FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kashevarova, AA Nazarenko, LP Schultz-Pedersen, S Skryabin, NA Salyukova, OA Chechetkina, NN Tolmacheva, EN Rudko, AA Magini, P Graziano, C Romeo, G Joss, S Tumer, Z Lebedev, IN AF Kashevarova, Anna A. Nazarenko, Lyudmila P. Schultz-Pedersen, Soren Skryabin, Nikolay A. Salyukova, Olga A. Chechetkina, Nataliya N. Tolmacheva, Ekaterina N. Rudko, Aleksey A. Magini, Pamela Graziano, Claudio Romeo, Giovanni Joss, Shelagh Tumer, Zeynep Lebedev, Igor N. TI Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability SO MOLECULAR CYTOGENETICS LA English DT Article DE Intellectual disability; 3p26.3 microdeletion; 3p26.3 microduplication; CNTN6; Reciprocal microdeletions/microduplications ID AUTISM SPECTRUM DISORDERS; ARRAY-CGH ANALYSIS; DEVELOPMENTAL DELAY; MENTAL-RETARDATION; DELETION; FEATURES; IMPACT; CHL1 AB Background: Detection of submicroscopic chromosomal alterations in patients with a idiopathic intellectual disability (ID) allows significant improvement in delineation of the regions of the genome that are associated with brain development and function. However, these chromosomal regions usually contain several protein-coding genes and regulatory elements, complicating the understanding of genotype-phenotype correlations. We report two siblings with ID and an unrelated patient with atypical autism who had 3p26.3 microdeletions and one intellectually disabled patient with a 3p26.3 microduplication encompassing only the CNTN6 gene. Results: Two 295.1-kb microdeletions and one 766.1-kb microduplication of 3p26.3 involving a single gene, CNTN6, were identified with an Agilent 60K array. Another 271.9-kb microdeletion of 3p26.3 was detected using an Affymetrix CytoScan HD chromosome microarray platform. The CHL1 and CNTN4 genes, although adjacent to the CNTN6 gene, were not affected in either of these patients. Conclusions: The protein encoded by CNTN6 is a member of the immunoglobulin superfamily and functions as a cell adhesion molecule that is involved in the formation of axon connections in the developing nervous system. Our results indicate that CNTN6 may be a candidate gene for ID. C1 [Kashevarova, Anna A.; Skryabin, Nikolay A.; Tolmacheva, Ekaterina N.; Lebedev, Igor N.] Inst Med Genet, Lab Cytogenet, Tomsk 634050, Russia. [Nazarenko, Lyudmila P.; Salyukova, Olga A.; Chechetkina, Nataliya N.] Inst Med Genet, Lab Hereditary Pathol, Tomsk 634050, Russia. [Nazarenko, Lyudmila P.; Salyukova, Olga A.; Lebedev, Igor N.] Siberian State Med Univ, Dept Med Genet, Tomsk, Russia. [Schultz-Pedersen, Soren] Private Pediat Clin Bornelaegen Aarhus, Aarhus, Denmark. [Skryabin, Nikolay A.] Tomsk State Univ, Lab Human Ontogenet, Tomsk 634050, Russia. [Rudko, Aleksey A.] Inst Med Genet, Genet Clin, Tomsk 634050, Russia. [Magini, Pamela; Graziano, Claudio; Romeo, Giovanni] Univ Bologna, Dept Gynecol Obstet & Pediat, Unit Med Genet, Bologna, Italy. [Joss, Shelagh] So Gen Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, Scotland. [Tumer, Zeynep] Rigshosp, Copenhagen Univ Hosp, Kennedy Ctr, Dept Clin Genet, DK-2100 Copenhagen, Denmark. RP Kashevarova, AA (reprint author), Inst Med Genet, Lab Cytogenet, 10 Nab Ushaiki, Tomsk 634050, Russia. EM anna.kashevarova@medgenetics.ru RI Skryabin, Nikolay/A-7862-2014; Lebedev, Igor/K-7454-2012 FU European Community's Seventh Framework Program, CHERISH [223692]; Russian Scientific Foundation [14-15-00772] FX The initial array CGH analysis of the male patients F and K and the real-time PCR confirmation of the findings were supported by the European Community's Seventh Framework Program, CHERISH (project 223692). Further investigations of patient F's sister and patient K's family via array CGH and real-time PCR to assess the CNTN6, CNTN4 and CHL1 genes were supported by the Russian Scientific Foundation (project 14-15-00772). 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Cytogenet. PD DEC 31 PY 2014 VL 7 AR 97 DI 10.1186/s13039-014-0097-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AZ5CK UT WOS:000348237600001 PM 25606055 ER PT J AU Kolevzon, A Lim, T Schmeidler, J Martello, T Cook, EH Silverman, JM AF Kolevzon, Alexander Lim, Teresa Schmeidler, James Martello, Toni Cook, Edwin H., Jr. Silverman, Jeremy M. TI Self-injury in autism spectrum disorder: An effect of serotonin transporter gene promoter variants SO PSYCHIATRY RESEARCH LA English DT Article DE Autism; Serotonin; Serotonin transporter gene; Self-injury; Aggression ID RIGID-COMPULSIVE BEHAVIORS; VIOLENT SUICIDAL-BEHAVIOR; POSSIBLE ASSOCIATION; PLATELET SEROTONIN; POLYMORPHISM; CHILDREN; AGGRESSION; METAANALYSIS; 5-HTTLPR; SLC6A4 AB Self-injurious behavior in autism spectrum disorder (ASD) has been associated with lower whole blood serotonin levels and the role of serotonin transporter gene promoter region (5HTTLPR) polymorphisms is of interest because of their effects on transporter functioning. This study examined the association between self-injurious behavior in ASD and allelic frequencies of 5HTTLPR. Sixty-four children and adolescents with ASD who were not taking serotonergic medication at the time of the assessment were included in the analysis. Self-injury was assessed using the Autism Diagnostic Interview-Revised (ADI-R) and whole blood serotonin levels were measured using high-pressure liquid chromatography (HPLC) with fluorometic detection. DNA was extracted from saliva and PCR amplified with fluorescent primers. Self-injury significantly increased with the number of La alleles of the 5HTTLPR and decreased with the number of Lg alleles. Self-injury in ASD may be associated with a specific genotype of the serotonin transporter gene promoter region. Future studies should continue to explore subgroups to clarify the underlying clinical and genetic heterogeneity in ASD. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Kolevzon, Alexander; Lim, Teresa; Schmeidler, James; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Kolevzon, Alexander; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Kolevzon, Alexander; Lim, Teresa] Icahn Sch Med Mt Sinai, Ctr Res & Treatment, Dept Seaver Autism, New York, NY 10029 USA. [Kolevzon, Alexander] Icahn Sch Med Mt Sinai, Inst Brain, Dept Friedman, New York, NY 10029 USA. [Kolevzon, Alexander] Icahn Sch Med Mt Sinai, Dept Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Martello, Toni] NYU, Dept Psychiat, Sch Med, New York, NY 10016 USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. RP Kolevzon, A (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM alexander.kolevzon@mssm.edu FU AACAP/Eli Lily Young Investigator Award; Beatrice and Samuel A. Seaver Foundation; Jean Young and Walden W. Shaw Foundation; Daniel X. & Mary Freedman Foundation for Academic Psychiatry FX This work was supported in part by the AACAP/Eli Lily Young Investigator Award (Dr. Kolevzon), the Beatrice and Samuel A. Seaver Foundation (Drs. Kolevzon and Silverman), Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center (Dr. Kolevzon), the Jean Young and Walden W. Shaw Foundation (Dr. Cook), and The Daniel X. & Mary Freedman Foundation for Academic Psychiatry (Dr. Cook). 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PD DEC 30 PY 2014 VL 220 IS 3 BP 987 EP 990 DI 10.1016/j.psychres.2014.09.018 PG 4 WC Psychiatry SC Psychiatry GA AY1OD UT WOS:000347361300038 PM 25446464 ER PT J AU Wang, Y Deng, Y Fung, GM Liu, WH Wei, XH Jiang, XQ Lui, SSY Cheung, EFC Chan, RCK AF Wang, Yi Deng, Yi Fung, Germaine Liu, Wen-hua Wei, Xin-hua Jiang, Xin-qing Lui, Simon S. Y. Cheung, Eric F. C. Chan, Raymond C. K. TI Distinct structural neural patterns of trait physical and social anhedonia: Evidence from cortical thickness, subcortical volumes and inter-regional correlations SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Anhedonia; Pallidum; Social interaction; Superior frontal gyrus; Inferior parietal gyrus ID HUMAN CEREBRAL-CORTEX; MAJOR DEPRESSIVE DISORDER; AUTISM SPECTRUM DISORDER; SCHIZOPHRENIA-SPECTRUM; NUCLEUS-ACCUMBENS; REDUCED THICKNESS; BRAIN; SCHIZOTYPY; SURFACE; INDIVIDUALS AB Anhedonia is an enduring trait accounting for the reduced capacity to experience pleasure. Few studies have investigated the brain structural features associated with trait anhedonia. In this study, the relationships between cortical thickness, volume of subcortical structures and scores on the Chapman physical and social anhedonia scales were examined in a non clinical sample (n=72, 35 males). FreeSurfer was used to examine the cortical thickness and the volume of six identified subcortical structures related to trait anhedonia. We found that the cortical thickness of the superior frontal gyrus and the volume of the pallidum in the left hemisphere were Correlated with anhedonia scores in both physical and social aspects. Specifically, positive correlations were found between levels of social anhedonia and the thickness of the postcentral and the inferior parietal gyri. Cortico-subcortical inter-correlations between these clusters were also observed. Our findings revealed distinct correlation patterns of neural substrates with trait physical and social anhedonia in a non-clinical sample. These findings contribute to the understanding of the pathologies underlying the anhedonia phenotype in schizophrenia and other psychiatric disorders. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Wang, Yi; Deng, Yi; Fung, Germaine; Chan, Raymond C. K.] Chinese Acad Sci, Inst Psychol, Neuropsychol & Appl Cognit Neurosci Lab, Key Lab Mental Hlth, Beijing 100101, Peoples R China. [Deng, Yi] Univ Calif Davis, MIND Inst, Cognit Anal & Brain Imaging Lab, Davis, CA 95616 USA. [Liu, Wen-hua] Guangzhou Med Univ, Sch Hlth Management, Guangzhou, Guangdong, Peoples R China. [Wei, Xin-hua; Jiang, Xin-qing] Guangzhou First Peoples Hosp, Dept Radiol, Guangzhou, Guangdong, Peoples R China. [Lui, Simon S. Y.; Cheung, Eric F. C.] Castle Peak Hosp, Hong Kong, Hong Kong, Peoples R China. [Chan, Raymond C. 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TI Freiburg Questionnaire of linguistic pragmatics (FQLP): psychometric properties based on a psychiatric sample SO BMC PSYCHIATRY LA English DT Article DE Autism; Asperger's syndrome; Questionnaire; Linguistic pragmatics; Screening; Clinical diagnostics; Language comprehension ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; NORMAL SEX-DIFFERENCES; ASPERGER-SYNDROME; SPECTRUM DISORDERS; FIGURATIVE LANGUAGE; ADULTS; CHILDREN; COMPREHENSION; QUOTIENT AB Background: Asperger's Syndrome (AS) is an autism spectrum disorder that is characterized by significant difficulties in social interaction and nonverbal communication, and restricted and repetitive patterns of behavior and interests. Difficulties with respect to pragmatic speech, reading emotional and social cues, differentiating between fact and fiction, and taking into account the influence of context on a statement are commonly described features. However, hitherto established questionnaires did not focus on these symptoms. Methods: In this study we present a short (11 questions) questionnaire which focuses on self-rated pragmatic speech abilities, the Freiburg Questionnaire of linguistic pragmatics (FQLP). Psychometric properties of the questionnaire were explored in a sample of 57 patients with Asperger's Syndrome, 66 patients with other psychiatric disorders, and a convenience sample of 56 people. Results: Reliability analysis showed a high Cronbach's a. Strong correlations could be demonstrated for the FQLP with the Autism Quotient and the Empathy Quotient. Concerning divergent validity a moderate correlation was found between the FQLP and self-rated symptoms of personality disorders. No significant correlation was found between the FQLP and the vocabulary skills. The receiver operating characteristics curve showed an excellent diagnostic accuracy of the FQLP (. 97). Conclusions: As the control group consisted of people without mental disorder and patients with different psychiatric disorders, the results indicate that the construct examined by the FQLP is quite specific to the peculiarities of AS. The FQLP is a reliable, brief and valid instrument. First results regarding sensitivity and specificity are highly promising. C1 [Riedel, Andreas; Suh, Heejung; Hermann, Ismene; Ebert, Dieter; Riemann, Dieter; Bubl, Emanuel; van Elst, Ludger Tebartz; Hoelzel, Lars P.] Univ Med Ctr Freiburg, Clin Psychiat & Psychotherapy, D-79104 Freiburg, Germany. [Haser, Verena] Univ Freiburg, Dept English Linguist, D-79106 Freiburg, Germany. RP Riedel, A (reprint author), Univ Med Ctr Freiburg, Clin Psychiat & Psychotherapy, Hauptstr 5, D-79104 Freiburg, Germany. EM andreas.riedel@uniklinik-freiburg.de FU Beringer-Stiftung.; German Research Foundation (DFG); Albert Ludwigs University Freiburg FX This study is funded by a grant of the Beringer-Stiftung. 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Pillalamarri, Vamsee Brand, Harrison Kuijk, Ewart W. de Luca, Kim L. Lansu, Nico Braat, A. Koen Menelaou, Androniki Hao, Wensi Korving, Jeroen Snijder, Simone van der Veken, Lars T. Hochstenbach, Ron Knegt, Alida C. Duran, Karen Renkens, Ivo Alekozai, Najla Jager, Myrthe Vergult, Sarah Menten, Bjoern de Bruijn, Ewart Boymans, Sander Ippel, Elly van Binsbergen, Ellen Talkowski, Michael E. Lichtenbelt, Klaske Cuppen, Edwin Kloosterman, Wigard P. TI Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements SO CELL REPORTS LA English DT Article ID AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIATION; PROSTATE-CANCER; DE-NOVO; STRUCTURAL VARIATION; GENE FUSIONS; REPAIR; ETV1; IDENTIFICATION; ABNORMALITIES AB Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted. C1 [van Heesch, Sebastiaan; Simonis, Marieke; Kuijk, Ewart W.; de Luca, Kim L.; Lansu, Nico; Hao, Wensi; Korving, Jeroen; de Bruijn, Ewart; Boymans, Sander; Cuppen, Edwin] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands. [van Heesch, Sebastiaan; Simonis, Marieke; Kuijk, Ewart W.; de Luca, Kim L.; Lansu, Nico; Hao, Wensi; Korving, Jeroen; de Bruijn, Ewart; Boymans, Sander; Cuppen, Edwin] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [van Roosmalen, Markus J.; Menelaou, Androniki; van der Veken, Lars T.; Hochstenbach, Ron; Duran, Karen; Renkens, Ivo; Alekozai, Najla; Jager, Myrthe; Ippel, Elly; van Binsbergen, Ellen; Lichtenbelt, Klaske; Cuppen, Edwin; Kloosterman, Wigard P.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, NL-3584 CG Utrecht, Netherlands. [Pillalamarri, Vamsee; Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Braat, A. Koen] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. [Snijder, Simone; Knegt, Alida C.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Vergult, Sarah; Menten, Bjoern] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. RP Cuppen, E (reprint author), Hubrecht Inst KNAW, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. EM e.cuppen@hubrecht.eu; w.kloosterman@umcutrecht.nl FU Cancer Genomics Center and Netherlands Center for Systems Biology programs of the Netherlands Genomics Initiative; Child Health Priority Program of the University Medical Center Utrecht, an NWO Vici grant [865.13.004]; Wilhelmina Children's Hospital; NIH [GM061354, HD065286, MH095867] FX We would like to thank A. de Graaff and the Hubrecht Imaging Center for supporting the imaging, M. van Dooren, L. van Zutven, and A. Baas for providing access to patient data, and A. Marcozzi for help with artwork. This work was supported by the Cancer Genomics Center and Netherlands Center for Systems Biology programs of the Netherlands Genomics Initiative, the Child Health Priority Program of the University Medical Center Utrecht, an NWO Vici grant (865.13.004) to E.C., a research grant from the Wilhelmina Children's Hospital to W.P.K., and the NIH (GM061354, HD065286, and MH095867 to M.E.T.). 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EM hoshino@ncnp.go.jp FU Ministry of Education, Culture, Sports, Science, and Technology of Japan [25115733, 25110742]; MEXT; Astellas foundation; Naito foundation; Takeda foundation; Uehara foundation; Intramural Research Grants for Neurological and Psychiatric Disorders of NCNP [24-12, 25-3]; Health Science Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health from the Japanese Ministry of Health, Labor and Welfare [H23-001]; JSPS KAKENHI [23700406, 25830030] FX We thank members of the Hoshino lab for useful discussions. This work is supported by Grants-in-Aid for Scientific Research on Innovative Areas "Mesoscopic Neurocircuitry" (grant 25115733) and "Synapse and Neurocircuit Pathology" (grant 25110742) of the Ministry of Education, Culture, Sports, Science, and Technology of Japan; grants from MEXT, Astellas foundation, Naito foundation, Takeda foundation, Uehara foundation, Intramural Research Grants (M.H., 24-12, 25-3) for Neurological and Psychiatric Disorders of NCNP, Health Science Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (M.H., H23-001) from the Japanese Ministry of Health, Labor and Welfare, and JSPS KAKENHI grant numbers 23700406 and 25830030 (K.H.). 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Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. Methods: The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. Results and Discussion: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. Conclusion: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity. C1 [Fairthorne, Jenny; Bourke, Jenny; Jacoby, Peter; Leonard, Helen] Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia. [Hammond, Geoff] Hlth Dept Western Australia, Perth, WA, Australia. RP Fairthorne, J (reprint author), Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia. EM Jenny.Fairthorne@telethonkids.org.au FU Australian Postgraduate Award; University of Western Australia Top-up Award FX Funding provided by Australian Postgraduate Award and University of Western Australia Top-up Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Anthony, Todd E. Wang, Chenran Li, Yi E. Guan, Jun-Lin Murphy, Geoffrey G. Zhu, Yuan TI Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1 SO ELIFE LA English DT Article DE Neurofibromatosis type 1; tumor suppressor gene; Bergmann glial cells; Granule cells; Unipolar Brush cells; cerebellum ID AUTISM SPECTRUM DISORDER; NEURAL STEM; PROGENITOR PROLIFERATION; GLIOMA FORMATION; BERGMANN GLIA; MUTANT MICE; IN-VIVO; CELL; CHILDREN; BRAIN AB Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK/ERK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. C1 [Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S.; Zhu, Yuan] Childrens Natl Med Ctr, Gilbert Family Neurofibromatosis Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. [Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S.; Li, Yi E.; Zhu, Yuan] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. [Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S.; Li, Yi E.; Zhu, Yuan] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. [Zhu, Yuan] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Bornhorst, Miriam] Univ Michigan, Sch Med, Mott Childrens Hosp, Dept Pediat,Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Murphy, Geoffrey G.] Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Murphy, Geoffrey G.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Anthony, Todd E.] Rockefeller Univ, Mol Biol Lab, New York, NY 10021 USA. [Wang, Chenran; Guan, Jun-Lin] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA. RP Zhu, Y (reprint author), Childrens Natl Med Ctr, Gilbert Family Neurofibromatosis Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. EM yzhu@childrensnational.org FU DOD [W81XWH-11-1-0251]; NIH/NINDS [1R01 NS053900]; NIH/NCI [1U54 CA168512-01] FX We thank Dr. L. Parada for support during the early phase of the study; G. Tomasek for technical assistance; members of the Zhu lab for support; Drs. A. Messing for providing hGFAP-cre mice, D. Rowitch for Math1-cre mice, L. Chang for Nestin-creER mice, N. Heintz for BLBP antibody, B. Novitch for Olig2 antibody; Drs. R. Packer, C. Wang, and J. Guan for critically reading the manuscript. This work is supported by grants from the DOD (W81XWH-11-1-0251), NIH/NINDS (1R01 NS053900) and NIH/NCI (1U54 CA168512-01) (Y.Z.). 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Sen, Saunak Sherr, Elliott H. TI Mapk/Erk activation in an animal model of social deficits shows a possible link to autism SO MOLECULAR AUTISM LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; BTBR MOUSE MODEL; SPECTRUM DISORDERS; FRAGILE-X; ERK; PATHWAY; NEUROGENESIS; BEHAVIOR; MICE; CONTRIBUTES AB Background: There is converging preclinical and clinical evidence to suggest that the extracellular signal-regulated kinase (ERK) signaling pathway may be dysregulated in autism spectrum disorders. Method: We evaluated Mapk/Erk1/2, cellular proliferation and apoptosis in BTBR mice, as a preclinical model of Autism. We had previously generated 410 F2 mice from the cross of BTBR with B6. At that time, six different social behaviors in all F2 mice were evaluated and scored. In this study, eight mice at each extreme of the social behavioral spectrum were selected and the expression and activity levels of Mapk/Erk in the prefrontal cortex and cerebellum of these mice were compared. Finally, we compared the Mapk/Erk signaling pathway in brain and lymphocytes of the same mice, testing for correlation in the degree of kinase activation across these separate tissues. Results: Levels of phosphorylated Erk (p-Erk) were significantly increased in the brains of BTBR versus control mice. We also observed a significant association between juvenile social behavior and phosphorylated mitogen-activated protein kinase kinase (p-Mek) and p-Erk levels in the prefrontal cortex but not in the cerebellum. In contrast, we did not find a significant association between social behavior and total protein levels of either Mek or Erk. We also tested whether steady-state levels of Erk activation in the cerebral cortex in individual animals correlated with levels of Erk activation in lymphocytes, finding a significant relationship for this signaling pathway. Conclusion: These observations suggest that dysregulation of the ERK signaling pathway may be an important mediator of social behavior, and that measuring activation of this pathway in peripheral lymphocytes may serve as a surrogate marker for central nervous system (CNS) ERK activity, and possibly autistic behavior. C1 [Faridar, Alireza; Jones-Davis, Dorothy; Rider, Eric; Li, Jiang; Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Gobius, Ilan; Morcom, Laura; Richards, Linda J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Richards, Linda J.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. [Sen, Saunak] Univ Calif San Francisco, Epidemiol & Biostat, San Francisco, CA 94158 USA. [Faridar, Alireza] Methodist Neurol Inst, Houston, TX 77030 USA. RP Sherr, EH (reprint author), Univ Calif San Francisco, Dept Neurol, 675 Nelson Rising Way,Suite 214B, San Francisco, CA 94158 USA. EM sherre@neuropeds.ucsf.edu RI Richards, Linda/P-6372-2014 OI Richards, Linda/0000-0002-7590-7390 FU Pfizer Inc.; National Health and Medical Research Council Australia (NHMRC) [1048849]; Principal Research Fellowship from the NHMRC FX The authors would like to express their gratitude to Professor Jacqueline Crawley and her team that generated and behaviorally tested F2 inbred mice over a period of two years in her laboratory. This work was funded in part by a grant from Pfizer Inc. to EHS and a grant (1048849) from the National Health and Medical Research Council Australia (NHMRC) to LJR. LJR is supported by a Principal Research Fellowship from the NHMRC. 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Autism PD DEC 22 PY 2014 VL 5 AR 57 DI 10.1186/2040-2392-5-57 PG 12 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6CA UT WOS:000350451000001 PM 25874073 ER PT J AU Raschle, NM Smith, SA Zuk, J Dauvermann, MR Figuccio, MJ Gaab, N AF Raschle, Nora Maria Smith, Sara Ashley Zuk, Jennifer Dauvermann, Maria Regina Figuccio, Michael Joseph Gaab, Nadine TI Investigating the Neural Correlates of Voice versus Speech-Sound Directed Information in Pre-School Children SO PLoS One LA English DT Article ID SUPERIOR TEMPORAL SULCUS; SCANNER BACKGROUND-NOISE; HUMAN AUDITORY-CORTEX; RIGHT-HEMISPHERE; CORTICAL REPRESENTATION; FUNCTIONAL-ANATOMY; BRAIN ACTIVATION; ISOLATED VOWELS; INFANT BRAIN; PERCEPTION AB Studies in sleeping newborns and infants propose that the superior temporal sulcus is involved in speech processing soon after birth. Speech processing also implicitly requires the analysis of the human voice, which conveys both linguistic and extra-linguistic information. However, due to technical and practical challenges when neuroimaging young children, evidence of neural correlates of speech and/ or voice processing in toddlers and young children remains scarce. In the current study, we used functional magnetic resonance imaging (fMRI) in 20 typically developing preschool children (average age = 5.8 y; range 5.2-6.8 y) to investigate brain activation during judgments about vocal identity versus the initial speech sound of spoken object words. FMRI results reveal common brain regions responsible for voice-specific and speech-sound specific processing of spoken object words including bilateral primary and secondary language areas of the brain. Contrasting voice-specific with speech-sound specific processing predominantly activates the anterior part of the right-hemispheric superior temporal sulcus. Furthermore, the right STS is functionally correlated with left-hemispheric temporal and right hemispheric prefrontal regions. This finding underlines the importance of the right superior temporal sulcus as a temporal voice area and indicates that this brain region is specialized, and functions similarly to adults by the age of five. We thus extend previous knowledge of voice-specific regions and their functional connections to the young brain which may further our understanding of the neuronal mechanism of speech-specific processing in children with developmental disorders, such as autism or specific language impairments. C1 [Raschle, Nora Maria; Smith, Sara Ashley; Zuk, Jennifer; Dauvermann, Maria Regina; Figuccio, Michael Joseph; Gaab, Nadine] Boston Childrens Hosp, Dept Dev Med, Div Dev Med, Labs Cognit Neurosci, Boston, MA 02115 USA. [Raschle, Nora Maria; Zuk, Jennifer; Dauvermann, Maria Regina; Gaab, Nadine] Harvard Univ, Sch Med, Boston, MA USA. [Raschle, Nora Maria] Psychiat Univ Clin Basel, Dept Child & Adolescent Psychiat, Basel, Switzerland. [Gaab, Nadine] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Raschle, NM (reprint author), Boston Childrens Hosp, Dept Dev Med, Div Dev Med, Labs Cognit Neurosci, Boston, MA 02115 USA. EM nora.raschle@childrens.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health & Human Development [1R01HD065762-01/02/03]; Charles H. Hood Foundation; Boston Children's Hospital Pilot Grant; Swiss National Foundation; Janggen-Pohn Stiftung; National Institute of Health Institutional Training Grant [NIH T32 DC000038-22] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (1R01HD065762-01/02/03 to N.G.); Charles H. Hood Foundation (to N.G.); Boston Children's Hospital Pilot Grant (to N.G.); the Swiss National Foundation (to N.M.R.); the Janggen-Pohn Stiftung (to N.M.R.); and the National Institute of Health Institutional Training Grant (NIH T32 DC000038-22 to J.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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The aims of this study were to examine whether adolescents with anorexia nervosa have autism spectrum and/or obsessive-compulsive traits, how many would meet diagnostic criteria for autism spectrum disorder, and whether these traits are shared by parents. Methods: A total of 150 adolescents receiving outpatient treatment for anorexia nervosa or subthreshold anorexia nervosa and their parents completed the autism spectrum disorder and eating disorder sections of the Development and Well-being Assessment. Patients also completed the Children Yale-Brown Obsessive-Compulsive Scale and other measures of psychiatric morbidity, and parents completed the short Autism Quotient and Obsessive-Compulsive Inventory Revised. Results: Adolescents with anorexia nervosa had a below average social aptitude (19% below cut-off) and high levels of peer relationship problems (39% above cut-off) and obsessive-compulsive symptoms (56% above cut-off). Six cases (4%, all females) were assigned a possible (n = 5) or definite (n = 1) diagnosis of autism spectrum disorder. Parental levels of autism spectrum and obsessive-compulsive traits were within the normal range. Conclusions: This study suggests that adolescents with anorexia nervosa have elevated levels of autism spectrum traits, obsessive-compulsive symptoms, and a small proportion fulfil diagnostic criteria for a probable autism spectrum disorder. These traits did not appear to be familial. This comorbidity has been associated with a poorer prognosis. Therefore, adaptation of treatment for this subgroup may be warranted. C1 [Rhind, Charlotte; Hibbs, Rebecca; Goddard, Elizabeth; Macdonald, Pamela; Schmidt, Ulrike; Tchanturia, Kate; Treasure, Janet] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, Sect Eating Disorders, London SE5 8AF, England. [Bonfioli, Elena] Univ Verona, Dept Publ Hlth & Community Med, I-37134 Verona, Italy. [Gowers, Simon] Univ Liverpool, Psychol Sci, Liverpool L69 3GL, Merseyside, England. [Tchanturia, Kate] Ilia State Univ, Tbilisi 0162, Rep of Georgia. [Micali, Nadia] UCL, Inst Child Hlth, Behav & Brain Sci Unit, London WC1N 1EH, England. RP Rhind, C (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol Med, Sect Eating Disorders, PO59 103 Denmark Hill, London SE5 8AF, England. EM charlotte.c.rhind@kcl.ac.uk FU National Institute for Health Research (NIHR) under its Research for Patient Benefit program [PB-PG-0609-19025] FX This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit program (PB-PG-0609-19025). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. CR acknowledges scholarship funding from the Psychiatry Research Trust (PRT Grant Reference: 29). This study was supported by the United Kingdom Clinical Research Collaboration-registered King's Clinical Trials Unit at King's Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR Evaluation, Trials and Studies Coordinating Centre. We also thank the Principal Investigators, who were involved in the recruitment of participants at the outpatient sites, listed alongside the site-specific ethical bodies who approved the study as follows: S Clark-Stone, 2gether NHS Foundation Trust; W Clarke, Anuerin Bevan Local Health Board; D Robertson, Birmingham and Solihull Mental Health NHS Foundation Trust; N Dawson, Bradford District Care Trust; C Schrieber-Kounine, Avon and Wiltshire Mental Health Partnership NHS Trust; J Shapleske, Cambridgeshire and Peterborough NHS Foundation Trust; J Whittaker, Central Manchester University Hospitals NHS Foundation Trust; A Jones, Cornwall Partnership NHS Trust; K Goss, Coventry and Warwickshire Partnership NHS Trust; H Crowson, Derbyshire Mental Health Services NHS Trust; K. Higgins, Dudley and Walsall Mental Health NHS Trust; N Green, Humber Mental Health Teaching NHS Trust; A Lodwick, Hywel dda Health Board; N Jacobs, Kent and Medway NHS and Social Care Partnership Trust; C Newell, Kimmeridge Court, Dorset Healthcare University NHS Foundation Trust; J Morgan, Leeds Partnership NHS Foundation Trust and St George's University of London; J Arcelus, Leicestershire Partnership NHS Trust; H Birchall, Lincolnshire Partnership NHS Foundation Trust; R Thompson, Norfolk and Waveney Mental Health Foundation Trust; H Stephens, North Bristol NHS Trust; I Lea, North Essex Partnership Foundation NHS Trust; L Addicott, Nottinghamshire Healthcare NHS Trust; S Sankar, Northamptonshire Healthcare NHS Trust; J Holliday, Oxford Health NHS Foundation Trust; B Waites, Powys Local Health Board; H Strachan, Royal Bolton Hospital; A Fennell, Black Country Partnership NHS Foundation Trust; A Wolton, Somerset Partnership NHS Foundation Trust; H Gahan, South Essex Partnership University NHS Foundation Trust; G Moss, Sheffield Children's Hospital; J Orme, Sheffield Health and Social Care NHS Foundation Trust; K Moore, South Staffordshire and Shropshire Healthcare NHS Foundation Trust; G Burgoyne, Suffolk Mental Health Partnership NHS Trust; I. Eisler, South London and Maudsley NHS Foundation Trust; B Bamford, South- West London and St George's Mental Health Trust; I Yi, Surrey and Borders Partnership NHS Foundation Trust; and P Parker, Worcestershire Mental Health Partnership NHS Trust. 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Autism PD DEC 20 PY 2014 VL 5 AR 56 DI 10.1186/2040-2392-5-56 PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6BZ UT WOS:000350450900001 PM 25553237 ER PT J AU Irimia, M Weatheritt, RJ Ellis, JD Parikshak, NN Gonatopoulos-Pournatzis, T Babor, M Quesnel-Vallieres, M Tapial, J Raj, B O'Hanlon, D Barrios-Rodiles, M Sternberg, MJE Cordes, SP Roth, FP Wrana, JL Geschwind, DH Blencowe, BJ AF Irimia, Manuel Weatheritt, Robert J. Ellis, Jonathan D. Parikshak, Neelroop N. Gonatopoulos-Pournatzis, Thomas Babor, Mariana Quesnel-Vallieres, Mathieu Tapial, Javier Raj, Bushra O'Hanlon, Dave Barrios-Rodiles, Miriam Sternberg, Michael J. E. Cordes, Sabine P. Roth, Frederick P. Wrana, Jeffrey L. Geschwind, Daniel H. Blencowe, Benjamin J. TI A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains SO CELL LA English DT Article ID PROTEIN-INTERACTION NETWORKS; AMYLOID PRECURSOR PROTEIN; LINKED MENTAL-RETARDATION; MESSENGER-RNA; FUNCTIONAL DIVERSITY; SPLICING REGULATION; NEURITE OUTGROWTH; NERVOUS-SYSTEM; FE65; ISOFORM AB Alternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide "microexons'' display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism. C1 [Irimia, Manuel; Weatheritt, Robert J.; Ellis, Jonathan D.; Gonatopoulos-Pournatzis, Thomas; Babor, Mariana; Quesnel-Vallieres, Mathieu; Raj, Bushra; O'Hanlon, Dave; Roth, Frederick P.; Blencowe, Benjamin J.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada. [Irimia, Manuel; Tapial, Javier] CRG, EMBL CRG Res Unit Syst Biol, Barcelona 08003, Spain. [Weatheritt, Robert J.] MRC Lab Mol Biol, Cambridge CB2 0QH, England. [Parikshak, Neelroop N.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst,Dept Neurol, Los Angeles, CA 90095 USA. [Sternberg, Michael J. E.] Univ London Imperial Coll Sci Technol & Med, Ctr Integrat Syst Biol & Bioinformat, Dept Life Sci, London SW7 2AZ, England. [Barrios-Rodiles, Miriam; Cordes, Sabine P.; Roth, Frederick P.; Wrana, Jeffrey L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Cordes, Sabine P.; Roth, Frederick P.; Wrana, Jeffrey L.; Blencowe, Benjamin J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada. RP Irimia, M (reprint author), Univ Toronto, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada. EM mirimia@gmail.com; b.blencowe@utoronto.ca RI Wrana, Jeffrey/F-8857-2013; Cordes, Sabine/A-5423-2012; Roth, Frederick/H-6308-2011 FU Canadian Institute of Health Research (CIHR) Postdoctoral Fellowship; NIMH NRSA fellowship; Department of Cell and Systems Biology, University of Toronto; Banting and Best CIHR Scholarship; EMBO; OSCI; CIHR; Ontario Research Fund; Alzheimer's Society, Canada; University of Toronto McLaughlin Centre; NIH/NHGRI [P50 HG004233, U01HG001715]; Krembil Foundation; Avon Foundation; NIMH [5R37MH060233, 5R01MH094714]; Simons Foundation [SFARI 206744]; Canada Excellence Research Chairs Program FX The authors thank the Eunice Kennedy Shriver NICHD Brain and Tissue Bank for Developmental Disorders, the Autism Tissue Program, and the Harvard Brain Tissue Resource Center for providing brain samples. Dax Torti and Danica Leung of the Donnelly Sequencing Centre are gratefully acknowledged for sequencing samples. The authors also thank Xinchen Wang for initial contributions to the RNA-seq analysis pipeline, Ulrich Braunschweig for assistance with CLIP-seq analyses, Benjamin Lang for advice on surface accessibility measurements, Nuno Barbosa-Morais for guidance on statistical testing, and Serge Gueroussov and Jonathan Roth for helpful discussions and comments on the manuscript. M.I. holds an LTF from the Human Frontiers Science Program Organization. R.J.W. holds a Canadian Institute of Health Research (CIHR) Postdoctoral Fellowship. N.N.P. holds an NIMH NRSA fellowship. M.B. is supported by a fellowship from the Department of Cell and Systems Biology, University of Toronto. M.Q.-V. holds a Banting and Best CIHR Scholarship. T.G.-P. is supported by fellowships from EMBO and OSCI. This research was supported by grants from the CIHR (B.J.B., J.L.W., S.P.C.), Ontario Research Fund (J.L.W., B.J.B., and others), Alzheimer's Society, Canada (B.J.B.), University of Toronto McLaughlin Centre (B.J.B.), NIH/NHGRI (P50 HG004233 and U01HG001715) (F.P.R.), the Krembil Foundation (F.P.R.), the Avon Foundation (F.P.R.), NIMH (5R37MH060233 and 5R01MH094714) (D.H.G.), and the Simons Foundation (SFARI 206744) (D.H.G.). F.P.R. was also supported by the Canada Excellence Research Chairs Program. B.J.B. holds the Banbury Chair of Medical Research at the University of Toronto. 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Angry facial expressions act as threatening stimuli, and capture humans' attention more rapidly than emotionally positive facial expressions -a phenomenon known as the Anger Superiority Effect (ASE). Despite atypical emotional processing, adults with Autism Spectrum Disorders (ASD) have been reported to show ASE similar to typically developed (TD) individuals. One important question is whether the basic process for ASE is intact in individuals with ASD or whether instead they acquire an alternative process that enables ASE. To address this question, we tested the prevalence of ASE in young children with and without ASD using a face-in-the-crowd task. ASE was clearly observed in TD children, whereas ASD children did not show the effect. In contrast to previous reports of ASE in adults or relatively older children with ASD, our results suggest that in ASD basic predispositional mechanisms to allocate attention quickly towards angry faces are not preserved. C1 [Isomura, Tomoko; Masataka, Nobuo] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan. [Ito, Hiroyasu] Natl Rehabil Ctr Persons Disabil, Res Inst, Tokorozawa, Saitama, Japan. [Ogawa, Shino] Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Isomura, T (reprint author), Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan. EM isomurat8818@gmail.com FU Japan Society for the Promotion of Science (JSPS) [23653316]; Ministry of Education Culture, Sports, Science and Technology (MEXT) [A06]; Excellent Graduate Schools, MEXT; [12J03878]; [09J02998] FX This research was supported by a KAKENHI grant from the Japan Society for the Promotion of Science (JSPS; # 23653316 to NM); Grants-in-Aid for JSPS fellows (# 12J03878 to TI and # 09J02998 to HI); a grant from the Ministry of Education Culture, Sports, Science and Technology (MEXT) via its Global Centers of Excellence (gCOE) program (# A06 to Kyoto University) and Grants for Excellent Graduate Schools, MEXT. This research was conducted as a part of a broader project on Developmental Disorders and Support for Acquiring Reading and Writing Skills headed by the Kokoro Research Center, Kyoto University, and we thank its director, Dr. Sakiko Yoshikawa, and members of the project for their support. We thank Dr. Ikuma Adachi and Dr. Hiroki Koda for valuable comments and suggestions about data analysis and manuscript improvement, Ms. Misako Ida for assistance in data collection, Dr. Masahiro Shibasaki for help in creating the task, and Dr. Elizabeth Nakajima and Dr. James R. Anderson for English revision and useful comments. We are grateful to all of the families that have kindly and generously given their time to participate in this study. 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Hernandez for assistance in various experiments. We appreciate the help of C. Guo and the transgenic facility at Howard Hughes Medical Institute's (HHMI) Janelia Farm Research Campus in generating the Auts2 cKO mice. We are grateful to V. Bardwell and L. Di Croce for providing us PCGF1 and RING1B antibodies, respectively. We also thank A. Tarakhovsky for his generous help to our mouse work after Hurricane Sandy and L. Vales for valuable discussions and extensive reading of the manuscript. This work was supported as follows: the biochemical analysis of AUTS2 by the National Institute of Health grant GM-64844, and the mouse work by a Pilot Award from the Simons Foundation Autism Research Initiative (SFARI). A. S. is supported by grants from NIH (1DP2MH100012-01), Seaver Autism Foundation, and The Brain and Behavioral Research Fund Young Investigator Award (number 18194). Z.G. was supported by the SFARI pilot award and by an NIH training grant (5T32CA160002). P.L. was supported by an NIH postdoctoral fellowship (1F32GM105275). J.M.S was supported by an NIH postdoctoral fellowship (F32AA022842) as well as by the Simons Foundation as a Junior Fellow. 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A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses. Findings: We could not replicate the previous association between rs4307059 and social communication impairment. 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Autism PD DEC 16 PY 2014 VL 5 AR 55 DI 10.1186/2040-2392-5-55 PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6BW UT WOS:000350450600001 PM 25540679 ER PT J AU Engel, D Woolley, AW Jing, LX Chabris, CF Malone, TW AF Engel, David Woolley, Anita Williams Jing, Lisa X. Chabris, Christopher F. Malone, Thomas W. TI Reading the Mind in the Eyes or Reading between the Lines? Theory of Mind Predicts Collective Intelligence Equally Well Online and Face-To-Face SO PLOS ONE LA English DT Article ID HIGH-FUNCTIONING AUTISM; EMOTIONAL INTELLIGENCE; INDIVIDUAL-DIFFERENCES; COGNITIVE-ABILITY; ASPERGER-SYNDROME; TEAM PERFORMANCE; NORMAL ADULTS; PERSONALITY; CHILDREN; COMMUNICATION AB Recent research with face-to-face groups found that a measure of general group effectiveness (called "collective intelligence") predicted a group's performance on a wide range of different tasks. The same research also found that collective intelligence was correlated with the individual group members' ability to reason about the mental states of others (an ability called "Theory of Mind" or "ToM"). Since ToM was measured in this work by a test that requires participants to "read" the mental states of others from looking at their eyes (the "Reading the Mind in the Eyes" test), it is uncertain whether the same results would emerge in online groups where these visual cues are not available. Here we find that: (1) a collective intelligence factor characterizes group performance approximately as well for online groups as for face-to-face groups; and (2) surprisingly, the ToM measure is equally predictive of collective intelligence in both face-to-face and online groups, even though the online groups communicate only via text and never see each other at all. This provides strong evidence that ToM abilities are just as important to group performance in online environments with limited nonverbal cues as they are face-to-face. It also suggests that the Reading the Mind in the Eyes test measures a deeper, domain-independent aspect of social reasoning, not merely the ability to recognize facial expressions of mental states. C1 [Engel, David; Jing, Lisa X.; Malone, Thomas W.] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. [Woolley, Anita Williams] Carnegie Mellon Univ, Tepper Sch Business, Pittsburgh, PA 15213 USA. [Chabris, Christopher F.] Union Coll, Dept Psychol, Schenectady, NY 12308 USA. [Engel, David; Woolley, Anita Williams; Jing, Lisa X.; Chabris, Christopher F.; Malone, Thomas W.] MIT, Ctr Collect Intelligence, Cambridge, MA 02139 USA. RP Engel, D (reprint author), MIT, Sloan Sch Management, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dengel@mit.edu; awoolley@cmu.edu; malone@mit.edu FU National Science Foundation [IIS-0963285, ACI-1322254, IIS-0963451]; U.S. Army Research Office [56692-MA, 64079-NS]; Cisco Systems, Inc. through MIT Center for Collective Intelligence FX This work was made possible by financial support from the National Science Foundation (grant numbers IIS-0963285, ACI-1322254, and IIS-0963451), the U.S. Army Research Office (grant numbers 56692-MA and 64079-NS) and Cisco Systems, Inc. through their sponsorship of the MIT Center for Collective Intelligence. The funding was awarded to TM, AW and CC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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This results in Fragile X syndrome, the most common heritable cause of intellectual disability and a major cause of autism spectrum disorders. The mechanism of gene silencing is not fully understood, and efforts to reverse this gene silencing have had limited success. Here, we show that the level of trimethylation of histone H3 on lysine 27, a hallmark of the activity of EZH2, a component of repressive Polycomb Group (PcG) complexes like PRC2, is increased on reactivation of the silenced allele by either the DNA demethylating agent 5-azadeoxycytidine or the SIRT1 inhibitor splitomicin. The level of H3K27me3 increases and decreases in parallel with the FMR1 mRNA level. Furthermore, reducing the levels of the FMR1 mRNA reduces the accumulation of H3K27me3. This suggests a model for FMR1 gene silencing in which the FMR1 mRNA generated from the reactivated allele acts in cis to repress its own transcription via the recruitment of PcG complexes to the FMR1 locus. C1 [Kumari, Daman; Usdin, Karen] Natl Inst Diabet Digest & Kidney Dis, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by a grant from the Intramural program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health to K.U. 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An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. Copy number variants were called by PennCNV and filtered for frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining results with previous studies and using a cut-off of > 100 kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448 kb) was also intermediate between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ. Patients with a positive family history can also harbour de novo mutations. C1 [Georgieva, Lyudmila; Rees, Elliott; Craddock, Nicholas; Holmans, Peter; O'Donovan, Michael C.; Owen, Michael J.; Kirov, George] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. [Moran, Jennifer L.; Chambert, Kimberly D.; McCarroll, Steven] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Milanova, Vihra] Med Univ, Dept Psychiat, Sofia, Bulgaria. [Purcell, Shaun; Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Purcell, Shaun; Sklar, Pamela] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Kirov, G (reprint author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. EM kirov@cardiff.ac.uk RI Holmans, Peter/F-4518-2015 OI Holmans, Peter/0000-0003-0870-9412 FU Medical Research Council (MRC) Centre [G0800509, G0801418]; MRC PhD Studentship; Janssen Research Foundation [045856]; Wellcome Trust [045856]; Research Councils UK FX The work at Cardiff University was funded by Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418) and an MRC PhD Studentship to E.R. Funding for the recruitment of trios in Bulgaria was provided by the Janssen Research Foundation in 1999-2004, Ref: 045856. Funding for the recruitment of BD samples in the UK was provided by the Wellcome Trust as a Training Fellowship to G.K. in 1996-1999, Ref: 045856. The samples were genotyped at the Broad Institute, USA, funded by a philanthropic gift to the Stanley Center for Psychiatric Research. Funding to pay the Open Access publication charges for this article was provided by Research Councils UK. 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We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94,176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, AD., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120,155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Gill, Kelly Elizabeth; Evans, Elizabeth; Kayser, Juergen; Bruder, Gerard; Corcoran, Cheryl Mary] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Ben-David, Shelly] NYU, Sch Social Work, New York, NY 10003 USA. [Messinger, Julie; Malaspina, Dolores] NYU, Dept Psychiat, New York, NY 10016 USA. RP Corcoran, CM (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. 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PD DEC 15 PY 2014 VL 220 IS 1-2 BP 201 EP 204 DI 10.1016/j.psychres.2014.07.018 PG 4 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400031 PM 25066961 ER PT J AU Thaler, NS Sutton, GP Allen, DN AF Thaler, Nicholas S. Sutton, Griffin P. Allen, Daniel N. TI Social cognition and functional capacity in bipolar disorder and schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE Bipolar disorder; Schizophrenia; Social cognition; Functional capacity ID PSYCHOTIC FEATURES; IMPAIRMENT; MIND; DEFICITS; NEUROCOGNITION; ADULTS; INTELLIGENCE; RECOGNITION; MARKERS; AUTISM AB Social cognition is a functionally relevant predictor of capacity in schizophrenia (SZ), though research concerning its value for bipolar disorder (BD) is limited. The current investigation examined the relationship between two social cognitive factors and functional capacity in bipolar disorder. This study included 48 individuals with bipolar disorder (24 with psychotic features) and 30 patients with schizophrenia. Multiple regression controlling for estimated IQ scores was used to assess the predictive value of social cognitive factors on the UCSD Performance-Based Functional Skills Assessment (UPSA). Results found that for the bipolar with psychosis and schizophrenia groups, the social/emotion processing factor predicted the UPSA. The theory of mind factor only predicted the UPSA for the schizophrenia group.. Findings support the clinical utility of evaluating emotion processing in individuals with a history of psychosis. For BD, theory of mind may be better explained by a generalized cognitive deficit. In contrast, social/emotion processing may be linked to distinct neurobiological processes associated with psychosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Thaler, Nicholas S.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Sutton, Griffin P.] Univ N Carolina, Dept Psychol, Wilmington, NC 28401 USA. [Allen, Daniel N.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. RP Thaler, NS (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. 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PD DEC 15 PY 2014 VL 220 IS 1-2 BP 309 EP 314 DI 10.1016/j.psychres.2014.08.035 PG 6 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400049 PM 25200189 ER PT J AU Duan, GQ Yao, ML Ma, YT Zhang, WJ AF Duan, Guiqin Yao, Meiling Ma, Yating Zhang, Wenjing TI Perinatal and background risk factors for childhood autism in central China SO PSYCHIATRY RESEARCH LA English DT Article DE Childhood autism; Central China; Perinatal risk factors ID LOW-BIRTH-WEIGHT; SPECTRUM DISORDERS; INFANTILE-AUTISM; NEONATAL JAUNDICE; MATERNAL SMOKING; FAMILY-HISTORY; PATERNAL AGE; DIAGNOSIS; CHILDREN; ETIOLOGY AB Perinatal and background risk factors for autism were identified in a cohort of autistic children in Zhengzhou, China, to formulate preventative and treatment strategies for high-risk families. In this case-control study, children were screened for suspected autism using the Autism Behavior Checklist (ABC) and diagnosed according to DSM-IV and the Childhood Autism Rating Scale (CARS). We collected perinatal histories and clinical data of 286 confirmed autistic children treated at the Third Affiliated Hospital Children's Psychological Clinic of Zhengzhou University from 2011 to 2013. The control group consisted of 286 healthy children from area kindergartens. Maternal age > 30 years, parental introversion as measured by the Eysenck Personality Questionnaire, low level of parental education, smoking, abortion threat, pregnancy complications, maternal illness during pregnancy, maternal mental health, family history of mental illness, neonatal jaundice, birth asphyxia, premature rupture of the fetal membrane, and gestational age < 37 weeks were significantly higher in the autism group. These factors were significantly correlated with behavioral symptoms as measured by ABC scores (Kendall rank correlation). Birth asphyxia, neonatal jaundice, maternal age, parental introversion, family history of mental illness, abortion threat, premature delivery, and smoking were identified as independent risk factors by multivariate logistic regression. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ma, Yating] Peking Univ, Inst Child & Adolescent Hlth, Sch Publ Hlth, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Duan, Guiqin; Yao, Meiling] Zhengzhou Univ, Affiliated Hosp 3, Ctr Children Psychol & Behav, Zhengzhou 450052, Henan Province, Peoples R China. [Zhang, Wenjing] Beijing Acad Educ Sci, Beijing 100045, Peoples R China. RP Duan, GQ (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Ctr Children Psychol & Behav, Zhengzhou 450052, Henan Province, Peoples R China. 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PD DEC 15 PY 2014 VL 220 IS 1-2 BP 410 EP 417 DI 10.1016/j.psychres.2014.05.057 PG 8 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400064 PM 25085792 ER PT J AU Bejerot, S Eriksson, JM Mortberg, E AF Bejerot, Susanne Eriksson, Jonna M. Mortberg, Ewa TI Social anxiety in adult autism spectrum disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Autism spectrum disorder; Social anxiety disorder; Autism spectrum quotient ID ASPERGER-SYNDROME; SELF-REPORT; ADOLESCENTS; VALIDITY; CHILDREN; PHOBIA; SCALE AB A link has been suggested between Autism Spectrum Disorder (ASD) and anxiety disorders. The aim of the study was to examine the severity of social anxiety measured by the Liebowitz Social Anxiety Scale Self-Report and prevalence of Social Anxiety Disorder (SAD) in adults with ASD, with SAD and a non-ASD comparison group. 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PD DEC 15 PY 2014 VL 220 IS 1-2 BP 705 EP 707 DI 10.1016/j.psychres.2014.08.030 PG 3 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400109 PM 25200187 ER PT J AU Rhind, C Mandy, W Treasure, J Tchanturia, K AF Rhind, Charlotte Mandy, William Treasure, Janet Tchanturia, Kate TI An exploratory study of evoked facial affect in adolescent females with anorexia nervosa SO PSYCHIATRY RESEARCH LA English DT Article DE Eating disorders; Emotion; Facial expression ID EMOTIONAL EXPRESSION; CHILDREN; BRAIN; DISORDERS; DURATION; SPECTRUM; ILLNESS; AUTISM; MODEL; SCALE AB The aim of this exploratory study was to investigate facial affect in adolescent females with anorexia nervosa (AN). Evoked facial affect was recorded whilst AN and control participants (n=34) viewed emotional films. Significantly less facial affect was found in AN adolescents, despite reporting no differences in subjective emotion experience. These findings correspond with previous studies in adults with AN. Altered facial affect may impair interpersonal functioning and contribute to illness maintenance. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Rhind, Charlotte; Treasure, Janet; Tchanturia, Kate] Kings Coll London, Inst Psychiat, Dept Psychol Med, Sect Eating Disorders, London SE5 8AF, England. [Mandy, William] UCL, Dept Hlth & Clin Psychol, London, England. [Tchanturia, Kate] South London & Maudsley NHS Trust, Eating Disorders Natl Serv, London, England. [Tchanturia, Kate] Tbilisi Illia Univ, Tbilisi, Rep of Georgia. RP Rhind, C (reprint author), Kings Coll London, Inst Psychiat, Dept Psychol Med, Sect Eating Disorders, De Crespigny Pk, London SE5 8AF, England. 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TI Understanding the behavioural phenotype of the precocial spiny mouse SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Acomys cahirinus; Exploratory activity; Fear and anxiety; Sensorimotor gating; Motor coordination; Social interaction ID ACOMYS-CAHIRINUS; PREPULSE INHIBITION; PERINATAL-DEVELOPMENT; OBJECT RECOGNITION; LOCOMOTOR-ACTIVITY; BRAIN-DEVELOPMENT; MENTAL-ILLNESS; TEST BATTERIES; SCHIZOPHRENIA; STARTLE AB The use of the spiny mouse (Acomys cahirinus) in experimental research is steadily increasing, due to the precocial nature of this species and the similarities in endocrinology to the human. The characterisation of normal behavioural traits throughout development has not been comprehensively measured in the spiny mouse. Therefore the aim of this study was to behaviourally phenotype the spiny mouse, with the use of behavioural paradigms commonly used to assess behaviour in rat and mouse models of human behavioural disorders such as autism, attention-deficit disorder, and schizophrenia. Male and female spiny mice were assessed at 1-5,10-15,20-25,40-45 and 80-85 days of age using the open field test, novel object recognition test, rotarod, elevated plus maze, a social interaction test, and prepulse inhibition. Exploratory activity, motor coordination, fear, anxiety and social behaviours could be accurately measured from 1 day of age. Open field exploration and motor coordination on a modified rotarod were precociously developed by 10-15 and 20-25 days of age, respectively, when they were equivalent to the performance of conventional adult mice. Learning and memory (assessed by the novel object recognition test), and sensory gating (prepulse inhibition) could be reliably determined only after 20-25 days of age, and performance on these tests differed significantly between male and female spiny mice, particularly in adulthood. This study characterises the behavioural traits of spiny mice and provides important information about critical periods of behavioural development throughout postnatal life. (C) 2014 Elsevier B.V. All rights reserved. C1 [Ratnayake, Udani; Quinn, Tracey; Dickinson, Hayley; Waker, David W.] Monash Univ, MIMR PHI Inst, Ritchie Ctr, Clayton, Vic 3168, Australia. [Ratnayake, Udani; Daruwalla, Kerman] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia. [Waker, David W.] Monash Univ, Dept Obstet & Gynaecol, Clayton, Vic 3168, Australia. RP Ratnayake, U (reprint author), Univ Melbourne, Florey Inst Neurosci & Mental Hlth, 30 Royal Parade, Parkville, Vic 3010, Australia. EM Udani.ratnayake@florey.edu.au FU NHMRC; ANZ Trustees; Victorian Government's Operational Infrastructure Support Program; Australian Postgraduate Award scholarships; NHMRC Career Development Fellowship FX This research has been undertaken in the authors' capacity as a staff member, student or affiliate of MIMR-PHI Institute, Monash University and with assistance of Lisa Davis and Annike Griffey. The NHMRC (to HD), ANZ Trustees (to HD; Provision of funds for PPI) and the Victorian Government's Operational Infrastructure Support Program supported this work. UR and TQ were in receipt of Australian Postgraduate Award scholarships during the period of this study. DW was an NHMRC Principal Research Fellow, and is now Senior Scientist at MIMR-PHI Institute. HD is funded by an NHMRC Career Development Fellowship. 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Brain Res. PD DEC 15 PY 2014 VL 275 BP 62 EP 71 DI 10.1016/j.bbr.2014.08.035 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AS7IX UT WOS:000344431100008 PM 25157432 ER PT J AU Meyer, LR Zhu, V Miller, A Roghair, RD AF Meyer, Lauritz R. Zhu, Vivian Miller, Alise Roghair, Robert D. TI Growth restriction, leptin, and the programming of adult behavior in mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Leptin; Growth restriction; Developmental origin; Behavior; ADHD; Autism ID LOW-BIRTH-WEIGHT; AUTISM SPECTRUM DISORDERS; GESTATIONAL-AGE INFANTS; POSTNATAL-GROWTH; PRETERM INFANTS; BORN PRETERM; OUTCOMES; CHILDREN; RATS; METAANALYSIS AB Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80 ng/g), and GR was identified by a wean-ling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6 s vs 87+/-7 s for controls, p < 0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p < 0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10 s vs 36+/-5 s, p < 0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. (C) 2014 Elsevier B.V. All rights reserved. C1 [Meyer, Lauritz R.; Zhu, Vivian; Miller, Alise; Roghair, Robert D.] Univ Iowa, Stead Family Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. RP Meyer, LR (reprint author), Stead Family Dept Pediat, 1270 CBRB, Iowa City, IA 52242 USA. 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Brain Res. PD DEC 15 PY 2014 VL 275 BP 131 EP 135 DI 10.1016/j.bbr.2014.08.054 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AS7IX UT WOS:000344431100018 PM 25196633 ER PT J AU Kolevzon, A Bush, L Wang, AT Halpern, D Frank, Y Grodberg, D Rapaport, R Tavassoli, T Chaplin, W Soorya, L Buxbaum, JD AF Kolevzon, Alexander Bush, Lauren Wang, A. Ting Halpern, Danielle Frank, Yitzchak Grodberg, David Rapaport, Robert Tavassoli, Teresa Chaplin, William Soorya, Latha Buxbaum, Joseph D. TI A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome SO MOLECULAR AUTISM LA English DT Article ID 22Q13.3 DELETION SYNDROME; AUTISM SPECTRUM DISORDERS; MOLECULAR CHARACTERIZATION; SPATIAL STATISTICS; SHANK3 GENE; DEFICITS; HAPLOINSUFFICIENCY; COMMUNICATION; MUTATIONS; PHENOTYPE AB Background: Autism spectrum disorder (ASD) is now understood to have multiple genetic risk genes and one example is SHANK3. SHANK3 deletions and mutations disrupt synaptic function and result in Phelan-McDermid syndrome (PMS), which causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. Recent evidence from preclinical studies with mouse and human neuronal models of SHANK3 deficiency suggest that insulin-like growth factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits. The objective of this study was to pilot IGF-1 treatment in children with PMS to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors. Methods: Nine children with PMS aged 5 to 15 were enrolled in a placebo-controlled, double-blind, crossover design study, with 3 months of treatment with IGF-1 and 3 months of placebo in random order, separated by a 4-week wash-out period. Results: Compared to the placebo phase, the IGF-1 phase was associated with significant improvement in both social impairment and restrictive behaviors, as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, respectively. IGF-1 was found to be well tolerated and there were no serious adverse events in any participants. Conclusions: This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. Results also provide proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function. C1 [Kolevzon, Alexander; Bush, Lauren; Wang, A. Ting; Halpern, Danielle; Frank, Yitzchak; Grodberg, David; Tavassoli, Teresa; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Kolevzon, Alexander; Wang, A. Ting; Buxbaum, Joseph D.] Friedman Brain Inst, New York, NY USA. [Kolevzon, Alexander; Buxbaum, Joseph D.] Mindich Child Hlth Inst, New York, NY USA. [Kolevzon, Alexander; Bush, Lauren; Wang, A. Ting; Halpern, Danielle; Frank, Yitzchak; Grodberg, David; Tavassoli, Teresa; Buxbaum, Joseph D.] Dept Psychiat, New York, NY USA. [Kolevzon, Alexander; Frank, Yitzchak; Rapaport, Robert] Dept Pediat, New York, NY USA. [Wang, A. Ting; Buxbaum, Joseph D.] Dept Neurosci, New York, NY USA. [Frank, Yitzchak] Dept Neurol, New York, NY USA. [Buxbaum, Joseph D.] Dept Genet, New York, NY USA. [Buxbaum, Joseph D.] Dept Genom Sci, New York, NY USA. [Rapaport, Robert] Dept Endocrinol, New York, NY USA. [Rapaport, Robert] Dept Diabet, New York, NY USA. [Kolevzon, Alexander; Bush, Lauren; Wang, A. Ting; Halpern, Danielle; Frank, Yitzchak; Grodberg, David; Rapaport, Robert; Tavassoli, Teresa; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Chaplin, William] St Johns Univ, Dept Psychol, New York, NY USA. [Soorya, Latha] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. RP Kolevzon, A (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM alexander.kolevzon@mssm.edu FU Beatrice and Samuel A Seaver Foundation; National Institutes of Health (NIMH) [R34 MH100276-01]; Phelan-McDermid Syndrome Foundation FX This work was supported by grants from the Beatrice and Samuel A Seaver Foundation and the National Institutes of Health (NIMH grant R34 MH100276-01 to AK). We would like to thank the Phelan-McDermid Syndrome Foundation for their support disseminating information about the trial - more information about PMS can be found through the Foundation at www.22q13.org or the Seaver Autism Center at www.shank3gene.org. We would also like to express our gratitude to the many families that work closely with us to better understand neurodevelopmental disability and a special thanks to the nine children and families who participated in this trial. 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Autism PD DEC 12 PY 2014 VL 5 AR 54 DI 10.1186/2040-2392-5-54 PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CC6BT UT WOS:000350450300001 PM 25685306 ER PT J AU Lu, ZY Wang, Y Chen, F Tong, HM Reddy, MVVVS Luo, L Seshadrinathan, S Zhang, L Holthauzen, LMF Craig, AM Ren, G Rudenko, G AF Lu, Zhuoyang Wang, Yun Chen, Fang Tong, Huimin Reddy, M. V. V. V. Sekhar Luo, Lin Seshadrinathan, Suchithra Zhang, Lei Holthauzen, Luis Marcelo F. Craig, Ann Marie Ren, Gang Rudenko, Gabby TI Calsyntenin-3 Molecular Architecture and Interaction with Neurexin 1 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Adhesion; Cell Surface Receptor; Protein-Protein Interaction; Single-particle Analysis; Synapse; Calsyntenins; Neurexins; Neuropsychiatric Disorders; Synaptic Organizers ID CELL-ADHESION; ELECTRON-MICROSCOPY; SYNAPSE DEVELOPMENT; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; LIGAND-BINDING; LNS DOMAIN; BETA; VISUALIZATION; NEUROLIGINS AB Background: Calsyntenin-3 (Cstn3) promotes synapse development, controversially interacting with neurexin 1 (n1). Results: Cstn3 binds n1 directly, and its structure adopts multiple forms. Conclusion: Cstn3 interacts with n1 via a novel mechanism and can produce distinct trans-synaptic bridges with n1. Significance: A complex portfolio of molecular interactions between proteins implicated in autism spectrum disorder and schizophrenia guide synapse development. Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1 (n1), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1 to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1 directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1 biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca2+, and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1 interact directly and that both Cstn3 monomers and tetramers bind n1 with nanomolar affinity. The interaction is promoted by Ca2+ and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1 compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1 to recruit and spatially organize proteins into networks essential for synaptic function. C1 [Reddy, M. V. V. V. Sekhar; Seshadrinathan, Suchithra; Rudenko, Gabby] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA. [Holthauzen, Luis Marcelo F.; Rudenko, Gabby] Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA. [Lu, Zhuoyang; Tong, Huimin; Zhang, Lei; Ren, Gang] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, Berkeley, CA 94720 USA. [Lu, Zhuoyang] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Xian 710049, Peoples R China. [Lu, Zhuoyang] Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Xian 710049, Peoples R China. [Luo, Lin; Craig, Ann Marie] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 2A1, Canada. [Wang, Yun; Chen, Fang] Univ Michigan, Ann Arbor, MI 48109 USA. RP Ren, G (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry Rm 2220,1 Cyclotron Rd,MS 67R2206, Berkeley, CA 94720 USA. EM gren@lbl.gov RI Foundry, Molecular/G-9968-2014 FU National Institutes of Health, NIMH [R01MH077303, R01MH070860]; Sealy Center for Structural Biology and Molecular Biophysics (UTMB); Brain and Behavior Research Foundation; United States Department of Energy [DE-AC02-05CH11231] FX This work was supported, in whole or in part, by National Institutes of Health, NIMH, Grants R01MH077303 and R01MH070860. This work was also supported by the Sealy Center for Structural Biology and Molecular Biophysics (UTMB) and the Brain and Behavior Research Foundation. Work at the Molecular Foundry was supported by the United States Department of Energy under Contract DE-AC02-05CH11231. 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Copy Number Variants (CNVs) responsible for complex phenotypes with Social Communication Disorder (SCD), may contribute to improve knowledge about the distinction between intellectual deficiency and autism spectrum disorders. Case presentation: We report the clinical and cytogenetic characterization of a patient (male, 33 years-old, first child of healthy Portuguese non-consanguineous parents) presenting with a complex phenotype including SCD without intellectual deficiency and carrying a mosaic supernumerary ring chromosome 19p. Microarray-Based Comparative Genomic Hybridization and Fluorescence in situ Hybridization were performed. Genetic analysis showed a large mosaic interstitial duplication 19p13.12p12 of the short arm of chromosome 19, spanning 8.35 Mb. Our data suggested a putative association between psychosocial dysfunction and mosaic pure trisomy 19p13.2p12. 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[Jiang, Liwen] Chinese Univ Hong Kong, Ctr Cell & Dev Biol, Sch Life Sci, Shatin, Hong Kong, Peoples R China. [Jiang, Liwen] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Shatin, Hong Kong, Peoples R China. [Yung, Wing-Ho] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. RP Ip, NY (reprint author), Hong Kong Univ Sci & Technol, Mol Neurosci Ctr, Ctr Stem Cell Res, Div Life Sci,State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China. EM boip@ust.hk FU Hong Kong Research Grants Council Theme-based Research Scheme [T13-607/12R]; National Key Basic Research Program of China [2013CB530900]; Research Grants Council of Hong Kong SAR [660810, 660110, 661111, 661013]; SH Ho Foundation FX We are grateful to Dr. Eric Klann for sharing protocols of the behavioral tests. 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Khoutorsky, Arkady Cao, Ruifeng Jafarnejad, Seyed Mehdi Prager-Khoutorsky, Masha Giannakas, Nikolaos Kaminari, Archontia Fragkouli, Apostolia Nader, Karim Price, Theodore J. Konicek, Bruce W. Graff, Jeremy R. Tzinia, Athina K. Lacaille, Jean-Claude Sonenberg, Nahum TI Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes SO CELL REPORTS LA English DT Article ID HIPPOCAMPAL AREA CA1; MOUSE MODEL; MENTAL-RETARDATION; PROTEIN-SYNTHESIS; SYNAPTIC PLASTICITY; EIF4E PHOSPHORYLATION; GENETIC REMOVAL; AUTISM; MINOCYCLINE; MICE AB Fragile X syndrome (FXS) is the leading genetic cause of autism. Mutations in Fmr1 (fragile X mental retardation 1 gene) engender exaggerated translation resulting in dendritic spine dysmorphogenesis, synaptic plasticity alterations, and behavioral deficits in mice, which are reminiscent of FXS phenotypes. Using postmortem brains from FXS patients and Fmr1 knockout mice (Fmr1(-/y)), we show that phosphorylation of the mRNA 5' cap binding protein, eukaryotic initiation factor 4E (eIF4E), is elevated concomitant with increased expression of matrix metalloproteinase 9 (MMP-9) protein. Genetic or pharmacological reduction of eIF4E phosphorylation rescued core behavioral deficits, synaptic plasticity alterations, and dendritic spine morphology defects via reducing exaggerated translation of Mmp9 mRNA in Fmr1(-/y) mice, whereas MMP-9 overexpression produced several FXS-like phenotypes. These results uncover a mechanism of regulation of synaptic function by translational control of Mmp-9 in FXS, which opens the possibility of new treatment avenues for the diverse neurological and psychiatric aspects of FXS. C1 [Gkogkas, Christos G.; Khoutorsky, Arkady; Cao, Ruifeng; Jafarnejad, Seyed Mehdi; Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada. [Gkogkas, Christos G.; Khoutorsky, Arkady; Cao, Ruifeng; Jafarnejad, Seyed Mehdi; Sonenberg, Nahum] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada. [Prager-Khoutorsky, Masha] McGill Univ, Montreal Gen Hosp, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. [Giannakas, Nikolaos; Kaminari, Archontia; Fragkouli, Apostolia; Tzinia, Athina K.] Natl Ctr Sci Res Demokritos, Inst Biosci & Applicat, Athens 15310, Greece. [Nader, Karim] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. [Price, Theodore J.] Univ Texas Dallas, Sch Behav & Brain Sci, Dallas, TX 75080 USA. [Konicek, Bruce W.; Graff, Jeremy R.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Lacaille, Jean-Claude] McGill Univ, GRSNC, Montreal, PQ H3C 3J7, Canada. [Lacaille, Jean-Claude] McGill Univ, Dept Neurosci, Montreal, PQ H3C 3J7, Canada. RP Gkogkas, CG (reprint author), Univ Edinburgh, Patrick Wild Ctr, Hugh Robson Bldg, Edinburgh EH8 9XD, Midlothian, Scotland. EM christos.gkogkas@ed.ac.uk; nahum.sonenberg@mcgill.ca FU CIHR [MOP-114994, MOP-125985]; Azrieli Foundation and Brain Canada team grant; Fonds de la Recherche du Quebe-Sante; FRQS; Groupe de Recherche sur le Systeme Nerveux Central); Canada Research Chair in Cellular and Molecular Neurophysiology; Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund; NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore and the Harvard Brain Tissue Resource Center [R24-MH 068855] FX This work was supported by a CIHR operating grant to N.S. (MOP-114994) and J.-C.L. (MOP-125985), the Azrieli Foundation and Brain Canada team grant to N. S. and J.-C.L., the Fonds de la Recherche du Quebe-Sante (grant to J.-C.L. FRQS; Groupe de Recherche sur le Systeme Nerveux Central). J.-C.L. is the recipient of the Canada Research Chair in Cellular and Molecular Neurophysiology. C.G.G. received support from the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund. Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore and the Harvard Brain Tissue Resource Center (grant number R24-MH 068855). We thank P. Hagerman and G. Espinal-Goyne for FXS postmortem brain samples and A. Sylvestre, S. Perreault, C. Lister, K. Gamache, and I. Harvey for technical assistance. J.R.G. and B.W.K. are employees of Eli Lilly and Company. 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Shankar, K. Welfare, W. S. Wilson, R. W. Khiroya, C. Munslow, G. Fiefield, D. Bothra, V. McCann, R. TI Measles outbreak in Greater Manchester, England, October 2012 to September 2013: epidemiology and control SO EUROSURVEILLANCE LA English DT Article ID CAUSAL ASSOCIATION; AUTISM AB This paper describes the epidemiology and management of a prolonged outbreak of measles across the 2.7 million conurbation of Greater Manchester in the United Kingdom. Over a period of one year (from October 2012 to September 2013), over a thousand suspected measles cases (n = 1,073) were notified across Greater Manchester; of these, 395 (37%) were laboratory-confirmed, 91 (8%) were classed as probable, 312 (29%) were classed as possible and 275 (26%) excluded. Most confirmed and probable cases occurred in children within two age groups -infants (too young to be eligible for measles-mumps-rubella (MMR) vaccination according to the national immunisation programme) and children aged 10-19 years (low vaccine uptake in this cohort because of unfounded alleged links between the MMR vaccine and autism). During this one year period, there were a series of local outbreaks and many of these occurred within the secondary school setting. A series of public health measures were taken to control this prolonged outbreak: setting up incident management teams to control local outbreaks, a concerted immunisation catch-up campaign (initially local then national) to reduce the pool of children partially or totally unprotected against measles, and the exclusion of close contacts from nurseries and school settings for a period of 10 days following the last exposure to a case of measles. C1 [Pegorie, M.; Shankar, K.; Welfare, W. S.; Fiefield, D.; Bothra, V.; McCann, R.] Publ Hlth England, Greater Manchester Publ Hlth England Ctr, Hlth Protect Team, Manchester, Lancs, England. [Welfare, W. S.; McCann, R.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Wilson, R. W.] Univ Manchester, Manchester Med Sch, Manchester, Lancs, England. [Khiroya, C.; Munslow, G.] Publ Hlth England, NHS England, Greater Manchester Screening & Immunisat Team, Manchester, Lancs, England. RP Pegorie, M (reprint author), Publ Hlth England, Greater Manchester Publ Hlth England Ctr, Hlth Protect Team, Manchester, Lancs, England. 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Heussler, Helen S. Banko, Jessica L. Weeber, Edwin J. TI An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome SO BMC NEUROLOGY LA English DT Article DE Angelman syndrome; Cognitive impairment; Ataxia; Epilepsy; Seizure; Autism ID SYNAPTIC PLASTICITY; MOUSE MODEL; MENTAL-RETARDATION; THERAPEUTIC TRIAL; IN-VIVO; RECEPTORS; EEG; EPILEPSY; UBE3A; MICE AB Background: Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug s effect on the cognitive and behavioral manifestations of the disorder. Methods: Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p < 0.05 using ANOVA and partial eta squared (eta(2)) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnetts post hoc testing. Results: Significant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period. Conclusion: The clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted. C1 [Grieco, Joseph C.; Ciarlone, Stephanie L.; Weeber, Edwin J.] Univ S Florida, Dept Mol Pharmacol & Physiol, Morsani Coll Med, Tampa, FL 33612 USA. [Gieron-Korthals, Maria] Univ S Florida, Dept Pediat, Morsani Coll Med, Tampa, FL 33612 USA. [Schoenberg, Mike R.; Philpot, Rex M.] Univ S Florida, Dept Psychiat, Morsani Coll Med, Tampa, FL 33612 USA. [Schoenberg, Mike R.; Philpot, Rex M.] Univ S Florida, Dept Behav Neurosci, Morsani Coll Med, Tampa, FL 33612 USA. [Gieron-Korthals, Maria; Schoenberg, Mike R.] Univ S Florida, Dept Neurol, Morsani Coll Med, Tampa, FL 33612 USA. [Schoenberg, Mike R.; Smith, Amanda G.; Banko, Jessica L.; Weeber, Edwin J.] Univ S Florida, Hlth S Byrd Alzheimers Res Inst, Tampa, FL 33613 USA. [Heussler, Helen S.] Univ Queensland, Mater Res Inst, St Lucia, Qld 4072, Australia. RP Weeber, EJ (reprint author), Univ S Florida, Dept Mol Pharmacol & Physiol, Morsani Coll Med, 12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM eweeber@health.usf.edu FU Foundation for Angelman Syndrome Therapeutics FX This research was funded by a grant from the Foundation for Angelman Syndrome Therapeutics. We would like to offer a special thank you to the staff that made this study possible including: University of South Florida Department of Psychiatry and Neuropsychology pyschometricians Anna Beattie, M.S. and Loriann Chambers M.P.H., University of South Florida Research Pharmacy technician Mark Pennington, CNMT, CPhT as well as the research staff at the Tampa General Hospital s Center for Outpatient Research Excellence including Orlando Fabelo, M.A., Kevin Khlar, M.A., Hayley Kourtellis, B.A. and, Karen Thomas, R.EEG PSG T. 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PD DEC 10 PY 2014 VL 14 AR 232 DI 10.1186/s12883-014-0232-x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AZ3YE UT WOS:000348159000001 PM 25491305 ER PT J AU Schuch, JB Muller, D Endres, RG Bosa, CA Longo, D Schuler-Faccini, L Ranzan, J Becker, MM Riesgo, RD Roman, T AF Schuch, Jaqueline Bohrer Muller, Diana Endres, Renata Giuliani Bosa, Cleonice Alves Longo, Danae Schuler-Faccini, Lavinia Ranzan, Josiane Becker, Michele Michelin Riesgo, Rudimar dos Santos Roman, Tatiana TI The role of beta 3 integrin gene variants in Autism Spectrum Disorders - Diagnosis and symptomatology SO GENE LA English DT Article DE Autism; ASD; ITGB3 gene; Echolalia; Association; Clinical symptoms ID WHOLE-BLOOD SEROTONIN; ITGB3; ASSOCIATION; POPULATION; SLC6A4; SUSCEPTIBILITY; INVOLVEMENT; FAMILIES; CHILDREN; SCREEN AB Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the beta 3 integrin locus (ITGB3), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P = 0.006; P-corr = 0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P = 0.008; P-corr = 0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (P-glcorr = 0.048; P-indcorr = 0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects. (C) 2014 Elsevier B.V. All rights reserved. C1 [Schuch, Jaqueline Bohrer; Muller, Diana; Longo, Danae; Schuler-Faccini, Lavinia; Roman, Tatiana] Univ Fed Rio Grande do Sul, Dept Genet, Biosci Inst, BR-91501970 Porto Alegre, RS, Brazil. [Endres, Renata Giuliani; Bosa, Cleonice Alves] Univ Fed Rio Grande do Sul, Dept Psychol, BR-90035003 Porto Alegre, RS, Brazil. [Ranzan, Josiane; Becker, Michele Michelin; Riesgo, Rudimar dos Santos] Univ Fed Rio Grande do Sul, Clin Hosp Porto Alegre, Child Neurol Unit, BR-90035903 Porto Alegre, RS, Brazil. RP Schuch, JB (reprint author), Univ Fed Rio Grande do Sul, Dept Genet, Caixa Postal 15053, BR-91501970 Porto Alegre, RS, Brazil. EM jaqbs.bio@gmail.com; cleobosa@uol.com.br; rriesgo@hcpa.ufrgs.br; troman29@yahoo.com.br FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [484403/2007-9]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [AUX-PE-PROEX-376/2009, 1234/2011]; Fundo de Incentivo a Pesquisa e Eventos-Clinics Hospital de Porto Alegre (FIPE-HCPA) [05-451]; Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [07/0045-3]; CNPq-Institutos do Milenio [420019/05-7] FX This study was funded by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, no 484403/2007-9), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, AUX-PE-PROEX-376/2009 and 1234/2011), Fundo de Incentivo a Pesquisa e Eventos-Clinics Hospital de Porto Alegre (FIPE-HCPA, no 05-451), Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, no 07/0045-3) and CNPq-Institutos do Milenio (no 420019/05-7). We would like to thank both the clinical staff at the Child Neurology Unit and technicians at the Laboratory of Biological Samples Collection from Clinics Hospital of Porto Alegre for their assistance with the clinical data and blood sample collections, respectively. We also thank Dr. Sandra Leistner-Segal at Medical Genetics Service from the Clinics Hospital of Porto Alegre for the fragile X syndrome genotyping, Prof. Sidia Maria Callegari-Jacques of the Department of Statistics from UFRGS and Prof. Claiton H. D. Bau of the Department of Genetics from UFRGS for helping with the statistical analyses. We lastly would like to thank to the families who kindly participated in this research. 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Nijhof, Bonnie Bosch, Danielle G. M. Kohansal-Nodehi, Mahdokht Keerthikumar, Shivakumar Heimel, J. Alexander TI Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE autism; excitation; inhibition; balance; gene expression; age effect ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; DOWN-REGULATION; GLUTAMATE-RECEPTOR-6 GENE; ASSOCIATION; RECEPTORS; MODEL; HIPPOCAMPAL; POPULATION; RESOURCE AB Autism spectrum disorders( ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and tha tgene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. 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Neurosci. PD DEC 8 PY 2014 VL 8 DI 10.3389/fnins.2014.00394 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AW9DH UT WOS:000346557300001 PM 25538548 ER PT J AU Qi, Y Shang, JY Ma, LJ Sun, BB Hu, XG Liu, B Zhang, GJ AF Qi, Yong Shang, Jun-yi Ma, Li-jun Sun, Bei-bei Hu, Xin-gang Liu, Bao Zhang, Guo-jun TI Inhibition of AMPK expression in skeletal muscle by systemic inflammation in COPD rats SO RESPIRATORY RESEARCH LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; AUTISM SPECTRUM DISORDERS; ACTIVATED PROTEIN-KINASE; RESVERATROL; DYSFUNCTION; EXERCISE; COENZYME; WEAKNESS; SIRT1 AB Background: Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation and inflammation. Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness. Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism. However, it remains unclear whether and how the expression levels of AMPK are affected in the COPD model rats which may lead to the dysfunction of the skeletal muscle in these rats. Methods: Here we developed a rat model of COPD, and we investigated the morphological changes of peripheral skeletal muscle and measured the levels of tumor necrosis factor - alpha (TNF-alpha) and AMPK in skeletal muscle by using approaches that include immunohistochemistry and polymerase chain reaction (PCR). Results: We found that the expression levels of both AMPK mRNA and protein in skeletal muscles were significantly reduced in the COPD model rats, in comparison to those from the control rats, the COPD model rats that received treatments with AICAR and resveratrol, whereas the expression levels of TNF-alpha were elevated in COPD rats. Conclusion: Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients. C1 [Qi, Yong; Shang, Jun-yi; Ma, Li-jun; Sun, Bei-bei; Hu, Xin-gang; Liu, Bao] Zhengzhou Univ, Peoples Hosp, Henan Prov Peoples Hosp, Dept Resp & Crit Care Med, Zhengzhou 450003, Peoples R China. [Zhang, Guo-jun] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Zhengzhou 450003, Peoples R China. RP Zhang, GJ (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, 1 Jianshe East Rd, Zhengzhou 450003, Peoples R China. 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Here we employ a novel psychophysical method for measuring empathic performance that quantitatively measures the ability of subjects to decode the experience of another person's pain. In 50 female subjects, we acquired functional magnetic resonance imaging data as they were exposed to a target subject experiencing variable degrees of pain, whilst performing an irrelevant attention-demanding task. We investigated the effect of variation in the oxytocin receptor gene (OXTR) and the serotonin transporter gene (SLC6A4) on the psychophysical and neurometric variability associated with empathic performance. The OXTR rs2268498 and rs53576 polymorphisms, but not the SLC6A4 5-HTTLPR, were associated with significant differences in empathic accuracy, with CC- and AA-carriers, respectively, displaying higher empathic accuracy. For OXTR rs2268498 there was also a genotype difference in the correlation between empathic accuracy and activity in the superior temporal sulcus (STS). In OXTR rs2268498 CC-carriers, high empathic accuracy was associated with stronger responsiveness of the right STS to the observed pain. Together, the results show that genetic variation in the OXTR has significant influence on empathic accuracy and that this may be linked to variable responsivity of the STS. C1 [Laursen, Helle Ruff; Siebner, Hartwig Roman; Haren, Tina; Madsen, Kristoffer; Hulme, Oliver; Henningsson, Susanne] Univ Copenhagen, Hvidovre Hosp, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark. [Siebner, Hartwig Roman] Univ Copenhagen, Bispebjerg Hosp, Dept Neurol, Copenhagen, Denmark. [Haren, Tina] Univ Copenhagen, Glostrup Hosp, Dept Neurorehabil, TBI Unit, Glostrup, Denmark. [Gronlund, Rikke] Univ Copenhagen, Hvidovre Hosp, Dept Clin Biochem, DK-2650 Hvidovre, Denmark. [Henningsson, Susanne] Rigshosp, Copenhagen Univ Hosp, Ctr Integrated Mol Brain Imaging, DK-2100 Copenhagen, Denmark. RP Henningsson, S (reprint author), Univ Copenhagen, Hvidovre Hosp, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, Kettegard Alle 30, DK-2650 Hvidovre, Denmark. EM susanneh@drcmr.dk FU Faculty of Health and Medical Sciences at the University of Copenhagen; Danish Council for Independent Research; Lundbeck Foundation; Swedish Research Council; Lundbeck Foundation Center for Integrated Molecular Brain Imaging (CIMBI); Danish Research Council (DFF-FSS) post-doctoral fellowship FX We thank Silas Nielsen for help with data collection. Helle Ruff Laursen was supported by a grant from the Faculty of Health and Medical Sciences at the University of Copenhagen and The Danish Council for Independent Research. Hartwig Roman Siebner was supported by a Grant of Excellence sponsored by The Lundbeck Foundation. Susanne Henningsson was funded partly by the Swedish Research Council and partly by a grant from the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (CIMBI). Oliver Hulme was reported by the Danish Research Council (DFF-FSS) post-doctoral fellowship. The MR-scanner was donated by the Simon Spies Foundation. 