WOS:000335105100019 PM 24629356 ER PT J AU Lionello-DeNolf, KM Farber, R Jones, BM Dube, WV AF Lionello-DeNolf, Karen M. Farber, Rachel Jones, B. Max Dube, William V. TI Thematic matching as remedial teaching for symbolic matching for individuals with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Matching-to-sample; Symbolic behavior; Thematic matching; Children with ASD ID COMMUNICATION-SYSTEM PECS; MENTALLY-RETARDED ADULTS; CONDITIONAL DISCRIMINATION; ERROR-CORRECTION; CHILDREN; DISABILITIES; EQUIVALENCE; ACQUISITION; SKILLS AB Matching-to-sample (MTS) is often used to teach symbolic relationships between spoken or printed words and their referents to children with intellectual and developmental disabilities. However, many children have difficulty learning symbolic matching, even though they may demonstrate generalized identity matching. The current study investigated whether training on symbolic MTS tasks in which the stimuli are physically dissimilar but members of familiar categories (i.e., thematic matching) can remediate an individual's difficulty learning symbolic MTS tasks involving non-representative stimuli. Three adolescent males diagnosed with autism spectrum disorder were first trained on symbolic MTS tasks with unfamiliar, non-representative form stimuli. Thematic matching was introduced after the participants failed to learn 0, 2 or 4 symbolic MTS tasks and before additional symbolic MTS tasks were introduced. After exposure to thematic matching, accuracy on symbolic MTS tasks with novel stimuli increased to above chance for all participants. For two participants, high accuracy (>90%) was achieved on a majority of these sessions. 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