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Behav. Neurosci. PD DEC 5 PY 2014 VL 8 AR 423 DI 10.3389/fnbeh.2014.00423 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AZ0PP UT WOS:000347947500001 PM 25538588 ER PT J AU Lind, SE Bowler, DM Raber, J AF Lind, Sophie E. Bowler, Dermot M. Raber, Jacob TI Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation? SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE autism spectrum disorder; episodic future thinking; episodic memory; mental simulation; scene construction; self-projection; spatial navigation; theory of mind ID HIGH-FUNCTIONING ADULTS; AUTOBIOGRAPHICAL MEMORY; DIAGNOSTIC INSTRUMENTS; SELF-PROJECTION; WORKING-MEMORY; INDIVIDUALS; SUPERIOR; BINDING; HUMANS; CONSTRUCTION AB This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of similar to 8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the memory island task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the animations task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed. C1 [Lind, Sophie E.] Univ Durham, Dept Psychol, Autism Res Team, Durham DH1 3LE, England. [Bowler, Dermot M.] City Univ London, Dept Psychol, Autism Res Grp, London EC1R 0JD, England. [Raber, Jacob] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Dept Behav Neurosci, Portland, OR 97201 USA. [Raber, Jacob] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Dept Neurol, Portland, OR 97201 USA. [Raber, Jacob] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Dept Radiat Med, Portland, OR 97201 USA. RP Lind, SE (reprint author), City Univ London, Dept Psychol, Autism Res Grp, Whiskin St, London EC1R 0JD, England. 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Psychol. PD DEC 5 PY 2014 VL 5 AR 1411 DI 10.3389/fpsyg.2014.01411 PG 20 WC Psychology, Multidisciplinary SC Psychology GA AX2TU UT WOS:000346798200002 PM 25538661 ER PT J AU Dharmadhikari, AV Gambin, T Szafranski, P Cao, WJ Probst, FJ Jin, WH Fang, P Gogolewski, K Gambin, A George-Abraham, JK Golla, S Boidein, F Duban-Bedu, B Delobel, B Andrieux, J Becker, K Holinski-Feder, E Cheung, SW Stankiewicz, P AF Dharmadhikari, Avinash V. Gambin, Tomasz Szafranski, Przemyslaw Cao, Wenjian Probst, Frank J. Jin, Weihong Fang, Ping Gogolewski, Krzysztof Gambin, Anna George-Abraham, Jaya K. Golla, Sailaja Boidein, Francoise Duban-Bedu, Benedicte Delobel, Bruno Andrieux, Joris Becker, Kerstin Holinski-Feder, Elke Cheung, Sau Wai Stankiewicz, Pawel TI Molecular and clinical analyses of 16q24.1 duplications involving FOXF1 identify an evolutionarily unstable large minisatellite SO BMC MEDICAL GENETICS LA English DT Article DE cis-regulation; Satellite repeats; Microhomology-mediated break-induced replication; Microduplication ID ALVEOLAR-CAPILLARY DYSPLASIA; LUNG DEVELOPMENTAL DISORDER; FORKHEAD BOX F1; PULMONARY VEINS; STRUCTURAL VARIATION; TRANSCRIPTION FACTOR; MENTAL-RETARDATION; BARRETTS-ESOPHAGUS; HUMAN GENOME; GENE FOXF1 AB Background: Point mutations or genomic deletions of FOXF1 result in a lethal developmental lung disease Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins. However, the clinical consequences of the constitutively increased dosage of FOXF1 are unknown. Methods: Copy-number variations and their parental origin were identified using a combination of array CGH, long-range PCR, DNA sequencing, and microsatellite analyses. Minisatellite sequences across different species were compared using a gready clustering algorithm and genome-wide analysis of the distribution of minisatellite sequences was performed using R statistical software. Results: We report four unrelated families with 16q24.1 duplications encompassing entire FOXF1. In a 4-year-old boy with speech delay and a caf-au-lait macule, we identified an similar to 15 kb 16q24.1 duplication inherited from the reportedly healthy father, in addition to a de novo similar to 1.09 Mb mosaic 17q11.2 NF1 deletion. In a 13-year-old patient with autism and mood disorder, we found an similar to 0.3 Mb duplication harboring FOXF1 and an similar to 0.5 Mb 16q23.3 duplication, both inherited from the father with bipolar disorder. In a 47-year old patient with pyloric stenosis, mesenterium commune, and aplasia of the appendix, we identified an similar to 0.4 Mb duplication in 16q24.1 encompassing 16 genes including FOXF1. The patient transmitted the duplication to her daughter, who presented with similar symptoms. In a fourth patient with speech and motor delay, and borderline intellectual disability, we identified an similar to 1.7 Mb FOXF1 duplication adjacent to a large minisatellite. This duplication has a complex structure and arose de novo on the maternal chromosome, likely as a result of a DNA replication error initiated by the adjacent large tandem repeat. Using bioinformatic and array CGH analyses of the minisatellite, we found a large variation of its size in several different species and individuals, demonstrating both its evolutionarily instability and population polymorphism. Conclusions: Our data indicate that constitutional duplication of FOXF1 in humans is not associated with any pediatric lung abnormalities. We propose that patients with gut malrotation, pyloric or duodenal stenosis, and gall bladder agenesis should be tested for FOXF1 alterations. We suggest that instability of minisatellites greater than 1 kb can lead to structural variation due to DNA replication errors. C1 [Dharmadhikari, Avinash V.; Stankiewicz, Pawel] Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX 77030 USA. [Dharmadhikari, Avinash V.; Gambin, Tomasz; Szafranski, Przemyslaw; Cao, Wenjian; Probst, Frank J.; Jin, Weihong; Fang, Ping; Cheung, Sau Wai; Stankiewicz, Pawel] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Gogolewski, Krzysztof; Gambin, Anna] Univ Warsaw, Inst Informat, Warsaw, Poland. [Gambin, Anna] Polish Acad Sci, Mossakowski Med Res Ctr, Warsaw, Poland. [George-Abraham, Jaya K.] Dells Childrens Med Ctr, Austin, TX USA. [Golla, Sailaja] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Golla, Sailaja] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Boidein, Francoise] Assoc Lille, St Vincent de Paul Cathol Hosp, Free Fac Med, Neuropediat Serv, Lille, France. [Duban-Bedu, Benedicte; Delobel, Bruno] Assoc Lille, St Vincent de Paul Cathol Hosp, Free Fac Med, Cytogenet Serv, Lille, France. [Andrieux, Joris] Univ Hosp, Med Genet Lab, Lille, France. [Becker, Kerstin; Holinski-Feder, Elke] Ctr Med Genet, Munich, Germany. RP Stankiewicz, P (reprint author), Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX 77030 USA. EM pawels@bcm.edu FU Wellcome Trust; NIH [1RO1HL101975]; Burroughs Wellcome Fund Career Award for Medical Scientists FX We thank Drs. C.R. Beck, C.M. Carvalho, G. Ira, P. Liu, J.R. Lupski, and F.Zhang, for helpful discussion. This study makes use of data generated by the Decipher Consortium. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust. This work was supported by NIH grant 1RO1HL101975 to P.S.F.J.P. is supported by a Burroughs Wellcome Fund Career Award for Medical Scientists. 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Genet. PD DEC 4 PY 2014 VL 15 AR 128 DI 10.1186/s12881-014-0128-z PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AZ3YD UT WOS:000348158900001 PM 25472632 ER PT J AU Cassels, TG Birch, SAJ AF Cassels, Tracy G. Birch, Susan A. J. TI Comparisons of an Open-Ended vs. Forced-Choice 'Mind Reading' Task: Implications for Measuring Perspective-Taking and Emotion Recognition SO PLOS ONE LA English DT Article ID FACIAL EXPRESSIONS; ASPERGER-SYNDROME; CHILDREN; PSYCHOPATHY; EMPATHY; AUTISM; ADULTS; EYES; PRESCHOOLERS; ASSOCIATION AB Perspective-taking and emotion recognition are essential for successful social development and have been the focus of developmental research for many years. Although the two abilities often overlap, they are distinct and our understanding of these abilities critically rests upon the efficacy of existing measures. Lessons from the literature differentiating recall versus recognition memory tasks led us to hypothesize that an open-ended emotion recognition measure would be less reliant on compensatory strategies and hence a more specific measure of emotion recognition abilities than a forced-choice task. To this end, we compared an open-ended version of the Reading the Mind in the Eyes Task with the original forced-choice version in two studies: 118 typically-developing 4- to 8-year-olds (Study 1) and 139 5- to 12-year-olds; 85 typically-developing and 54 with learning disorders (Study 2). We found that the open-ended version of the task was a better predictor of empathy and more reliably discriminated typically-developing children from those with learning disorders. As a whole, the results suggest that the open-ended version is a more sensitive measure of emotion recognition specifically. C1 [Cassels, Tracy G.; Birch, Susan A. J.] Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. RP Cassels, TG (reprint author), Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. EM tracy@psych.ubc.ca FU Hampton Research Endowment Fund, UBC; Social Sciences and Humanities Research Council of Canada, Canada Graduate Scholarship, Doctoral [767-2008-1754] FX This work was supported by funding from the Hampton Research Endowment Fund, UBC [$41,595] to Dr. Susan Birch, and the Social Sciences and Humanities Research Council of Canada, Canada Graduate Scholarship, Doctoral to Tracy G. Cassels [$105,000] Award No: 767-2008-1754. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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The Impact of Genre on the Narrative Processing of Other Minds SO PLOS ONE LA English DT Article ID EMPATHY; NEUROSCIENCE; SIMULATION; ATTENTION; RELEVANCE; EVOLUTION; COGNITION; AUTISM; BIAS AB Do narratives shape how humans process other minds or do they presuppose an existing theory of mind? This study experimentally investigated this problem by assessing subject responses to systematic alterations in the genre, levels of intentionality, and linguistic complexity of narratives. It showed that the interaction of genre and intentionality level are crucial in determining how narratives are cognitively processed. Specifically, genres that deployed evolutionarily familiar scenarios (relationship stories) were rated as being higher in quality when levels of intentionality were increased; conversely, stories that lacked evolutionary familiarity (espionage stories) were rated as being lower in quality with increases in intentionality level. 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Y. van Karnebeek, Clara Wasserman, Wyeth W. TI FLAGS, frequently mutated genes in public exomes SO BMC MEDICAL GENOMICS LA English DT Article ID DE-NOVO MUTATIONS; KABUKI SYNDROME; DEVELOPMENTAL DELAY; MISSENSE MUTATIONS; HAPLOTYPE MAP; HUMAN GENOME; DISEASE; DISORDERS; VARIANTS; AUTISM AB Background: Dramatic improvements in DNA-sequencing technologies and computational analyses have led to wide use of whole exome sequencing (WES) to identify the genetic basis of Mendelian disorders. More than 180 novel rare-disease-causing genes with Mendelian inheritance patterns have been discovered through sequencing the exomes of just a few unrelated individuals or family members. As rare/novel genetic variants continue to be uncovered, there is a major challenge in distinguishing true pathogenic variants from rare benign mutations. Methods: We used publicly available exome cohorts, together with the dbSNP database, to derive a list of genes (n = 100) that most frequently exhibit rare (< 1%) non-synonymous/splice-site variants in general populations. We termed these genes FLAGS for FrequentLy mutAted GeneS and analyzed their properties. Results: Analysis of FLAGS revealed that these genes have significantly longer protein coding sequences, a greater number of paralogs and display less evolutionarily selective pressure than expected. FLAGS are more frequently reported in PubMed clinical literature and more frequently associated with diseased phenotypes compared to the set of human protein-coding genes. We demonstrated an overlap between FLAGS and the rare-disease causing genes recently discovered through WES studies (n = 10) and the need for replication studies and rigorous statistical and biological analyses when associating FLAGS to rare disease. Finally, we showed how FLAGS are applied in disease-causing variant prioritization approach on exome data from a family affected by an unknown rare genetic disorder. Conclusions: We showed that some genes are frequently affected by rare, likely functional variants in general population, and are frequently observed in WES studies analyzing diverse rare phenotypes. We found that the rate at which genes accumulate rare mutations is beneficial information for prioritizing candidates. We provided a ranking system based on the mutation accumulation rates for prioritizing exome-captured human genes, and propose that clinical reports associating any disease/phenotype to FLAGS be evaluated with extra caution. C1 [Shyr, Casper; Tarailo-Graovac, Maja; Gottlieb, Michael; Lee, Jessica J. Y.; Wasserman, Wyeth W.] Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC, Canada. [Tarailo-Graovac, Maja; Wasserman, Wyeth W.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Shyr, Casper; Tarailo-Graovac, Maja; van Karnebeek, Clara; Wasserman, Wyeth W.] Treatable Intellectual Disabil Endeavour British, Vancouver, BC, Canada. [Shyr, Casper] Univ British Columbia, Bioinformat Grad Program, Vancouver, BC V5Z 1M9, Canada. [Lee, Jessica J. Y.] Univ British Columbia, Genome Sci & Technol Grad Program, Vancouver, BC V5Z 1M9, Canada. [van Karnebeek, Clara] British Columbia Childrens Hosp, Div Biochem Dis, Vancouver, BC V6H 3V4, Canada. [van Karnebeek, Clara] Univ British Columbia, Dept Pediat, Vancouver, BC V6T 1W5, Canada. RP Wasserman, WW (reprint author), Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC, Canada. EM wyeth@cmmt.ubc.ca FU B.C. Children's Hospital Foundation as "1st Collaborative Area of Innovation"; Genome BC [SOF-195]; Genome Canada grant [1/4CDE]; Canadian Institutes of Health Research [301221]; CIHR-CGSD; NSERC-CREATE; CIHR-Computational Biology Undergraduate Summer Student Health Research; Genome BC grant FX We are indebted to the patient and her family for participation in this study; Drs. J. Wu, J. Rozmus, S. Vercauteren, K. Hildebrand, T. Dewan and A. Garcera for clinical evaluation and management of the patient; Mrs. X. Han for Sanger sequencing; Mr. B. Sayson for data management; Mrs. M. Higginson for DNA extraction, sample handling and technical data; Dr. C. Vilarino-Guell for timely whole exome sequencing; Dr. W. Cheung for MeSHOP support; Mr. D. Arenillas and Mr. M. Hatas for systems support, and Dora Pak for research management support. This work was supported by funding from the B.C. Children's Hospital Foundation as "1st Collaborative Area of Innovation" (www.tidebc.org); Genome BC (SOF-195 grant); Genome BC and Genome Canada grants 1/4CDE (ABC4DE Project); and the Canadian Institutes of Health Research #301221 grant. CS is funded by CIHR-CGSD, JJYL is funded by NSERC-CREATE, and MG is funded by CIHR-Computational Biology Undergraduate Summer Student Health Research. 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Genomics PD DEC 3 PY 2014 VL 7 AR 64 DI 10.1186/s12920-014-0064-y PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AZ7KC UT WOS:000348397000001 PM 25466818 ER PT J AU Stanco, A Pla, R Vogt, D Chen, YR Mandal, S Walker, J Hunt, RF Lindtner, S Erdman, CA Pieper, AA Hamilton, SP Xu, D Baraban, SC Rubenstein, JLR AF Stanco, Amelia Pla, Ramon Vogt, Daniel Chen, Yiran Mandal, Shyamali Walker, Jamie Hunt, Robert F. Lindtner, Susan Erdman, Carolyn A. Pieper, Andrew A. Hamilton, Steven P. Xu, Duan Baraban, Scott C. Rubenstein, John L. R. TI NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons SO NEURON LA English DT Article ID MEDIAL GANGLIONIC EMINENCE; AUTISM SPECTRUM DISORDERS; GABAERGIC CELL SUBTYPES; RAT FRONTAL-CORTEX; NEOCORTICAL INTERNEURONS; NEURONAL MIGRATION; IMMUNOREACTIVE INTERNEURONS; MEGALENCEPHALY SYNDROMES; GENE; BRAIN AB Little is known about genetic mechanisms that regulate the ratio of cortical excitatory and inhibitory neurons. We show that NPAS1 and NPAS3 transcription factors (TFs) are expressed in progenitor domains of the mouse basal ganglia (subpallium, MGE, and CGE). NPAS1(-/-) mutants had increased proliferation, ERK signaling, and expression of Arx in the MGE and CGE. NPAS1(-/-) mutants also had increased neocortical inhibition (sIPSC and mIPSC) and generated an excess of somatostatin(+) (SST) (MGE-derived) and vasoactive intestinal polypeptide(+) (VIP) (CGE-derived) neocortical interneurons, but had a normal density of parvalbumin(+) (PV) (MGE-derived) interneurons. In contrast, NPAS3(-/-) mutants showed decreased proliferation and ERK signaling in progenitors of the ganglionic eminences and had fewer SST+ and VIP+ interneurons. NPAS1 repressed activity of an Arx enhancer, and Arx overexpression resulted in increased proliferation of CGE progenitors. These results provide insights into genetic regulation of cortical interneuron numbers and cortical inhibitory tone. C1 [Stanco, Amelia; Pla, Ramon; Vogt, Daniel; Mandal, Shyamali; Lindtner, Susan; Erdman, Carolyn A.; Hamilton, Steven P.; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Neurosci Program, San Francisco, CA 94158 USA. [Stanco, Amelia; Pla, Ramon; Vogt, Daniel; Mandal, Shyamali; Lindtner, Susan; Erdman, Carolyn A.; Hamilton, Steven P.; Rubenstein, John L. R.] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA. [Chen, Yiran; Xu, Duan] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Walker, Jamie] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Hunt, Robert F.; Baraban, Scott C.] Univ Calif San Francisco, Neurosci Program, Dept Neurol Surg, San Francisco, CA 94143 USA. [Pieper, Andrew A.] Univ Iowa, Carver Coll Med, Dept Psychiat & Neurol, Iowa City, IA 52242 USA. RP Stanco, A (reprint author), Univ Calif San Francisco, Dept Psychiat, Neurosci Program, San Francisco, CA 94158 USA. EM amelia.stanco@ucsf.edu; john.rubenstein@ucsf.edu FU Simons Foundation; Nina Ireland; Althea Foundation; NIMH [R37 MH049428, 5-RO1-MH087986]; Weston Havens Foundation; Jaffe Family Foundation [NIMHT32 MH089920, R01NS071785, F32NS077747, R01EB009756] FX We are grateful to S. McKnight and his lab at University of Texas Southwestern Medical Center for the generous gift of NPAS1 and NPAS3 antibodies, the NPAS1+/- and NPAS3+/- mice, the NPAS1 ISH construct (J. Walker), and the CMV-ARNT and CMV-NPAS1 mammalian expression vectors (L. Wu). We acknowledge the Autism Genetic Resource Exchange (AGRE) and Simons Foundation Autism Research Initiative (SFARI) for ASD genomic DNA samples, and SFARI as well for phenotypic data made available on SFARI Base. We also wish to thank all the families who donated samples, and the principal investigators involved in their collection (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, and E. Wijsman). Approved researchers can obtain the Simons Simplex Collection (SSC) population data set by applying at https://base.sfari.org. This work was supported by research grants to J. L. R. R. (Simons Foundation, Nina Ireland, Althea Foundation, NIMH R37 MH049428, Weston Havens Foundation), to A. S. (NIMHT32 MH089920), to S. C. B. (R01NS071785), to R.F.H. (F32NS077747), to D.X. (R01EB009756), to S.P.H. (Jaffe Family Foundation), and to A.A.P. and Steven L. McKnight (NIMH 5-RO1-MH087986). This work was also funded in part by an unrestricted endowment provided to Steven L. McKnight by an anonymous donor, used as support for J.W. 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We thank Dr. Daping Fan (University of South Carolina) for expert guidance in RNAi constructs, and Mariel Piechowicz for assistance with blind data analysis. 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Animal fmr1-knockout (KO) models are not only of interest for the study of FXS, but have also important implications for our understanding of autism spectrum disorder (ASD). Here we report the behavioral changes in fmr1-knockout zebrafish in an open field with two white and two transparent walls. The neophobic responses that in wild-type (WT) zebrafish normally occur during the first 5-10 min in an unfamiliar environment (such as freezing, hypo-activity and preferences for the bottom and opaque walls of the tank), were weakened in fmr1 mutants, suggesting a reduction of novelty-induced anxiety. The fmr1-KO zebrafish showed somewhat increased vertical activity beyond the 'neophobic phase', but no overall hyperactivity. The mutants demonstrated a clear habituation-independent preference for the transparent walls. Whether this was attributable to altered spatial information processing or to reduced avoidance of open spaces is discussed. Finally, since restrictive repetitive (or stereotypical) behaviors are frequently present in FXS and ASD patients, we analyzed relative turning angles, directional and preferential turning ratios and performed frequency-domain analysis. However, no indications of abnormal movement patterning were detected. The possible reasons for the absence of stereotypical behaviors are discussed in terms of behavioral endpoint selection and of eliciting conditions. Overall, our findings are consistent with those reported in fmr1-KO mice and suggest that further analysis of the fmr1-KO zebrafish model has potential to deepen our understanding of FXS and ASD. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kima, Lily; He, Lucy; Maaswinkel, Hans; Zhu, Liqun; Weng, Wei] xyZfish, Res & Dev, Ronkonkoma, NY 11779 USA. [Sirotkin, Howard] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. RP Maaswinkel, H (reprint author), xyZfish, Res & Dev, 2200 Smithtown Ave, Ronkonkoma, NY 11779 USA. 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Psychiatry PD DEC 3 PY 2014 VL 55 SI SI BP 40 EP 49 DI 10.1016/j.pnpbp.2014.03.007 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AR0EG UT WOS:000343240000005 ER PT J AU Krawiec, P Pac-Kozuchowska, E Melges, B Mroczkowska-Juchkiewicz, A Skomra, S Pawlowska-Kamieniak, A Kominek, K AF Krawiec, Paulina Pac-Kozuchowska, Elzbieta Melges, Beata Mroczkowska-Juchkiewicz, Agnieszka Skomra, Stanislaw Pawlowska-Kamieniak, Agnieszka Kominek, Katarzyna TI From hypertransaminasemia to mucopolysaccharidosis IIIA SO ITALIAN JOURNAL OF PEDIATRICS LA English DT Article DE Mucopolysaccharidosis type IIIA; Sanfilippo syndrome; Hypertransaminasemia ID SYNDROME TYPE-A; SANFILIPPO-SYNDROME AB Mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome) is a metabolic disorder characterized by the deficiency of a lysosomal enzyme catalyzing the catabolic pathway of heparan sulphate. MPS III presents with progressive mental deterioration, speech delay and behavioural problems with subtle somatic features, which can often lead to misdiagnosis with idiopathic developmental/speech delay, attention deficit/hyperactivity disorder or autism. We report a case of a 5-year-old boy with developmental delay and behaviour problems admitted to the Department of Paediatrics due to chronic hypertransaminasemia. The patient developed normally until the age of 2 years when he was referred to a paediatric neurologist for suspected motor and speech delay. Liver function tests were unexpectedly found elevated at the age of 3.5 years. Physical examination revealed obesity, mildly coarse facial features and stocky hands. He showed mental retardation and mild motor delay. The clinical picture strongly suggested mucopolysaccharidosis. The diagnosis of MPS IIIA was confirmed by decreased activity of heparan N-sulfatase in leucocytes. 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A second goal was to determine whether these alterations can serve as neurocognitive markers of autism. The approach is based on previous advances in fMRI analysis methods that permit (a) the identification of a concept, such as the thought of a physical object, from its fMRI pattern, and (b) the ability to assess the semantic content of a concept from its fMRI pattern. These factor analysis and machine learning methods were applied to the fMRI activation patterns of 17 adults with high-functioning autism and matched controls, scanned while thinking about 16 social interactions. One prominent neural representation factor that emerged (manifested mainly in posterior midline regions) was related to self-representation, but this factor was present only for the control participants, and was near-absent in the autism group. Moreover, machine learning algorithms classified individuals as autistic or control with 97% accuracy from their fMRI neurocognitive markers. The findings suggest that psychiatric alterations of thought can begin to be biologically understood by assessing the form and content of the altered thought's underlying brain activation patterns. C1 [Just, Marcel Adam; Cherkassky, Vladimir L.; Buchweitz, Augusto; Keller, Timothy A.] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Just, Marcel Adam; Cherkassky, Vladimir L.; Buchweitz, Augusto; Keller, Timothy A.] Carnegie Mellon Univ, Ctr Cognit Brain Imaging, Pittsburgh, PA 15213 USA. [Mitchell, Tom M.] Carnegie Mellon Univ, Machine Learning Dept, Pittsburgh, PA 15213 USA. [Buchweitz, Augusto] Pontificia Univ Catolica Rio Grande do Sul, Brain Inst Rio Grande do Sul InsCer RS, Porto Alegre, RS, Brazil. RP Just, MA (reprint author), Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. EM just@cmu.edu FU National Institute of Mental Health Grant [MH029617]; National Institute of Child Health and Human Development Grant [HD055748] FX This work was supported by the National Institute of Mental Health Grant MH029617 and the National Institute of Child Health and Human Development Grant HD055748. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Kullmann, Paul H. M. Twomey, Margaret A. Miriyala, Jayalakshmi Philpot, Benjamin D. Zylka, Mark J. TI Topoisomerase 1 inhibition reversibly impairs synaptic function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE synapse; topoisomerase; transcription ID SYNCHRONOUS OSCILLATORY ACTIVITY; NEURODEVELOPMENTAL DISORDERS; II-BETA; AUTISM; GENE; NEURONS; NEUROLIGINS; EXPRESSION; NEUREXINS; CHILDREN AB Topotecan is a topoisomerase 1 (TOP1) inhibitor that is used to treat various forms of cancer. We recently found that topotecan reduces the expression of multiple long genes, including many neuronal genes linked to synapses and autism. However, whether topotecan alters synaptic protein levels and synapse function is currently unknown. Here we report that in primary cortical neurons, topotecan depleted synaptic proteins that are encoded by extremely long genes, including Neurexin-1, Neuroligin-1, Cntnap2, and GABA(A)beta 3. Topotecan also suppressed spontaneous network activity without affecting resting membrane potential, action potential threshold, or neuron health. Topotecan strongly suppressed inhibitory neurotransmission via pre- and postsynaptic mechanisms and reduced excitatory neurotransmission. The effects on synaptic protein levels and inhibitory neurotransmission were fully reversible upon drug washout. Collectively, our findings suggest that TOP1 controls the levels of multiple synaptic proteins and is required for normal excitatory and inhibitory synaptic transmission. C1 [Mabb, Angela M.; Kullmann, Paul H. M.; Twomey, Margaret A.; Miriyala, Jayalakshmi; Philpot, Benjamin D.; Zylka, Mark J.] Univ N Carolina, Dept Cell Biol & Physiol, Ctr Neurosci, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. RP Philpot, BD (reprint author), Univ N Carolina, Dept Cell Biol & Physiol, Ctr Neurosci, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. EM benjamin_philpot@med.unc.edu; zylka@med.unc.edu FU Angelman Syndrome Foundation; Simons Foundation [SFARI 10-3625]; National Institute of Mental Health [R01MH093372]; National Institutes of Health [DP1ES024088]; Joseph E. Wagstaff Postdoctoral Research Fellowship from the Angelman Syndrome Foundation; National Institute of Neurological Disorders and Stroke Grant [P30NS045892]; Eunice Kennedy Shriver National Institute of Childhood Health and Development Grant [P30HD03110] FX We thank Tal Kafri and Ping Zhang at the University of North Carolina (UNC) Lentiviral Core for assistance with the preparation of lentiviral vectors and Vladimir Ghukasyan at the UNC Confocal and Multiphoton Imaging Core, Ian King, and Gabriela Salazar for technical assistance. This work was supported by a grant from the Angelman Syndrome Foundation, Simons Foundation Grant SFARI 10-3625, and National Institute of Mental Health Grant R01MH093372 (to B.D.P. and M.J.Z.) and by National Institutes of Health Pioneer Award DP1ES024088 (to M.J.Z.). A.M.M. was supported by a Joseph E. Wagstaff Postdoctoral Research Fellowship from the Angelman Syndrome Foundation. The Confocal and Multiphoton Imaging Core is funded by the National Institute of Neurological Disorders and Stroke Grant P30NS045892 and The Eunice Kennedy Shriver National Institute of Childhood Health and Development Grant P30HD03110. 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PD DEC 2 PY 2014 VL 111 IS 48 BP 17290 EP 17295 DI 10.1073/pnas.1413204111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NN UT WOS:000345920800070 PM 25404338 ER PT J AU Woodfield, C Jung, E Ashby, C AF Woodfield, Casey Jung, Eunyoung Ashby, Christine TI "Hoping for Greatness": Exploring the Notion of "Novicity" in Communication Support Partnerships SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE AAC (Alternative Augmentative Communication); FC (Facilitated Communication); novice facilitator; typer; communication training ID FACILITATED COMMUNICATION; SPECTRUM DISORDERS; EDUCATION SETTINGS; AUTISM; STUDENTS; DISABILITIES; PARAPROFESSIONALS; INDEPENDENCE; PERSPECTIVES; INDIVIDUALS AB This research explores the stage of novicity in communicative partnerships between new facilitators and the individuals with disabilities who use supported typing as their primary method of communication with whom they work. 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This study examined reading (word and text reading accuracy, reading comprehension), phonological decoding (nonword reading) and oral language comprehension (receptive vocabulary) in 49 children and adolescents with ASD and 49 typical peers of the same age. Levels of word and text reading accuracy were within age appropriate levels, but reading comprehension and vocabulary were below average; 31% of the sample showed a significant discrepancy between reading comprehension and word reading accuracy (compared to only 10% of a group of typically developing peers). Even when children with ASD were equated with typical peers on word reading they showed significant nonword decoding difficulties. Variance in phonological decoding was also a significant predictor of reading comprehension for the ASD group (but not for the typical peers). 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TI THE PERCEIVED EFFECTS OF VISUAL DESIGN AND FEATURES ON STUDENTS WITH AUTISM SPECTRUM DISORDER SO JOURNAL OF ARCHITECTURAL AND PLANNING RESEARCH LA English DT Article ID CHILDREN; COMMUNICATION; PERFORMANCE; IMPACT; MODEL; ADHD AB The challenge of providing learner-centered environments is complicated by the increase in the prevalence of students with autism spectrum disorder (ASD). The majority of children with ASD have hypersensitivities with heightened senses. The purpose of this study was to explore the relationship between the design of built learning environments and the behavior of students with ASD. We used a mixed-method approach that included a focus group (n = 11) and a questionnaire directed at special-education teachers (n = 604). We identified sensory triggers that have a negative impact on the behavior of students with ASD. The main visual triggers we found were visual changes in the environment/distraction, undefined space, and sources of light. 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Archit. Plan. Res. PD WIN PY 2014 VL 31 IS 4 BP 282 EP 298 PG 17 WC Environmental Studies; Urban Studies SC Environmental Sciences & Ecology; Urban Studies GA CD1MH UT WOS:000350838500002 ER PT J AU Algoe, SB Way, BM AF Algoe, Sara B. Way, Baldwin M. TI Evidence for a role of the oxytocin system, indexed by genetic variation in CD38, in the social bonding effects of expressed gratitude SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE close relationships; gratitude; emotion expression; CD38; oxytocin ID CHRONIC LYMPHOCYTIC-LEUKEMIA; AUTISM SPECTRUM DISORDER; CLOSE RELATIONSHIPS; POSITIVE EMOTIONS; BLOOD-PRESSURE; SEXUAL DESIRE; ROMANTIC LOVE; RECIPROCITY; ATTACHMENT; BENEFITS AB Oxytocin is thought to play a central role in promoting close social bonds via influence on social interactions. The current investigation targeted interactions involving expressed gratitude between members of romantic relationships because recent evidence suggests gratitude and its expression provides behavioral and psychological 'glue' to bind individuals closer together. Specifically, we took a genetic approach to test the hypothesis that social interactions involving expressed gratitude would be associated with variation in a gene, CD38, which has been shown to affect oxytocin secretion. A polymorphism (rs6449182) that affects CD38 expression was significantly associated with global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love) after lab-based interactions, observed behavioral expression of gratitude toward a romantic partner in the lab, and frequency of expressed gratitude in daily life. A separate polymorphism in CD38 (rs3796863) previously associated with plasma oxytocin levels and social engagement was also associated with perceived responsiveness in the benefactor after an expression of gratitude. The combined influence of the two polymorphisms was associated with a broad range of gratitude-related behaviors and feelings. The consistent pattern of findings suggests that the oxytocin system is associated with solidifying the glue that binds adults into meaningful and important relationships. C1 [Algoe, Sara B.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Way, Baldwin M.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Way, Baldwin M.] Ohio State Univ, Ohio State Inst Behav Med Res, Columbus, OH 43210 USA. RP Algoe, SB (reprint author), Univ N Carolina, Dept Psychol, CB 3270, Chapel Hill, NC 27599 USA. EM algoe@unc.edu FU National Institute of Mental Health [MH59615]; National Center for Advancing Translational Sciences [8KL2TR000112-05] FX This work was supported by a grant from the National Institute of Mental Health (MH59615) and a grant from the National Center for Advancing Translational Sciences (8KL2TR000112-05). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank Ms Sara DeMaria for her excellent technical assistance, as well as the exceptional team of 30 research assistants who helped with the Carolina Couples Study, lead by Jenny Bridgers (full list available on first author's website). Barbara Fredrickson, B. Keith Payne and Crystal Schiller provided insightful feedback on an earlier manuscript draft. CR Algoe S. 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Cogn. Affect. Neurosci. PD DEC PY 2014 VL 9 IS 12 BP 1855 EP 1861 DI 10.1093/scan/nst182 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC1MU UT WOS:000350105900001 PM 24396004 ER PT J AU Brandenburg-Goddard, MN van Rijn, S Rombouts, SARB Veer, IM Swaab, H AF Brandenburg-Goddard, Marcia N. van Rijn, Sophie Rombouts, Serge A. R. B. Veer, Ilya M. Swaab, Hanna TI A comparison of neural correlates underlying social cognition in Klinefelter syndrome and autism SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE Klinefelter; autism; social cognition; fMRI; facial affect processing ID EXTRA X-CHROMOSOME; OF-THE-LITERATURE; CYTOARCHITECTONIC MAPS; DIAGNOSTIC INTERVIEW; FACIAL EXPRESSIONS; EXECUTIVE FUNCTION; BRAIN IMAGES; MEN 47,XXY; DISORDER; FMRI AB Klinefelter syndrome (KS) is a genetic syndrome characterized by the presence of an extra X chromosome that appears to increase the risk of psychopathology, such as autism symptoms. This study used functional magnetic resonance imaging to determine underlying mechanisms related to this risk, with the aim of gaining insight into neural mechanisms behind social-cognitive dysfunction in KS and autism, and understanding similarities and differences in social information processing deficits. Fourteen boys with KS, seventeen boys with autism spectrum disorders (ASD) and nineteen non-clinical male controls aged 10-18 years were scanned while matching and labeling facial expressions (i.e. face processing and affect labeling, respectively). No group differences in neural activation were found during face processing. However, during affect labeling, the ASD group showed increased activation in the amygdala compared with controls, while the KS group showed increased activation in frontal areas compared with both controls and the ASD group. No group differences in task performance were found. Although behavioral symptoms of social dysfunction appear similar both in boys with KS and ASD, this is the first study to demonstrate different underlying etiologies. These results may aid in identifying different pathways to autism symptoms, which may help understanding variability within the ASD spectrum. C1 [Brandenburg-Goddard, Marcia N.; van Rijn, Sophie; Swaab, Hanna] Leiden Univ, NL-2333 AK Leiden, Netherlands. [Brandenburg-Goddard, Marcia N.; van Rijn, Sophie; Rombouts, Serge A. R. B.; Veer, Ilya M.; Swaab, Hanna] Leiden Inst Brain & Cognit, NL-2333 ZA Leiden, Netherlands. [Rombouts, Serge A. R. B.] Leiden Univ, Inst Psychol, NL-2333 AK Leiden, Netherlands. [Rombouts, Serge A. R. B.] Leiden Univ, Med Ctr, Dept Radiol, NL-2333 AK Leiden, Netherlands. [Veer, Ilya M.] Charite, Div Mind & Brain Res, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. RP Brandenburg-Goddard, MN (reprint author), Leiden Univ, Fac Social & Behav Sci, Dept Clin Child & Adolescent Studies, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands. EM m.n.brandenburg@fsw.leidenuniv.nl FU Netherlands Organization for Scientific Research (NWO) [016.095.060] FX This work was supported by the Netherlands Organization for Scientific Research (NWO) (016.095.060 to S.v.R). 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Cogn. Affect. Neurosci. PD DEC PY 2014 VL 9 IS 12 BP 1926 EP 1933 DI 10.1093/scan/nst190 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC1MU UT WOS:000350105900009 PM 24396006 ER PT J AU Sims, TB Neufeld, J Johnstone, T Chakrabarti, B AF Sims, Thomas B. Neufeld, Janina Johnstone, Tom Chakrabarti, Bhismadev TI Autistic traits modulate frontostriatal connectivity during processing of rewarding faces SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE autism; empathy; mimicry; reward; fMRI ID EMOTIONAL FACIAL EXPRESSIONS; MIRROR NEURON SYSTEM; SPECTRUM QUOTIENT AQ; FUNCTIONING AUTISM; ASPERGER-SYNDROME; ALE METAANALYSIS; BRAIN IMAGES; EMG EVIDENCE; MIMICRY; IMITATION AB Deficits in facial mimicry have been widely reported in autism. Some studies have suggested that these deficits are restricted to spontaneous mimicry and do not extend to volitional mimicry. We bridge these apparently inconsistent observations by testing the impact of reward value on neural indices of mimicry and how autistic traits modulate this impact. Neutral faces were conditioned with high and low reward. Subsequently, functional connectivity between the ventral striatum (VS) and inferior frontal gyrus (IFG) was measured while neurotypical adults (n = 30) watched happy expressions made by these conditioned faces. We found greater VS-IFG connectivity in response to high reward vs low reward happy faces. This difference was negatively proportional to autistic traits, suggesting that reduced spontaneous mimicry of social stimuli seen in autism, may be related to a failure in the modulation of the mirror system by the reward system rather than a circumscribed deficit in the mirror system. C1 [Sims, Thomas B.; Neufeld, Janina; Johnstone, Tom; Chakrabarti, Bhismadev] Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. RP Chakrabarti, B (reprint author), Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. EM b.chakrabarti@reading.ac.uk FU Medical Research Council New Investigator Grant; University of Reading Ph.D. studentship FX The work was supported by a Medical Research Council New Investigator Grant to B.C. T.B.S. is supported by a University of Reading Ph.D. studentship. 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Cogn. Affect. Neurosci. PD DEC PY 2014 VL 9 IS 12 BP 2010 EP 2016 DI 10.1093/scan/nsu010 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CC1MU UT WOS:000350105900018 PM 24493838 ER PT J AU Fernandez, RW Nurilov, M Feliciano, O McDonald, IS Simon, AF AF Fernandez, Robert W. Nurilov, Marat Feliciano, Omar McDonald, Ian S. Simon, Anne F. TI Straightforward Assay for Quantification of Social Avoidance in Drosophila melanogaster SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 94; social behavior; social avoidance; Drosophila melanogaster; Drosophila; Stress Odorant - dSO; T-maze apparatus; neurogenetics ID AUTISM SPECTRUM DISORDER; BEHAVIOR; EXPERIENCE; COURTSHIP; GENE AB Drosophila melanogaster is an emerging model to study different aspects of social interactions. For example, flies avoid areas previously occupied by stressed conspecifics due to an odorant released during stress known as the Drosophila stress odorant (dSO). Through the use of the T-maze apparatus, one can quantify the avoidance of the dSO by responder flies in a very affordable and robust assay. Conditions necessary to obtain a strong performance are presented here. A stressful experience is necessary for the flies to emit dSO, as well as enough emitter flies to cause a robust avoidance response to the presence of dSO. Genetic background, but not their group size, strongly altered the avoidance of the dSO by the responder flies. Canton-S and Elwood display a higher performance in avoiding the dSO than Oregon and Samarkand strains. This behavioral assay will allow identification of mechanisms underlying this social behavior, and the assessment of the influence of genes and environmental conditions on both emission and avoidance of the dSO. Such an assay can be included in batteries of simple diagnostic tests used to identify social deficiencies of mutants or environmental conditions of interest. C1 [Fernandez, Robert W.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Nurilov, Marat; Feliciano, Omar] CUNY York Coll, Dept Biol, New York, NY USA. [McDonald, Ian S.; Simon, Anne F.] Univ Western Ontario, Dept Biol, London, ON N6A 3K7, Canada. RP Simon, AF (reprint author), Univ Western Ontario, Dept Biol, London, ON N6A 3K7, Canada. EM asimon28@uwo.ca FU PSC-CUNY; Professional Staff Congress and; City University of New York; Western University; National Alliance for Hispanic Health's Alliance/Merck Ciencia (Science) Hispanic Scholars Program; University Fellowship from the Yale Graduate School of Arts and Sciences FX This work was supported by PSC-CUNY research awards, jointly funded by The Professional Staff Congress and The City University of New York to A.F.S.; by internal funding from Western University to A.F.S. and I.S.M.; by a training support from the National Alliance for Hispanic Health's Alliance/Merck Ciencia (Science) Hispanic Scholars Program and a University Fellowship from the Yale Graduate School of Arts and Sciences to R.W.F. CR Ali Y. 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PD DEC PY 2014 IS 94 AR e52011 DI 10.3791/52011 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB1AE UT WOS:000349358000016 ER PT J AU Li, R Fu, F Zhang, YL Li, DZ Liao, C AF Li, Ru Fu, Fang Zhang, Yong-Ling Li, Dong-Zhi Liao, Can TI Prenatal diagnosis of 17q12 duplication and deletion syndrome in two fetuses with congenital anomalies SO Taiwanese Journal of Obstetrics & Gynecology LA English DT Article DE 17q12 deletion; 17q12 duplication; chromosome microarray analysis; prenatal diagnosis ID SUPERIOR VENA-CAVA; OF-THE-LITERATURE; GENOMIC REARRANGEMENTS; HYPERECHOGENIC KIDNEYS; MICRODELETION SYNDROME; CLINICAL SPECTRUM; CHROMOSOME 17Q12; RENAL-DISEASE; RECURRENT; AUTISM AB Objective: The objective of this study was to characterize the genetic abnormalities in two fetuses with congenital anomalies in prenatal screening. Materials and methods: The mother of Fetus 1 was 26 years old and had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound and magnetic resonance imaging (MRI) at 28 weeks of gestation showed mild ventriculomegaly, microcephaly, and agenesis of the corpus callosum. The mother of Fetus 2 was 25 years old and also had a second trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 32 weeks of gestation showed the presence of hyperechogenic and enlarged kidneys with multicystic renal dysplasia bilaterally and a persistent left superior vena cava (PLSVC). Both pregnant women underwent cord blood samplings because of the abnormal imaging results. Karyotype analysis revealed normal results in the two fetuses. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the cord blood and parental blood samples. Ultimately, the pregnancies were both terminated. Results: CMA detected a 1.56-Mb duplication at 17q12 in Fetus 1 and a 1.93-Mb deletion of 17q12 in Fetus 2. Both the duplicated and deleted regions included the HNF1B and LHX1 genes. Neither the duplication nor deletion was inherited from the parents. Conclusion: This study is the first to report the prenatal diagnosis of a 17q12 duplication syndrome. Our results further confirmed that genes in this region, including HNF1B and LHX1, are essential for normal brain and kidney development, and also indicated some genes that may be associated with the cardiovascular abnormality. Combined with imaging examination, the use of CMA will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Li, Ru; Fu, Fang; Zhang, Yong-Ling; Li, Dong-Zhi; Liao, Can] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Prenatal Diagnost Ctr, Guangzhou, Guangdong, Peoples R China. RP Liao, C (reprint author), Guangzhou Women & Childrens Med Ctr, Dept Prenatal Diagnost Ctr, 9 Jinsui Rd, Guangzhou, Guangdong, Peoples R China. EM canliao@hotmail.com FU National Natural Science Foundation of China [81100435]; Guangzhou Science and Technology Bureau Project [201300000086]; Guangdong Provincial Medical Research Foundation [A2013515] FX This work was supported by the National Natural Science Foundation of China (81100435), Guangzhou Science and Technology Bureau Project (201300000086) and Guangdong Provincial Medical Research Foundation (A2013515). 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PD DEC PY 2014 VL 8 IS 3 BP 35 EP 47 PG 13 WC Art; Engineering, Multidisciplinary; Engineering, Manufacturing; Social Sciences, Interdisciplinary SC Art; Engineering; Social Sciences - Other Topics GA AZ9ZO UT WOS:000348573800003 ER PT J AU Azouz, HG Kozou, H Khalil, M Abdou, RM Sakr, M AF Azouz, Hanan Galal Kozou, Hesham Khalil, Mona Abdou, Rania M. Sakr, Mohamed TI The correlation between central auditory processing in autistic children and their language processing abilities SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Autism; Language; Central auditory processing disorder ID DISORDERS; BRAIN AB Aim: To study the auditory profile at different levels of the auditory system in children with ASD and to verify the role of (Central) auditory processing disorder as an essential pathology of the autistic disorder or as an associated co-morbidity, and to establish the correlation between CAP findings and the language delay in these cases. Patients: The study included 30 children with definite autistic disorder according to DSM-IV-TR criteria and ADI-R among those attending the outpatient neuropsychiatry clinic of Alexandria University Children Hospital at El Shatby. An informed consent was taken from all patients in this part of the study. Confidentiality of the records was maintained. Methods: All cases were subjected to complete history taking and examination; special assessment to language skills and evoked potentials were done. Results: The results concluded that (central) auditory processing disorder is an essential pathology of the autistic disorder. Autistic children possess a dysfunctioning or an immature central auditory nervous system at both the brainstem and cortical levels. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Azouz, Hanan Galal; Khalil, Mona; Sakr, Mohamed] Univ Alexandria, Dept Pediat, Fac Med, Alexandria, Egypt. 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J. Pediatr. Otorhinolaryngol. PD DEC PY 2014 VL 78 IS 12 BP 2297 EP 2300 DI 10.1016/j.ijporl.2014.10.039 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA AY6FY UT WOS:000347663800051 PM 25468467 ER PT J AU Pasiali, V LaGasse, AB Penn, SL AF Pasiali, Varvara LaGasse, A. Blythe Penn, Saundra L. TI The Effect of Musical Attention Control Training (MACT) on Attention Skills of Adolescents with Neurodevelopmental Delays: A Pilot Study SO JOURNAL OF MUSIC THERAPY LA English DT Article DE attention; autism spectrum disorders; music therapy; neurodevelopmental disorder ID TRAUMATIC BRAIN-INJURY; SPECTRUM DISORDERS; CHILDREN; AUTISM; PERFORMANCE; NETWORKS; DEFICITS; THERAPY; ADHD; RESPONSIVENESS AB Background: Given the effect of musical training on the rate and accuracy of processing auditory information, therapeutic uses of music may potentially have remedial benefits for individuals with neurodevelopmental deficits. However, additional studies are needed to establish efficacy of music therapy interventions for attention skills in children/adolescents with neurodevelopmental disabilities including those with Autism Spectrum Disorders (ASD). Objective: To establish feasibility and preliminary efficacy of a group music therapy protocol to improve attention skills (sustained, selective, attentional control/switching) in adolescents diagnosed with autism and/or developmental delays. Methods: This single group pretest/posttest study took place in a private school for high functioning adolescents with neurodevelopmental delays. Nine students (4 males, 5 females), ages 13 to 20, participated in the study. Autism severity was assessed using the CARS2-HF and indicated the following distribution for study participants: severe (n = 3), mild (n = 4), or minimal/no (n = 2) symptoms. We assessed feasibility of implementing a 45-min Musical Attention Control Training (MACT) intervention delivered by a board-certified music therapist eight times over 6 weeks in a school setting. We also examined preliminary efficacy of the MACT to improve attention skills using the Test of Everyday Attention for Children (TEA-Ch). Results: Parental consent rate was 100%. All nine participants successfully completed testing measures and 6 weeks of the intervention. Average participation rate was 97%. Data analysis showed positive trends and improvements on measures of attentional control/switching and selective attention. Conclusions: The results showed that the intervention and testing measures were feasible to implement and acceptable to the participants who all completed the protocol. Data analysis demonstrated positive trends indicating that more research on the use of music therapy attention training in high-functioning adolescents with neurodevelopmental disabilities is warranted. C1 [Pasiali, Varvara; Penn, Saundra L.] Queens Univ Charlotte, Charlotte, NC 28274 USA. [LaGasse, A. Blythe] Colorado State Univ, Ft Collins, CO 80523 USA. RP Pasiali, V (reprint author), Queens Univ Charlotte, 1900 Selwyn Ave, Charlotte, NC 28274 USA. EM pasialiv@queens.edu CR Abikoff H, 1996, J LEARN DISABIL, V29, P238 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Ames C, 2010, DEV REV, V30, P52, DOI 10.1016/j.dr.2009.12.003 Belmonte M. K., 2000, AUTISM, V4, P269, DOI DOI 10.1177/1362361300004003004 Belmonte MK, 2004, J NEUROSCI, V24, P9228, DOI 10.1523/JNEUROSCI.3340-04.2004 Brabender V. 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Cobigo, Virginie Lunsky, Yona TI Strengths and Limitations of Health and Disability Support Administrative Databases for Population-Based Health Research in Intellectual and Developmental Disabilities SO JOURNAL OF POLICY AND PRACTICE IN INTELLECTUAL DISABILITIES LA English DT Article DE administrative data; data linkage; intellectual disabilities; service planning; prevalence ID AUTISM SPECTRUM DISORDERS; PREVALENCE; SURVEILLANCE; INDIVIDUALS; ADULTS; ONTARIO AB Individuals with intellectual and developmental disabilities (IDD) experience high rates of social and health disadvantage. Planning effective services that meet the needs of this vulnerable population requires good population-based data that are collected on a routine, ongoing basis. However, in most jurisdictions, none of the commonly available data (e.g., health or disability benefits administrative data) completely captures the IDD population. To more accurately identify persons with IDD in a population, one solution is to link data across multiple sources. To do this, the authors report on an effort to create a linked database to identify a cohort of adults, aged 18-64, with IDD in Ontario and use these data to examine how the linkage can help study health and healthcare access. The linked dataset was created using four health and one disability income support databases. Standardized differences were used to compare sociodemographic and clinical characteristics of the IDD cohorts identified through the health, disability income support, and linked datasets. Indirect estimation was used to evaluate which IDD subgroups might be over- or underestimated if only a single source of data was available. The linked database identified a cohort of 66,484 adults with IDD (0.78% prevalence). The health and disability income support data each uniquely identified approximately a third of the cohort. Health data were more likely to identify younger adults (18-24 years), those with psychiatric illnesses, and hospitalized individuals. The disability income support data were more likely to identify adults aged 35-54 and those living in lower income neighborhoods. By linking multiple databases, the authors were able to identify a much larger cohort of individuals with IDD than if they had used a single data source. It also enabled the creation of a more accurate sociodemographic and clinical profile of this population as each source captured different segments of it. C1 [Lin, Elizabeth; Selick, Avra; Lunsky, Yona] Ctr Addict & Mental Hlth, Toronto, ON M5S 2S1, Canada. [Isaacs, Barry] Surrey Pl Ctr, Toronto, ON M5S 2C2, Canada. [Wilton, Andrew S.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Balogh, Robert] Univ Ontario Inst Technol, Oshawa, ON, Canada. [Cobigo, Virginie] Univ Ottawa, Ottawa, ON, Canada. [Ouellette-Kuntz, Helene] Queens Univ, Ongwanada Resource Ctr, Kingston, ON, Canada. RP Lin, E (reprint author), Ctr Addict & Mental Hlth, Prov Syst Support Program, 33 Russell St, Toronto, ON M5S 2S1, Canada. 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PD DEC PY 2014 VL 11 IS 4 BP 235 EP 244 DI 10.1111/jppi.12098 PG 10 WC Health Policy & Services; Rehabilitation SC Health Care Sciences & Services; Rehabilitation GA AZ8GG UT WOS:000348452600001 ER PT J AU Schelinski, S Riedel, P von Kriegstein, K AF Schelinski, Stefanie Riedel, Philipp von Kriegstein, Katharina TI Visual abilities are important for auditory-only speech recognition: Evidence from autism spectrum disorder SO NEUROPSYCHOLOGIA LA English DT Article DE Autism; Multisensory; Speech recognition; Voice recognition; Lip-reading; Face recognition ID SUPERIOR TEMPORAL SULCUS; FACE MEMORY TEST; VOICE-RECOGNITION; ASPERGER-SYNDROME; BIOLOGICAL MOTION; FUNCTIONING AUTISM; SOCIAL-PERCEPTION; CHILDREN; INTEGRATION; BRAIN AB In auditory-only conditions, for example when we listen to someone on the phone, it is essential to fast and accurately recognize what is said (speech recognition). Previous studies have shown that speech recognition performance in auditory-only conditions is better if the speaker is known not only by voice, but also by face. Here, we tested the hypothesis that such an improvement in auditory-only speech recognition depends on the ability to lip-read. To test this we recruited a group of adults with autism spectrum disorder (ASD), a condition associated with difficulties in lip-reading, and typically developed controls. All participants were trained to identify six speakers by name and voice. Three speakers were learned by a video showing their face and three others were learned in a matched control condition without face. After training, participants performed an auditory-only speech recognition test that consisted of sentences spoken by the trained speakers. As a control condition, the test also included speaker identity recognition on the same auditory material. The results showed that, in the control group, performance in speech recognition was improved for speakers known by face in comparison to speakers learned in the matched control condition without face. The ASD group lacked such a performance benefit. For the ASD group auditory-only speech recognition was even worse for speakers known by face compared to speakers not known by face. In speaker identity recognition, the ASD group performed worse than the control group independent of whether the speakers were learned with or without face. Two additional visual experiments showed that the ASD group performed worse in lip-reading whereas face identity recognition was within the normal range. The findings support the view that auditory-only communication involves specific visual mechanisms. Further, they indicate that in ASD, speaker-specific dynamic visual information is not available to optimize auditory-only speech recognition. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Schelinski, Stefanie; Riedel, Philipp; von Kriegstein, Katharina] Max Planck Inst Human Cognit & Brain Sci, D-04103 Leipzig, Germany. [Riedel, Philipp] Tech Univ Dresden, Fac Med Carl Gustav Carus, D-01307 Dresden, Germany. [von Kriegstein, Katharina] Humboldt Univ, D-12489 Berlin, Germany. RP Schelinski, S (reprint author), Max Planck Inst Human Cognit & Brain Sci, Stephanstr 1a, D-04103 Leipzig, Germany. EM schelinski@cbs.mpg.de; philipp.riedel@uniklinikum-dresden.de; kriegstein@cbs.mpg.de RI von Kriegstein, Katharina/C-3135-2008 FU Max Planck Research Group FX This work was funded by a Max Planck Research Group grant to INK. We thank Brad Duchaine for providing the Cambridge Face Memory Test (CFMT). We thank Laura Smith and Richard Hunger for comments on an earlier version of the manuscript. 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TI Sensory Processing, Participation, and Recovery in Adults With Serious Mental Illnesses SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE sensory processing; mental illness; community participation; recovery ID QUALITY-OF-LIFE; BIPOLAR DISORDER; SCHIZOPHRENIA; DEFICITS; INFORMATION; DYSFUNCTION; PSYCHOSIS; AUTISM AB Objective: People with serious mental illnesses (SMI) have different sensory processing patterns compared to the general population. The purpose of the study was to examine the relationship between different sensory processing patterns and community participation and recovery-oriented outcomes to inform the development of innovative rehabilitation interventions, including those resulting in more accommodating environments. Methods: A quasi-experimental, comparative research design was conducted by using data obtained from 95 adults with SMI who received public mental health services. Participants completed a sensory processing profile and measures of community participation, recovery, and quality of life. Comparisons were made between sensory profile categories for each dependent variable using multivariate analyses of variance. Results: The category with more evidence of self-reported low registration and sensory sensitivity than most reported less participation and lower levels of recovery than did their peers with processing patterns in typical ranges. The category with more self-reported sensory sensitivity than most reported lower quality of life. Finally, the category in the "similar" to "more than most" range on self-reported sensory seeking had higher levels of participation and recovery. Conclusions and Implications for Practice: Assessment of sensory processing patterns in adults with SMI can inform sensory-based interventions that might result in greater community participation and other recovery outcomes. 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A mixed factorial design with one within-subjects variable (type of robots) and two between-subjects variables (type of development and gender) was used. The data suggest that both TO and ASD children perceive robots mainly as toys, while children with ASD also perceive robots as machines. A high diversity of preferences for different robots was revealed, but also a high preference for simplified designs, with exaggerated facial features. This study provides an innovative instrument for studying children's perception about social robots, and offers valuable information, with implications on the design of social robots. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Peca, Andreea; Pintea, Sebastian; Costescu, Cristina] Univ Babes Bolyai, Dept Clin Psychol & Psychotherapy, Cluj Napoca 400015, Cluj, Romania. [Simut, Ramona] Vrije Univ Brussel, Clin & Lift Span Psychol Dept, Brussels, Belgium. [Vanderborght, Bram] Vrije Univ Brussel, Robot & Multibody Mech Res Grp, Brussels, Belgium. 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EM genevieve.konopka@utsouthwestern.edu FU NIMH [R00MH090238]; March of Dimes Foundation Basil O'Connor Starter Scholar Research Award [5-FY13-199]; Once Upon a Time Foundation; CREW Dallas FX Thanks to Wesley Runnels, Stefano Berto, and Guang-Zhong Wang for assistance with the boxes. G.K. is a Jon Heighten Scholar in Autism Research at UT Southwestern. This work was supported by the NIMH (R00MH090238), a March of Dimes Foundation Basil O'Connor Starter Scholar Research Award (5-FY13-199), Once Upon a Time Foundation, and CREW Dallas to G.K. 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A high rate of abnormal social behavioural traits or perceptual deficits is observed in children with unilateral temporal lobe epilepsy. In the present study, perception of auditory and visual social signals, carried by faces and voices, was evaluated in children or adolescents with temporal lobe epilepsy.Methods. We prospectively investigated a sample of 62 children with focal non-idiopathic epilepsy early in the course of the disorder. The present analysis included 39 children with a confirmed diagnosis of temporal lobe epilepsy. Control participants (72), distributed across 10 age groups, served as a control group. Our socio-perceptual evaluation protocol comprised three socio-visual tasks (face identity, facial emotion and gaze direction recognition), two socio-auditory tasks (voice identity and emotional prosody recognition), and three control tasks (lip reading, geometrical pattern and linguistic intonation recognition). All 39 patients also benefited from a neuropsychological examination.Results. As a group, children with temporal lobe epilepsy performed at a significantly lower level compared to the control group with regards to recognition of facial identity, direction of eye gaze, and emotional facial expressions. We found no relationship between the type of visual deficit and age at first seizure, duration of epilepsy, or the epilepsy-affected cerebral hemisphere. Deficits in socio-perceptual tasks could be found independently of the presence of deficits in visual or auditory episodic memory, visual non-facial pattern processing (control tasks), or speech perception. A normal FSIQ did not exempt some of the patients from an underlying deficit in some of the socio-perceptual tasks.Conclusion. Temporal lobe epilepsy not only impairs development of emotion recognition, but can also impair development of perception of other socio-perceptual signals in children with or without intellectual deficiency. Prospective studies need to be designed to evaluate the results of appropriate re-education programs in children presenting with deficits in social cue processing. C1 [Laurent, Agathe; Arzimanoglou, Alexis; Panagiotakaki, Eleni] Univ Hosp Lyon HCL, Hop Femme Mere Enfant, Paediat Neurophysiol Dept, Lyon, France. [Laurent, Agathe; de Schonen, Scania] Paris Descartes Univ, Lab Psychol & Percept, Paris, France. [Arzimanoglou, Alexis] CNRS, Lyon Neurosci Res Ctr CRNL, DYCOG Team, INSERM,U1028,UMR5292, Lyon, France. [Sfaello, Ignacio] CETES, Inst Neurol Infanto Juvenil, Cordoba, Argentina. [Kahane, Philippe] Grenoble Univ Hosp, Dept Neurol, Epilepsy Unit, Grenoble, France. [Ryvlin, Philippe] Univ Hosp Lyon HCL, Pierre Wertheimer Hosp, Funct Neurol & Epileptol Dept, Lyon, France. [Hirsch, Edouard] Univ Hosp Strasbourg HUS, Dept Neurol, Strasbourg, France. RP Laurent, A (reprint author), Hop Femme Mere Enfant, Epilepsy Sleep & Paediat Neurophysiol Dept, 59 Blvd Pinel, F-69500 Lyon, France. EM agathelaurent1977@gmail.com FU CNRS; Fondation Francaise pour la Recherche sur l'Epilepsie (FFRE); Ligue Francaise Contre l'Epilepsie (LFCE); Pfizer Foundation FX This study was approved by the Ethics Review Board of the Hospital la Salpetriere in Paris, France (CCPPRB NoDGS20040025; Amendment: 03024) and supported by grants of the CNRS, The Fondation Francaise pour la Recherche sur l'Epilepsie (FFRE), The Ligue Francaise Contre l'Epilepsie (LFCE), and the Pfizer Foundation. Special thanks to: Drs I. Sfaello (Cordoba, Argentina and previously Paris-Robert Debre) and M. Zibovicius for the functional neuroimaging studies; Acknowledgements to Drs. M. Bourgeois and C. Sainte-Rose (Paris-Necker), L. Minotti (Grenoble), K. Ostrowsky-Coste (Lyon) and MP Valenti (Strasbourg) for having included patients in the study; to our colleagues Caroline Seegmuller (Strasbourg) and Pomine Pellegrino-Thomas (Paris-Robert Debre) for advice; to the patients, control groups and their families for their participation; and editing by Bio-english.com. 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PD DEC PY 2014 VL 16 IS 4 BP 456 EP 470 DI 10.1684/epd.2014.0716 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA AY9PC UT WOS:000347881900007 PM 25498848 ER PT J AU Yin, AL Qiu, YW Jia, B Song, TR Yu, YH Alberts, I Zhong, M AF Yin, Ailan Qiu, Yuwen Jia, Bei Song, Tianrong Yu, Yanhong Alberts, Ian Zhong, Mei TI The developmental pattern of the RAS/RAF/Erk1/2 pathway in the BTBR autism mouse model SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Ras/Raf/Erk 1/2 signaling; Autism; BTBR mice; Autism mouse model; Synapse ID SPECTRUM DISORDERS; SYNAPTIC PLASTICITY; NEURODEVELOPMENTAL DISORDERS; GENETIC VARIANT; INBRED STRAINS; CELL-LINE; ERK; MICE; MEMORY; BEHAVIOR AB BTBR mice exhibit several autistic-like behaviors and are currently used as a model for understanding mechanisms that may be responsible for the pathogenesis of autism. Ras/Raf/ERK1/2 signaling has been suggested to play an important role in neural development, learning, memory, and cognition. Two studies reported that a deletion of a locus on chromosome 16 containing the mitogen-activated protein kinase 3 (MAPK3) gene, which encodes ERK1, is associated with autism. In the present study, Ras/Raf/ERK1/2 signaling was found to be up-regulated in BTBR mice relative to matched control B6 mice, to further suggest involvement in the pathogenesis of autism. To further characterize the developmental pattern of Ras/Raf/ERK1/2 signaling, varying stages during development were sampled to reveal an up-regulation in newborn and 2-week old BTBR mice relative to age-matched B6 mice. By the age of 3-week, Ras/Raf/ERK1/2 signaling in the brain of BTBR mice was unaltered relative to B6 mice, with this trend maintained in 6-week samples. These results suggest that the alteration of Ras/Raf/ERK signaling in the early developmental stages in mice could contribute to the noted autistic phenotype. Furthermore, these findings support the value of BTBR mice to serve as a human analog for autistic etiological research and aid in a better understanding of the developmental mechanisms of autism. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Yin, Ailan; Qiu, Yuwen; Jia, Bei; Song, Tianrong; Zhong, Mei] Nanfang Hosp, Dept Obstet & Gynecol, Guangzhou, Guangdong, Peoples R China. [Yin, Ailan; Yu, Yanhong] Southern Med Univ, Guangzhou, Guangdong, Peoples R China. [Alberts, Ian] CUNY, LarGuardia CC, Dept Nat Sci, New York, NY 11101 USA. RP Zhong, M (reprint author), Nanfang Hosp, Dept Obstet & Gynecol, Guangzhou, Guangdong, Peoples R China. 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However, the presumed role of 5-HT in ASD raises new questions in fundamental neuroscience. Specifically, it is not clear if the current piecemeal approach to 5-HT signaling in the mammalian body is effective and whether new conceptual approaches may be required. This review briefly discusses 5-HT production and circulation in the central nervous system and outside of it, especially with regard to ASD, and proposes a more encompassing approach that questions the utility of the "neurotransmitter" concept. It then introduces the idea of a generalized 5-HT packet that may offer insights into possible links between serotonergic varicosities and blood platelets. These approaches have theoretical significance, but they are also well positioned to advance our understanding of some long-standing problems in autism research. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. RP Janusonis, S (reprint author), Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. EM skirmantas.janusonis@psych.ucsb.edu FU Hellman Family Faculty Fellowships; UCSB Academic Senate Grants FX Our research has been supported by Hellman Family Faculty Fellowships and UCSB Academic Senate Grants. I thank Michelle Maile and Angela Chen for expert immunohistochemistry and confocal microscopy. 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J. Dev. Neurosci. PD DEC PY 2014 VL 39 SI SI BP 9 EP 15 DI 10.1016/j.ijdevneu.2014.05.009 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300003 PM 24886833 ER PT J AU Peterson, C AF Peterson, Candida TI Theory of mind understanding and empathic behavior in children with autism spectrum disorders SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE ASD (autism spectrum disorder); Theory of mind; Empathy; False belief test; Emotional contagion ID ASPERGER-SYNDROME; YOUNG-CHILDREN; CONVERSATION; ADULTS; RESPONSES; EMOTIONS; OTHERS AB This paper begins with a review of past research on theory of mind and empathy in children with ASD. Using varied operational definitions of empathy ranging from physiological heart rate through story vignettes to reports by privileged observers (e.g., teachers) of children's empathic behavior, results of previous studies are limited and contradictory. Thus new evidence is needed to answer two key questions: Are children with ASD less empathic than typically developing children? Do individual differences in theory of mind (ToM) understanding among children with ASD predict differences in their behavioral empathy? An original empirical study of 76 children aged 3-12 years (37 with ASD; 39 with typical development) addressed these. Results showed that children with ASD were significantly less empathic, according to their teachers, than typically developing children. However, this was not because of their slower ToM development. Findings showed equally clearly that ToM understanding was unrelated to empathy in children with ASD. The same was true for typically developing children once age and verbal maturity were controlled. Indeed, even the subgroup of older children with ASD in the sample who passed false belief tests were significantly less empathic than younger preschoolers who failed them. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Peterson, Candida] Univ Queensland, Brisbane, Qld 4072, Australia. RP Peterson, C (reprint author), Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. EM candi@psy.uq.edu.au CR ASTINGTON JW, 1995, COGNITION EMOTION, V9, P151, DOI 10.1080/02699939508409006 Baron-Cohen S, 2004, J AUTISM DEV DISORD, V34, P163, DOI 10.1023/B:JADD.0000022607.19833.00 BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Blair RJR, 2005, CONSCIOUS COGN, V14, P698, DOI 10.1016/j.concog.2005.06.004 Charman T, 1997, DEV PSYCHOL, V33, P781, DOI 10.1037//0012-1649.33.5.781 Dadds MR, 2008, CHILD PSYCHIAT HUM D, V39, P111, DOI 10.1007/s10578-007-0075-4 de Rosnay M, 2014, J CHILD LANG, V41, P1179, DOI 10.1017/S0305000913000433 Dissanayake C., 2003, INDIVIDUAL DIFFERENC, P213 Dunn L. 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TI Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: understanding anxiety in autism spectrum disorder SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Autism; Emotion regulation; Anxiety; Mechanism; Developmental psychopathology ID HIGH-FUNCTIONING AUTISM; MEDIAL PREFRONTAL CORTEX; RESPIRATORY SINUS ARRHYTHMIA; THREAT-RELATED STIMULI; GENERALIZED ANXIETY; EXECUTIVE FUNCTION; POTENTIATED STARTLE; MAGNETIC-RESONANCE; NEGATIVE EMOTION; SELF-REGULATION AB Anxiety is one of the most common clinical problems among children, adolescents, and adults with autism spectrum disorder (ASD), yet we know little about its etiology in the context of ASD. We posit that emotion regulation (ER) impairments are a risk factor for anxiety in ASD. Specifically, we propose that one reason why anxiety disorders are so frequently comorbid with ASD is because ER impairments are ubiquitous to ASD, stemming from socio-cognitive, physiological, and neurological processes related to impaired cognitive control, regulatory processes, and arousal. In this review, we offer a developmental model of how ER impairments may arise in ASD, and when (moderating influences) and how (meditational mechanisms) they result in anxiety. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [White, Susan W.; Richey, John A.; Endick, Thomas H.] Virginia Tech, Dept Psychol, Blacksburg, VA 24061 USA. [Mazefsky, Carla A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Chiu, Pearl H.] Virginia Tech, Caril Res Inst, Blacksburg, VA 24061 USA. RP White, SW (reprint author), Ctr Child Study, 460 Turner St, Blacksburg, VA 24060 USA. 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J. Dev. Neurosci. PD DEC PY 2014 VL 39 SI SI BP 22 EP 36 DI 10.1016/j.ijdevneu.2014.05.012 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300005 PM 24951837 ER PT J AU Rieffe, C De Bruine, M De Rooij, M Stockmann, L AF Rieffe, Carolien De Bruine, Marieke De Rooij, Mark Stockmann, Lex TI Approach and avoidant emotion regulation prevent depressive symptoms in children with an Autism Spectrum Disorder SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Coping; Emotion regulation; Worry; Autism ID AWARENESS QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; INTERNALIZING SYMPTOMS; DIAGNOSTIC INTERVIEW; MISSING DATA; ADOLESCENTS; CHILDHOOD; INVENTORY; EQUATIONS; COMMUNITY AB The prevalence of depression is high in children with Autism Spectrum Disorders (ASDs), but its etiology has not yet been studied in this group. Emotion dysregulation is a well-known contributor to the development of depression in typically developing (TD) children, which might also apply to children with ASD. In this study, we examined the longitudinal relationship between three different ways of emotion regulation (approach, avoidance and worry/rumination) and depressive symptoms in children with ASD and a group of TD children which were compatible with the ASD group (age 9-15-years old). Children filled out self-report questionnaires at 3 time points (with a 9-month break between each session). To account for missing data multiple imputations were used. A regression model with clustered bootstrapping was used to establish which factors contributed to depression and to identify possible differences between the ASD and TD group. Approach and avoidant strategies prevented the development of depressive symptoms in both respective groups, whereas elevated levels of worry/rumination in turn increased children's depressive symptoms. Besides differences in absolute levels (children with ASD scored higher on symptoms of depression and lower on approach strategies than the TD group), no other differences between the groups emerged. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Rieffe, Carolien; De Bruine, Marieke] Leiden Univ, NL-2300 RB Leiden, Netherlands. [De Rooij, Mark] Leiden Univ, Inst Psychol, Methodol & Stat Unit, NL-2300 RB Leiden, Netherlands. [Stockmann, Lex] Ctr Autism, Leiden, Netherlands. RP Rieffe, C (reprint author), Leiden Univ, FSW, Postbus 9555, NL-2300 RB Leiden, Netherlands. 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J. Dev. Neurosci. PD DEC PY 2014 VL 39 SI SI BP 44 EP 48 DI 10.1016/j.ijdevneu.2014.02.003 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300007 PM 24603281 ER PT J AU Fava, L Strauss, K AF Fava, Leonardo Strauss, Kristin TI Response to Early Intensive Behavioral Intervention for autism-An umbrella approach to issues critical to treatment individualization SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Autism; Early Intensive Behavioral Intervention; Treatment; Individualization; Outcome ID PERVASIVE DEVELOPMENTAL DISORDER; PARENT VERBAL RESPONSIVENESS; YOUNG-CHILDREN; SPECTRUM DISORDERS; JOINT ATTENTION; PRESCHOOL-CHILDREN; MENTAL-RETARDATION; LISTENING PREFERENCES; PSYCHIATRIC-DISORDERS; EARLY RECOGNITION AB Integrating knowledge across the disciplines of genetics, neurological, and behavioral science targets, so far, early identification of children with autism and thus early access to intervention. Cross-discipline collaboration might be substantially improve treatment efficacy via individualized treatment based on the child and family needs, consistency across treatment providers and careful planning of skill curricula, setting and techniques. This paper documents the current state of five main issues critical to treatment individualization where cross-discipline collaboration is warranted: (1) developmental timing, (2) treatment intensity, (3) heterogeneity in treatment response, (4) program breath and flexibility, and (5) formats of treatment provision. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Fava, Leonardo; Strauss, Kristin] Assoc Treatment & Res Autism & Related Syndromes, I-00186 Rome, Italy. [Strauss, Kristin] Ernst Moritz Arndt Univ Greifswald, Dept Hlth & Prevent, Greifswald, Germany. RP Fava, L (reprint author), Assoc Treatment & Res Autism & Related Syndromes, Via Scrofa 57, I-00186 Rome, Italy. 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J. Dev. Neurosci. PD DEC PY 2014 VL 39 SI SI BP 49 EP 58 DI 10.1016/j.ijdevneu.2014.05.004 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300008 PM 24866707 ER PT J AU Waddington, H Sigafoos, J Lancioni, GE O'Reilly, MF Van der Meer, L Carnett, A Stevens, M Roche, L Hodis, F Green, VA Sutherland, D Lang, R Marschik, PB AF Waddington, Hannah Sigafoos, Jeff Lancioni, Giulio E. O'Reilly, Mark F. Van der Meer, Larah Carnett, Amarie Stevens, Michelle Roche, Laura Hodis, Flaviu Green, Vanessa A. Sutherland, Dean Lang, Russell Marschik, Peter B. TI Three children with autism spectrum disorder learn to perform a three-step communication sequence using an iPad (R)-based speech-generating device SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Augmentative and alternative communication; Autism spectrum disorders; iPad-based speech-generating device; Multi-step requesting; Social communication; Systematic instruction ID OF-THE-LITERATURE; DEVELOPMENTAL-DISABILITIES; SOCIAL COMMUNICATION; BEHAVIOR PROBLEMS; AAC OPTIONS; INDIVIDUALS; INTERVENTIONS; IPAD AB Background: Many children with autism spectrum disorder (ASD) have limited or absent speech and might therefore benefit from learning to use a speech-generating device (SGD). The purpose of this study was to evaluate a procedure aimed at teaching three children with ASD to use an iPad (R)-based SGD to make a general request for access to toys, then make a specific request for one of two toys, and then communicate a thank-you response after receiving the requested toy. Method: A multiple-baseline across participants design was used to determine whether systematic instruction involving least-to-most-prompting, time delay, error correction, and reinforcement was effective in teaching the three children to engage in this requesting and social communication sequence. Generalization and follow-up probes were conducted for two of the three participants. Results: With intervention, all three children showed improvement in performing the communication sequence. This improvement was maintained with an unfamiliar communication partner and during the follow-up sessions. Conclusion: With systematic instruction, children with ASD and severe communication impairment can learn to use an iPad-based SGD to complete multi-step communication sequences that involve requesting and social communication functions. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Waddington, Hannah; Van der Meer, Larah; Carnett, Amarie; Stevens, Michelle; Roche, Laura; Hodis, Flaviu; Green, Vanessa A.] 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, Coll Educ, Sch Hlth Sci, Christchurch 1, New Zealand. [Lang, Russell] Texas State Univ, Clin Autism Res Evaluat & Support, San Marcos, DC USA. [Marschik, Peter B.] Med Univ Graz, Ctr Physiol Med, Inst Physiol, Res Unit iDN Interdisciplinary Dev Neurosci,IN, 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 FU New Zealand Government through the Marsden Fund Council [10-VUW-071]; Victoria University of Wellington; University of Canterbury; New Zealand Institute of Language, Brain Behavior FX Support for this research was provided from the New Zealand Government through the Marsden Fund Council, administered by the Royal Society of New Zealand (Grant Number 10-VUW-071); and by Victoria University of Wellington, The University of Canterbury, and The New Zealand Institute of Language, Brain & Behavior. 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PD DEC PY 2014 VL 39 SI SI BP 59 EP 67 DI 10.1016/j.ijdevneu.2014.05.001 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300009 PM 24819024 ER PT J AU Foley, KA MacFabe, DF Vaz, A Ossenkopp, KP Kavaliers, M AF Foley, Kelly A. MacFabe, Derrick F. Vaz, Alisha Ossenkopp, Klaus-Peter Kavaliers, Martin TI Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats: Implications for autism spectrum disorders SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Microbiota; Short chain fatty acid; Maternal immune activation; Sex differences; Neurodevelopmental disorders; Social interaction ID MATERNAL IMMUNE ACTIVATION; IN-UTERO EXPOSURE; GUT MICROBIOTA; VALPROIC ACID; BRAIN-DEVELOPMENT; ANIMAL-MODEL; FETAL-BRAIN; CHILDREN; PRODUCT; DISEASE AB Emerging evidence suggests that the gut microbiome plays an important role in immune functioning, behavioral regulation and neurodevelopment. Altered microbiome composition, including altered short chain fatty acids, and/or immune system dysfunction, may contribute to neurodevelopmental disorders such as autism spectrum disorders (ASD), with some children with ASD exhibiting both abnormal gut bacterial metabolite composition and immune system dysfunction. This study describes the effects of prenatal propionic acid (PPA), a short chain fatty acid and metabolic product of many antibiotic resistant enteric bacteria, and of prenatal lipopolysaccharide (LPS), a bacterial mimetic and microbiome component, on social behavior in male and female neonatal, adolescent and adult rats. Pregnant Long Evans rats were injected once a day with either a low level of PPA (500 mg/kg SC) on gestation days G12-16, LPS (50 mu g/kg SC) on G12, or vehicle control on G12 or G12-16. Sex- and age-specific, subtle effects on behavior were observed. Both male and female PPA treated pups were impaired in a test of their nest seeking response, suggesting impairment in olfactory-mediated neonatal social recognition. As well, adolescent males, born to PPA treated dams, approached a novel object more than control animals and showed increased levels of locomotor activity compared to prenatal PPA females. Prenatal LPS produced subtle impairments in social behavior in adult male and female rats. These findings raise the possibility that brief prenatal exposure to elevated levels of microbiome products, such as PPA or LPS, can subtly influence neonatal, adolescent and adult social behavior. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Foley, Kelly A.; Ossenkopp, Klaus-Peter; Kavaliers, Martin] Univ Western Ontario, Grad Program Neurosci, London, ON N6A 5B7, Canada. [Foley, Kelly A.; MacFabe, Derrick F.; Vaz, Alisha; Ossenkopp, Klaus-Peter; Kavaliers, Martin] Univ Western Ontario, Dept Psychol, London, ON N6A 5C2, Canada. [Ossenkopp, Klaus-Peter; Kavaliers, Martin] Univ Western Ontario, Dept Psychol, Kilee Patchell Evans Autism Res Grp, London, ON N6A 5C2, Canada. [MacFabe, Derrick F.] Univ Western Ontario, Dept Psychiat & Psychol, Div Dev Disabil, Kilee Patchell Evans Autism Res Grp, London, ON N6A 5C2, Canada. RP Foley, KA (reprint author), Univ Western Ontario, Social Sci Ctr, Dept Psychol, Grad Program Neurosci, Room 7418,1151 Richmond St, London, ON N6A 5C2, Canada. EM kellyafoley@gmail.com; dmacfabe@uwo.ca; avaz3@uwo.ca; ossenkop@uwo.ca; kavalier@uwo.ca FU GoodLife Children's Charities; Autism Research Institute; Natural Science and Engineering Research Council of Canada Discovery Grants; Ontario Graduate Scholarship FX Thank you to Lindsay Szota for acting as a second rater for interrater reliability of social behavior. We would also like to express our utmost thanks to David Patchell-Evans, for his tireless devotion to persons with autism, and his daughter, Kilee Patchell-Evans. This research was supported by contributions from GoodLife Children's Charities and Autism Research Institute to Derrick MacFabe and by Natural Science and Engineering Research Council of Canada Discovery Grants to Klaus-Peter Ossenkopp and Martin Kavaliers. Kelly Foley was supported by the Ontario Graduate Scholarship. 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J. Dev. Neurosci. PD DEC PY 2014 VL 39 SI SI BP 68 EP 78 DI 10.1016/j.ijdevneu.2014.04.001 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AZ1NT UT WOS:000348006300010 PM 24747144 ER PT J AU Simmons, ES Paul, R Volkmar, F AF Simmons, Elizabeth Schoen Paul, Rhea Volkmar, Fred TI Assessing Pragmatic Language in Autism Spectrum Disorder: The Yale in vivo Pragmatic Protocol SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; DYNAMIC ASSESSMENT; CHILDREN; INTERVENTION; STABILITY AB Purpose: This study compared pragmatic language in youths (9-17 years) with autism spectrum disorder (ASD) and those with typical development (TD) on the Yale in vivo Pragmatic Protocol (YiPP), a semistructured, dynamic conversational assessment. Method: Participants (n = 118) were divided into groups based on age and diagnosis. Each completed the YiPP, which included 4 pragmatic domains (discourse management, communicative functions, conversational repair, presupposition). The participant's response to each probe was scored correct or incorrect; incorrect scores elicited cues from the examiner, and level of cue required for a correction was also scored. Results: The YiPP showed high reliability and internal consistency, with moderate concurrent validity, sensitivity, and specificity. The group with ASD performed worse overall on YiPP probes compared to their TD counterparts on both error (d = 0.96) and cue (d = 0.91) scores. Item analyses revealed greater gaps between older students with ASD and their TD peers than between the 2 younger groups. Conclusions: These data suggest that a probe measure designed to assess pragmatic abilities in children with ASD within a conversational context has some validity for contributing to diagnostic classification and can identify specific areas of pragmatic vulnerabilities as part of a clinical assessment. C1 [Simmons, Elizabeth Schoen; Volkmar, Fred] Yale Univ, New Haven, CT 06520 USA. [Paul, Rhea] Sacred Heart Univ, Fairfield, CT USA. [Paul, Rhea] Haskins Labs Inc, Fairfield, CT USA. RP Simmons, ES (reprint author), Yale Univ, New Haven, CT 06520 USA. EM elizabeth.schoen@yale.edu FU Research Grant - National Institute of Child Health and Human Development (NICHD)-Autism and Related Disorders: Development and Outcome [P0-HD03008] FX Preparation of this article was supported by Research Grant P0-HD03008 funded by the National Institute of Child Health and Human Development (NICHD)-Autism and Related Disorders: Development and Outcome. 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Weismer, Susan Ellis TI Use of the ADOS for Assessing Spontaneous Expressive Language in Young Children With ASD: A Comparison of Sampling Contexts SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID FRAGILE-X-SYNDROME; AUTISM SPECTRUM DISORDERS; PARENT VERBAL RESPONSIVENESS; DOWN-SYNDROME; NARRATIVE ABILITY; SKILLS; BOYS; TODDLERS; CONVERSATION; PRESCHOOLERS AB Purpose: The current study compared the spontaneous expressive language of children with autism spectrum disorder (ASD) across multiple language sampling contexts: the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999) and play with an examiner or parent. Method: Participants were children with ASD (n = 63; 55 boys) with a mean age of 45 months (SD = 3.94, range = 37-53). The number of utterances produced; percentage of intelligible utterances; number of different words; mean length of utterance; and the number of requests, comments, and instances of turn-taking were calculated for the ADOS, examiner-child play, and parent-child play. Children were categorized into Tager-Flusberg et al.' s (2009) developmental language phases for each context. Results: Effects of sampling context were identified for all variables examined. The ADOS resulted in fewer utterances and lower structural and pragmatic language performance than examiner-child play and/or parent-child play. Categorization of children into language phases differed across contexts. Conclusions: Use of the ADOS as a language sampling context may lead to underestimating the abilities of young children with ASD relative to play with an examiner or parent. Researchers and clinicians should be aware of context effects, particularly for assessments designed to observe autism symptoms. C1 [Kover, Sara T.; Davidson, Meghan M.; Sindberg, Heidi A.; Weismer, Susan Ellis] Univ Wisconsin, Madison, WI 53706 USA. RP Kover, ST (reprint author), Univ Washington, Seattle, WA 98195 USA. EM skover@u.washington.edu FU National Institutes of Health [R01 DC07223, T32 DC05359, P30 HD03352] FX Preliminary data were presented at the June 2013 Symposium on Research in Child Language Disorders (Madison, WI). This research was supported by National Institutes of Health Grants R01 DC07223 (Susan Ellis Weismer, Principal Investigator [PI]), T32 DC05359 (Susan Ellis Weismer, PI), and P30 HD03352 (Marsha Mailick, PI). We are grateful to the families and children who participated in this research. We offer special thanks to Madeleine Swenson, Sarah Allen, and Jane Hohman for their tireless efforts in transcription and coding. 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PD DEC PY 2014 VL 57 IS 6 BP 2221 EP 2233 DI 10.1044/2014_JSLHR-L-13-0330 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4MK UT WOS:000348195300015 PM 25093577 ER PT J AU Johnels, JA Gillberg, C Falck-Ytter, T Miniscalco, C AF Johnels, Jakob Asberg Gillberg, Christopher Falck-Ytter, Terje Miniscalco, Carmela TI Face-Viewing Patterns in Young Children With Autism Spectrum Disorders: Speaking up for the Role of Language Comprehension SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID GAZE BEHAVIOR; SOCIAL SCENES; TODDLERS; LOOKING; DISABILITY; ATTENTION; INFANTS; SPEECH; ADULTS AB Purpose: The aim was to examine whether viewing patterns toward the mouth, eyes, and nonmouth-noneyes areas differed between young children with autism spectrum disorder (ASD) and typically developing (TD) children when viewing a person speaking. The role of language comprehension in such viewing patterns was also examined. Method: Eleven children with ASD (approximately 4.5 years old) and 29 TD toddlers (approximately 2.5 years old) participated. The groups were matched on language comprehension raw scores from the Reynell Developmental Language Scales III. All children viewed short films of a woman speaking while their eye movements were recorded with eye-tracking equipment. Results: Children with ASD spent proportionally less time viewing the mouth and more time viewing the nonmouth-noneyes areas. Time viewing the eyes did not differ between groups. Increased mouth viewing was associated with lower language comprehension in the group with ASD. Conclusion: Variability in language comprehension is an important factor to monitor when interpreting face-viewing patterns in young children with ASD, particularly with regard to mouth viewing. The results may help explain divergent findings in this field of research. 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Therefore, this study introduces a systems-level model, which suggests that gut microbes and intestinal inflammation influence the onset of regressive autism through increasing gut permeability. This computational model provides a framework for quantitative understanding of how imbalances in populations of gut microbes alters the whole-body and brain distributions of neurotoxins produced by GI tract bacteria. Our results indicate that increased levels of the bacteria Bacteroides vulgatus lead to increased brain levels of propionic acid, a neurotoxin which has been known to cause symptoms characteristic of autism when injected into the brain of rats. Our results further indicate that immune response to virulence factors produced by bacteria in the gut leads to increased systemic levels of inflammatory cytokines, such as IL-1 beta, which significantly alter the permeability of the gut epithelial layer and the blood-brain barrier. Due to the large size of cytokines, however, we predict the time required for concentrations in the brain to stabilize to be on the order of years. This suggests that treatments preventing autism development could be administered after identifying microbial biomarkers of disease but before debilitating brain inflammation leads to regressive autism progression. Future research extending this work could provide new treatment options and diagnostic techniques to help combat regressive autism. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Downs, Ryan; Perna, Jonathon; Vitelli, Andrew; Cook, Daniel; Dhurjati, Prasad] Univ Delaware, Dept Chem & Biomol Engn, Newark, DE 19716 USA. RP Dhurjati, P (reprint author), Univ Delaware, Dept Chem & Biomol Engn, 150 Acad St, Newark, DE 19716 USA. 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Hypotheses PD DEC PY 2014 VL 83 IS 6 BP 649 EP 655 DI 10.1016/j.mehy.2014.09.005 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY5EJ UT WOS:000347595600004 PM 25288537 ER PT J AU Strifert, K AF Strifert, Kim TI The link between oral contraceptive use and prevalence in autism spectrum disorder SO MEDICAL HYPOTHESES LA English DT Article ID MEDAKA ORYZIAS-LATIPES; ENVIRONMENTAL-FACTORS; ETHINYLESTRADIOL; EXPRESSION; PREGNANCY; CHILDREN; WOMEN AB Autism spectrum disorder (ASD) is a group of developmental disabilities that include full syndrome autism, Asperger's syndrome, and other pervasive developmental disorders. The identified prevalence of ASD has increased in a short time period across multiple studies causing some to conclude that it has reached epidemic proportions in the U.S. Many possible explanations for the rise in numbers of individuals diagnosed with ASD have been offered and yet, causes and contributing factors for ASD are inadequately understood. Current evidence suggests that both genetics and environment play a part in causing ASD. One possible risk factor for the increase in prevalence has been profoundly overlooked in the existing biomedical and epidemiologic literature. As the prevalence of ASD has risen in the last sixty years, so has the prevalence of the usage of the oral contraceptives and other modern hormonal delivery methods. In 1960 about one million American women were using oral contraceptives, today close to 11 million women in the U.S. use oral contraceptives. Eighty-two percent of sexually active women in the U.S. have used oral contraceptives at some point during their reproductive years. Thus, the growth in use of progesterone/estrogen-based contraceptives in the United State has reached near-ubiquitous levels among women in the child-bearing age range. The suppression of ovulation produced by estrogen-progesterone is an indisputable abnormality. It is logical to consider the outcome of the ovum that would have been normally released from the ovary during ovulation. To date there is no comprehensive research into the potential neurodevelopmental effects of oral contraceptive use on progeny. The issue has been only sparsely considered in the biomedical literature. This article hypothesizes that the compounds, estrogen and progesterone, used in oral contraceptives modify the condition of the oocyte and give rise to a potent risk factor that helps explain the recent increase in the prevalence of ASD's. 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The purpose of this study was to implement an operant methodology for recognizing the functional properties of challenging behavior in people with intellectual disabilities. Four adults diagnosed with profound intellectual disability received assessment under several experimental conditions using a functional analysis methodology: social attention as positive reinforcement, negative reinforcement such as the termination of demands, positive tangible reinforcements, absence of social contingencies, and escape from noisy stimuli. Results showed that different types of reinforcement or avoiding contingencies affected the rate of aggression, self-injury, disruption, stereo-typy, or socially offensive behaviors, and functional analysis may potentially be a viable alternative for identifying challenging behaviors. C1 [Delgado-Casas, C.; Navarro, J. I.; Garcia-Gonzalez-Gordon, R.; Marchena, E.] Univ Cadiz, Puerto Real 11510, Spain. 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TI VALIDITY AND RELIABILITY EVIDENCE OF THE TOCA-C IN A SAMPLE OF GREEK STUDENTS SO PSYCHOLOGICAL REPORTS LA English DT Article ID AUTISM SPECTRUM DISORDERS; CHILD-BEHAVIOR CHECKLIST; DIFFICULTIES QUESTIONNAIRE; CEREBRAL-PALSY; INTELLECTUAL DISABILITY; PRESCHOOL-CHILDREN; SOCIAL COMPETENCE; COMMUNITY SAMPLE; AGE-CHILDREN; STRENGTHS AB Validity and reliability evidence of the Teacher Observation of Classroom Adaptation-Checklist (TOCA-C) was examined in 186 Greek students through exploratory factor analysis, divergent and concurrent validity, internal consistency, and test-retest reliability. The TOCA-C showed a high internal consistency for the three factors of Concentration Problems, Disruptive/Aggressive Behaviour, and Prosocial Behaviour (alpha s = .89-.96), and acceptable two-week test-retest reliability. The three-factor solution explained 74.50% of the total variance. 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Ruiz, Susan Mosher Gansler, David A. Sawyer, Kayle S. Oscar-Berman, Marlene TI Social Cognition Deficits and Associations with Drinking History in Alcoholic Men and Women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Social Cognition; Emotion; Alcoholism; Gender; Advanced Clinical Solutions ID FACIAL EXPRESSION RECOGNITION; AFFECTIVE STIMULI; BRAIN; PERCEPTION; DEPENDENCE; DYSFUNCTION; DISORDERS; PROSODY; AUTISM; CORTEX AB BackgroundPrevious studies have demonstrated the presence of a social cognition factor as an element of general cognition in healthy control and clinical populations. Recently developed measures of social cognition include the social perception and faces subtests of the Wechsler Advanced Clinical Solutions (ACS) Social Cognition module. While these measures have been validated on various clinical samples, they have not been studied in alcoholics. Alcoholism has been associated with emotional abnormalities and diminished social cognitive functioning as well as neuropathology of brain areas underlying social processing abilities. We used the ACS Social Perception and Faces subtests to assess alcoholism-related impairments in social cognition. MethodsSocial cognitive functioning was assessed in 77 abstinent alcoholic individuals (37 women) and 59 nonalcoholic control participants (29 women), using measures of the ACS Social Cognition module and subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) that contain a social cognition component (Picture Completion and Comprehension). Group and gender differences in ACS and WAIS-IV performance were assessed, as well as relationships between measures of alcoholism severity and social cognitive functioning. ResultsAlcoholics performed significantly worse than nonalcoholics on the ACS measures of Affect Naming and Faces Content. Alcoholic men were impaired relative to alcoholic women on Prosody Face Matching and Faces Content scores. Among alcoholics, longer durations of heavy drinking were associated with poorer performance on Affect Naming, and a greater number of daily drinks were associated with lower Prosody Face Matching performance. For alcoholic women, a longer duration of abstinence was associated with better performance on Affect Naming. ConclusionsAlcoholic men and women showed different patterns of associations between alcoholism indices and clinically validated social cognition assessments. These findings extend into the social cognition domain, previous literature demonstrating the presence of cognitive deficits in alcoholism, their association with alcoholism severity, and variability by gender. Moreover, because impairments in social cognition can persist despite extended abstinence, they have important implications for relapse prevention. C1 [Valmas, Mary M.; Ruiz, Susan Mosher; Sawyer, Kayle S.; Oscar-Berman, Marlene] VA Boston Healthcare Syst, Psychol Res Serv, Boston, MA USA. [Valmas, Mary M.; Gansler, David A.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Valmas, Mary M.; Ruiz, Susan Mosher; Sawyer, Kayle S.; Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, 72 East Concord St L-815, Boston, MA 02118 USA. EM oscar@bu.edu FU National Institutes of Health, NIAAA [R01-AA07112, K05-AA00219]; Medical Research Service of the U.S. Department of Veterans Affairs FX This research was supported by grants from the National Institutes of Health, NIAAA R01-AA07112 and K05-AA00219, and the Medical Research Service of the U.S. Department of Veterans Affairs. 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HIKIKOMORI RISK IN JAPAN AND THE DEVIATION FROM SEEKING HARMONY SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID YOUTH AB There is an increasing number of youth in Japan who are dropping out of society and isolating themselves in their bedrooms from years to decades at a time. These so-called hikikomori or social isolates have been described by Japanese clinicians as suffering most commonly from an autism spectrum disorder. However, such claims come out of examining biased samples of hikikomori who have already been referred to mental health professionals. Alternatively, we argue that the tendency for hikikomori represents an increasing marginalization of Japanese youth who are consciously rejecting dominant cultural values of harmony-seeking and consequently deviating in their motivation to conform to others' behaviors. The current study tests for this alternative argument for hikikomori tendencies. One hundred ninety-five participants were recruited from Japanese universities and divided into high risk vs. low risk of becoming hikikomori according to an instrument that measures such risks. As expected, high risk students shared similar. social perceptions about pervasive values in their society as low risk students, thereby ruling out deficits in social perception as being associated with hikikomori risk. Instead, high risk students were not motivated to conform to others' behaviors relative to low risk students and this difference was fully mediated by differences in preferred levels of harmony-seeking. Furthermore, high risk students scored lower on both local identity and global identity relative to low risk students, thereby reifying their marginalized identity in Japanese society. C1 [Norasakkunkit, Vinai] Gonzaga Univ, Spokane, WA 99258 USA. [Uchida, Yukiko] Kyoto Univ, Kyoto 6068501, Japan. 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Soc. Clin. Psychol. PD DEC PY 2014 VL 33 IS 10 BP 918 EP 935 PG 18 WC Psychology, Clinical; Psychology, Social SC Psychology GA AY3OR UT WOS:000347493300006 ER PT J AU Li, JJ Shi, MY Ma, ZH Zhao, SC Euskirchen, G Ziskin, J Urban, A Hallmayer, J Snyder, M AF Li, Jingjing Shi, Minyi Ma, Zhihai Zhao, Shuchun Euskirchen, Ghia Ziskin, Jennifer Urban, Alexander Hallmayer, Joachim Snyder, Michael TI Integrated systems analysis reveals a molecular network underlying autism spectrum disorders SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE autism spectrum disorders; corpus callosum; functional modules; oligodendrocytes; protein interaction network ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; CORPUS-CALLOSUM; BRAIN-DEVELOPMENT; PROTEIN NETWORK; DISEASE; GENE; VARIANTS; IMPLICATE; RESOURCE AB Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. C1 [Li, Jingjing; Shi, Minyi; Ma, Zhihai; Euskirchen, Ghia; Snyder, Michael] Stanford Univ, Sch Med, Dept Genet, Stanford Ctr Genom & Personalized Med, Stanford, CA 94305 USA. [Zhao, Shuchun; Ziskin, Jennifer] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Urban, Alexander; Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Snyder, M (reprint author), Stanford Univ, Sch Med, Dept Genet, Stanford Ctr Genom & Personalized Med, Stanford, CA 94305 USA. EM mpsnyder@stanford.edu RI Ma, Zhihai/E-7130-2015 FU Banting Postdoctoral Fellowship; NIH; Department of Genetics FX Special thanks should be given to families of the brain tissue donors for their contribution to advancing autism research. We gratefully thank the Autism Speaks' Autism Tissue Program, The Centre for Applied Genomics, Hospital for Sick Children in Toronto, and NICHD Brain and Tissue Bank for providing us brain DNA and tissue samples in this study. We also thank Mariko Bennett, Chris Bennett and Sergiu Pasca for insightful discussion and help on this project. We also sincerely thank the anonymous reviewers for providing highly constructive comments. JL is supported by Banting Postdoctoral Fellowship. This research was funded by grants from the NIH and the Department of Genetics. 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TI A Wearable Camera Detects Gaze Peculiarities during Social Interactions in Young Children with Pervasive Developmental Disorders SO IEEE TRANSACTIONS ON AUTONOMOUS MENTAL DEVELOPMENT LA English DT Article DE Atypical gaze to human faces; eye-tracking; facial expressions; pervasive developmental disorders; social attention; social sounds; visual perception ID AUTISM SPECTRUM DISORDER; JOINT ATTENTION; HOME VIDEOTAPES; 6-MONTH-OLD INFANTS; PRESCHOOL-CHILDREN; VISUAL EXPERIENCE; CHILDHOOD AUTISM; SPEECH; RECOGNITION; IMPAIRMENT AB We report on the study of gazes, conducted on children with pervasive developmental disorders (PDD), by using a novel head-mounted eye-tracking device called the WearCam. Due to the portable nature of the WearCam, we are able to monitor naturalistic interactions between the children and adults. The study involved a group of 3- to 11-year-old children (n=13) with PDD compared to a group of typically developing (TD) children (n=13) between 2- and 6-years old. We found significant differences between the two groups, in terms of the proportion and the frequency of episodes of directly looking at faces during the whole set of experiments. We also conducted a differentiated analysis, in two social conditions, of the gaze patterns directed to an adult's face when the adult addressed the child either verbally or through facial expression of emotion. We observe that children with PDD show a marked tendency to look more at the face of the adult when she makes facial expressions rather than when she speaks. C1 [Magrelli, Silvia; Noris, Basilio; Billard, Aude G.] Ecole Polytech Fed Lausanne, Learning Algorithms & Syst Lab, CH-1015 Lausanne, Switzerland. [Jermann, Patrick] Ecole Polytech Fed Lausanne, CEDE, Ctr Digital Educ, CH-1015 Lausanne, Switzerland. [Ansermet, Francois; Hentsch, Francois] Hop Univ Geneve, Dept Child & Adolescent Med, Serv Child & Adolescent Psychiat, Geneva, Switzerland. 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PD DEC PY 2014 VL 6 IS 4 BP 274 EP 285 DI 10.1109/TAMD.2014.2327812 PG 12 WC Computer Science, Artificial Intelligence; Robotics; Neurosciences SC Computer Science; Robotics; Neurosciences & Neurology GA AX1TO UT WOS:000346729100005 ER PT J AU Erbetta, A Bulgheroni, S Contarino, V Chiapparini, L Esposito, S Vago, C Riva, D AF Erbetta, Alessandra Bulgheroni, Sara Contarino, Valeria Chiapparini, Luisa Esposito, Silvia Vago, Chiara Riva, Daria TI Neuroimaging Findings in 41 Low-Functioning Children With Autism Spectrum Disorder: A Single-Center Experience SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE autism spectrum disorder; conventional magnetic resonance imaging (MRI); structural brain abnormalities; children ID QUALITY-STANDARDS-SUBCOMMITTEE; VIRCHOW-ROBIN SPACES; DEVELOPMENTAL DISORDERS; MENTAL-RETARDATION; PRACTICE PARAMETER; NEUROLOGY-SOCIETY; AMERICAN-ACADEMY; CISTERNA MAGNA; BRAIN; DIAGNOSIS AB The data on the rate of brain imaging abnormalities in autistic spectrum disorders are still inconsistent. A recent study on patients with high-functioning autism found that approximately 90% of children had normal magnetic resonance imaging (MRI) scans whereas an unexpected high rate of MRI abnormalities was reported in 77 nonsyndromic autistic children with or without intellectual disability. The aim of this study was to evaluate the prevalence of neuroradiologic findings in low-functioning autistic children compared to controls matched for age. Minor brain abnormalities were found in 44% of patients and 22% of controls. Our main result is the high rate of mega cisterna magna in autistic patients. High rate of minor neuroradiologic abnormalities in low-functioning autistic patients could contribute to the research about the various endophenotypes and complete the clinical assessment of children with autistic spectrum disorder and intellectual disability. C1 [Erbetta, Alessandra; Contarino, Valeria; Chiapparini, Luisa] Fdn IRCCS Ist Neurol C Besta, Neuroradiol Div, I-20133 Milan, Italy. 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Child Neurol. PD DEC PY 2014 VL 29 IS 12 BP 1626 EP 1631 DI 10.1177/0883073813511856 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AX4NB UT WOS:000346908000014 PM 24346312 ER PT J AU Maramara, LA He, WZ Ming, X AF Maramara, Lauren A. He, Wenzhuan Ming, Xue TI Pre- and Perinatal Risk Factors for Autism Spectrum Disorder in a New Jersey Cohort SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE autism spectrum disorders; perinatal risk factors; prenatal risk factors; advanced paternal age; advanced maternal age ID PATERNAL AGE; BIRTH COMPLICATIONS; INFANTILE-AUTISM; NEONATAL FACTORS; MATERNAL AGE; POPULATION; METAANALYSIS; PREGNANCY; CHILDREN; PAIRS AB This study evaluated the prevalence of pre- and perinatal risk factors in a cohort of children with autism spectrum disorders compared with the New Jersey population. Our cohort included 268 individuals with an autism spectrum disorder. Birth histories were obtained by a self-administered questionnaire. The autism spectrum disorders cohort rates of 7 perinatal risk factors were significantly higher than New Jersey state rates: mother's age 35 years or older, low birth weight, multiple gestation, prematurity, vaginal bleeding, prolonged labor, and hypoxia. Analysis of clustering of risk factors in the cohort showed no significant differences across maternal and paternal age groups. Older mothers in the cohort had a higher risk of infant hypoxia. Multiple risk factors during pregnancy appear to be associated with a higher risk of autism spectrum disorders in offspring, supporting the hypothesis that environmental influences in conjunction with genetics contribute to the causes of autism spectrum disorders. C1 [Maramara, Lauren A.; He, Wenzhuan; Ming, Xue] Rutgers New Jersey Med Sch, Dept Neurosci & Neurol, Newark, NJ 07103 USA. RP Ming, X (reprint author), Rutgers New Jersey Med Sch, Dept Neurosci & Neurol, 90 Bergen St,DOC 8100, Newark, NJ 07103 USA. FU Knights of Columbus, East Hanover Chapter, NJ FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Knights of Columbus, East Hanover Chapter, NJ. 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Here the case of a 4-year-old autistic boy is presented, who was found to have evidence of a neuronal migration disorder on magnetic resonance imaging (MRI) during a workup for seizures. Genetic testing did not reveal any of the gene mutations known to be associated with neuronal migration disorders but did reveal a microduplication at chromosome 15q13.3, a locus that has been previously associated with autism, cognitive impairment, and seizures. Although the concurrent presence of the genetic and structural abnormalities does not necessarily imply causality, the simultaneous independent occurrence of both conditions is certainly unusual. It is possible that there may be an association between this duplication syndrome and aberrant neuronal migration. C1 [Beal, Jules C.] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Bronx, NY 10467 USA. [Beal, Jules C.] Albert Einstein Coll Med, Epilepsy Management Ctr, Bronx, NY 10467 USA. [Beal, Jules C.] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Beal, JC (reprint author), Dept Neurol, 111 E 210th ST, Bronx, NY 10467 USA. 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Child Neurol. PD DEC PY 2014 VL 29 IS 12 BP NP186 EP NP188 DI 10.1177/0883073813510356 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AX4NB UT WOS:000346908000005 PM 24282185 ER PT J AU Park, YJ Won, SS Nam, M Chung, JH Kwack, KB AF Park, YoungJoon Won, SeongSik Nam, Min Chung, Joo-Ho Kwack, KyuBum TI Interaction Between MAOA and FOXP2 in Association With Autism and Verbal Communication in a Korean Population SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE MAOA; FOXP2; autism spectrum disorder ID MONOAMINE-OXIDASE; SPECTRUM DISORDERS; SODIUM DEPRIVATION; GENE; BRAIN; HERITABILITY; STIMULATION; PHENOTYPE; OXYTOCIN; CHILDREN AB Expression levels of monoamine oxidase A (MAOA), the enzyme that related to monoamine neurotransmitters metabolism such as serotonin, are related to schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a transcription factor, is associated with abnormal language development and is expressed in several areas of the central nervous system in response to serotonin. For this reason, we undertook interaction analysis between MAOA and FOXP2 in autism spectrum disorder, including testing the verbal communication score of the childhood autism rating scale. In interaction analysis, the FOXP2-TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323-rs1801291-rs3027407) haplotype were significantly associated with autism spectrum disorder in males. However, when the interaction term was omitted, neither MAOA nor FOXP2 was associated with autism spectrum disorder or verbal communication. These results indicate that language and speech ability is affected by an interaction between FOXP2 and MAOA, but not by either gene separately. C1 [Park, YoungJoon; Won, SeongSik; Kwack, KyuBum] CHA Univ, Coll Life Sci, Dept Biomed Sci, Songnam 463836, South Korea. [Nam, Min] Seoul Metropolitan Childrens Hosp, Seoul, South Korea. [Chung, Joo-Ho] Kyung Hee Univ, Sch Med, Kohwang Med Res Inst, Seoul, South Korea. RP Kwack, KB (reprint author), CHA Univ, Coll Life Sci, Dept Biomed Sci, 222 Yatabdong, Songnam 463836, South Korea. EM kbkwack@cha.ac.kr FU Korea Health 21 R&D Project, the Ministry of Health and Welfare, Republic of Korea [A040002]; Priority Research Centers Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2009-0093821] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grants from the Korea Health 21 R&D Project, the Ministry of Health and Welfare, Republic of Korea (A040002), and from the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093821). 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In particular, a potential link with exposure to environmental mercury has been suggested. Male sex constitutes a second risk factor for autism. A third potential genetic risk factor is decreased Reelin expression. Male heterozygous reeler (rl(+/-)) mice show an autism-like phenotype, including Purkinje cells (PCs) loss and behavioral rigidity. We evaluated the complex interactions between 3 risk factors, i.e. genetic status, sex, and exposure to methylmercury (MeHg), in rl(+/-) mice. Mice were exposed to MeHg during the prenatal and early postnatal period, either at a subtoxic dose (2 ppm in Dams' drinking water), or at a toxic dose (6 ppm Dams' drinking water), based on observations in other rodent species and mice strains. We show that: (a) 2 ppm MeHg does not cause PCs loss in the different animal groups, and does not enhance PCs loss in rl(+/-) males; consistent with a lack of overt neurotoxicity, 2 ppm MeHg per se does not cause behavioral alterations (separation-induced ultrasonic calls in newborns, or sociability and social preference in adults); (b) in stark contrast, 6 ppm MeHg causes a dramatic reduction of PCs number in all groups, irrespective of genotype and sex. Cytochrome C release from mitochondria of PCs is enhanced in 6 ppm MeHg-exposed groups, with a concomitant increase of mu-calpain active subunit. At the behavioral level, 6 ppm MeHg exposure strongly increases ultrasonic vocalizations in all animal groups. Notably, 6 ppm MeHg significantly decreases sociability in rl(+/-) male mice, while the 2 ppm group does not show such as decrease. At a subtoxic dose, MeHg does not enhance the autism-like phenotype of male rl(+/-) mice. At the higher MeHg dose, the scenario is more complex, with some "autism-like" features (loss of sociability, preference for sameness) being evidently affected only in rl(+/-) males, while other neuropathological and behavioral parameters being altered in all groups, independently from genotype and sex. Mitochondrial abnormalities appear to play a crucial role in the observed effects. (C) 2014 Elsevier Inc. All rights reserved. C1 [Biamonte, Filippo; Marino, Ramona; De Luca, Roberto; Keller, Flavio] Univ Campus Biomed, Lab Dev Neurosci & Neural Plast, I-00198 Rome, Italy. [Latini, Laura; Molinari, Marco] Santa Lucia Fdn, IRCCS, I-00143 Rome, Italy. [Giorgi, Filippo Sean] Univ Pisa, Dept Clin & Expt Med, Neurol Sect, I-56126 Pisa, Italy. [Zingariello, Maria] Univ Campus Biomed, Lab Histol, Rome, Italy. [D'Ilio, Sonia] Ist Super Sanita, Ctr Nazl Sostanze Chim, I-00161 Rome, Italy. [Majorani, Costanza; Petrucci, Francesco; Violante, Nicola; Senofonte, Oreste] Ist Super Sanita, Dipartimento Ambiente & Prevenz Primaria, I-00161 Rome, Italy. RP Molinari, M (reprint author), Fdn S Lucia, Expt Neurorehabil Lab, Direttore UO & Sez Mielolesi, Via Ardeatina 306, I-00179 Rome, Italy. EM m.molinari@hsantalucia.it; f.keller@unicampus.it RI Molinari, Marco/A-9624-2010 OI Molinari, Marco/0000-0001-9808-9688 FU Autism Speaks [4191]; Italian Health Ministry "Ricerca Corrente" FX The work described in this paper was partly supported by a grant from Autism Speaks (grant 4191) to F.K., by the Italian Health Ministry "Ricerca Corrente" to M.M. 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DEC PY 2014 VL 45 BP 67 EP 80 DI 10.1016/j.neuro.2014.09.006 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100008 PM 25305366 ER PT J AU Sobolewski, M Conrad, K Allen, JL Weston, H Martin, K Lawrence, BP Cory-Slechta, DA AF Sobolewski, Marissa Conrad, Katherine Allen, Joshua L. Weston, Hiromi Martin, Kyle Lawrence, B. Paige Cory-Slechta, Deborah A. TI Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals SO NEUROTOXICOLOGY LA English DT Article DE Endocrine disrupting chemical; Mixture; Behavioral toxicity; Sex-specific ID SPRAGUE-DAWLEY RAT; MALE C57BL/6 MICE; BISPHENOL-A; NEONATAL EXPOSURE; OBJECT RECOGNITION; DEVELOPMENTAL EXPOSURE; NUCLEUS-ACCUMBENS; PRENATAL STRESS; FEMALE RATS; ATRAZINE AB Humans are increasingly and consistently exposed to a variety of endocrine disrupting chemicals (EDCs), chemicals that have been linked to neurobehavioral disorders such as ADHD and autism. Many of such EDCs have been shown to adversely influence brain mesocorticolimbic systems raising the potential for cumulative toxicity. As such, understanding the effects of developmental exposure to mixtures of EDCs is critical to public health protection. Consequently, this study compared the effects of a mixture of four EDCs to their effects alone to examine potential for enhanced toxicity, using behavioral domains and paradigms known to be mediated by mesocorticolimbic circuits (fixed interval (FI) schedule controlled behavior, novel object recognition memory and locomotor activity) in offspring of pregnant mice that had been exposed to vehicle or relatively low doses of four EDCs, atrazine (ATR - 10 mg/kg), perfluorooctanoic acid (PFOA - 0.1 mg/kg), bisphenol-A (BPA - 50 mu g/kg), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - 0.25 mu g/kg) alone or combined in a mixture (MIX), from gestational day 7 until weaning. EDC-treated males maintained significantly higher horizontal activity levels across three testing sessions, indicative of delayed habituation, whereas no effects were found in females. Statistically significant effects of MIX were seen in males, but not females, in the form of increased FI response rates, in contrast to reductions in response rate with ATR, BPA and TCDD, and reduced short term memory in the novel object recognition paradigm. MIX also reversed the typically lower neophobia levels of males compared to females. With respect to individual EDCs, TCDD produced notable increases in FI response rates in females, and PFOA significantly increased ambulatory locomotor activity in males. Collectively, these findings show the potential for enhanced behavioral effects of EDC mixtures in males and underscore the need for animal studies to fully investigate mixtures, including chemicals that converge on common physiological substrates to examine potential mechanisms of toxicity with full dose effect curves to assist in interpretations of relevant mechanisms. (C) 2014 Elsevier Inc. All rights reserved. C1 [Sobolewski, Marissa; Conrad, Katherine; Allen, Joshua L.; Weston, Hiromi; Martin, Kyle; Lawrence, B. Paige; Cory-Slechta, Deborah A.] Univ Rochester, Med Ctr, Dept Environm Med, Rochester, NY 14642 USA. RP Sobolewski, M (reprint author), Univ Rochester, Med Ctr, Dept Environm Med, 575 Elmwood Ave,Box EHSC, Rochester, NY 14642 USA. EM Marissa_Sobolewski@urmc.rochester.edu; Katherine_Bachmann@urmc.rochester.edu; Joshua_Allen@urmc.rochester.edu; Hiromi_Ishitobi@urmc.rochester.edu; Kyle_Martin@urmc.rochester.edu; Paige_Lawrence@urmc.rochester.edu; Deborah_Cory-slechta@urmc.rochester.edu FU [P30 ES001247]; [T32 ES007026-36] FX This work was supported by P30 ES001247 and T32 ES007026-36. 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Neurology; Pharmacology & Pharmacy; Toxicology GA AX5GQ UT WOS:000346955100013 PM 25454719 ER PT J AU Liu, W Huo, X Liu, DC Zeng, X Zhang, Y Xu, XJ AF Liu, Wei Huo, Xia Liu, Daichun Zeng, Xiang Zhang, Yu Xu, Xijin TI S100 beta in heavy metal-related child attention-deficit hyperactivity disorder in an informal e-waste recycling area SO NEUROTOXICOLOGY LA English DT Article DE Attention-deficit/hyperactivity disorder (ADHD); Child behavior; Electronic waste; Heavy metal; Serum S100 beta ID AUTISM SPECTRUM DISORDERS; TRAUMATIC BRAIN-INJURY; BLOOD LEAD LEVELS; DEFICIT/HYPERACTIVITY DISORDER; ENVIRONMENT INTERACTIONS; CADMIUM LEVELS; EXPOSURE; PREVALENCE; CHINA; GENE AB Exposure to lead even at low levels correlates with attention-deficit/hyperactivity disorder (ADHD). However, lead-contaminated environments are often contaminated with other heavy metals that could exacerbate lead-induced ADHD. We conducted this study to evaluate the relationship between multiple heavy metals and child behaviors, and the involvement of S100 calcium-binding protein beta (S100 beta) expression in child ADHD in Guiyu, an internationally-known e-waste contaminated recycling town. Two hundred and forty kindergarten children, 3- to 7-years of age, who lived in Guiyu, were recruited for this study. Child behavioral assessment was derived from parent and teacher ratings. Serum S100 beta was assayed by an enzyme-linked immunosorbent assay (ELISA). Lead (Pb), cadmium (Cd) and manganese (Mn) levels in whole blood were measured using graphite furnace atomic absorption spectrometry (GFAAS). The prevalence of children with ADHD symptoms in Guiyu was 18.6%, with the percentage of children suspected to have behavior problems being 46.2% or 46.5%, based on the Rutter parents' or teachers' scale scores, respectively. Child blood levels of Pb, Cd, and Mn correlated with certain behavioral abnormalities, such as conduct problems and antisocial behavior. Serum S100 beta levels were associated with heavy metal levels in blood, and certain behavioral abnormalities. These findings suggest that exposure to various environmental heavy metals in Guiyu might result in child behavior disorders. Results also indicate that S100 beta may provide information for laboratory evaluation of neurotoxicity. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liu, Wei; Huo, Xia; Liu, Daichun; Zeng, Xiang; Zhang, Yu; Xu, Xijin] Shantou Univ, Coll Med, Lab Environm Med & Dev Toxicol, Shantou 515041, Peoples R China. [Liu, Wei; Huo, Xia; Liu, Daichun; Zeng, Xiang; Zhang, Yu; Xu, Xijin] Shantou Univ, Coll Med, Prov Key Lab Infect Dis & Mol Immunopathol, Shantou 515041, Peoples R China. [Zeng, Xiang] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700RB Groningen, Netherlands. [Xu, Xijin] Shantou Univ, Coll Med, Dept Cell Biol & Genet, Shantou 515041, Peoples R China. RP Xu, XJ (reprint author), Shantou Univ, Coll Med, Lab Environm Med & Dev Toxicol, 22 Xinling Rd, Shantou 515041, Peoples R China. EM xuxj@stu.edu.cn FU National Natural Science Foundation of China [21177080] FX The authors are grateful to Dr. Stanley Lin for his critical reading and editing of the manuscript. This work was supported by the National Natural Science Foundation of China (21177080). 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Madankumar, R. Rosner, M. Reznik, S. E. TI Increased placental trophoblast inclusions in placenta accreta SO PLACENTA LA English DT Article DE Placenta accreta; Trophoblast inclusions ID AUTISM; RISK AB Introduction: Trophoblast inclusions (Tls) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of nonaneuploid, non-accreta placentas have Tls. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study Tls as a potential surrogate indicator of abnormal placental genetics. Methods: Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. Results: Forty percent of cases with placenta accreta demonstrated Tls compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). Discussion: Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. Conclusion: This study has shown that Tls are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of Tls. Published by Elsevier Ltd. C1 [Adler, E.; Reznik, S. E.] Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. [Madankumar, R.] North Shore Long Isl Jewish Hlth Syst, Dept Obstet & Gynecol, Glen Cove, NY USA. [Rosner, M.] Montefiore Med Ctr, Dept Obstet & Gynecol, Bronx, NY 10467 USA. [Reznik, S. E.] St Johns Univ, Dept Pharmaceut Sci, Queens, NY USA. RP Adler, E (reprint author), Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. 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TI Identification of Rare Causal Variants in Sequence-Based Studies: Methods and Applications to VPS13B, a Gene Involved in Cohen Syndrome and Autism SO PLOS GENETICS LA English DT Article ID ESTIMATING RELATIVE RISKS; GENOME-WIDE ASSOCIATION; SPECTRUM DISORDERS; MISSENSE MUTATIONS; DISEASE VARIANTS; PROTEIN; REGRESSION; COMMON; SUSCEPTIBILITY; FRAGMENTATION AB Pinpointing the small number of causal variants among the abundant naturally occurring genetic variation is a difficult challenge, but a crucial one for understanding precise molecular mechanisms of disease and follow-up functional studies. We propose and investigate two complementary statistical approaches for identification of rare causal variants in sequencing studies: a backward elimination procedure based on groupwise association tests, and a hierarchical approach that can integrate sequencing data with diverse functional and evolutionary conservation annotations for individual variants. Using simulations, we show that incorporation of multiple bioinformatic predictors of deleteriousness, such as PolyPhen-2, SIFT and GERP++scores, can improve the power to discover truly causal variants. As proof of principle, we apply the proposed methods to VPS13B, a gene mutated in the rare neurodevelopmental disorder called Cohen syndrome, and recently reported with recessive variants in autism. We identify a small set of promising candidates for causal variants, including two loss-of-function variants and a rare, homozygous probably-damaging variant that could contribute to autism risk. C1 [Ionita-Laza, Iuliana; McCallum, Kenneth] Columbia Univ, Dept Biostat, New York, NY 10027 USA. [Capanu, Marinela] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [De Rubeis, Silvia; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [De Rubeis, Silvia; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 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, Friedman Brain Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Mindich Child Hlth & Dev Inst, New York, NY USA. RP Ionita-Laza, I (reprint author), Columbia Univ, Dept Biostat, New York, NY 10027 USA. EM ii2135@columbia.edu FU National Institute of Health [R01MH095797, MH100233] FX This work has been supported in part by grants R01MH095797 and MH100233 from the National Institute of Health. 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 DEC PY 2014 VL 10 IS 12 AR e1004729 DI 10.1371/journal.pgen.1004729 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AX0NW UT WOS:000346649900003 PM 25502226 ER PT J AU Hiller, RM Weber, N Young, RL AF Hiller, Rachel M. Weber, Nathan Young, Robyn L. TI The Validity and Scalability of the Theory of Mind Scale With Toddlers and Preschoolers SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE theory of mind; toddlers; scale; validity ID TYPICALLY DEVELOPING-CHILDREN; FALSE-BELIEF; AUTISM; DEAFNESS; STEPS; TASKS AB Despite the importance of theory of mind (ToM) for typical development, there remain 2 key issues affecting our ability to draw robust conclusions. One is the continued focus on false belief as the sole measure of ToM. The second is the lack of empirically validated measures of ToM as a broad construct. Our key aim was to examine the validity and reliability of the 5-item ToM scale (Peterson, Wellman, & Liu, 2005). In particular, we extended on previous research of this scale by assessing its scalability and validity for use with children from 2 years of age. Sixty-eight typically developing children (aged 24 to 61 months) were assessed on the scale's 5 tasks, along with a sixth Sally-Anne false-belief task. Our data replicated the scalability of the 5 tasks for a Rasch-but not Guttman-scale. Guttman analysis showed that a 4-item scale may be more suitable for this age range. Further, the tasks showed good internal consistency and validity for use with children as young as 2 years of age. Overall, the measure provides a valid and reliable tool for the assessment of ToM, and in particular, the longitudinal assessment of this ability as a construct. C1 [Hiller, Rachel M.; Weber, Nathan; Young, Robyn L.] Flinders Univ S Australia, Sch Psychol, Bedford Pk, SA, Australia. RP Hiller, RM (reprint author), Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. 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Assess. PD DEC PY 2014 VL 26 IS 4 BP 1388 EP 1393 DI 10.1037/a0038320 PG 6 WC Psychology, Clinical SC Psychology GA AX1HK UT WOS:000346698200032 PM 25528165 ER PT J AU Jalan-Sakrikar, N Field, JR Klar, R Mattmann, ME Gregory, KJ Zamorano, R Engers, DW Bollinger, SR Weaver, CD Days, EL Lewis, LM Utley, TJ Hurtado, M Rigault, D Acher, F Walker, AG Melancon, BJ Wood, MR Lindsley, CW Conn, PJ Xiang, ZX Hopkins, CR Niswender, CM AF Jalan-Sakrikar, Nidhi Field, Julie R. Klar, Rebecca Mattmann, Margrith E. Gregory, Karen J. Zamorano, Rocio Engers, Darren W. Bollinger, Sean R. Weaver, C. David Days, Emily L. Lewis, L. Michelle Utley, Thomas J. Hurtado, Miguel Rigault, Delphine Acher, Francine Walker, Adam G. Melancon, Bruce J. Wood, Michael R. Lindsley, Craig W. Conn, P. Jeffrey Xiang, Zixiu Hopkins, Corey R. Niswender, Colleen M. TI Identification of Positive Allosteric Modulators VU0155094 (ML397) and VU0422288 (ML396) Reveals New Insights into the Biology of Metabotropic Glutamate Receptor 7 SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Allosteric modulator; metabotropic glutamate receptor; electrophysiology; hippocampus ID PARKINSONS-DISEASE; AGONIST AMN082; IN-VIVO; PHARMACOLOGICAL MODULATION; AMYGDALA PLASTICITY; PROBE-DEPENDENCE; RODENT MODELS; CHROMOSOME 3; LU AF21934; L-DOPA AB Metabotropic glutamate receptor 7 (mGlu(7)) is a member of the group III mGlu receptors (mGlus), encompassed by mGlu(4), mGlu(6), mGlu(7), and mGlu(8). mGlu(7) is highly expressed in the presynaptic active zones of both excitatory and inhibitory synapses, and activation of the receptor regulates the release of both glutamate and GABA. mGlu(7) is thought to be a relevant therapeutic target for a number of neurological and psychiatric disorders, and polymorphisms in the GRM7 gene have been linked to autism, depression, ADHD, and schizophrenia. Here we report two new pan-group III mGlu positive allosteric modulators, VU0155094 and VU0422288, which show differential activity at the various group III mGlus. Additionally, both compounds show probe dependence when assessed in the presence of distinct orthosteric agonists. By pairing studies of these nonselective compounds with a synapse in the hippocampus that expresses only mGlu(7), we have validated activity of these compounds in a native tissue setting. These studies provide proof-of-concept evidence that mGlu(7) activity can be modulated by positive allosteric modulation, paving the way for future therapeutics development. C1 [Jalan-Sakrikar, Nidhi; Field, Julie R.; Klar, Rebecca; Mattmann, Margrith E.; Zamorano, Rocio; Engers, Darren W.; Bollinger, Sean R.; Weaver, C. David; Days, Emily L.; Lewis, L. Michelle; Utley, Thomas J.; Hurtado, Miguel; Walker, Adam G.; Melancon, Bruce J.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Xiang, Zixiu; Hopkins, Corey R.; Niswender, Colleen M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37212 USA. [Jalan-Sakrikar, Nidhi; Field, Julie R.; Klar, Rebecca; Mattmann, Margrith E.; Zamorano, Rocio; Engers, Darren W.; Bollinger, Sean R.; Utley, Thomas J.; Hurtado, Miguel; Walker, Adam G.; Melancon, Bruce J.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Xiang, Zixiu; Hopkins, Corey R.; Niswender, Colleen M.] Vanderbilt Univ, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37212 USA. [Weaver, C. David; Days, Emily L.; Lewis, L. Michelle] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37212 USA. [Wood, Michael R.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Dept Chem, Nashville, TN 37212 USA. [Gregory, Karen J.] Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia. [Rigault, Delphine; Acher, Francine] Univ Paris 05, F-75006 Paris, France. RP Niswender, CM (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Ctr Neurosci Drug Discovery, 12478C MRB 4, Nashville, TN 37212 USA. EM Colleen.niswender@vanderbilt.edu FU NIH [N5078262]; International Rett Syndrome Foundation Basic Research Award; Autism Speaks Treatment Award; Howard Hughes Medical Institute/Vanderbilt University Medical Center Certificate Program in Molecular Medicine (HHMI/VUMC CPMM); Weatherstone Predoctoral Fellowship from Autism Speaks; Vanderbilt Molecular Libraries Screening Centers Network [NS053536]; Specialized Chemistry Center within the Molecular Libraries Probe Centers Networks; NHMRC (Australia) Overseas Biomedical Postdoctoral training fellowship; PhRMA Foundation Postdoctoral Fellowship; [NS031373]; [U54 MH074427]; [U54 MH084659]; [T32 MH093366]; [T32 NS007491] FX Supported by NIH Grant N5078262, an International Rett Syndrome Foundation Basic Research Award, and an Autism Speaks Treatment Award (to C.M.N.) and NS031373 (P.J.C.). R.K. was partially supported through the Howard Hughes Medical Institute/Vanderbilt University Medical Center Certificate Program in Molecular Medicine (HHMI/VUMC CPMM) and a Weatherstone Predoctoral Fellowship from Autism Speaks. Primary high throughput screening was supported by Grant NS053536 (C.M.N.) at the Vanderbilt Molecular Libraries Screening Centers Network, supported by U54 MH074427 (C.D.W. and PJ.C.). Vanderbilt is a Specialized Chemistry Center within the Molecular Libraries Probe Centers Networks, supported by U54 MH084659 (C.W.L.). M.E.M. was supported via T32 MH093366. K.J.G. is supported by NHMRC (Australia) Overseas Biomedical Postdoctoral training fellowship. A.G.W. was supported by T32 NS007491 and a PhRMA Foundation Postdoctoral Fellowship. 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Neurosci. PD DEC PY 2014 VL 5 IS 12 BP 1221 EP 1237 DI 10.1021/cn500153z PG 17 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AX1AY UT WOS:000346682000012 PM 25225882 ER PT J AU Kaganovich, N Schumaker, J AF Kaganovich, Natalya Schumaker, Jennifer TI Audiovisual integration for speech during mid-childhood: Electrophysiological evidence SO BRAIN AND LANGUAGE LA English DT Article DE Audiovisual speech perception; Electrophysiology; Child language development ID AUTISM SPECTRUM DISORDERS; AUDITORY-CORTEX ACTIVATION; VISUAL SPEECH; DEVELOPMENTAL-CHANGES; INTERINDIVIDUAL DIFFERENCES; MULTISENSORY INTERACTIONS; INTRACRANIAL RECORDINGS; LEARNING-DISABILITIES; TEMPORAL INTEGRATION; HUMAN INFANTS AB Previous studies have demonstrated that the presence of visual speech cues reduces the amplitude and latency of the N1 and P2 event-related potential (ERP) components elicited by speech stimuli. However, the developmental trajectory of this effect is not yet fully mapped. We examined ERP responses to auditory, visual, and audiovisual speech in two groups of school-age children (7-8-year-olds and 10-11-year-olds) and in adults. Audiovisual speech led to the attenuation of the N1 and P2 components in all groups of participants, suggesting that the neural mechanisms underlying these effects are functional by early school years. Additionally, while the reduction in N1 was largest over the right scalp, the P2 attenuation was largest over the left and midline scalp. The difference in the hemispheric distribution of the N1 and P2 attenuation supports the idea that these components index at least somewhat disparate neural processes within the context of audiovisual speech perception. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kaganovich, Natalya; Schumaker, Jennifer] Purdue Univ, Dept Speech Language & Hearing Sci, W Lafayette, IN 47907 USA. [Kaganovich, Natalya] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Kaganovich, N (reprint author), Purdue Univ, Dept Speech Language & Hearing Sci, Lyles Porter Hall,715 Clin Dr, W Lafayette, IN 47907 USA. EM kaganovi@purdue.edu FU National Institute on Deafness and Other Communicative Disorders, National Institutes of Health [P30DC010745, R03DC013151] FX This research was supported in part by grants P30DC010745 and R03DC013151 from the National Institute on Deafness and Other Communicative Disorders, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute on Deafness and Other Communicative Disorders or the National Institutes of Health. We are thankful to Daniel Noland for assistance with programming and to Dana Anderson, Camille Hagedorn, Danielle Macias, Courtney Rowland, and Casey Spelman for their assistance with different stages of data collection and processing. Bobbie Sue Ferrel-Brey's acting skills were invaluable during audiovisual recordings. Last, but not least, we are immensely grateful to children and their families for participation. 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PD DEC PY 2014 VL 139 BP 36 EP 48 DI 10.1016/j.bandl.2014.09.011 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA AX4FK UT WOS:000346888900004 PM 25463815 ER PT J AU Mahy, CEV Moses, LJ Kliegel, M AF Mahy, Caitlin E. V. Moses, Louis J. Kliegel, Matthias TI The development of prospective memory in children: An executive framework SO DEVELOPMENTAL REVIEW LA English DT Article DE Prospective memory development; Executive function; Model; Intention; Delay; Ongoing task ID COMPLEX PROSPECTIVE MEMORY; AUTISM SPECTRUM DISORDER; EPISODIC FUTURE THINKING; LATENT VARIABLE ANALYSIS; LIFE-SPAN; PRESCHOOL-CHILDREN; WORKING-MEMORY; TASK INTERRUPTION; YOUNG-CHILDREN; INDIVIDUAL-DIFFERENCES AB Prospective memory (PM), the ability to remember to carry out one's intentions in the future, is critical for children's daily functioning and their ability to become independent from caregivers. This review assesses the current state of research on children's prospective memory. Using an executive functioning framework the literature can, be organized into studies examining four factors that influence PM. We discuss studies that have manipulated the nature of the intention, the content or length of the retention interval, the nature of the ongoing task, and the nature of the PM cue. Further, we propose a model that attempts to account for the development of PM across childhood based on advances in executive control. Finally, we suggest promising future directions for research. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mahy, Caitlin E. V.] Brock Univ, Dept Psychol, St Catharines, ON L2S 3A1, Canada. [Moses, Louis J.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. [Kliegel, Matthias] Univ Geneva, Dept Psychol, Geneva, Switzerland. RP Mahy, CEV (reprint author), Brock Univ, Dept Psychol, 500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada. 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Singh, Judy TI Mindfulness-Based Positive Behavior Support (MBPBS) for Mothers of Adolescents with Autism Spectrum Disorder: Effects on Adolescents' Behavior and Parental Stress SO MINDFULNESS LA English DT Article DE Autism spectrum disorder; Mindfulness; MBPBS; Aggressive and destructive behaviors; Compliance with parental requests; Parental stress ID INTELLECTUAL DISABILITY; CHALLENGING BEHAVIORS; DECREASES AGGRESSION; YOUNG-CHILDREN; MENTAL-HEALTH; ANTIPSYCHOTICS; SCIENCE; PEOPLE AB Some parents have to deal with the challenging behaviors of their children with autism spectrum disorder (ASD), including aggressive and destructive behaviors. While pharmacological and behavioral interventions have been the treatments of choice, sometimes the pharmacological treatments are not very effective or the behavioral interventions are so labor intensive that parents fail to implement them consistently, thus leading to treatment failure and parental stress. In this proof-of-concept study, we assessed the effects of providing mindfulness-based positive behavior support (MBPBS) training to three mothers on the challenging and compliance behaviors of their adolescents with ASD. The MBPBS program included a series of meditations aimed at personal transformation during an 8-week program. The training in mindfulness-based practices was paired with applications to their interactions with their adolescent children using a positive behavior support model, whereby the mothers learned how to apply behavioral contingencies with intuitive awareness. Results showed that the adolescents' challenging behaviors decreased and compliance behaviors increased commensurate with the mothers' training in MBPBS. In addition, statistically significant reductions in the mothers' stress levels were correlated with the MBPBS training. These findings provide initial support for MBPBS in assisting parents to effectively manage the challenging behaviors of their children with ASD and in increasing their positive social interactions with them, but without raising their own stress levels. C1 [Singh, Nirbhay N.] Georgia Regents Univ, Dept Psychiat & Hlth Behav, Med Coll Georgia, Augusta, GA 30912 USA. [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, Bari, Italy. [Winton, Alan S. W.] Massey Univ, Sch Psychol, Palmerston North, New Zealand. [Karazsia, Bryan T.] Coll Wooster, Dept Psychol, Wooster, OH 44691 USA. [Myers, Rachel E.] Kennesaw State Univ, WellStar Sch Nursing, Kennesaw, GA USA. [Latham, Larry L.] Dept Econ Secur, Div Dev Disabil, Phoenix, AZ USA. [Singh, Judy] MacTavish Behav Hlth, Raleigh, NC USA. RP Singh, NN (reprint author), Georgia Regents Univ, Dept Psychiat & Hlth Behav, Med Coll Georgia, 997 St Sebastian Way, Augusta, GA 30912 USA. 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Gen. Psychol. PD DEC PY 2014 VL 18 IS 4 BP 263 EP 272 DI 10.1037/gpr0000015 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AX0LO UT WOS:000346644100002 ER PT J AU Jobst, A Dehning, S Ruf, S Notz, T Buchheim, A Henning-Fast, K Meissner, D Meyer, S Bondy, B Muller, N Zill, P AF Jobst, Andrea Dehning, Sandra Ruf, Simone Notz, Tobias Buchheim, Anna Henning-Fast, Kristina Meissner, Dominik Meyer, Sebastian Bondy, Brigitta Mueller, Norbert Zill, Peter TI Oxytocin and vasopressin levels are decreased in the plasma of male schizophrenia patients SO ACTA NEUROPSYCHIATRICA LA English DT Article DE attachment; oxytocin; schizophrenia; social deficits; vasopressin ID NEGATIVE SYNDROME SCALE; INTRANASAL OXYTOCIN; CEREBROSPINAL-FLUID; SOCIAL COGNITION; SYMPTOMS; DEFICITS; HUMANS; RATS; MIND; WOMEN AB Objective: Impaired social functioning and autistic symptoms are characteristics of schizophrenia. The social hormones oxytocin (OT) and arginine-vasopressin (AVP) both modulate social interaction and therefore may be involved in the pathogenesis of schizophrenia. We investigated whether men with schizophrenia show altered OT and AVP levels compared with healthy controls (HC) and whether autism symptoms are associated with OT levels. Methods: Forty-one men with non-acute schizophrenia and 45 matched HC were enroled. Schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Blood samples were collected on 2 days, and plasma OT and AVP levels were measured by ELISA immunoassay. Results: The schizophrenia patients had significantly lower plasma OT levels than the HC; a similar trend was found for AVP. Plasma OT levels were associated with severe life events, fewer important attached persons, and a higher score on the PANSS negative scale; the most dominant PANSS items were 'preoccupation', 'emotional withdrawal', and 'passive/apathetic social withdrawal'. Conclusion: These findings support an association between the social hormones OT and AVP and schizophrenia. We suggest that OT metabolism may be altered in schizophrenia, but other possible causes for decreased plasma OT levels in schizophrenia patients include decreased OT synthesis, mRNA expression, and translation. Especially the 'autistic' symptoms of schizophrenia seem to be closely linked to an altered metabolism of OT, the 'attachment' hormone. C1 [Jobst, Andrea; Dehning, Sandra; Ruf, Simone; Notz, Tobias; Henning-Fast, Kristina; Meissner, Dominik; Meyer, Sebastian; Bondy, Brigitta; Mueller, Norbert; Zill, Peter] Univ Munich, Dept Psychiat & Psychotherapy, D-80336 Munich, Germany. [Buchheim, Anna] Univ Innsbruck, Dept Psychol, A-6020 Innsbruck, Austria. RP Jobst, A (reprint author), Univ Munich, Dept Psychiat & Psychotherapy, Nussbaumstr 7, D-80336 Munich, Germany. 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PD DEC PY 2014 VL 26 IS 6 BP 347 EP 355 DI 10.1017/neu.2014.20 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AW5RM UT WOS:000346331700004 PM 25288094 ER PT J AU Li, LY Jiang, N Zhao, Y AF Li, Li-Ya Jiang, Nan Zhao, Yue TI Could acupuncture have a role in the treatment of autism spectrum disorder via modulation of BDNF expression and activation? SO ACUPUNCTURE IN MEDICINE LA English DT Article DE ACUPUNCTURE; NEUROPHYSIOLOGY; PSYCHOLOGY ID NEUROTROPHIC FACTOR EXPRESSION; NEUROPROTECTIVE ROLE; ELECTROACUPUNCTURE; STIMULATION; PATHWAY; NERVE; RATS AB Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions characterised by early-onset difficulties in social communication and unusually restricted repetitive behaviour and interests. Multiple lines of evidence directly or indirectly suggest an involvement in autism of the brain-derived neurotrophic factor (BDNF), which plays a pivotal role in the development and plasticity of the brain. Recent studies have demonstrated the neuroprotective effect of acupuncture-induced activation of BDNF in many neurological disorders. In view of these findings, we hypothesise the potential therapeutic effect of acupuncture-induced activation of BDNF in the treatment of ASD. C1 [Li, Li-Ya; Jiang, Nan; Zhao, Yue] Tianjin Med Univ, Sch Nursing, Tianjin 300070, Peoples R China. RP Zhao, Y (reprint author), Tianjin Med Univ, Sch Nursing, Observ Rd, Tianjin 300070, Peoples R China. EM yuezhaotjmedu@163.com FU Tianjin Medical University Graduated Research FX This study was funded by Tianjin Medical University Graduated Research. 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Med. PD DEC PY 2014 VL 32 IS 6 BP 503 EP 505 DI 10.1136/acupmed-2014-010602 PG 3 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AW4TC UT WOS:000346272300009 PM 25257393 ER PT J AU Payakachat, N Tilford, JM Kuhlthau, KA van Exel, NJ Kovacs, E Bellando, J Pyne, JM Brouwer, WBF AF Payakachat, Nalin Tilford, J. Mick Kuhlthau, Karen A. van Exel, N. Job Kovacs, Erica Bellando, Jayne Pyne, Jeffrey M. Brouwer, Werner B. F. TI Predicting Health Utilities for Children With Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE mapping; predictive algorithms; equating measure; autism; health utilities; clinical measure; behavioral measure; quality of life measure ID QUALITY-OF-LIFE; GENERIC CORE SCALES; ECONOMIC-EVALUATION; COST-EFFECTIVENESS; INTELLECTUAL DISABILITY; INTERVENTIONS; SCORES; INDEX; EQ-5D; PEDSQL(TM)-4.0 AB Comparative effectiveness of interventions for children with autism spectrum disorders (ASDs) that incorporates costs is lacking due to the scarcity of information on health utility scores or preference-weighted outcomes typically used for calculating quality-adjusted life years (QALYs). This study created algorithms for mapping clinical and behavioral measures for children with ASDs to health utility scores. The algorithms could be useful for estimating the value of different interventions and treatments used in the care of children with ASDs. Participants were recruited from two Autism Treatment Network sites. Health utility data based on the Health Utilities Index Mark 3 (HUI3) for the child were obtained from the primary caregiver (proxy-reported) through a survey (N=224). During the initial clinic visit, proxy-reported measures of the Child Behavior Checklist, Vineland II Adaptive Behavior Scales, and the Pediatric Quality of Life Inventory 4.0 (start measures) were obtained and then merged with the survey data. Nine mapping algorithms were developed using the HUI3 scores as dependent variables in ordinary least squares regressions along with the start measures, the Autism Diagnostic Observation Schedule, to measure severity, child age, and cognitive ability as independent predictors. In-sample cross-validation was conducted to evaluate predictive accuracy. Multiple imputation techniques were used for missing data. The average age for children with ASDs in this study was 8.4 (standard deviation=3.5) years. Almost half of the children (47%) had cognitive impairment (IQ70). Total scores for all of the outcome measures were significantly associated with the HUI3 score. The algorithms can be applied to clinical studies containing start measures of children with ASDs to predict QALYs gained from interventions. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Payakachat, Nalin; Tilford, J. Mick] Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, Little Rock, AR 72223 USA. [Tilford, J. Mick] Univ Arkansas Med Sci, Dept Hlth Policy & Management, Little Rock, AR 72223 USA. [Tilford, J. Mick; Bellando, Jayne] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72223 USA. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Adolescent Hlth Policy, Boston, MA 02114 USA. [van Exel, N. Job; Brouwer, Werner B. F.] Erasmus Univ, Dept Hlth Policy & Management, Rotterdam, Netherlands. [Kovacs, Erica] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Pyne, Jeffrey M.] Univ Arkansas Med Sci, Inst Psychiat Res, Little Rock, AR 72223 USA. RP Payakachat, N (reprint author), Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, 4301 W Markham St,522, Little Rock, AR 72223 USA. EM npayakachat@uams.edu FU National Institute of Mental Health [R01MH089466, R03MH102495]; Translational Research Institute through the NIH National Center for Research Resources [UL1TR000039]; National Center for Advancing Translational Sciences; U.S. Department of Health and Human Services [UA3MC11054]; Health Resources and Services Administration; Maternal and Child Health Research Program FX The project was supported by Grant No. R01MH089466 from the National Institute of Mental Health with JMT and KAK serving as principal investigators, and Grant No. R03MH102495 with NP as the principal investigator. JMT also was supported by the Translational Research Institute, Grant No. UL1TR000039 through the NIH National Center for Research Resources and National Center for Advancing Translational Sciences. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors acknowledge the members of the Autism Treatment Network for use of the data. The data for the study were collected as part of the Autism Treatment Network, a program of Autism Speaks. Further support came from a cooperative agreement (UA3MC11054) from the U.S. Department of Health and Human Services, Health Resources and Services Administration, and Maternal and Child Health Research Program, to the Massachusetts General Hospital. The work described in this article represents the independent efforts of the authors with no restrictions from the funding source or the Autism Treatment Network. None of the authors of this study reported a conflict of interest associated with the preparation of the manuscript. 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However, other studies show that children with language impairments, but without the social communication problems, are at risk of motor difficulties as well. The aim of the present study was to determine if children with ASD have syndrome-specific motor deficits in comparison to children with specific language impairment (SLI). We used an independent groups design with three groups of children (8-10 years old) matched on age and nonverbal IQ: an ASD group, an SLI group, and a typically developing (TD) group. All of the children completed an individually administered, standardized motor assessment battery. We found that the TD group demonstrated significantly better motor skills than either the ASD or SLI groups. Detailed analyses of the motor subtests revealed that the ASD and SLI groups had very similar motor profiles across a range of fine and gross motor skills, with one exception. We conclude that children with ASD, and SLI, are at risk of clinically significant motor deficits. 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TI Abstract Analogical Reasoning in High-Functioning Children with Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorders; analogical reasoning; development; social cognition ID LATENT SEMANTIC ANALYSIS; EXECUTIVE FUNCTION; YOUNG-CHILDREN; COMMUNICATION DEFICITS; RELATIONAL SHIFT; JOINT ATTENTION; WISC-IV; TASK; INTELLIGENCE; INDIVIDUALS AB Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD. Autism Res2014, 7: 677-686. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Green, Adam E.; Gallagher, Natalie M.; Fearon, Edward W.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA. [Mosner, Maya G.; Yerys, Benjamin E.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Balhana, Carlos D.] MITRE, Mclean, VA USA. RP Green, AE (reprint author), Georgetown Univ, Dept Psychol, 302C White Gravenor Hall,3700 O St NW,Box 571001, Washington, DC 20057 USA. EM aeg58@Georgetown.edu FU NIMH [5K23MH086111, 1R21MH092615, 1RC1MH088791]; Pennsylvania Department of Health (SAP) [4100042728, 4100047863]; Pfizer; Robert Wood Johnson Foundation [66727]; Isadore and Bertha Gudelsky Foundation; American Legacy Foundation FX We would like to thank the families for the time and effort in completing this study. This research was sponsored in part by the NIMH (5K23MH086111 and 1R21MH092615 to B.E. Yerys and 1RC1MH088791 to R. Schultz), a grant from the Pennsylvania Department of Health (SAP #4100042728 and 4100047863, to R. Schultz), a grant from Pfizer (to R. Schultz), a grant from the Robert Wood Johnson Foundation (#66727 to R. Schultz), a grant from the Isadore and Bertha Gudelsky Foundation (to L. 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Kidd, Evan Prendergast, Luke Baker, Emma Dissanayake, Chery Prior, Margot TI Severity of Autism is Related to Children's Language Processing SO AUTISM RESEARCH LA English DT Article DE lexical processing; severity of ASD; eye tracking; children ID SPECTRUM DISORDERS; WORD RECOGNITION; EYE-MOVEMENTS; COMPREHENSION AB Problems in language processing have been associated with autism spectrum disorder (ASD), with some research attributing the problems to overall language skills rather than a diagnosis of ASD. Lexical access was assessed in a looking-while-listening task in three groups of 5- to 7-year-old children; two had high-functioning ASD (HFA), an ASD severe (ASD-S) group (n=16) and an ASD moderate (ASD-M) group (n=21). The third group were typically developing (TD) (n=48). Participants heard sentences of the form Where's the x? and their eye movements to targets (e.g., train), phonological competitors (e.g., tree), and distractors were recorded. Proportions of looking time at target were analyzed within 200ms intervals. Significant group differences were found between the ASD-S and TD groups only, at time intervals 1000-1200 and 1200-1400ms postonset. The TD group was more likely to be fixated on target. These differences were maintained after adjusting for language, verbal and nonverbal IQ, and attention scores. An analysis using parent report of autistic-like behaviors showed higher scores to be associated with lower proportions of looking time at target, regardless of group. Further analysis showed fixation for the TD group to be significantly faster than for the ASD-S. In addition, incremental processing was found for all groups. The study findings suggest that severity of autistic behaviors will impact significantly on children's language processing in real life situations when exposed to syntactically complex material. They also show the value of using online methods for understanding how young children with ASD process language. Autism Res2014, 7: 687-694. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Bavin, Edith L.; Baker, Emma; Dissanayake, Chery] La Trobe Univ, Sch Psychol Sci, Melbourne, Vic 3083, Australia. [Kidd, Evan] Australian Natl Univ, Res Sch Psychol, ARC Ctr Excellence Dynam Language, Canberra, ACT, Australia. [Prendergast, Luke] La Trobe Univ, Dept Math & Stat, Melbourne, Vic 3083, Australia. [Baker, Emma; Dissanayake, Chery; Prior, Margot] La Trobe Univ, Olga Tennison Autism Res Ctr, Melbourne, Vic 3083, Australia. [Prior, Margot] Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia. RP Bavin, EL (reprint author), La Trobe Univ, Sch Psychol Sci, Melbourne, Vic 3083, Australia. 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Ashwin, Chris Brosnan, Mark TI Physiological Responses to Social and Nonsocial Stimuli in Neurotypical Adults With High and Low Levels of Autistic Traits: Implications for Understanding Nonsocial Drive in Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE AQ; Autism Spectrum Disorder; non-social psychophysiology; social cognition ID FUSIFORM FACE AREA; SKIN-CONDUCTANCE RESPONSES; HIGH-FUNCTIONING AUTISM; MALE BRAIN THEORY; ASPERGER-SYNDROME; AMYGDALA THEORY; CHILDREN; ACTIVATION; GAZE; PERCEPTION AB Researchers have suggested that the two primary cognitive features of autism spectrum disorder (ASD), a drive toward nonsocial processing and a reduced drive toward social processing, may be unrelated to each other in the neurotypical (NT) population and may therefore require separate explanations. Drive toward types of processing may be related to physiological arousal to categories of stimuli, such as social (e.g., faces) or nonsocial (e.g., trains). This study investigated how autistic traits in an NT population might relate to differences in physiological responses to nonsocial compared with social stimuli. NT participants were recruited to examine these differences in those with high vs. low degrees of ASD traits. Forty-six participants (21 male, 25 female) completed the Autism Spectrum Quotient (AQ) to measure ASD traits before viewing a series of 24 images while skin conductance response (SCR) was recorded. Images included six nonsocial, six social, six face-like cartoons, and six nonsocial (relating to participants' personal interests). Analysis revealed that those with a higher AQ had significantly greater SCR arousal to nonsocial stimuli than those with a low AQ, and the higher the AQ, the greater the difference between SCR arousal to nonsocial and social stimuli. This is the first study to identify the relationship between AQ and physiological response to nonsocial stimuli, and a relationship between physiological response to both social and nonsocial stimuli, suggesting that physiological response may underlie the atypical drive toward nonsocial processing seen in ASD, and that at the physiological level at least the social and nonsocial in ASD may be related to one another. Autism Res2014, 7: 695-703. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Singleton, Clarence J.; Ashwin, Chris; Brosnan, Mark] Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. RP Singleton, CJ (reprint author), Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. 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PD DEC PY 2014 VL 7 IS 6 BP 695 EP 703 DI 10.1002/aur.1422 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AW7TR UT WOS:000346467700006 PM 25346292 ER PT J AU Zwicker, JD Emery, JCH AF Zwicker, Jennifer D. Emery, J. C. Herbert TI Autism Research Funding Allocation: Can Economics Tell Us If We Have Got It Right? SO AUTISM RESEARCH LA English DT Article DE autism; research funding; economic evaluation; funding allocation AB There is a concern that the allocation of autism spectrum disorder (ASD) research funding may be misallocating resources, overemphasizing basic science at the expense of translational and clinical research. Anthony Bailey has proposed that an economic evaluation of autism research funding allocations could be beneficial for funding agencies by identifying under- or overfunded areas of research. In response to Bailey, we illustrate why economics cannot provide an objective, technical solution for identifying the best allocation of research resources. Economic evaluation has its greatest power as a late-stage research tool for interventions with identified objectives, outcomes, and data. This is not the case for evaluating whether research areas are over- or underfunded. Without an understanding of how research funding influences the likelihood and value of a discovery, or without a statement of the societal objectives for ASD research and level of risk aversion, economic analysis cannot provide a useful normative evaluation of ASD research. Autism Res2014, 7: 704-711. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Zwicker, Jennifer D.] Univ Calgary, Sch Publ Policy, Calgary, AB T2P 1H9, Canada. [Emery, J. C. Herbert] Univ Calgary, Dept Econ, Calgary, AB T2P 1H9, Canada. RP Zwicker, JD (reprint author), Univ Calgary, Sch Publ Policy, Downtown Campus,906 8th Ave SW,5th Floor, Calgary, AB T2P 1H9, Canada. EM zwicker1@ucalgary.ca FU Alberta Innovates Health Solutions [10003547] FX Grant sponsor Alberta Innovates Health Solutions; Grant number: 10003547. 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PD DEC PY 2014 VL 7 IS 6 BP 704 EP 711 DI 10.1002/aur.1423 PG 8 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AW7TR UT WOS:000346467700007 PM 25288440 ER PT J AU Elmose, M Happe, F AF Elmose, Mette Happe, Francesca TI Being Aware of Own Performance: How Accurately Do Children With Autism Spectrum Disorder Judge Own Memory Performance? SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorder; self-awareness; meta-memory; theory of mind ID VISUAL MEMORY; ADULTS; MIND; FRACTIONATION; JUDGMENTS; RECALL; SELF AB Self-awareness was investigated by assessing accuracy of judging own memory performance in a group of children with autism spectrum disorder (ASD) compared with a group of typically developing (TD) children. Effects of stimulus type (social vs. nonsocial), and availability of feedback information as the task progressed, were examined. Results overall showed comparable levels and patterns of accuracy in the ASD and TD groups. A trend level effect (p = 061, d=0.60) was found, with ASD participants being more accurate in judging own memory for nonsocial than social stimuli and the opposite pattern for TD participants. These findings suggest that awareness of own memory can be good in children with ASD. It is discussed how this finding may be interpreted, and it is suggested that further investigation into the relation between content, frequency, and quality of self-awareness, and the context of self-awareness, is needed. Autism Res2014, 7: 712-719. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Elmose, Mette] Univ Southern Denmark, Dept Psychol, DK-5230 Odense M, Denmark. [Happe, Francesca] Inst Psychiat, MRC Social Genet Dev & Psychiat Res Ctr, London, England. RP Elmose, M (reprint author), Univ Southern Denmark, Dept Psychol, Campusvej 55, DK-5230 Odense M, Denmark. 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R., 1973, WORKING BRAIN INTRO Minshew NJ, 2005, J AUTISM DEV DISORD, V35, P45, DOI 10.1007/s10803-004-1030-x Roebers CM, 2003, J EXP CHILD PSYCHOL, V85, P352, DOI 10.1016/S0022-0965(03)00076-6 Sattler J.M., 1992, ASSESSMENT CHILDREN Lockl K, 2002, INT J BEHAV DEV, V26, P327, DOI 10.1080/01650250143000210 Schneider W, 2000, COGNITIVE DEV, V15, P115, DOI 10.1016/S0885-2014(00)00024-1 Webb S. J., 2008, MEMORY AUTISM THEORI, P188, DOI 10.1017/CBO9780511490101.012 Wechsler D, 1991, WECHSLER INTELLIGENC, V3rd Williams D, 2010, AUTISM, V14, P474, DOI 10.1177/1362361310366314 World Health Organisation, 1992, ICD 10 CLASS MENT BE NR 32 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 DEC PY 2014 VL 7 IS 6 BP 712 EP 719 DI 10.1002/aur.1421 PG 8 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AW7TR UT WOS:000346467700008 PM 25339388 ER PT J AU Alderson-Day, B AF Alderson-Day, Ben TI Verbal Problem-Solving Difficulties in Autism Spectrum Disorders and Atypical Language Development SO AUTISM RESEARCH LA English DT Article DE developmental psychology; language development; executive function; problem solving; inner speech ID HIGH-FUNCTIONING AUTISM; ASPERGERS-SYNDROME; INNER SPEECH; HEARING INDIVIDUALS; EXECUTIVE CONTROL; CHILDREN; DEAF; CATEGORIZATION; IMPAIRMENT; ADULTS AB Children with autism spectrum disorders (ASDs) adopt less efficient strategies than typically developing (TD) peers on the Twenty Questions Task (TQT), a measure of verbal problem-solving skills. Although problems with the TQT are typically associated with executive dysfunction, they have also been reported in children who are deaf, suggesting a role for atypical language development. To test the contribution of language history to ASD problem solving, TQT performance was compared in children with high-functioning autism (HFA), children with Asperger syndrome (AS) and TD children. The HFA group used significantly less efficient strategies than both AS and TD children. No group differences were evident on tests of question understanding, planning or verbal fluency. Potential explanations for differences in verbal problem-solving skill are discussed with reference to the development of inner speech and use of visual strategies in ASD. Autism Res2014, 7: 720-730. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 Univ Durham, Dept Psychol, Sci Labs, Durham DH1 3LE, England. RP Alderson-Day, B (reprint author), Univ Durham, Dept Psychol, Sci Labs, South Rd, Durham DH1 3LE, England. EM benjamin.alderson-day@durham.ac.uk FU University of Edinburgh College of Humanities and Social Sciences Studentship; Wellcome Trust [WT098455] FX This research was completed as part of a doctoral degree by the author at the University of Edinburgh and supported by a University of Edinburgh College of Humanities and Social Sciences Studentship. Margaret McGonigle-Chalmers and Robert Logie are thanked for their help and support for the research. Thanks are also due to Charles Fernyhough for comments on the manuscript. The author declares no conflicts of interest.The author is currently supported by Wellcome Trust grant WT098455. 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Piven, Joseph TI When Father Doesn't Know Best: Selective Disagreement Between Self-Report and Informant Report of the Broad Autism Phenotype in Parents of a Child with Autism SO AUTISM RESEARCH LA English DT Article DE clinical psychiatry; clinical psychology; social cognition; personality assessment; personality traits; informant reports; broad autism phenotype ID INTERGENERATIONAL TRANSMISSION; PERSONALITY PATHOLOGY; PREDICTIVE-VALIDITY; SPECTRUM DISORDER; SOCIAL-COGNITION; INDIVIDUALS; PERSPECTIVE; TRAITS; ACCURACY AB The Broad Autism Phenotype Questionnaire (BAPQ) is a reliable tool for identifying three autism-related traitssocial aloofness, pragmatic language abnormalities and rigid personalitywithin families of a person with autism and the general population. Although little is known concerning agreement between self-report and informant report versions of the BAPQ, identifying individual characteristics affecting agreement between the two can highlight important considerations for maximizing its yield, particularly when only one version is administered. Here, analysis of self-report and informant report of the BAPQ completed by 444 parents of a child with autism revealed moderate to strong agreement between the two versions for all three broad autism phenotype (BAP) traits when the self-reporting parent did not possess the trait being assessed. In contrast, disagreement selectively occurred when the assessed parent was positive for the BAP trait being rated. This pattern was driven primarily by fathers who were positive for a BAP trait endorsing lower levels of that trait relative to informant report. This discrepancy did not occur for mothers, nor did it occur for fathers lacking BAP traits. Because this pattern was specific to fathers positive for BAP traits, it likely reflects selective blind spots in their self-reporting and not poorer self-reporting by fathers more broadly, nor a general tendency of overreporting by informant mothers. The presence of BAP traits in informing parents, however, largely did not reduce agreement between self-report and informant report. In sum, self-report may underestimate the presence of BAP traits in fathers but is generally consistent with informant report for mothers. Autism Res2014, 7: 731-739. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Sasson, Noah J.; Faso, Daniel J.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA. [Parlier, Morgan; Daniels, Julie L.; Piven, Joseph] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC USA. [Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Sasson, NJ (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, 800 W Campbell Rd,GR41, Richardson, TX 75080 USA. EM nsasson@utdallas.edu FU Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center (IDDRC) at UNC-Chapel Hill [HD003110]; Centers for Disease Control and Prevention [U10 DD000184-06, U50/CCU422345] FX We greatly appreciate the help of Renee Clark and the Research Registry Core of the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center (IDDRC) at UNC-Chapel Hill (Grant Number HD003110). This work was further supported by the Centers for Disease Control and Prevention (Grant Numbers: U10 DD000184-06, U50/CCU422345). We also would like to thank Dr. Robert Ackerman for his assistance with statistical analysis. Finally, we thank all the parents who participated in this research. The authors report no conflict of interests. 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PD DEC PY 2014 VL 7 IS 6 BP 731 EP 739 DI 10.1002/aur.1425 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AW7TR UT WOS:000346467700010 PM 25339495 ER PT J AU Anclair, M Hiltunen, AJ AF Anclair, Malin Hiltunen, Arto J. TI Cognitive Behavioral Therapy for Stress-Related Problems: Two Single-Case Studies of Parents of Children With Disabilities SO CLINICAL CASE STUDIES LA English DT Article DE CBT; ACT; stress; parents of disabled children; single-case studies ID QUALITY-OF-LIFE; CHILDHOOD; BURNOUT; MOTHERS; HEALTH AB Many parents who have children suffering from some form of chronic illness or mental disorder may experience chronic stress reactions of various types. Cognitive behavioral therapy (CBT) has been proved to be effective in reducing stress-related problems, but there seems to be no study to date in which CBT has been tested on this specific parent group. Two case studies were therefore performed. Case 1 centered on a 47-year-old married woman, who has lived in Sweden for 12 months. She described how she had become increasingly exhausted, and she wanted help to find strategies enabling her to cope with everyday life. Case 2 featured a 45-year-old single mother, who had been on part-time sick leave due to depression and stress. She described how she had always been anxious and worried and had had two episodes of depression. Both women had sons diagnosed with autism/Asperger syndrome. One of the women met the criteria for pathological burnout, while the other woman was just below the limit. The focus of the therapy for both women was on exhaustion, depression, and sleeping difficulties. In addition, therapy in Case 1 involved under-stimulation and in Case 2, anxiety. When the therapy ended, genuine improvements were registered for both clients. 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The current review article describes how a transdiagnostic emotion regulation framework may inform cognitive-behavioral interventions for youth with ASD, which until now have focused almost exclusively on anxiety. Research is needed to empirically test how a transdiagnostic intervention can address the processes of emotion regulation and assist youth with ASD to cope with their emotional disorders. C1 [Weiss, Jonathan A.] York Univ, Toronto, ON M3J 1P3, Canada. RP Weiss, JA (reprint author), York Univ, Dept Psychol, 4700 Keele St, Toronto, ON M3J 1P3, Canada. 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Psychol.-Sci. Pract. PD DEC PY 2014 VL 21 IS 4 BP 331 EP 350 DI 10.1111/cpsp.12084 PG 20 WC Psychology, Clinical SC Psychology GA AW5UC UT WOS:000346338200002 ER PT J AU Wakeford, S Hinvest, N Ring, H Brosnan, M AF Wakeford, SallyAnn Hinvest, Neal Ring, Howard Brosnan, Mark TI Autistic characteristics in adults with epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Autism; Autistic traits; Autism spectrum disorders; Comorbidity; Asperger condition; Asperger disorder; Empathizing; Systemizing ID TEMPORAL-LOBE EPILEPSY; SPECTRUM QUOTIENT AQ; FACIAL EMOTION RECOGNITION; ASPERGER-SYNDROME; FUNCTIONING AUTISM; CHILDREN; DISORDERS; POPULATION; VALIDITY; AMYGDALA AB Introduction: The reported prevalence of autism spectrum disorders in people with epilepsy ranges from 15% to 47%. Despite the high comorbidity, there has been a lack of systematic studies of autistic characteristics in epilepsy. Little is known about the relationship of epilepsy to the core characteristics of autism. The aim of this research was to measure autistic traits and characteristics in adults with epilepsy who do not have a diagnosis of any autism disorder. Method: We investigated autistic characteristics in adults with epilepsy and those without epilepsy employing the Autism Spectrum Quotient (group with epilepsy, n=40; control group, n=38) and systemizing and empathizing abilities employing the Intuitive Physics test and the Adult Eyes Task-Revised (group with epilepsy, n=19; control group, n=23). Results: Significantly more autistic behavioral traits, as measured by the AQ, were related to having epilepsy, but intact systemizing and empathizing abilities in these adults suggest that, in adults with epilepsy, autism-like symptoms may be present in the absence of wider cognitive profiles characteristic of autism. Conclusion: Increased autistic characteristics found in adults with epilepsy without an ASD diagnosis suggest that epilepsy syndromes may incorporate behavioral aspects of autism in the absence of some of its core cognitive features. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wakeford, SallyAnn; Hinvest, Neal; Brosnan, Mark] Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. [Ring, Howard] Univ Cambridge, Dept Psychiat, Cambridge, England. RP Wakeford, S (reprint author), Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. EM s.wakeford@bath.edu FU National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care [East of England] at Cambridgeshire; Peterborough NHS Foundation Trust FX The authors would like to thank Epilepsy Action for the nonfinancial support of this research by assisting in the recruitment of participants at their conferences. During the preparation of this research paper Howard Ring received support from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care [East of England] at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. 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PD DEC PY 2014 VL 41 BP 203 EP 207 DI 10.1016/j.yebeh.2014.09.045 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AW3LH UT WOS:000346187700039 PM 25461216 ER PT J AU Kanazawa, O AF Kanazawa, Osamu TI Reappraisal of abnormal EEG findings in children with ADHD: On the relationship between ADHD and epileptiform discharges SO EPILEPSY & BEHAVIOR LA English DT Article DE Attention-deficit hyperactivity disorder (ADHD); Electroencephalography (EEG); Epileptiform discharge; Epilepsy; Autism spectrum disorder (ASD) ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; FRONTAL-LOBE EPILEPSY; ELECTROENCEPHALOGRAM; METHYLPHENIDATE; PREVALENCE; UTILITY; AUTISM; PEOPLE; SLEEP AB Introduction: Attention-deficit hyperactivity disorder is suggested to be closely related to epilepsy. A recent large-scale study revealed that ADHD in children is often accompanied by epilepsy. In Japan, methylphenidate (MPH) as a sustained-action tablet and atomoxetine (ATX) became commercially available as medications for children recently. Since then, the number of prescriptions of both medicines has increased rapidly. Methylphenidate, as a psychostimulant, has been a source of concern because of the perceived lowered threshold for convulsions in children. Based on this background, reappraisal of EEG findings in children with ADHD is important in order to detect indications of potential comorbid epilepsy and to investigate the developmental mechanisms of the neurophysiological manifestations in patients with ADHD. Material and method: EEG findings in children newly diagnosed with ADHD and their relationship with clinical findings were investigated. The author evaluated 208 patients with ADHD newly diagnosed between 2008 and 2013. Of these, there were 145 patients for whom EEG findings were obtained along with a clinical follow-up for at least threemonths. Patients with IQ < 70 were excluded in order to obtain a homogenous group of patients with ADHD. The male-to-female ratio was 130: 15, and the age range was between 5 years, 9 months and 19 years, 9 months, with mean age of 11 years, 4 months. Results: The results revealed that about half (48.3%) of the children with ADHD had abnormal EEG findings and that 22.1% of them had epileptiform discharges. Patients without comorbidity of autism spectrum disorder (ore homogenous group with ADHD) were especially likely to show abnormal EEG findings (51.0%) including epileptiform discharges (24.5%). Afebrile seizures, that is, epileptic seizures, occurred in a boy three days after commencement of administration with MPH as a sustained-action tablet. In four patients with a past history of epilepsy, neither relapse of EEG abnormality nor epileptic seizures were observed during the follow-up period. Conclusion: There was to be a significantly close relationship between ADHD and epileptiform discharges. Therefore, in patients with ADHD, it is important to obtain more precise information about seizures and presence of epilepsy from the personal and family histories, as well as to undertake a thorough EEG examination. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kanazawa, Osamu] Saitama Med Univ, Dept Neuropsychiat & Psychosomat Internal Med, Iruma, Saitama 3500495, Japan. RP Kanazawa, O (reprint author), 2-7-29 Isehara Cho, Kawagoe, Saitama 3501108, Japan. EM kanaosa@saitama-med.ac.jp CR Altunel A, 2013, J CLIN NEUROPHYSIOL, V30, P357, DOI 10.1097/WNP.0b013e31829d75db Bakke KA, 2011, EUR J PAEDIATR NEURO, V15, P532, DOI 10.1016/j.ejpn.2011.04.014 Barbaresi WJ, 2014, J DEV BEHAV PEDIATR, V35, P448, DOI 10.1097/DBP.0000000000000099 Bechtel N, 2012, EPILEPSIA, V53, P325, DOI 10.1111/j.1528-1167.2011.03377.x Bedoin N, 2012, EPILEPSY BEHAV, V25, P81, DOI 10.1016/j.yebeh.2012.05.025 Berg AT, 2012, EPILEPSY BEHAV, V23, P193, DOI 10.1016/j.yebeh.2012.01.015 Braakman HMH, 2011, EPILEPSIA, V52, P849, DOI 10.1111/j.1528-1167.2011.03057.x Cerminara C, 2013, EPILEPSY BEHAV, V27, P337, DOI 10.1016/j.yebeh.2013.02.022 Cohen R, 2013, J CHILD NEUROL, V28, P120, DOI 10.1177/0883073812440327 Cornelio-Nieto JO, 2011, REV NEUROL S1, V52, P97 Davis SM, 2010, PEDIATR NEUROL, V42, P325, DOI 10.1016/j.pediatrneurol.2010.01.005 Fosi T, 2013, EPILEPSIA, V54, P2071, DOI 10.1111/epi.12399 Hale TS, 2009, NEUROPSYCHOLOGIA, V47, P2082, DOI 10.1016/j.neuropsychologia.2009.03.021 Kanemura H, 2013, EPILEPSY BEHAV, V27, P443, DOI 10.1016/j.yebeh.2013.03.014 Kawatani M, 2012, BRAIN DEV-JPN, V34, P723, DOI 10.1016/j.braindev.2011.11.009 Koneski JAS, 2010, ARQ NEURO-PSIQUIAT, V68, P107, DOI 10.1590/S0004-282X2010000100023 Lo-Castro A, 2014, BRAIN DEV-JPN, V36, P185, DOI 10.1016/j.braindev.2013.04.013 Loo SK, 2012, NEUROTHERAPEUTICS, V9, P569, DOI 10.1007/s13311-012-0131-z Millichap JG, 2011, CLIN EEG NEUROSCI, V42, P180 Parisi P, 2010, BRAIN DEV-JPN, V32, P10, DOI 10.1016/j.braindev.2009.03.005 Pineda E, 2013, EPILEPSY BEHAV, V31, P267 Polanczyk GV, 2014, INT J EPIDEMIOL, V43, P434, DOI 10.1093/ije/dyt261 Reilly CJ, 2011, RES DEV DISABIL, V32, P883, DOI 10.1016/j.ridd.2011.01.019 Sheen VL, 2013, PEDIATR NEUROL, V49, P54, DOI 10.1016/j.pediatrneurol.2012.12.036 Socanski D, 2013, SEIZURE-EUR J EPILEP, V22, P651, DOI 10.1016/j.seizure.2013.04.021 Socanski D, 2010, EPILEPSY BEHAV, V19, P483, DOI 10.1016/j.yebeh.2010.08.005 Suren P, 2012, PEDIATRICS, V130, P152 Torres A, 2011, EPILEPSY BEHAV, V20, P95, DOI 10.1016/j.yebeh.2010.11.002 Yonekawa T, 2011, EPILEPSY BEHAV, V22, P697, DOI 10.1016/j.yebeh.2011.08.027 Zhang DQ, 2014, J CHILD NEUROL, V29, P54, DOI 10.1177/0883073812470004 NR 30 TC 0 Z9 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2014 VL 41 BP 251 EP 256 DI 10.1016/j.yebeh.2014.09.078 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AW3LH UT WOS:000346187700048 PM 25461225 ER PT J AU Brown, A Crowe, L Andresen, BS Anderson, V Boneh, A AF Brown, Amy Crowe, Louise Andresen, Brage S. Anderson, Vicki Boneh, Avihu TI Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Fatty acid oxidation; Very long chain acyl-CoA dehydrogenase deficiency; Neuropsychological assessment; Newborn screening; Developmental outcomes ID PERFORMANCE-BASED MEASURES; EXECUTIVE FUNCTION; METABOLISM; BEHAVIOR; IMPACT AB Background: Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of fatty acid oxidation with an estimated incidence of between 1:31,500 and 1:125,000. There is limited information regarding neurodevelopmental outcomes, probably because the disorder is perceived as affecting the skeletal and heart muscles, and many children are deemed asymptomatic. The aim of this study was to utilise a comprehensive neuropsychological assessment battery that assessed IQ language, attention, memory, executive functioning, motor skills, behaviour, and social skills in children 4 to 10 years old diagnosed with VLCAD deficiency through newborn screening. Method: Seven children completed neuropsychological assessment and one child was only involved in part of the study (2 female, 6 male). Parents completed questionnaires regarding executive functioning, behaviour and social skills. Results: IQ scores ranged from average to the superior range. No deficits were found in fine or gross motor skills. One patient had a mild language deficit, and two patients had previously required speech therapy. Verbal memory, attention and executive functioning skills were generally average or above. Visual memory scores were mostly above average. Parents' questionnaires identified one child as having social skills deficits, and two as having behavioural problems such as hyperactivity. One child rated high on an autism spectrum subscale; another was formally diagnosed with autism spectrum disorder both children were symptomatic at birth. Conclusions: VLCAD deficiency does not have a significant impact on cognitive or motor skills. Some children may be vulnerable to speech, social and behavioural issues. (C) 2014 Elsevier Inc. All rights reserved. C1 [Brown, Amy; Crowe, Louise; Anderson, Vicki] Royal Childrens Hosp, Murdoch Childrens Res Inst, Australian Ctr Child Neuropsychol Studies, Melbourne, Vic, Australia. [Brown, Amy; Anderson, Vicki; Boneh, Avihu] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Andresen, Brage S.] Univ Southern, Dept Biochem & Mol Biol, Odense, Denmark. 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Genet. Metab. PD DEC PY 2014 VL 113 IS 4 BP 278 EP 282 DI 10.1016/j.ymgme.2014.10.005 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Genetics & Heredity; Research & Experimental Medicine GA AX0DG UT WOS:000346623000008 PM 25456746 ER PT J AU Heller, HC Salehi, A Chuluun, B Das, D Lin, B Moghadam, S Garner, CC Colas, D AF Heller, H. Craig Salehi, Ahmad Chuluun, Bayarsaikhan Das, Devsmita Lin, Bill Moghadam, Sarah Garner, Craig C. Colas, Damien TI Nest building is impaired in the Ts65Dn mouse model of Down syndrome and rescued by blocking 5HT2a receptors SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Attention; Ts65Dn; Ts1Rhr; Goal directed behavior; SR-46349; Eplivanserin; Risperidone; Pentylenetetrazole ID AUTISM SPECTRUM DISORDER; GENE-DOSAGE IMBALANCE; ENVIRONMENTAL ENRICHMENT; COGNITIVE PERFORMANCE; SUSTAINED ATTENTION; ALZHEIMERS-DISEASE; CRITICAL REGION; MICE; SEROTONIN; BEHAVIOR AB Down syndrome (DS) has an incidence of about 1/700 births, and is therefore the most common cause of cognitive and behavioral impairments in children. Recent studies on mouse models of DS indicate that a number of pharmacotherapies could be beneficial for restoring cognitive abilities in individuals with DS. Attention deficits that are present in DS account in part for learning and memory deficiencies yet have been scarcely studied in corresponding models. Investigations of this relevant group of behaviors is more difficult in mouse models because of the difficulty in homologizing mouse and human behaviors and because standard laboratory environments do not always elicit behaviors of interest. Here we characterize nest building as a goal-directed behavior that is seriously impaired in young Ts65Dn mice, a genetic model of DS. We believe this impairment may reflect in part attention deficits, and we investigate the physiological, genetic, and pharmacological factors influencing its expression. Nesting behavior in young Ts65Dn mice was severely impaired when the animals were placed in a novel environment. But this context-dependent impairment was transient and reversible. The genetic determinants of this deficiency are restricted to a similar to 100 gene segment on the murine chromosome 16. Nest building behavior is a highly integrated phenotypic trait that relies in part on limbic circuitry and on the frontal cortex in relation to cognitive and attention processes. We show that both serotonin content and 5HT2a receptors are increased in the frontal cortex of Ts65Dn mice and that pharmacological blockage of 5HT2a receptors in Ts65Dn mice rescues their context dependent nest building impairment. We propose that the nest-building trait could represent a marker of attention related deficits in DS models and could be of value in designing pharmacotherapies for this specific aspect of DS. 5HT2a modulation may improve goal-directed behavior in DS. (C) 2014 Elsevier Inc. All rights reserved. C1 [Heller, H. Craig; Chuluun, Bayarsaikhan; Colas, Damien] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Salehi, Ahmad; Das, Devsmita; Garner, Craig C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Salehi, Ahmad; Das, Devsmita; Lin, Bill; Moghadam, Sarah] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP Heller, HC (reprint author), 371 Serra Mall, Stanford, CA 94305 USA. EM hcheller@stanford.edu; colas@stanford.edu FU Down Syndrome Research and Treatment Foundation; Research Down Syndrome Foundation; Lejeune Foundation (Paris) FX This work was supported by grants from the Down Syndrome Research and Treatment Foundation, the Research Down Syndrome Foundation and the Lejeune Foundation (Paris). We thank Ms Sabine Hertz for help in initial nesting design and characterization and Grace Hagiwara for her valuable assistance. 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Azadi, Bahare Asherson, Philip Bolton, Patrick McLoughlin, Grainne TI Altered neurophysiological responses to emotional faces discriminate children with ASD, ADHD and ASD plus ADHD SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE ASD; ADHD; Comorbidity; Emotion; Event related potentials (ERP) ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; EVENT-RELATED POTENTIALS; FACIAL EXPRESSIONS; YOUNG-CHILDREN; BRAIN RESPONSES; NEURAL SYSTEMS; TIME-COURSE; FUNCTIONAL CONNECTIVITY AB There are high rates of overlap between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Emotional impairment in the two disorders, however, has not been directly compared using event-related potentials (ERPs) that are able to measure distinct temporal stages in emotional processing. The N170 and N400 ERP components were measured during presentation of emotional face stimuli to boys with ASD (n = 19), ADHD (n = 18), comorbid ASD +ADHD (n = 29) and typically developing controls (n = 26). Subjects with ASD (ASD/ASD +ADHD) displayed reduced N170 amplitude across all stimuli, particularly for fearful versus neutral facial expressions. Conversely, subjects with ADHD (ADHD/ASD +ADHD) demonstrated reduced modulation of N400 amplitude by fearful expressions in parietal scalp regions and happy facial expressions in central scalp regions. These findings indicate a dissociation between disorders on the basis of distinct stages of emotion processing; while children with ASD show alterations at the structural encoding stage, children with ADHD display abnormality at the contextual processing stage. The comorbid ASD +ADHD group presents as an additive condition with the unique deficits of both disorders. This supports the use of objective neural measurement of emotional processing to delineate pathophysiological mechanisms in complex overlapping disorders. (C) 2014 Elsevier B.V. All rights reserved. C1 [Tye, Charlotte; Asherson, Philip; Bolton, Patrick; McLoughlin, Grainne] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Battaglia, Marco] Univ Laval, Quebec City, PQ, Canada. [Battaglia, Marco] Inst Univ Sante Mentale Quebec, Quebec City, PQ, Canada. [Bertoletti, Eleonora] Univ Vita Salute San Raffaele, Acad Ctr Study Behav Plast, Milan, Italy. [Tye, Charlotte; Ashwood, Karen L.; Azadi, Bahare; Bolton, Patrick] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [McLoughlin, Grainne] Univ Calif San Diego, Inst Neural Computat, Swartz Ctr Computat Neurosci, La Jolla, CA 92093 USA. RP Tye, C (reprint author), Inst Psychiat, MRCSGDP Ctr, De Crespigny Pk, London SE5 8AF, England. EM charlotte.tye@kcl.ac.uk FU National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health (BRC); Waterloo Foundation [G686984]; Steel Charitable Trust [G38575208]; NIHR Senior Investigator award; BRC at the South London; Maudsley NHS Trust Hospital, London FX The authors would like to gratefully acknowledge the participating families and all staff involved in this study, in particular Sally Cartwright, Sarah Lewis and Stuart Newman. This work was supported by a grant from the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health (BRC), the Waterloo Foundation (G686984) and the Steel Charitable Trust (G38575208). Professor Bolton is supported by a NIHR Senior Investigator award and the BRC at the South London & Maudsley NHS Trust Hospital, London. 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Psychol. PD DEC PY 2014 VL 103 BP 125 EP 134 DI 10.1016/j.biopsycho.2014.08.013 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA AW0HF UT WOS:000345971200017 PM 25179537 ER PT J AU Broder-Fingert, S Ferrone, CF Giauque, A Connors, SL AF Broder-Fingert, Sarabeth Ferrone, Christine F. Giauque, Ann Connors, Susan L. TI Residents' Knowledge and Comfort With Caring for Children With Autism Spectrum Disorder SO CLINICAL PEDIATRICS LA English DT Article ID PHYSICIAN SURVEY C1 [Broder-Fingert, Sarabeth] MassGen Hosp Children, Boston, MA 02114 USA. [Ferrone, Christine F.; Giauque, Ann; Connors, Susan L.] MassGen Hosp Lurie Ctr Autism, Lexington, MA USA. RP Broder-Fingert, S (reprint author), MassGen Hosp Children, 175 Cambridge St,Cpz 501c, Boston, MA 02114 USA. EM sbroder-finger@partners.org FU Agency for Healthcare Research and Quality, National Research Service Award [T32 HS000063]; Lurie Center for Autism at the Massachusetts General Hospital/MassGeneral Hospital for Children FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Sarabeth Broder-Fingert, MD, is funded through the Agency for Healthcare Research and Quality, National Research Service Award T32 HS000063. The authors also wish to acknowledge the Lurie Center for Autism at the Massachusetts General Hospital/MassGeneral Hospital for Children for their support of this work. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Blumberg SJ, 2013, NATL CTR HLTH STAT, V2013, P65 Dosreis S, 2006, J DEV BEHAV PEDIATR, V27, pS88, DOI 10.1097/00004703-200604002-00006 Golnik A, 2009, PEDIATRICS, V123, P966, DOI 10.1542/peds.2008-1321 Golnik AE, 2009, J AUTISM DEV DISORD, V39, P996, DOI 10.1007/s10803-009-0714-7 Liptak GS, 2006, J AUTISM DEV DISORD, V36, P871, DOI 10.1007/s10803-006-0119-9 NR 6 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 EI 1938-2707 J9 CLIN PEDIATR JI Clin. Pediatr. PD DEC PY 2014 VL 53 IS 14 BP 1390 EP 1392 DI 10.1177/0009922814526982 PG 3 WC Pediatrics SC Pediatrics GA AW1YN UT WOS:000346084900011 PM 24647693 ER PT J AU Gillespie-Lynch, K Kapp, SK Shane-Simpson, C Smith, DS Hutman, T AF Gillespie-Lynch, Kristen Kapp, Steven K. Shane-Simpson, Christina Smith, David Shane Hutman, Ted TI Intersections Between the Autism Spectrum and the Internet: Perceived Benefits and Preferred Functions of Computer-Mediated Communication SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorder; Internet; computer-mediated communications; blogging ID QUALITATIVE-ANALYSIS; ASPERGER SYNDROME; SPECIAL INTERESTS; ADULTS; EXPERIENCES; DISORDERS; CHILDREN; COMMUNITY; STUDENTS; QUOTIENT AB An online survey compared the perceived benefits and preferred functions of computer-mediated communication of participants with (N = 291) and without ASD (N = 311). Participants with autism spectrum disorder (ASD) perceived benefits of computer-mediated communication in terms of increased comprehension and control over communication, access to similar others, and the opportunity to express their true selves. They enjoyed using the Internet to meet others more, and to maintain connections with friends and family less, than did participants without ASD. People with ASD enjoyed aspects of computer-mediated communication that may be associated with special interests or advocacy, such as blogging, more than did participants without ASD. This study suggests that people with ASD may use the Internet in qualitatively different ways from those without ASD. Suggestions for interventions are discussed. C1 [Gillespie-Lynch, Kristen; Shane-Simpson, Christina] CUNY, New York, NY USA. [Kapp, Steven K.; Smith, David Shane; Hutman, Ted] Univ Calif Los Angeles, Los Angeles, CA USA. RP Gillespie-Lynch, K (reprint author), CUNY Coll Staten Isl, Dept Psychol, 4S-234, Staten Isl, NY 10314 USA. 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TI EFFECTS OF SERIAL AND CONCURRENT TRAINING ON ACQUISITION AND GENERALIZATION SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE generalization; sufficient exemplar; tact; serial; concurrent ID RETARDED-CHILDREN; VOCAL IMITATION; AUTISM; REPERTOIRE; BEHAVIOR AB Despite a large body of research demonstrating that generalization to novel stimuli can be produced by training sufficient exemplars, the methods by which exemplars can be trained remain unclear. The purpose of the current study was to evaluate 2 methods, serial and concurrent presentation of stimuli, to train sufficient exemplars. Five preschool children with developmental delays were taught to identify letters or letter sounds using serial and concurrent presentation. Generalization to untrained exemplars was evaluated for targets trained using each method. Participants reached the mastery criterion in fewer training sessions, on average, using the concurrent method of presentation than the serial method, and the concurrent method also resulted in greater generalization to untrained exemplars. C1 [Wunderlich, Kara L.; Vollmer, Timothy R.] Univ Florida, Gainesville, FL 32611 USA. [Donaldson, Jeanne M.] Texas Tech Univ, Lubbock, TX 79409 USA. [Phillips, Cara L.] Kennedy Krieger Inst, Baltimore, MD USA. [Phillips, Cara L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Vollmer, TR (reprint author), Univ Florida, Dept Psychol, 945 Ctr Dr, Gainesville, FL 32611 USA. 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Toussaint, Karen TI INCREASING THE SALIENCY OF BEHAVIOR-CONSEQUENCE RELATIONS FOR CHILDREN WITH AUTISM WHO EXHIBIT PERSISTENT ERRORS SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE acquisition; autism; conditional discrimination; discrete-trial training; discriminated operant; error correction; response cost; schedule discrimination; second-order schedule ID SINGLE-CASE DESIGNS; TOKEN REINFORCEMENT; STIMULUS-CONTROL; ACQUISITION; STUDENTS; METAANALYSIS; PIGEONS; MOTOR AB Some children with autism spectrum disorders (ASD) display persistent errors that are not responsive to commonly used prompting or error-correction strategies; one possible reason for this is that the behavior-consequence relations are not readily discriminable (Davison & Nevin, 1999). In this study, we increased the discriminability of the behavior-consequence relations in conditional-discrimination acquisition tasks for 3 children with ASD using schedule manipulations in concert with a unique visual display designed to increase the saliency of the differences between consequences in effect for correct responding and for errors. A multiple baseline design across participants was used to show that correct responding increased for all participants, and, after 1 or more exposures to the intervention, correct responding persisted to varying degrees across participants when the differential reinforcement baseline was reintroduced to assess maintenance. These findings suggest that increasing the saliency of behavior-consequence relations may help to increase correct responding in children with ASD who exhibit persistent errors. 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TI AN EVALUATION OF INTERACTIVE COMPUTER TRAINING TO TEACH INSTRUCTORS TO IMPLEMENT DISCRETE TRIALS WITH CHILDREN WITH AUTISM SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; discrete-trial instruction; computer training ID STAFF IMPLEMENTATION; SKILLS; ACQUISITION; FEEDBACK; STUDENTS; IMPACT AB Discrete-trial instruction (DTI) is a teaching strategy that is often incorporated into early intensive behavioral interventions for children with autism. Researchers have investigated time- and cost-effective methods to train staff to implement DTI, including self-instruction manuals, video modeling, and interactive computer training (ICT). ICT combines the best components of self-instruction manuals and video models, and have the same benefits; however, there is limited research on this training method. Therefore, the purpose of this study was to investigate ICT to teach university students to implement DTI with children with autism. All participants' teaching fidelity increased during both role-plays with an adult and instructional sessions with a child with autism. In addition, participants demonstrated an increase in teaching fidelity with untrained instructional programs. All participants were able to complete training in an average of 2 hr, and social validity ratings were high. C1 [Pollard, Joy S.; Higbee, Thomas S.; Akers, Jessica S.; Brodhead, Matthew T.] Utah State Univ, Logan, UT 84322 USA. RP Higbee, TS (reprint author), Utah State Univ, Dept Special Educ & Rehabil, 2865 Old Main Hill, Logan, UT 84322 USA. EM tom.higbee@usu.edu CR Arnal L., 2007, DEV DISABILITIES B, V35, P131 Catania CN, 2009, J APPL BEHAV ANAL, V42, P387, DOI 10.1901/jaba.2009.42-387 Downs A, 2008, RES DEV DISABIL, V29, P235, DOI 10.1016/j.ridd.2007.05.001 Fazzio D, 2009, RES AUTISM SPECT DIS, V3, P57, DOI 10.1016/j.rasd.2008.04.002 Granpeesheh D, 2010, RES AUTISM SPECT DIS, V4, P11, DOI 10.1016/j.rasd.2009.07.004 Jeanson B, 2010, RES AUTISM SPECT DIS, V4, P718, DOI 10.1016/j.rasd.2010.01.010 Kekkonen-Moneta S, 2002, BRIT J EDUC TECHNOL, V33, P423, DOI 10.1111/1467-8535.00279 KOEGEL RL, 1977, J APPL BEHAV ANAL, V10, P197, DOI 10.1901/jaba.1977.10-197 McCulloch EB, 2013, EDUC TRAIN AUTISM DE, V48, P132 Moore JW, 2007, J APPL BEHAV ANAL, V40, P197, DOI 10.1901/jaba.2007.24-06 Nosik MR, 2011, RES DEV DISABIL, V32, P1694, DOI 10.1016/j.ridd.2011.02.022 Nosik MR, 2013, RES DEV DISABIL, V34, P461, DOI 10.1016/j.ridd.2012.08.011 Ruiz JG, 2006, ACAD MED, V81, P207, DOI 10.1097/00001888-200603000-00002 Sarokoff RA, 2004, J APPL BEHAV ANAL, V37, P535, DOI 10.1901/jaba.2004.37-535 Sarokoff RA, 2008, RES AUTISM SPECT DIS, V2, P125, DOI 10.1016/j.rasd.2007.04.002 Thiessen C, 2009, BEHAV MODIF, V33, P360, DOI 10.1177/0145445508327443 Thomson K, 2009, RES AUTISM SPECT DIS, V3, P590, DOI 10.1016/j.rasd.2009.01.003 Vladescu JC, 2012, J APPL BEHAV ANAL, V45, P419, DOI 10.1901/jaba.2012.45-419 Wright JM, 2008, J ENVIRON EDUC, V39, P33, DOI 10.3200/JOEE.39.2.33-46 NR 19 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 WIN PY 2014 VL 47 IS 4 BP 765 EP 776 DI 10.1002/jaba.152 PG 12 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900008 PM 25124298 ER PT J AU Seaver, JL Bourret, JC AF Seaver, Jessica L. Bourret, Jason C. TI AN EVALUATION OF RESPONSE PROMPTS FOR TEACHING BEHAVIOR CHAINS SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE acquisition; assessment; autism; chain; children; prompting ID MENTALLY-RETARDED ADOLESCENTS; CHILDREN; AUTISM; SKILLS AB Individuals who have been diagnosed with autism spectrum disorders can have difficulty acquiring new skills, and teaching procedures found to be efficient with 1 individual may not be efficient with others. However, relatively little research has evaluated methods to identify efficient, individualized response-prompt and prompt-fading procedures. We evaluated an assessment of multiple response prompts and prompt-fading procedures with 10 individuals with an autism spectrum disorder. The prompt types assessed were verbal and gestural, model, and physical. Prompt-fading procedures assessed were least to most, most to least, and a progressive delay. Each assessment was conducted at least twice, and the findings of both prompt-type and prompt-fading assessments were generally reliable. A final validity test showed the assessment outcomes to have generality that may extend to other clinically significant responses. C1 Western New England Univ, Springfield, MA USA. [Seaver, Jessica L.] New England Ctr Children, Southborough, MA 01772 USA. RP Seaver, JL (reprint author), New England Ctr Children, 33 Turnpike Rd, Southborough, MA 01772 USA. 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TI EVALUATION OF THE EFFICIENCY OF LISTENER AND TACT INSTRUCTION FOR CHILDREN WITH AUTISM SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; receptive language; expressive language; listener identification; tact; efficiency; emergence; naming ID YOUNG-CHILDREN; EXPRESSIVE LANGUAGE; PRESCHOOL-CHILDREN; CATEGORIZATION; BEHAVIOR AB Recent literature reviews have highlighted the need to better understand the relation between speaker and listener behavior when teaching learners with autism spectrum disorders (ASD). The current study used a modified parallel-treatments design to compare directly the degree to which tact and listener behavior emerged during instruction in the opposite relation for 4 children with ASD. Results showed tact training to be either equally or more efficient than listener training for all participants. However, varied patterns of emergent responding across participants indicate a need for further research. Data on collateral responding during instruction did not suggest that the presence or absence of overt collateral behaviors were predictive of emergence. The results highlight the importance for clinicians and educators to assess emergent tact and listener repertoires periodically. C1 [Delfs, Caitlin H.; Conine, Daniel E.; Frampton, Sarah E.; Shillingsburg, M. Alice; Robinson, Hannah C.] Marcus Autism Ctr, Atlanta, GA 30329 USA. [Delfs, Caitlin H.; Shillingsburg, M. Alice] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Delfs, CH (reprint author), Marcus Autism Ctr, 1920 Briarcliff Rd NE, Atlanta, GA 30329 USA. EM caitlin.delfs@choa.org CR Alpern G. D., 2007, DEV PROFILE Barbera M. L., 2007, VERBAL BEHAV APPROAC EIKESETH S, 1992, J EXP ANAL BEHAV, V58, P123, DOI 10.1901/jeab.1992.58-123 Gast D. L., 1988, ED TREATMENT CHILDRE, V11, P270 Gilic Lina, 2011, Anal Verbal Behav, V27, P157 Gilliam J. E., 1995, GILLIAM AUTISM RATIN Greer R Douglas, 2010, Anal Verbal Behav, V26, P73 Greer R. 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W., 2008, ASSESSMENT BASICS LA Petursdottir AI, 2011, J APPL BEHAV ANAL, V44, P859, DOI 10.1901/jaba.2011.44-859 Sautter RA, 2011, J APPL BEHAV ANAL, V44, P227, DOI 10.1901/jaba.2011.44-227 Schopler E., 1988, CHILDHOOD AUTISM RAT Skinner B. F., 1957, VERBAL BEHAV Sparrow SS, 2005, VINELAND ADAPTIVE BE Sprinkle Evelyn C, 2012, Anal Verbal Behav, V28, P111 Sundberg M. L., 2008, VERBAL BEHAV MILESTO Sundberg M. L., 1998, TEACHING LANGUAGE CH Wechsler D., 2003, WECHSLER INTELLIGENC Wynn JW, 2003, BEHAV INTERVENT, V18, P245, DOI 10.1002/bin.142 NR 34 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 WIN PY 2014 VL 47 IS 4 BP 793 EP 809 DI 10.1002/jaba.166 PG 17 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900010 PM 25324150 ER PT J AU Delfs, CH Frampton, SE AF Delfs, Caitlin H. Frampton, Sarah E. TI PRACTICAL IMPLICATIONS OF EVALUATING THE EFFICIENCY OF LISTENER AND TACT INSTRUCTION FOR CHILDREN WITH AUTISM SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE clinical recommendations; autism; receptive language; expressive language; listener identification; tact; efficiency; emergence; naming ID BEHAVIOR AB Recent literature reviews have highlighted the need to better understand the relation between speaker and listener behavior when teaching learners with autism spectrum disorder (ASD). The current paper outlines the practical implications of evaluating the emergence of tact and listener behavior during instruction for the opposite relation, as presented in the preceding article Evaluating the Efficiency of Listener and Tact Instruction for Children with Autism. Modifications of those procedures for clinical use as well as future directions for research in this area are presented. C1 [Delfs, Caitlin H.; Frampton, Sarah E.] Marcus Autism Ctr, Atlanta, GA 30329 USA. [Delfs, Caitlin H.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Delfs, CH (reprint author), Marcus Autism Ctr, 1920 Briarcliff Rd NE, Atlanta, GA 30329 USA. EM caitlin.delfs@choa.org CR Catania A. C., 1998, LEARNING Delfs C. H., 2014, J APPL BEHAV ANAL, V47 Fiorile Carol A, 2007, Anal Verbal Behav, V23, P71 Gilic Lina, 2011, Anal Verbal Behav, V27, P157 Grow Laura, 2013, Behav Anal Pract, V6, P56 Horne PJ, 1996, J EXP ANAL BEHAV, V65, P185, DOI 10.1901/jeab.1996.65-185 LeBlanc L. A., 2009, DERIVED RELATIONAL R, P79 Lerman Dorothea C, 2011, Behav Anal Pract, V4, P53 Miguel C. F., 2009, DERIVED RELATIONAL R, P129 PARTINGTON JW, 1994, J APPL BEHAV ANAL, V27, P733, DOI 10.1901/jaba.1994.27-733 Petursdottir AI, 2011, J APPL BEHAV ANAL, V44, P859, DOI 10.1901/jaba.2011.44-859 Rehfeldt RA, 2011, J APPL BEHAV ANAL, V44, P109, DOI 10.1901/jaba.2011.44-109 SIDMAN M, 1982, J EXP ANAL BEHAV, V37, P5, DOI 10.1901/jeab.1982.37-5 Wolery M., 1992, TEACHING STUDENTS MO NR 14 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 WIN PY 2014 VL 47 IS 4 BP 810 EP 813 DI 10.1002/jaba.176 PG 4 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900011 PM 25345666 ER PT J AU Day-Watkins, J Murray, R Connell, JE AF Day-Watkins, Jessica Murray, Rachel Connell, James E. TI TEACHING HELPING TO ADOLESCENTS WITH AUTISM SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; helping behavior; video modeling; adolescents; generalization AB This study is a replication and extension of Reeve, Reeve, Townsend, and Poulson (2007) evaluating the effects of a treatment package that included multiple-exemplar training, video modeling, prompting, and reinforcement on helping of 3 adolescents with autism. Results demonstrated that all participants acquired the helping responses. Probes before and after intervention also demonstrated generalization of helping across settings and categories of helping behavior. C1 [Day-Watkins, Jessica] Temple Univ, Philadelphia, PA 19122 USA. [Murray, Rachel] Comprehens Learning Ctr, Southampton, PA USA. [Connell, James E.] Drexel Univ, Philadelphia, PA USA. RP Day-Watkins, J (reprint author), Caldwell Coll, Dept Appl Behav Anal, 120 Bloomfield Ave, Caldwell, NJ 07006 USA. EM jday@caldwell.edu CR HARRIS SL, 1990, J APPL BEHAV ANAL, V23, P297, DOI 10.1901/jaba.1990.23-297 Reeve SA, 2007, J APPL BEHAV ANAL, V40, P123, DOI 10.1901/jaba.2007.11-05 Reichow B, 2010, J AUTISM DEV DISORD, V40, P149, DOI 10.1007/s10803-009-0842-0 NR 3 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 WIN PY 2014 VL 47 IS 4 BP 850 EP 855 DI 10.1002/jaba.156 PG 6 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900016 PM 25168515 ER PT J AU Gunby, KV Rapp, JT AF Gunby, Kristin V. Rapp, John T. TI THE USE OF BEHAVIORAL SKILLS TRAINING AND IN SITU FEEDBACK TO PROTECT CHILDREN WITH AUTISM FROM ABDUCTION LURES SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE abduction prevention; autism; behavioral skills training; high-p sequence ID PREVENTION SKILLS; YOUNG-CHILDREN AB We examined the effects of behavioral skills training with in situ feedback on safe responding by children with autism to abduction lures that were presented after a high-probability (high-p) request sequence. This sequence was intended to simulate a grooming or recruitment process. Results show that all 3 participants ultimately acquired the safety response to abduction lures presented after a high-p sequence and maintained the safety response at a 1-month follow-up. C1 [Gunby, Kristin V.; Rapp, John T.] St Cloud State Univ, St Cloud, MN USA. RP Rapp, JT (reprint author), Auburn Univ, Cary 229, Auburn, AL 36849 USA. EM jtr0014@auburn.edu CR ELLIOTT M, 1995, CHILD ABUSE NEGLECT, V19, P579, DOI 10.1016/0145-2134(95)00017-3 Gunby KV, 2010, J APPL BEHAV ANAL, V43, P107, DOI 10.1901/jaba.2010.43-107 Johnson BM, 2005, J APPL BEHAV ANAL, V38, P67, DOI 10.1901/jaba.2005.26-04 MACE FC, 1988, J APPL BEHAV ANAL, V21, P123, DOI 10.1901/jaba.1988.21-123 Miltenberger Raymond G, 2008, Behav Anal Pract, V1, P30 POCHE C, 1981, J APPL BEHAV ANAL, V14, P169, DOI 10.1901/jaba.1981.14-169 NR 6 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 WIN PY 2014 VL 47 IS 4 BP 856 EP 860 DI 10.1002/jaba.173 PG 5 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900017 PM 25311885 ER PT J AU Bergstrom, R Najdowski, AC Tarbox, J AF Bergstrom, Ryan Najdowski, Adel C. Tarbox, Jonathan TI A SYSTEMATIC REPLICATION OF TEACHING CHILDREN WITH AUTISM TO RESPOND APPROPRIATELY TO LURES FROM STRANGERS SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE abduction; autism; lure; prevention; safety; stranger ID ABDUCTION-PREVENTION SKILLS; YOUNG-CHILDREN AB We evaluated the effects of behavioral skills training in the home for teaching children with autism to abstain from going with strangers and immediately inform a familiar adult of the stranger's attempt to lure them in the natural environment. All participants learned to respond correctly to lures in the home and demonstrated concomitant changes in untrained natural settings. In situ training and an added incentive were necessary for 1 participant. C1 [Bergstrom, Ryan; Najdowski, Adel C.; Tarbox, Jonathan] Ctr Autism & Related Disorders Inc, Autism Res Grp, Thousand Oaks, CA 91360 USA. RP Najdowski, AC (reprint author), Ctr Autism & Related Disorders Inc, Autism Res Grp, 325 E Hillcrest Dr, Thousand Oaks, CA 91360 USA. EM a.najdowski@centerforautism.com CR Finkelhor D., 2002, NISMART NATL INCIDEN Gunby K. V., 2014, J APPL BEHAV ANAL, V47 Gunby KV, 2010, J APPL BEHAV ANAL, V43, P107, DOI 10.1901/jaba.2010.43-107 Himle MB, 2004, J APPL BEHAV ANAL, V37, P1, DOI 10.1901/jaba.2004.37-1 Johnson BM, 2005, J APPL BEHAV ANAL, V38, P67, DOI 10.1901/jaba.2005.26-04 Johnson BM, 2006, J APPL BEHAV ANAL, V39, P25, DOI 10.1901/jaba.2006.167-04 POCHE C, 1981, J APPL BEHAV ANAL, V14, P169, DOI 10.1901/jaba.1981.14-169 WILSON C, 1992, AUST PSYCHOL, V27, P114, DOI 10.1080/00050069208257591 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 WIN PY 2014 VL 47 IS 4 BP 861 EP 865 DI 10.1002/jaba.175 PG 5 WC Psychology, Clinical SC Psychology GA AW3HJ UT WOS:000346176900018 PM 25327476 ER PT J AU Choi, JE Widjaja, F Careaga, M Bent, S Ashwood, P Hendren, RL AF Choi, Jae Eun Widjaja, Felicia Careaga, Milo Bent, Stephen Ashwood, Paul Hendren, Robert L. TI Change in Plasma Cytokine Levels During Risperidone Treatment in Children with Autism SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID SCHIZOPHRENIA; CELLS; SERUM AB Background: Atypical antipsychotics decrease irritability in autism. They also affect the cytokine network. Psychological stress, depression, and, possibly, autism spectrum disorder (ASD) are associated with the production of pro-inflammatory cytokines. We sought to determine if risperidone treatment led to changes in plasma cytokine levels. Methods: Forty-five subjects from an open-label study of risperidone treatment of children and adolescents with ASD, ages 4-18 years, had an analysis of 27 different cytokines at baseline and after 8 weeks of treatment using multiplex assays (Millipore) and read on the Luminex 100((TM)) platform. We examined changes in each of the cytokine levels in the entire group, and also compared changes in cytokines in responders versus nonresponders. Results: After 8 weeks of risperidone treatment, 2 of the 27 plasma cytokines showed statistically significant decreases in median levels: Eotaxin (p=0.0003) and monocyte chemoattractant protein-1 (MCP-1) (p=0.0024). Six of the 48 subjects met two criteria for responders to risperidone, and the median values of interleukin (IL)-5 were significantly higher (p=0.005) in the overall responder group than in nonresponders. Conclusions: Two cytokines, eotaxin and MCP-1, which have previously been identified as abnormally elevated in children with autism, decreased during treatment with risperidone. This suggests a possible mechanism of action of risperidone treatment and a balancing of the immune system in affected subjects in this very preliminary study. C1 [Choi, Jae Eun] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Widjaja, Felicia; Hendren, Robert L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Careaga, Milo; Ashwood, Paul] Univ Calif Davis, Davis, CA 95616 USA. [Bent, Stephen] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. RP Hendren, RL (reprint author), Univ Calif San Francisco, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM Robert.Hendren@ucsf.edu FU NIMH [R21MH080026] FX This study was supported by R21MH080026 (RLH) from NIMH. 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Child Adolesc. Psychopharmacol. PD DEC 1 PY 2014 VL 24 IS 10 BP 586 EP 589 DI 10.1089/cap.2013.0108 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AW6AF UT WOS:000346351200009 PM 24828014 ER PT J AU Dang, W Zhang, Q Zhu, YS Lu, XY AF Dang, Wei Zhang, Qian Zhu, Yong-Sheng Lu, Xiao-Yun TI The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Autism susceptibility candidate 2; Heroin dependence; Single-nucleotide polymorphisms; Han population ID GENOME-WIDE ASSOCIATION; MOLECULAR-GENETICS; REWARD; TWINS AB The single-nucleotide polymorphisms (SNP) rs6943555 in autism susceptibility candidate 2 (AUTS2) has been reported to be significantly associated with alcohol consumption in Europeans. In this study, we identified the SNP in AUTS2 contributing to the genetic susceptibility to heroin dependence. The potential association between heroin dependence and 21 SNPs (rs2270162, rs2851510, rs513150, rs595681, rs210606, rs10237984, rs13228123, rs10235781, rs6969375, rs6943555, rs10251416, rs17141963, rs12669427, rs723340, rs2293507, rs2293508, rs6960426, rs9886351, rs2293501, rs10277450, rs1918425) of AUTS2 was examined in a Chinese Han population using the MassARRAY system. The participants included 426 patients with heroin dependence and 416 healthy controls. Single SNP association, haplotype association, and clinical phenotype association were analyzed. Single SNP association revealed that AA homozygotes of rs6943555 were significantly over-represented in the patients with heroin dependence compared with the control subjects (P = 0.0019). The patients with heroin dependence had a significantly higher frequency of the A allele (P = 0.0003, odd ratio (OR) = 1.429, 95 % confidence interval (CI) = 1.175-1.738). Strong linkage disequilibrium (LD) was observed in five blocks (D'aEuro parts per thousand > 0.9). In block 2, significantly more A-A haplotypes (P = 0.006 after Bonferroni corrections) and significantly fewer T-A haplotypes (P = 0.040) were found in the patients with heroin dependence. The genotype and clinical phenotype correlation study of the rs6943555 carriers showed that the amount of heroin self-injection was lower in the patients with the AA genotype relative to AT + TT genotypes (P < 0.01). Our results confirmed that, in addition to heroin consumption, the SNP rs6943555 of AUTS2 may also play an important role in the etiology of heroin dependence. C1 [Dang, Wei; Zhu, Yong-Sheng; Lu, Xiao-Yun] Xi An Jiao Tong Univ, Coll Forens Sci, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Shaanxi, Peoples R China. [Dang, Wei] Xian Mental Hlth Ctr, Ward 6, Xian, Shannxi, Peoples R China. [Zhang, Qian; Zhu, Yong-Sheng] Ningxia Med Univ, Key Lab Fertil Preservat & Maintenance, Minist Educ, Yinchuan 750004, Peoples R China. RP Lu, XY (reprint author), Xi An Jiao Tong Univ, Coll Forens Sci, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Shaanxi, Peoples R China. EM zhuyongsheng3000@aliyun.com; luxy05@mail.xjtu.edu.cn FU Science and Technology Bureau Projects of Xi'an [SF1210 (1-d)]; Research and Development Foundation of Science and Technology of Shaanxi Province; National Science Foundation of China [NSFC 31100900]; Postdoctoral Science Foundation of China [137033] FX This research was partially supported by the Science and Technology Bureau Projects of Xi'an (SF1210 (1-d)), the Research and Development Foundation of Science and Technology of Shaanxi Province and the National Science Foundation of China (#NSFC 31100900), and Postdoctoral Science Foundation of China (137033). The funding sources had input into the design of this study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication. 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Neurophysiol. PD DEC 1 PY 2014 VL 112 IS 11 BP 2669 EP 2671 DI 10.1152/jn.00242.2014 PG 3 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AW1AN UT WOS:000346023000001 PM 24872530 ER PT J AU Winkler-Schwartz, A Garfinkle, J Shevell, MI AF Winkler-Schwartz, Alexander Garfinkle, Jarred Shevell, Michael I. TI Autism Spectrum Disorder in a Term Birth Neonatal Intensive Care Unit Population SO PEDIATRIC NEUROLOGY LA English DT Article DE autism; term born; neonatal; high risk ID PERVASIVE DEVELOPMENTAL DISORDERS; RISK-FACTORS; CEREBRAL-PALSY; CHILDREN; PREVALENCE; EPILEPSY; CLASSIFICATION; DEFINITION; SURVIVORS AB BACKGROUND: Nonspecific perinatal risk factors have been revealed to be associated with the development of autism spectrum disorder. However, term at-risk infants, as a distinct population, are underrepresented in the literature. This study examines the incidence and neonatal risk factors for autism spectrum disorder in term neonatal intensive care unit survivors. METHODS: We performed a retrospective analysis from a single university-practice database of neonates admitted to the neonatal intensive care unit and followed by a single pediatric neurologist. Term infants (>= 37 weeks), born between 1991 and 2011, with at least 2 years (or 1 year if found to be neurologically normal) of follow-up were included. Principle outcomes were autism spectrum disorder, cerebral palsy, global developmental delay, and epilepsy. RESULTS: One hundred eighty infants were included from a database of 564 neonates. Twelve (6.6%) developed autism spectrum disorder, 53 (29.4%) cerebral palsy, 77 (42.7%) global developmental delay, and 47 (26.1%) epilepsy. Seventy-one (39.4%) developed no adverse outcomes. Nine patients with autism spectrum disorder (75%) were diagnosed with at least one other adverse outcome. No neonatal or perinatal variables were evident to be significantly associated with later autism spectrum disorder. CONCLUSIONS: In term neonatal intensive care unit survivors, autism spectrum disorder occurs at a greater frequency than in the general population and often develops alongside comorbid conditions. This highlights the importance of screening term neonatal intensive care unit survivors for autism spectrum disorder, particularly when comorbidities are present. C1 [Winkler-Schwartz, Alexander; Garfinkle, Jarred; Shevell, Michael I.] McGill Univ, Dept Neurol Neurosurg, Montreal, PQ H3H 1P3, Canada. [Shevell, Michael I.] McGill Univ, Dept Pediat, Montreal, PQ H3H 1P3, Canada. [Garfinkle, Jarred; Shevell, Michael I.] McGill Univ, Montreal Childrens Hosp, Div Pediat Neurol, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. RP Shevell, MI (reprint author), McGill Univ, Montreal Childrens Hosp, Div Pediat Neurol, Ctr Hlth, Room C-414,2300 Tupper, Montreal, PQ H3H 1P3, Canada. 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Neurol. PD DEC PY 2014 VL 51 IS 6 BP 776 EP 780 DI 10.1016/j.pediatrneurol.2014.07.009 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AW2JM UT WOS:000346113900005 PM 25303867 ER PT J AU Xie, SN Shi, JX Wang, JM Li, N Yang, SB Zhang, J AF Xie, Shengnan Shi, Jumxin Wang, Jianmin Li, Neng Yang, Senbei Zhang, Jing TI Head Circumference Growth Reference Charts of Children Younger Than 7 Years in Chinese Rural Areas SO PEDIATRIC NEUROLOGY LA English DT Article DE China; rural area; children; head circumference; growth reference chart ID INFANTS; AUTISM AB BACKGROUND: The head circumference growth reference charts for children in China are presently based on urban children. However, the references may not apply to rural children because of the differences between urban and rural areas, such as economy, culture, and dietary habits. Our objective was to provide a reliable continuous set of head circumference growth reference charts for male and female children less than 7 years of age in Chinese rural areas. METHODS: Children in our study were identified by multistage stratified cluster sampling from rural areas of 10 provinces in China. Questionnaire survey and anthropometric measurements were conducted in data collection. Head circumference was measured with a nonelastic tape on a line passing over the glabella and posterior occipital protrusion in children. We compared the fiftieth percentile of our cross-sectional data with the data of Chinese cities, World Health Organization, and the United States. RESULTS: A total of 95,904 children (48,722 boys and 47,182 girls) were included in the study. We present age- and sex-appropriate head circumference growth charts younger than 7 years for Chinese rural areas. The head circumference percentiles of the children in rural China are much smaller than the children in Chinese urban areas, World Health Organization, and the US percentiles after 2 years old. CONCLUSIONS: Head circumference percentiles can be applied in growth monitoring, but current head circumference growth references promulgated in urban China may not be suitable for rural areas in China. Providing head circumference growth reference charts for rural Chinese children who are younger than 7 years old is very important. C1 [Xie, Shengnan; Wang, Jianmin; Li, Neng; Yang, Senbei; Zhang, Jing] Huazhong Univ Sci & Technol, Tongii Med Coll, Sch Publ Hlth, Dept Woman & Childs Care & Adolescence Hlth, Wuhan 430030, Hubei, Peoples R China. [Shi, Jumxin] Nationwide Childrens Hosp, Ctr Injury Res & Policy, Res Inst, Columbus, OH USA. RP Zhang, J (reprint author), Huazhong Univ Sci & Technol, Tongii Med Coll, Sch Publ Hlth, Dept Woman & Childs Care & Adolescence Hlth, 13 Hangkong Rd, Wuhan 430030, Hubei, Peoples R China. EM fyebzj@126.com CR Ashwal S, 2009, NEUROLOGY, V73, P887, DOI 10.1212/WNL.0b013e3181b783f7 Cheong JLY, 2008, PEDIATRICS, V121, pE1534, DOI 10.1542/peds.2007-2671 Cui L., CHINA YOUTH NEWS VER Elmali F, 2012, PEDIATR NEUROL, V46, P307, DOI 10.1016/j.pediatrneurol.2012.02.016 [付强 Fu Qiang], 2012, [中国卫生统计, Chinese Journal of Health Statistics], V29, P177 Gale CR, 2006, PEDIATRICS, V118, P1486, DOI 10.1542/peds.2005-2629 Gale CR, 2004, BRAIN, V127, P321, DOI 10.1093/brain/awh034 Gao QY, 2006, CJCHC, V14, P220 Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 Lainhart JE, 2006, AM J MED GENET A, V140A, P2257, DOI 10.1002/ajmg.a.31465 Li Hui, 2009, Zhonghua Er Ke Za Zhi, V47, P173 Li PF, 2013, J HUAZHONG NORMAL UN, V47, P536 Li XY, 2008, J APPL CLIN PEDIAT, V23, P841 [刘爱东 LIU Aidong], 2008, [卫生研究, Journal of Hygiene Research], V37, P324 Rollins JD, 2010, J PEDIATR-US, V156, P907, DOI 10.1016/j.jpeds.2010.01.009 Rollins JD, 2010, J PEDIAT, V156, P911 Schienkiewitz A, 2011, ACTA PAEDIATR, V100, pe28, DOI 10.1111/j.1651-2227.2011.02173.x Shiovitz S, 2010, BREAST CANCER RES TR, V124, P459, DOI 10.1007/s10549-010-0839-6 Thompson PM, 2005, J NEUROSCI, V25, P4146, DOI 10.1523/JNEUROSCI.0165-05.2005 [旺庆 Wang Qing], 2013, [解剖学杂志, Chinese Journal of Anatomy], V36, P824 Werner B, 2006, ACTA PAEDIATR, V95, P1601, DOI 10.1080/08035250600735594 WHO Multicentre Growth Reference Study Group, 2006, ACTA PAEDIAT S, V450, P76 WHO Multicentre Growth Reference Study Group, 2007, MULT GROWTH REF STUD, VGeneva Xie SN, 2014, CHIN J EPIDEMIOL, V35, P82 Zahl SM, 2008, PEDIATRICS, V121, pE416, DOI 10.1542/peds.2007-1598 [张静 Zhang Jing], 2012, [中华流行病学杂志, Chinese Journal of Epidemiology], V33, P131 NR 26 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 EI 1873-5150 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD DEC PY 2014 VL 51 IS 6 BP 814 EP 819 DI 10.1016/j.pediatrneurol.2014.08.014 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AW2JM UT WOS:000346113900011 PM 25456302 ER PT J AU Bernhardt, BC Valk, SL Silani, G Bird, G Frith, U Singer, T AF Bernhardt, Boris C. Valk, Sofie L. Silani, Giorgia Bird, Geoffrey Frith, Uta Singer, Tania TI Selective Disruption of Sociocognitive Structural Brain Networks in Autism and Alexithymia SO CEREBRAL CORTEX LA English DT Article DE ASD; connectivity; cortical thickness; insula; social brain ID TEMPORAL-LOBE EPILEPSY; INSULAR FUNCTIONAL CONNECTIVITY; CEREBRAL CORTICAL THICKNESS; GRAPH-THEORETICAL ANALYSIS; SURFACE-BASED ANALYSIS; OLD-WORLD MONKEY; SPECTRUM DISORDERS; WHITE-MATTER; INDIVIDUAL-DIFFERENCES; ASPERGER-SYNDROME AB Autism spectrum conditions (ASC) are neurodevelopmental disorders characterized by abnormal social cognition. A core feature of ASC is disrupted Theory of Mind (ToM), our ability to take the mental perspective of others. ASC is also associated with alexithymia, a trait characterized by altered emotional interoception and empathy. Here, we applied structural MRI covariance analysis to assess whether ASC and alexithymia differentially affect structural brain networks associated with sociocognitive and socioaffective functions. Based on previous functional MRI findings, we expected disrupted ToM networks (centered on dorsomedial prefontal cortex [dmPFC], and temporo-parietal junction [TPJ]) in ASC, while alexithymia would affect networks centered on fronto-insular cortex (FI), regions associated with interoception of emotion and empathy. Relative to controls, ASC indeed showed reduced covariance in networks centered on dmPFC and TPJ, but not within FI networks. Irrespective of ASC, covariance was negatively modulated by alexithymia in networks extending from FI to posterior regions. Network findings were complemented by self-reports, indicating decreased perspective taking but normal empathic concern in ASC. Our results show divergent effects of ASC and alexithymia on inter-regional structural networks, suggesting that networks mediating socioaffective processes may be separable from networks mediating sociocognitive processing. C1 [Bernhardt, Boris C.; Valk, Sofie L.; Singer, Tania] Max Planck Inst Human Cognit & Brain Sci, Dept Social Neurosci, D-04103 Leipzig, Germany. [Silani, Giorgia; Bird, Geoffrey; Frith, Uta; Singer, Tania] UCL, Inst Cognit Neurosci, London, England. [Silani, Giorgia] Int Sch Adv Studies SISSA ISAS, Cognit Neurosci Sect, Trieste, Italy. [Bird, Geoffrey] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr MRC, London WC2R 2LS, England. RP Singer, T (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Social Neurosci, Stephanstr 1a, D-04103 Leipzig, Germany. EM singer@cbs.mpg.de FU European Research Council under the European Community's Seventh Framework Program (FP7)/ERC [205557]; Swiss National Science Foundation; Medical Research Council UK [G9617036]; Erasmus Mundus scholarship FX This work was also supported by grants to T.S. from the European Research Council under the European Community's Seventh Framework Program (FP7/2007-2013)/ERC Grant agreement no 205557 [EMPATHICBRAIN] as well as from the Swiss National Science Foundation (SNF NCCR Affective Sciences: 'Neuronal and developmental mechanisms of human empathy'; SNF NCCR Neural Plasticity and Repair: 'Plasticity of the empathic and attentional brain'). In addition, it was funded by the Medical Research Council UK (Grant no. G9617036, to U.F). S.L.V. received an Erasmus Mundus scholarship. 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Cortex PD DEC PY 2014 VL 24 IS 12 BP 3258 EP 3267 DI 10.1093/cercor/bht182 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AU8HX UT WOS:000345838300014 PM 23863687 ER PT J AU Glennon, J Purper-Ouakil, D Bakker, M Zuddas, A Hoekstra, P Schulze, U Castro-Fornieles, J Santosh, PJ Arango, C Kolch, M Coghill, D Flamarique, I Penzol, MJ Wan, M Murray, M Wong, ICK Danckaerts, M Bonnot, O Falissard, B Masi, G Fegart, JM Vicari, S Carucci, S Dittmann, RW Buitelaar, JK AF Glennon, Jeffrey Purper-Ouakil, Diane Bakker, Mireille Zuddas, Alessandro Hoekstra, Pieter Schulze, Ulrike Castro-Fornieles, Josefina Santosh, Paramala J. Arango, Celso Koelch, Michael Coghill, David Flamarique, Itziar Penzol, Maria J. Wan, Mandy Murray, Macey Wong, Ian C. K. Danckaerts, Marina Bonnot, Olivier Falissard, Bruno Masi, Gabriele Fegart, Joerg M. Vicari, Stefano Carucci, Sara Dittmann, Ralf W. Buitelaar, Jan K. CA PERS Consortium TI Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Conduct disorder; Randomised clinical trials; Risperidone; Pharmacovigilance; Psychopharmacology ID OPPOSITIONAL DEFIANT DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; AUTISM SPECTRUM DISORDERS; CONDUCT DISORDER; 2ND-GENERATION ANTIPSYCHOTICS; WEIGHT-GAIN; SUBAVERAGE INTELLIGENCE; REFERRED CHILDREN; RECEPTOR GENE; RATING-SCALE AB In children and adolescents with conduct disorder (CD), pharmacotherapy is considered when non-pharmacological interventions do not improve symptoms and functional impairment. Risperidone, a second-generation antipsychotic is increasingly prescribed off-label in this indication, but its efficacy and tolerability is poorly studied in CD, especially in young people with normal intelligence. The Paediatric European Risperidone Studies (PERS) include a series of trials to assess short-term efficacy, tolerability and maintenance effects of risperidone in children and adolescents with CD and normal intelligence as well as long-term tolerability in a 2-year pharmacovigilance. In addition to its core studies, secondary PERS analyses will examine moderators of drug effects. As PERS is a large-scale academic project involving a collaborative network of expert centres from different countries, it is expected that results will lead to strengthen the evidence base for the use of risperidone in CD and improve standards of care. Challenging issues faced by the PERS consortium are described to facilitate future developments in paediatric neuropsychopharmacology. C1 [Glennon, Jeffrey; Bakker, Mireille; Buitelaar, Jan K.] RUNMC Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Purper-Ouakil, Diane] CHRU Montpellier Hop St Eloi, F-34295 Montpellier 5, France. [Purper-Ouakil, Diane] Ctr Psychiat & Neurosci, INSERM U894 Team 1, INSERM Team 1, Paris, France. [Zuddas, Alessandro; Carucci, Sara] Univ Cagliari, Cagliari Univ Hosp, Dept Biomed Sci, Cagliari, Italy. [Hoekstra, Pieter] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Schulze, Ulrike; Koelch, Michael; Fegart, Joerg M.] Univ Ulm, Dept Child & Adolescent Psychiatry Psychotherapy, D-89069 Ulm, Germany. [Castro-Fornieles, Josefina; Flamarique, Itziar] Univ Barcelona, CIBERSAM, Hosp Clin Barcelona,Dept Child & Adolescent Psych, IDIBAPS,Neurosci Inst,FCRB, Barcelona, Spain. [Santosh, Paramala J.] S London & Maudsley NHS Fdn Trust, Ctr Intervent Paediat Psychopharmacol, London, England. [Santosh, Paramala J.] Kings Coll London, Dept Child Psychiat, London, England. [Arango, Celso; Penzol, Maria J.] Univ Complutense, CIBERSAM, Hosp Gen Univ Gregorio Maranon,IiSGM, Fac Med,Child & Adolescent Psychiat Dept, E-28040 Madrid, Spain. [Coghill, David] Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Div Neurosci, Dundee, Scotland. [Wan, Mandy] Univ London, Univ Coll London, Sch Pharm, London, England. [Murray, Macey] UCL Sch Pharm, Ctr Paediat Pharm Res, Dept Practice & Policy, London, England. [Wong, Ian C. K.] Univ Hong Kong, Ctr Safe Medicat Practice & Res, Dept Pharmacol & Pharm, Pokfulam, Hong Kong, Peoples R China. [Danckaerts, Marina] UPC Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium. [Bonnot, Olivier] Unite Univ Psychiat IEnfant & Adolescent, Nantes, France. [Falissard, Bruno] INSERM, U669, Paris, France. [Masi, Gabriele] IRCCS Fdn Stella Maris, Pisa, Italy. [Vicari, Stefano] IRCCS Children Hosp Bambino Gesu, Rome, Italy. [Dittmann, Ralf W.] Cent Inst Mental Hlth, CIMH, Mannheim, Germany. RP Purper-Ouakil, D (reprint author), CHRU Montpellier Hop St Eloi, 80 Ave Augustin Fliche, F-34295 Montpellier 5, France. EM J.Glennon@donders.ru.nl; d-purper_ouakil@chu-montpellier.fr; m.bakker@cns.umcn.nl; azuddas@unica.it; p.hoekstra@accare.nl; Ulrike.Schulze@uniklinik-ulm.de; JCASTRO@clinic.ub.es; paramala.1.santosh@kcl.ac.uk; carango@hggm.es; michael.koelch@uniklinik-ulm.de; david.coghill@btinternet.com; IFLAMARI@clinic.ub.es; mjpenzol@iisgm.com; Mandy.Wan@gstt.nhs.uk; macey.murray@ucl.ac.uk; wongick@hku.hk; marina.danckaerts@uzleuven.be; olivier.bonnot@psl.aphp.fr; bruno.falissard@gmail.com; gabriele.masi@inpe.unipi.it; Joerg.Fegert@uniklinik-ulm.de; stefano.vicari@opbg.net; sara.carucci@gmail.com; ralf.dittmann@zi-mannheim.de; J.Buitelaar@psy.umcn.nl FU European Community [241959] FX The research leading to this publication has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 241959. We also acknowledge the ECNP child and adolescent neuropsychopharmacology network, the ECNP-Network Initiative and the reviewers of the manuscript. 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Child Adolesc. Psych. PD DEC PY 2014 VL 23 IS 12 BP 1149 EP 1160 DI 10.1007/s00787-013-0498-3 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AU5IC UT WOS:000345639200004 PM 24337449 ER PT J AU Ray, S Miller, M Karalunas, S Robertson, C Grayson, DS Cary, RP Hawkey, E Painter, JG Kriz, D Fombonne, E Nigg, JT Fair, DA AF Ray, Siddharth Miller, Meghan Karalunas, Sarah Robertson, Charles Grayson, David S. Cary, Robert P. Hawkey, Elizabeth Painter, Julia G. Kriz, Daniel Fombonne, Eric Nigg, Joel T. Fair, Damien A. TI Structural and Functional Connectivity of the Human Brain in Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder: A Rich Club-Organization Study SO HUMAN BRAIN MAPPING LA English DT Article DE attention-deficit; hyperactivity disorder; autism spectrum disorders; high angular resolution diffusion imaging; rs-fMRI; connectivity; rich-club organization; DW-MRI; diffusion tensor imaging ID DEFICIT HYPERACTIVITY DISORDER; DEFAULT-MODE NETWORK; SYMPTOM SEVERITY; SOCIAL DEFICITS; CHILDREN; ADHD; ABNORMALITIES; SCHIZOPHRENIA; COMMUNICATION; NEUROSCIENCE AB Attention-deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n=20), a group with ASD (7-13 years, n=16), and typically developing controls (TD) (8-12 years, n=20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena and (2) outside a rich-club network phenomena. The ASD and ADHD groups had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange dataset with ASD (n=85) and TD (n=101). The ADHD group exhibited a lower generalized fractional anisotropy and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood. Hum Brain Mapp 35:6032-6048, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Ray, Siddharth] Univ Texas Hlth Sci Ctr Houston, Dept Diagnost & Intervent Imaging, Houston, TX 77030 USA. [Ray, Siddharth; Robertson, Charles; Grayson, David S.; Cary, Robert P.; Hawkey, Elizabeth; Painter, Julia G.; Kriz, Daniel; Fombonne, Eric; Nigg, Joel T.; Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Miller, Meghan] Calif State Univ Sacramento, Dept Psychiat & Behav Sci, Davis MIND Inst, Sacramento, CA 95819 USA. [Karalunas, Sarah; Fombonne, Eric; Nigg, Joel T.; Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Grayson, David S.] Univ Calif Davis, Ctr Neurosci, Dept Psychiat, Davis, CA 95616 USA. [Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97201 USA. [Fair, Damien A.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA. RP Fair, DA (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. EM faird@ohsu.edu FU Simons Foundation [177894, R01 MH086654, R01 MH86654]; Oregon Clinical and Translational Institute [UL1TR000128]; [R01 MH096773]; [K99/R00 MH091238] FX Contract grant number(s): R01 MH096773 and K99/R00 MH091238 (to D. A. F.); Contract grant sponsor: Simons Foundation; Contract grant number(s): 177894 and R01 MH086654 and R01 MH86654 (to J. T. N.); Contract grant sponsor: Oregon Clinical and Translational Institute; Contract grant number: UL1TR000128 (to D. A. F.). 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Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 6032 EP 6048 DI 10.1002/hbm.22603 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900023 PM 25116862 ER PT J AU Ye, AX Leung, RC Schafer, CB Taylor, MJ Doesburg, SM AF Ye, Annette X. Leung, Rachel C. Schaefer, Carmen B. Taylor, Margot J. Doesburg, Sam M. TI Atypical Resting Synchrony in Autism Spectrum Disorder SO HUMAN BRAIN MAPPING LA English DT Article DE autism spectrum disorder; resting-state; neural oscillations; functional connectivity; magnetoencephalography; graph theory; developmental cognitive neuroscience; phase synchrony; social cognition ID GAMMA-BAND SYNCHRONIZATION; BRAIN FUNCTIONAL NETWORKS; PHASE-LAG INDEX; BASAL GANGLIA; WHITE-MATTER; FACIAL EXPRESSIONS; SPATIAL NAVIGATION; SYMPTOM SEVERITY; SOCIAL DEFICITS; NEURAL SYSTEMS AB Autism spectrum disorder (ASD) is increasingly understood to be associated with aberrant functional brain connectivity. Few studies, however, have described such atypical neural synchrony among specific brain regions. Here, we used magnetoencephalography (MEG) to characterize alterations in functional connectivity in adolescents with ASD through source space analysis of phase synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and 15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided reconstruction of neural activity at various cortical and subcortical regions was performed and inter-regional phase synchrony was calculated in physiologically relevant frequency bands. Using a multilevel approach, we characterized atypical resting-state synchrony within specific anatomically defined networks as well as altered network topologies at both regional and whole-network scales. Adolescents with ASD demonstrated frequency-dependent alterations in inter-regional functional connectivity. Hyperconnectivity was observed among the frontal, temporal, and subcortical regions in beta and gamma frequency ranges. In contrast, parietal and occipital regions were hypoconnected to widespread brain regions in theta and alpha bands in ASD. Furthermore, we isolated a hyperconnected network in the gamma band in adolescents with ASD which encompassed orbitofrontal, subcortical, and temporal regions implicated in social cognition. Results from graph analyses confirmed that frequency-dependent alterations of network topologies exist at both global and local levels. We present the first source-space investigation of oscillatory phase synchrony in resting-state MEG in ASD. This work provides evidence of atypical connectivity at physiologically relevant time scales and indicates that alterations of functional connectivity in adolescents with ASD are frequency dependent and region dependent. Hum Brain Mapp 35:6049-6066, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Ye, Annette X.; Leung, Rachel C.; Schaefer, Carmen B.; Taylor, Margot J.; Doesburg, Sam M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Ye, Annette X.; Taylor, Margot J.; Doesburg, Sam M.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Ye, Annette X.; Leung, Rachel C.; Taylor, Margot J.; Doesburg, Sam M.] Hosp Sick Children Res Inst, Toronto, ON, Canada. [Leung, Rachel C.; Taylor, Margot J.; Doesburg, Sam M.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Schaefer, Carmen B.] Heidelberg Univ, Inst Anat & Cell Biol, D-69115 Heidelberg, Germany. [Taylor, Margot J.; Doesburg, Sam M.] Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. [Taylor, Margot J.] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada. RP Ye, AX (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. 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Brain Mapp. PD DEC PY 2014 VL 35 IS 12 BP 6049 EP 6066 DI 10.1002/hbm.22604 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AS6WA UT WOS:000344398900024 PM 25116896 ER PT J AU Ruiz-Robledillo, N Gonzalez-Bono, E Moya-Albiol, L AF Ruiz-Robledillo, Nicolas Gonzalez-Bono, Esperanza Moya-Albiol, Luis TI Lack of institutional support entails disruption in cortisol awakening response in caregivers of people with high-functioning autism SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE caregivers; cortisol awakening response; health; high-functioning autism; institutional support ID RANDOMIZED CONTROLLED-TRIAL; DEVELOPMENTAL-DISABILITIES; SPECTRUM DISORDERS; SALIVARY CORTISOL; BEHAVIOR PROBLEMS; CHILDREN; STRESS; PARENTS; HEALTH; INTERVENTION AB Several studies have found disruptions in cortisol awakening response in informal caregivers. Institutional support may modulate these effects, and this study analyses how the health of caregivers is affected when institutional support is provided for families of people with high-functioning autism. Self-reported health, depression and cortisol awakening response were analysed in three groups: supported caregivers, non-supported caregivers and non-caregivers. Non-supported caregivers presented higher somatic symptoms and lower cortisol awakening response than the supported caregiver and non-caregiver groups. A high number of somatic symptoms and low functionality of offspring were related to a lower cortisol awakening response only in the non-supported caregiver group. These findings demonstrate the importance of institutional support for improving the health of caregivers. C1 [Ruiz-Robledillo, Nicolas; Gonzalez-Bono, Esperanza; Moya-Albiol, Luis] Univ Valencia, Valencia 46010, Spain. 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Health Psychol. PD DEC PY 2014 VL 19 IS 12 BP 1586 EP 1596 DI 10.1177/1359105313496444 PG 11 WC Psychology, Clinical SC Psychology GA AU7ED UT WOS:000345762600011 PM 23933951 ER PT J AU Hubbard, KL Anderson, SE Curtin, C Must, A Bandini, LG AF Hubbard, Kristie L. Anderson, Sarah E. Curtin, Carol Must, Aviva Bandini, Linda G. TI A Comparison of Food Refusal Related to Characteristics of Food in Children with Autism Spectrum Disorder and Typically Developing Children SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Autism spectrum disorder; Nutrition; Feeding; Children; Fruit and vegetable intake ID SENSORY PROFILE; DIETARY PATTERNS; YOUNG-CHILDREN; SYMPTOMS; SELECTIVITY; VALIDATION; BEHAVIORS AB Parents of children with autism spectrum disorder (ASD) frequently report child food refusal based on characteristics of food. Our study sought to determine whether parent report of food refusal based on the characteristics of food was greater in children with ASD than in typically developing children, associated with a greater percentage of foods refused of those offered, and associated with fruit and vegetable intake. A modified food frequency questionnaire was used to determine overall food refusal as well as fruit and vegetable intake. Parent-reported food refusal related to characteristics of food (eg, texture/consistency, temperature, brand, color, shape, taste/smell, foods mixed together, or foods touching other foods) was compared between 53 children with ASD and 58 typically developing children aged 3 to 11 years in the Children's Activity and Meal Patterns Study (2007-2008). Children with ASD were significantly more likely to refuse foods based on texture/consistency (77.4% vs 36.2%), taste/smell (49.1% vs 5.2%), mixtures (45.3% vs 25.9%), brand (15.1% vs 1.7%), and shape (11.3% vs 1.7%). No differences between groups were found for food refusal based on temperature, foods touching other foods, or color. Irrespective of ASD status, the percentage of foods refused of those offered was associated with parent reports of food refusal based on all characteristics examined, except temperature. Food refusal based on color was inversely associated with vegetable consumption in both groups. Routine screening for food refusal among children with ASD is warranted to prevent dietary inadequacies that may be associated with selective eating habits. Future research is needed to develop effective and practical feeding approaches for children with ASD. C1 [Hubbard, Kristie L.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Anderson, Sarah E.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Curtin, Carol] Univ Massachusetts, Sch Med, Charlestown, MA USA. [Curtin, Carol] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Univ Ctr Excellence Dev Disabil, Charlestown, MA USA. [Curtin, Carol; Bandini, Linda G.] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Leadership Educ Neurodev Disabil Programs, Charlestown, MA USA. [Must, Aviva] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Must, Aviva] Tufts Univ, Sch Med, Publ Hlth Profess Degree Programs, Boston, MA 02111 USA. [Bandini, Linda G.] Univ Massachusetts, Sch Med, Dept Pediat, Charlestown, MA USA. [Bandini, Linda G.] Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA. RP Hubbard, KL (reprint author), Tufts Univ, Friedman Sch Nutr Sci & Policy, 150 Harrison Ave, Boston, MA 02111 USA. EM Kristie.hubbard@tufts.edu FU National Institutes of Health [HD048989, HD004147-33A2]; Boston Obesity Nutrition Research Center [DK046200-14] FX This work was supported by National Institutes of Health grant nos. HD048989 and HD004147-33A2, and the Boston Obesity Nutrition Research Center grant no. DK046200-14. 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Acad. Nutr. Diet. PD DEC PY 2014 VL 114 IS 12 BP 1981 EP 1987 DI 10.1016/j.jand.2014.04.017 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AU4FK UT WOS:000345565100014 PM 24928779 ER PT J AU Chawarska, K Shic, F Macari, S Campbell, DJ Brian, J Landa, R Hutman, T Nelson, CA Ozonoff, S Tager-Flusberg, H Young, GS Zwaigenbaum, L Cohen, IL Charman, T Messinger, DS Klin, A Johnson, S Bryson, S AF Chawarska, Katarzyna Shic, Frederick Macari, Suzanne Campbell, Daniel J. Brian, Jessica Landa, Rebecca Hutman, Ted Nelson, Charles A. Ozonoff, Sally Tager-Flusberg, Helen Young, Gregory S. Zwaigenbaum, Lonnie Cohen, Ira L. Charman, Tony Messinger, Daniel S. Klin, Ami Johnson, Scott Bryson, Susan TI 18-Month Predictors of Later Outcomes in Younger Siblings of Children With Autism Spectrum Disorder: A Baby Siblings Research Consortium Study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ASD; high-risk siblings; infants; broader autism phenotype; predictors of outcomes ID RISK; DIAGNOSIS AB Objective: Younger siblings of children with autism spectrum disorder (ASD) are at high risk (HR) for developing ASD as well as features of the broader autism phenotype. Although this complicates early diagnostic considerations in this cohort, it also provides an opportunity to examine patterns of behavior associated specifically with ASD compared to other developmental outcomes. Method: We applied Classification and Regression Trees (CART) analysis to individual items of the Autism Diagnostic Observation Schedule (ADOS) in 719 HR siblings to identify behavioral features at 18 months that were predictive of diagnostic outcomes (ASD, atypical development, and typical development) at 36 months. Results: Three distinct combinations of features at 18 months were predictive of ASD outcome: poor eye contact combined with lack of communicative gestures and giving; poor eye contact combined with a lack of imaginative play; and lack of giving and presence of repetitive behaviors, but with intact eye contact. These 18-month behavioral profiles predicted ASD versus non-ASD status at 36 months with 82.7% accuracy in an initial test sample and 77.3% accuracy in a validation sample. Clinical features at age 3 years among children with ASD varied as a function of their 18-month symptom profiles. Children with ASD who were misclassified at 18 months were higher functioning, and their autism symptoms increased between 18 and 36 months. Conclusion: These findings suggest the presence of different developmental pathways to ASD in HR siblings. Understanding such pathways will provide clearer targets for neural and genetic research and identification of developmentally specific treatments for ASD. C1 [Chawarska, Katarzyna; Shic, Frederick; Macari, Suzanne] Yale Univ, Sch Med, New Haven, CT USA. [Campbell, Daniel J.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Brian, Jessica] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Landa, Rebecca] Johns Hopkins Sch Med, Kennedy Krieger Inst, Baltimore, MD USA. [Hutman, Ted; Johnson, Scott] Univ Calif Los Angeles, Los Angeles, CA USA. [Nelson, Charles A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nelson, Charles A.] Boston Childrens Hosp, Boston, MA 02115 USA. [Ozonoff, Sally; Young, Gregory S.] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Davis, CA 95616 USA. [Tager-Flusberg, Helen] Boston Univ, Boston, MA 02215 USA. [Zwaigenbaum, Lonnie] Univ Alberta, Edmonton, AB, Canada. [Cohen, Ira L.] New York State Inst Basic Res Dev Disabil, Albany, NY USA. [Charman, Tony] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Messinger, Daniel S.] Univ Miami, Coral Gables, FL 33124 USA. [Klin, Ami] Childrens Healthcare Atlanta, Marcus Autism Ctr, Atlanta, GA USA. [Klin, Ami] Emory Univ, Atlanta, GA 30322 USA. [Bryson, Susan] Dalhousie Univ, Halifax, NS, Canada. RP Chawarska, K (reprint author), Yale Child Study Ctr, 40 Temple,Suite 7D, New Haven, CT 06510 USA. EM Katarzyna.chawarska@yale.edu FU Autism Speaks (AS); National Institutes of Health (NIH) [P01 HD003008, R01MH087554, CTSA UL1 RR024139, MH096961, MH068172, HD055784, MH068398, R01DC010290, R21DC008637, R01HD057284, R01GM105004, P50MH100029, R01MH083727, R01MH059630]; UK Medical Research Council; European Science Foundation [BM1004]; FAR; Canadian Institutes of Health Research (CIHR); NeuroDevNet; Simons Foundation; AS; AS Canada FX Autism Speaks (AS) provided funding for the creation of the Baby Siblings Research Consortium (BSRC) database. Data collection, analyses, and manuscript preparation were supported by the National Institutes of Health (NIH) grants P01 HD003008, Project 1 (K.C.), R01MH087554 (Principal Investigator [PI]: K.C.), CTSA UL1 RR024139 (F.S.), MH096961 (T.H.), MH068172 (T.H.), HD055784 (T.H. and S.J.), MH068398 (PI: S.O.), R01DC010290 (Multiple Principal Investigators [MPI): H.T.F. and C.A.N.), R21DC008637 (PI H.T F.), R01HD057284 and R01GM105004 (D.S.M.), P50MH100029 (A.K.), R01MH083727 (A.K.), and R01MH059630 (R.L.), UK Medical Research Council (T.C.), European Science Foundation Cooperation in Science and Technology (COST) Action BM1004 (ESSEA) under FP7 (T.C.), FAR Fund (MPI: K.C., F.S, Fred Volkmar, MD), Canadian Institutes of Health Research (CIHR) (J.B., S.B., L.Z.), NeuroDevNet (J.B., S B., L.Z.), Simons Foundation (PI: C.A N.), AS Pilot Grant (PI: H.T.F), AS Postdoctoral Fellowship (D J.C), and AS Canada (J.B., S.B., L.Z.). 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Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2014 VL 53 IS 12 BP 1317 EP 1327 DI 10.1016/j.jaac.2014.09.015 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AU7WG UT WOS:000345808600009 PM 25457930 ER PT J AU Braund, CC Roosevelt, GE McCourt, EA Weisz, K AF Braund, Cortney C. Roosevelt, Genie E. McCourt, Emily A. Weisz, Keith TI The 2012 PEMpix Photograph Competition Award Winner Making a Case for Pringles-Flavored Carrots SO PEDIATRIC EMERGENCY CARE LA English DT Article DE vitamin A deficiency; xerophthalmia; corneal ulcer ID AUTISTIC-CHILD; DEFICIENCY; XEROPHTHALMIA; KERATOMALACIA AB This is a case report of a 14-year-old boy with autism who presented with photophobia. Physical examination was significant for bilateral corneal ulcers. Differential diagnosis of this chief complaint and the management of the suspected condition are discussed. This case was presented at the Section of Emergency Medicine Meeting at the National Conference and Exhibition of the American Academy of Pediatrics in 2012 and was awarded first place in the PEMpix photograph competition. C1 [Braund, Cortney C.; Roosevelt, Genie E.; Weisz, Keith] Univ Colorado Denver, Childrens Hosp Colorado, Dept Pediat, Sect Emergency Med, Aurora, CO 80045 USA. [McCourt, Emily A.] Univ Colorado Denver, Childrens Hosp Colorado, Dept Pediat Ophthalmol, Aurora, CO 80045 USA. RP Braund, CC (reprint author), Univ Colorado Denver, Childrens Hosp Colorado, Dept Pediat, Sect Emergency Med, 13123 East 16th Ave,Box 251, Aurora, CO 80045 USA. 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Emerg. Care PD DEC PY 2014 VL 30 IS 12 BP 900 EP 901 PG 2 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA AU9KX UT WOS:000345912500016 PM 25469602 ER PT J AU Pyhala, R Hovi, P Lahti, M Sammallahti, S Lahti, J Heinonen, K Pesonen, AK Strang-Karlsson, S Eriksson, JG Andersson, S Jarvenpaa, AL Kajantie, E Raikkonen, K AF Pyhala, Riikka Hovi, Petteri Lahti, Marius Sammallahti, Sara Lahti, Jari Heinonen, Kati Pesonen, Anu-Katriina Strang-Karlsson, Sonja Eriksson, Johan G. Andersson, Sture Jarvenpaa, Anna-Liisa Kajantie, Eero Raikkonen, Katri TI Very Low Birth Weight, Infant Growth, and Autism-Spectrum Traits in Adulthood SO PEDIATRICS LA English DT Article DE autism-spectrum; preterm birth; very low birth weight; infant growth ID FOR-GESTATIONAL-AGE; YOUNG-ADULTS; PRETERM BIRTH; PSYCHIATRIC-DISORDERS; POSTNATAL-GROWTH; MENTAL-HEALTH; BORN PRETERM; QUOTIENT AQ; CHILDREN; OUTCOMES AB OBJECTIVES: We examined whether adults born preterm at very low birth weight (VLBW; <1500 g) differ from term-born adults in autism-spectrum traits, and whether among VLBW adults, growth in infancy is associated with these traits. METHODS: A total of 110 VLBW and 104 term-born adults of the Helsinki Study of Very Low Birth Weight Adults completed the Autism-Spectrum Quotient yielding total, social interaction, and attention to detail sum scores. Growth in weight, length, and head circumference from birth to term and from term to 1 year of corrected age was determined as standardized residuals reflecting growth conditional on previous history. RESULTS: VLBW adults scored higher than term-born controls on social interaction sum score, indicating higher autism-spectrum traits. In contrast, they scored lower on attention to detail sum score, indicating lower autism-spectrum traits. Within the VLBW group, faster growth in weight, length, and head circumference from birth to term was associated with lower total and social interaction sum scores. In this group, growth from term to 1 year was not associated with autism-spectrum traits. CONCLUSIONS: Among those born preterm at VLBW, the risk for higher levels of autism-spectrum traits, particularly related to social interaction, may persist into adulthood. Faster growth from birth to term may ameliorate these effects, suggesting that targeted interventions could aid long-term neurodevelopment. C1 [Pyhala, Riikka; Lahti, Marius; Sammallahti, Sara; Lahti, Jari; Heinonen, Kati; Pesonen, Anu-Katriina; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Inst Clin Med, FIN-00014 Helsinki, Finland. [Hovi, Petteri; Strang-Karlsson, Sonja; Andersson, Sture; Jarvenpaa, Anna-Liisa; Kajantie, Eero] Univ Helsinki, Childrens Hosp, FIN-00014 Helsinki, Finland. [Hovi, Petteri; Strang-Karlsson, Sonja; Andersson, Sture; Jarvenpaa, Anna-Liisa; Kajantie, Eero] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Hovi, Petteri; Eriksson, Johan G.; Kajantie, Eero] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, FIN-00014 Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Kajantie, Eero] Oulu Univ, Cent Hosp, Med Res Ctr Oulu, Dept Obstet & Gynaecol, SF-90220 Oulu, Finland. [Kajantie, Eero] Univ Oulu, Oulu, Finland. RP Pyhala, R (reprint author), Univ Helsinki, Inst Behav Sci, POB 9, FIN-00014 Helsinki, Finland. EM riikka.pyhala@helsinki.fi FU Academy of Finland; Emil Aaltonen Foundation; Finnish Foundation for Diabetes Research; Finnish Medical Society Duodecim; Foundation for Pediatric Research; Finnish Special Governmental Subsidy for Health Sciences; Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Maud Kuistila Memorial Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Yrjo Jahnsson Foundation FX This study was part of the Helsinki Study of Very Low Birth Weight Adults funded by the Academy of Finland, the Emil Aaltonen Foundation, the Finnish Foundation for Diabetes Research, the Finnish Medical Society Duodecim, Foundation for Pediatric Research, the Finnish Special Governmental Subsidy for Health Sciences, the Jalmari and Rauha Ahokas Foundation, the Juho Vainio Foundation, the Maud Kuistila Memorial Foundation, the Novo Nordisk Foundation, the Paivikki and Sakari Sohlberg Foundation, the Signe and Ane Gyllenberg Foundation, the Sigrid Juselius Foundation, and the Yrjo Jahnsson Foundation. 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Guthrie, Whitney Woods, Juliann Schatschneider, Christopher Holland, Renee D. Morgan, Lindee Lord, Catherine TI Parent-Implemented Social Intervention for Toddlers With Autism: An RCT SO PEDIATRICS LA English DT Article DE autism; early intervention; toddlers; parent-implemented; outcomes ID RANDOMIZED CONTROLLED-TRIAL; DISORDER EARLY IDENTIFICATION; SPECTRUM DISORDERS; DEVELOPMENTAL PROFILE; JOINT ATTENTION; YOUNG-CHILDREN; UNITED-STATES; 2ND YEAR; PART C; COMMUNICATION AB OBJECTIVES: To compare the effects of two 9-month parent-implemented interventions within the Early Social Interaction (ESI) Project. Both individual-ESI, offered 2 or 3 times per week at home or in the community, and group-ESI, offered once per week in a clinic, taught parents how to embed strategies to support social communication throughout everyday activities. METHODS: Participants in the randomized controlled trial included 82 children diagnosed with autism spectrum disorder at 16 to 20 months. Children were matched on pretreatment nonverbal developmental level and pairs were randomly assigned to treatment condition. Child outcomes included measures of social communication, autism symptoms, adaptive behavior, and developmental level. Child outcomes are reported from baseline to the end of the 9-month interventions. RESULTS: Children in individual-ESI showed differential change on a standardized examiner-administered observational measure of social communication, as they improved at a faster rate than children in group-ESI. Individual-ESI also showed differential efficacy on a parent report measure of communication, daily living, and social skills, as they showed improvement or stability, whereas group-ESI led to worsening or no significant change on these skills. Finally, individual-ESI showed differential change on examiner-administered measures of receptive language skills, as children in individual-ESI improved significantly, whereas group-ESI showed no change. CONCLUSIONS: These findings support the efficacy of individual-ESI compared with group-ESI on child outcomes, suggesting the importance of individualized parent coaching in natural environments. The efficacy of a parent-implemented intervention using little professional time has potential for community viability, which is particularly important in light of the lack of main effects on child outcomes of most other parent-implemented interventions. C1 [Wetherby, Amy M.; Morgan, Lindee] Florida State Univ, Dept Clin Sci, Tallahassee, FL 32303 USA. [Wetherby, Amy M.; Guthrie, Whitney; Woods, Juliann; Holland, Renee D.; Morgan, Lindee] Florida State Univ, Autism Inst, Tallahassee, FL 32303 USA. [Woods, Juliann] Florida State Univ, Sch Commun Sci & Disorders, Tallahassee, FL 32303 USA. [Guthrie, Whitney; Schatschneider, Christopher] Florida State Univ, Dept Psychol, Tallahassee, FL 32303 USA. [Lord, Catherine] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. RP Wetherby, AM (reprint author), Florida State Univ, Autism Inst, 1940 North Monroe St,Suite 72, Tallahassee, FL 32303 USA. EM amy.wetherby@med.fsu.edu FU National Institute of Mental Health [R01MH077730/R01MH078165]; Autism Speaks; Simons Foundation; National Institutes of Health (NIH) FX Supported in part by the National Institute of Mental Health grant R01MH077730/R01MH078165 (A.M.W., C.L.) and funding from Autism Speaks (A.M.W., C.L.) and the Simons Foundation (C.L.). Funded by the National Institutes of Health (NIH). 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PM10; NOx; autism; ADHD; twins ID DEFICIT HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDER; TELEPHONE INTERVIEW; UNITED-STATES; A-TAC; CHILDREN; SWEDEN; INFLAMMATION; ASSOCIATION; POPULATION AB Background: Recent studies have reported associations between air pollution exposure and neurodevelopmental disorders in children, but the role of pre- and postnatal exposure has not been elucidated. Aim: We aimed to explore the risk for autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) among children in relation to pre- and postnatal exposure to air pollution from road traffic. Methods: Parents of 3,426 twins born in Stockholm during 1992-2000 were interviewed, when their children were 9 or 12 years old, for symptoms of neurodevelopmental disorders. Residence time-weighted concentrations of particulate matter with a diameter <10 mu m (PM10) and nitrogen oxides (NOx) from road traffic were estimated at participants' addresses during pregnancy, the first year, and the ninth year of life using dispersion modeling, controlling for seasonal variation. Multivariate regression models were used to examine the association between air pollution exposure and neurodevelopmental outcomes, adjusting for potential confounding factors. Results: No clear or consistent associations were found between air pollution exposure during any of the three time windows and any of the neurodevelopmental outcomes. For example, a 5-95% difference in exposure to NOx during pregnancy was associated with odds ratios (ORs) of 0.92 (95% confidence interval (CI): 0.44-1.96) and 0.90 (95% CI: 0.58-1.40) for ASD and ADHD respectively. A corresponding range in exposure to PM10 during pregnancy was related to ORs of 1.01 (95% CI: 0.52-1.96) and 1.00 (95% CI: 0.68-1.47) for ASD and ADHD. Conclusions: Our data do not provide support for an association between pre- or postnatal exposure to air pollution from road traffic and neurodevelopmental disorders in children. C1 [Gong, Tong; Almqvist, Catarina; Lichtenstein, Paul; Lundholm, Cecilia] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Almqvist, Catarina] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden. [Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders KIND, Dept Womens & Childrens Hlth, SE-17177 Stockholm, Sweden. [Bolte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. [Anckarsater, Henrik] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Pharmacol, Gothenburg, Sweden. [Lind, Tomas; Pershagen, Goran] Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden. [Pershagen, Goran] Karolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden. RP Gong, T (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. EM tong.gong@ki.se FU Swedish Research Council for Health, Working Life and Welfare [FORTE 2012-0573]; Swedish Research Council (VR) [2011-3060]; FORTE; FORMAS; VINNOVA; Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIM-SAM) framework [340-2013-5867]; HKH Kronprinsessan Lovisas forening for barnasjukvard; Strategic Research Program in Epidemiology at Karolinska Institutet FX Financial support was provided through the Swedish Research Council for Health, Working Life and Welfare (FORTE 2012-0573), the Swedish Research Council (VR) 2011-3060, VR in partnership with FORTE, FORMAS, and VINNOVA (cross-disciplinary research program concerning children's and young people's mental health), VR through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIM-SAM) framework, grant No. 340-2013-5867, HKH Kronprinsessan Lovisas forening for barnasjukvard, and the Strategic Research Program in Epidemiology at Karolinska Institutet. 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Hum. Genet. PD DEC PY 2014 VL 17 IS 6 BP 553 EP 562 DI 10.1017/thg.2014.58 PG 10 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA AU6IR UT WOS:000345707600007 PM 25229653 ER PT J AU De Wolf, V Crepel, A Schuit, F van Lommel, L Ceulemans, B Steyaert, J Seuntjens, E Peeters, H Devriendt, K AF De Wolf, Veerle Crepel, An Schuit, Frans van Lommel, Leentje Ceulemans, Berten Steyaert, Jean Seuntjens, Eve Peeters, Hilde Devriendt, Koen TI A Complex Xp11.22 Deletion in a Patient With Syndromic Autism: Exploration of FAM120C as a Positional Candidate Gene for Autism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autism spectrum disorder; candidate gene; deletion; FAM120C; X-linked ID LINKED MENTAL-RETARDATION; CLEFT LIP/CLEFT PALATE; FRAGILE-X-SYNDROME; MESSENGER-RNA; SPECTRUM DISORDERS; FGD1 GENE; PHF8 GENE; EXPRESSION; MUTATION; CHROMOSOME AB We present a male patient with sporadic Aarskog syndrome, cleft palate, mild intellectual disability, and autism spectrum disorder (ASD). A submicroscopic discontiguous deletion was detected on chromosome Xp11.2 encompassing FGD1, FAM120C, and PHF8. That the deletion encompassed FGD1 (exons 2-8) explains the Aarskog features while the deletion of PHF8 most likely explains the cleft palate and mild intellectual disability. We identify FAM120C as a novel X-linked candidate gene for autism for two reasons: first, a larger deletion encompassing FAM120C segregates with autism in a previously reported family and second, there is recent evidence that FAM120C interacts with CYFIP1, part of the FMRP (Fragile X Mental Retardation Protein) network. In the current study, resequencing of FAM120C in 87 Belgian male patients with autism spectrum disorder identified no novel mutations. Expression of Fam120c in mouse tissues showed enriched expression in pituitary, cerebellum, cortex, and pancreatic islets of Langerhans. Additionally, we found a cortical expression pattern of Fam120c similar to that of Fmr1. In conclusion, FAM120C is a novel candidate gene for autism spectrum disorder based on genetic evidence and the brain expression pattern. Thereby we highlight a role for FMRP network genes in ASD. (c) 2014 Wiley Periodicals, Inc. C1 [De Wolf, Veerle; Crepel, An; Peeters, Hilde; Devriendt, Koen] Katholieke Univ Leuven, Univ Hosp Leuven, Ctr Human Genet, Leuven, Belgium. [De Wolf, Veerle; Crepel, An; Steyaert, Jean; Peeters, Hilde; Devriendt, Koen] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [Schuit, Frans; van Lommel, Leentje] Katholieke Univ Leuven, Dept Cellular & Mol Med, Leuven, Belgium. [Ceulemans, Berten] Univ Antwerp, Antwerp Univ Hosp UZA, Dept Neurol Pediat Neurol, Edegem, Belgium. [Steyaert, Jean] Katholieke Univ Leuven, Dept Child & Adolescent Psychiat, Leuven, Belgium. [Steyaert, Jean] Univ Limburg, Acad Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Steyaert, Jean] Maastricht Univ, Res Inst Growth & Dev GROW, Maastricht, Netherlands. [Seuntjens, Eve] Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Mol Biol Celgen, Leuven, Belgium. RP Devriendt, K (reprint author), Univ Leuven, Ctr Human Genet, Herestr 49, B-3000 Leuven, Belgium. EM koenraad.devriendt@uzleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 FU Concerted Research Actions KULeuven [GOA/12/015]; Foundation Marguerite-Marie Delacroix; Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) [IAP P7/43-BeMGI]; Fund for Scientific Research-Flanders FWO, Belgium; Clinical Research Foundation of UZLeuven, Belgium FX Grant sponsor: Concerted Research Actions KULeuven; Grant number: GOA/12/015; Grant sponsor: Foundation Marguerite-Marie Delacroix; Grant sponsor: Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP); Grant number: IAP P7/43-BeMGI; Grant sponsor: Fund for Scientific Research-Flanders FWO, Belgium; Grant sponsor: Clinical Research Foundation of UZLeuven, Belgium. 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J. Med. Genet. A PD DEC PY 2014 VL 164A IS 12 BP 3035 EP 3041 DI 10.1002/ajmg.a.36752 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AU0DJ UT WOS:000345293300011 PM 25258334 ER PT J AU Quintero-Rivera, F Woo, JS Bomberg, EM Wallace, WD Peredo, J Dipple, KM AF Quintero-Rivera, Fabiola Woo, Jennifer S. Bomberg, Eric M. Wallace, W. Dean Peredo, Jane Dipple, Katrina M. TI Duodenal Atresia in 17q12 Microdeletion Including HNF1B: A New Associated Malformation in this Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 17q12 microdeletion; duodenal atresia; hepatocyte nuclear factor beta (HNF1B); renal cysts; prenatal; pathology; TCF2; review ID HEPATOCYTE NUCLEAR FACTOR-1-BETA; AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIANTS; PRUNE-BELLY-SYNDROME; GENOMIC REARRANGEMENTS; CLINICAL SPECTRUM; INTELLECTUAL DISABILITY; CHROMOSOME 17Q12; ZEBRAFISH GUT; RENAL-DISEASE AB Deletions of chromosome 17q12 [OMIM 614527] encompass a wide range of phenotypes, including renal cysts, diabetes mellitus, pancreatic structural abnormalities, genital tract anomalies, developmental delay, learning difficulties, and more recently, autism spectrum disorder and schizophrenia. To date, gastrointestinal malformations have not been fully characterized in this syndrome. In this case report, we describe a four-year-old girl with a 17q12 microdeletion who was born with duodenal atresia, bilateral renal cysts, left kidney dysplasia, a midline cystic structure at the conus medullaris, and dysmorphic features. Both the patient and her affected father were found to have a deletion of 17q12, which encompasses the HNF1B (hepatocyte nuclear factor beta). It is hypothesized that HNF1B may play a role in intestinal differentiation and development. Our clinical report further expands the pre-and post-natal presentation of this rare microdeletion syndrome. (c) 2014 Wiley Periodicals, Inc. C1 [Quintero-Rivera, Fabiola; Woo, Jennifer S.; Wallace, W. Dean] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Quintero-Rivera, Fabiola; Dipple, Katrina M.] UCLA Clin Genom Ctr, Los Angeles, CA USA. [Bomberg, Eric M.; Peredo, Jane; Dipple, Katrina M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Dipple, Katrina M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. RP Quintero-Rivera, F (reprint author), Dept Pathol & Lab Med, 1000 Vet Ave 22-26, Los Angeles, CA 90048 USA. 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A PD DEC PY 2014 VL 164A IS 12 BP 3076 EP 3082 DI 10.1002/ajmg.a.36767 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AU0DJ UT WOS:000345293300016 PM 25256560 ER PT J AU Malli, T Duba, HC Erdel, M Marschon, R Kranewitter, W Deutschbauer, S Kralik, J Diel, E Guenther, B Mueller, D Webersinke, G AF Malli, Theodora Duba, Hans-Christoph Erdel, Martin Marschon, Renate Kranewitter, Wolfgang Deutschbauer, Sabine Kralik, Johanna Diel, Evita Gueenther, Barbara Mueller, Doris Webersinke, Gerald TI Disruption of the ARID1B and ADAMTS6 Loci due to a t(5;6)(q12.3;q25.3) in a Patient With Developmental Delay SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE ADAMTS6; ARID1B; developmental delay; intellectual disability; speech impairment ID CHROMATIN-REMODELING COMPLEX; COFFIN-SIRIS SYNDROME; INTELLECTUAL DISABILITY; CELL-CYCLE; SWI/SNF; HAPLOINSUFFICIENCY; IDENTIFICATION; EXPRESSION; MUTATIONS; FAMILY AB Here, we report on a male patient with developmental delay, speech impairment, mild dysmorphic features, and borderline intellectual disability, bearing a de novo balanced t(5;6)(q11;q25.3). By combining FISH and long distance inverse PCR, we identified two genes, ADAMTS6 and ARID1B, which were disrupted at the translocation breakpoints. Due to the opposing transcriptional directions of the two genes, no fusion transcripts could be formed. ADAMTS6 on chromosome 5 encodes a zinc metalloprotease. To date, there has been no information about the substrates and the exact role of this enzyme protein. ARID1B on chromosome 6 is involved in chromatin remodeling and transcriptional activation and is known to play a role in neural development. To our knowledge, this is the fourth translocation involving ARID1B reported in association with intellectual disability. ARID1B haploinsufficiency has already been described in patients with intellectual disabilities with or without corpus callosum abnormalities, Coffin-Siris syndrome and autism (OMIM 614562 and OMIM 614556). A review of patients with ARID1B mutations reveals their broad phenotypic variability. The phenotype of the present patient is of the mildest described to date and further underscores this observation. We conclude that the most prominent and consistent clinical findings in patients with ARID1B haploinsufficiency are developmental delay, speech impairment and intellectual disability and propose that patients with unresolved genetic background and these clinical findings should be considered for ARID1B mutation screening. (c) 2014 Wiley Periodicals, Inc. C1 [Malli, Theodora; Erdel, Martin; Marschon, Renate; Kranewitter, Wolfgang; Deutschbauer, Sabine; Kralik, Johanna; Webersinke, Gerald] Hosp Barmherzige Schwestern Linz, Dept Internal Med 1, Lab Mol Biol & Tumor Cytogenet, Upper Austria, Austria. [Duba, Hans-Christoph; Gueenther, Barbara; Mueller, Doris] Gen Womens & Childrens Hosp, Dept Human Genet, Linz, Upper Austria, Austria. [Diel, Evita] VKKJ Amstetten, Outpatient Clin, Amstetten, Lower Austria, Austria. RP Webersinke, G (reprint author), Hosp Barmherzige Schwestern, Dept Internal Med, Lab Mol Biol & Tumor Cytogenet, Seilerstaette 4, A-4010 Linz, Austria. EM gerald.webersinke@bhs.at FU Verein zur Foerderung der Humangenetik an der Medizinischen Universitaet Innsbruck FX We thank the patient and his family for their cooperation. We thank the Verein zur Foerderung der Humangenetik an der Medizinischen Universitaet Innsbruck for language editing cost support. 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A PD DEC PY 2014 VL 164A IS 12 BP 3126 EP 3131 DI 10.1002/ajmg.a.36738 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AU0DJ UT WOS:000345293300024 PM 25250687 ER PT J AU Prontera, P Ottaviani, V Toccaceli, D Rogaia, D Ardisia, C Romani, R Stangoni, G Pierini, A Donti, E AF Prontera, Paolo Ottaviani, Valentina Toccaceli, Daniela Rogaia, Daniela Ardisia, Carmen Romani, Rita Stangoni, Gabriela Pierini, Angiolo Donti, Emilio TI Recurrent similar to 100 Kb Microdeletion in the Chromosomal Region 14q11.2, Involving CHD8 Gene, is Associated with Autism and Macrocephaly SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE microdeletion 14q11.2; CHD8 gene; SUPT16H gene; autism; macrocephaly; recurrent syndrome ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; LOCI AB The most frequent causes of Intellectual Disability (ID)/Autism Spectrum Disorders (ASDs) are chromosomal abnormalities, genomic rearrangements and submicroscopic deletions coupled with duplications. We report here on an 11-year-old girl showing autism, macrocephaly, and facial dysmorphism, in which array-CGH showed a de novo microdeletion of approximate to 114Kb in the 14q11.2 chromosomal region, involving the SUPT16H, CHD8, and RAB2B genes. Four patients with ID and/or ASD and/or macrocephaly with overlapping deletions have been previously described: three showed very large rearrangements (>1Mb), while one had a microdeletion of approximate to 101Kb, largely overlapping the one reported herein. The minimal critical region, considering present and previous cases, contains the SUPT16H and CHD8 genes. Notably, recent studies also disclosed CHD8 heterozygous loss-of-function mutations in patients with ASD and macrocephaly. Our finding shows the presence of a recurrent microdeletion associated with a clinically recognizable phenotype, and further on underlines the pivotal role of CHD8 gene in the pathogenesis of the disorder. (c) 2014 Wiley Periodicals, Inc. 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PD DEC PY 2014 VL 30 IS 4 BP 298 EP 313 DI 10.3109/07434618.2014.966206 PG 16 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA AU3MN UT WOS:000345517600002 PM 25384797 ER PT J AU Hemsley, B Balandin, S AF Hemsley, Bronwyn Balandin, Susan TI A Metasynthesis of Patient-Provider Communication in Hospital for Patients with Severe Communication Disabilities: Informing New Translational Research SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Communication disability; Complex communication needs; Patient safety; Patient care; Augmentative and alternative communication; Metasynthesis ID HEALTH-CARE PROVIDERS; OF-THE-LITERATURE; CEREBRAL-PALSY; COMPLEX COMMUNICATION; INTELLECTUAL DISABILITIES; ENVIRONMENTAL-FACTORS; INTERNATIONAL CLASSIFICATION; DEVELOPMENTAL-DISABILITY; SUPPORTING ADULTS; ADVERSE EVENTS AB Poor patient-provider communication in hospital continues to be cited as a possible causal factor in preventable adverse events for patients with severe communication disabilities. Yet to date there are no reports of empirical interventions that investigate or demonstrate an improvement in communication in hospital for these patients. The aim of this review was to synthesize the findings of research into communication in hospital for people with severe communication disabilities arising from lifelong and acquired stable conditions including cerebral palsy, autism, intellectual disability, aphasia following stroke, but excluding progressive conditions and those solely related to sensory impairments of hearing or vision. Results revealed six core strategies suggested to improve communication in hospital: (a) develop services, systems, and policies that support improved communication, (b) devote enough time to communication, (c) ensure adequate access to communication tools (nurse call systems and communication aids), (d) access personally held written health information, (e) collaborate effectively with carers, spouses, and parents, and (f) increase the communicative competence of hospital staff. Currently there are no reports that trial or validate any of these strategies specifically in hospital settings. Observational and evaluative research is needed to investigate the ecological validity of strategies proposed to improve communication. C1 [Hemsley, Bronwyn] Univ Newcastle, Sch Humanities & Social Sci, Fac Educ & Arts, Callaghan, NSW 2304, Australia. [Balandin, Susan] Deakin Univ, Fac Hlth, Sch Hlth & Social Dev, Geelong, Vic 3217, Australia. 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Altern. Commun. PD DEC PY 2014 VL 30 IS 4 BP 329 EP 343 DI 10.3109/07434618.2014.955614 PG 15 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA AU3MN UT WOS:000345517600004 PM 25229213 ER PT J AU Bunning, K Gona, JK Newton, CR Hartley, S AF Bunning, Karen Gona, Joseph K. Newton, Charles R. Hartley, Sally TI Caregiver Perceptions of Children who have Complex Communication Needs Following a Home-based Intervention Using Augmentative and Alternative Communication in Rural Kenya: An Intervention Note SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Low-income country; Developmental condition; Home-based intervention; Augmentative and alternative communication ID YOUNG-CHILDREN; INTELLECTUAL DISABILITIES; BEHAVIORAL INTERVENTION; CEREBRAL-PALSY; HEALTH; BARRIERS; AUTISM; SURVEILLANCE; IMPAIRMENTS; COUNTRIES AB A high level of unmet communication need exists amongst children with developmental disabilities in sub-Saharan Africa. This study investigated preliminary evidence of the impact associated with a home-based, caregiver-implemented intervention employing AAC methods, with nine children in rural Kenya who have complex communication needs. The intervention used mainly locally-sourced low-tech materials, and was designed to make use of the child's strengths and the caregiver's natural expertise. A pretest-posttest design was used in the study. Data were gathered using an adapted version of the Communication Profile, which was based on the International Classification of Functioning, Disability, and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was applied to data from the first two sections of the Communication Profile-Adapted. Qualitative analysis was conducted on the final section. The data provided evidence of statistically significant positive changes in caregiver perceptions of communication at the levels of Body Structure and Function, and Activities for Communication. Also, analysis of the Participation for Communication section revealed some expansion to the children's social activities. The potential impact of the home-based intervention would benefit from investigation on a larger scale. 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Altern. Commun. PD DEC PY 2014 VL 30 IS 4 BP 344 EP 356 DI 10.3109/07434618.2014.970294 PG 13 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA AU3MN UT WOS:000345517600005 PM 25379627 ER PT J AU Skurtveit, S Selmer, R Roth, C Hernandez-Diaz, S Handal, M AF Skurtveit, S. Selmer, R. Roth, C. Hernandez-Diaz, S. Handal, M. TI Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Children; depression; language competence; MoBa; pregnancy; SSRI exposure ID SEROTONIN REUPTAKE INHIBITORS; FOLIC-ACID SUPPLEMENTS; MATERNAL DEPRESSION; NORWEGIAN-MOTHER; CHILD-COHORT; NEURODEVELOPMENT; FLUOXETINE; OUTCOMES; AUTISM; DRUGS AB ObjectiveTo examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. DesignPopulation-based prospective pregnancy cohort study. SettingThe Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. Population45266 women with 51748 singleton pregnancies. MethodsThe association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. Main outcome measuresChildren's language competence at age three measured by maternal report on a validated language grammar scale. ResultsWomen reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and long-term symptoms, respectively. ConclusionsProlonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect. C1 [Skurtveit, S.; Selmer, R.; Roth, C.; Handal, M.] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Skurtveit, S.] Univ Oslo, Norwegian Ctr Addict Res, Oslo, Norway. [Hernandez-Diaz, S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Skurtveit, S (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404 Nydalen, Oslo, Norway. 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This article focuses on the intricacies of social interaction, emphasizing the link between alignment and affiliation, and the range and importance of verbal and nonverbal interactive devices available to children. Analysis of the way in which two girls, one of whom has been diagnosed with Asperger's Syndrome, engage in spontaneous activities demonstrates the potential for interactional difficulty due to the unscripted nature of the interaction. The article argues for further research into how improvised, unscripted interactions are initiated within moment-by-moment talk, how they unfold, and how they are brought to a close in everyday contexts in order to understand how children create their social worlds. C1 [Rendle-Short, Johanna] Australian Natl Univ, Hackett, ACT 2602, Australia. [Cobb-Moore, Charlotte; Danby, Susan] Queensland Univ Technol, Brisbane, Qld 4001, Australia. 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PD DEC PY 2014 VL 16 IS 6 BP 792 EP 815 DI 10.1177/1461445614546248 PG 24 WC Communication SC Communication GA AU2PO UT WOS:000345460600005 ER PT J AU Kumari, D Bhattacharya, A Nadel, J Moulton, K Zeak, NM Glicksman, A Dobkin, C Brick, DJ Schwartz, PH Smith, CB Klann, E Usdin, K AF Kumari, Daman Bhattacharya, Aditi Nadel, Jeffrey Moulton, Kristen Zeak, Nicole M. Glicksman, Anne Dobkin, Carl Brick, David J. Schwartz, Philip H. Smith, Carolyn B. Klann, Eric Usdin, Karen TI Identification of Fragile X Syndrome Specific Molecular Markers in Human Fibroblasts: A Useful Model to Test the Efficacy of Therapeutic Drugs SO HUMAN MUTATION LA English DT Article DE Fragile X syndrome; FMR1; FMRP; protein synthesis; S6K1; fibroblasts ID CEREBRAL PROTEIN-SYNTHESIS; TISSUE-SPECIFIC EXPRESSION; MOUSE MODEL; MESSENGER-RNA; TRANSLATIONAL CONTROL; SYNAPTIC PLASTICITY; MENTAL-RETARDATION; KNOCKOUT MICE; STEM-CELLS; FMRP AB Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and autism. It is caused by the absence of the fragile X mental retardation 1 (FMR1) gene product, fragile X mental retardation protein (FMRP), an RNA-binding protein involved in the regulation of translation of a subset of brain mRNAs. In Fmr1 knockout mice, the absence of FMRP results in elevated protein synthesis in the brain as well as increased signaling of many translational regulators. Whether protein synthesis is also dysregulated in FXS patients is not firmly established. Here, we demonstrate that fibroblasts from FXS patients have significantly elevated rates of basal protein synthesis along with increased levels of phosphorylated mechanistic target of rapamycin (p-mTOR), phosphorylated extracellular signal regulated kinase 1/2, and phosphorylated p70 ribosomal S6 kinase 1 (p-S6K1). The treatment with small molecules that inhibit S6K1 and a known FMRP target, phosphoinositide 3-kinase (PI3K) catalytic subunit p110, lowered the rates of protein synthesis in both control and patient fibroblasts. Our data thus demonstrate that fibroblasts from FXS patients may be a useful in vitro model to test the efficacy and toxicity of potential therapeutics prior to clinical trials, as well as for drug screening and designing personalized treatment approaches. C1 [Kumari, Daman; Usdin, Karen] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Bhattacharya, Aditi; Zeak, Nicole M.; Klann, Eric] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Nadel, Jeffrey; Moulton, Kristen; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bethesda, MD 20892 USA. [Glicksman, Anne; Dobkin, Carl] New York State Inst Basic Res Dev Disabil, Dept Human Genet, New York, NY USA. [Brick, David J.; Schwartz, Philip H.] Childrens Hosp Orange Cty Res Inst, Orange, CA USA. RP Kumari, D (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, 8 Ctr Dr,Bldg 8,Room 2A19, Bethesda, MD 20892 USA. EM damank@helix.nih.gov FU Intramural Research Programs of the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health Center for Regenerative Medicine; National Institute of Mental Health [NS034007, NS047384]; New York State Department of People with Developmental Disabilities; Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [R01HD059967] FX Contract grant sponsors: Intramural Research Programs of the National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health Center for Regenerative Medicine and the National Institute of Mental Health; Extramural Program of the National Institutes of Health (NS034007 and NS047384 to E.K.); New York State Department of People with Developmental Disabilities; Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (R01HD059967). 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Mutat. PD DEC PY 2014 VL 35 IS 12 BP 1485 EP 1494 DI 10.1002/humu.22699 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AU3MK UT WOS:000345517300012 PM 25224527 ER PT J AU Tellegen, CL Sanders, MR AF Tellegen, Cassandra L. Sanders, Matthew R. TI A Randomized Controlled Trial Evaluating a Brief Parenting Program With Children With Autism Spectrum Disorders SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE randomized controlled trial; Triple P; Stepping Stones Triple P; autism spectrum disorders (ASD); behavioral family intervention ID STONES TRIPLE-P; DISABILITY AB Objective: This randomized controlled trial evaluated the efficacy of Primary Care Stepping Stones Triple P, a brief individualized parenting program, in a sample of parents of children with autism spectrum disorder (ASD). Method: Sixty-four parents of children aged 2-9 years (M = 5.67, SD = 2.14) with an ASD diagnosis participated in the study. Eighty-six percent of children were male, and 89% of parents identified their child's ethnicity as Australian/White. Families were randomly assigned to 1 of 2 conditions (intervention or care-as-usual) and were assessed at 3 time points (preintervention, postintervention, and 6-month follow-up). Parents completed a range of questionnaires to assess changes in child behavior (Eyberg Child Behavior Inventory) and parent outcomes (Parenting Scale, Depression Anxiety Stress Scale-21, Parent Problem Checklist, Relationship Quality Inventory, Parental Stress Scale) and 30-min home observations of parent-child interactions. Results: Relative to the care-as-usual group, significant short-term improvements were found in the intervention group on parent-reported child behavior problems, dysfunctional parenting styles, parenting confidence, and parental stress, parental conflict, and relationship happiness. No significant intervention effects were found on levels of parental depression or anxiety, or on observed child disruptive and parent aversive behavior. The effect sizes for significant variables ranged from medium to large. Short-term effects were predominantly maintained at 6-month follow-up, and parents reported high levels of goal achievement and satisfaction with the program. Conclusions: The results indicate that a brief low intensity version of Stepping Stones Triple P is an efficacious intervention for parents of children with ASD. C1 [Tellegen, Cassandra L.; Sanders, Matthew R.] Univ Queensland, Parenting & Family Support Ctr, Sch Psychol, St Lucia, Qld 4072, Australia. RP Tellegen, CL (reprint author), Univ Queensland, Parenting & Family Support Ctr, Sch Psychol, St Lucia, Qld 4072, Australia. 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Vives, Laura Malig, Maika Denman, Laura Raja, Archana Stuart, Andrew Tang, Joyce Munson, Brenton Shaffer, Lisa G. Amemiya, Chris T. Wilson, Richard K. Eichler, Evan E. TI Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability SO NATURE GENETICS LA English DT Article ID COPY-NUMBER VARIATION; RECENT SEGMENTAL DUPLICATIONS; HUMAN GENOME; INVERTED REPEATS; RECURRENT MICRODELETIONS; DNA PALINDROMES; INCREASE RISK; SEQUENCE; REARRANGEMENTS; DISORDERS AB Recurrent deletions of chromosome 15q13.3 associate with intellectual disability, schizophrenia, autism and epilepsy. To gain insight into the instability of this region, we sequenced it in affected individuals, normal individuals and nonhuman primates. We discovered five structural configurations of the human chromosome 15q13.3 region ranging in size from 2 to 3 Mb. These configurations arose recently (similar to 0.5-0.9 million years ago) as a result of human-specific expansions of segmental duplications and two independent inversion events. All inversion breakpoints map near GOLGA8 core duplicons a similar to 14-kb primate-specific chromosome 15 repeat that became organized into larger palindromic structures. GOLGA8-flanked palindromes also demarcate the breakpoints of recurrent 15q13.3 microdeletions, the expansion of chromosome 15 segmental duplications in the human lineage and independent structural changes in apes. The significant clustering (P = 0.002) of breakpoints provides mechanistic evidence for the role of this core duplicon and its palindromic architecture in promoting the evolutionary and disease-related instability of chromosome 15. C1 [Antonacci, Francesca; Miroballo, Mattia] Univ Bari Aldo Moro, Dipartimento Biol, Bari, Italy. [Dennis, Megan Y.; Huddleston, John; Sudmant, Peter H.; Vives, Laura; Malig, Maika; Denman, Laura; Raja, Archana; Munson, Brenton; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Huddleston, John; Vives, Laura; Raja, Archana; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Steinberg, Karyn Meltz; Graves, Tina A.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] Signature Genom Labs LLC, Spokane, WA USA. [Stuart, Andrew; Tang, Joyce; Amemiya, Chris T.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Shaffer, Lisa G.] Genet Vet Sci Inc, Paw Print Genet, Spokane, WA USA. RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. EM eee@gs.washington.edu RI Antonacci, Francesca/F-5457-2013 FU US National Institutes of Health [HG002385, HG004120]; National Institute of Neurological Disorder and Stroke of the US National Institutes of Health [K99NS083627] FX We thank M. Ventura, C. Campbell and H.C. Mefford for useful discussions and T. Brown for critical review of the manuscript. We also thank S. Diede, W Tanaka, B. Brewer, C. Payen, L. Harshman and K. Penewit for experimental advice and support for the palindromic snapback assay. We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W Stone, J. Sutcliffe, C. Walsh, Z. Warren and E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. This work was supported, in part, by US National Institutes of Health grants HG002385 and HG004120 to E.E.E. M.Y.D. is supported by the National Institute of Neurological Disorder and Stroke of the US National Institutes of Health (award K99NS083627). E.E.E. is an investigator of the Howard Hughes Medical Institute. 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PD DEC PY 2014 VL 46 IS 12 BP 1293 EP 1302 DI 10.1038/ng.3120 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AU3YU UT WOS:000345547300010 PM 25326701 ER PT J AU La Fata, G Gartner, A Dominguez-Iturza, N Dresselaers, T Dawitz, J Poorthuis, RB Averna, M Himmelreich, U Meredith, RM Achsel, T Dotti, CG Bagni, C AF La Fata, Giorgio Gaertner, Annette Dominguez-Iturza, Nuria Dresselaers, Tom Dawitz, Julia Poorthuis, Rogier B. Averna, Michele Himmelreich, Uwe Meredith, Rhiannon M. Achsel, Tilmann Dotti, Carlos G. Bagni, Claudia TI FMRP regulates multipolar to bipolar transition affecting neuronal migration and cortical circuitry SO NATURE NEUROSCIENCE LA English DT Article ID FRAGILE-X-SYNDROME; INTERMEDIATE PROGENITOR CELLS; CEREBRAL-CORTEX; DEVELOPING NEOCORTEX; MENTAL-RETARDATION; GABA(A) RECEPTOR; KNOCKOUT MICE; BRAIN; EXPRESSION; AUTISM AB Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity. C1 [La Fata, Giorgio; Gaertner, Annette; Dominguez-Iturza, Nuria; Averna, Michele; Achsel, Tilmann; Dotti, Carlos G.; Bagni, Claudia] Katholieke Univ Leuven, VIB Ctr Biol Dis, Leuven, Belgium. [La Fata, Giorgio; Gaertner, Annette; Dominguez-Iturza, Nuria; Averna, Michele; Achsel, Tilmann; Dotti, Carlos G.; Bagni, Claudia] Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium. [La Fata, Giorgio; Gaertner, Annette; Dominguez-Iturza, Nuria; Averna, Michele; Achsel, Tilmann; Dotti, Carlos G.; Bagni, Claudia] Katholieke Univ Leuven, Leuven Inst Neurodegenerat Dis, Leuven, Belgium. [Dresselaers, Tom; Himmelreich, Uwe] Katholieke Univ Leuven, Leuven, Belgium. [Dawitz, Julia; Poorthuis, Rogier B.; Meredith, Rhiannon M.] Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Amsterdam, Netherlands. [Dotti, Carlos G.] Ctr Biol Mol Severo Ochoa, Madrid, Spain. [Bagni, Claudia] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy. RP Bagni, C (reprint author), Katholieke Univ Leuven, VIB Ctr Biol Dis, Leuven, Belgium. EM claudia.bagni@med.kuleuven.be FU VIB grant; FWO grant [ZKC6058-00-W01]; KUL-program financing IMIR [PF10/017]; FRAXA; Dutch Medical Research Council NWO VIDI [917.10.372]; SAO; Associazione Italians Sindrome X Fragile; NEUROBRAINNET LAP [7/16]; Flemish Methusalem grant; Innovation Ingenio-Consolider; [FWO-G.0705.11]; [FWO-G.0667.09]; [FWO-ZKC5858]; [FWO-G0.666.10N] FX We are very grateful to E. Lemmens for administrative support, K. Jonckers, J. Royaert and I. Beheydt for their help and assistance with primary neurons and mouse colonies. We are thankful to T. Voets and S. Munck (coordinator of LiMoNe) for providing us excellent suggestions on the calcium imaging, P. Fazzari for helping with the synapses quantification, and M. Regoli for suggestions on the statistical analysis. G.L.F., N.D.-I. and MA. were supported by grants FWO-G.0705.11 and FWO-G.0667.09 to C.B. T.A. was supported by a VIB grant to C.B. A.G. was partially supported by a VIB grant to CB. and C.G.D. as well by an FWO grant (ZKC6058-00-W01) to A.G. U.H. and T.D. received financial support from the KUL-program financing IMIR (PF10/017). T.D. was supported by FWO-ZKC5858. R.M.M. J.D. and R.B.P. were supported by grants from FRAXA and Dutch Medical Research Council NWO VIDI (#917.10.372). G.L.F. is part of the Brain Train network (http://www.brain-train.nl/braintrain-program/partners/). This work was supported by grants from VIB, SAO, FWO-G.0705.11 and FWO-G.0667.09, and Associazione Italians Sindrome X Fragile to C.B., and FWO-G0.666.10N, NEUROBRAINNET LAP 7/16, Flemish Methusalem grant, and Innovation Ingenio-Consolider, CSD2010-00045 to C.G.D. 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PD DEC PY 2014 VL 17 IS 12 BP 1693 EP 1700 DI 10.1038/nn.3870 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AU2ZY UT WOS:000345484000016 PM 25402856 ER PT J AU Zhang, Y Bonnan, A Bony, G Ferezou, I Pietropaolo, S Ginger, M Sans, N Rossier, J Oostra, B LeMasson, G Frickla, A AF Zhang, Yu Bonnan, Audrey Bony, Guillaume Ferezou, Isabelle Pietropaolo, Susanna Ginger, Melanie Sans, Nathalie Rossier, Jean Oostra, Ben LeMasson, Gwen Frickla, Andreas TI Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1-(/y) mice SO NATURE NEUROSCIENCE LA English DT Article ID FRAGILE-X-SYNDROME; CA1 PYRAMIDAL NEURONS; KNOCK-OUT MICE; FMR1 KO MICE; POTASSIUM CHANNELS; MOUSE MODEL; BK CHANNELS; H-CHANNELS; PLASTICITY; INHIBITION AB Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (Si) was hyperexcited in response to tactile sensory stimulation in Fmr1(-/y) mice. This correlated with neuronal and dendritic hyperexcitability of Si pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output. Using dendritic electrophysiological recordings, calcium imaging, pharmacology, biochemistry and a computer model, we found that this defect was, at least in part, attributable to the reduction and dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued several core hyperexcitability phenomena by targeting Bk-Ca channels. Our results provide strong evidence pointing to the utility of BKCa channel openers for the treatment of the sensory hypersensitivity aspects of FXS. C1 [Zhang, Yu; Bonnan, Audrey; Bony, Guillaume; Ginger, Melanie; Sans, Nathalie; LeMasson, Gwen; Frickla, Andreas] INSERM, Neuroctr Magendie, U862, Bordeaux, France. [Zhang, Yu; Bonnan, Audrey; Bony, Guillaume; Ginger, Melanie; Sans, Nathalie; LeMasson, Gwen; Frickla, Andreas] Univ Bordeaux, Neuroctr Magendie, U862, Bordeaux, France. [Ferezou, Isabelle; Rossier, Jean] ESPCI ParisTech, CNRS UMR 7637, Neurobiol Lab, Paris, France. [Pietropaolo, Susanna] Univ Bordeaux, INCIA, Talence, France. [Pietropaolo, Susanna] CNRS, INCIA, Talence, France. [Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. RP Frickla, A (reprint author), INSERM, Neuroctr Magendie, U862, Bordeaux, France. EM andreas.frick@inserm.fr FU FRAXA Research Foundation; INSERM; CNRS; Conseil de la Region d'Aquitaine; Fondation Jerome Lejeune; Federation pour la Recherche sur le Cerveau; Fondation pour la Recherche Medicale [SPF20130526794]; Labex-BRAIN [ANR-10-LABEX-43]; Max Planck Society; Deutsche Forschungsgemeinschaft FX We thank B. Sakmann, P. Seeburg, the Max Planck Society and the Deutsche Forschungsgemeinschaft for initial support of this study. We thank J.-C. Delpech, S. Dos Santos Carvalho and W. Crusio for technical and scientific advice. Some data was acquired using equipment of the Bordeaux Imaging Center, the ESPCI ParisTech and Biochemistry Facility of the Bordeaux Neurocampus. This research was funded by FRAXA Research Foundation, INSERM, CNRS, Conseil de la Region d'Aquitaine, Fondation Jerome Lejeune, Federation pour la Recherche sur le Cerveau, Fondation pour la Recherche Medicale (SPF20130526794) and Labex-BRAIN (ANR-10-LABEX-43). 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Neurosci. PD DEC PY 2014 VL 17 IS 12 BP 1701 EP 1709 DI 10.1038/nn.3864 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AU2ZY UT WOS:000345484000017 PM 25383903 ER PT J AU Plichta, MM Grimm, O Morgen, K Mier, D Sauer, C Haddad, L Tost, H Esslinger, C Kirsch, P Schwarz, AJ Meyer-Lindenberg, A AF Plichta, Michael M. Grimm, Oliver Morgen, Katrin Mier, Daniela Sauer, Carina Haddad, Leila Tost, Heike Esslinger, Christine Kirsch, Peter Schwarz, Adam J. Meyer-Lindenberg, Andreas TI Amygdala habituation: A reliable fMRI phenotype SO NEUROIMAGE LA English DT Article DE Amygdala habituation; fMRI; Retest reliability; Intra-class correlation coefficient (ICC); Emotion; Faces ID AUTISM SPECTRUM DISORDERS; TEST-RETEST RELIABILITY; PREFRONTAL CORTEX; FUNCTIONAL MRI; FACIAL EXPRESSIONS; EMOTIONAL STIMULI; NEUTRAL FACES; FEARFUL FACES; RESPONSES; ADOLESCENCE AB Amygdala function is of high interest for cognitive, social and psychiatric neuroscience, emphasizing the need for reliable assessments in humans. Previous work has indicated unsatisfactorily low within-subject reliability of amygdala activation fMRI measures. Based on basic science evidence for strong habituation of amygdala response to repeated stimuli, we investigated whether a quantification of habituation provides additional information beyond the usual estimate of the overall mean activity. We assessed the within-subject reliability of amygdala habituation measures during a facial emotion matching paradigm in 25 healthy subjects. We extracted the amygdala signal decrement across the course of the fMRI run for the two test-retest measurement sessions and compared reliability estimates with previous findings based on mean response amplitude. Retest-reliability of the session-wise amygdala habituation was significantly higher than the evoked amygdala mean amplitude (intraclass correlation coefficients (ICC) = 0.53 vs. 0.16). To test the task-specificity of this finding, we compared the retest-reliability of amygdala habituation across two different tasks. Significant amygdala response decrement was also seen in a cognitive task (n-back working memory) that did not per se activate the amygdala, but was totally unreliable in that context (ICC similar to 0.0), arguing for task-specificity. Together the results show that emotion-dependent amygdala habituation is a robust and considerably more reliable index than the mean amplitude, and provides a robust potential endpoint for within-subject designs including pharmaco-fMRI studies. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). C1 [Plichta, Michael M.; Grimm, Oliver; Morgen, Katrin; Haddad, Leila; Tost, Heike; Esslinger, Christine; Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-68159 Mannheim, Germany. [Schwarz, Adam J.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Mier, Daniela; Sauer, Carina; Kirsch, Peter] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Clin Psychol, D-68159 Mannheim, Germany. RP Plichta, MM (reprint author), Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, J5, D-68159 Mannheim, Germany. EM Michael.Plichta@zi-mannheim.de FU Innovative Medicines Initiative Joint Undertaking (IMI) [115008] FX NEWMEDS - the work leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking (IMI) under Grant Agreement No. 115008. 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Fein, George TI Automated MRI cerebellar size measurements using active appearance modeling SO NEUROIMAGE LA English DT Article DE Cerebellum; MRI; Segmentation; Active Appearance Models; Automated Analysis ID HUMAN BRAIN; TISSUE CLASSIFICATION; PROBABILISTIC ATLAS; IMAGE REGISTRATION; SEGMENTATION; VALIDATION; EXTRACTION; ALGORITHM; CHILDREN; VERMIS AB Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies. We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB's FIRST. This approach involves training Active Appearance Models (AAMs) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I-V, VI-VII, and VIII-X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting. The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM approach offers superior reliability and validity. Extensions of CATK to cerebellar hemisphere parcels are envisioned. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). C1 [Price, Mathew; Cardenas, Valerie A.; Fein, George] Neurobehav Res Inc, Ala Moana Pacific Ctr, Honolulu, HI 96814 USA. RP Fein, G (reprint author), Neurobehav Res Inc, Ala Moana Pacific Ctr, 1585 Kapiolani Blvd Suite 1030, Honolulu, HI 96814 USA. EM george@nbresearch.com FU National Institute on Alcohol Abuse and Alcoholism [SBIR R43 AA021945] FX This work was made possible by the National Institute on Alcohol Abuse and Alcoholism (SBIR R43 AA021945). 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Psychol. PD DEC PY 2014 VL 35 IS 6 BP 831 EP 840 DI 10.1111/pops.12056 PG 10 WC Political Science; Psychology, Social SC Government & Law; Psychology GA AU4JA UT WOS:000345575600007 ER PT J AU Reilly, C Atkinson, P Menlove, L Gillberg, C O'Nions, E Happe, F Neville, BGR AF Reilly, Colin Atkinson, Patricia Menlove, Leanne Gillberg, Christopher O'Nions, Elizabeth Happe, Francesca Neville, Brian G. R. TI Pathological Demand Avoidance in a population-based cohort of children with epilepsy: Four case studies SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Epilepsy; Pathological demand avoidance; Autism Spectrum Disorder ID DEVELOPMENTAL COORDINATION DISORDER; CHILDHOOD-ONSET EPILEPSY; QUALITY-OF-LIFE; SCREENING QUESTIONNAIRE; COMORBIDITIES AB Childhood epilepsy is associated with a range of neurobehavioural comorbidities including Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), motor impairments and emotional problems. These difficulties frequently have a greater impact on quality of life than seizures. Pathological Demand Avoidance (PDA) is a term increasingly in use in the UK and Europe to describe behaviours associated with an extreme resistance to demands and requests and the need to be in control in social interactions. In a population-based group of 85 children with epilepsy, four (5%) were identified as displaying significant symptoms of PDA, were assessed using the Extreme Demand Avoidance Questionnaire (EDA-Q) and are described in detail. As well as significant symptoms of PDA, the four children met criteria for a range of neurobehavioural disorders; all four had cognitive impairment (IQ < 85) and met DSM-IV-TR criteria for ADHD. Three, in addition, met criteria for ASD and Developmental Coordination Disorder (DCD) and two for Oppositional Defiant Disorder (ODD). All four experienced their first seizure before 5 years of age. School and parent reports indicated very significant functional impairment and management concerns, particularly with respect to complying with everyday demands. Symptoms of PDA should be considered when evaluating neurobehavioural comorbidity in childhood epilepsy. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Reilly, Colin; Menlove, Leanne; Neville, Brian G. R.] Young Epilepsy, Res Dept, Lingfield RH7 6PW, Surrey, England. [Atkinson, Patricia] Crawley Hosp, Child Dev Ctr, Crawley RH11 7DH, W Sussex, England. [Reilly, Colin; Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [O'Nions, Elizabeth] UCL, Div Psychol & Language Sci, London WC1E 7HB, England. [Happe, Francesca] Kings Coll London, Inst Psychiat PO 80, Francesca Happe MRC Social Genet & Dev Psychiat C, London SE5 8AF, England. [Neville, Brian G. R.] UCL, Inst Child Hlth, Neurosci Unit, London WC1 N 3LU, England. RP Reilly, C (reprint author), Young Epilepsy, Res Dept, Lingfield RH7 6PW, Surrey, England. 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TI Comparison of behavior analytic and eclectic early interventions for young children with autism after three years SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Early intervention; Applied behavior analysis; Eclectic treatment; Outcomes; Longitudinal studies ID METAANALYSIS; OUTCOMES; TRIAL AB In a previous study, we compared the effects of just over one year of intensive behavior analytic intervention (IBT) provided to 29 young children diagnosed with autism with two eclectic (i.e., mixed-method) interventions (Howard, Sparkman, Cohen, Green, & Stanislaw, 2005). One eclectic intervention (autism programming; AP) was designed specifically for children with autism and was intensive in that it was delivered for an average of 25-30 h per week (n = 16). The other eclectic intervention (generic programming; GP) was delivered to 16 children with a variety of diagnoses and needs for an average of 15-17 h per week. This paper reports outcomes for children in all three groups after two additional years of intervention. With few exceptions, the benefits of IBT documented in our first study were sustained throughout Years 2 and 3. At their final assessment, children who received IBT were more than twice as likely to score in the normal range on measures of cognitive, language, and adaptive functioning than were children who received either form of eclectic intervention. Significantly more children in the IBT group than in the other two groups had IQ language, and adaptive behavior test scores that increased by at least one standard deviation from intake to final assessment. Although the largest improvements for children in the IBT group generally occurred during Year 1, many children in that group whose scores were below the normal range after the first year of intervention attained scores in the normal range of functioning with one or two years of additional intervention. In contrast, children in the two eclectic treatment groups were unlikely to attain scores in the normal range after the first year of intervention, and many of those who had scores in the normal range in the first year fell out of the normal range in subsequent years. There were no consistent differences in outcomes at Years 2 and 3 between the two groups who received eclectic interventions. These results provide further evidence that intensive behavior analytic intervention delivered at an early age is more likely to produce substantial improvements in young children with autism than common eclectic interventions, even when the latter are intensive. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Howard, Jane S.; Stanislaw, Harold] Calif State Univ Stanislaus, Dept Psychol, Turlock, CA 95382 USA. [Howard, Jane S.; Sparkman, Coleen R.] Kendall Ctr Therapeut Pathways, Modesto, CA 95354 USA. [Green, Gina] Assoc Profess Behav Analysts, San Diego, CA 92119 USA. 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Dev. Disabil. PD DEC PY 2014 VL 35 IS 12 BP 3326 EP 3344 DI 10.1016/j.ridd.2014.08.021 PG 19 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100014 PM 25190094 ER PT J AU Andersson, GW Miniscalco, C Gillberg, C AF Andersson, Gunilla Westman Miniscalco, Carmela Gillberg, Christopher TI Preschoolers assessed for autism: Parent and teacher experiences of the diagnostic process SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Assessment; Children; Parents; Preschool; Teachers; Early diagnosis ID SPECTRUM DISORDERS; YOUNG-CHILDREN; COMMUNICATION; TODDLERS; STRESS; INTERVENTIONS; PROFILES; DEFICITS; GIRLS; BOYS AB Many parents of young children with autism spectrum disorder (ASD) have often been recommended to "wait and see" when they have first expressed concerns. This comparative, descriptive, partly longitudinal questionnaire study aimed to evaluate parent/preschool teacher experiences as regards time of first concern about the child and about the diagnostic process at a specialized Child Neuropsychiatry Clinic. Participants were parents and teachers of 34 preschool children with suspected ASD (26 boys, 8 girls, mean age 37 months) drawn from a general population cohort. Most of the parents, and the teachers, had their first concern about the child's development before the child's second birthday. Generally, they were satisfied with the diagnostic process and did not regret their participation in it. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Andersson, Gunilla Westman; Miniscalco, Carmela; Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. RP Andersson, GW (reprint author), Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. 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PD DEC PY 2014 VL 35 IS 12 BP 3392 EP 3402 DI 10.1016/j.ridd.2014.08.027 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100021 PM 25194515 ER PT J AU Konst, MJ Matson, JL Goldin, RL Williams, LW AF Konst, Matthew J. Matson, Johnny L. Goldin, Rachel L. Williams, Lindsey W. TI Socialization and nonverbal communication in atypically developing infants and toddlers SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Atypical development; Cerebral Palsy; Down's syndrome; Autism Spectrum Disorder; Social skills; Nonverbal communication ID PROFOUND MENTAL-RETARDATION; AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDER; QUALITY-OF-LIFE; II DASH-II; CEREBRAL-PALSY; SOCIAL-SKILLS; INTELLECTUAL DISABILITY; DIAGNOSTIC-ASSESSMENT; YOUNG-CHILDREN AB Emphasis on early identification of atypical development has increased as evidence supporting the efficacy of intervention has grown. These increases have also directly affected the availability of funding and providers of early intervention services. A majority of research has focused on interventions specific to an individual's primary diagnoses. For example, interventions for those with cerebral palsy (CP) have traditionally focused on physiological symptoms, while intervention for individuals with Autism Spectrum Disorder (ASD) focus on socialization, communication, and restricted interests and repetitive behaviors. However deficits in areas other than those related to their primary diagnoses (e.g., communication, adaptive behaviors, and social skills) are prevalent in atypically developing populations and are significant predictors of quality of life. Therefore, the purpose of the current study was to examine impairments in socialization and nonverbal communication in individuals with Down's syndrome (DS), CP, and those with CP and comorbid ASD. 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TI Environmental risk factors associated with the persistence of conduct difficulties in children with intellectual disabilities and autistic spectrum disorders SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Conduct difficulties; Problem behavior; Socio-economic position; Environmental factors; Autism; Intellectual disability ID BEHAVIOR PROBLEMS; PREVENTIVE INTERVENTION; DEVELOPMENTAL DELAY; MENTAL-HEALTH; SOCIOECONOMIC POSITION; PHYSICAL AGGRESSION; PRESCHOOL-CHILDREN; EMOTIONAL-PROBLEMS; CHILDHOOD; ADOLESCENTS AB We investigated the association between exposure to environmental risks in early childhood and the prevalence and persistence of conduct difficulties (CD) in children with intellectual disability (ID) who did not have autistic spectrum disorder (ASD), children with ASD and typically developing (TD) children. Results indicated that: (1) exposure to risk was associated with elevated prevalence of CD at age three and, for TD children and children with ID, increased risk of CD persisting to ages five and seven; (2) at all levels of risk, children with ASD were more likely to show persistent CD than other children; (3) children with ID were no more likely to show persistent CD than TD children at low levels of exposure to environmental risk. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Emerson, Eric; Einfeld, Stewart; Stancliffe, Roger J.] Univ Sydney, Sydney, NSW 2006, Australia. [Blacher, Jan] Univ Calif Riverside, Riverside, CA 92521 USA. [Emerson, Eric; Hatton, Chris; Robertson, Janet] Univ Lancaster, Lancaster LA1 4YW, England. RP Emerson, E (reprint author), Univ Lancaster, Lancaster LA1 4YW, England. 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PD DEC PY 2014 VL 35 IS 12 BP 3508 EP 3517 DI 10.1016/j.ridd.2014.08.039 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100031 PM 25238636 ER PT J AU MacDonald, R Parry-Cruwys, D Dupere, S Ahearn, W AF MacDonald, Rebecca Parry-Cruwys, Diana Dupere, Sally Ahearn, William TI Assessing progress and outcome of early intensive behavioral intervention for toddlers with autism SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE ABA; Applied behavior analysis; Autism; EIBI; Early intensive behavioral intervention; Outcome ID JOINT ATTENTION; YOUNG-CHILDREN; PRETEND PLAY; SPECTRUM DISORDERS; PREDICTORS; LANGUAGE; SKILLS; IMITATION AB Intensive behavioral intervention for young children diagnosed with autism can produce large gains in social, cognitive, and language development. Although several studies have identified behaviors that are possible indicators of best outcome, changes in performance are typically measured using norm-referenced standardized scores referencing overall functioning level rather than via repeated observational measures of autism-specific deficits (i.e., social behavior). In the current study, 83 children with autism (CWA), aged 1, 2 and 3 years, and 58 same-aged typically developing children (TDC) were directly observed in the areas of cognitive skills, joint attention (JA), play, and stereotypic behavior using a measure called the Early Skills Assessment Tool (ESAT; MacDonald et al., 2006). CWA were assessed at entry into an EIBI program and again after 1 year of treatment. Changes in performance were compared pre- and post-treatment as well as to the normative data by age. Results indicate significant gains on the ESAT across all age groups with the greatest gains seen in the children who entered treatment prior to their second birthday. Increases were seen on direct measures of JA, play, imitation and language while decreases were seen in stereotypy regardless of level of performance at entry into EIBI. The ESAT, a direct measurement tool, served as a sensitive tool to measure changes in autism symptomatology following EIBI treatment. (C) 2014 Elsevier Ltd. All rights reserved. C1 [MacDonald, Rebecca; Parry-Cruwys, Diana; Dupere, Sally; Ahearn, William] New England Ctr Children, Southborough, MA 01772 USA. RP MacDonald, R (reprint author), New England Ctr Children, 33 Turnpike Rd, Southborough, MA 01772 USA. 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PD DEC PY 2014 VL 35 IS 12 BP 3632 EP 3644 DI 10.1016/j.ridd.2014.08.036 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100045 PM 25241118 ER PT J AU Chang, YJ Kang, YS Liu, FL AF Chang, Yao-Jen Kang, Ya-Shu Liu, Fang-Lin TI A computer-based interactive game to train persons with cognitive impairments to perform recycling tasks independently SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Interactive game; Cognitive impairments; Community-based rehabilitation ID HELD PROMPTING SYSTEM; SEVERE MENTAL-ILLNESS; QUALITY-OF-LIFE; VOCATIONAL TASKS; INTELLECTUAL DISABILITIES; SUPPORTED EMPLOYMENT; INDIVIDUALS; PEOPLE; STUDENTS; AUTISM AB This study assessed the possibility of training three people with cognitive impairments using a computer-based interactive game. A game was designed to provide task prompts in recycling scenarios, identify incorrect task steps on the fly, and help users learn to make corrections. Based on a multiple baseline design, the data showed that the three participants considerably increased their target response, which improved their vocational job skills during the intervention phases and enabled them to maintain the acquired job skills after intervention. The practical and developmental implications of the results are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chang, Yao-Jen; Liu, Fang-Lin] Chung Yuan Christian Univ, Dept Elect Engn, Chungli 320, Taiwan. [Kang, Ya-Shu] Chung Yuan Christian Univ, Dept Special Educ, Chungli 320, Taiwan. [Chang, Yao-Jen] Chung Yuan Christian Univ, Holist Med Device Dev Ctr, Chungli 320, Taiwan. RP Chang, YJ (reprint author), Chung Yuan Christian Univ, Dept Elect Engn, Chungli 320, Taiwan. 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PD DEC PY 2014 VL 35 IS 12 BP 3672 EP 3677 DI 10.1016/j.ridd.2014.09.009 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100049 PM 25262012 ER PT J AU Sun, X Allison, C Auyeung, B Baron-Cohen, S Brayne, C AF Sun, Xiang Allison, Carrie Auyeung, Bonnie Baron-Cohen, Simon Brayne, Carol TI Parental concerns, socioeconomic status, and the risk of autism spectrum conditions in a population-based study SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism Spectrum Conditions; Parental concern; Socioeconomic status; Screening ID PERVASIVE DEVELOPMENTAL DISORDERS; CAST CHILDHOOD ASPERGER; YOUNG-CHILDREN; DIFFICULTIES QUESTIONNAIRE; EARLY INTERVENTION; PREVALENCE; STRENGTHS; TODDLERS; AGE; UK AB A total number of 11,635 screening packs were distributed to 5-10 year-old children in 136 schools in Cambridgeshire to investigate the associations between levels of parental concern (none/minor/strong), socioeconomic status and the risk of having Autism Spectrum Conditions (ASC). The variables for investigating associations and possible confounders were extracted for analysis, including parental concern question score, SES, age of the child, sex, maternal age at birth, paternal age at birth, mother's age of leaving education, father's age of leaving education, birth order and the number of children in the family. The SES, age of the child, sex and mother's age at leaving education were associated with parental concern. Parents with higher SES reported higher levels of concern (Chi-square = 11.8; p = 0.02). However, a higher SES was not associated with the risk of having ASC (p = 0.50). After adjusting for potential confounders, the odds of children meeting ASC criteria whose parents had reported strong parental concern were 8.5 times (odds ratio: 8.5; 95%CI: 4.5, 16.2; p < 0.001) the odds of children having ASC whose parents reported minor concern. No child met ASC criteria where parents expressed no concerns. Parents with higher social class express more concerns than those from lower social classes. However, the concerns reported by parents in higher SES did not appear to be specific for ASC as there was no relationship between ASC and SES. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Sch 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] Jockey Club Sch Publ Hlth & Primary Care, Shatin, Hong Kong, Peoples R China. [Auyeung, Bonnie] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. RP Sun, X (reprint author), Univ Cambridge, Sch Med, Cambridge Inst Publ Hlth, Forvie Site, Cambridge CB2 0SR, England. 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PD DEC PY 2014 VL 35 IS 12 BP 3678 EP 3688 DI 10.1016/j.ridd.2014.07.037 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AU3ET UT WOS:000345496100050 PM 25262013 ER PT J AU Ogura, K Takeshita, K Arakawa, C Shimojima, K Yamamoto, T AF Ogura, Kaeko Takeshita, Kenzo Arakawa, Chikako Shimojima, Keiko Yamamoto, Toshiyuki TI Neuropsychological Profiles of Patients With 2q37.3 Deletion Associated With Developmental Dyspraxia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE 2q37; 3 deletion; intellectual disability; autism spectrum disorder; developmental dyspraxia; brachydactyly mental retardation syndrome (BDMR); Albright hereditary osteodystrophy-like syndrome (AHO-like); histone deacetylase 4 gene (HDAC4) ID MENTAL-RETARDATION SYNDROME; BRACHYDACTYLY TYPE-E; CHILDHOOD AUTISM; CANDIDATE REGION; CHILDREN; HDAC4; MUTATIONS; SPECTRUM; FEATURES; FAMILY AB Patients with 2q37 deletions manifest brachydactyly mental retardation syndrome (BDMR). Recent advances in human molecular research have revealed that alterations in the histone deacetylase 4 gene (HDAC4) are responsible for the clinical manifestations of BDMR. Here, we report two male patients with 2q37.3 deletions. One of the patients showed a typical BDMR phenotype, and HDAC4 was included in the deletion region. HDAC4 was preserved in the other patient, and he showed a normal intelligence level with the delayed learning of complex motor skills. Detailed neuropsychological examinations revealed similar neuropsychological profiles in these two patients (visuo-spatial dyspraxia) that suggested developmental dyspraxia. These observations suggested that some other candidate genes for neuronal development exist in the telomeric region of HDAC4. (c) 2014 Wiley Periodicals, Inc. C1 [Ogura, Kaeko] Res Inst Natl Rehabil Ctr Persons Disabil, Dev Disabil Study Sect, Dept Rehabil Brain Funct, Tokorozawa, Saitama, Japan. [Ogura, Kaeko] Tohoku Univ, Grad Sch Med, Dept Behav Neurol & Cognit Neurosci, Sendai, Miyagi 980, Japan. [Takeshita, Kenzo] NPO Child Guidance Ctr, Fukuoka, Japan. [Arakawa, Chikako] Nihon Univ, Sch Med, Dept Pediat & Child Hlth, Tokyo, Japan. [Shimojima, Keiko; Yamamoto, Toshiyuki] Tokyo Womens Med Univ, Inst Integrated Med Sci, Tokyo 1628666, Japan. RP Yamamoto, T (reprint author), Tokyo Womens Med Univ, Inst Integrated Med Sci, Shinjuku Ward, 8-1 Kawada Cho, Tokyo 1628666, Japan. EM yamamoto.toshiyuki@twmu.ac.jp FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT); Ministry of Health, Labor, and Welfare, Japan; Japan Society for the Promotion of Science (J.S.P.S) FX Grant sponsor: Ministry of Education, Culture, Sports, Science, and Technology (MEXT); Grant sponsor: Ministry of Health, Labor, and Welfare, Japan; Grant sponsor: Japan Society for the Promotion of Science (J.S.P.S). 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J. Med. Genet. B PD DEC PY 2014 VL 165 IS 8 BP 684 EP 690 DI 10.1002/ajmg.b.32274 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AU0PZ UT WOS:000345327200008 PM 25329715 ER PT J AU Calton, M Dickson, P Harper, RM Goldowitz, D Mittleman, G AF Calton, M. Dickson, P. Harper, R. M. Goldowitz, D. Mittleman, G. TI Impaired Hypercarbic and Hypoxic Responses from Developmental Loss of Cerebellar Purkinje Neurons: Implications for Sudden Infant Death Syndrome SO CEREBELLUM LA English DT Article DE Cerebellum; Sudden infant death; Autism spectrum disorders; Lurcher; Respiration ID BRAIN-STEM; JOUBERT-SYNDROME; CARDIORESPIRATORY RESPONSES; RESPIRATORY RHYTHMOGENESIS; NEUROPATHOLOGICAL FINDINGS; CEREBRAL ABNORMALITIES; CELL DEGENERATION; MOBIUS-SYNDROME; RETT SYNDROME; AIR HUNGER AB Impaired responsivity to hypercapnia or hypoxia is commonly considered a mechanism of failure in sudden infant death syndrome (SIDS). The search for deficient brain structures mediating flawed chemosensitivity typically focuses on medullary regions; however, a network that includes Purkinje cells of the cerebellar cortex and its associated cerebellar nuclei also helps mediate responses to carbon dioxide (CO2) and oxygen (O-2) challenges and assists integration of cardiovascular and respiratory interactions. Although cerebellar nuclei contributions to chemoreceptor challenges in adult models are well described, Purkinje cell roles in developing models are unclear. We used a model of developmental cerebellar Purkinje cell loss to determine if such loss influenced compensatory ventilatory responses to hypercapnic and hypoxic challenges. Twenty-four Lurcher mutant mice and wildtype controls were sequentially exposed to 2 % increases in CO2 (0-8 %) or 2 % reductions in O-2 (21-13 %) over 4 min, with return to room air (21 % O-2/79 % N2/0 % CO2) between each exposure. 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Ayres, Kevin M. Bryant, Kathryn J. Foster, Ashley L. TI Comparison of the Effects of Continuous Video Modeling, Video Prompting, and Video Modeling on Task Completion by Young Adults with Moderate Intellectual Disability SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID DAILY LIVING SKILLS; DEVELOPMENTAL-DISABILITIES; COOKING SKILLS; INDIVIDUALS; STUDENTS; AUTISM; SELF; PICTURE; INTERVENTIONS; METAANALYSIS AB This study compared the effects of three procedures (video prompting: VP, video modeling: VM, and continuous video modeling: CVM) on task completion by three high school students with moderate intellectual disability. The comparison was made across three sets of fundamentally different tasks (putting away household items in clusters of two items; multi-step cleaning tasks whereby each step in the task was completed one time; and multi-component folding tasks whereby steps were performed repetitively). The study combined a multiple probe across behaviors design with an adapted alternating treatments design replicated across three participants. Overall, VP was more effective across the three students for 6 of the 9 tasks, followed by CVM (2 of 9 tasks), and VM (1 of 9 tasks). These data further suggest that the type of task and student characteristics may influence the effectiveness of the three video procedures. C1 [Mechling, Linda C.; Bryant, Kathryn J.; Foster, Ashley L.] Univ N Carolina, Wilmington, NC 28404 USA. [Ayres, Kevin M.] Univ Georgia, Athens, GA 30602 USA. RP Mechling, LC (reprint author), Univ N Carolina, Dept Educ Young Children & Special Educ, 601 S Coll Rd, Wilmington, NC 28404 USA. EM mechlingl@uncw.edu CR Ayres Kevin M., 2007, Journal of Special Education Technology, V22 Banda DR, 2011, EDUC TRAIN AUTISM DE, V46, P514 Bellini S, 2007, EXCEPT CHILDREN, V73, P264 Cannella-Malone H, 2006, EDUC TRAIN DEV DISAB, V41, P344 Cannella-Malone H., 2010, J POSITIVE BEHAV INT, DOI 10.1177.1098300710366593 Delano ME, 2007, REM SPEC EDUC, V28, P33, DOI 10.1177/07419325070280010401 Gast D. L., 2010, SINGLE SUBJECT RES B Goodson J, 2007, RES DEV DISABIL, V28, P458, DOI 10.1016/j.ridd.2006.06.002 Graves TB, 2005, EDUC TRAIN DEV DISAB, V40, P34 Horn J. A., 2008, INT J BEHAV CONSULTA, V4, P279 Mason RA, 2012, RES DEV DISABIL, V33, P1076, DOI 10.1016/j.ridd.2012.01.016 Mechling L, 2010, EDUC TRAIN AUTISM DE, V45, P230 Mechling L. C., 2012, CONTINUOUS VID UNPUB Mechling LC, 2014, EDUC TRAIN AUTISM DE, V49, P368 Mechling LC, 2009, J AUTISM DEV DISORD, V39, P1420, DOI 10.1007/s10803-009-0761-0 Mechling LC, 2009, EDUC TRAIN DEV DISAB, V44, P218 Mechling LC, 2012, EDUC TRAIN AUTISM DE, V47, P223 Mechling LC, 2011, EDUC TRAIN AUTISM DE, V46, P369 Mechling LC, 2009, EXCEPTIONALITY, V17, P103, DOI 10.1080/09362830902805889 Rayner C, 2009, RES AUTISM SPECT DIS, V3, P291, DOI 10.1016/j.rasd.2008.09.001 Reeve S. A., 2010, EDUC TREAT CHILD, V33, P351, DOI DOI 10.1353/ETC.0.0103 Rehfeldt RA, 2003, BEHAV INTERVENT, V18, P209, DOI 10.1002/bin.139 Sancho K., 2010, EDUC TREAT CHILD, V33, P421, DOI DOI 10.1353/ETC.0.0097 Shukla-Mehta S., 2010, FOCUS AUTISM OTHER D, V25, P23 Taber-Doughty T., 2008, J SPECIAL ED TECHNOL, V23, P283 Van Laarhoven T, 2010, FOCUS AUTISM DEV DIS, V25, P195, DOI 10.1177/1088357610380412 Van Laarhoven T, 2009, EDUC TRAIN DEV DISAB, V44, P509 Wolery M., 2010, SINGLE SUBJECT RES B NR 28 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 DEC PY 2014 VL 49 IS 4 BP 491 EP 504 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600001 ER PT J AU Batu, S AF Batu, Sema TI Effects of Teaching Simultaneous Prompting through Visual Supports to Parents of Children with Developmental Disabilities SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SEVERE INTELLECTUAL DISABILITIES; SEVERE MENTAL-RETARDATION; CONSTANT-TIME DELAY; YOUNG-ADULTS; LEISURE SKILLS; AUTISM; INSTRUCTION; TEACHERS; PRESCHOOLERS; CAREGIVERS AB The present study was designed to examine the effectiveness of visual supports on teaching simultaneous prompting procedure to mothers to provide home-based instruction to their children with developmental disabilities. Three preschool-aged children with moderate developmental disabilities and their mothers were the participants. A multiple probe design across behaviors was used and was replicated across participants in order to examine the effectiveness of visual support on teaching simultaneous prompting procedure to the mothers for them to provide home-based instruction to their children with developmental disabilities. Results of the study revealed that mothers learned to use simultaneous prompting for teaching chained skills to their children. Children acquired skills which were taught by their mothers at home and maintained their target skills two weeks after the training was completed. Also, both target groups could generalize their acquired skills. C1 [Batu, Sema] Anadolu Univ, TR-26470 Eskisehir, Turkey. RP Batu, S (reprint author), Anadolu Univ, Engelliler Arastirma Enstitusu, TR-26470 Eskisehir, Turkey. EM esbatu@anadolu.edu.tr CR Batu S, 2008, EDUC TRAIN DEV DISAB, V43, P541 Bidwell MA, 2004, BEHAV INTERVENT, V19, P263, DOI 10.1002/bin.165 Cavkaytar A., 1998, THESIS ANADOLU U TUR Cavkaytar A, 2007, EDUC TRAIN DEV DISAB, V42, P85 DiPipi-Hoy C, 2004, J SPEC EDUC, V38, P144, DOI 10.1177/00224669040380030201 Dollar CA, 2012, RES DEV DISABIL, V33, P189, DOI 10.1016/j.ridd.2011.09.001 Fetko KS, 1999, EDUC TRAIN MENT RET, V34, P318 Gumuseli A. I., 2004, OZEL OKULLAR BIRLIGI, V2, P14 HILTON A, 1993, EDUC TRAIN MENT RET, V28, P199 Hine JF, 2006, TOP EARLY CHILD SPEC, V26, P83, DOI 10.1177/02711214060260020301 Keen D, 2007, J DEV PHYS DISABIL, V19, P291, DOI 10.1007/s10882-007-9044-x Maciag KG, 2000, EDUC TRAIN MENT RET, V35, P306 Marcus A, 2009, J APPL BEHAV ANAL, V42, P335, DOI 10.1901/jaba.2009.42-335 MORAN DR, 1991, CHILD FAM BEHAV THER, V13, P13, DOI 10.1300/J019v13n01_02 MORROW SA, 1987, RES DEV DISABIL, V8, P113, DOI 10.1016/0891-4222(87)90043-6 NAC, 2009, NAT AUT CTR NAT STAN O'Neill R. E., 2011, SINGLE CASE RES DESI Olcay Gul S., 2012, THESIS ANADOLU U TUR Ozcan N, 2009, EDUC TRAIN DEV DISAB, V44, P237 Parrot K. A., 2000, J BEHAV ED, V10, P3, DOI 10.1023/A:1016639721684 Pennington RC, 2012, EDUC TREAT CHILD, V35, P389 Quill KA, 1997, J AUTISM DEV DISORD, V27, P697, DOI 10.1023/A:1025806900162 Reagon K. A., 2006, EDUC TREAT CHILD, V29, P517 Riesen T., 2003, J BEHAV ED, V12, P241, DOI DOI 10.1023/A:1026076406656 Schuster J. W., 1993, J BEHAV ED, V3, P299, DOI 10.1007/BF00961557 Seung HK, 2006, J INTELL DISABIL RES, V50, P139, DOI 10.1111/j.1365-2788.2005.00767.x Sewell TJ, 1998, J EARLY INTERVENTION, V21, P132 Sonmez N., 2011, ULUSLARARASI INSAN B, V8, P1151 Tait K, 2004, DISABIL REHABIL, V26, P1241, DOI 10.1080/09638280412331280253 Tekin-Iftar E., 2012, OZEL EGITIMDE YANLIS Tekin-Iftar E, 2008, EDUC TRAIN DEV DISAB, V43, P249 Wall ME, 1997, EDUC TRAIN MENT RET, V32, P213 Wall ME, 1997, EDUC TRAIN MENT RET, V32, P340 West EA, 2008, FOCUS AUTISM DEV DIS, V23, P229, DOI 10.1177/1088357608324715 NR 34 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 DEC PY 2014 VL 49 IS 4 BP 505 EP 516 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600002 ER PT J AU Ahlgrim-Delzell, L Browder, D Wood, L AF Ahlgrim-Delzell, Lynn Browder, Diane Wood, Leah TI Effects of Systematic Instruction and an Augmentative Communication Device on Phonics Skills Acquisition for Students with Moderate Intellectual Disability Who Are Nonverbal SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SEVERE DEVELOPMENTAL-DISABILITIES; EARLY LITERACY PROGRAM; ALTERNATIVE COMMUNICATION; READING-INSTRUCTION; MENTAL-RETARDATION; WORD RECOGNITION; YOUNG-CHILDREN; INTERVENTION; INDIVIDUALS AB Percentages of correct responses to decoding probes (i.e., phoneme identification, blending phonemes to identify words, blending phonemes to identify pictures) were measured across three participants with moderate intellectual disability or autism in elementary school. Time delay and system of least prompts were used in conjunction with an AAC device, which enabled participants to produce phoneme blends and receive articulatory feedback. Participants were taught the initial levels of a phonics curriculum designed by the research team. Each level introduced a new set of three phonemes. During the five lessons within each level, participants were taught to identify letter sounds, segment and blend CVC words, identify sight words, read connected text, and answer comprehension questions related to the stories. Using a GoTalk 32 Express, participants produced target phonemes and words, as well as blended phonemes to form words. All participants improved across the three target skills, indicating a functional relationship between phonics skills and the systematic delivery of the phonics curriculum using an AAC device. C1 [Ahlgrim-Delzell, Lynn; Browder, Diane; Wood, Leah] Univ N Carolina, Charlotte, NC 28223 USA. RP Ahlgrim-Delzell, L (reprint author), Univ N Carolina, Dept Educ Leadership, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM laahlgri@uncc.edu CR Al Otaiba S., 2004, TEACHING EXCEPTIONAL, V36, P28 Allor JH, 2010, EDUC TRAIN AUTISM DE, V45, P3 Austin P., 1990, EDMARK FUNCTIONAL WO Bradford S, 2006, EDUC TRAIN DEV DISAB, V41, P333 Browder D, 2012, REM SPEC EDUC, V33, P237, DOI 10.1177/0741932510387305 Browder D, 2009, EXCEPT CHILDREN, V75, P343 Browder D. M., 2007, EARLY LITERACY SKILL Browder DM, 2008, EXCEPT CHILDREN, V75, P33 Browder DM, 2006, EXCEPT CHILDREN, V72, P392 Chiang H., 2007, FOCUS AUTISM OTHER D, V22, P259, DOI DOI 10.1177/10883576070220040801 CONNERS FA, 1992, AM J MENT RETARD, V96, P577 Dolch E. W., 1955, METHODS READING Dunn L. M., 1997, PEABODY PICTURE VOCA, V3rd Engleman S., 1988, CORRECTIVE READING W Englemann S., 1982, THEORY INSTRUCTION Fallon KA, 2004, J SPEECH LANG HEAR R, V47, P1424, DOI 10.1044/1092-4388(2004/106) Flores M. 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E., 1998, PREVENTING READING D Sonday A., 2000, SONDAY SYSTEM LETS P Soto G, 2008, AUGMENT ALTERN COMM, V24, P76, DOI 10.1080/07434610701740612 Truxler JE, 2007, AUGMENT ALTERN COMM, V23, P164, DOI 10.1080/07434610601151803 U.S. Department of Education, 2011, WHAT WORKS CLEAR PRO Wolery M., 1994, J BEHAV ED, V4, P415, DOI 10.1007/BF01539542 NR 35 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 DEC PY 2014 VL 49 IS 4 BP 517 EP 532 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600003 ER PT J AU Leaf, JB Dale, S Kassardjian, A Tsuji, KH Taubman, M McEachin, JJ Leaf, RB Oppenheim-Leaf, ML AF Leaf, Justin B. Dale, Stephanie Kassardjian, Alyne Tsuji, Kathleen H. Taubman, Mitchell McEachin, John J. Leaf, Ronald B. Oppenheim-Leaf, Misty L. TI Comparing Different Classes of Reinforcement to Increase Expressive Language for Individuals with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID IDENTIFYING REINFORCERS; STIMULUS PREFERENCE; CHILDREN; BEHAVIOR; DISABILITIES AB One of the basic principles of applied behavior analysis is that behavior change is largely due to that behavior being reinforced. Therefore the use of positive reinforcement is a key component of most behavioral programs for individuals diagnosed with autism. In this study we compared four different classes of reinforcers (i.e., food, praise, toys, and feedback) on the rate of skill acquisition for three individuals diagnosed with autistic disorder. Using a parallel treatments design, the results of this study showed that all four classes of reinforcement were effective for teaching all of the participants. Results also indicated that food reinforecers were more efficient and more preferred. Finally, participants performance during teaching was idiosyncratic across the three participants. C1 [Leaf, Justin B.; Dale, Stephanie; Kassardjian, Alyne; Tsuji, Kathleen H.; Taubman, Mitchell; McEachin, John J.; Leaf, Ronald B.] Autism Partnership Fdn, Seal Beach, CA USA. [Oppenheim-Leaf, Misty L.] Behav Therapy & Learning Ctr, Calgary, AB, Canada. RP Leaf, JB (reprint author), 200 Marina Dr, Seal Beach, CA 90740 USA. EM Jblautpar@aol.com CR Allyon T., 1968, J APPL BEHAV ANAL, V1, P13 Carr JE, 2000, J APPL BEHAV ANAL, V33, P353, DOI 10.1901/jaba.2000.33-353 Catania C. A., 1998, LEARNING 4 EDITION Charlop M. 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Train. Autism Dev. Disabil. PD DEC PY 2014 VL 49 IS 4 BP 533 EP 546 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600004 ER PT J AU Flores, MM Hinton, VM Strozier, SD Terry, SL AF Flores, Margaret M. Hinton, Vanessa M. Strozier, Shaunita D. Terry, Shermeka L. TI Using the Concrete-representational-abstract Sequence and the Strategic Instruction Model to Teach Computation to Students with Autism Spectrum Disorders and Developmental Disabilities SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SCHEMA-BASED INSTRUCTION; MATHEMATICS; FACTS AB There is a need for further investigation of evidence-based practices for students with autism spectrum disorders and developmental disabilities leading to students' success within the general education curriculum (Cihak & Foust, 2008; Rockwell, Griffin, & Jones, 2011; Schaefer-Whitby, Travers, & Harnik, 2009). The purpose of this study was to investigate the concrete-representational-abstract instructional sequence and the Strategic Instruction Model (CRA-SIM) with regard to mathematics computation performance of students with ASD and DD. Eleven elementary students with ASD and DD participated in four weeks of instruction with regard to basic additional and subtraction using CRA-SIM. A paired samples t test statistical procedure was conducted to evaluate the differences in student progress across curriculum-based measures over the course of the study. Results indicated that the students made significant progress across three CBMs administered over the course of the study. Measures of effect size also indicated that CRA-SIM had a strong effect on student performance. These results, descriptive performance results, and their implications will be discussed. C1 [Flores, Margaret M.; Hinton, Vanessa M.; Terry, Shermeka L.] Auburn Univ, Auburn, AL 36849 USA. [Strozier, Shaunita D.] Valdosta State Univ, Valdosta, GA USA. RP Flores, MM (reprint author), Auburn Univ, Dept Special Educ Rehabil & Counseling, 2084 Haley Ctr, Auburn, AL 36849 USA. EM mmf0010@auburn.edu CR Beck R., 1995, BASIC SKILL BUILDERS Boutot E. A., 2011, AUTISM SPECTRUM DISO Browder DM, 2008, EXCEPT CHILDREN, V74, P407 Butler FM, 2001, MENT RETARD, V39, P20, DOI 10.1352/0047-6765(2001)039<0020:TMTSWM>2.0.CO;2 Calik N. C., 2010, INT J SPECIAL ED, V25, P195 Cihak DF, 2008, FOCUS AUTISM DEV DIS, V23, P131, DOI 10.1177/1088357608318950 Constable S., 2013, TEACHING EXCEPTIONAL, V45, P6 Donaldson J. B., 2010, TEACHING EXCEPTIONAL, V42, P40 Fletcher D., 2012, EDUC TRAIN AUTISM DE, V45, P449 FUCHS LS, 1993, SCHOOL PSYCHOL REV, V22, P27 Ganz J., 2011, TEACHING EXCEPTIONAL, V43, P8 Harris C. 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K., 1988, LEARNING DISABILITIE, V4, P52 Rockwell SB, 2011, FOCUS AUTISM DEV DIS, V26, P87, DOI 10.1177/1088357611405039 Schaefer-Whitby P. J., 2009, BEHAVIOUR, V19, P3 Scott K., 1993, EXCEPTIONALITY, V4, P125, DOI 10.1207/s15327035ex0402_6 U.S. Department of Education, 2002, NO CHILD LEFT DESKT Wagner M., 2006, ACAD ACHIEVEMENT FUN Witzel B., 2007, MATH TEACHING MIDDLE, V13, P244 Witzel B. S., 2003, LEARNING DISABILITIE, V3, P49, DOI DOI 10.1111/1540-5826.00068 NR 32 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 DEC PY 2014 VL 49 IS 4 BP 547 EP 554 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600005 ER PT J AU O'Hara, M Hall, LJ AF O'Hara, Meghan Hall, Laura J. TI Increasing Engagement of Students with Autism at Recess through Structured Work Systems SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SPECTRUM DISORDERS; SOCIAL-SKILLS; CHILDREN; BEHAVIOR; PEERS; TIME; PLAY AB Students with autism spectrum disorder (ASD) who attend public schools benefit from supplementary structure throughout their day, including during recess periods on the playground. The following study used a concurrent multiple-baseline design to evaluate the effects of a structured work system taught by the special education teacher using graduated guidance on the engagement of three elementary age students with ASD. Results revealed increases in engagement compared with baseline most clearly for two of the three students. The importance of incorporating prompt fading strategies when implementing any visual support system is discussed. C1 [O'Hara, Meghan; Hall, Laura J.] San Diego State Univ, San Diego, CA 92182 USA. 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TI ASD Academic Transitions: Trends in Parental Perspective SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID AUTISM SPECTRUM DISORDERS; SELF-DETERMINATION; YOUNG-CHILDREN; STUDENTS; DISABILITIES; EDUCATION; SCHOOL AB Academic transitions are a necessary and important part of an ASD student's life. Parental involvement and perspective is a vital part of each transition planning process. The primary goal of this research was to identify trends in parent perspectives regarding ASD academic transitions through meta-synthesis of current research. The research also seeks to identify shifts in parent perceptions of the importance of specific transitional program elements during different academic transitional periods. Results indicated a clear trend within each academic transition category as well as trends throughout the transition periods. The main trend in parental perspective throughout the transitions is the de-structuration of the transition planning process and increased personalization with the advancement of each academic transition. Possible uses of research results to ease the transition planning process for parents are summarized and discussed. C1 [Lee, Cindy; McCoy, Kathleen M.; Zucker, Stanley H.; Mathur, Sarup R.] Arizona State Univ, Tempe, AZ 85287 USA. RP McCoy, KM (reprint author), Arizona State Univ, Mary Lou Fulton Teachers Coll, POB 871811, Tempe, AZ 85287 USA. EM Kathleen.McCoy@asu.edu CR Anderson M. L., 2006, COUNSELING ADULTS TR Brekken L., 1990, TRANSITION ISSUES MO California Department of Education, 2005, HDB TRANS EARL CHILD California Department of Education, 2001, HDB DEV IND FAM SERV Camarena PM, 2009, FOCUS AUTISM DEV DIS, V24, P115, DOI 10.1177/1088357609332675 Dillon GV, 2012, FOCUS AUTISM DEV DIS, V27, P111, DOI 10.1177/1088357612441827 Dolyniuk C. 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PD DEC PY 2014 VL 49 IS 4 BP 576 EP 593 PG 18 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600008 ER PT J AU Murphy, C Martin, GL Yu, CT AF Murphy, Colleen Martin, Garry L. Yu, C. T. TI The Predictive Validity of the Assessment of Basic Learning Abilities versus Parents' Predictions with Children with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID INTELLECTUAL DISABILITIES; PEOPLE AB The Assessment of Basic Learning Abilities (ABLA) is an empirically validated clinical tool for assessing the learning ability of persons with intellectual disabilities and children with autism. An ABLA tester uses standardized prompting and reinforcement procedures to attempt to teach, individually, each of six tasks, called levels, to a testee, until a pass or a fail criterion is met on each level. The six levels are ordered in difficulty from Level I to Level 6. We examined the predictive validity of the ABLA performance of nine children with autism who passed ABLA Levels 2 or 3, and failed higher levels. We attempted to teach 20 criterion tasks to each child, using standardized prompting and reinforcement procedures, until each child met either the pass or the fail criterion of the ABLA on each task. We predicted that each child would pass the criterion tasks that corresponded to his/her previously passed ABLA levels, and would fail the criterion tasks that corresponded to his/her previously failed ABLA levels. A parent of each child was also asked to predict the child's pass-fail learning performance on the 20 criterion tasks. Ninety-two percent of the predictions based on the children's ABLA performance were confirmed, and the ABLA was significantly more accurate than the parents for predicting the children's performance on the criterion tasks. C1 [Martin, Garry L.] Univ Manitoba, Winnipeg, MB R3T 2M6, Canada. St Amant Res Ctr, Winnipeg, MB, Canada. RP Martin, GL (reprint author), Univ Manitoba, 129 St Pauls Coll, Winnipeg, MB R3T 2M6, Canada. EM garry.martin@ad.umanitoba.ca CR Condillac R. A., 2002, THESIS U TORONTO TOR Cummings A., 2000, J DEV DISABILITIES, V7, P109 DeWiele L., 2011, KERR MEYERSON ASSESS DeWiele L. A., 1996, INT J PRACTICAL APPR, V20, P7 Kerr N., 1977, REHABIL PSYCHOL, V24, P95 Martin G., 2011, BEHAV MODIFICATION W, V9th Martin G. L., 2000, J DEV DISABILITIES, V7, P10 Martin GL, 2008, BEHAV MODIF, V32, P228, DOI 10.1177/0145445507309022 Morris D., 2002, THESIS U TORONTO TOR Sakko G, 2004, AM J MENT RETARD, V109, P44, DOI 10.1352/0895-8017(2004)109<44:VNMAAW>2.0.CO;2 Schwartzman LJV, 2009, EDUC TRAIN DEV DISAB, V44, P271 Stubbings V, 1998, AM J MENT RETARD, V102, P473 Thorsteinsson JR, 2007, AM J MENT RETARD, V112, P130, DOI 10.1352/0895-8017(2007)112[130:PLAOPW]2.0.CO;2 Vause T, 2007, J APPL RES INTELLECT, V20, P483, DOI 10.1111/j.1468-3148.2006.00351.x Vause T., 2000, J DEV DISABILITIES, V7, P37 Viel J, 2011, RES AUTISM SPECT DIS, V5, P1370, DOI 10.1016/j.rasd.2011.01.019 Ward R., 2000, J DEV DISABILITIES, V7, P142 NR 17 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 DEC PY 2014 VL 49 IS 4 BP 601 EP 611 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AT8PA UT WOS:000345193600010 ER PT J AU Gilman, SL AF Gilman, Sander L. TI Madness as disability SO HISTORY OF PSYCHIATRY LA English DT Article DE Autism; bipolar disease; disability; madness AB How does society imagine mental illness? Does this shift radically over time and with different social attitudes as well as scientific discoveries about the origins and meanings of mental illness? What happens when we begin to think about mental illness as madness, as a malleable concept constantly shifting its meaning? We thus look at the meanings associated with general paralysis of the insane' in the nineteenth century and autism today in regard to disability. In this case study we examine the claims by scholars such as the anthropologist Emily Martin and the psychiatrist Kay Jamison as to the relationship between mental illness, disability and creativity. Today, the health sciences have become concerned with mental illness as a form of disability. How does this change the meaning of madness for practitioners and patients? C1 Emory Univ, Atlanta, GA 30312 USA. RP Gilman, SL (reprint author), Emory Univ, S Callaway Hall, Atlanta, GA 30312 USA. EM slgilma@emory.edu CR Blume H, 1998, ATLANTIC Bucknill John Charles, 1858, MANUAL PSYCHOL MED Callard F, 2012, MENTAL ILLNESS DISCR Chivers S, 2010, PROBLEM BODY PROJECT Couser T, 1997, RECOVERING BODIES IL Davis Lennard J., 2000, DEFECTS ENGENDERING, P54 Foucault Michel, 2006, HIST MADNESS Francis A., 2013, SAVING NORMAL INSIDE Fromm E., 1955, SANE SOC Garland-Thomson R., 1997, EXTRAORDINARY BODIES Gilman SL, 1982, SEEING INSANE CULTUR Gilman SL, 1993, CASE SIGMUND FREUD M Goffman E., 1961, ASYLUMS ESSAYS SOCIA Griesinger W, 1868, ARCH PSYCHIAT NERVEN, V1, piii Hellker P, 2011, COLL ENGL, V73, P485 Laing RD, 1965, DIVIDED SELF EXISTEN Longmore P., 2001, NEW DISABILITY HIST Millard Candice, 2011, DESTINY REPUBLIC TAL Murray S, 2012, AUTISM Pelka F, 2012, WHAT WE HAVE DONE OR Porter Roy, 2003, MADNESS BRIEF HIST Quayson Ato, 2007, AESTHETIC NERVOUSNES Rekers G, 1995, S SMITH VICTIM MURDE Robinson D. N., 1998, WILD BEASTS IDLE HUM Savarese ET, 2010, DISABILITY STUDIES Q, V30, P1 Shorter Edward, 1998, HIST PSYCHIAT ERA AS Stiker H. -J., 1999, HIST DISABILITY Szasz T. S., 1961, MYTH MENTAL ILLNESS Trent Jr James W., 1994, INVENTING FEEBLE MIN Wendell S., 1996, REJECTED BODY FEMINI NR 30 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0957-154X EI 1740-2360 J9 HIST PSYCHIATR JI Hist. Psychiatr. PD DEC PY 2014 VL 25 IS 4 BP 441 EP 449 DI 10.1177/0957154X14545846 PG 9 WC History Of Social Sciences; Psychiatry SC Social Sciences - Other Topics; Psychiatry GA AT9BY UT WOS:000345224100007 PM 25395442 ER PT J AU Elberling, H Linneberg, A Olsen, EM Houmann, T Rask, CU Goodman, R Skovgaard, AM AF Elberling, Hanne Linneberg, Allan Olsen, Else Marie Houmann, Tine Rask, Charlotte Ulrikka Goodman, Robert Skovgaard, Anne Mette TI Infancy predictors of hyperkinetic and pervasive developmental disorders at ages 5-7 years: results from the Copenhagen Child Cohort CCC2000 SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Infancy; predictors; autism spectrum disorder; hyperactivity disorder; mother-infant relationship; birth cohort; longitudinal study; CCC2000 ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ADOLESCENT PSYCHIATRIC-DISORDERS; AUTISM SPECTRUM DISORDERS; MENTAL-HEALTH PROBLEMS; RISK-FACTORS; PSYCHOPATHOLOGY; TRAJECTORIES; PREVALENCE; SYMPTOMS; EPIDEMIOLOGY AB BackgroundEpidemiological studies infancy predictors of mental disorders are scarce. MethodsThe study is part of a longitudinal birth-cohort study, The Copenhagen Child Cohort CCC2000. Infant mental health and development and mother-infant relations were assessed by community health nurses from birth to age 10months. Data on the perinatal period were obtained from Danish National Registers. Mental health outcome at age 5-7years was investigated in 1,585 children who were assessed by the Developmental and Well-Being Assessment (DAWBA) and diagnosed according to the ICD-10. ResultsPredictors of autism spectrum disorders were problems of oral-motor development OR 5.02 (95% CI: 1.63-15.42) and overall development OR 4.24 (95% CI: 1.35-13.33). A deviant pattern of activity and interests were predictive of autism spectrum disorder, OR 5.34 (95% CI 1.45-19.70) and hyperkinetic disorder, OR 4.71 (95% CI: 1.28-17.39). Hyperkinetic disorder was furthermore predicted by mother-infant relationship problems, OR 8.07 (95% CI: 2.90-22.47). The significant associations between infant developmental problems and autism spectrum disorders persisted in multiple logistic regression analyses controlled for maternal psychological problems and mother-infant relationship problems, OR 3.21 (95% CI: 1.09-9.45). Mother-infant relationship problems remained strongly associated to hyperkinetic disorders in the multivariate analyses controlled for child development problems and maternal psychological problems, OR 5.20 (95% CI: 1.55-17.47). No significant infancy predictors were found regarding emotional and behavioural disorders at age 5-7years. ConclusionPredictors of autism spectrum/pervasive developmental disorders and hyperkinetic disorders at child age 5-7years were identified between birth and child age 10months in community health settings. The study results suggest potential areas of early preventive intervention, which have to be further explored regarding the psychometric qualities of the identification of infants at risk, and concerning methods to handle and intervene towards these children in the general child health surveillance. C1 [Elberling, Hanne; Olsen, Else Marie; Houmann, Tine; Skovgaard, Anne Mette] Child & Adolescent Psychiat Ctr, DK-2600 Glostrup, Denmark. [Elberling, Hanne; Linneberg, Allan] Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark. [Linneberg, Allan; Skovgaard, Anne Mette] Univ Copenhagen, Fac Hlth Sci, Dept Neurol Psychiat & Sensory Sci, DK-1168 Copenhagen, Denmark. [Rask, Charlotte Ulrikka] Aarhus Univ Hosp, Res Clin Funct Disorders & Psychosomat, Child & Adolescent Psychiat Ctr Risskov, DK-8000 Aarhus, Denmark. [Goodman, Robert] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London WC2R 2LS, England. RP Elberling, H (reprint author), Child & Adolescent Psychiat Ctr, Nordre Ringvej 69, DK-2600 Glostrup, Denmark. EM hanne.elberling@regionh.dk FU Copenhagen County Research Foundation; Health Insurance Foundation; Mrs C. Hermansens Fund; Foundation of Butcher Max Worzner and wife; Psychiatric Foundation; Tryg Foundation; Augustinus Foundation; Danish Association for Mental Health FX The study was supported by The Copenhagen County Research Foundation, The Health Insurance Foundation, Mrs C. Hermansens Fund, the Foundation of Butcher Max Worzner and wife, The Psychiatric Foundation of 1967, The Tryg Foundation, The Augustinus Foundation and The Danish Association for Mental Health. The authors declare that they have no potential or competing conflicts of interest. R. G. is director and owner of Youth in Mind, which provides no-cost and low-cost software and websites related to the SDQ and DAWBA. The authors thank the consultant child and adolescent psychiatrists: Elisabeth Zambach and Merete Frantzen for contributing to the DAWBA investigation and Anne Helms Andreasen for statistical advice. 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Lord, Catherine TI Heterogeneity and plasticity in the development of language: a 17-year follow-up of children referred early for possible autism SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Early intervention; heterogeneity; language impairment; plasticity ID DIAGNOSTIC OBSERVATION SCHEDULE; IMPAIRMENT; TRAJECTORIES; DISORDERS; SPECTRUM; OUTCOMES; INDIVIDUALS; ABILITIES; GROWTH; SPEECH AB BackgroundDelayed, abnormal language is a common feature of autism and language therapy often a significant component of recommended treatment. However, as with other disorders with a language component, we know surprisingly little about the language trajectories and how varied these might be across different children. Thus, we know little about how and when language problems might resolve, whether there are periods of relative stability or lack of change and what periods might offer more favourable circumstances for intervention. MethodsExpressive and receptive language was measured on six occasions between age 2 and 19 on a cohort of 192 children initially referred for autism. Latent class growth models were fitted to characterize the patterns of heterogeneous development. ResultsLatent class growth analysis identified seven classes. Between age 6 and 19, all classes tracked in parallel. Between ages 2 and 6, development was more heterogeneous with considerable variation in relative progress. In all groups, receptive and expressive language developed very largely in tandem. ConclusionsThe results confirmed previous analysis of children with specific language impairment where progress beyond age 6 was remarkably uniform. Greater variation was evident before this age with some groups making clearly better or worse progress compared to others. While this developmental heterogeneity may simply be a reflection of variation in preexisting and unchanging biological disposition, it may also reflect, at least in part, greater sensitivity in the early years to environments that are more or less supportive of language development. These findings contribute to the case for the importance of early intervention. C1 [Pickles, Andrew] Kings Coll London, Inst Psychiat, Dept Biostat, London SE5 8AF, England. [Anderson, Deborah K.] Univ Michigan, Canc Trials Off, Ann Arbor, MI 48109 USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Brain Dev, New York, NY USA. RP Pickles, A (reprint author), Kings Coll London, Inst Psychiat, Dept Biostat, De Crespigny Pk, London SE5 8AF, England. EM andrew.pickles@kcl.ac.uk RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU National Institute of Mental Health [R01 MH066496]; UK Medical Research Council [G0802307]; National Institute for Health Research (NIHR); Mental Health Biomedical Research Centre at South London; Maudsley NHS Foundation Trust and King's College London; ADOS FX This work was primarily supported by a grant from National Institute of Mental Health (R01 MH066496). Additional support came from the UK Medical Research Council (G0802307) and the National Institute for Health Research (NIHR), Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. C. L. receives royalties from the publisher of the ADOS and ADI-R; all proceeds from its use in this study were donated to charity. D. A. receives occasional translation fees from the publisher of the ADOS. A. P. receives royalties from the publisher of the SCQ. 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Child Psychol. Psychiatry PD DEC PY 2014 VL 55 IS 12 BP 1354 EP 1362 DI 10.1111/jcpp.12269 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AU0LJ UT WOS:000345313900012 PM 24889883 ER PT J AU Stavropoulos, KKM Carver, LJ AF Stavropoulos, Katherine K. M. Carver, Leslie J. TI Reward anticipation and processing of social versus nonsocial stimuli in children with and without autism spectrum disorders SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorder; social motivation; event-related potentials; social stimuli ID EVENT-RELATED POTENTIALS; PRECEDING NEGATIVITY PRIOR; FEEDBACK STIMULI; FACE; ATTENTION; OUTCOMES; INTERVENTION; PERCEPTION; ACTIVATION; PUNISHMENT AB BackgroundHow children respond to social and nonsocial rewards has important implications for both typical and atypical social-cognitive development. Individuals with autism spectrum disorders (ASD) are thought to process rewards differently than typically developing (TD) individuals. However, there is little direct evidence to support this claim. MethodsTwo event-related potentials were measured. The stimulus preceding negativity (SPN) was utilized to measure reward anticipation, and the feedback related negativity (FRN) was utilized to measure reward processing. Participants were 6- to 8-year-olds with (N=20) and without (N=23) ASD. Children were presented with rewards accompanied by incidental face or nonface stimuli. Nonface stimuli were composed of scrambled face elements in the shape of arrows, controlling for low-level visual properties. ResultsChildren with ASD showed smaller responses while anticipating and processing rewards accompanied by social stimuli than TD children. Anticipation and processing of rewards accompanied by nonsocial stimuli was intact in children with ASD. ConclusionsThis is the first study to measure both reward anticipation and processing in ASD while controlling for reward properties. The findings provide evidence that children with autism have reward anticipation and processing deficits for social stimuli only. Our results suggest that while typically developing children find social stimuli more salient than nonsocial stimuli, children with ASD may have the opposite preference. C1 [Stavropoulos, Katherine K. M.; Carver, Leslie J.] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Stavropoulos, KKM (reprint author), Univ Calif San Diego, Dept Psychol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM kmeltzof@ucsd.edu FU Autism Speaks Dennis Weatherstone Predoctoral Fellowship [7844]; National Institute of Child Health and Human Development [HD052804-01A2]; National Institute of Neurological Disorders and Stroke [NS071580-01] FX K.K.M.S. is supported by an Autism Speaks Dennis Weatherstone Predoctoral Fellowship (#7844). 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Psychiatry PD DEC PY 2014 VL 55 IS 12 BP 1398 EP 1408 DI 10.1111/jcpp.12270 PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AU0LJ UT WOS:000345313900017 PM 24890037 ER PT J AU Anestis, MD Anestis, JC Zawilinski, LL Hopkins, TA Lilienfeld, SO AF Anestis, Michael D. Anestis, Joye C. Zawilinski, Laci L. Hopkins, Tiffany A. Lilienfeld, Scott O. TI Equine-Related Treatments For Mental Disorders Lack Empirical Support: A Systematic Review of Empirical Investigations SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE equine assisted psychotherapy; therapeutic horseback riding; pseudoscience; evidence based psychotherapy ID DOLPHIN-ASSISTED THERAPY; FLAWED CONCLUSIONS; CHILDREN; PSYCHOTHERAPIES; INTERVENTIONS; AUTISM; WORLD AB Context: Equine-related treatments (ERT) for mental disorders are becoming increasingly popular for a variety of diagnoses; however, they have been subjected only to limited systematic investigation. Objective: To examine the quality of and results from peer-reviewed research on ERT for mental disorders and related outcomes. Method: Peer-reviewed studies (k = 14) examining treatments for mental disorders or closely related outcomes were identified from databases and article reference sections. Results: All studies were compromised by a substantial number of threats to validity, calling into question the meaning and clinical significance of their findings. Additionally, studies failed to provide consistent evidence that ERT is superior to the mere passage of time in the treatment of any mental disorder. Conclusion: The current evidence base does not justify the marketing and utilization of ERT for mental disorders. Such services should not be offered to the public unless and until well-designed studies provide evidence that justify different conclusions. C (C) 2014 Wiley Periodicals, Inc. 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SO MOLECULAR PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; INTESTINAL MICROBIOTA; WIDE ASSOCIATION; BRAIN AXIS; BEHAVIOR; HEALTH; INFECTION; MODEL; DEPRESSION; POPULATION AB Research into the genomics of schizophrenia promises much, but so far is resplendent with failures to replicate, and has yielded little of therapeutic potential. Within our bodies resides a dynamic population of gut microbes forming a symbiotic superorganism comprising a myriad of bacteria of approximately 1014 cells, containing 100 times the number of genes of the human genome and weighing approximately the same as the human brain. Recent preclinical investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. We are pivotally dependent on the neuroactive substances produced by such bacteria. 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EM t.dinan@ucc.ie FU Science Foundation Ireland (Alimentary Pharmabiotic Centre) [SFI/12/RC/2273]; Health Research Board of Ireland [HRA_POR/2011/23, HRA_POR/2012/32]; European Community [FP7/2007-2013] FX We are supported in part by Science Foundation Ireland in the form of a centre grant (Alimentary Pharmabiotic Centre Grant Number SFI/12/RC/2273); by the Health Research Board of Ireland (Grant Numbers HRA_POR/2011/23 and HRA_POR/2012/32); and received funding from the European Community's Seventh Framework Programme Grant MyNewGut under Grant Agreement No. FP7/2007-2013. The Centre has conducted studies in collaboration with several companies including GSK, Pfizer, Cremo, Suntory, Wyeth and Mead Johnson. 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Psychiatr. PD DEC PY 2014 VL 19 IS 12 BP 1252 EP 1257 DI 10.1038/mp.2014.93 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AU2CL UT WOS:000345423500002 PM 25288135 ER PT J AU van Elst, LT Maier, S Fangmeier, T Endres, D Mueller, GT Nickel, K Ebert, D Lange, T Hennig, J Biscaldi, M Riedel, A Perlov, E AF van Elst, L. Tebartz Maier, S. Fangmeier, T. Endres, D. Mueller, G. T. Nickel, K. Ebert, D. Lange, T. Hennig, J. Biscaldi, M. Riedel, A. Perlov, E. TI Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis SO MOLECULAR PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BORDERLINE PERSONALITY-DISORDER; CARRIER SLC25A12 GENE; H-1 MR SPECTROSCOPY; ASPERGER-SYNDROME; ALZHEIMERS-DISEASE; BRAIN INFLAMMATION; PREFRONTAL CORTEX; POSTMORTEM BRAIN AB Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas. C1 [van Elst, L. Tebartz; Maier, S.; Fangmeier, T.; Endres, D.; Mueller, G. T.; Nickel, K.; Ebert, D.; Biscaldi, M.; Perlov, E.] Univ Freiburg, Sect Expt Neuropsychiat, Clin Psychiat & Psychotherapy, D-79104 Freiburg, Germany. [van Elst, L. Tebartz; Fangmeier, T.; Ebert, D.; Biscaldi, M.; Riedel, A.] Univ Freiburg, Univ Zentrum Autismus Spektrum, D-79104 Freiburg, Germany. [Lange, T.; Hennig, J.] Univ Med Ctr Freiburg, Dept Radiol, Freiburg, Germany. [Lange, T.] Univ Freiburg, Freiburg Inst Adv Studies FRIAS, D-79104 Freiburg, Germany. [Biscaldi, M.] Univ Freiburg, Dept Child & Adolescent Psychiat & Psychotherapy, D-79104 Freiburg, Germany. RP van Elst, LT (reprint author), Univ Freiburg, Sect Expt Neuropsychiat, Clin Psychiat & Psychotherapy, Hauptstr 5, D-79104 Freiburg, Germany. EM tebartzvanelst@uniklinik-freiburg.de FU federal Ministry of Education and Research [BMBF 01GV0606] FX Part of the study was supported by a grant from the federal Ministry of Education and Research to LTVE (BMBF 01GV0606). 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Psychiatr. PD DEC PY 2014 VL 19 IS 12 BP 1314 EP 1325 DI 10.1038/mp.2014.62 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AU2CL UT WOS:000345423500009 ER PT J AU Lu, LN Guo, H Peng, Y Xun, GL Liu, YL Xiong, ZM Tian, D Liu, YL Li, W Xu, XJ Zhao, JP Hu, ZM Xia, K AF Lu, Lina Guo, Hui Peng, Yu Xun, Guanglei Liu, Yanling Xiong, Zhimin Tian, Di Liu, Yalan Li, Wei Xu, Xiaojuan Zhao, Jingping Hu, Zhengmao Xia, Kun TI Common and rare variants of the THBS1 gene associated with the risk for autism SO PSYCHIATRIC GENETICS LA English DT Article DE autism; mutation screening; synaptogenesis; THBS1 ID GROWTH-FACTOR-BETA; II RECEPTOR; THROMBOSPONDIN; NEUROLIGINS; PROTEINS; DROSOPHILA; CALCIUM; BINDING AB ObjectivesAutism is a severe neurodevelopmental disorder. Many susceptible or causative genes have been identified, and most of them are related to synaptogenesis. The THBS1 gene encodes thrombospondin 1, which plays a critical role in synaptogenesis of the central nervous system in the developing brain. However, no study has been carried out revealing that THBS1 is an autism risk gene.MethodsWe analyzed the whole coding region and the 5-untranslated region of the THBS1 gene in 313 autistic patients by Sanger sequencing, which was also used to analyze the identified variants in 350 normal controls. Association analysis was carried out using PLINK or R. Haplotype analysis was carried out using Haploview. Functional prediction and conservation analysis of missense variants were carried out using ANNOVAR.ResultsTwelve variants, including five common variants and seven rare variants, were identified in the THBS1 coding region and the 5-untranslated region. Among them, one common variant (c.1567A>G:p.T523A) was significantly associated with autism (P<0.05). Two rare variants (c.2429G>A:p.R810Q, c.3496G>C:p.E1166Q) were absent in the 350 controls and were not reported in the single nucleotide polymorphism database (dbSNP). Combined association analysis of the rare variants (minor allele frequency<0.01) in patients and Asian samples in the 1000 genome project revealed a significant association between these rare variants and autism (P=0.039).ConclusionOur data revealed that both common and rare variants of the THBS1 gene are associated with risk for autism, suggesting that THBS1 is a novel susceptible gene for autism. C1 [Lu, Lina; Guo, Hui; Peng, Yu; Hu, Zhengmao; Xia, Kun] Cent S Univ, Sch Life Sci, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Xun, Guanglei; Zhao, Jingping] Cent S Univ, Mental Hlth Inst, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Lu, Lina; Guo, Hui; Peng, Yu; Liu, Yanling; Xiong, Zhimin; Tian, Di; Liu, Yalan; Li, Wei; Xu, Xiaojuan; Hu, Zhengmao; Xia, Kun] Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China. [Xia, Kun] Cent S Univ, Key Lab Med Informat Res, Changsha, Hunan, Peoples R China. [Xun, Guanglei] Mental Hlth Ctr Shandong Prov, Jinan, Shandong, Peoples R China. RP Xia, K (reprint author), Cent S Univ, State Key Lab Med Genet, 110 Xiangya Rd, Changsha, Hunan, Peoples R China. EM xiakun@sklmg.edu.cn FU National Basic Research Program of China [2012CB517902]; National Natural Science Foundation of China [81330027, 81161120544, 81301172] FX The authors thank all the families that participated and collaborated with us in this study. They also thank the Yilin (Elim) Autism Training Department of the Qingdao Municipal Autism Research Institute, which provided a lot of help in the collecting samples. They also thank Professor Jiada Li, who assisted with proofreading of the manuscript. This work was supported by the National Basic Research Program of China (2012CB517902) and the National Natural Science Foundation of China (81330027, 81161120544 and 81301172). 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Genet. PD DEC PY 2014 VL 24 IS 6 BP 235 EP 240 DI 10.1097/YPG.0000000000000054 PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AT4OI UT WOS:000344918900001 PM 25304225 ER PT J AU Jones, RM Cadby, G Blangero, J Abraham, LJ Whitehouse, AJO Moses, EK AF Jones, Rachel M. Cadby, Gemma Blangero, John Abraham, Lawrence J. Whitehouse, Andrew J. O. Moses, Eric K. TI MACROD2 gene associated with autistic-like traits in a general population sample SO PSYCHIATRIC GENETICS LA English DT Article DE association; autistic-like traits; MACROD2; Raine study; single nucleotide polymorphism ID GENOME-WIDE ASSOCIATION; SPECTRUM QUOTIENT AQ; COPY NUMBER VARIANT; DISORDERS; LINKAGE; COMMON; SCHIZOPHRENIA; PHENOTYPE; RISK; SUSCEPTIBILITY AB There is now substantial evidence that autistic-like traits in the general population lie on a continuum, with clinical autism spectrum disorders (ASD) representing the extreme end of this distribution. In this study, we sought to evaluate five independently identified genetic associations with ASD with autistic-like traits in the general population. In the study cohort, clinical phenotype and genomewide association genotype data were obtained from the Western Australian Pregnancy Cohort (Raine) Study. The outcome measure used was the Autism Spectrum Quotient (AQ), a quantitative measure of autistic-like traits of individuals in the cohort. Total AQ scores were calculated for each individual, as well as scores for three subscales. Five candidate single nucleotide polymorphism (SNP) associations with ASD, reported in previously published genomewide association studies, were selected using a nominal cutoff value of P less than 1.0x10(-5). We tested whether these five SNPs were associated with total AQ and the subscales, after adjustment for possible confounders. SNP rs4141463 located in the macro domain containing 2 (MACROD2) gene was significantly associated with the Communication/Mindreading subscale. No other SNP was significantly associated with total AQ or the subscales. The MACROD2 gene is a strong positional candidate risk factor for autistic-like traits in the general population. C1 [Jones, Rachel M.; Cadby, Gemma; Abraham, Lawrence J.; Moses, Eric K.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia. [Jones, Rachel M.] Univ Western Australia, Sch Populat Hlth, Perth, WA 6009, Australia. [Abraham, Lawrence J.] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia. [Whitehouse, Andrew J. O.] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia. [Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. RP Jones, RM (reprint author), Univ Western Australia, Ctr Genet Origins Hlth & Dis, 35 Stirling Highway, Perth, WA 6009, Australia. EM rachel.jones@uwa.edu.au FU National Health and Medical Research Council [572613]; Career Development Fellowship from the NHMRC [1004065]; National Health and Medical Research Council (NHMRC); University of Western Australia (UWA); Curtin University; UWA Faculty of Medicine, Dentistry and Health Sciences; Raine Medical Research Foundation; Telethon Institute for Child Health Research; Women's and Infants Research Foundation; NHMRC [572613] FX Grant sponsor: National Health and Medical Research Council; Grant number: 572613. A.J.O.W. was supported by a Career Development Fellowship from the NHMRC (#1004065). The authors would like to acknowledge the National Health and Medical Research Council (NHMRC) for their long-term contribution toward funding the study over the last 20 years. Core Management of the Raine Study has been funded by the University of Western Australia (UWA), Curtin University, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Raine Medical Research Foundation, the Telethon Institute for Child Health Research, and the Women's and Infants Research Foundation. This study was partly funded by NHMRC Project Grant #572613. The authors are extremely grateful to all of the families who took part in this study and the whole Raine Study team, which includes the Cohort Manager, Data Manager, and data collection team. 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Genet. PD DEC PY 2014 VL 24 IS 6 BP 241 EP 248 DI 10.1097/YPG.0000000000000052 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AT4OI UT WOS:000344918900002 PM 25360606 ER PT J AU Radoeva, PD Coman, IL Salazar, CA Gentile, KL Higgins, AM Middleton, FA Antshel, KM Fremont, W Shprintzen, RJ Morrow, BE Kates, WR AF Radoeva, Petya D. Coman, Ioana L. Salazar, Cynthia A. Gentile, Karen L. Higgins, Anne Marie Middleton, Frank A. Antshel, Kevin M. Fremont, Wanda Shprintzen, Robert J. Morrow, Bernice E. Kates, Wendy R. TI Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes SO PSYCHIATRIC GENETICS LA English DT Article DE autism spectrum disorder; 22q11; 2 deletion; catechol-O-methyltransferase; proline dehydrogenase; velocardiofacial syndrome ID CARDIO-FACIAL SYNDROME; CATECHOL-O-METHYLTRANSFERASE; SCHIZOPHRENIA; CHILDREN; GENES; PHENOTYPES; SYMPTOMS; GENETICS; MEMORY; ADULTS AB Velocardiofacial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for psychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. There is emerging evidence for the involvement of catechol-O-methyltransferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH) in the psychiatric phenotype of individuals with VCFS. Here, we tested the hypothesis that PRODH and COMT are associated with ASD in youths with VCFS. We found that individuals with VCFS and the low-activity alleles of both PRODH and COMT (rs4819756A and rs4680A) were more likely to present with ASD as compared with individuals with VCFS and the high-activity alleles of these genes [P<0.05; odds ratio=6.0 (95% confidence interval=1.27-28.26; N=87)]. Our results suggest that PRODH and COMT may interact to contribute to the ASD phenotype in individuals with VCFS. C1 [Radoeva, Petya D.; Gentile, Karen L.; Middleton, Frank A.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Coman, Ioana L.; Salazar, Cynthia A.; Antshel, Kevin M.; Fremont, Wanda; Kates, Wendy R.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Higgins, Anne Marie; Shprintzen, Robert J.] Virtual Ctr Velocardiofacial Syndrome, Manlius, NY USA. [Morrow, Bernice E.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. RP Kates, WR (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM katesw@upstate.edu FU NIH [MH64824, MH65481, RO1HL084410]; Dennis Weatherstone Pre-Doctoral Fellowship [7076]; Upstate Golisano Children's Hospital FX NIH Grants MH64824 and MH65481 (to W. K.), RO1HL084410 (to B. M.); Dennis Weatherstone Pre-Doctoral Fellowship (Grant #7076 to P. R.); Grant from the Upstate Golisano Children's Hospital (to W.K.). 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PD DEC PY 2014 VL 24 IS 6 BP 269 EP 272 DI 10.1097/YPG.0000000000000062 PG 4 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AT4OI UT WOS:000344918900007 PM 25325218 ER PT J AU Tordjman, S Anderson, GM Kermarrec, S Bonnot, O Geoffray, MM Brailly-Tabard, S Chaouch, A Colliot, I Trabado, S Bronsard, G Coulon, N Botbol, M Charbuy, H Camus, F Touitou, Y AF Tordjman, Sylvie Anderson, George M. Kermarrec, Solenn Bonnot, Olivier Geoffray, Marie-Maude Brailly-Tabard, Sylvie Chaouch, Amel Colliot, Isabelle Trabado, Severine Bronsard, Guillaume Coulon, Nathalie Botbol, Michel Charbuy, Henriette Camus, Francoise Touitou, Yvan TI Altered circadian patterns of salivary cortisol in low-functioning children and adolescents with autism SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Cortisol; Autism; Circadian rhythm; Basal cortisol levels; Stress response; Repeated stress; Sensitization to stressors; Flattened cortisol patterns; Trait anxiety ID PITUITARY-ADRENAL AXIS; DEXAMETHASONE SUPPRESSION TEST; METASTATIC BREAST-CANCER; PLASMA BETA-ENDORPHIN; SPECTRUM DISORDERS; DIURNAL CORTISOL; SERUM CORTISOL; SOCIAL STRESS; STIMULATING-HORMONE; ANXIETY DISORDERS AB Background: Reports of higher stress responsivity, altered sleep-wake cycle and a melatonin deficit in autism have stimulated interest in the cortisol circadian rhythm in individuals with autism. Methods: The study was conducted on 55 low-functioning children and adolescents with autism (11.3 +/- 4.1 years-old) and 32 typically developing controls (11.7 +/- 4.9 years-old) matched for age, sex and puberty. Behavioral assessment was performed using the Autism Diagnostic Observation Schedule (ADOS). Salivary samples for measurement of cortisol were collected during a 24-h period (at least 0800 h-Day1, 1600 h, 0800 h-Day2 for 46 individuals with autism and 27 controls, and 0800 h-Day1, 1100 h, 1600 h, 2400 h, 0800 h-Day2 for 13 individuals with autism and 20 controls). Overnight (2000 h-0800 h) urinary cortisol excretion was also measured. Results: The autism group displayed significantly higher levels of salivary cortisol at all timepoints, flatter daytime and nighttime slopes, higher 0800 h cortisol levels on Day2 compared to Day1, and greater variances of salivary and urinary cortisol. There was a significant relationship between salivary cortisol levels and impairments in social interaction and verbal language. Overnight urinary cortisol excretion was similar in the autism and control groups. Conclusion: Anticipation of the stressful collection procedure appears to contribute to the higher 0800 h-Day2 versus 0800 h-Day1 salivary cortisol levels in autism. This sensitization to stressors might be as, or even more, important clinically than exposure to novelty in autism. The similar group means for overnight urinary cortisol excretion indicate that basal HPA axis functioning is unaltered in low-functioning autism. The elevated salivary cortisol levels observed in autism over the 24-h period in a repeated stressful condition, flattened diurnal cortisol patterns and the apparent effect of anticipation are consistent with prior findings in high trait anxiety. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Tordjman, Sylvie; Kermarrec, Solenn] CHGR, Pole Hosp Univ Psychiat Enfant & Adolescent Renne, F-35000 Rennes, France. [Tordjman, Sylvie; Kermarrec, Solenn] Univ Rennes 1, F-35000 Rennes, France. [Tordjman, Sylvie; Kermarrec, Solenn; Coulon, Nathalie] Univ Paris 05, CNRS, Lab Psychol Percept, UMR 8158, Paris, France. [Anderson, George M.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Bonnot, Olivier] CHU Nantes, Serv Univ Psychiat Enfant & Adolescent, F-44035 Nantes 01, France. [Geoffray, Marie-Maude] Hop Vinatier, Serv Univ Psychiat Enfant & Adolescent, Bron, France. [Brailly-Tabard, Sylvie; Trabado, Severine] Univ Paris 11, INSERM, U693, Fac Med Paris Sud, Le Kremlin Bicetre, France. [Brailly-Tabard, Sylvie; Chaouch, Amel; Colliot, Isabelle; Trabado, Severine] CHU Bicetre, AP HP, Serv Genet Mol Pharmacogenet & Hormonol, Le Kremlin Bicetre, France. [Bronsard, Guillaume] Conseil Gen Bouches du Rhone, Maison Dept Adolescent, Marseille, France. [Bronsard, Guillaume] Conseil Gen Bouches du Rhone, Ctr Medicopsychopedagog, Marseille, France. [Bronsard, Guillaume] Fac Med Marseille, Lab Sante Publ EA3279, Marseille, France. [Botbol, Michel] UBO, EA4686, Serv Hosp Univ Psychiat Enfant & Adolescent Brest, Brest, France. [Charbuy, Henriette] Paris 6 Sch Med, Paris, France. [Camus, Francoise; Touitou, Yvan] Rothschild Fdn, Chronobiol Unit, Paris, France. RP Tordjman, S (reprint author), CHGR, Pole Hosp Univ Psychiat Enfant & Adolescent, 154 Rue Chatillon, F-35000 Rennes, France. EM s.tordjman@yahoo.fr FU INSERM (Institut national de la sante et de la recherche medicate, France) [931009]; LPP (Laboratoire Psychologie de la Perception, France) FX Pr. Sylvie Tordjman gratefully acknowledges the support of INSERM (Institut national de la sante et de la recherche medicate, CRE No 931009, France) and the support of LPP (Laboratoire Psychologie de la Perception, France). 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In the current study, event-related potentials (ERPs) were measured in 12 individuals with ASD, aged 8-22 years, and 12 age- and gender-matched normal controls, to investigate the electrophysiological response to BM and a control visual stimulus. By introducing a novel experimental paradigm that can dissociate the electrophysiological responses to motion processing and the global shape processing of BM, we found that: (1) the timing of the response was preserved in ASD groups, whereas (2) the ERP response to BM was significantly enhanced compared with scrambled point-light motion (SM) in normal controls; the responses to both BM and SM were not significantly different in subjects with ASD. Because we did not find a significant group effect on the peak and mean amplitude induced by BM, it is presumed that this atypical response in individuals with ASD was due to over-sensitivity to the local motion signals. This experimental paradigm showed atypical local motion processing of BM in individuals with ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hirai, Masahiro; Kakigi, Ryusuke] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Integrat Physiol, Okazaki, Aichi 4448585, Japan. [Hirai, Masahiro; Gunji, Atsuko; Inoue, Yuki; Kita, Yosuke; Hayashi, Takashi; Inagaki, Masumi] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Dev Disorders, Kodaira, Tokyo 1878553, Japan. [Gunji, Atsuko] Yokohama Natl Univ, Coll Educ & Human Sci, Yokohama, Kanagawa 2408501, Japan. [Hirai, Masahiro] Aichi Human Serv Ctr, Inst Dev Res, Dept Functioning Sci, Kasugai, Aichi 4800392, Japan. [Inoue, Yuki] Shimada Ryoiku Ctr Hachioji, Tokyo 1930931, Japan. [Hayashi, Takashi] Nishikawa Clin, Dept Dev Med, Ube, Yamaguchi 7550151, Japan. [Nishimaki, Kengo] Natl Rehabil Ctr Persons Disabil, Dept Med Treatment 3, Pediat & Child Psychiat Sect, Tokorozawa, Saitama 3598555, Japan. RP Hirai, M (reprint author), Jichi Med Univ, Ctr Dev Adv Med Technol, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan. 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PD DEC PY 2014 VL 8 IS 12 BP 1623 EP 1634 DI 10.1016/j.rasd.2014.08.014 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700001 ER PT J AU Ugur, C Gurkan, CK AF Ugur, Cagatay Gurkan, Cihat Kagan TI Serum vitamin D and folate levels in children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Vitamin D; Calcium; Folate ID FOLIC-ACID SUPPLEMENTS; AUTOIMMUNITY; DEFICIENCY; SYMPTOMS; RISK AB It has recently proposed that vitamin D and folate may be involved in the aetiology of autism. We investigated the serum levels of vitamin D, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and folate in 54 young children, aged 3-8 years, with autism spectrum disorders (ASD) and in 54 age and gender matched normal controls. Vitamin D. Ca, P. ALP and folate levels in children with ASD were not different from control group. The correlational analysis in children with ASD revealed that Aberrant Behaviour Checklist, Autism Behaviour Checklist, and Childhood Autism Rating Scale scores and the level of cognitive development were not correlated with these laboratory findings. Our findings do not support the idea that serum levels of vitamin D and folate might be low in children with ASD. Nevertheless, it is possible that vitamin D and folate deficiency may be playing a role in development of ASD at earlier ages or during prenatal period. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ugur, Cagatay; Gurkan, Cihat Kagan] Ankara Univ, Sch Med, Dept Child & Adolescent Psychiat, Cebeci Hosp, TR-06230 Ankara, Turkey. RP Gurkan, CK (reprint author), Ankara Univ, Sch Med, Dept Child & Adolescent Psychiat, Cebeci Hosp, TR-06230 Ankara, Turkey. 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Autism Spectr. Disord. PD DEC PY 2014 VL 8 IS 12 BP 1641 EP 1647 DI 10.1016/j.rasd.2014.09.002 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700003 ER PT J AU Blacher, J Cohen, SR Azad, G AF Blacher, J. Cohen, S. R. Azad, G. TI In the eye of the beholder: Reports of autism symptoms by Anglo and Latino mothers SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Latino families; Screening; Ethnicity; Culture; Parent report; Diagnosis ID SPECTRUM DISORDERS; SOCIOECONOMIC-STATUS; AMERICAN FAMILIES; CHILDREN; DIAGNOSIS; AGE; DISABILITIES; PREVALENCE; ETHNICITY; ADULTS AB Latino children with autism spectrum disorder (ASD) are under-identified and under-diagnosed. Children suspected of ASD (28 Anglo and 55 Latino) were assessed via the Autism Diagnostic Observation Schedule (ADOS) and the mother Intake Form. A sub-sample of 40 children were assessed with the Autism Disagnostic Interview-Revised (ADIR). The primary objective was to determine whether Anglo and Latino mothers differed in their symptom reports, and whether their children differed in the professional classifications. Anglo mothers reported significantly more developmental concerns and ASD symptoms than Latino mothers, yet Latino children meeting diagnostic criteria for autism on the ADOS obtained higher ASD severity scores than Anglo children. The authors set forth three possible explanations for such discrepancies between parents and professionals in perceptions and reporting of autism symptoms: (1) Latino mothers are not as aware of the symptoms, and thus do not report them; and (2) Latino mothers are aware of general developmental delay but not as concerned as Anglo mothers until social communication deficits become more apparent. (3) Latino mothers' parenting practices and cultural beliefs about child-rearing might mask both the ASD symptomatology exhibited by their children and their recognition of it. (C) 2014 Published by Elsevier Ltd. C1 [Blacher, J.] Univ Calif Riverside, Grad Sch Educ, Attn SEARCH Family Autism Resource Ctr, Riverside, CA 92521 USA. [Cohen, S. R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Azad, G.] Univ Penn, Philadelphia, PA 19104 USA. RP Blacher, J (reprint author), Univ Calif Riverside, Grad Sch Educ, Attn SEARCH Family Autism Resource Ctr, Riverside, CA 92521 USA. EM jan.blacher@ucr.edu; shanarcohen@ucsd.edu; gaziazad@upenn.edu CR American Psychiatric Association, 2000, DIAGNOSTIC AND STATI American Psychiatric Association, 2013, DIAGNOSTIC AND STATI Arcia E, 2000, J CHILD FAM STUD, V9, P333, DOI 10.1023/A:1026444507343 Begeer S, 2009, J AUTISM DEV DISORD, V39, P142, DOI 10.1007/s10803-008-0611-5 Bridges M, 2012, EARLY CHILD RES Q, V27, P555, DOI 10.1016/j.ecresq.2012.01.005 Centers for Disease Control and Prevention, 2006, MORBIDITY AND MORTAL, V55, P486 Centers for Disease Control Prevention (CDC), 2014, MMWR RECOMM REP, V63, P1 Coonrod EE, 2004, INFANT YOUNG CHILD, V17, P258 Cuccaro ML, 1996, J AUTISM DEV DISORD, V26, P461, DOI 10.1007/BF02172830 Cuccaro ML, 2007, AM J MED GENET B, V144B, P1022, DOI 10.1002/ajmg.b.30535 Fine SE, 2005, J AUTISM DEV DISORD, V35, P461, DOI 10.1007/s10803-005-5036-9 Fombonne E., 2004, BMC PUBLIC HEALTH, V4, P1 Fountain C., 2012, PEDIATRICS, V129, P1 Gannotti ME, 2001, PHYS THER, V81, P1512 Garcia SB, 2000, REM SPEC EDUC, V21, P90, DOI 10.1177/074193250002100204 Gilliam JE, 2006, GILLIAM AUTISM RATIN Harry B., 1999, CULTURE IN SPECIAL E Hill A, 2001, PSYCHOPATHOLOGY, V34, P187, DOI 10.1159/000049305 Kalyanpur M., 2000, INT J DISABIL DEV ED, V47, P119, DOI 10.1080/713671106 Kogan MD, 2009, PEDIATRICS, V124, P1395, DOI 10.1542/peds.2009-1522 Le Couteur A., 2003, THE AUTISM DIAGNOSTI Levy SE, 2003, J DEV BEHAV PEDIATR, V24, P418, DOI 10.1097/00004703-200312000-00003 Liptak GS, 2008, J DEV BEHAV PEDIATR, V29, P152, DOI 10.1097/DBP.0b013e318165c7a0 Livas-Dlott A, 2010, DEV PSYCHOL, V46, P566, DOI 10.1037/a0018016 Lord C., 2008, AUTISM DIAGNOSTIC OB Magana S, 2006, AM J ORTHOPSYCHIAT, V76, P346, DOI 10.1037/0002-9432.76.3.346 Magana S, 2013, J AUTISM DEV DISORD, V43, P1098, DOI 10.1007/s10803-012-1652-3 Mandell DS, 2009, AM J PUBLIC HEALTH, V99, P493, DOI 10.2105/AJPH.2007.131243 Mandell DS, 2002, J AM ACAD CHILD PSY, V41, P1447, DOI 10.1097/01.CHI.0000024863.60748.53 Mandell DS, 2005, MENT RETARD DEV D R, V11, P110, DOI 10.1002/mrdd.20061 Mandell DS, 2005, PEDIATRICS, V116, P1480, DOI 10.1542/peds.2005-0185 Nelson A., 2002, UNEQUAL TREATMENT CO Overton T, 2007, J AUTISM DEV DISORD, V37, P1996, DOI 10.1007/s10803-006-0349-x Palmer RF, 2010, AM J PUBLIC HEALTH, V100, P270, DOI 10.2105/AJPH.2008.150565 Reese L, 1995, INT J ED RES, V23, P57, DOI DOI 10.1016/0883-0355(95)93535-4 Reijneveld S, 2005, EUR CHILD ADOLES PSY, V14, P145, DOI 10.1007/s00787-005-0454-y Risi S, 2006, J AM ACAD CHILD PSY, V45, P1094, DOI 10.1097/01.chi.0000227880.42780.0e Semel Institute UCLA, 2010, ECPHP CHILD REGISTRA Sheridan S. 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PD DEC PY 2014 VL 8 IS 12 BP 1648 EP 1656 DI 10.1016/j.rasd.2014.08.017 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700004 ER PT J AU Li, J Zhu, LQ Liu, J Li, X AF Li, Jing Zhu, Liqi Liu, Jing Li, Xue TI Social and non-social deficits in children with high-functioning autism and their cooperative behaviors SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE High-functioning autism (HFA); Cooperation; Theory of mind (ToM); Executive function; Central coherence ID THEORY-OF-MIND; WEAK CENTRAL COHERENCE; EXECUTIVE FUNCTION; ASPERGER-SYNDROME; SPECTRUM DISORDERS; JOINT ATTENTION; INHIBITORY CONTROL; COGNITIVE-STYLE; YOUNG-CHILDREN; INTENTIONS AB The persistent deficits in social communication and social interactions of individuals with high-functioning autism (HFA) may impair their cooperative behaviors. This study investigated the relationship between social and non-social deficits in children with HFA and the cooperative behaviors of such children. Theory of mind (ToM), executive function, and central coherence of children with HFA and typically developing (TD) children, aged 6-12 years, were investigated, and the effects of these social and non-social deficits on children's cooperativeness were examined. The classical prisoner's dilemma game (PDG) and cooperative implemental tasks were used to assess children's cooperativeness. ToM was measured using a series of classical false belief tasks and the face test. The Wisconsin Card Sorting Task (WCST) and the Embedded Figures Test (EFT) were administered to assess executive function and central coherence, respectively. The results showed that there was no significant difference in cooperation in PDG between HFA and TD children, while cooperation in children with HFA in the interruption period of the implemental tasks was significantly lower than that of TD children. Children with HFA had social deficits and had more poorly developed ToM than TD children, and executive function in children with HFA was poorer than that in TD children. Different types of deficits were predictive of HFA children's degree of cooperation on different tasks: the social perceptual component of ToM and executive function predicted children's cooperativeness in the PDC, and executive function predicted HFA children's cooperativeness during the interruption period of an implemental task. By contrast, central coherence did not predict either of the two types of cooperation. It might indicate that the two different types of cooperative tasks may require different mental abilities. (C) 2014 Elsevier Ltd. All rights reserved. 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Autism Spectr. Disord. PD DEC PY 2014 VL 8 IS 12 BP 1657 EP 1671 DI 10.1016/j.rasd.2014.08.016 PG 15 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700005 ER PT J AU Asano, R Tsuchiya, KJ Takei, N Harada, T Kugizaki, Y Nakahara, R Nakayasu, C Okumura, A Suzuki, Y Takagai, S Mori, N AF Asano, Ryosuke Tsuchiya, Kenji J. Takei, Nori Harada, Taeko Kugizaki, Yumeno Nakahara, Ryuji Nakayasu, Chikako Okumura, Akemi Suzuki, Yukiko Takagai, Shu Mori, Norio CA HBC Study Team TI Broader autism phenotype as a risk factor for postpartum depression: Hamamatsu Birth Cohort (HBC) Study SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Postpartum depression; Broader autism phenotype; Epidemiology; Birth cohort; Pregnant women; Japan ID SEROTONIN TRANSPORTER; POSTNATAL DEPRESSION; SPECTRUM DISORDERS; CHILDREN; FAMILIES; PARENTS; MOOD; MOTHERS; TRAITS; BRAIN AB The broader autism phenotype (BAP), which refers to the expression of behavioral and cognitive propensities that are milder but qualitatively similar to those defining autism spectrum disorder, can play a crucial role in postpartum depression (PPD). We investigated whether pregnant women's BAP would increase the risk for PPD, using a representative birth cohort in Japan. Pregnant women were enrolled in the Hamamatsu Birth Cohort (HBC) Study during their mid-gestation (N = 841) and were followed up until 3 months after delivery. BAP was measured mainly during the 2nd trimester of the pregnancy by using the Broader Phenotype Autism Symptoms Scale. Participants scoring 9 points or higher on the Edinburgh Postnatal Depression Scale at least once during the first 3 months after childbirth were diagnosed with PPD. Among participants, 128 (15.2%) women were found to have PPD. Multiple logistic regression analyses showed that BAP were associated with PPD (OR = 1.19, 95% CI [1.07-1.31]), even after controlling for other potential confounders. In addition, the association was not moderated by history of depression and/or anxiety disorders, including concurrent depressive and anxiety symptoms during pregnancy. The findings suggest that pregnant women with BAP have an elevated risk for PPD. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). C1 [Asano, Ryosuke; Tsuchiya, Kenji J.; Takei, Nori; Harada, Taeko; Kugizaki, Yumeno; Nakahara, Ryuji; Nakayasu, Chikako; Okumura, Akemi; Suzuki, Yukiko; Takagai, Shu; Mori, Norio] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan. [Tsuchiya, Kenji J.; Takei, Nori; Takagai, Shu] Osaka Univ, Dept Child Dev, United Grad Sch Child Dev, Suita, Osaka 565, Japan. [Tsuchiya, Kenji J.; Takei, Nori; Takagai, Shu] Kanazawa Univ, Kanazawa, Ishikawa 9201192, Japan. [Tsuchiya, Kenji J.; Takei, Nori; Takagai, Shu] Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan. [Tsuchiya, Kenji J.; Takagai, Shu; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat, Hamamatsu, Shizuoka 4313192, Japan. [Takei, Nori] Kings Coll London, Inst Psychiat, Div Psychol Med, London WC2R 2LS, England. 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Autism Spectr. Disord. PD DEC PY 2014 VL 8 IS 12 BP 1672 EP 1678 DI 10.1016/j.rasd.2014.08.010 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700006 ER PT J AU LaLonde, KB MacNeill, BR Eversole, LW Ragotzy, SP Poling, A AF LaLonde, Kate B. MacNeill, Brian R. Eversole, Laura Wolfe Ragotzy, Steven P. Poling, Alan TI Increasing physical activity in young adults with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Exercise; Walking; Reinforcement; Goal setting; Autism spectrum disorders; Pedometer AB Although regular physical exercise is clearly beneficial, many people with autism spectrum disorders do not exercise regularly. The present study used a multiple-baseline-across-participants design with a reversal to demonstrate that a treatment package comprising goal-setting and reinforcement substantially increased walking by young adults with autism spectrum disorders while at school. During the initial baseline condition participants were given pedometers to wear. Once each participant's number of steps stabilized, she/he sets daily goals for minimum number of steps taken and received access to valued objects or activities (reinforcers) for meeting those goals. By the end of the first treatment condition each of five participants was successfully meeting his or her goal and walking at or above 10,000 steps each day. Walking decreased when a return to baseline was implemented, then increased when treatment was reinstated. Social validity assessment indicated that both the participants and their teacher found the intervention highly acceptable. These findings suggest that simple strategies based on goal setting and reinforcement merit further investigation as interventions for increasing exercise. (C) 2014 Elsevier Ltd. All rights reserved. C1 [LaLonde, Kate B.; MacNeill, Brian R.; Poling, Alan] Western Michigan Univ, Dept Psychol, Kalamazoo, MI 49008 USA. [Eversole, Laura Wolfe; Ragotzy, Steven P.] Kalamazoo Reg Educ Serv Agcy, Kalamazoo, MI USA. RP LaLonde, KB (reprint author), Western Michigan Univ, Dept Psychol, Kalamazoo, MI 49008 USA. 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Department of Health and Human Services, 2008, 2008 PHYSICAL ACTIVI VanWormer JJ, 2004, J APPL BEHAV ANAL, V37, P421, DOI 10.1901/jaba.2004.37-421 NR 14 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 DEC PY 2014 VL 8 IS 12 BP 1679 EP 1684 DI 10.1016/j.rasd.2014.09.001 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700007 ER PT J AU McFadden, B Kamps, D Heitzman-Powell, L AF McFadden, Brandon Kamps, Debra Heitzman-Powell, Linda TI Social communication effects of peer-mediated recess intervention for children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Peer training; Social communication skills; Recess ID INCLUSIVE SCHOOL SETTINGS; SPECTRUM DISORDERS; YOUNG-CHILDREN; BEHAVIOR; SKILLS; INITIATIONS; STUDENTS; PRESCHOOLERS; TIME AB Children with ASD face enormous challenges in the area of social functioning. Research has shown that impairments in social functioning distinguish this population from both typically developing children and children with disabilities. This study incorporated several evidence-based social skills-teaching procedures (i.e., direct instruction, priming, prompting, peer-mediation, contingent reinforcement, and token economies) directly in the recess setting to increase appropriate social behaviors for four children with ASD (ages 6-8). Elements of peer networks and pivotal response training (two types of social skills intervention packages in the literature) were included. Results showed significant increases in social communication between focus children and their peers, as well as generalization of skills to non-intervention recesses. (C) 2014 Published by Elsevier Ltd. C1 [McFadden, Brandon] Integrated Behav Technol Inc, Basehor, KS USA. [Kamps, Debra] Univ Kansas, Kansas City, KS 66101 USA. [Heitzman-Powell, Linda] Univ Kansas, Med Ctr, Kansas City, KS 66101 USA. RP Kamps, D (reprint author), Univ Kansas, Juniper Gardens Childrens Project, 444 Minnesota Ave,3rd Floor, Kansas City, KS 66101 USA. 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PD DEC PY 2014 VL 8 IS 12 BP 1699 EP 1712 DI 10.1016/j.rasd.2014.08.015 PG 14 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700009 ER PT J AU Lum, M Garnett, M O'Connor, E AF Lum, Michelle Garnett, Michelle O'Connor, Erin TI Health communication: A pilot study comparing perceptions of women with and without high functioning autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE High functioning autism; Communication; Healthcare; Stigma; Women ID ASPERGER-SYNDROME; SOCIAL ANXIETY; LIKERT SCALES; ADULTS; CARE; CHILDREN; MIND; INDIVIDUALS; ADOLESCENTS; MORTALITY AB Research indicates significant health disparities for individuals with autism. Insight into characteristic sensory, cognitive, communication, social, emotional, and behavioural challenges that may influence health communication for patients with autism is vital to address potential disparities. Women with high functioning autism spectrum disorder (ASD) may have specific healthcare needs, and are likely to independently represent themselves and others in healthcare. A pilot study compared perceptions of healthcare experiences for women with and without ASD using on-line survey based on characteristics of ASD likely to influence healthcare. Fifty-eight adult female participants (32 with ASD diagnosis, 26 without ASD diagnosis) were recruited on-line from autism support organisations. Perceptions measured included self-reporting of pain and symptoms, healthcare seeking behaviours, the influence of emotional distress, sensory and social anxiety, maternity experiences, and the influence of autistic status disclosure. Results partially support the hypothesis that ASD women experience greater healthcare challenges. Women with ASD reported greater challenges in healthcare anxiety, communication under emotional distress, anxiety relating to waiting rooms, support during pregnancy, and communication during childbirth. Self-disclosure of diagnostic status and lack of ASD awareness by healthcare providers rated as highly problematic. Results offer detailed insight into healthcare communication and disparities for women with ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lum, Michelle; O'Connor, Erin] Queensland Univ Technol, Kelvin Grove, Qld 4059, Australia. [Garnett, Michelle] Minds & Hearts Clin, West End, Qld 4101, Australia. RP Lum, M (reprint author), Queensland Univ Technol, Fac Hlth, Sch Psychol & Counselling, Victoria Pk Rd, Kelvin Grove, Qld 4059, Australia. 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PD DEC PY 2014 VL 8 IS 12 BP 1713 EP 1721 DI 10.1016/j.rasd.2014.09.009 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700010 ER PT J AU Ratcliffe, B Wong, M Dossetor, D Hayes, S AF Ratcliffe, Belinda Wong, Michelle Dossetor, David Hayes, Susan TI Teaching social-emotional skills to school-aged children with Autism Spectrum Disorder: A treatment versus control trial in 41 mainstream schools SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorder; ASD; Emotional competence; Social-emotional intervention; Group treatment; School-based intervention ID DIFFICULTIES QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; FUTURE-RESEARCH; YOUNG-CHILDREN; INTERVENTIONS; ADOLESCENTS; STRENGTHS; PEERS; PSYCHOPATHOLOGY; RECOMMENDATIONS AB This study examined the effectiveness of 'Emotion-Based Social Skills Training (EBSST)' a manualised social-emotional intervention designed to improve emotional competence in school-aged children with Autism Spectrum Disorder (ASD). Participants were 217 children (aged 7-13 years) with ASD without Intellectual Disability attending 41 mainstream primary schools in NSW Australia. Data on emotional competence, social skills and mental health difficulties were collected using teacher and parent informant report questionnaires in a pre-test/post-test control group design. One hundred and six students took part in the treatment and 111 students were in the control group. School Counsellors delivered the 16 session treatment to groups of 3-8 students in their schools. Teachers and parents also received six sessions of EBSST in separate groups. Participants received a booster session at six months follow-up. EBSST improved teacher reported emotional competence as measured by the Emotions Development Questionnaire (EDQ). The effect size was large and improvements were sustained at 6 months follow-up. Parent reported emotional competence and more general measures of social skills and mental health were insensitive to change across informants. This study has important implications for students, teachers and parents and provides a valuable basis for further research and development of EBSST and the EDQ. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Ratcliffe, Belinda; Wong, Michelle; Dossetor, David] Childrens Hosp, Dept Psychol Med, Westmead, NSW 2145, Australia. [Hayes, Susan] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. RP Ratcliffe, B (reprint author), Childrens Hosp, Dept Psychol Med, Locked Bag 4001, Westmead, NSW 2145, Australia. 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Renee TI Acquisition of sentence frame discrimination using the iPad (TM) as a speech generating device in young children with developmental disabilities SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorder; Developmental delay; Speech generating device; iPad (TM); Tact ID EXCHANGE COMMUNICATION-SYSTEM; AUTISM SPECTRUM DISORDERS; PICTURE EXCHANGE; INDIVIDUALS; PREFERENCE; MODES; PECS AB This study evaluated the use of the iPad (TM) and application Proloqu2Go as a speech generating device (SGD) for the acquisition of a tact (labeling) repertoire in three preschool aged children with Autism Spectrum Disorder or developmental delay. Additionally, discrimination between picture icons and sentence frames were investigated. Using a five second time delay, with full physical prompts, participants were taught to label four items using the carrier phrases "I see" and "I have". Following the acquisition of those frames in isolation, training on discriminating between those frames was introduced. The results indicate that the training procedures were effective for this purpose, thus contributing to the already existing literature on the use of handheld computing devices as SGD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lorah, Elizabeth R.; Parnell, Ashley; Speight, D. Renee] Univ Arkansas, Fayetteville, AR 72701 USA. RP Lorah, ER (reprint author), Univ Arkansas, Fayetteville, AR 72701 USA. 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PD DEC PY 2014 VL 8 IS 12 BP 1734 EP 1740 DI 10.1016/j.rasd.2014.09.004 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AT8MG UT WOS:000345186700012 ER PT J AU Yi, L Fan, YB Li, J Huang, D Wang, XQ Tan, WL Zou, XB Lee, K AF Yi, Li Fan, Yuebo Li, Jiao Huang, Dan Wang, Xueqin Tan, Wenle Zou, Xiaobing Lee, Kang TI Distrust and retaliatory deception in children with Autism Spectrum Disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorder; Trust; Distrust; Deception; Theory of Mind ID FALSE-BELIEF; PRESCHOOLERS; LIES; MIND; INDIVIDUALS; SENSITIVITY; BEHAVIOR; SPEAKERS; ABILITY; VERSION AB This study examined trust and retaliatory deception in children with Autism Spectrum Disorder (ASD). In Experiment 1, school-aged children with ASD and ability-matched typically developing (TD) children participated in a game to find a hidden prize. An adult repeatedly misinformed children about the whereabouts of the prize. Although children with ASD did not blindly trust all information provided by the informant, they were significantly more trusting of the deceptive adult than TD children. Further, children with ASD were less likely to retaliate by deceiving the adult than TD children. Experiment 2 showed that children with ASD who distrusted a deceptive adult were less flexible and therefore less able to generalize their distrust to different situations compared to TD children. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Yi, Li; Li, Jiao; Tan, Wenle] 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, Dept Stat Sci, Sch Math & Computat Sci, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Xueqin] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510275, Guangdong, Peoples R China. [Zou, Xiaobing] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China. [Lee, Kang] Univ Toronto, Dr Eric Jackman Inst Child Study, Toronto, ON M5S 1A1, Canada. 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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Neurosci. PD DEC PY 2014 VL 25 IS 6 BP 841 EP 850 DI 10.1515/revneuro-2014-0056 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AT6BQ UT WOS:000345024100008 PM 25222596 ER PT J AU Bhat, S Acharya, UR Adeli, H Bairy, GM Adeli, A AF Bhat, Shreya Acharya, U. Rajendra Adeli, Hojjat Bairy, G. Muralidhar Adeli, Amir TI Automated diagnosis of autism: in search of a mathematical marker SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE autism; chaos theory; EEG; nonlinear analysis; wavelets ID EEG-BASED DIAGNOSIS; FUZZY SYNCHRONIZATION LIKELIHOOD; NEURAL NETWORK METHODOLOGY; ALZHEIMERS-DISEASE; SPECTRUM DISORDER; SEIZURE DETECTION; RECURRENCE PLOTS; COMPONENT ANALYSIS; WAVELET TRANSFORM; GROUND MOTIONS AB Autism is a type of neurodevelopmental disorder affecting the memory, behavior, emotion, learning ability, and communication of an individual. An early detection of the abnormality, due to irregular processing in the brain, can be achieved using electroencephalograms (EEG). The variations in the EEG signals cannot be deciphered by mere visual inspection. Computer-aided diagnostic tools can be used to recognize the subtle and invisible information present in the irregular EEG pattern and diagnose autism. This paper presents a state-of-the-art review of automated EEG-based diagnosis of autism. Various time domain, frequency domain, time-frequency domain, and nonlinear dynamics for the analysis of autistic EEG signals are described briefly. A focus of the review is the use of nonlinear dynamics and chaos theory to discover the mathematical biomarkers for the diagnosis of the autism analogous to biological markers. A combination of the time-frequency and nonlinear dynamic analysis is the most effective approach to characterize the nonstationary and chaotic physiological signals for the automated EEG-based diagnosis of autism spectrum disorder (ASD). 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J. Psychol. PD DEC PY 2014 VL 55 IS 6 BP 585 EP 592 DI 10.1111/sjop.12138 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AT9AL UT WOS:000345219900010 PM 24954681 ER PT J AU Sokhadze, EM El-Baz, AS Tasman, A Sears, LL Wang, Y Lamina, EV Casanova, MF AF Sokhadze, Estate M. El-Baz, Ayman S. Tasman, Allan Sears, Lonnie L. Wang, Yao Lamina, Eva V. Casanova, Manuel F. TI Neuromodulation Integrating rTMS and Neurofeedback for the Treatment of Autism Spectrum Disorder: An Exploratory Study SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Article DE Autism spectrum disorder; Transcranial magnetic stimulation (TMS); Neurofeedback; EEG gamma activity; Theta/beta ratio; Executive functions ID TRANSCRANIAL MAGNETIC STIMULATION; GAMMA-FREQUENCY OSCILLATIONS; HIGH-FUNCTIONING AUTISM; FRONTAL-CORTEX; 40-HZ EEG; PROCESSING ABNORMALITIES; MINICOLUMNAR PATHOLOGY; COGNITIVE NEUROSCIENCE; GABAERGIC INHIBITION; REPETITIVE BEHAVIOR AB Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social interaction, language, stereotyped behaviors, and restricted range of interests. In previous studies low frequency repetitive transcranial magnetic stimulation (rTMS) has been used, with positive behavioral and electrophysiological results, for the experimental treatment in ASD. In this study we combined prefrontal rTMS sessions with electroencephalographic (EEG) neurofeedback (NFB) to prolong and reinforce TMS-induced EEG changes. The pilot trial recruited 42 children with ASD (similar to 14.5 years). Outcome measures included behavioral evaluations and reaction time test with event-related potential (ERP) recording. For the main goal of this exploratory study we used rTMS-neurofeedback combination (TMS-NFB, N = 20) and waitlist (WTL, N = 22) groups to examine effects of 18 sessions of integrated rTMS-NFB treatment or wait period) on behavioral responses, stimulus and response-locked ERPs, and other functional and clinical outcomes. The underlying hypothesis was that combined TMS-NFB will improve executive functions in autistic patients as compared to the WTL group. Behavioral and ERP outcomes were collected in pre- and post-treatment tests in both groups. 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TI A Multi-Rater Study on Being Teased Among Children/Adolescents With Autism Spectrum Disorder (ASD) and Their Typically Developing Siblings: Associations With ASD Symptoms SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorders; symptoms; bullying; teasing ID SOCIAL-SKILLS PROBLEMS; PEER-VICTIMIZATION; ASPERGER SYNDROME; CHILDREN; ADOLESCENTS; STUDENTS; SCHOOL; RISK; PERCEPTIONS; INVOLVEMENT AB The study examined teasing experiences among 74 individuals with autism spectrum disorder (ASD; M age = 115.7 months [9.6 years]; 83.8% male). Experiences were examined from parent, teacher, and child's own perspectives. Factors potentially associated with being teased were investigated. Comparison data were ascertained on typically developing siblings (n = 68; M age = 116.5 months [9.7 years]; 52.9% male). Select items on the Child Behavior Checklist 6-18 and the Teacher Report Form 6-18 were utilized to calculate the prevalence of being teased; qualitative data from a subgroup of verbally fluent children with ASD (n = 50) were analyzed to provide child self-report teasing data. Children with ASD were more likely to be teased than their typically developing siblings. Characteristics that were significantly associated with being teased included higher cognitive functioning, less severe ASD symptomatology, and more time spent in inclusive educational settings. Clinical implications are discussed. C1 [Nowell, Kerri P.; Brewton, Christie M.] Univ Houston, Houston, TX 77204 USA. [Goin-Kochel, Robin P.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Nowell, KP (reprint author), Univ Houston, Dept Educ Psychol, 491 Farish Hall, Houston, TX 77204 USA. EM knowell@uh.edu CR Achenbach T. M., 2009, CHILD BEHAV CHECKLIS Achenbach T. 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Disabil. PD DEC PY 2014 VL 29 IS 4 BP 195 EP 205 DI 10.1177/1088357614522292 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AT0EG UT WOS:000344609400001 ER PT J AU Hundert, J Rowe, S Harrison, E AF Hundert, Joel Rowe, Sarah Harrison, Erin TI The Combined Effects of Social Script Training and Peer Buddies on Generalized Peer Interaction of Children With ASD in Inclusive Classrooms SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE social; skills; autism spectrum disorder; applied behavior analysis ID AUTISM; SKILLS; PLAY; DISABILITIES; INTERVENTION; PRESCHOOLERS; SETTINGS; STUDENTS; PACKAGE; BEHAVIOR AB One of the challenges in supporting young children with Autism Spectrum Disorder (ASD) in inclusive classrooms is the generalization of improved social behaviors. Using a multiple-baseline design across participants, this study examined the generalized effects of social script training alone and combined with peer buddies on the interactive play of three children with ASD to play settings in inclusive classrooms where the training was not in effect. Social script training alone increased the interactive play of children with ASD when the intervention was in place, but did not generalize to another play setting when social script training was not being conducted. The addition of peer buddies combined with social script training produced a generalized increase in peer interaction to play settings in inclusive classrooms when theme-related play materials and adult assistance were unavailable. Implications of these results for inclusion of young children with ASD are discussed. C1 [Hundert, Joel] Behav Inst, Hamilton, ON L8N 1V1, Canada. [Rowe, Sarah; Harrison, Erin] McMaster Univ, Hamilton, ON, Canada. 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PD DEC PY 2014 VL 29 IS 4 BP 206 EP 215 DI 10.1177/1088357614522288 PG 10 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AT0EG UT WOS:000344609400002 ER PT J AU Radley, KC Ford, WB Battaglia, AA McHugh, MB AF Radley, Keith C. Ford, W. Blake Battaglia, Allison A. McHugh, Melissa B. TI The Effects of a Social Skills Training Package on Social Engagement of Children With Autism Spectrum Disorders in a Generalized Recess Setting SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE social skills; socialization; modeling; social; skills ID YOUNG-CHILDREN; INTERVENTIONS; METAANALYSIS; SCHOOL; LONELINESS; STUDENTS; BEHAVIOR; OUTCOMES; ADULTS AB The present study provides a preliminary evaluation of the effects of the Superheroes Social Skills program, a practice-ready, multimedia social skills program, on social engagements of elementary-age children with autism spectrum disorders (ASD). Four children with ASD between the ages of 8 and 10 with current placements in inclusive public school settings participated in an 8-week intervention utilizing the intermediate skill components of the Superheroes Social Skills program. The intervention was presented once per week for approximately 30 min in the school settings. Analysis of data suggests that social engagements of participants during generalized recess periods increased following the introduction of intervention. Data on frequency of initiations and responses, as well as sociometric outcomes, were also collected as a secondary dependent variable and are discussed. Results suggest that pullout social skills training may result in effects that are generalized to more naturalistic settings. Limitations of the current study and suggestions for future research are reviewed. C1 [Radley, Keith C.; Ford, W. Blake; Battaglia, Allison A.; McHugh, Melissa B.] Univ So Mississippi, 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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PD DEC PY 2014 VL 29 IS 4 BP 216 EP 229 DI 10.1177/1088357614525660 PG 14 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AT0EG UT WOS:000344609400003 ER PT J AU Kamps, D Mason, R Thiemann-Bourque, K Feldmiller, S Turcotte, A Miller, T AF Kamps, Debra Mason, Rose Thiemann-Bourque, Kathy Feldmiller, Sarah Turcotte, Amy Miller, Todd TI The Use of Peer Networks to Increase Communicative Acts of Students With Autism Spectrum Disorders SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorders; communication; peer training ID SOCIAL-SKILLS INTERVENTIONS; HIGH-FUNCTIONING CHILDREN; SCHOOL-AGE-CHILDREN; YOUNG-CHILDREN; JOINT ATTENTION; STIMULUS-CONTROL; CONTROLLED-TRIAL; DISABILITIES; INDIVIDUALS; INITIATIONS AB Peer networks including social groups using typical peers, scripted instruction, visual text cues, and reinforcement were examined with students with autism spectrum disorders (ASD). 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PD DEC PY 2014 VL 29 IS 4 BP 230 EP 245 DI 10.1177/1088357614539832 PG 16 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AT0EG UT WOS:000344609400004 ER PT J AU Morgan, LJ Rubin, E Coleman, JJ Frymark, T Wang, BP Cannon, LJ AF Morgan, Lindee J. Rubin, Emily Coleman, Jaumeiko J. Frymark, Tobi Wang, Beverly P. Cannon, Laura J. TI Impact of Social Communication Interventions on Infants and Toddlers With or At-Risk for Autism: A Systematic Review SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; autism spectrum disorder; social communication; pervasive developmental disorder; speech-language pathology; intervention ID RANDOMIZED CONTROLLED-TRIAL; SPECTRUM DISORDERS; JOINT ATTENTION; YOUNG-CHILDREN; PARENTS; MODEL; ENGAGEMENT; LANGUAGE; THERAPY AB This is a systematic review of the impact of communication interventions on the social communication skills of infants and toddlers with or at-risk for autism spectrum disorder (ASD). A priori clinical questions accompanied by specific inclusion and exclusion criteria informed the extensive literature search that was conducted in multiple databases (e.g., PubMed). Twenty-six studies were accepted for this review. Outcomes were reported by social communication category (i.e., joint attention, social reciprocity, and language and related cognitive skills) and communication developmental stage (i.e., prelinguistic, emerging language). Primarily positive treatment effects were revealed in the majority of outcome categories for which social communication data were available. However, the presence of intervention and outcome measure heterogeneity precluded a clear determination of intervention effects. Future research should address these issues while also evaluating multiple outcomes and adding a strong family component designed to enhance child active engagement. C1 [Morgan, Lindee J.] Florida State Univ, Autism Inst, Tallahassee, FL 32306 USA. [Rubin, Emily] Marcus Autism Ctr, Atlanta, GA USA. [Coleman, Jaumeiko J.; Frymark, Tobi; Wang, Beverly P.] Amer Speech Language Hearing Assoc, Rockville, MD 20850 USA. [Cannon, Laura J.] Univ Maryland, College Pk, MD 20742 USA. 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Disabil. PD DEC PY 2014 VL 29 IS 4 BP 246 EP 256 DI 10.1177/1088357614539835 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AT0EG UT WOS:000344609400005 ER PT J AU Hebert, MLJ Kehayia, E Prelock, P Wood-Dauphinee, S Snider, L AF Hebert, Michele L. J. Kehayia, Eva Prelock, Patricia Wood-Dauphinee, Sharon Snider, Laurie TI Does occupational therapy play a role for communication in children with autism spectrum disorders? SO INTERNATIONAL JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE Autism spectrum disorders (ASD); Early childhood; Intervention ID MODEL AB This study investigates occupational therapy for early communication in children with autism spectrum disorders (ASD). The research explored the role of occupational therapists in supporting children with ASD to become better communicators by considering their inter-professional collaboration with speech-language pathologists. Convenience samples of 21 clinical occupational therapists and speech-language pathologists were recruited to participate in semi-structured audio-recorded focus groups, using a qualitative design. Distinct views included a child-centred focus from speech-language pathologists, whereas occupational therapists spoke of the child through societal viewpoints, which later pointed to occupational therapists 'proficiency in enabling skill generalization in ASD. An equal partnership was consistently reported between these clinicians, who identified the same objectives, shared strategies, joint treatments, and ongoing collaboration as the four main facilitators to inter-professional collaboration when treating children with ASD. Three unique roles of occupational therapy comprised developing non-verbal and verbal communication pre-requisites, adapting the setting, educating-partnering-advocating for the child, and providing occupation-based intervention. These three themes meshed with the discipline-specific occupational therapy domains represented in the Person-Environment-Occupation framework. When working in inter-professional collaboration, speech-language pathologists and occupational therapists agree that occupational therapy is indispensable to early intervention in enabling communication in ASD. C1 [Hebert, Michele L. J.; Kehayia, Eva; Wood-Dauphinee, Sharon; Snider, Laurie] McGill Univ, Montreal, PQ H3G 1Y5, Canada. [Hebert, Michele L. J.; Kehayia, Eva] Jewish Rehabil Hosp CRIR, Laval, PQ, Canada. [Prelock, Patricia] Univ Vermont, Coll Med, Burlington, VT USA. [Snider, Laurie] Montreal Childrens Hosp CRIR, Montreal, PQ, Canada. RP Hebert, MLJ (reprint author), McGill Univ, Sch Phys & Occupat Therapy, 3654 Promenade Sir William Osler, Montreal, PQ H3G 1Y5, Canada. EM michele.lj.hebert@mail.mcgill.ca CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT [Anonymous], 2009, NAT STAND PROJ ADDR Brodsky D, 2013, BMJ QUAL SAF, V22, P374, DOI 10.1136/bmjqs-2012-000909 Butler-Kisber L., 2011, QUALITATIVE INQUIRY Canadian Association of Occupational Therapists, 2006, CAOT POS STAT AUT SP Center for Disease Control, 2012, 61 CDC, V61, P1 Chakrabarti S, 2001, JAMA-J AM MED ASSOC, V285, P3093, DOI 10.1001/jama.285.24.3093 Clark G., 2004, AUTISM, P107 D'Amour Danielle, 2005, J Interprof Care, V19 Suppl 1, P8, DOI 10.1080/13561820500081604 Dillman D. 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PD DEC PY 2014 VL 16 IS 6 BP 594 EP 602 DI 10.3109/17549507.2013.876665 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AT4QK UT WOS:000344925300006 PM 24460071 ER PT J AU Rogers, SJ Vismara, L Wagner, AL McCormick, C Young, G Ozonoff, S AF Rogers, S. J. Vismara, L. Wagner, A. L. McCormick, C. Young, G. Ozonoff, S. TI Autism Treatment in the First Year of Life: A Pilot Study of Infant Start, a Parent-Implemented Intervention for Symptomatic Infants SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Infants; Early intervention; Parents; Early Start Denver Model ID RANDOMIZED CONTROLLED-TRIAL; LOW-INCOME FAMILIES; SPECTRUM DISORDERS; HIGH-RISK; BEHAVIORAL TREATMENT; PREMATURE-INFANTS; HOME INTERVENTION; MOTOR DEVELOPMENT; PRETERM INFANTS; BABY SIBLINGS AB The goal of early autism screening is earlier treatment. We pilot-tested a 12-week, low-intensity treatment with seven symptomatic infants ages 7-15 months. Parents mastered the intervention and maintained skills after treatment ended. Four comparison groups were matched from a study of infant siblings. The treated group of infants was significantly more symptomatic than most of the comparison groups at 9 months of age but was significantly less symptomatic than the two most affected groups between 18 and 36 months. At 36 months, the treated group had much lower rates of both ASD and DQs under 70 than a similarly symptomatic group who did not enroll in the treatment study. It appears feasible to identify and enroll symptomatic infants in parent-implemented intervention before 12 months, and the pilot study outcomes are promising, but testing the treatment's efficacy awaits a randomized trial. C1 [Rogers, S. J.; McCormick, C.; Young, G.; Ozonoff, S.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. [Vismara, L.] York Univ, Toronto, ON M3J 2R7, Canada. [Wagner, A. L.] Univ Calif Davis, Davis, CA 95616 USA. RP Rogers, SJ (reprint author), Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA. EM sally.rogers@ucdmc.ucdavis.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN 4 TR, V2000 Attermeier S. M., 1991, CAROLINA CURRICULUM BARRERA ME, 1990, INF MENTAL HLTH J, V11, P142, DOI 10.1002/1097-0355(199022)11:2<142::AID-IMHJ2280110206>3.0.CO;2-K BROOKSGUNN J, 1992, J PEDIATR-US, V120, P350, DOI 10.1016/S0022-3476(05)80896-0 Bryson SE, 2008, J AUTISM DEV DISORD, V38, P731, DOI 10.1007/s10803-007-0440-y Bryson SE, 2007, J AUTISM DEV DISORD, V37, P12, DOI 10.1007/s10803-006-0328-2 Carter AS, 2011, J CHILD PSYCHOL PSYC, V52, P741, DOI 10.1111/j.1469-7610.2011.02395.x Chapman RS, 2000, J CHILD PSYCHOL PSYC, V41, P33, DOI 10.1017/S0021963099004953 Charlop-Christy M. H., 2000, J POSIT BEHAV INTERV, V2, P98, DOI DOI 10.1177/109830070000200203 Davis N. 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PD DEC PY 2014 VL 44 IS 12 BP 2981 EP 2995 DI 10.1007/s10803-014-2202-y PG 15 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500002 PM 25212413 ER PT J AU Kocovska, E Andorsdottir, G Weihe, P Halling, J Fernell, E Stora, T Biskupsto, R Gillberg, IC Shea, R Billstedt, E Bourgeron, T Minnis, H Gillberg, C AF Kocovska, Eva Andorsdottir, Gudrid Weihe, Pal Halling, Jonrit Fernell, Elisabeth Stora, Tormodur Biskupsto, Rannva Gillberg, I. Carina Shea, Robyn Billstedt, Eva Bourgeron, Thomas Minnis, Helen Gillberg, Christopher TI Vitamin D in the General Population of Young Adults with Autism in the Faroe Islands SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ASD; Vitamin D; Calcitriol; Total population; Faroe Islands ID CIRCULATING 25-HYDROXYVITAMIN D; D DEFICIENCY; SPECTRUM DISORDERS; RISK-FACTORS; SERUM-LEVELS; D-RECEPTOR; CHILDREN; ASSOCIATION; PREVALENCE; 25(OH)D AB Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D-3 (25(OH)D-3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15-24 years) had significantly lower 25(OH)D-3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D-3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D-3 in the ASD group suggests some underlying pathogenic mechanism. C1 [Kocovska, Eva; Fernell, Elisabeth; Gillberg, I. Carina; Billstedt, Eva; Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gillberg Neuropsychiat Ctr, S-41119 Gothenburg, Sweden. [Kocovska, Eva; Minnis, Helen] Univ Glasgow, Royal Hosp Sick Children, Inst Hlth & Wellbeing, Coll Med Vet & Life Sci, Glasgow G3 8SJ, Lanark, Scotland. [Andorsdottir, Gudrid; Biskupsto, Rannva] Minist Hlth, Genet Biobank Faroes, DK-100 Torshavn, Faroe Islands, Denmark. [Weihe, Pal; Halling, Jonrit] Faroese Hosp Syst, Dept Occupat Med & Publ Hlth, DK-100 Torshavn, Faroe Islands, Denmark. [Fernell, Elisabeth] Skaraborgs Hosp, Ctr Res & Dev, S-54185 Skovde, Sweden. [Stora, Tormodur] Natl Hosp Faroe Isl, Ctr Psychiat, DK-100 Torshavn, Faroe Islands, Denmark. [Shea, Robyn] Sandwell & West Birmingham Hosp NHS Trust, City Hosp, Dept Clin Biochem, Birmingham B18 7QH, W Midlands, England. [Bourgeron, Thomas] Inst Pasteur, Human Genet & Cognit Funct Unit, Paris, France. [Bourgeron, Thomas] Inst Pasteur, CNRS, URA 2182, Paris, France. [Bourgeron, Thomas] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. RP Kocovska, E (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. EM eva.kocovska@gnc.gu.se; gudrid@biobank.gov.fo; pal@health.fo; jonrit@health.fo; elisabeth.fernell@gnc.gu.se; lstost@ls.fo; rannvabi@gmail.com; carina.gillberg@gnc.gu.se; robyn.shea@nhs.net; eva.billstedt@gnc.gu.se; thomasb@pasteur.fr; helen.minnis@glasgow.ac.uk; christopher.gillberg@gnc.gu.se CR Adams JS, 2010, J CLIN ENDOCR METAB, V95, P471, DOI 10.1210/jc.2009-1773 Agborsangaya C, 2010, NUTR CANCER, V62, P51, DOI 10.1080/01635580903191460 Ahn J, 2010, HUM MOL GENET, V19, P2739, DOI 10.1093/hmg/ddq155 American Psychiatric Association, 1994, DIAGN STAT MENT DIS Cannell J. 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PD DEC PY 2014 VL 44 IS 12 BP 2996 EP 3005 DI 10.1007/s10803-014-2155-1 PG 10 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500003 PM 24927807 ER PT J AU Gray, KM Keating, CM Taffe, JR Brereton, AV Einfeld, SL Reardon, TC Tonge, BJ AF Gray, Kylie M. Keating, Caroline M. Taffe, John R. Brereton, Avril V. Einfeld, Stewart L. Reardon, Tessa C. Tonge, Bruce J. TI Adult Outcomes in Autism: Community Inclusion and Living Skills SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Community inclusion; Living skills; Adult outcomes ID DEVELOPMENTAL BEHAVIOR CHECKLIST; FOLLOW-UP; SPECTRUM DISORDERS; PSYCHOMETRIC PROPERTIES; INTELLECTUAL DISABILITY; INFANTILE PSYCHOSIS; SOCIAL COMPETENCE; ASPERGER-SYNDROME; YOUNG-ADULTS; CHILDREN AB Longitudinal research has demonstrated that social outcomes for adults with autism are restricted, particularly in terms of employment and living arrangements. However, understanding of individual and environmental factors that influence these outcomes is far from complete. This longitudinal study followed a community sample of children and adolescents with autism into adulthood. Social outcomes in relation to community inclusion and living skills were examined, including the predictive role of a range of individual factors and the environment (socio-economic disadvantage). Overall, the degree of community inclusion and living skills was restricted for the majority, and while childhood IQ was an important determinant of these outcomes, it was not the sole predictor. The implications of these findings in relation to interventions are discussed. C1 [Gray, Kylie M.; Keating, Caroline M.; Taffe, John R.; Brereton, Avril V.; Reardon, Tessa C.; Tonge, Bruce J.] Monash Univ, Dept Psychiat, Sch Clin Sci, Ctr Dev Psychiat & Psychol, Clayton, Vic, Australia. [Gray, Kylie M.] Monash Med Ctr, Early Life Mental Hlth Serv, Clayton, Vic 3168, Australia. [Einfeld, Stewart L.] Univ Sydney, Fac Hlth Sci, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. RP Gray, KM (reprint author), Monash Med Ctr, Early Life Mental Hlth Serv, 246 Clayton Rd, Clayton, Vic 3168, Australia. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3006 EP 3015 DI 10.1007/s10803-014-2159-x PG 10 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500004 PM 24915930 ER PT J AU Losh, M Gordon, PC AF Losh, Molly Gordon, Peter C. TI Quantifying Narrative Ability in Autism Spectrum Disorder: A Computational Linguistic Analysis of Narrative Coherence SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Endophenotype; Language; Narrative; Phenotype ID LATENT SEMANTIC ANALYSIS; PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING CHILDREN; LANGUAGE DISORDERS; INDIVIDUALS; DISCOURSE AB Autism is a neurodevelopmental disorder characterized by serious difficulties with the social use of language, along with impaired social functioning and ritualistic/repetitive behaviors (American Psychiatric Association in Diagnostic and statistical manual of mental disorders: DSM-5, 5th edn. American Psychiatric Association, Arlington, 2013). While substantial heterogeneity exists in symptom expression, impairments in language discourse skills, including narrative (or storytelling), are universally observed in autism (Tager-Flusberg et al. in Handbook on autism and pervasive developmental disorders, 3rd edn. Wiley, New York, pp 335-364, 2005). This study applied a computational linguistic tool, Latent Semantic Analysis (LSA), to objectively characterize narrative performance in high-functioning individuals with autism and typically-developing controls, across two different narrative contexts that differ in the interpersonal and cognitive demands placed on the narrator. Results indicated that high-functioning individuals with autism produced narratives comparable in semantic content to those produced by controls when narrating from a picture book, but produced narratives diminished in semantic quality in a more demanding narrative recall task. This pattern is similar to that detected from analyses of hand-coded picture book narratives in prior research, and extends findings to an additional narrative context that proves particularly challenging for individuals with autism. Results are discussed in terms of the utility of LSA as a quantitative, objective, and efficient measure of narrative ability. C1 [Losh, Molly] Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL 60208 USA. [Gordon, Peter C.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. RP Losh, M (reprint author), Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL 60208 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3016 EP 3025 DI 10.1007/s10803-014-2158-y PG 10 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500005 PM 24915929 ER PT J AU Siegel, M Milligan, B Chemelski, B Payne, D Ellsworth, B Harmon, J Teer, O Smith, KA AF Siegel, Matthew Milligan, Briana Chemelski, Bruce Payne, David Ellsworth, Beth Harmon, Jamie Teer, Olivia Smith, Kahsi A. TI Specialized Inpatient Psychiatry for Serious Behavioral Disturbance in Autism and Intellectual Disability SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Psychiatric; Hospitalization; Intellectual disability ID SPECTRUM DISORDERS; CHILDREN; CARE; IRRITABILITY; ARIPIPRAZOLE; ADOLESCENTS; SYMPTOMS; ADULTS; KAPPA; UNIT AB Psychiatric hospitalization of children with autism spectrum disorder and/or intellectual disability is common, however, the effectiveness of this intervention is largely unknown. Thirty-eight clinically-referred children 8-19 years old admitted to a specialized inpatient psychiatry unit were assessed by a consistent caregiver on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale at admission, discharge and 2 months post discharge. There was a decrease in the mean ABC-I score from admission (27.3, SD 7.4) to discharge (11.9, SD 8.8), which was sustained at 2 months post discharge (14.8, SD 9.3) (p < 0.001). Seventy-eight percent of the subjects were rated as "Improved" on the clinician Clinical Global Impressions Improvement scale at discharge. The study is limited by lack of a control group, but offers preliminary evidence for specialized inpatient psychiatry as an intervention for serious behavioral disturbance in this population. C1 [Siegel, Matthew; Milligan, Briana; Chemelski, Bruce; Payne, David; Ellsworth, Beth; Harmon, Jamie; Teer, Olivia] Spring Harbor Hosp, Dev Disorders Program, Westbrook, ME 04092 USA. 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PD DEC PY 2014 VL 44 IS 12 BP 3026 EP 3032 DI 10.1007/s10803-014-2157-z PG 7 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500006 PM 24925543 ER PT J AU Jones, L Goddard, L Hill, EL Henry, LA Crane, L AF Jones, Lydia Goddard, Lorna Hill, Elisabeth L. Henry, Lucy A. Crane, Laura TI Experiences of Receiving a Diagnosis of Autism Spectrum Disorder: A Survey of Adults in the United Kingdom SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Diagnosis; Survey; Adults; Depression; Anxiety ID HIGH-FUNCTIONING ADULTS; ASPERGER-SYNDROME; AUTOBIOGRAPHICAL MEMORY; PSYCHOMETRIC PROPERTIES; PARENTS; CHILDREN; DISCLOSURE; DETERMINANTS; SATISFACTION; PERCEPTIONS AB A total of 128 adults with high-functioning autism spectrum disorders were surveyed concerning the process they went through to obtain their diagnosis and the subsequent support they received. Results suggested that routes to diagnosis were quite heterogeneous and overall levels of satisfaction with the diagnostic process were mixed; 40 % of respondents were 'very/quite' dissatisfied, whilst 47 % were 'very/quite' satisfied. The extent of delays, number of professionals seen, quality of information given at diagnosis and levels of post-diagnostic support predicted overall satisfaction with the diagnostic process. Important areas and suggestions for improvement were noted for all stages of the diagnostic pathway. Respondents also displayed above average levels of depressed mood and anxiety, with greater support being requested in this area. C1 [Jones, Lydia; Goddard, Lorna; Hill, Elisabeth L.] Univ London, London, England. [Henry, Lucy A.; Crane, Laura] City Univ London, Language & Commun Sci Div, London EC1V 0HB, England. [Crane, Laura] London S Bank Univ, London, England. RP Crane, L (reprint author), City Univ London, Language & Commun Sci Div, 10 Northampton Sq, London EC1V 0HB, England. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3033 EP 3044 DI 10.1007/s10803-014-2161-3 PG 12 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500007 PM 24915932 ER PT J AU Georgiades, S Boyle, M Szatmari, P Hanna, S Duku, E Zwaigenbaum, L Bryson, S Fombonne, E Volden, J Mirenda, P Smith, I Roberts, W Vaillancourt, T Waddell, C Bennett, T Elsabbagh, M Thompson, A AF Georgiades, Stelios Boyle, Michael Szatmari, Peter Hanna, Steven Duku, Eric Zwaigenbaum, Lonnie Bryson, Susan Fombonne, Eric Volden, Joanne Mirenda, Pat Smith, Isabel Roberts, Wendy Vaillancourt, Tracy Waddell, Charlotte Bennett, Teresa Elsabbagh, Mayada Thompson, Ann CA Pathways ASD Study Team TI Modeling the Phenotypic Architecture of Autism Symptoms from Time of Diagnosis to Age 6 SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism symptoms; Classification; Phenotypic heterogeneity ID SPECTRUM DISORDERS; DSM-5 CRITERIA; HETEROGENEITY; CLASSIFICATION; BEHAVIOR; CHILDREN AB The latent class structure of autism symptoms from the time of diagnosis to age 6 years was examined in a sample of 280 children with autism spectrum disorder. Factor mixture modeling was performed on 26 algorithm items from the Autism Diagnostic Interview - Revised at diagnosis (Time 1) and again at age 6 (Time 2). At Time 1, a "2-factor/3-class" model provided the best fit to the data. At Time 2, a "2-factor/2-class" model provided the best fit to the data. Longitudinal (repeated measures) analysis of variance showed that the "2-factor/3-class" model derived at the time of diagnosis allows for the identification of a subgroup of children (9 % of sample) who exhibit notable reduction in symptom severity. C1 [Georgiades, Stelios; Boyle, Michael; Hanna, Steven; Duku, Eric; Bennett, Teresa; Thompson, Ann] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON L8S 4L8, Canada. [Szatmari, Peter] Univ Toronto, Hosp Sick Children, Ctr Addict & Mental Hlth, Toronto, ON M5G 1X8, Canada. [Zwaigenbaum, Lonnie; Volden, Joanne] Univ Alberta, Edmonton, AB, Canada. [Bryson, Susan; Smith, Isabel] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. [Fombonne, Eric; Elsabbagh, Mayada] McGill Univ, Montreal, PQ, Canada. [Mirenda, Pat] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Roberts, Wendy] Univ Toronto, Toronto, ON, Canada. [Vaillancourt, Tracy] Univ Ottawa, Ottawa, ON, Canada. [Waddell, Charlotte] Simon Fraser Univ, Vancouver, BC, Canada. RP Georgiades, S (reprint author), McMaster Univ, Offord Ctr Child Studies, 1280 Main St West, Hamilton, ON L8S 4L8, Canada. EM georgis@mcmaster.ca RI Vaillancourt, Tracy/F-8949-2015 CR Achenbach T, 2000, MANUAL ASEBA PRESCHO American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bodfish J. 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K., 2008, MPLUS 5 1 WINDOWS Nylund KL, 2007, STRUCT EQU MODELING, V14, P535 Ozonoff S, 2012, J CHILD PSYCHOL PSYC, V53, P1092, DOI 10.1111/j.1469-7610.2012.02614.x Pandolfi V, 2009, J AUTISM DEV DISORD, V39, P986, DOI 10.1007/s10803-009-0716-5 Rutter M., 2003, ADI R AUTISM DIAGNOS Rutter M, 2011, J CHILD PSYCHOL PSYC, V52, P647, DOI 10.1111/j.1469-7610.2011.02367.x Rutter M, 2013, J AUTISM DEV DISORD, V43, P1749, DOI 10.1007/s10803-012-1713-7 Sparrow SS, 2005, VINELAND ADAPTIVE BE Szatmari P, 2011, BMJ-BRIT MED J, V342, DOI 10.1136/bmj.d2456 Walton KE, 2011, J ABNORM CHILD PSYCH, V39, P553, DOI 10.1007/s10802-010-9478-y Wiggins L. D., 2011, J AUTISM DEV DISORD, V42, P191 NR 31 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 DEC PY 2014 VL 44 IS 12 BP 3045 EP 3055 DI 10.1007/s10803-014-2167-x PG 11 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500008 PM 24958435 ER PT J AU Granader, Y Wallace, GL Hardy, KK Yerys, BE Lawson, RA Rosenthal, M Wills, MC Dixon, E Pandey, J Penna, R Schultz, RT Kenworthy, L AF Granader, Yael Wallace, Gregory L. Hardy, Kristina K. Yerys, Benjamin E. Lawson, Rachel A. Rosenthal, Michael Wills, Meagan C. Dixon, Eunice Pandey, Juhi Penna, Rebecca Schultz, Robert T. Kenworthy, Lauren TI Characterizing the Factor Structure of Parent Reported Executive Function in Autism Spectrum Disorders: The Impact of Cognitive Inflexibility SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Cognitive flexibility; Executive functioning; Behavior Rating Inventory of Executive Function; Factor analysis ID CONFIRMATORY FACTOR-ANALYSIS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BEHAVIOR RATING INVENTORY; TRAUMATIC BRAIN-INJURY; DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; REAL-WORLD; CHILDREN; SYMPTOMS; FLEXIBILITY AB Parents of children with autism spectrum disorders (ASD) consistently report executive functioning (EF) deficits. This study investigates the factor structure of the Behavior Rating Inventory of Executive Function (BRIEF) as reported by parents of children with ASD and typically developing children (TDC). BRIEFs for 411 children with ASD and 467 TDC were examined. Confirmatory factor analysis of a nine-factor model met thresholds for goodness-of-fit in TDC, but not in the ASD sample. We found globally elevated EF problems in the ASD sample, especially on the Shift scale. These findings confirm that children with ASD exhibit significant EF deficits. Further investigation is needed to understand the pervasive nature of cognitive inflexibility in children with ASD. C1 [Granader, Yael; Hardy, Kristina K.; Lawson, Rachel A.; Rosenthal, Michael; Wills, Meagan C.; Kenworthy, Lauren] Childrens Natl Med Ctr, Rockville, MD 20850 USA. [Wallace, Gregory L.; Dixon, Eunice] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Wallace, Gregory L.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA. [Yerys, Benjamin E.; Pandey, Juhi; Penna, Rebecca; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Yerys, Benjamin E.; Pandey, Juhi; Penna, Rebecca; Schultz, Robert T.] Univ Penn, Philadelphia, PA 19104 USA. [Lawson, Rachel A.] Loyola Univ Maryland, Baltimore, MD USA. RP Granader, Y (reprint author), Childrens Natl Med Ctr, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3056 EP 3062 DI 10.1007/s10803-014-2169-8 PG 7 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500009 PM 24972681 ER PT J AU Buck, TR Viskochil, J Farley, M Coon, H McMahon, WM Morgan, J Bilder, DA AF Buck, Tara R. Viskochil, Joseph Farley, Megan Coon, Hilary McMahon, William M. Morgan, Jubel Bilder, Deborah A. TI Psychiatric Comorbidity and Medication Use in Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Psychiatric comorbidity; Psychotropic medication; Intellectual disability ID MINI PAS-ADD; INTELLECTUAL DISABILITY; ASPERGER-SYNDROME; REFERRED POPULATION; UNITED-STATES; PREVALENCE; CHILDREN; INDIVIDUALS; HEALTH; PSYCHOPATHOLOGY AB The purpose of this study was to investigate comorbid psychiatric disorders and psychotropic medication use among adults with autism spectrum disorder (ASD) ascertained as children during a 1980's statewide Utah autism prevalence study (n = 129). Seventy-three individuals (56.6 %) met criteria for a current psychiatric disorder; 89 participants (69.0 %) met lifetime criteria for a psychiatric disorder. Caregivers reported a psychiatric diagnosis in 44 participants (34.1 %). Anxiety disorder had the highest current and lifetime prevalence (39.5 and 52.7 %, respectively). Participants with intellectual disability (n = 94, 72.8 %) were significantly less likely to have community-based diagnoses of anxiety (chi(2) = 5.37, p = 0.02) or depression (chi(2) = 13.18, p < 0.001) reported by caregivers. Seventy-six participants (58.9 %) were taking a parts per thousand yen1 psychotropic medication. Comorbid psychiatric disorders occur frequently in adults with ASD, though identifying these disorders poses a challenge in community settings. A greater understanding of the presentation of these conditions within this population will increase assessment validity and the potential for efficacious intervention. C1 [Buck, Tara R.; Farley, Megan; Coon, Hilary; McMahon, William M.; Morgan, Jubel; Bilder, Deborah A.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Viskochil, Joseph; Bilder, Deborah A.] Utah Autism Res Program, Salt Lake City, UT 84108 USA. RP Bilder, DA (reprint author), Utah Autism Res Program, 650 Komas Dr,Suite 206, Salt Lake City, UT 84108 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3063 EP 3071 DI 10.1007/s10803-014-2170-2 PG 9 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500010 PM 24958436 ER PT J AU Vernon, TW AF Vernon, Ty W. TI Fostering a Social Child with Autism: A Moment-By-Moment Sequential Analysis of an Early Social Engagement Intervention SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Sequential Analysis; Early Social Intervention; Naturalistic Developmental Behavioral Intervention; Pivotal Response Treatment ID YOUNG-CHILDREN; SPECTRUM DISORDERS; JOINT ATTENTION; EARLY RECOGNITION; PIVOTAL RESPONSE; INITIATIONS; BEHAVIORS; PARENTS; VIDEO; PRESCHOOLERS AB Young children with autism often experience limited social motivation and responsiveness that restricts establishment of crucial social momentum. These characteristics can lead to decreased opportunities for parental engagement and the social learning associated with these moments. Early social interventions that capitalize on pre-existing interests may be able to re-establish this developmentally critical feedback loop, in which both child and parent social behaviors simultaneously increase and influence one another. This investigation examined the moment-by-moment, micro-transactional relationship between parent and child social behavior gains observed in an early intervention study. Time-window sequential analyses revealed the presence of clinically and statistically significant sequential associations between parent and child social behaviors during an embedded social interaction intervention, but not in a comparable motivational intervention that utilized highly preferred toys and objects. Specifically, the onset of parent eye contact, directed positive affect, or offer of a reinforcing incentive predicted the immediate occurrence of child eye contact and positive affect in the experimental social intervention condition. 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PD DEC PY 2014 VL 44 IS 12 BP 3072 EP 3082 DI 10.1007/s10803-014-2173-z PG 11 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500011 PM 24974256 ER PT J AU Kotey, S Ertel, K Whitcomb, B AF Kotey, Stanley Ertel, Karen Whitcomb, Brian TI Co-occurrence of Autism and Asthma in a Nationally-Representative Sample of Children in the United States SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Asthma; Autoimmune; Screening; Allergy ID SPECTRUM DISORDERS; CHILDHOOD AUTISM; PREVALENCE; ALLERGY; BRAIN; RISK AB Few large epidemiological studies have examined the co-occurrence of autism and asthma. We performed a cross-sectional study to examine this association using the 2007 National Survey of Children's Health dataset (n = 77,951). We controlled for confounders and tested for autism-secondhand smoke interaction. Prevalence of asthma and autism were 14.5 % (n = 11,335) and 1.81 % (n = 1,412) respectively. Unadjusted odds ratio (OR) for asthma among autistic children was 1.35 (95 % CI 1.18-1.55). Adjusting for covariates (age, gender, body mass index, race, brain injury, secondhand smoke and socio-economic status) attenuated the OR to 1.19 (95 % CI 1.03-1.36). Autism-secondhand smoke interaction was insignificant (p = 0.38). Asthma is approximately 35 % more common in autistic children; screening may be an efficient approach to reduce risk of morbidity due to asthma. C1 [Kotey, Stanley; Ertel, Karen; Whitcomb, Brian] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Kotey, S (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, 715 N Pleasant St, Amherst, MA 01003 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3083 EP 3088 DI 10.1007/s10803-014-2174-y PG 6 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500012 PM 24997632 ER PT J AU Blijd-Hoogewys, EMA Bezemer, ML van Geert, PLC AF Blijd-Hoogewys, E. M. A. Bezemer, M. L. van Geert, P. L. C. TI Executive Functioning in Children with ASD: An Analysis of the BRIEF SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Executive function; Cognitive flexibility; BRIEF; IQ ID AUTISM SPECTRUM DISORDERS; DEFICIT HYPERACTIVITY DISORDER; FLUID INTELLIGENCE; WORKING-MEMORY; REAL-WORLD; SCHOOL-AGE; PERFORMANCE; DYSFUNCTION; EPIDEMIOLOGY; DEFINITIONS AB The Behavior Rating Inventory of Executive Functions (BRIEF) screens for executive function deficits in 5- to 18-year-olds. Data of three autism subgroups, according to DSM-IV-TR criteria (N = 35 Autistic Disorder, N = 27 Asperger's Disorder and N = 65 PDD-NOS), were analyzed. The total group has elevated scores on almost all BRIEF scales. The Shift scale is clinically elevated, reflecting a deficit in cognitive flexibility. The BRIEF scales are not found to discriminate among the autism spectrum disorder (ASD) subgroups. The relation between BRIEF and IQ is complex. Possible influencing factors are discussed. Finally, it is recommended to omit the Negativity scale as a validity index in children with ASD and to consider a high score on this index as a unique characteristic of their BRIEF profile, reflecting rigidity problems. C1 [Blijd-Hoogewys, E. M. A.; Bezemer, M. L.] INTER PSY, Autism Team, NL-9723 ZM Groningen, Netherlands. [Blijd-Hoogewys, E. M. A.; Bezemer, M. L.] INTER PSY, Infant Team, NL-9723 ZM Groningen, Netherlands. [Blijd-Hoogewys, E. M. A.; van Geert, P. L. C.] Univ Groningen, Dept Dev Psychol, NL-9712 TS Groningen, Netherlands. [Blijd-Hoogewys, E. M. A.; Bezemer, M. L.] Autism Team North Netherlands, NL-9728 JR Groningen, Netherlands. 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Trembath, David Dissanayake, Cheryl TI Stress and Family Quality of Life in Parents of Children with Autism Spectrum Disorder: Parent Gender and the Double ABCX Model SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Stress; Family quality of life; Child behaviour; Family sense of coherence ID HIGH-FUNCTIONING AUTISM; PRESCHOOL-CHILDREN; INTELLECTUAL DISABILITY; SYNDROME SPECIFICITY; DEVELOPMENTAL DELAY; BEHAVIOR PROBLEMS; MENTAL-HEALTH; DOWN-SYNDROME; YOUNG-ADULTS; MOTHERS AB Past research has supported the utility of the Double ABCX model of family adaptation for parents raising a child with autism spectrum disorder (ASD). What remains unclear is the impact of family-related variables on outcomes in both mothers and fathers within the same family. We explored the potential predictors of maternal and paternal stress and family quality of life in an Australian sample of 196 parents of children with ASD aged 3-16 years. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3101 EP 3118 DI 10.1007/s10803-014-2178-7 PG 18 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500014 PM 24997633 ER PT J AU Daly, BP Nicholls, EG Patrick, KE Brinckman, DD Schultheis, MT AF Daly, Brian P. Nicholls, Elizabeth G. Patrick, Kristina E. Brinckman, Danielle D. Schultheis, Maria T. TI Driving Behaviors in Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Adults; Driving; Violations ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; YOUNG-ADULTS; SELF-REPORT; QUESTIONNAIRE; INDIVIDUALS; ADOLESCENTS; ATTRIBUTION; PERCEPTION; ABILITIES AB This pilot study investigated driving history and driving behaviors between adults diagnosed with autism spectrum disorders (ASD) as compared to non-ASD adult drivers. Seventy-eight licensed drivers with ASD and 94 non-ASD comparison participants completed the Driver Behavior Questionnaire. Drivers with ASD endorsed significantly lower ratings of their ability to drive, and higher numbers of traffic accidents and citations relative to non-ASD drivers. Drivers with ASD also endorsed significantly greater numbers of difficulties on the following subscales: intentional violations, F(1, 162) = 6.15, p = .01, eta (p) (2) = .04; mistakes, F(1, 162) = 10.15, p = .002, eta (p) (2) = .06; and slips/lapses, F(1, 162) = 11.33, p = .001, eta (p) (2) = .07. These findings suggest that individuals with ASD who are current drivers may experience more difficulties in driving behaviors and engage in more problematic driving behaviors relative to non-ASD drivers. C1 [Daly, Brian P.; Nicholls, Elizabeth G.; Patrick, Kristina E.; Brinckman, Danielle D.; Schultheis, Maria T.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Daly, BP (reprint author), Drexel Univ, Dept Psychol, 3401 Chestnut St, Philadelphia, PA 19104 USA. 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PD DEC PY 2014 VL 44 IS 12 BP 3119 EP 3128 DI 10.1007/s10803-014-2166-y PG 10 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500015 PM 24925544 ER PT J AU Yang, HC Lee, IC Lee, IC AF Yang, Hsiu-Ching Lee, I-Chen Lee, I-Ching TI Visual Feedback and Target Size Effects on Reach-to-Grasp Tasks in Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Kinematics; Reach to grasp; Visual feedback; Target size ID KINEMATIC ANALYSIS; SPECTRUM DISORDER; ASPERGER-SYNDROME; PREHENSION MOVEMENTS; SENSORY PROFILE; YOUNG-CHILDREN; PERFORMANCE; ABNORMALITIES; CONSTRAINTS; IMPAIRMENT AB This study explores the effects of visual condition and target size during four reach-to-grasp tasks between autistic children and healthy controls. Twenty children with autism and 20 healthy controls participated in the study. Qualisys motion capture system and kinematic measures were used to record movement. 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CA Victorian ASELCC Team TI Effectiveness and Feasibility of the Early Start Denver Model Implemented in a Group-Based Community Childcare Setting SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Early Start Denver Model; Effectiveness; Community implementation; Early intervention ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; RANDOMIZED CONTROLLED-TRIAL; EARLY INTERVENTION; OUTCOMES; TODDLERS AB A recent study documented the efficacy of the Early Start Denver Model (ESDM) delivered in a 1:1 fashion. In the current study we investigated the effectiveness and feasibility of the ESDM in the context of a long-day care community service, with a child-staff ratio of 1:3. Outcomes of 27 preschoolers with ASD undergoing 15-25 h per week of ESDM over 12 months were compared to those of 30 peers with ASD undergoing a different intervention program delivered in a similar community long-day care service. Children in both groups made gains in cognitive, adaptive and social skills. Participants in the ESDM group showed significantly higher gains in developmental rate and receptive language. C1 [Vivanti, Giacomo; Dissanayake, Cheryl] La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Melbourne, Vic 3086, Australia. [Vivanti, Giacomo; Duncan, Ed; Victorian ASELCC Team] La Trobe Univ, Victorian Autism Specif Early Learning & Care Ctr, Melbourne, Vic 3086, Australia. [Paynter, Jessica; Fothergill, Hannah] AEIOU Fdn, Res & Psychol Dept, Brisbane, Qld, Australia. [Rogers, Sally J.] Univ Calif Davis, Med Ctr, MIND Inst, Sacramento, CA 95817 USA. RP Vivanti, G (reprint author), La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Bundoora Campus, Melbourne, Vic 3086, Australia. EM g.vivanti@latrobe.edu.au CR Anagnostou E., 2011, AUTISM SPECTRUM DISO, P1259 Anderson D. 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R., 2010, EVIDENCE BASED PSYCH NR 43 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 DEC PY 2014 VL 44 IS 12 BP 3140 EP 3153 DI 10.1007/s10803-014-2168-9 PG 14 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500017 PM 24974255 ER PT J AU Cicchetti, DV Lord, C Koenig, K Klin, A Volkmar, FR AF Cicchetti, Domenic V. Lord, Catherine Koenig, Kathy Klin, Ami Volkmar, Fred R. TI Reliability of the ADI-R for the Single Case-Part II: Clinical Versus Statistical Significance SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Clinical significance; Statistical significance; Inter-rater reliability; Multiple raters, one patient ID INTER-RATER RELIABILITY; RATING-SCALES; AGREEMENT AB In an earlier investigation, the authors assessed the reliability of the ADI-R when multiple clinicians evaluated a single case, here a female 3 year old toddler suspected of having an autism spectrum disorder (Cicchetti et al. in J Autism Dev Disord 38:764-770, 2008). Applying the clinical criteria of Cicchetti and Sparrow (Am J Men Def 86:127-137, 1981); and those of Cicchetti et al. (Child Neuropsychol 126-137, 1995): 74 % of the ADI-R items showed 100 % agreement; 6 % showed excellent agreement; 7 % showed good agreement; 3 % manifested average agreement; and the remaining 10 % evidenced poor agreement. In this follow-up investigation, the authors described and applied a novel method for determining levels of statistical significance of the reliability coefficients obtained in the earlier investigation. It is based upon a modification of the Z test for comparing a given level of inter-examiner reliability with a lower limit value of 70 % (Dixon and Massey in Introduction to statistical analysis. McGraw-Hill, New York, 1957). Results indicated that every item producing a clinically acceptable level of inter-examiner reliability was also statistically significant. However, the reverse was not true, since a number of the items with statistically significant reliability levels did not reach levels of agreement that were clinically meaningful. This indicated that clinical significance was an accurate marker of statistical significance. The generalization of these findings to other areas of diagnostic interest and importance is also examined. C1 [Cicchetti, Domenic V.; Koenig, Kathy; Volkmar, Fred R.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Cicchetti, Domenic V.] Yale Home Off, North Branford, CT 06471 USA. [Lord, Catherine] Columbia Univ, Cornell Med Coll, NY Presbyterian Hosp, New York, NY USA. [Klin, Ami] Emory Univ, Atlanta, GA 30322 USA. RP Cicchetti, DV (reprint author), Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. EM dom.cicchetti@yale.edu CR Cicchetti D. V., 1995, CHILD NEUROPSYCHOL, V1, P126 Cicchett D, 2009, PSYCHIAT RES, V166, P269, DOI 10.1016/j.psychres.2008.01.014 Cicchetti DV, 2008, J AUTISM DEV DISORD, V38, P764, DOI 10.1007/s10803-007-0448-3 CICCHETTI DV, 1981, AM J MENT DEF, V86, P127 CICCHETTI DV, 1976, BRIT J PSYCHIAT, V129, P452, DOI 10.1192/bjp.129.5.452 COHEN J, 1968, PSYCHOL BULL, V70, P213, DOI 10.1037/h0026256 Dixon W. 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TI Evidence for Diminished Multisensory Integration in Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Sensory processing; Audiovisual; Multisensory integration; Audition; Vision ID AUDIOVISUAL SPEECH-PERCEPTION; SUPERIOR VISUAL-SEARCH; ENHANCED DISCRIMINATION; TEMPORAL INTEGRATION; CHILDREN; SYNCHRONY; WINDOW; INDIVIDUALS; PERFORMANCE; CHILDHOOD AB Individuals with autism spectrum disorders (ASD) exhibit alterations in sensory processing, including changes in the integration of information across the different sensory modalities. In the current study, we used the sound-induced flash illusion to assess multisensory integration in children with ASD and typically-developing (TD) controls. Thirty-one children with ASD and 31 age and IQ matched TD children (average age = 12 years) were presented with simple visual (i.e., flash) and auditory (i.e., beep) stimuli of varying number. In illusory conditions, a single flash was presented with 2-4 beeps. In TD children, these conditions generally result in the perception of multiple flashes, implying a perceptual fusion across vision and audition. In the present study, children with ASD were significantly less likely to perceive the illusion relative to TD controls, suggesting that multisensory integration and cross-modal binding may be weaker in some children with ASD. These results are discussed in the context of previous findings for multisensory integration in ASD and future directions for research. C1 [Stevenson, Ryan A.; Wallace, Mark T.] Vanderbilt Univ, Med Ctr, Dept Hearing & Speech Sci, Vanderbilt Kennedy Ctr,Vanderbilt Brain Inst, Nashville, TN USA. [Stevenson, Ryan A.] Univ Toronto, Dept Psychol, Toronto, ON M5S 3G3, Canada. [Siemann, Justin K.] Vanderbilt Univ, Grad Program Neurosci, Nashville, TN 37235 USA. [Woynaroski, Tiffany G.; Camarata, Stephen M.] Vanderbilt Univ, Med Ctr, Dept Hearing & Speech Sci, Nashville, TN USA. [Schneider, Brittany C.; Eberly, Haley E.] Vanderbilt Univ, Program Neurosci, Nashville, TN 37235 USA. RP Stevenson, RA (reprint author), Univ Toronto, Dept Psychol, 100 St George St,Rm 523, Toronto, ON M5S 3G3, Canada. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3161 EP 3167 DI 10.1007/s10803-014-2179-6 PG 7 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500019 PM 25022248 ER PT J AU Troyb, E Orinstein, A Tyson, K Eigsti, IM Naigles, L Fein, D AF Troyb, Eva Orinstein, Alyssa Tyson, Katherine Eigsti, Inge-Marie Naigles, Letitia Fein, Deborah TI Restricted and Repetitive Behaviors in Individuals with a History of ASDs Who Have Achieved Optimal Outcomes SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Optimal outcome; Restricted and repetitive behaviors; Autism ID AUTISM SPECTRUM DISORDERS; FOLLOW-UP; CHILDREN; INTERVENTION; ADOLESCENTS; PREDICTORS; ADULTS; AGE; IQ; COMMUNICATION AB Studies of autism spectrum disorders (ASDs) suggest that restricted and repetitive behaviors (RRBs) are particularly difficult to remediate. We examined present and past RRBs in 34 individuals who achieved optimal outcomes (OOs; lost their ASD diagnosis), 45 high-functioning individuals with ASD (HFA) and 34 typically developing (TD) peers. The OO group exhibited minimal residual RRBs at the time of the study. All OO participants were reported to have at least one RRB in early childhood and almost 90 % met the RRB cutoff for ASD in early childhood, but RRBs were not more present in the OO than the TD group at the time of the study. History of RRBs in the HFA and OO groups differed only in oversensitivity to noise and insistence on sameness. Reports of current behavior indicated that RRB's had almost totally disappeared in the OO group. Thus, although RRB's were present in the OO group in childhood, they resolved along with social and communication deficits. C1 [Troyb, Eva; Orinstein, Alyssa; Tyson, Katherine; Eigsti, Inge-Marie; Naigles, Letitia; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3168 EP 3184 DI 10.1007/s10803-014-2182-y PG 17 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500020 PM 25030967 ER PT J AU Falk, NH Norris, K Quinn, MG AF Falk, Nicholas Henry Norris, Kimberley Quinn, Michael G. TI The Factors Predicting Stress, Anxiety and Depression in the Parents of Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Mothers; Fathers; Stress; Anxiety; Depression; Autism ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; FIT INDEXES; MOTHERS; BEHAVIORS; HEALTH; FAMILY; PERCEPTIONS; SUPPORT; FATHERS AB The factors predicting stress, anxiety and depression in the parents of children with autism remain poorly understood. In this study, a cohort of 250 mothers and 229 fathers of one or more children with autism completed a questionnaire assessing reported parental mental health problems, locus of control, social support, perceived parent-child attachment, as well as autism symptom severity and perceived externalizing behaviours in the child with autism. Variables assessing parental cognitions and socioeconomic support were found to be more significant predictors of parental mental health problems than child-centric variables. A path model, describing the relationship between the dependent and independent variables, was found to be a good fit with the observed data for both mothers and fathers. C1 [Falk, Nicholas Henry; Norris, Kimberley; Quinn, Michael G.] Univ Tasmania, Sch Psychol, Hobart, Tas 7005, Australia. [Falk, Nicholas Henry] Univ Tasmania, Hobart, Tas 7053, Australia. RP Falk, NH (reprint author), Univ Tasmania, C-O 29 Taroona Crescent, Hobart, Tas 7053, Australia. 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Ingersoll, Brooke TI A Further Investigation of Goal-Directed Intention Understanding in Young Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Intention understanding; Social cognition ID JOINT ATTENTION; BEHAVIORAL REENACTMENT; FAILED ATTEMPTS; INTENDED ACTS; OTHERS; IMPAIRMENTS; EMULATION; IMITATION; ROLES AB Findings from research investigating goal-directed intention understanding in children with autism spectrum disorders (ASD) have been equivocal, in part because of the varying methodologies used across studies. This study compares both object-oriented and social-communicatively cued goal-directed intention understanding in children with ASD and typically-developing children. Relative to matched controls, children with ASD did not exhibit deficits in object-oriented intention understanding. While children with ASD also demonstrated the ability to understand intention when cued by social-communication indicators, typically-developing children differentiated between intentional and unintentional acts at a significantly greater level. Group differences in performance were eliminated if only trials in which children attended to the experimenter's face were considered. Results suggest that children with ASD have intact object-oriented intention understanding abilities, and are able to use social-communicative cues to understand intention. However, their ability to demonstrate social-communicatively cued intention understanding is limited by a lack of attention to relevant social-communicative information. C1 [Berger, Natalie I.; Ingersoll, Brooke] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. RP Berger, NI (reprint author), Michigan State Univ, Dept Psychol, Psychol Bldg,316 Phys Rd Room 69F, E Lansing, MI 48824 USA. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3204 EP 3214 DI 10.1007/s10803-014-2181-z PG 11 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500022 PM 25001543 ER PT J AU Vasa, RA Carroll, LM Nozzolillo, AA Mahajan, R Mazurek, MO Bennett, AE Wink, LK Bernal, MP AF Vasa, Roma A. Carroll, Laura M. Nozzolillo, Alixandra A. Mahajan, Rajneesh Mazurek, Micah O. Bennett, Amanda E. Wink, Logan K. Bernal, Maria Pilar TI A Systematic Review of Treatments for Anxiety in Youth with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Anxiety; Autism spectrum disorders; Treatments; Children; Adolescents ID COGNITIVE-BEHAVIORAL THERAPY; PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; RANDOMIZED CONTROLLED-TRIAL; INTELLECTUAL DISABILITY; PSYCHOMETRIC PROPERTIES; CHILDHOOD ANXIETY; OPEN-LABEL; DSM-IV; CHILDREN AB This study systematically examined the efficacy and safety of psychopharmacological and non-psychopharmacological treatments for anxiety in youth with autism spectrum disorders (ASD). Four psychopharmacological, nine cognitive behavioral therapy (CBT), and two alternative treatment studies met inclusion criteria. Psychopharmacological studies were descriptive or open label, sometimes did not specify the anxiety phenotype, and reported behavioral activation. Citalopram and buspirone yielded some improvement, whereas fluvoxamine did not. Non-psychopharmacological studies were mainly randomized controlled trials (RCTs) with CBT demonstrating moderate efficacy for anxiety disorders in youth with high functioning ASD. Deep pressure and neurofeedback provided some benefit. All studies were short-term and included small sample sizes. Large scale and long term RCTs examining psychopharmacological and non-psychopharmacological treatments are sorely needed. C1 [Vasa, Roma A.; Mahajan, Rajneesh] Kennedy Krieger Inst, Baltimore, MD 21211 USA. [Vasa, Roma A.; Mahajan, Rajneesh] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Carroll, Laura M.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Nozzolillo, Alixandra A.] Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Mazurek, Micah O.] Univ Missouri, Dept Hlth Psychol, Columbia, MO 65212 USA. 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PD DEC PY 2014 VL 44 IS 12 BP 3215 EP 3229 DI 10.1007/s10803-014-2184-9 PG 15 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500023 PM 25070468 ER PT J AU Kim, SH Junker, D Lord, C AF Kim, So Hyun Junker, Doerte Lord, Catherine TI Observation of Spontaneous Expressive Language (OSEL): A New Measure for Spontaneous and Expressive Language of Children with Autism Spectrum Disorders and Other Communication Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Language; Assessment ID PERVASIVE DEVELOPMENTAL DISORDER; GRAMMATICAL MORPHEMES; ASPERGER-SYNDROME; AGREEMENT; INTERVENTION; IMPAIRMENT; CRITERIA AB A new language measure, the Observation of Spontaneous Expressive Language (OSEL), is intended to document spontaneous use of syntax, pragmatics, and semantics in 2-12-year-old children with Autism Spectrum Disorder (ASD) and other communication disorders with expressive language levels comparable to typical 2-5 year olds. Because the purpose of the OSEL is to provide developmental norms for use of language, the first step involves assessment of the scale's feasibility, validity, and reliability using a sample of 180 2-5 year-old typically developing children. Pilot data from the OSEL shows strong internal consistency, high reliabilities and validity. Once replicated with a large population-based sample and in special populations, the scale should be helpful in designing appropriate interventions for children with ASD and other communication disorders. C1 [Kim, So Hyun] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06510 USA. [Junker, Doerte] Milan Area Sch, Milan, MI 48160 USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Dev Brain, White Plains, NY 10605 USA. RP Kim, SH (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, 40 Temple St Suite 7-D, New Haven, CT 06510 USA. 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L., 2011, PRESCHOOL LANGUAGE S NR 51 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 DEC PY 2014 VL 44 IS 12 BP 3230 EP 3244 DI 10.1007/s10803-014-2180-0 PG 15 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500024 PM 25022249 ER PT J AU Muth, A Honekopp, J Falter, CM AF Muth, Anne Hoenekopp, Johannes Falter, Christine M. TI Visuo-Spatial Performance in Autism: A Meta-analysis SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Visuo-spatial; Figure Disembedding; Mental Rotation; Block Design; Navon Figures ID HIGH-FUNCTIONING AUTISM; WEAK CENTRAL COHERENCE; EMBEDDED FIGURES TASK; SUPERIOR DISEMBEDDING PERFORMANCE; MALE-BRAIN THEORY; SPECTRUM DISORDERS; ASPERGER-SYNDROME; SEX-DIFFERENCES; VISUAL-SEARCH; FIELD-INDEPENDENCE AB Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design (d = 0.32) and Figure Disembedding (d = 0.26) showed superior performance for ASD with large heterogeneity that is unaccounted for. No clear differences were found for Mental Rotation. ASD samples showed a stronger local processing preference for Navon tasks (d = 0.35); less clear evidence for performance differences of a similar magnitude emerged. We discuss the meta-analysis results together with other findings relating to visuo-spatial processing and three cognitive theories of ASD: Weak Central Coherence, Enhanced Perceptual Functioning and Extreme Male Brain theory. C1 [Muth, Anne] Bangor Univ, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales. [Hoenekopp, Johannes] Northumbria Univ, Dept Psychol, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. [Falter, Christine M.] Univ Hosp Cologne, Dept Psychiat, Cologne, Germany. RP Muth, A (reprint author), Bangor Univ, Sch Psychol, Penrallt Rd, Bangor LL57 2AS, Gwynedd, Wales. 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PD DEC PY 2014 VL 44 IS 12 BP 3245 EP 3263 DI 10.1007/s10803-014-2188-5 PG 19 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500025 PM 25022252 ER PT J AU Germani, T Zwaigenbaum, L Bryson, S Brian, J Smith, I Roberts, W Szatmari, P Roncadin, C Sacrey, LAR Garon, N Vaillancourt, T AF Germani, Tamara Zwaigenbaum, Lonnie Bryson, Susan Brian, Jessica Smith, Isabel Roberts, Wendy Szatmari, Peter Roncadin, Caroline Sacrey, Lori Ann R. Garon, Nancy Vaillancourt, Tracy TI Brief Report: Assessment of Early Sensory Processing in Infants at High-Risk of Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Sensory; Infant siblings ID PRESCHOOL-CHILDREN; BEHAVIORS; TEMPERAMENT; SIBLINGS; MOTOR; AGE AB This study assessed sensory processing differences between 24-month infants at high-risk of autism spectrum disorder (ASD), each with an older sibling with ASD, and low-risk infants with no family history of ASD. Sensory processing differences were assessed using the Infant/Toddler Sensory Profile, a parent-reported measure. Groups were compared based on 3-year outcomes: (a) high-risk infants subsequently diagnosed with ASD; (b) high-risk infants without an ASD diagnosis; and (c) low-risk infants without an ASD diagnosis. Analyses showed that high-risk infants diagnosed with ASD have more difficulty with auditory processing (i.e., responses to auditory stimuli) and lower registration (i.e., lacking sensation awareness) compared to controls. Thus, behavioral responses to sensory input represent early risk markers of ASD, particularly in high-risk infants. C1 [Germani, Tamara; Zwaigenbaum, Lonnie; Sacrey, Lori Ann R.] Univ Alberta, Dept Pediat, Fac Med & Dent, Edmonton, AB, Canada. [Germani, Tamara] Glenrose Rehabil Hosp, Dept Pediat, Autism Res Ctr E209, Edmoton, AB T5G 0B7, Canada. [Zwaigenbaum, Lonnie; Sacrey, Lori Ann R.] Glenrose Rehabil Hosp, Autism Res Ctr, Edmoton, AB T5G 0B7, Canada. [Bryson, Susan; Smith, Isabel] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. [Brian, Jessica] Bloorview Res Inst, Toronto, ON, Canada. [Brian, Jessica; Roberts, Wendy; Szatmari, Peter] Univ Toronto, Toronto, ON, Canada. [Roberts, Wendy; Szatmari, Peter] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Szatmari, Peter] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Roncadin, Caroline] Peels Children Ctr, Mississauga, ON, Canada. [Garon, Nancy] Mt Allison Univ, Sackville, NB E0A 3C0, Canada. [Vaillancourt, Tracy] Univ Ottawa, Ottawa, ON, Canada. RP Germani, T (reprint author), Glenrose Rehabil Hosp, Dept Pediat, Autism Res Ctr E209, 10230-111 Ave, Edmoton, AB T5G 0B7, Canada. 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Autism Dev. Disord. PD DEC PY 2014 VL 44 IS 12 BP 3264 EP 3270 DI 10.1007/s10803-014-2175-x PG 7 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500026 PM 24970108 ER PT J AU DeVilbiss, EA Lee, BK AF DeVilbiss, Elizabeth A. Lee, Brian K. TI Brief Report: Trends in US National Autism Awareness from 2004 to 2014: The Impact of National Autism Awareness Month SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism awareness; Web 2.0; Google trends AB We sought to evaluate the potential for using historical web search data on autism spectrum disorders (ASD)-related topics as an indicator of ASD awareness. Analysis of Google Trend data suggested that National Autism Awareness Month and televised reports concerning autism are an effective method of promoting online search interest in autism. C1 [DeVilbiss, Elizabeth A.; Lee, Brian K.] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lee, Brian K.] AJ Drexel Autism Inst, Philadelphia, PA USA. RP Lee, BK (reprint author), Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 3215 Market St, Philadelphia, PA 19104 USA. EM bklee@drexel.edu CR [Anonymous], 2007, O WINFREY SHOW [Anonymous], 2005, TODAY SHOW Elsabbagh M, 2012, AUTISM RES, V5, P160, DOI 10.1002/aur.239 Glynn RW, 2011, BMC CANCER, V11, DOI 10.1186/1471-2407-11-442 Lee BK, 2010, EPIDEMIOLOGY, V21, P760, DOI 10.1097/EDE.0b013e3181f5a75f Russell G, 2014, J AUTISM DEV DISORD, V44, P31, DOI 10.1007/s10803-013-1849-0 NR 6 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 DEC PY 2014 VL 44 IS 12 BP 3271 EP 3273 DI 10.1007/s10803-014-2160-4 PG 3 WC Psychology, Developmental SC Psychology GA AT3AM UT WOS:000344806500027 PM 24915931 ER PT J AU Pontifex, MB Fine, JG da Cruz, K Parks, AC Smith, AL AF Pontifex, Matthew B. Fine, Jodene G. da Cruz, Katelin Parks, Andrew C. Smith, Alan L. TI THE ROLE OF PHYSICAL ACTIVITY IN REDUCING BARRIERS TO LEARNING IN CHILDREN WITH DEVELOPMENTAL DISORDERS SO MONOGRAPHS OF THE SOCIETY FOR RESEARCH IN CHILD DEVELOPMENT LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; FUNCTIONAL MAGNETIC-RESONANCE; AEROBIC FITNESS; PREADOLESCENT CHILDREN; EXECUTIVE FUNCTIONS; COGNITIVE CONTROL; PSYCHIATRIC-DISORDERS; ACADEMIC-ACHIEVEMENT AB Emerging research suggests that physical activity may be an effective non-pharmaceutical intervention approach for childhood developmental disorders. Findings indicate that both single bouts of activity and chronic physical activity associate with improved mental health and classroom performance in children with attention-deficit/hyperactivity disorder and children with autism spectrum disorders. This review describes the research in this area and identifies limitations and challenges to the translation of these findings to promote physical activity in clinical practice and educational policy. C1 [Pontifex, Matthew B.; Parks, Andrew C.; Smith, Alan L.] Michigan State Univ, Dept Kinesiol, Coll Educ, E Lansing, MI 48824 USA. [Fine, Jodene G.; da Cruz, Katelin] Michigan State Univ, Dept Counseling Educ Psychol & Special Educ, Coll Educ, E Lansing, MI 48824 USA. [Fine, Jodene G.] MSU Dept Psychiat, E Lansing, MI 48824 USA. RP Pontifex, MB (reprint author), Michigan State Univ, Dept Kinesiol, 27P IM Sports Circle,308 W Circle Dr, E Lansing, MI 48824 USA. 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PD DEC PY 2014 VL 79 IS 4 BP 93 EP 118 DI 10.1111/mono.12132 PG 26 WC Psychology, Developmental SC Psychology GA AT2WN UT WOS:000344795100006 PM 25387417 ER PT J AU Funahashi, Y Karashima, C Hoshiyama, M AF Funahashi, Yoshimi Karashima, Chieko Hoshiyama, Minoru TI Compensatory Postural Sway While Seated Posture During Tasks in Children with Autism Spectrum Disorder SO OCCUPATIONAL THERAPY INTERNATIONAL LA English DT Article DE ASD; postural control; paediatric occupational therapy ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; MOTOR-SKILL; BEHAVIORS; PROPRIOCEPTION; DYSFUNCTION; MOVEMENTS; INTERVIEW; DYSPRAXIA; DEFICIT AB Postural stability while seated was investigated in 16 children with autism spectrum disorder (ASD) and 16 typically developed (TD) children, aged 7-8years. The lateral and antero-posterior (A-P) deviations of the centre of pressure (COP) were serially measured during sequential, upper limb, desk-top tasks, including nine subtests. The average COP deviation was larger, especially in the lateral direction, in the group of children with ASD compared with TD children. However, the larger COP deviation in the children with ASD was not generalized across tasks. Analyses of subtests revealed that deviations were different on three and four (of eight) subtests in the lateral and A-P directions, respectively. The time needed to complete each subtest was not correlated with the lateral COP deviation but with A-P deviation during the subtest in the children with ASD. Preserved task performance with marked body sway in the children with ASD suggested that the body sway was not a functionally abnormal movement that disturbed performance but could be a compensatory movement to actually facilitate performance. A new approach with occupational therapy to support such compensatory movement of ASD children could be considered in their school life. Further studies, including those in the classroom, to clarify the relationship between daily task performance and body instability are necessary. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Funahashi, Yoshimi; Karashima, Chieko; Hoshiyama, Minoru] Nagoya Univ, Grad Sch Med, Dept Occupat Therapy, Sch Hlth Sci,Higashi Ku, Nagoya, Aichi 4618673, Japan. RP Karashima, C (reprint author), Nagoya Univ, Postgrad Sch Hlth Sci, Dept Occupat Therapy, Higashi Ku, 1-1-20 Daiko Minami, Nagoya, Aichi 4618673, Japan. EM karashim@met.nagoya-u.ac.jp FU Japan Society for the Promotion of Science [C-24500576, C-24591292] FX This study was partially supported by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science (C-24500576, C-24591292). 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Ther. Int. PD DEC PY 2014 VL 21 IS 4 BP 166 EP 175 DI 10.1002/oti.1375 PG 10 WC Rehabilitation SC Rehabilitation GA AT2TU UT WOS:000344789800003 PM 24956573 ER PT J AU Vrieze, SI Malone, SM Vaidyanathan, U Kwong, A Kang, HM Zhan, XW Flickinger, M Irons, D Jun, G Locke, AE Pistis, G Porcu, E Levy, S Myers, RM Oetting, W Mcgue, M Abecasis, G Iacono, WG AF Vrieze, Scott I. Malone, Stephen M. Vaidyanathan, Uma Kwong, Alan Kang, Hyun Min Zhan, Xiaowei Flickinger, Matthew Irons, Daniel Jun, Goo Locke, Adam E. Pistis, Giorgio Porcu, Eleonora Levy, Shawn Myers, Richard M. Oetting, William Mcgue, Matt Abecasis, Goncalo Iacono, William G. TI In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes SO PSYCHOPHYSIOLOGY LA English DT Article DE Endophenotype; Psychophysiology; Whole genome sequencing; Rare variant; P300; Startle; Antisaccade; EEG ID MOLECULAR-GENETIC BASIS; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; WIDE ASSOCIATION; GENOTYPE IMPUTATION; HERITABILITY; SCHIZOPHRENIA; DNA; REVEALS; DISEASE AB Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range=802-1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range=3,088-4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation. C1 [Vrieze, Scott I.; Kwong, Alan; Kang, Hyun Min; Zhan, Xiaowei; Flickinger, Matthew; Jun, Goo; Locke, Adam E.; Pistis, Giorgio; Porcu, Eleonora; Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Malone, Stephen M.; Vaidyanathan, Uma; Irons, Daniel; Mcgue, Matt; Iacono, William G.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Levy, Shawn; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Oetting, William] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. RP Iacono, WG (reprint author), Univ Minnesota, 75 E River Rd, Minneapolis, MN 55455 USA. EM goncalo@umich.edu; wiacono@umn.edu FU NIH [DA024417, DA05147, AA09367, DA13240, DA036216, DA034606, HG007022, HL117626] FX This research was supported by NIH grants DA024417, DA05147, AA09367, DA13240, DA036216, DA034606, HG007022, and HL117626. Dr. Vrieze is now at the Department of Psychology and Neuroscience, and the Institute for Behavioral Genetics, at the University of Colorado Boulder. 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Sourander, Andre TI Bipolar disorder and parental psychopathology SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Bipolar disorder; Schizophrenia; Register; Population-based study; Epidemiology; Parental psychopathology ID AUTISM SPECTRUM DISORDERS; GENOME-WIDE ASSOCIATION; RISK-FACTORS; SCHIZOAFFECTIVE DISORDER; MENTAL-DISORDERS; PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; DEPRESSIVE DISORDER; SCHIZOPHRENIA; POPULATION AB Few population-based studies have examined the association between parental psychopathology and bipolar disorder (BPD) in offspring. One limitation is lack of control for potential confounding by indicators of parental socio-economic status or maternal smoking during pregnancy. Furthermore, none of them included analyses restricted to parental diagnoses received prior to the birth of the offspring. Associations could not be affected by child-related factors affecting the parent in such analyses. This study explores associations between those parental psychiatric disorders diagnosed at any point of time as well as those diagnosed before offspring birth, and BPD in offspring. In this nested case-control study, we identified 1,861 cases, age up to 25 years, 3,643 matched controls, and their parents from Finnish national registers. The associations were examined using conditional logistic regression, calculating odds ratios (OR) and adjusting for region of birth, parental age and education and mother's smoking during pregnancy. Anytime diagnosed parental disorders associating with BPD in offspring (95 % confidence interval) were BPD [OR (maternal) 5.2 (2.52-10.62); OR (paternal) 8.1 (3.77-17.26)], schizophrenia and related psychoses [OR (maternal) 3.1 (1.69-5.84); OR (paternal) 4.5 (1.97-10.27)], other affective disorders [OR (maternal) 3.0 (2.08-4.21); OR (paternal) 3.0 (1.97-4.47)] and maternal anxiety disorders OR 2.6 (1.08-6.42). Statistically significant associations were also found for parental schizophrenia and related psychoses, and other affective disorders, diagnosed before offspring birth. BPD is associated with many parental psychiatric disorders, particularly BPD and schizophrenia and related psychoses. The associations must be partially due to child-independent factors. Covariate adjustments had only a minor impact on the associations. C1 [Sucksdorff, Dan; Chudal, Roshan; Suominen, Auli; Jokiranta, Elina; Sourander, Andre] Univ Turku, Dept Child Psychiat, Fac Med, Res Ctr Child Psychiat,Inst Clin Med, Turku 20014, Finland. [Brown, Alan S.; Sourander, Andre] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Brown, Alan S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Sourander, Andre] Turku Univ Hosp, Dept Child Psychiat, FIN-20520 Turku, Finland. RP Sucksdorff, D (reprint author), Univ Turku, Dept Child Psychiat, Fac Med, Res Ctr Child Psychiat,Inst Clin Med, Lemminkaisenkatu 3 Teutori 3rd Floor, Turku 20014, Finland. EM dansuc@utu.fi RI Chudal, Roshan/C-1067-2015 FU NARSAD Independent Investigator Award, USA; Sigrid Juselius Foundation, Finland; National Institutes of Health [5K02-MH65422]; Finnish Epilepsy Society FX The study was supported by grants from NARSAD Independent Investigator Award, USA (Andre Sourander), the Sigrid Juselius Foundation, Finland (Andre Sourander), National Institutes of Health with grant number 5K02-MH65422 (Alan S. Brown), and the Finnish Epilepsy Society (Elina Jokiranta). They had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. 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Several researchers have suggested that this will lead to a significant decrease in prevalence for the disorder. Because social skills have been established as a core symptom since autism was first described, the present study examines differences in social functioning using the Matson Evaluation of Social Skills in Youngsters-II (MESSY-II) among children diagnosed with ASD (ages 3-16 years) using DSM-IV-TR criteria, children diagnosed using the DSM-5, and a control group of typically developing children. In the present study of 205 children and adolescents, significant differences were found between the control group and the ASD groups combined. Differences between the DSM-5 group and the DSM-IV group were not found related to inappropriate social skills, suggesting that those who no longer meet diagnostic criteria for ASD exhibit similar social deficits as those who continue to meet criteria for ASD. Concerning socially appropriate behavior, significantly more impairment was found in the DSM-5 group compared with the DSM-IV group, though both groups evinced severe impairments. The implications of these findings are important. Individuals who no longer meet criteria for ASD have clinically significant social deficits and do not differ significantly from those who continue to meet criteria for ASD. Thus, children no longer meeting ASD criteria continue to need interventions that are effective for treating social deficits in autism. C1 [Beighley, Jennifer S.; Matson, Johnny L.] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Beighley, JS (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Dev. Phys. Disabil. PD DEC PY 2014 VL 26 IS 6 BP 689 EP 701 DI 10.1007/s10882-014-9382-4 PG 13 WC Rehabilitation SC Rehabilitation GA AT0AA UT WOS:000344598100003 ER PT J AU Rueda, P Fernandez-Berrocal, P Schonert-Reichl, KA AF Rueda, Pilar Fernandez-Berrocal, Pablo Schonert-Reichl, Kimberly A. TI Perspective-Taking and Empathic Concern as Mediators for Happiness and Positive Affect in Adolescents With and Without Asperger Syndrome SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Asperger syndrome; Happiness; Affect; Mediators; Empathy ID HIGH-FUNCTIONING AUTISM; NEGATIVE AFFECT; EMOTIONAL EMPATHY; SPECTRUM DISORDER; DEPRESSIVE SYMPTOMS; SOCIAL-SKILLS; MENTAL-HEALTH; PANAS SCALES; CHILDREN; ADULTS AB The present study explored the mediating role of cognitive and affective components of empathy in the relationship between happiness and positive and negative affect in adolescents with Asperger Syndrome (AS) and their non-AS peers. For that purpose, we measured empathy, subjective happiness, and affect experienced by a group of 42 adolescents with AS compared to 44 of their non-AS peers. Adolescents in both groups were matched on age, sex, and IQ, and were administered a battery of measures assessing their self-reports of empathy, perspective-taking, subjective happiness, and positive and negative affect. Findings revealed that adolescents with AS, in contrast to their peers without AS, reported less subjective happiness, less positive affect, and lower affective balance. No differences were found between the two groups on negative affect. A mediating role of both cognitive and affective components of empathy was found between happiness, positive affect, and affective balance experienced in relation to AS. Theoretical and practical implications of these results are discussed. C1 [Rueda, Pilar] Fac Psicol, Dept Psicol Basica, Malaga 29071, Spain. [Fernandez-Berrocal, Pablo] Univ Malaga, E-29071 Malaga, Spain. 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TI Understanding, Experiences, and Reactions to Bullying Experiences in Boys with an Autism Spectrum Disorder SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE ASD; Boys; School; Bullying ID CHILDREN; HEALTH; INCLUSION; PARENTS; STRESS; VICTIMIZATION; PERSPECTIVES; ADOLESCENTS; FRIENDSHIP; SYMPTOMS AB Most previous studies of bullying in young people with an Autism Spectrum Disorder (ASD) have relied on data from adults' rather than the person with an ASD themselves, thus limiting our understanding of the bullying experience from the child's perspective. To investigate this issue, 48 high-functioning boys with an ASD, and their mothers, completed an online questionnaire about various aspects of bullying. There were some minor discrepancies between mothers' and their sons' reported frequency of bullying. Boys demonstrated an understanding of the behaviour that constitutes bullying that was consistent with the wider literature, enhancing the validity of their responses about their experiences. Sources of bullying included friends, and bullying mostly occurred in the playground. These boys had ineffective coping strategies for bullying, and many reported significant physical and emotional negative reactions. Many boys found that telling adults made their bullying experiences worse, and most kept their bullying experiences to themselves until they reached home, then adopting a range of negative (tantrums) and positive (staying alone to calm down) behaviours. Unfortunately, over half of these boys sought to absent themselves from school as their preferred method for coping with their bullying experiences. These findings have major implications for interventions within schools to reduce bullying and to provide access to learning and social activities. C1 [Bitsika, Vicki; Sharpley, Christopher F.] Bond Univ, Ctr Autism Spectrum Disorders, Gold Coast, Qld, Australia. [Sharpley, Christopher F.] Univ New England, Brain Behav Res Grp, Armidale, NSW, Australia. RP Sharpley, CF (reprint author), Univ New England, Brain Behav Res Grp, Armidale, NSW, Australia. 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Dev. Phys. Disabil. PD DEC PY 2014 VL 26 IS 6 BP 747 EP 761 DI 10.1007/s10882-014-9393-1 PG 15 WC Rehabilitation SC Rehabilitation GA AT0AA UT WOS:000344598100007 ER PT J AU Ramirez, H Cengher, M Fienup, DM AF Ramirez, Heyde Cengher, Mirela Fienup, Daniel M. TI The Effects of Simultaneous Prompting on the Acquisition of Calculating Elapsed Time in Children with Autism SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Elapsed time; Simultaneous prompting; Conditional discrimination; Chained behavior ID DEVELOPMENTAL-DISABILITIES; SKILLS; INSTRUCTION; STUDENTS AB Simultaneous prompting has been effective in teaching a variety of skills, of different levels of complexity, to children with learning difficulties. The current study replicated and extended previous research by teaching three children with Autism to calculate elapsed time. Elapsed time is the duration from a start to end time. 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PD DEC PY 2014 VL 26 IS 6 BP 763 EP 774 DI 10.1007/s10882-014-9394-0 PG 12 WC Rehabilitation SC Rehabilitation GA AT0AA UT WOS:000344598100008 ER PT J AU Barger, B Campbell, J Simmons, C AF Barger, Brian Campbell, Jonathan Simmons, Christina TI Measuring Five Factor Personality Traits in Autism During Early Childhood SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Temperament; Personality; Five factor model; Autism quotient ID HIGH-FUNCTIONING AUTISM; SPECTRUM QUOTIENT AQ; INDIVIDUAL-DIFFERENCES; ASPERGER-SYNDROME; EXECUTIVE DYSFUNCTION; GENERAL-POPULATION; PROBLEM BEHAVIOR; SELF-REGULATION; HIGH-RISK; TEMPERAMENT AB This study reports data indicating that the Five Factor facets measured with the Inventory of Children's Individual Differences- Short Form (ICID-S; Deal, Halverson, Martin, Victor, & Baker, Journal of Personality Assessment, 89, 162-166, 2007) differentiate children with an autism spectrum disorder (ASD) from typically developing children during early childhood. 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Dev. Phys. Disabil. PD DEC PY 2014 VL 26 IS 6 BP 775 EP 792 DI 10.1007/s10882-014-9392-2 PG 18 WC Rehabilitation SC Rehabilitation GA AT0AA UT WOS:000344598100009 ER PT J AU Warfield, ME Chiri, G Leutz, WN Timberlake, M AF Warfield, M. E. Chiri, G. Leutz, W. N. Timberlake, M. TI Family well-being in a participant-directed autism waiver program: the role of relational coordination SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism waiver program; parenting stress; participant direction; relational coordination ID DEVELOPMENTAL-DISABILITIES; SUPPORT PROGRAM; SERVICE COORDINATION; PERSONAL ASSISTANCE; CONSUMER-DIRECTION; CASE-MANAGEMENT; CHILDREN; CARE; PARENTS; QUALITY AB BackgroundMassachusetts is one of a very limited number of states exclusively employing participant-direction to deliver autism waiver services to children. A crucial element of this waiver program is the work conducted by the state's Department of Developmental Services (DDS) staff and state-approved providers with waiver families to facilitate the implementation of the participant-direction model. Our study investigates the effect of the collaboration between state providers and family caregivers on family well-being. MethodsWe conducted a survey of 74 families who have been utilising waiver services for at least 6 months. Participants were asked to rate the coordination with providers as well as to report on parenting stress and impact of waiver services on family functioning. Data from in-home child and family assessments conducted by the state were also abstracted from program records. ResultsAfter controlling for a host of variables hypothesised to affect the outcomes of interest, we found that the family's view of how well they coordinated with formal providers is significantly associated all of the outcomes. Families who reported greater coordination with state providers experienced lower parenting stress and reported a more positive impact on family functioning. Child externalising behavioural problems and caregiver's health rating also contributed to parenting stress and family functioning. ConclusionsOur findings highlight the importance of establishing a collaborative partnership with waiver families in promoting family well-being. These results suggest that training and/or resources that foster team building and communication can positively impact family functioning among families with young children with autism. C1 [Warfield, M. E.; Chiri, G.; Leutz, W. N.; Timberlake, M.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02453 USA. RP Warfield, ME (reprint author), Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02453 USA. 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PD DEC PY 2014 VL 58 IS 12 BP 1091 EP 1104 DI 10.1111/jir.12102 PG 14 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AS4GK UT WOS:000344231300001 PM 25330124 ER PT J AU Tomlinson, M Yasamy, MT Emerson, E Officer, A Richler, D Saxena, S AF Tomlinson, M. Yasamy, M. T. Emerson, E. Officer, A. Richler, D. Saxena, S. TI Setting global research priorities for developmental disabilities, including intellectual disabilities and autism SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; developmental disabilities; global research priority setting; intellectual disabilities; low and middle income countries ID HEALTH RESEARCH; MENTAL-HEALTH; CHALLENGES; FRAMEWORK AB ObjectivesThe prevalence of intellectual disabilities (ID) has been estimated at 10.4/1000 worldwide with higher rates among children and adolescents in lower income countries. The objective of this paper is to address research priorities for development disabilities, notably ID and autism, at the global level and to propose the more rational use of scarce funds in addressing this under-investigated area. MethodsAn expert group was identified and invited to systematically list and score research questions. They applied the priority setting methodology of the Child Health and Nutrition Research Initiative (CHNRI) to generate research questions and to evaluate them using a set of five criteria: answerability, feasibility, applicability and impact, support within the context and equity. FindingsThe results of this process clearly indicated that the important priorities for future research related to the need for effective and efficient approaches to early intervention, empowerment of families supporting a person with developmental disability and to address preventable causes of poor health in people with ID and autism. ConclusionsFor the public health and other systems to become more effective in delivering appropriate support to persons with developmental disabilities, greater (and more targeted) investment in research is required to produce evidence of what works consistent with international human rights standards. C1 [Tomlinson, M.] Univ Stellenbosch, Dept Psychol, ZA-7602 Stellenbosch, South Africa. [Yasamy, M. T.; Officer, A.; Saxena, S.] WHO, CH-1211 Geneva, Switzerland. [Emerson, E.] Univ Sydney, Ctr Disabil & Policy, Sydney, NSW 2006, Australia. [Emerson, E.] Univ Lancaster, Ctr Disabil Res, Lancaster, England. [Richler, D.] Joseph P Kennedy Jr Fdn, Toronto, ON, Canada. RP Tomlinson, M (reprint author), Univ Stellenbosch, Dept Psychol, Private Bag X1, ZA-7602 Stellenbosch, South Africa. 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T., 2011, PLOS MED, V8 NR 31 TC 2 Z9 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD DEC PY 2014 VL 58 IS 12 BP 1121 EP 1130 DI 10.1111/jir.12106 PG 10 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AS4GK UT WOS:000344231300003 PM 24397279 ER PT J AU Kwok, SYCL Leung, CLK Wong, DFK AF Kwok, S. Y. C. L. Leung, C. L. K. Wong, D. F. K. TI Marital satisfaction of Chinese mothers of children with autism and intellectual disabilities in Hong Kong SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; intellectual disability; mental health; parents ID CAREGIVER BURDEN INVENTORY; QUALITY-OF-LIFE; MENTAL-ILLNESS; DOWN-SYNDROME; PSYCHOLOGICAL DISTRESS; AFFILIATE STIGMA; SOCIAL SUPPORT; FAMILY; PARENTS; DIVORCE AB BackgroundPrevious research showed an association among perceived stigma, perceived caregiving burden and marital satisfaction of mothers. However, little is known about their relationship among mothers of young children with disabilities in the Chinese context. The mediating role of perceived caregiving burden between perceived stigma and marital satisfaction was seldom explored. Hence, the present study aims to investigate the relationship between perceived stigma, perceived caregiving burden and marital satisfaction of Chinese mothers of children with intellectual disabilities or autism spectrum disorders in Hong Kong. MethodsA cross-sectional survey using convenience sampling was conducted with mothers of pre-school children with disabilities aged from 2 to 6. A total of 160 completed questionnaires were collected from five special child care centres in Hong Kong. ResultsThe findings in the hierarchical regression analyses showed that perceived stigma and perceived caregiving burden were significant predictors of mothers' marital satisfaction. Perceived burden, including perceived social burden, emotional burden and developmental burden but excluding time-dependence and physical burden, were found to be significant mediators between perceived stigma and marital satisfaction. ConclusionTo address the negative consequences brought on by stigma, measures can be taken to prevent stigmatisation and minimise the harmful effects. To alleviate mothers' perceived burden, Acceptance and Commitment Therapy, mutual support groups and psycho-educational and skills training programmes can be conducted for the mothers. C1 [Kwok, S. Y. C. L.; Leung, C. L. K.; Wong, D. F. K.] City Univ Hong Kong, Dept Appl Social Studies, Hong Kong, Hong Kong, Peoples R China. RP Kwok, SYCL (reprint author), City Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. 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PD DEC PY 2014 VL 58 IS 12 BP 1156 EP 1171 DI 10.1111/jir.12116 PG 16 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AS4GK UT WOS:000344231300006 PM 24450394 ER PT J AU Wagner, SE Hesson, A AF Wagner, Suzanne Evans Hesson, Ashley TI Individual Sensitivity to the Frequency of Socially Meaningful Linguistic Cues Affects Language Attitudes SO JOURNAL OF LANGUAGE AND SOCIAL PSYCHOLOGY LA English DT Article DE language attitudes; variation; (ing); broader autism phenotype; impression formation ID SPEECH-PERCEPTION; INFORMATION; BEHAVIOR AB In forming an impression of a speaker, listeners are attentive to the frequency of nonstandard language features, using it to calibrate their judgments. We show that the ability to track and socially evaluate nonstandard variant frequency is subject to individual differences. Listeners judged an aspiring newscaster on the standardness of her speech in a series of read-aloud passages that had been manipulated for proportional frequency of a nonstandard pronunciation. Judgments of conditions at the poles of the frequency continuum were predicted by listener sociodemographic factors. For conditions in the middle of the frequency continuum, listener judgments were predicted by Broader Autism Phenotype Questionnaire scores for communication skills. Language attitudes may therefore be affected by both social and cognitive listener attributes, where cognitive attributes are most relevant for ambiguous inputs. C1 [Wagner, Suzanne Evans; Hesson, Ashley] Michigan State Univ, E Lansing, MI 48824 USA. RP Wagner, SE (reprint author), Michigan State Univ, 619 Red Cedar Rd, E Lansing, MI 48824 USA. 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TI Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Depression; Anxiety; Stress; Oxytocin; DASS scale; SNP; RNA expression ID ALZHEIMERS-DISEASE; INTEGRATIVE NEUROSCIENCE; SOCIAL-BEHAVIOR; OXTR; HUMANS; AUTISM; POPULATION; INTERACT; SUPPORT; POLYMORPHISMS AB Background: Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression. Methods: In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the. Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples. Results: A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues. Conclusions: These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Myers, Amanda J.; Nemeroff, Charles B.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Williams, Leanne; Gatt, Justine M.] Univ Sydney, Sydney Med Sch, Brain Dynam Ctr, Westmead, NSW 2145, Australia. [Williams, Leanne; Gatt, Justine M.] Westmead Hosp, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Williams, Leanne] Stanford Univ, Dept Psychiat & Behav Neurosci, Stanford, CA 94305 USA. [Gatt, Justine M.] Univ New S Wales, Sch Psychol, Randwick, NSW 2052, Australia. [Gatt, Justine M.; McAuley-Clark, Erica Z.; Dobson-Stone, Carol; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Dobson-Stone, Carol; Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. RP Myers, AJ (reprint author), Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Rosenstiel Med Sci Bldg,Room 6152A,D-106, Miami, FL 33136 USA. EM amyers@med.miami.edu FU Australian Research Council [LP0455104]; Brain Resource Ltd FX Genotyping was sponsored by an Australian Research Council Linkage Project grant (LP0455104) with Brain Resource Ltd as the industry partner. Data analysis was supported by NIA AG041232 and NIMH MH094759. 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Psychiatr. Res. PD DEC PY 2014 VL 59 BP 93 EP 100 DI 10.1016/j.jpsychires.2014.08.021 PG 8 WC Psychiatry SC Psychiatry GA AS3WJ UT WOS:000344205700013 PM 25262417 ER PT J AU Gabriele, S Lombardi, F Sacco, R Napolioni, V Altieri, L Tirindelli, MC Gregorj, C Bravaccio, C Rousseau, F Persico, AM AF Gabriele, Stefano Lombardi, Federica Sacco, Roberto Napolioni, Valerio Altieri, Laura Tirindelli, Maria Cristina Gregorj, Chiara Bravaccio, Carmela Rousseau, Francis Persico, Antonio M. TI The GLO1 C332 (Ala111) allele confers autism vulnerability: Family-based genetic association and functional correlates SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Advanced glycation end-products; Autism; Autism spectrum disorder; Glyoxalase; Methylglyoxal; Pervasive developmental disorders ID PRINCIPAL PATHOGENETIC COMPONENTS; HUMAN GLYOXALASE-I; DE-NOVO MUTATIONS; SPECTRUM DISORDERS; OXIDATIVE STRESS; COMMON VARIANTS; BRAIN; AGE; EXPRESSION; CELLS AB Glyoxalase I (GLO1) is a homodimeric Zn2+-dependent isomerase involved in the detoxification of methylglyoxal and in limiting the formation of advanced glycation end-products (AGE). We previously found the rs4746 A332 (Glu111) allele of the GLO1 gene, which encodes for glyoxalase I, associated with "unaffected sibling" status in families with one or more children affected by Autism Spectrum Disorder (ASD). To identify and characterize this protective allele, we sequenced GLO1 exons and exon-intron junctions, detecting two additional SNPs (rs1049346, rs1130534) in linkage disequilibrium with rs4746. A family-based association study involving 385 simplex and 20 multiplex Italian families yielded a significant association with autism driven only by the rs4746 C332 (Ala111) allele itself (P < 0.05 and P < 0.001 under additive and dominant/recessive models, respectively). Glyoxalase enzymatic activity was significantly reduced both in leukocytes and in post-mortem temporocortical tissue (N = 38 and 13, respectively) of typically developing C332 allele carriers (P < 0.05 and < 0.01), with no difference in Glo1 protein levels. Conversely, AGE amounts were significantly higher in the same C332 post-mortem brains (P = 0.001), with a strong negative correlation between glyoxalase activity and AGE levels (tau = -0.588, P < 0.01). Instead, 19 autistic brains show a dysregulation of the glyoxalase-AGE axis (tau = -0.209, P = 0.260), with significant blunting of glyoxalase activity and AGE amounts compared to controls (P < 0.05), and loss of rs4746 genotype effects. In summary, the GLO1 C332 (Ala111) allele confers autism vulnerability by reducing brain glyoxalase activity and enhancing AGE formation, but years after an autism diagnosis the glyoxalase-AGE axis appears profoundly disrupted, with loss of C332 allelic effects. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Gabriele, Stefano; Lombardi, Federica; Sacco, Roberto; Napolioni, Valerio; Altieri, Laura; Persico, Antonio M.] Univ Campus Biomed, Unit Child & Adolescent NeuroPsychiat, Lab Mol Psychiat & Neurogenet, I-00128 Rome, Italy. [Gabriele, Stefano; Lombardi, Federica; Sacco, Roberto; Napolioni, Valerio; Altieri, Laura; Persico, Antonio M.] IRCCS Fdn Santa Lucia, Dept Expt Neurosci, Rome, Italy. [Tirindelli, Maria Cristina; Gregorj, Chiara] Univ Campus Biomed, I-00128 Rome, Italy. [Bravaccio, Carmela] Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy. [Rousseau, Francis] IntegraGen SA, Evry, France. [Persico, Antonio M.] Mafalda Luce Ctr Pervas Dev Disorders, Milan, Italy. RP Persico, AM (reprint author), Univ Campus Biomed, 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 (PRIN) [2006058195, 2008BACT54_002]; Italian Ministry of Health [RFPS-2007-5-640174]; Italian Ministry of Health (CCM program - progetto NIDA); Fondazione Gaetano e Mafalda Luce (Milan, 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 CCM program 2012 - progetto NIDA), the Fondazione Gaetano e Mafalda Luce (Milan, Italy), Autism Speaks (Princeton, NJ), the Autism Research Institute (San Diego, CA), and the Innovative Medicines Initiative Joint Undertaking (EU-AIMS, n. 115300). 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PD DEC PY 2014 VL 59 BP 108 EP 116 DI 10.1016/j.jpsychires.2014.07.021 PG 9 WC Psychiatry SC Psychiatry GA AS3WJ UT WOS:000344205700015 PM 25201284 ER PT J AU Hirose, K Miyata, J Sugihara, G Kubota, M Sasamoto, A Aso, T Fukuyama, H Murai, T Takahashi, H AF Hirose, Kimito Miyata, Jun Sugihara, Genichi Kubota, Manabu Sasamoto, Akihiko Aso, Toshihiko Fukuyama, Hidenao Murai, Toshiya Takahashi, Hidehiko TI Fiber tract associated with autistic traits in healthy adults SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Autism; Tract-based spatial statistics; Tractography; Posterior superior temporal sulcus; Inferior fronto-occipital fasciculus ID HIGH-FUNCTIONING AUTISM; FRONTO-OCCIPITAL FASCICULUS; SUPERIOR TEMPORAL SULCUS; SPECTRUM QUOTIENT AQ; SPATIAL-STATISTICS; CORPUS-CALLOSUM; GENERAL-POPULATION; SOCIAL-PERCEPTION; ASPERGER-SYNDROME; YOUNG-CHILDREN AB Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with impairment of social communication and restricted and repetitive behaviors. Reduced fractional anisotropy (FA), a measure of white matter integrity, in the posterior superior temporal sulcus (pSTS) is related to ASD. However, there are several major fibers in pSTS, and it is unknown which of them is associated with ASD. We investigated FA in correlation with autistic traits assessed by autism spectrum quotient (AQ) in 91 healthy adults using tract-based spatial statistics (TBSS). Then, of the fibers in pSTS, we identified the one in which FA was linked to the AQ score using tractography. TESS revealed that AQ was correlated with FA of white matter in several regions such as the frontal lobe, parietal lobe, occipital lobe and temporal lobe including pSTS. With further analysis using tractography, we confirmed that FA alteration in pSTS was located on the inferior fronto-occipital fasciculus (IFOF). IFOF has a critical role in processing socio-emotional information. Our findings suggest that of the fibers in pSTS, IFOF is a key fiber that links to autistic traits in healthy adults. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hirose, Kimito; Miyata, Jun; Sugihara, Genichi; Kubota, Manabu; Sasamoto, Akihiko; Murai, Toshiya; Takahashi, Hidehiko] Kyoto Univ, Grad Sch Med, Dept Psychiat, Sakyo Ku, Kyoto 6068507, Japan. [Aso, Toshihiko; Fukuyama, Hidenao] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Sakyo Ku, Kyoto 6068507, Japan. RP Takahashi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Psychiat, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan. EM hidehiko@kuhp.kyoto-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [24243061, 23390290, 22220003, 23118004, 23120009]; Japan Society for the Promotion of Science [23680045, 23791329]; Ministry of Health, Labour and Welfare [H25-seishin-jitsuyouka-ippan-001] FX This work was supported by grants-in-aid for scientific research A (24243061), B (23390290), S (22220003), and on Innovative Areas (23118004, 23120009), from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Young Scientists A (23680045), B (23791329) from the Japan Society for the Promotion of Science, and a Health and Labour Science Research Grant for Research on Applying Health Technology (H25-seishin-jitsuyouka-ippan-001) from the Ministry of Health, Labour and Welfare. 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Psychiatr. Res. PD DEC PY 2014 VL 59 BP 117 EP 124 DI 10.1016/j.jpsychires.2014.09.001 PG 8 WC Psychiatry SC Psychiatry GA AS3WJ UT WOS:000344205700016 PM 25266474 ER PT J AU Erickson, CA Ray, B Maloney, B Wink, LK Bowers, K Schaefer, TL McDougle, CJ Sokol, DK Lahiri, DK AF Erickson, Craig A. Ray, Balmiki Maloney, Bryan Wink, Logan K. Bowers, Katherine Schaefer, Tori L. McDougle, Christopher J. Sokol, Deborah K. Lahiri, Debomoy K. TI Impact of acamprosate on plasma amyloid-beta precursor protein in youth: A pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Amyloid precursor protein; Autism spectrum disorder; Acamprosate; Glutamate; Biomarker; GABA ID BRAIN OVERGROWTH; MESSENGER-RNAS; GLUTAMATE RECEPTORS; ALZHEIMERS-DISEASE; MENTAL-RETARDATION; HEAD CIRCUMFERENCE; SECRETED FORMS; OPEN-LABEL; RAT-BRAIN; FMRP AB Background: Understanding of the pathophysiology of autism spectrum disorder (ASD) remains limited. Brain overgrowth has been hypothesized to be associated with the development of ASD. A derivative of amyloid-beta precursor protein (APP), secreted APP alpha (sAPP alpha), has neuroproliferative effects and has been shown to be elevated in the plasma of persons with ASD compared to control subjects. Reduction in sAPP alpha holds promise as a novel molecular target of treatment in ASD. Research into the neurochemistry of ASD has repeatedly implicated excessive glutamatergic and deficient GABAergic neurotransmission in the disorder. With this in mind, acamprosate, a novel modulator of glutamate and GABA function, has been studied in ASD. No data is available on the impact of glutamate or GABA modulation on sAPP alpha function. Methods: Plasma APP derivative levels pre- and post-treatment with acamprosate were determined in two pilot studies involving youth with idiopathic and fragile X syndrome (FXS)-associated ASD. We additionally compared baseline APP derivative levels between youth with FXS-associated or idiopathic ASD. Results: Acamprosate use was associated with a significant reduction in plasma sAPP(total) and sAPP alpha. levels but no change occurred in A beta 40 or A beta 42 levels in 15 youth with ASD (mean age: 11.1 years). Youth with FXS-associated ASD (n = 12) showed increased sAPP alpha processing compared to age-, gender- and IQ-match youth with idiopathic ASD (n = 11). Conclusions: Plasma APP derivative analysis holds promise as a potential biomarker for use in ASD targeted treatment. Reduction in sAPP (total) and sAPP alpha may be a novel pharmacodynamic property of acamprosate. Future study is required to address limitations of the current study to determine if baseline APP derivative analysis may predict subgroups of persons with idiopathic or FXS-associated ASD who may respond best to acamprosate or to potentially other modulators of glutamate and/or GABA neurotransmission. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Erickson, Craig A.; Wink, Logan K.; Bowers, Katherine; Schaefer, Tori L.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Ray, Balmiki; Maloney, Bryan; Sokol, Deborah K.; Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. [McDougle, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lurie Ctr Autism, Boston, MA USA. RP Lahiri, DK (reprint author), Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Neurosci Res Bldg,320 West 15th St,NB 200C, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu FU United States Department of Defense; American Academy of Child and Adolescent Psychiatry; John Merck Fund; Cincinnati Children's Hospital Medical Center; Simons Foundation; Angelman Syndrome Foundation; National Fragile X Foundation/United States Centers for Disease Control; Baxter Healthcare FX None (TS, KB, CJM, BR, DKS); Logan Wink, Consultant to Otsuka Pharmaceuticals; Craig Erickson, Equity in Confluence Pharmaceuticals, Consultant to the Roche Group and Alcobra Pharmaceuticals, Research Grant Support from the United States Department of Defense, The American Academy of Child and Adolescent Psychiatry, The John Merck Fund, Cincinnati Children's Hospital Medical Center, The Simons Foundation, the Angelman Syndrome Foundation, and the National Fragile X Foundation/United States Centers for Disease Control; Debomoy Lahiri: Scientific advisory board- QR Pharma, Yuma Therapeutics, Entia Biosciences; International advisory board- Drug Discovery and Therapy World Congress; Stock options, QR Pharma; Patent involving memantine (mode of action is not related to that of acamprosate); Editor in Chief, Current Alzheimer Research; Research Grant Support from Baxter Healthcare. 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Psychiatr. Res. PD DEC PY 2014 VL 59 BP 220 EP 228 DI 10.1016/j.jpsychires.2014.07.011 PG 9 WC Psychiatry SC Psychiatry GA AS3WJ UT WOS:000344205700030 PM 25300441 ER PT J AU Suaifan, GARY Shehadeh, MB Al-Ijel, HAN Al-Jamal, KT Taha, MO AF Suaifan, Ghadeer A. R. Y. Shehadeh, Mayadah B. Al-Ijel, Hebah A. N. Al-Jamal, Khuloud T. Taha, Mutasem O. TI Ritodrine inhibits neuronal nitric oxide synthase, a potential link between tocolysis and autism SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article DE Autism; Molecular docking; In vitro evaluation; Neuronal nitric oxide synthase; Tocolysis ID AMIDE BOND PEPTIDOMIMETICS; SELECTIVE INHIBITORS; PRETERM LABOR; AMNIOTIC-FLUID; LIGAND INTERACTIONS; DIPEPTIDE AMIDES; LATE PREGNANCY; FETAL SERUM; HYDROCHLORIDE; ASSOCIATION AB Statistical association between congenital autism and prenatal exposure to ritodrine (4-(2-((1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-ylamino)ethyl)phenol) as a tocolytic agent was a matter of concern. Moreover, neuronal nitric oxide momentous role in various behavioral and cognitive functions was reported. In this context, a correlation between prenatal exposures to ritodrine, neuronal nitric oxide level and autism occurrence must be investigated. For this reason, we proposed possible inhibition of neuronal nitric oxide synthase (nNOS) by ritodrine. An insight toward our hypothesis approval was done through docking ritodrine into the catalytic pocket of nNOS. Apparently, ritodrine shared at least five critical binding interactions with a potent nNOS inhibitor (PDB code: JI7). Subsequent in vitro experiment pointed out that ritodrine indeed inhibited the enzymatic activity of nNOS at low micromolar level. As a conclusion, ritodrine should not be used as a tocolytic agent but as a novel non peptidomimetic nNOS inhibitor lead scaffold for future optimization. (A) Ritodrine chemical structure (B) Docked pose of ritodrine into nNOS-binding pocket (PDB code: 3B3P, resolution 2.6 C-0) (C) Docked pose of inhibitor JI7 (green) as produced by docking simulation and the crystallographic structure of this inhibitor within nNOS. C1 [Suaifan, Ghadeer A. R. Y.; Shehadeh, Mayadah B.; Al-Ijel, Hebah A. N.; Taha, Mutasem O.] Univ Jordan, Dept Pharmaceut Sci, Fac Pharm, Amman 11942, Jordan. [Suaifan, Ghadeer A. R. Y.; Taha, Mutasem O.] Univ Jordan, Drug Discovery Unit, Fac Pharm, Amman 11942, Jordan. [Al-Jamal, Khuloud T.] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England. RP Suaifan, GARY (reprint author), Univ Jordan, Dept Pharmaceut Sci, Fac Pharm, Amman 11942, Jordan. EM gh.suaifan@ju.edu.jo FU Deanship of the Scientific Research, The University of Jordan [1444] FX The authors would like to acknowledge the Deanship of the Scientific Research, The University of Jordan (Grant number 1444) and Hamdi Mango Center for Scientific Research and Sandeep Khosla (King's College London) for help with in vitro assays. 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PD DEC PY 2014 VL 23 IS 12 BP 5102 EP 5109 DI 10.1007/s00044-014-1066-1 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AS3GI UT WOS:000344165100009 ER PT J AU Petursdottir, AI Lepper, TL Peterson, SP AF Petursdottir, Anna Ingeborg Lepper, Tracy L. Peterson, Sean P. TI Effects of Collateral Response Requirements and Exemplar Training on Listener Training Outcomes in Children SO PSYCHOLOGICAL RECORD LA English DT Article DE Listener training; Intraverbals; Naming; Tacts; Children ID YOUNG-CHILDREN; EQUIVALENCE; LANGUAGE; CATEGORIZATION; COMPREHENSION; ECHOLALIA; BEHAVIOR; AUTISM AB We evaluated the effects of collateral response requirements during listener training on the emergence of vocal foreign-language tacts and intraverbals among 4- and 5-year-old children. In Experiment 1, participants were first exposed to auditory-visual match-to-sample training without collateral response requirements. Four participants did not perform to criterion in probes for derived vocal responses, and were exposed to a two-phase intervention that involved adding echoic and native-language tact requirements to match-to-sample trials. Performance did not improve as a result of the intervention. However, all participants passed tact probes after receiving direct tact and intraverbal training with a subset of the stimuli, and two of four participants also passed the intraverbal probes. Experiment 2 addressed potential limitations of Experiment 1 with three additional participants, but collateral response requirements still failed to affect the emergence of tacts and intraverbals. C1 [Petursdottir, Anna Ingeborg; Lepper, Tracy L.; Peterson, Sean P.] Texas Christian Univ, Dept Psychol, Ft Worth, TX 76129 USA. [Peterson, Sean P.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Petursdottir, AI (reprint author), Texas Christian Univ, Dept Psychol, TCU Box 298920, Ft Worth, TX 76129 USA. 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PD DEC PY 2014 VL 64 IS 4 BP 703 EP 717 DI 10.1007/s40732-014-0051-x PG 15 WC Psychology, Multidisciplinary SC Psychology GA AS6EN UT WOS:000344357500007 ER PT J AU Kenny, N Barnes-Holmes, D Stewart, I AF Kenny, Neil Barnes-Holmes, Dermot Stewart, Ian TI Competing Arbitrary and Non-Arbitrary Relational Responding in Normally Developing Children and Children Diagnosed with Autism SO PSYCHOLOGICAL RECORD LA English DT Article DE Autism; Arbitrary Relational Responding; Relational Frame Theory ID MENTALLY-RETARDED ADULTS; CONDITIONAL DISCRIMINATION; STIMULUS EQUIVALENCE; EXECUTIVE FUNCTION; YOUNG-CHILDREN; METHODOLOGICAL NOTE; VERBAL-BEHAVIOR; INDIVIDUALS; RETARDATION; ACQUISITION AB The current study seeks to further investigate the previously reported disruptive effect of competing non-arbitrary stimulus relations on derived relational responding (Stewart et al. The Psychological Record, 52, 77-88, 2002; Kenny et al. The Psychological Record, 2014). 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TI Teaching a Deictic Relational Repertoire to Children with Autism SO PSYCHOLOGICAL RECORD LA English DT Article DE Perspective-taking; Autism; Deictic relations ID PERSPECTIVE-TAKING; FALSE BELIEF; SPECTRUM DISORDER; YOUNG-CHILDREN; MIND; DEFICIT AB Perspective-taking skills are crucial for successful social interactions and individuals with autism often have great difficulty in this area. Recent research in the area of Relational Frame Theory has developed an analysis of deictic relations, thought to underlie perspective-taking. A few studies have shown that performance on a deictic relations protocol correlates with other measures of perspective taking, and that deictic relations can be learned through operant conditioning procedures. The current study examined the effects of increased deictic relational responding, on Theory of Mind scores, with children with autism. Five children with autism participated in this study, two of whom were designated as control participants. The results suggest that the current form of deictic relational training can be taught to children with autism, but this may not be sufficient to change more generalized perspective-taking skills, as measured by a Theory of Mind assessment. C1 [Jackson, Marianne L.; Mendoza, Dena R.; Adams, Amanda N.] Calif State Univ Fresno, Dept Psychol, Fresno, CA 93740 USA. RP Jackson, ML (reprint author), Calif State Univ Fresno, Dept Psychol, 2576 E San Ramon Ave M-S ST11, Fresno, CA 93740 USA. 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Rec. PD DEC PY 2014 VL 64 IS 4 BP 791 EP 802 DI 10.1007/s40732-014-0078-z PG 12 WC Psychology, Multidisciplinary SC Psychology GA AS6EN UT WOS:000344357500014 ER PT J AU Tozer, R Atkin, K Wenham, A AF Tozer, Rosemary Atkin, Karl Wenham, Aniela TI 'My brother likes meeting new people, but don't ask him any direct questions': involving adults with autism plus learning disability in a qualitative research project SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE Autism; communication; family support; learning (intellectual) disabilities ID SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; SIBLINGS; CHILDREN; LIFE; COMMUNICATION; ISSUES AB Adult siblings of people with autism and a learning disability have hitherto been largely overlooked by research, policy and practice in the UK. As part of a qualitative study focussing on adult siblings, we met twelve people with autism plus severe learning disability with their brother or sister. Individually tailored resources were used to make the meeting accessible and positive. Sibling involvement was essential to the participation, and inclusion of adults with autism plus learning disability strengthened the research findings, making them more valid and more relevant to policy and practice. This article describes our experiences of facilitating this involvement, the methods used and understandings gained, with the aim of encouraging practitioners and researchers to do likewise. C1 [Tozer, Rosemary; Atkin, Karl; Wenham, Aniela] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. RP Tozer, R (reprint author), Univ York, Dept Hlth Sci, Seebohm Rowntree Bldg,Area 4, York YO10 5DD, N Yorkshire, England. 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J. Learn. Disabil. PD DEC PY 2014 VL 42 IS 4 BP 292 EP 300 DI 10.1111/bld.12073 PG 9 WC Education, Special SC Education & Educational Research GA AS1OP UT WOS:000344050400006 ER PT J AU Horne-Moyer, HL Moyer, BH Messer, DC Messer, ES AF Horne-Moyer, H. Lynn Moyer, Brian H. Messer, Drew C. Messer, Elizabeth S. TI The Use of Electronic Games in Therapy: a Review with Clinical Implications SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Psychotherapy; Electronic games; Serious games; Cognitive behavior therapy; Group therapy ID COGNITIVE-BEHAVIORAL THERAPY; AUTISM SPECTRUM DISORDER; VIDEO GAMES; EXERCISE REGIMEN; BRAIN-INJURY; CHILDREN; INTERVENTION; DEPRESSION; HEALTH; PSYCHOTHERAPY AB Therapists and patients enjoy and benefit from interventions that use electronic games (EG) in health care and mental health settings, with a variety of diagnoses and therapeutic goals. We reviewed the use of electronic games designed specifically for a therapeutic purpose, electronic games for psychotherapy (EGP), also called serious games, and commercially produced games used as an adjunct to psychotherapy, electronic games for entertainment (EGE). Recent research on the benefits of EG in rehabilitation settings, EGP, and EGE indicates that electronic methods are often equivalent to more traditional treatments and may be more enjoyable or acceptable, at least to some consumers. Methodological concerns include the lack of randomized controlled trials (RCT) for many applications. Suggestions are offered for using EG in therapeutic practice. C1 [Horne-Moyer, H. Lynn] Medaille Coll, Buffalo, NY 14214 USA. [Moyer, Brian H.; Messer, Drew C.; Messer, Elizabeth S.] Elect Gaming Therapy Inc, Williamsville, NY 14221 USA. RP Messer, DC (reprint author), Elect Gaming Therapy Inc, 8616 Main St,Suite 4, Williamsville, NY 14221 USA. 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PD DEC PY 2014 VL 16 IS 12 AR 520 DI 10.1007/s11920-014-0520-6 PG 9 WC Psychiatry SC Psychiatry GA AR9KX UT WOS:000343893600007 PM 25312026 ER PT J AU Singh, MK Ketter, T Chang, KD AF Singh, Manpreet K. Ketter, Terence Chang, Kiki D. TI Distinguishing Bipolar Disorder From Other Psychiatric Disorders in Children SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Pediatric bipolar disorder; Bipolar spectrum; Depression; ADHD; Anxiety; Mood dysregulation ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MAJOR DEPRESSIVE DISORDER; DEFICIT HYPERACTIVITY DISORDER; MOOD DYSREGULATION DISORDER; CYCLOTHYMIC DISORDER; SPECTRUM DISORDERS; I DISORDER; CLINICAL CHARACTERISTICS; MANIC SYMPTOMS; YOUTH SAMPLE AB Pediatric onset bipolar disorder (BD) is a challenging diagnosis with potentially debilitating outcomes. This review aims to critically evaluate recently published literature relevant to the diagnosis of BD in youth, emphasizing interesting and important new findings characterizing pediatric BD and reporting updates in the diagnostic and statistical manual relevant to this disorder in youth. Challenges regarding the diagnosis of BD will be discussed, in addition to important distinctions with other childhood disorders, including other bipolar spectrum disorders; major depressive disorder; dysthymia; disruptive mood dysregulation disorder (DMDD); attention-deficit/hyperactivity disorder (ADHD) and other disruptive behavioral disorders; anxiety disorders, including post-traumatic stress disorder (PTSD); psychotic disorders; autism spectrum disorders; substance use disorders; and borderline personality disorder. The review concludes with a comment on past research limitations and future directions in the field. C1 [Singh, Manpreet K.; Ketter, Terence; Chang, Kiki D.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Singh, MK (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, 401 Quarry Rd, Stanford, CA 94305 USA. EM mksingh@stanford.edu FU Stanford Child Health Research Institute; National Institute of Mental Health; Stanford University; GlaxoSmithKline; Merck FX Manpreet K. Singh declares no conflict of interest. Dr. Singh receives research support from Stanford Child Health Research Institute.Kiki D. Chang receives research support from the National Institute of Mental Health and Stanford University. Dr. Chang is also an unpaid consultant for GlaxoSmithKline, Eli Lilly, and Bristol-Myers Squibb. He is on the Data Safety Monitoring Board for Sunovion. In the past two years, he has received research support from GlaxoSmithKline and Merck. 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Psychiatry Rep. PD DEC PY 2014 VL 16 IS 12 AR 516 DI 10.1007/s11920-014-0516-2 PG 11 WC Psychiatry SC Psychiatry GA AR9KX UT WOS:000343893600004 PM 25315116 ER PT J AU Budday, S Steinmann, P Kuhl, E AF Budday, Silvia Steinmann, Paul Kuhl, Ellen TI The role of mechanics during brain development SO JOURNAL OF THE MECHANICS AND PHYSICS OF SOLIDS LA English DT Article DE Brain development; Cortical folding; Thin films; Growth; Instabilities ID CEREBRAL-CORTEX; COMPLIANT SUBSTRATE; COMPUTATIONAL MODEL; GROWING SURFACES; ELASTIC TISSUES; NERVOUS-SYSTEM; FINITE GROWTH; INSTABILITY; EVOLUTION; MALFORMATIONS AB Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated with neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Foppl-von Karman theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Budday, Silvia; Steinmann, Paul] Univ Erlangen Nurnberg, Dept Mech Engn, Chair Appl Mech, D-91058 Erlangen, Germany. [Kuhl, Ellen] Stanford Univ, Dept Mech Engn, Dept Bioengn, Stanford, CA 94305 USA. [Kuhl, Ellen] Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA. RP Kuhl, E (reprint author), Stanford Univ, Dept Mech Engn, Dept Bioengn, 496 Lomita Mall, Stanford, CA 94305 USA. 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Biol. Med. PD WIN PY 2014 VL 57 IS 1 SI SI BP 118 EP 131 PG 14 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA AR1OZ UT WOS:000343355800009 PM 25345706 ER PT J AU Romero-Martinez, A de Andres-Garcia, S Ruiz-Robledillo, N Gonzalez-Bono, E Moya-Albiol, L AF Romero-Martinez, A. de Andres-Garcia, S. Ruiz-Robledillo, N. Gonzalez-Bono, E. Moya-Albiol, L. TI High cognitive sensitivity to activational effects of testosterone in parents of offspring with autism spectrum disorders SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Autism spectrum disorders; Endophenotype; Neuropsychology; Parents; Testosterone ID EMPATHY QUOTIENT EQ; 4TH DIGIT LENGTH; UNDER-THE-CURVE; SYSTEMATIZING QUOTIENT; GENERAL-POPULATION; FETAL TESTOSTERONE; ASPERGER-SYNDROME; RATIO 2D-4D; PHENOTYPE; CHILDREN AB The existence of mild forms of autistic-like characteristics in parents of children with autism spectrum disorders (ASDs) has been defined as a broader autistic phenotype (BAP). Excessive prenatal exposure to testosterone (T) seems to play a role in its development. The aims of this study were to characterize whether ASD parents show masculinized brains or high T prenatal exposure compared to a normative population, using cognitive questionnaires, and also to examine the T level changes in response to different cognitive tasks. ASD parents were found to present higher autistic and lower empathic trait scores than controls. They also have higher T levels and magnitude of T response to cognitive tasks. Specific correlation patterns between masculinized brain types and T levels were observed only in ASD parents. Thus, it seems that first-degree relatives of people with ASD have high T levels during task performance, which, in turn, produce slight cognitive masculinization. Our findings should be considered for understanding the role of androgens in the etiology of ASD. Nevertheless, the masculinization parameters described throughout the study are subtle and require further analysis. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Romero-Martinez, A.; de Andres-Garcia, S.; Ruiz-Robledillo, N.; Gonzalez-Bono, E.; Moya-Albiol, L.] Univ Valencia, Dept Psychobiol, Valencia 46010, Spain. RP Moya-Albiol, L (reprint author), Univ Valencia, Dept Psychobiol, Ave Blasco Ibanez 21, Valencia 46010, Spain. 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PD DEC PY 2014 VL 71 BP 45 EP 50 DI 10.1016/j.paid.2014.07.020 PG 6 WC Psychology, Social SC Psychology GA AQ6XN UT WOS:000342957300009 ER PT J AU Ghanbari, Y Smith, AR Schultz, RT Verma, R AF Ghanbari, Yasser Smith, Alex R. Schultz, Robert T. Verma, Ragini TI Identifying group discriminative and age regressive sub-networks from DTI-based connectivity via a unified framework of non-negative matrix factorization and graph embedding SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Diffusion MRI; Connectivity analysis; Non-negative matrix factorization; Graph embedding; Autism and development ID INDEPENDENT COMPONENT ANALYSIS; AUTISM SPECTRUM DISORDER; HIGH-FUNCTIONING AUTISM; WHITE-MATTER INTEGRITY; DIFFUSION-TENSOR MRI; FALSE DISCOVERY RATE; BRAIN CONNECTIVITY; ALZHEIMERS-DISEASE; CORPUS-CALLOSUM; DIMENSIONALITY REDUCTION AB Diffusion tensor imaging (DTI) offers rich insights into the physical characteristics of white matter (WM) fiber tracts and their development in the brain, facilitating a network representation of brain's traffic pathways. Such a network representation of brain connectivity has provided a novel means of investigating brain changes arising from pathology, development or aging. The high dimensionality of these connectivity networks necessitates the development of methods that identify the connectivity building blocks or sub-network components that characterize the underlying variation in the population. In addition, the projection of the subject networks into the basis set provides a low dimensional representation of it, that teases apart different sources of variation in the sample, facilitating variation-specific statistical analysis. We propose a unified framework of non-negative matrix factorization and graph embedding for learning sub-network patterns of connectivity by their projective non-negative decomposition into a reconstructive basis set, as well as, additional basis sets representing variational sources in the population like age and pathology. The proposed framework is applied to a study of diffusion-based connectivity in subjects with autism that shows localized sparse sub-networks which mostly capture the changes related to pathology and developmental variations. (C) 2014 Elsevier B.V. All rights reserved. C1 [Ghanbari, Yasser; Smith, Alex R.; Verma, Ragini] Univ Penn, Ctr Biomed Image Comp & Analyt, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Dept Pediat, Philadelphia, PA 19104 USA. RP Verma, R (reprint author), Sect Biomed Image Anal, 3600 Market St,Suite 380, Philadelphia, PA 19104 USA. EM Ragini.Verma@uphs.upenn.edu FU National Institutes of Health [MH092862, MH098010]; Pennsylvania Department of Health: SAP [4100042728, 4100047863] FX This research was supported by the following grants from National Institutes of Health: MH092862 and MH098010 (PI: Ragini Verma), and grants from the Pennsylvania Department of Health: SAP # 4100042728 and SAP # 4100047863 (PI: Robert T. Schultz). 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Image Anal. PD DEC PY 2014 VL 18 IS 8 SI SI BP 1337 EP 1348 DI 10.1016/j.media.2014.06.006 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AP7SS UT WOS:000342277600009 PM 25037933 ER PT J AU Savadjiev, P Rathi, Y Bouix, S Smith, AR Schultz, RT Verma, R Westin, CF AF Savadjiev, Peter Rathi, Yogesh Bouix, Sylvain Smith, Alex R. Schultz, Robert T. Verma, Ragini Westin, Carl-Fredrik TI Fusion of white and gray matter geometry: A framework for investigating brain development SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Geometry; Cortex; White matter; Neurodevelopment; Autism ID SURFACE-BASED ANALYSIS; AUTISM SPECTRUM DISORDER; HUMAN CEREBRAL-CORTEX; DIFFUSION MRI; SHAPE; SEGMENTATION; CHILDREN; SYSTEM; TRACTS; SPECIFICATION AB Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter. In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework. We then incorporate this method into a novel framework for "fusing" white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004). (C) 2014 Elsevier B.V. All rights reserved. C1 [Savadjiev, Peter; Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Math Imaging, Boston, MA 02115 USA. [Savadjiev, Peter; Rathi, Yogesh; Bouix, Sylvain] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Smith, Alex R.; Verma, Ragini] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. [Schultz, Robert T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Savadjiev, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA. 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Image Anal. PD DEC PY 2014 VL 18 IS 8 SI SI BP 1349 EP 1360 DI 10.1016/j.media.2014.06.013 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AP7SS UT WOS:000342277600010 PM 25066750 ER PT J AU Coronato, A De Pietro, G Paragliola, G AF Coronato, Antonio De Pietro, Giuseppe Paragliola, Giovanni TI A situation-aware system for the detection of motion disorders of patients with Autism Spectrum Disorders SO EXPERT SYSTEMS WITH APPLICATIONS LA English DT Article DE Artificial Intelligence; Human behavior recognition; Intelligent agents ID STEREOTYPICAL MOTOR MOVEMENTS; RECOGNITION AB Patients with Autism Spectrum Disorders (ASD) show symptoms that in general fall into three areas: (1) social impairment; (2) communication difficulties; and, (3) repetitive and stereotyped behaviors. This paper presents a method and an infrastructure for the detection of the stereotyped motion disorders of patients with ASD. The method adopts Artificial Intelligence techniques for the identification of stereotyped motion disorders and the Situation-Awareness paradigm for the reduction of misclassifications and the extraction of further information useful for clinicians. Signals caught by accelerometers are pre-processed to obtain features that, in turn, are passed to the classifier that classifies the current temporal frame in order to detect stereotyped motions. Once a stereotyped motion is detected, events are generated for intelligent situation-aware components, which collect information related to the frequency and period of the day of the disorders, and help also to reduce false positives and misclassifications by verifying spatio-temporal constraints. Quantitatively, the off-line classifier has shown an accuracy of over 99%; whereas the on-line classifier has an accuracy of 92%. The research activity has been conducted in cooperation with clinicians of the Department of Child Psychiatry at the Children's Hospital Santobon-o-Pausilipon in Naples, a prototype is deployed and tested at the hospital. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Coronato, Antonio; De Pietro, Giuseppe; Paragliola, Giovanni] CNR, Inst High Performance Comp & Networking ICAR, I-00185 Rome, Italy. RP Paragliola, G (reprint author), CNR, Inst High Performance Comp & Networking ICAR, I-00185 Rome, Italy. 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PD DEC 1 PY 2014 VL 41 IS 17 BP 7868 EP 7877 DI 10.1016/j.eswa.2014.05.011 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Operations Research & Management Science SC Computer Science; Engineering; Operations Research & Management Science GA AO6LC UT WOS:000341462600018 ER PT J AU Tan, CSS Luyten, K Van den Bergh, J Schoning, J Coninx, K AF Tan, Chiew Seng Sean Luyten, Kris Van den Bergh, Jan Schoning, Johannes Coninx, Karin TI The Role of Physiological Cues during Remote Collaboration SO PRESENCE-TELEOPERATORS AND VIRTUAL ENVIRONMENTS LA English DT Article ID VISUAL INFORMATION; EMPATHY QUOTIENT; NEGATIVE AFFECT; COMMUNICATION; EMOTION; TASK; COMPETITION; COHESION; STRESS; AUTISM AB Empathic communication allows individuals to perceive and understand the feeling and emotion of the person with whom they are interacting. This could be particularly important during remote collaboration (such as remote assistance or distance learning) to enhance the social and emotional understanding of geographically distributed partners. However, supporting awareness in remote collaboration is very challenging especially when the interaction with the remote parties results in less information that can be communicated than in a physical interaction. We explore the effect of visualization using physiological cues that allow users to interpret emotional behaviors of remote parties with whom they are interacting in real time. The proposed visual representation allows users to infer emotional patterns from physiological cues that can potentially influence their communication approach toward a more aggressive style or maintain passive and peaceful interaction. We conducted a study involving participants who were paired up for a collaborative assessment task, interacting via voice only, video-conference, or a visual representation of the physiological measurements. Participants perceived the usage of our visual representation with higher group cohesiveness than using voice-only interaction. Further analysis shows that the visual representation significantly increases the positive affect score (i.e., participants are perceived to be more alert and demonstrate less distress) during remote collaboration. We discuss the possibilities of the proposed visual representation to support empathic communication during remote collaboration, and the benefits to the remote partners of having positive affect and group cohesiveness. C1 [Tan, Chiew Seng Sean; Luyten, Kris; Van den Bergh, Jan; Schoning, Johannes; Coninx, Karin] Hasselt Univ, Expertise Ctr Digital Media, TUL iMinds, Diepenbeek, Belgium. 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One conceptualization of problem behavior is that it serves a communication function, i.e., the person has learned that certain misbehaviors may be reinforced in some way. The present article describes "functional behavior assessment," a group of state-of-the-art methodologies that allow a caregiver to determine the cause of the behavior, so that treatment-based on that cause-will be more effective. Different methods of functional assessment are described, along with a step-by-step implementation sequence. The results of a functional assessment should lead to more effective programming, resulting in quicker elimination of the behavioral concerns, and allow the person to gain access to greater independence and more reinforcement. C1 [Zane, Thomas; Carlson, Mark; Estep, David; Quinn, Miice] Beverly Sch Deaf, Childrens Ctr Commun, Beverly, MA 01915 USA. [Zane, Thomas; Carlson, Mark; Estep, David; Quinn, Miice] Endicott Coll, Inst Behav Studies, Beverly, MA 01915 USA. 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Ghaziuddin, Neera TI Maintenance Electroconvulsive Therapy for Aggression and Self-Injurious Behavior in Two Adolescents With Autism and Catatonia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FOLLOW-UP; SPECTRUM DISORDERS; ECT; DEPRESSION; CHILD AB Frequent aggression toward others and repetitive self-injurious behaviors (SIB) can be features of catatonia in patients with autism. Similar to catatonia secondary to other etiologies, catatonia associated with autism responds well to treatment with benzodiazepines and/or electroconvulsive therapy (ECT). The authors report here on two adolescent patients with autism who presented with severe aggression, one of whom also engaged in repetitive SIB. With ongoing treatment with maintenance ECT, dramatic reduction in aggression and SIB were noted, allowing both patients a reasonable quality of life in their own homes. Attempts to taper off ECT coincided with return of aggression symptoms, although not SIB. 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Neuropsychiatr. Clin. Neurosci. PD WIN PY 2014 VL 26 IS 1 BP 64 EP 72 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AB9OW UT WOS:000332125500040 PM 24515677 ER PT J AU Wang, HY Berg, C AF Wang, Hsin-Yen Berg, Christine TI Participation of Young Adults with High-Functioning Autism in Taiwan: A Pilot Study SO OTJR-OCCUPATION PARTICIPATION AND HEALTH LA English DT Article DE activity; autism; participation ID SPECTRUM DISORDERS; CLINICAL-PRACTICE; PHYSICAL-ACTIVITY; ASPERGER-SYNDROME; TRANSITION; CHILDREN; HEALTH; ADOLESCENCE; EMPLOYMENT; PATTERNS AB This pilot study aimed to investigate the activity participation of young adults, with high-functioning autism (HFA) living in Taiwan. Eleven young adults with HFA, their caring adults, and 11 matched typically developing youth were recruited across Taiwan. The Adolescent and Young Adult Participation Sort-Taiwanese version (AYAPS-T) was administered to all three groups to compare the activity participation. In addition, youth with HFA identified activities in which they desired to participate and barriers hindering their participation. The results of this study suggest that youth with HFA had lower participation rates in activities across different domains than their typically developing peers. Youth with HFA were able to identify the activities they desired to do and the barriers hindering their participation. No significant differences in participation were found between the results reported by the caring adults and youth with HFA. Occupational therapy practitioners may work on eliminating the personal and environmental barriers that impede participation as youth with HFA transition out of secondary school. C1 [Wang, Hsin-Yen] Texas Childrens Hosp, Houston, TX 77064 USA. 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Particip. Health PD WIN PY 2014 VL 34 IS 1 BP 41 EP 51 DI 10.3928/15394492-20131209-01 PG 11 WC Rehabilitation SC Rehabilitation GA 289LO UT WOS:000329684200006 PM 24669398 ER PT J AU Shogren, KA Kennedy, W Dowsett, C Little, TD AF Shogren, Karrie A. Kennedy, William Dowsett, Chantelle Little, Todd D. TI Autonomy, Psychological Empowerment, and Self-Realization: Exploring Data on Self-Determination From NLTS2 SO EXCEPTIONAL CHILDREN LA English DT Article ID QUALITY-OF-LIFE; LEARNING-DISABILITIES; STUDENT PARTICIPATION; HIGH-SCHOOL; DETERMINATION INTERVENTIONS; INTELLECTUAL DISABILITY; COGNITIVE DISABILITIES; ADULT OUTCOMES; DIRECTED-IEP; TRANSITION AB The authors used data from the National Longitudinal Transition Study-2 (NLTS2; SRI International, 2000) to examine the aspects of self-determination assessed in NLTS2 and measurement equivalence and latent differences across the 12 disability categories recognized in the Individuals With Disabilities Education Act (IDEA; 2004). NLTS2 included a direct assessment with items representing 3 of the 4 essential characteristics of self-determination-autonomy, self-realization, and psychological empowerment. The authors established measurement equivalence, but significant latent differences occurred across specific disability groups. Students with high-incidence disabilities (learning disabilities, emotional disturbances, speech or language impairments, and other health impairments) showed similar latent means and variances, as did students with sensory disabilities (visual and hearing impairments) and cognitive disabilities (autism, multiple disabilities, and deaf-blindness). Students with intellectual disability, traumatic brain injury, and orthopedic impairments could not be collapsed with any other group. Across the 6 collapsed disability groups, significant differences existed in the latent variances and limited mean level differences. C1 [Shogren, Karrie A.] Univ Illinois, Urbana, IL USA. 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PD WIN PY 2014 VL 80 IS 2 BP 221 EP 235 PG 15 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 287GY UT WOS:000329531200007 ER PT J AU Perkins, TJ Stokes, MA McGillivray, JA Mussap, AJ Cox, IA Maller, JJ Bittar, RG AF Perkins, Thomas John Stokes, Mark Andrew McGillivray, Jane Anne Mussap, Alexander Julien Cox, Ivanna Anne Maller, Jerome Joseph Bittar, Richard Garth TI Increased left hemisphere impairment in high-functioning autism: A tract based spatial statistics study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Autism spectrum disorder; Diffusion Tensor Imaging; Fractional Anisotropy; Radial Diffusivity ID SUPERIOR LONGITUDINAL FASCICULUS; WHITE-MATTER INTEGRITY; SPECTRUM DISORDERS; CORPUS-CALLOSUM; IMAGING TRACTOGRAPHY; INFANTILE-AUTISM; FRONTAL-LOBE; IN-VIVO; DT-MRI; BRAIN AB There is evidence emerging born Diffusion Tensor Imaging (DTI) research that autism spectrum disorders (ASD) are associated with greater impairment in the left hemisphere. Although this has been quantified with volumetric region of interest analyses, it has yet to be tested with white matter integrity analysis. In the present study, tract based spatial statistics was used to contrast white matter integrity of 12 participants with high-functioning autism or Aspergers syndrome (HFA/AS) with 12 typically developing individuals. Fractional Anisotropy (FA) was examined, in addition to axial, radial and mean diffusivity (AD, RD and MD). In the left hemisphere, participants with HFA/AS demonstrated significantly reduced FA in predominantly thalamic and fronto-parietal pathways and increased RD. Symmetry analyses confirmed that in the HFA/AS group, WM disturbance was significantly greater in the left compared to right hemisphere. These findings contribute to a growing body of literature suggestive of reduced FA in ASD, and provide preliminary evidence for RD impairments in the left hemisphere. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Perkins, Thomas John; Stokes, Mark Andrew; McGillivray, Jane Anne; Mussap, Alexander Julien; Cox, Ivanna Anne; Bittar, Richard Garth] Deakin Univ, Fac Hlth, Sch Psychol, Cognit Neurosci Unit,Dept Psychol, Geelong, Vic 3217, Australia. [Maller, Jerome Joseph] Alfred & Monash Univ, Cent Clin Sch, Monash Alfred Psychiat Res Ctr, Melbourne, Vic, Australia. [Bittar, Richard Garth] Precis Brain Spine & Pain Ctr, Sydney, NSW, Australia. [Bittar, Richard Garth] Royal Melbourne Hosp, Dept Neurosurg, Melbourne, Vic, Australia. RP Perkins, TJ (reprint author), Deakin Univ, Fac Hlth, Sch Psychol, Cognit Neurosci Unit,Dept Psychol, 221 Burwood Highway, Geelong, Vic 3217, Australia. 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Neuroimaging PD NOV 30 PY 2014 VL 224 IS 2 BP 119 EP 123 DI 10.1016/j.pscychresns.2014.08.003 PG 5 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AR8LN UT WOS:000343826800008 PM 25159311 ER PT J AU Pasalich, DS Dadds, MR Hawes, DJ AF Pasalich, Dave S. Dadds, Mark R. Hawes, David J. TI Cognitive and affective empathy in children with conduct problems: Additive and interactive effects of callous-unemotional traits and autism spectrum disorders symptoms SO PSYCHIATRY RESEARCH LA English DT Article DE Empathy; Oppositional defiant disorder; Callous-unemotional; Autism spectrum disorders; Warmth ID SOCIAL RESPONSIVENESS SCALE; PSYCHOPATHIC TRAITS; WARMTH; ASSOCIATION; ATTACHMENT; CHILDHOOD; ATTENTION; DEFICITS AB Callous-unemotional (CU) traits and autism spectrum disorders (ASD) symptoms are characterized by problems in empathy; however, these behavioral features are rarely examined together in children with conduct problems. This study investigated additive and interactive effects of CU traits and ASD symptoms in relation to cognitive and affective empathy in a non-ASD clinic-referred sample. Participants were 134 children aged 3 to 9 years (M=5.60; 79% boys) with oppositional defiant/conduct disorder, and their parents. Clinicians, teachers, and parents reported on dimensions of child behavior, and parental reports of family dysfunction and direct observations of parental warmth/responsiveness assessed quality of family relationships. Results from multiple regression analysis showed that, over and above the effects of child conduct problem severity and quality of family relationships, both ASD symptoms and CU traits were uniquely associated with deficits in cognitive empathy. Moreover, CU traits demonstrated an independent association with affective empathy, and this relationship was moderated by ASD symptoms. That is, there was a stronger negative association between CU traits and affective empathy at higher versus lower levels of ASD symptoms. These findings suggest including both CU traits and ASD-related social impairments in models delineating the atypical development of empathy in children with conduct problems. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Pasalich, Dave S.] Simon Fraser Univ, Dept Psychol, Burnaby, BC V5A 1S6, Canada. [Pasalich, Dave S.] Child & Family Res Inst, Vancouver, BC, Canada. [Dadds, Mark R.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Hawes, David J.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. RP Pasalich, DS (reprint author), Simon Fraser Univ, Dept Psychol, Inst Reduct Youth Violence, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM dave_pasalich@sfu.ca FU National Health and Medical Research Council of Australia; Australian Research Council; Michael Smith Foundation for Health Research Postdoctoral Fellowship FX This study was in part funded by grants from the National Health and Medical Research Council of Australia and the Australian Research Council. Additional support for this study was provided by a Michael Smith Foundation for Health Research Postdoctoral Fellowship to Dave S. Pasalich. We are very grateful for the teachers, parents, and children that participated in this study. 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Hurd, Peter L. TI Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population SO BMC NEUROSCIENCE LA English DT Article DE Social behavior; Anxiety; Williams syndrome; Autism; GTF2I gene ID AUTISM-SPECTRUM; FUNCTIONING AUTISM; YOUNG-CHILDREN; HUMAN BRAIN; MICE; DUPLICATION; PERSONALITY; EXPRESSION; ANXIETY; REGION AB Background: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor lli) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated. Results: We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies. Conclusions: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations. C1 [Crespi, Bernard J.] Simon Fraser Univ, Dept Biol, Burnaby, BC V5A 1S6, Canada. [Hurd, Peter L.] Univ Alberta, Dept Psychol & Neurosci, Edmonton, AB T6G 2R3, Canada. [Hurd, Peter L.] Univ Alberta, Mental Hlth Inst, Edmonton, AB T6G 2R3, Canada. RP Crespi, BJ (reprint author), Simon Fraser Univ, Dept Biol, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM crespi@sfu.ca FU NSERC FX We are grateful to Jinko Graham and Brad McNeney for advice, to Silven Read for technical assistance, and to NSERC for financial support. 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PD NOV 28 PY 2014 VL 15 AR 127 DI 10.1186/s12868-014-0127-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AX9FA UT WOS:000347207900001 PM 25429715 ER PT J AU Seery, A Tager-Flusberg, H Nelson, CA AF Seery, Anne Tager-Flusberg, Helen Nelson, Charles A. TI Event-related potentials to repeated speech in 9-month-old infants at risk for autism spectrum disorder SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Event-related potentials; Speech processing; Infancy; Endophenotype; Auditory evoked potentials; Language ID AUDITORY EVOKED-RESPONSES; WEAK CENTRAL COHERENCE; GAMMA-BAND RESPONSES; 1ST-DEGREE RELATIVES; COGNITIVE PHENOTYPE; SOURCE LOCALIZATION; ASPERGER-SYNDROME; NONNATIVE SPEECH; 1ST YEAR; CHILDREN AB Background: Atypical neural responses to repeated auditory and linguistic stimuli have been reported both in individuals with autism spectrum disorder (ASD) and their first-degree relatives. Recent work suggests that the younger siblings of children with ASD have atypical event-related potentials (ERPs) to repeated tones at 9 months of age; however, the functional significance is unclear, and it is unknown whether this atypicality is also present in response to linguistic stimuli. Methods: We analyzed ERPs to repetitive and deviant consonant-vowel stimuli at 9 months in 35 unaffected high-risk-for-autism (HRA) infant siblings of children with ASD and 45 low-risk control (LRC) infants. We examined a positive component, the P150, over frontal and central electrode sites and investigated the relationships between this component and later behavior. Results: Over frontal electrodes, HRA infants had larger-amplitude ERPs to repetitions of the standard than LRC infants, whereas ERPs to the deviant did not differ between HRA and LRC infants. Furthermore, for HRA infants, the amplitude of ERPs to the standards was positively correlated with later language ability. Conclusions: Our work suggests that atypical ERPs to repeated speech during infancy are a possible endophenotype of ASD but that this atypicality is associated with beneficial, rather than disordered, language development. Potential mechanisms driving these relationships and implications for development are discussed. C1 [Seery, Anne] NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. [Tager-Flusberg, Helen] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Nelson, Charles A.] Boston Childrens Hosp, Div Dev Med, Labs Cognit Neurosci, Boston, MA 02215 USA. [Nelson, Charles A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Seery, A (reprint author), NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. EM anne.seery@nyumc.org FU NIDCD [R21 DC 08637, R01 DC 10290]; Simons Foundation [137186]; Autism Speaks Pilot Grants Program; Autism Speaks Weatherstone Fellowship Program FX This study was supported by funding from the NIDCD (R21 DC 08637, to HTF; R01 DC 10290, to HTF and CN), the Simons Foundation (137186, to CN), the Autism Speaks Pilot Grants Program (to HTF), and the Autism Speaks Weatherstone Fellowship Program (to AS). We would like to thank the participants and families for their time and dedication to the project. Furthermore, thank you to the large community of staff and students who have been involved with the Infant Sibling Project over the years and who have contributed to data collection, data processing, and helpful discussions regarding data analysis. Finally, thank you to all of the interns who have helped with the data processing, in particular for this project Rakhi Desai, Hana Kahn, and Alexandra Yellin. 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TI Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes SO MOLECULAR BRAIN LA English DT Article DE Synapse; Proteomics; Mass spectrometry; Supercomplex; Post-mortem brain; MAGUK; Psychiatric disorder ID NMDA RECEPTOR SUBUNITS; QUANTITATIVE PROTEOMICS; SIGNALING COMPLEXES; ALZHEIMERS-DISEASE; BRAIN; DENSITY; QUANTIFICATION; PSD-95; COMPONENTS; EVOLUTION AB Background: Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes have not been directly isolated from human synapses and the feasibility of their isolation from post-mortem tissue is unknown. Results: Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases. Conclusions: We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders. C1 [Bayes, Alex; Gou, Gemma] Biomed Res Inst Sant Pau, IIB Sant Pau, Mol Physiol Synapse Lab, Barcelona 08025, Spain. [Bayes, Alex; Gou, Gemma] Univ Autonoma Barcelona, Bellaterra 08193, Cerdanyola Del, Spain. [Collins, Mark O.] Univ Sheffield, Dept Biomed Sci, Western Bank, Ctr Membrane Interact & Dynam, Sheffield S10 2TN, S Yorkshire, England. [Galtrey, Clare M.] St George Hosp, Dept Neurol, London, England. [Simonnet, Clemence; Roy, Marcia; Croning, Mike D. R.; van de Lagemaat, Louie N.; Whittle, Ian R.; Grant, Seth G. N.] Univ Edinburgh, Ctr Clin Brain Sci, Genes Cognit Programme, Edinburgh EH16 4SB, Midlothian, Scotland. [Simonnet, Clemence; Roy, Marcia; Croning, Mike D. R.; van de Lagemaat, Louie N.; Whittle, Ian R.; Grant, Seth G. N.] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland. [Milward, David] Linguamatics, Cambridge CB4 0WG, England. [Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Acad Dept Neuropathol, Edinburgh EH16 4SB, Midlothian, Scotland. [Choudhary, Jyoti S.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. RP Grant, SGN (reprint author), Univ Edinburgh, Ctr Clin Brain Sci, Genes Cognit Programme, Edinburgh EH16 4SB, Midlothian, Scotland. EM seth.grant@ed.ac.uk FU Proyectos de investigacion no orientada [BFU2012-34398]; Career Integration grant CIG [304111]; Subprograma Ramon y Cajal [RYC-2011-08391]; NIHR Academic Clinical Fellowship; Medical Research Council; Wellcome Trust; European Union program (Project GENCODYS) [241995]; European Union program (Project EUROSPIN) [242498]; European Union program (Project SYNSYS) [242167] FX AB was funded by Proyectos de investigacion no orientada, BFU2012-34398, Career Integration grant CIG, Ref. 304111, Subprograma Ramon y Cajal, RYC-2011-08391. 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Brain PD NOV 28 PY 2014 VL 7 AR 88 DI 10.1186/s13041-014-0088-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AX4WQ UT WOS:000346929900001 PM 25429717 ER PT J AU Hwang, YS AF Hwang, Yoon-Suk TI 'Miss mum': mind and affective experience of Korean learners identified with autism spectrum and cognitive difficulties SO DISABILITY & SOCIETY LA English DT Article DE cognitive difficulties; mind; qualitative inquiry; autism; Korean culture; affective experience ID CHILDREN; DISORDERS; AMERICAN; CULTURE; EMPATHY AB Responding to the call for culturally informed research on autism spectrum (AS) to allow for the provision of appropriate services, this paper qualitatively explores the affective experience of five Korean learners identified with AS and cognitive difficulties by listening to their voices. The learners, supported by the use of visual aids and a choice of their preferred mode of communication, expressed the complexity of their inner experience that encompassed abilities as well as difficulties. The findings highlight the commonalities of experience between Korean and non-Korean individuals with AS, along with some aspects specific to the Korean cultural context. C1 Griffith Univ, Griffith Inst Educ Res, Brisbane, Qld 4111, Australia. RP Hwang, YS (reprint author), Griffith Univ, Griffith Inst Educ Res, Brisbane, Qld 4111, Australia. 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I go on to consider Wittgenstein's criteriological view of mind, propose a synthesis of theory to describe autism, and suggest that public criteria of a non-autistic ontology enable many autistic people to eventually develop the understanding of other (non-autistic) minds that, in turn, enables them to survive, and even thrive. 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PD NOV 26 PY 2014 VL 29 IS 10 BP 1672 EP 1676 DI 10.1080/09687599.2014.949625 PG 5 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA AT3PD UT WOS:000344845500012 ER PT J AU Kelsch, W Li, ZJ Wieland, S Senkov, O Herb, A Gongrich, C Monyer, H AF Kelsch, Wolfgang Li, Zhijun Wieland, Sebastian Senkov, Oleg Herb, Anne Goengrich, Christina Monyer, Hannah TI GluN2B-Containing NMDA Receptors Promote Glutamate Synapse Development in Hippocampal Interneurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GluN2B; hippocampus; interneurons; NMDARs; postnatal development; seizures ID NEURONAL PATTERNS; EXPRESSION; CORTEX; BRAIN; AMPA; MICE; DISRUPTION; SYSTEM; AUTISM; GENES AB In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2B(Delta GAD67)). In GluN2B(Delta GAD67) mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2B(Delta GAD67) mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons. C1 [Kelsch, Wolfgang; Wieland, Sebastian] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. [Li, Zhijun; Senkov, Oleg; Herb, Anne; Goengrich, Christina; Monyer, Hannah] Heidelberg Univ, Fac Med, Dept Clin Neurobiol, D-69120 Heidelberg, Germany. [Li, Zhijun; Senkov, Oleg; Herb, Anne; Goengrich, Christina; Monyer, Hannah] German Canc Res Ctr, DKFZ, D-69120 Heidelberg, Germany. [Senkov, Oleg] DZNE, Mol Neuroplast Grp, D-39120 Magdeburg, Germany. [Goengrich, Christina] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RP Monyer, H (reprint author), Heidelberg Univ, Fac Med, Dept Clin Neurobiol, D-69120 Heidelberg, Germany. EM h.monyer@dkfz-heidelberg.de FU Deutsche Forschungsgemeinschaft Emmy-Noether Grant [KE1661/1-1]; Schilling Foundation FX The work was supported by a Deutsche Forschungsgemeinschaft Emmy-Noether Grant (KE1661/1-1) to W.K. and Schilling Foundation to H.M. We thank Irmgard Preugschat-Gumprecht and Ulla Amtmann for technical help and Dr. Peggy Schneider for initial help with video tracking. 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Neurosci. PD NOV 26 PY 2014 VL 34 IS 48 BP 16022 EP 16030 DI 10.1523/JNEUROSCI.1210-14.2014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AU9OJ UT WOS:000345923600019 PM 25429143 ER PT J AU Shpyleva, S Ivanovsky, S de Conti, A Melnyk, S Tryndyak, V Beland, FA James, SJ Pogribny, IP AF Shpyleva, Svitlana Ivanovsky, Samuil de Conti, Aline Melnyk, Stepan Tryndyak, Volodymyr Beland, Frederick A. James, S. Jill Pogribny, Igor P. TI Cerebellar Oxidative DNA Damage and Altered DNA Methylation in the BTBR T plus tf/J Mouse Model of Autism and Similarities with Human Post Mortem Cerebellum SO PLOS ONE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; GLUTATHIONE REDOX IMBALANCE; SPECTRUM DISORDERS; REPAIR; EXPRESSION; STRESS; CELLS; MICE; OGG1; GENE AB The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC). The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of autism. C1 [Shpyleva, Svitlana; de Conti, Aline; Melnyk, Stepan; James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Shpyleva, Svitlana; Ivanovsky, Samuil; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. EM james.jill@uams.edu; igor.pogribny@fda.hhs.gov FU Jane Botsford Johnson Foundation FX Funding support for this study was provided by the Jane Botsford Johnson Foundation. Recipient of funding - SS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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language-ready brain; thalamus; cortex; basal ganglia; cerebellum; biolinguistics; vocal learning ID CELL-ADHESION MOLECULE; RUBINSTEIN-TAYBI-SYNDROME; GROWTH-FACTOR-BETA; AUTISM SPECTRUM DISORDERS; MAP KINASE PHOSPHATASE-1; GENOME-WIDE ASSOCIATION; IMMEDIATE-EARLY GENE; LEFT-RIGHT ASYMMETRY; C/EBP-BETA; TRANSCRIPTION FACTOR AB This study builds on the hypothesis put forth in Boackx and Benitez-Burraco (2014), according to which the developmental changes expressed at the levels of brain morphology and neural connectivity that resulted in a more globular braincase in our species were crucial to understand the origins of our language-ready brain. Specifically, this paper explores the links between two well-known 'language-related' genes like FOXP2 and ROB01 implicated in vocal learning and the initial set of genes of interest put forth in Boackx and BenitezBurraco (2014), with RUNX2 as focal point. Relying on the existing literature, we uncover potential molecular links that could be of interest to future experimental inquiries into the biological foundations of language and the testing of our initial hypothesis. Our discussion could also be relevant for clinical linguistics and for the interpretation of results from paleogenomics. C1 [Boeckx, Cedric] Catalan Inst Adv Studies & Res ICREA, Barcelona, Spain. [Boeckx, Cedric] Univ Barcelona, Dept Linguist, E-08007 Barcelona, Spain. [Benitez-Burraco, Antonio] Univ Huelva, Dept Spanish Philol & Its Didact, Huelva, Spain. RP Boeckx, C (reprint author), Univ Barcelona, Dept Linguist, Gran Via CortsCatalanes 585, E-08007 Barcelona, Spain. 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SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD NOV 25 PY 2014 VL 5 AR 1324 DI 10.3389/fpsyg.2014.01324 PG 22 WC Psychology, Multidisciplinary SC Psychology GA AU3QK UT WOS:000345528400001 PM 25505436 ER PT J AU Sato, W Kubota, Y Kochiyama, T Uono, S Yoshimura, S Sawada, R Sakihama, M Toichi, M AF Sato, Wataru Kubota, Yasutaka Kochiyama, Takanori Uono, Shota Yoshimura, Sayaka Sawada, Reiko Sakihama, Morimitsu Toichi, Motomi TI Increased putamen volume in adults ith autism spectrum disorder SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism spectrum disorder (ASD); MRI volumetry; basal ganglia; caudate; putamen; nucleus accumbens and globus pallidus ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA; RATING-SCALE; ASPERGERS-SYNDROME; BRAIN ANATOMY; TOKYO VERSION; BOYS; DYSFUNCTIONS; METAANALYSIS; STRIATUM AB Basal ganglia (BG) abnormalities are implicated in the pathophysiology of autism spectrum disorder (ASD). However, studies measuring the volume of the entire BG in individuals with ASD have reported discrepant findings, and no study conducted volume measurement of the entire substructures of the BG (the caudate, putamen, nucleus accumbens, and globus pallidus) in individuals with ASD. We delineated the BG substructures and measured their volumes in 29 adults with ASD without intellectual disabilities and 29 age- and gender-matched typically developed adult controls. We acquired T1-weighted anatomical images and performed semiautomated delineation and volume measurements of the above-mentioned subregions. Total cerebral volumes, sex, and ages were partialed out. Compared with controls, the putamen was significantly larger in the ASD group. The increased volume of the putamen found in high-functioning adults with ASD suggests that structural or histological abnormalities of the putamen may underlie the pathologies of ASD, such as repetitive and stereotyped behaviors and impaired social interactions. C1 [Sato, Wataru; Kochiyama, Takanori; Sawada, Reiko] Kyoto Univ, Primate Res Inst, Hakubi Project, Kyoto, Aichi 6068501, Japan. [Sato, Wataru; Toichi, Motomi] Org Promoting Dev Disorder Res, Kyoto, Japan. [Kubota, Yasutaka] Shiga Univ, Hlth & Med Serv Ctr, Hikone, Shiga 5228522, Japan. [Uono, Shota; Yoshimura, Sayaka; Toichi, Motomi] Kyoto Univ, Grad Sch Med, Fac Human Hlth Sci, Kyoto, Japan. [Sakihama, Morimitsu] Rakuwa Kai Otowa Hosp, Kyoto, Japan. RP Kubota, Y (reprint author), Shiga Univ, Hlth & Med Serv Ctr, 1-1-1 Baba, Hikone, Shiga 5228522, Japan. EM yka@edu.shiga-u.ac.jp FU Japan Society for the Promotion of Science (JSPS) Program for Next Generation World-Leading Researchers [LZ008]; Sakamoto Research Institute of Psychopathology; Organization for Promoting Developmental Disorder Research FX The authors thank Emi Yokoyama, Akemi Inoue, and Kazusa Minemoto for help with subject recruitment. This study was supported by funds from the Japan Society for the Promotion of Science (JSPS) Program for Next Generation World-Leading Researchers No. LZ008, the Sakamoto Research Institute of Psychopathology, and the Organization for Promoting Developmental Disorder Research. 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Hum. Neurosci. PD NOV 25 PY 2014 VL 8 AR 957 DI 10.3389/fnhum.2014.00957 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AU0KX UT WOS:000345312700001 PM 25505401 ER PT J AU Guipponi, M Santoni, FA Setola, V Gehrig, C Rotharmel, M Cuenca, M Guillin, O Dikeos, D Georgantopoulos, G Papadimitriou, G Curtis, L Meary, A Schurhoff, F Jamain, S Avramopoulos, D Leboyer, M Rujescu, D Pulver, A Campion, D Siderovski, DP Antonarakis, SE AF Guipponi, Michel Santoni, Federico A. Setola, Vincent Gehrig, Corinne Rotharmel, Maud Cuenca, Macarena Guillin, Olivier Dikeos, Dimitris Georgantopoulos, Georgios Papadimitriou, George Curtis, Logos Meary, Alexandre Schuerhoff, Franck Jamain, Stephane Avramopoulos, Dimitri Leboyer, Marion Rujescu, Dan Pulver, Ann Campion, Dominique Siderovski, David P. Antonarakis, Stylianos E. TI Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes SO PLOS ONE LA English DT Article ID DE-NOVO MUTATIONS; ASSOCIATION; AUTISM; RISK; DIFFERENTIATION; DISORDERS; VARIANTS; PATTERNS; SPECTRUM; NETWORK AB Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7x10(-8) per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene. C1 [Guipponi, Michel; Santoni, Federico A.; Gehrig, Corinne; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. [Guipponi, Michel; Santoni, Federico A.; Gehrig, Corinne; Antonarakis, Stylianos E.] Univ Hosp Geneva, Geneva, Switzerland. [Setola, Vincent; Siderovski, David P.] W Virginia Univ, Sch Med, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. [Rotharmel, Maud; Cuenca, Macarena; Guillin, Olivier; Campion, Dominique] Ctr Hosp Rouvray, Sotteville Les Rouen, France. [Rotharmel, Maud; Cuenca, Macarena; Guillin, Olivier; Campion, Dominique] INSERM, U1079, F-75654 Paris 13, France. [Dikeos, Dimitris; Georgantopoulos, Georgios; Papadimitriou, George] Univ Athens, Sch Med, Dept Psychiat 1, GR-11527 Athens, Greece. [Curtis, Logos] Dept Mental Hlth & Psychiat, Geneva, Switzerland. [Meary, Alexandre; Schuerhoff, Franck; Jamain, Stephane; Leboyer, Marion] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. [Meary, Alexandre; Schuerhoff, Franck; Jamain, Stephane; Leboyer, Marion] Univ Paris Est, Fac Med, Creteil, France. [Meary, Alexandre; Schuerhoff, Franck; Jamain, Stephane; Leboyer, Marion] Hop A Chenevier H Mondor, Assistance Publ Hop Paris, Creteil, France. [Meary, Alexandre; Schuerhoff, Franck; Jamain, Stephane; Leboyer, Marion] Fdn Fondamental, Creteil, France. [Avramopoulos, Dimitri; Pulver, Ann] Johns Hopkins Sch Med, Epidemiol & Genet Program Psychiat, Baltimore, MD USA. [Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany. [Antonarakis, Stylianos E.] Inst Genet & Genom Geneva iGE3, Geneva, Switzerland. RP Guipponi, M (reprint author), Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. EM Michel.Guipponi@unige.ch FU Swiss National Center of Competence in Research (NCCR) SYNAPSY - The Synaptic Bases of Mental Diseases - of the Swiss National Science Foundation; ERC; NIH [R01 GM082892]; UNC IDDRC, NICHD [P30 HD03110] FX This work was supported by grants from the Swiss National Center of Competence in Research (NCCR) SYNAPSY - The Synaptic Bases of Mental Diseases - of the Swiss National Science Foundation and ERC grant to SEA. Work in the Siderovski lab was funded by NIH grant R01 GM082892 and behavioral studies were supported by the UNC IDDRC, NICHD grant P30 HD03110. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Cerebral c-aminobutyric acid (GABA)-ergic levels are associated with a variety of neurological and psychiatric disorders. However, the role of the GABA system in different dimensions of empathy has not been investigated. Materials and Methods: Thirty-two right-handed healthy volunteers took part in this study. We used proton magnetic resonance spectroscopy to determine GABA concentrations in the anterior insula (AI) and the anterior cingulate cortex (ACC) and to examine the relationship between the GABA concentrations and the subcomponents of empathy evaluated by the Interpersonal Reactivity Index (IRI). Result: Pearson correlation analyses (two-tailed) showed that AI GABA was significantly associated with the empathy concern score (r=0.584, p<0.05) and the personal distress score (r=0.538, p<0.05) but not significantly associated with other empathy subscales. No significant correlation was found between ACC GABA and empathy subscores. 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As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of G LA by exposing female mice to low dose G LA during both preand postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of G LA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 two genes implicated in autism-like deficits was observed in the brain of G LA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. C1 [Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hebert, Betty; Richard, Olivier; Menuet, Arnaud; Briault, Sylvain; Pichon, Jacques; Montecot-Dubourg, Celine; Mortaud, Stephane] CNRS 3b, UMR7355, F-45071 Orleans, France. [Perche, Olivier; Briault, Sylvain] Ctr Hosp Reg, Dept Genet, Orleans, France. [Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Pichon, Jacques; Montecot-Dubourg, Celine; Mortaud, Stephane] Univ Orleans, Orleans, France. [Mazaud-Guittot, Severine; Lesne, Laurianne; Jegou, Bernard] Univ Rennes 1, IRSET INSERM U1085, Rennes, France. RP Laugeray, A (reprint author), CNRS 3b, UMR7355, INSERM, Rue Ferollerie, F-45071 Orleans, France. EM alaugeray@yahoo.fr FU French National Research Agency - ANR [CESA-10-007 - NEUROPEST]; Region Centre FX This work was supported by the French National Research Agency - ANR (CESA-10-007 - NEUROPEST), and Region Centre (Doctoral fellowship to Ameziane Herzine). The authors wish to thank Dr. Valerie Quesniaux for English editing. Part of the research was presented at the third PPTOX conference (Paris, May 14-16, 2012). 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Behav. Neurosci. PD NOV 20 PY 2014 VL 8 DI 10.3389/fnbeh.2014.00390 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AZ0OC UT WOS:000347943600001 PM 25477793 ER PT J AU Ashwin, C Chapman, E Howells, J Rhydderch, D Walker, I Baron-Cohen, S AF Ashwin, Chris Chapman, Emma Howells, Jessica Rhydderch, Danielle Walker, Ian Baron-Cohen, Simon TI Enhanced olfactory sensitivity in autism spectrum conditions SO MOLECULAR AUTISM LA English DT Article DE Asperger syndrome; Autism; Autistic traits; Olfaction; Sensory hypersensitivity ID RAPID CLINICAL-EVALUATION; SIGNAL-DETECTION ANALYSIS; EMBEDDED FIGURES TEST; EYED VISUAL-ACUITY; ALCOHOL SNIFF TEST; FUNCTIONING AUTISM; ASPERGER-SYNDROME; ODOR IDENTIFICATION; ABSOLUTE PITCH; DISORDERS AB Background: People with autism spectrum conditions (ASC) report heightened olfaction. Previous sensory experiments in people with ASC have reported hypersensitivity across visual, tactile, and auditory domains, but not olfaction. The aims of the present study were to investigate olfactory sensitivity in ASC, and to test the association of sensitivity to autistic traits. Methods: We recruited 17 adult males diagnosed with ASC and 17 typical adult male controls and tested their olfactory sensitivity using the Alcohol Sniff Test (AST), a standardised clinical evaluation of olfactory detection. The AST involves varying the distance between subject and stimulus until an odour is barely detected. Participants with ASC also completed the Autism Spectrum Quotient (AQ) as a measure of autism traits. Results: The ASC group detected the odour at a mean distance of 24.1 cm (SD = 11.5) from the nose, compared to the control group, who detected it at a significantly shorter mean distance of 14.4 cm (SD = 5.9). Detection distance was independent of age and IQ for both groups, but showed a significant positive correlation with autistic traits in the ASC group (r = 0.522). Conclusions: This is the first experimental demonstration, as far as the authors are aware, of superior olfactory perception in ASC and showing that greater olfactory sensitivity is correlated with a higher number of autistic traits. This is consistent with results from previous findings showing hypersensitivity in other sensory domains and may help explain anecdotal and questionnaire accounts of heightened olfactory sensitivity in ASC. Results are discussed in terms of possible underlying neurophysiology. C1 [Ashwin, Chris; Chapman, Emma; Howells, Jessica; Rhydderch, Danielle; Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge CB2 8AH, England. [Ashwin, Chris; Walker, Ian] Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. 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Solution NMR study reported that this R102Q mutant had long-range chemical shift effects on the HC and the C-terminal tail (L3). To understand the influence of the R102Q mutation on the HC and L3 of NCS-1, we have investigated the conformational dynamics and the structural flexibility of wild type (WT) NCS-1 and its R102Q mutant by conducting extensive all-atom molecular dynamics (MD) simulations. On the basis of six independent 450 ns MD simulations, we have found that the R102Q mutation in NCS-1 protein (1) dramatically reduces the flexibility of loops L2 and L3, (2) facilitates L3 in a more extended state to occupy the hydrophobic crevice to a larger extent, (3) significantly affects the intersegment salt bridges, and (4) changes the subspace of the free energy landscape of NCS-1 protein. Analysis of the salt bridge network in both WT and the R102Q variant demonstrates that the R102Q-mutation-induced salt bridge alternations play a critical role on the reduced flexibility of L2 and L3. These results reveal the important role of salt bridges on the structural properties of NCS-1 protein and that R102Q mutation disables the dynamic relocation of C-terminus, which may block the binding of NCS-1 protein to its receptors. This study may provide structural insights into the autistic spectrum disorder associated with R102Q mutation. C1 [Zhu, Yuzhen; Wu, Ying; Zou, Yu; Zhang, Qingwen] Shanghai Univ Sport, Coll Phys Educ & Training, Shanghai 200438, Peoples R China. [Luo, Yin] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China. [Ma, Buyong] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Zhang, QW (reprint author), Shanghai Univ Sport, Coll Phys Educ & Training, 399 Chang Hai Rd, Shanghai 200438, Peoples R China. 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In keeping with these observations, were view here that 88% of high-risk genes for autism influence neural induction and early maturation of the neuroblast. In addition, 80% of these same genes influence later stages of differentiation, including neurite and synapse development, suggesting that these gene products exhibit long-lasting developmental effects on cell development as well as elements of redundancy in processes of neural proliferation, growth, and maturation. We also address the putative genetic overlap of autism with conditions like epilepsy and schizophrenia, with implications to shared and divergent etiologies. This review imports the necessity of a frame shift in our understanding of the neurodevelopmental basis of autism to include all stages of neuronal maturation, ranging from neural induction to synaptogenesis. C1 [Casanova, Emily L.; Casanova, Manuel F.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40202 USA. 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Additionally, autoimmunity immune dysfunction, and neuroinflammation are also considered as etiological mechanisms of this disorder. This study aimed to elucidate the relationship between glutamatergic/GABAergic imbalance and neuroinflammation as two recently-discovered autism-related etiological mechanisms. Methods: Twenty autistic patients aged 3 to 15 years and 19 age-and gender-matched healthy controls were included in this study. The plasma levels of glutamate, GABA and glutamate/GABA ratio as markers of excitotoxicity together with TNF-alpha, IL-6, IFN-gamma and IFI16 as markers of neuroinflammation were determined in both groups. Results: Autistic patients exhibited glutamate excitotoxicity based on a much higher glutamate concentration in the autistic patients than in the control subjects. Unexpectedly higher GABA and lower glutamate/GABA levels were recorded in autistic patients compared to control subjects. TNF-a and IL-6 were significantly lower, whereas IFN-gamma and IFI16 were remarkably higher in the autistic patients than in the control subjects. Conclusion: Multiple regression analysis revealed associations between reduced GABA level, neuroinflammation and glutamate excitotoxicity. This study indicates that autism is a developmental synaptic disorder showing imbalance in GABAergic and glutamatergic synapses as a consequence of neuroinflammation. C1 [El-Ansary, Afaf] King Saud Univ, Dept Biochem, Coll Sci, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila] Autism Res & Treatment Ctr, Riyadh, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila] King Saud Univ, Shaik Al Amodi Autism Res Chair, Riyadh 11495, Saudi Arabia. [Al-Ayadhi, Laila] King Saud Univ, Fac Med, Dept Physiol, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf] Natl Res Ctr, Dept Med Chem, Cairo, Egypt. 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Neuroinflamm. PD NOV 19 PY 2014 VL 11 AR 189 DI 10.1186/s12974-014-0189-0 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AW6KS UT WOS:000346379100001 PM 25407263 ER PT J AU Gomez, AM Froemke, RC Burden, SJ AF Gomez, Andrea M. Froemke, Robert C. Burden, Steven J. TI Synaptic Plasticity and Cognitive Function Are Disrupted in the Absence of Lrp4 SO ELIFE LA English DT Article DE synapse; low-density lipoprotein-related receptor; behavior; learning; hippocampus; long-term potentiation ID CENANI-LENZ SYNDROME; RECEPTOR-RELATED PROTEIN-4; AUTISM SPECTRUM DISORDERS; MYASTHENIA-GRAVIS; PYRAMIDAL CELLS; MUTATIONS; HIPPOCAMPUS; INTEGRATION; MECHANISMS; SCLEROSTIN AB Lrp4, the muscle receptor for neuronal Agrin, is expressed in the hippocampus and areas involved in cognition. The function of Lrp4 in the brain, however, is unknown, as Lrp4(-/-) mice fail to form neuromuscular synapses and die at birth. Lrp4(-/-) mice, rescued for Lrp4 expression selectively in muscle, survive into adulthood and showed profound deficits in cognitive tasks that assess learning and memory. To learn whether synapses form and function aberrantly, we used electrophysiological and anatomical methods to study hippocampal CA3-CA1 synapses. In the absence of Lrp4, the organization of the hippocampus appeared normal, but the frequency of spontaneous release events and spine density on primary apical dendrites were reduced. CA3 input was unable to adequately depolarize CA1 neurons to induce long-term-potentiation. Our studies demonstrate a role for Lrp4 in hippocampal function and suggest that patients with mutations in Lrp4 or autoantibodies to Lrp4 should be evaluated for neurological deficits. C1 [Gomez, Andrea M.; Froemke, Robert C.; Burden, Steven J.] NYU, Langone Med Sch, Helen L & Martin S Kimmel Ctr Biol & Med Skirball, Inst Biomol Med,Mol Neurobiol Program,Grad Progra, New York, NY 10016 USA. RP Gomez, AM (reprint author), NYU, Langone Med Sch, Helen L & Martin S Kimmel Ctr Biol & Med Skirball, Inst Biomol Med,Mol Neurobiol Program,Grad Progra, 540 First Ave, New York, NY 10016 USA. 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TI Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; DE-NOVO MUTATIONS; SPECTRUM DISORDERS; OXIDATIVE STRESS; INTERACTION DATABASE; ENRICHMENT ANALYSIS; MULTIPLE-SCLEROSIS; BREAST-CANCER; LOCI AB Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P < 0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical "noise'' that warrant further analysis for causal variants. C1 [Correia, Catarina; Vicente, Astrid M.] Inst Nacl Saude Doutor Ricardo Jorge, Dept Promocao Saude & Doencas Nao Transmissiveis, P-1649016 Lisbon, Portugal. [Correia, Catarina; Vicente, Astrid M.] Univ Lisbon, Fac Sci, Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal. [Correia, Catarina; Vicente, Astrid M.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Oliveira, Guiomar] Ctr Hosp & Univ Coimbra, Hosp Pediat, Ctr Desenvolvimento, Unidade Neurodesenvolvimento & Autismo, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Ctr Invest & Formacao Clin HP CHUC, P-3000602 Coimbra, Portugal. [Oliveira, Guiomar] Univ Coimbra, Fac Med, P-3000548 Coimbra, Portugal. RP Vicente, AM (reprint author), Inst Nacl Saude Doutor Ricardo Jorge, Dept Promocao Saude & Doencas Nao Transmissiveis, P-1649016 Lisbon, Portugal. EM astrid.vicente@insa.min-saude.pt FU Autism Speaks (USA); Health Research Board (HRB, Ireland) [AUT/2006/1, AUT/2006/2, PD/2006/48]; Medical Research Council (MRC, UK); Genome Canada/Ontario Genomics Institute; Hilibrand Foundation (USA); US National Institutes of Health (NIH) [HD055751, HD055782, HD055784, MH52708, MH55284, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261]; NS049261), the Canadian Institutes for Health Research (CIHR); Assistance Publique - Hopitaux de Paris (France), Autism Speaks UK; Canada Foundation for Innovation/Ontario Innovation Trust; Deutsche Forschungsgemeinschaft (Germany) [Po 255/17-4]; EC Sixth FP AUTISM MOLGEN; Fundacao Calouste Gulbenkian (Portugal); Fondation de France; Fondation FondaMental (France); Fondation Orange (France); Fondation pour la Recherche Medicale (France); Fundacao para a Ciencia e Tecnologia (Portugal); Hospital for Sick Children Foundation and University of Toronto (Canada); INSERM (France); Institut Pasteur (France); Ministry of Health (convention 181 of 19 October 2001); John P. Hussman Foundation (USA); McLaughlin Centre (Canada); Ontario Ministry of Research and Innovation (Canada); Seaver Foundation (USA); Swedish Science Council; Centre for Applied Genomics (Canada); Utah Autism Foundation (USA); Wellcome Trust (UK) [075491/Z/04]; National Institute of Mental Health [1U24MH081810]; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/64281/2009] FX The AGP study was funded by Autism Speaks (USA), the Health Research Board (HRB, Ireland; AUT/2006/1, AUT/2006/2, PD/2006/48), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH Grants: HD055751, HD055782, HD055784, MH52708, MH55284, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261), the Canadian Institutes for Health Research (CIHR), Assistance Publique - Hopitaux de Paris (France), Autism Speaks UK, Canada Foundation for Innovation/Ontario Innovation Trust, Deutsche Forschungsgemeinschaft (Grant: Po 255/17-4) (Germany), EC Sixth FP AUTISM MOLGEN, Fundacao Calouste Gulbenkian (Portugal), Fondation de France, Fondation FondaMental (France), Fondation Orange (France), Fondation pour la Recherche Medicale (France), Fundacao para a Ciencia e Tecnologia (Portugal), the Hospital for Sick Children Foundation and University of Toronto (Canada), INSERM (France), Institut Pasteur (France), the Italian Ministry of Health (convention 181 of 19 October 2001), the John P. Hussman Foundation (USA), McLaughlin Centre (Canada), Ontario Ministry of Research and Innovation (Canada), the Seaver Foundation (USA), the Swedish Science Council, The Centre for Applied Genomics (Canada), the Utah Autism Foundation (USA) and the Wellcome Trust core award 075491/Z/04 (UK). The Autism Genetic Resource Exchange 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). Catarina Correia is supported by grant SFRH/BPD/64281/2009 from the Fundacao para a Ciencia e Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Roche, Laetitia Nystrom, Par Falck-Ytter, Terje TI Human Infants Detect Other People's Interactions Based on Complex Patterns of Kinematic Information SO PLOS ONE LA English DT Article ID BIOLOGICAL MOTION PERCEPTION; POINT-LIGHT DISPLAYS; RECOGNITION MEMORY; BODY ACTIONS; DISCRIMINATION; NOVELTY; AUTISM; FAMILIARITY; PREFERENCE; SPEECH AB Do infants perceive other people's interactions by means of a mechanism that integrates biological motion information across the observed individuals? In support of this view, the present study demonstrates that infants (N = 28, Age = 14 months) discriminate between point light displays representing disrupted and non-disrupted interactions between people, even though the two interaction types are identical at the level of individual point light agents. Moreover, a second experiment (sample 2: N = 28, Age = 14 months) indicated that visual preference in this context is influenced by an audiovisual integration processes that takes into account the presence of an interaction between people. All these results were found exclusively for upright displays -when stimuli were shown upside-down (disrupting biological motion processing), performance was random. Collectively, these findings point to an important role for biological motion in social perception in human infants. C1 [Galazka, Martyna A.; Nystrom, Par; Falck-Ytter, Terje] Uppsala Univ, Dept Psychol, Uppsala Child & Babylab, Uppsala, Sweden. [Roche, Laetitia] INSERM, U930, Tours, France. [Roche, Laetitia] Univ Tours, Unit Imaging & Brain 930, Team Autism 1, Tours, France. [Falck-Ytter, Terje] Karolinska Inst KIND, Ctr Neurodev Disorders, Stockholm, Sweden. RP Galazka, MA (reprint author), Uppsala Univ, Dept Psychol, Uppsala Child & Babylab, Uppsala, Sweden. EM martyna.galazka@psyk.uu.se; laetitia.alexandra.roche@gmail.com FU Bank of Sweden Tercentenary Foundation [P12-0270:1]; Swedish Research Council; FAS; FORMAS; VINNOVA [259-2012-24]; ESF COST Action BM1004 'Enhancing the Scientific Study of Early Autism' (ESSEA); European Research Council [ERC-2012-StG 312292-CACTUS] FX TFY was supported by the Bank of Sweden Tercentenary Foundation [P12-0270:1] and the Swedish Research Council in partnership with FAS, FORMAS, and VINNOVA [Cross-disciplinary research programme concerning children's and young people's mental health; grant number 259-2012-24]. The work of TFY, PN and LR was supported by the ESF COST Action BM1004 'Enhancing the Scientific Study of Early Autism' (ESSEA). The work of MG was supported by the European Research Council (ERC-2012-StG 312292-CACTUS). 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, different from the case of children diagnosed with ASD in childhood, it is difficult in adults to identify the ASD symptoms underlying psychopathology and to differentiate ASD from other psychiatric disorders in general psychiatric practice. This study aimed to verify the utility of the Social Responsiveness Scale-Adult version (SRS-A), a quantitative measure for identifying ASD symptoms, in non-clinical and clinical adult populations in Japan. Methods: The total sample aged 19 to 59 years consisted of a non-clinical population (n = 592) and clinical population with and without ASD (n = 142). We examined score distributions of the Japanese version of the scale, and the effects of gender, age, and rater on the distribution. We analyzed factor structure and internal consistency in the non-clinical normative sample, and analyzed convergent, divergent, and discriminative validities in the clinical sample. We applied receiver operator characteristic (ROC) analysis to determine optimal cutoff scores discriminating the ASD clinical population from the non-ASD clinical population. Results: The score distributed continuously, which replicated findings in children. For non-clinical adults, except in men aged 19 to 24 years, we found no or few gender, age, or rater effects. Both single- and two-factor models were supported for adults. Total SRS-A scores demonstrated high internal consistency and capably discriminated adults with ASD from those with non-ASD psychiatric disorders such as major depressive disorder, schizophrenia, and bipolar disorder with an overlap across diagnoses. Moderate to high correlations of the SRS-A with other-rated ASD measures indicated sufficient convergent validity. Based on the ROC analysis, we recommend cutoff points by gender for use in clinical settings. Conclusion: This study provides additional supportive evidence that the Japanese version SRS-A can reliably and validly measure ASD symptoms in non-clinical and clinical adult populations, and thus can serve as a useful tool for ASD research as well as for secondary screening in Japanese adults. C1 [Takei, Reiko; Takahashi, Hidetoshi; Kamio, Yoko] Natl Ctr Neurol & Psychiat, Dept Child & Adolescent Mental Hlth, Natl Inst Mental Hlth, Kodaira, Tokyo 1878553, Japan. [Matsuo, Junko; Kunugi, Hiroshi] Natl Ctr Neurol & Psychiat, Dept Mental Disorder Res, Kodaira, Tokyo 1878553, Japan. [Uchiyama, Tokio] Fukushima Univ, Dept Fac Human Dev, Grad Sch, Fukushima, Japan. RP Kamio, Y (reprint author), Natl Ctr Neurol & Psychiat, Dept Child & Adolescent Mental Hlth, Natl Inst Mental Hlth, 4-1-1 Ogawa Higashi, Kodaira, Tokyo 1878553, Japan. EM kamio@ncnp.go.jp FU Ministry of Health, Labour and Welfare of Japan [H22-SEISHIN-IPPAN-016, H20-KOKORO-004] FX This study was supported by research grants from the Ministry of Health, Labour and Welfare of Japan (H22-SEISHIN-IPPAN-016 to Dr. Uchiyama and H20-KOKORO-004 to Dr. Kamio). We would like to thank Drs. Satoshi Hashimoto, Kaoruko Izumi, Yoshihiro Nabeshima, Mari Umeda, Hirohisa Hida, Itsuka Seido, Masatsugu Tsujii, Yoshiyuki Shimoda, Ikuko Nakano, Yuki Kawakubo, Hidenori Yamasue, Miho Kuroda, Naoji Kondo, Reiko Fukatsu, and Takeshi Nishiyama for data collection. Special thanks goes to Dr. Ryoji Yukihiro for statistical advice. The authors have no conflicts of interest to declare with respect to this article. 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PD NOV 17 PY 2014 VL 34 IS 8 SI SI BP 817 EP 830 DI 10.1080/07351690.2014.968024 PG 14 WC Psychology, Psychoanalysis SC Psychology GA AU6AW UT WOS:000345685400004 ER PT J AU Li, ZC Tang, JS Li, H Chen, S He, Y Liao, YH Wei, Z Wan, GB Xiang, X Xia, K Chen, XG AF Li, Zongchang Tang, Jinsong Li, Hong Chen, Shan He, Ying Liao, Yanhui Wei, Zhen Wan, Guobin Xiang, Xi Xia, Kun Chen, Xiaogang TI Shorter telomere length in peripheral blood leukocytes is associated with childhood autism SO SCIENTIFIC REPORTS LA English DT Article ID SPECTRUM DISORDERS; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; EPIGENETIC REGULATION; CANCER-MORTALITY; INCIDENT CANCER; LIFE-SPAN; RISK; METAANALYSIS; DYSFUNCTION AB Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Epidemiologic studies have shown that the abnormal telomere length in leukocytes is associated with some mental disorders and age-related diseases. However, the association between leukocyte telomere length and autism has not been investigated. Here we investigated the possible association between relative telomere length (RTL) in peripheral blood leukocytes and childhood autism by using an established real-time polymerase chain reaction method. We observed significantly shorter RTL in patients with childhood autism than in controls (p=0.006). Individuals with shorter RTL had a significantly increased presence of childhood autism compared with those who had long RTL. In patients, we found that family training interventions have a significant effect on telomere length (P=0.012), but no correlations between RTL and clinical features (paternal age, maternal age, age of onset, illness of duration, CARS score and ABC score) were observed in this study. These results provided the first evidence that shorter leukocytes telomere length is significantly associated with childhood autism. The molecular mechanism underlying telomere length may be implicated in the development of autism. C1 [Li, Zongchang; Tang, Jinsong; Li, Hong; Chen, Shan; He, Ying; Liao, Yanhui; Chen, Xiaogang] Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha, Hunan, Peoples R China. [Li, Zongchang; Chen, Shan] Wenzhou Med Univ, Inst Genom Med, Wenzhou, Zhejiang, Peoples R China. [Wei, Zhen; Wan, Guobin] Nanfang Univ Med Sci, Affiliated Shenzhen Maternal & Child Hlth Care Ho, Dept Womens Hlth Care, Shenzhen, Guangdong, Peoples R China. [Xiang, Xi] BGI Ark Biotechnol Co Ltd, Shenzhen, Guangdong, Peoples R China. [Xia, Kun; Chen, Xiaogang] Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China. [Chen, Xiaogang] Cent S Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, Changsha, Hunan, Peoples R China. [Chen, Xiaogang] Cent S Univ, Natl Technol Inst Psychiat, Changsha, Hunan, Peoples R China. RP Tang, JS (reprint author), Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha, Hunan, Peoples R China. EM tangjinsonghn@gmail.com; chenxghn@gmail.com FU National Natural Science Foundation of China [30900486, 81371480, 81271484]; National Key Basic Research and Development Program (973) [2012CB517904] FX The study was supported by the National Natural Science Foundation of China (Grant No. 30900486 and 81371480 to J.T, 81271484 to X.C), the National Key Basic Research and Development Program (973) (Grant No. 2012CB517904 to X.C). 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Fan, Chia-Yu Gupta, Tarun Chiang, Ann-Shyn Certel, Sarah J. TI Astrocyte-specific regulation of hMeCP2 expression in Drosophila SO BIOLOGY OPEN LA English DT Article DE MeCP2; Rett Syndrome; Sleep; Astrocytes; Drosophila ID MECP2 DUPLICATION SYNDROME; AUTISM SPECTRUM DISORDERS; CPG-BINDING PROTEIN-2; RETT-SYNDROME; NEURODEVELOPMENTAL DISORDERS; GLUTAMATE TRANSPORTERS; GLIAL DIFFERENTIATION; SLEEP HOMEOSTASIS; BRAIN-DEVELOPMENT; NERVOUS-SYSTEM AB Alterations in the expression of Methyl-CpG-binding protein 2 (MeCP2) either by mutations or gene duplication leads to a wide spectrum of neurodevelopmental disorders including Rett Syndrome and MeCP2 duplication disorder. Common features of Rett Syndrome (RTT), MeCP2 duplication disorder, and neuropsychiatric disorders indicate that even moderate changes in MeCP2 protein levels result in functional and structural cell abnormalities. In this study, we investigated two areas of MeCP2 pathophysiology using Drosophila as a model system: the effects of MeCP2 glial gain-of-function activity on circuits controlling sleep behavior, and the cell-type specific regulation of MeCP2 expression. In this study, we first examined the effects of elevated MeCP2 levels on microcircuits by expressing human MeCP2 (hMeCP2) in astrocytes and distinct subsets of amine neurons including dopamine and octopamine (OA) neurons. Depending on the cell-type, hMeCP2 expression reduced sleep levels, altered daytime/nighttime sleep patterns, and generated sleep maintenance deficits. Second, we identified a 498 base pair region of the MeCP2e2 isoform that is targeted for regulation in distinct subsets of astrocytes. Levels of the full-length hMeCP2e2 and mutant RTT R106W protein decreased in astrocytes in a temporally and spatially regulated manner. In contrast, expression of the deletion Delta 166 hMeCP2 protein was not altered in the entire astrocyte population. qPCR experiments revealed a reduction in full-length hMeCP2e2 transcript levels suggesting transgenic hMeCP2 expression is regulated at the transcriptional level. Given the phenotypic complexities that are caused by alterations in MeCP2 levels, our results provide insight into distinct cellular mechanisms that control MeCP2 expression and link microcircuit abnormalities with defined behavioral deficits. Biology Open C1 [Hess-Homeier, David L.; Certel, Sarah J.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. [Gupta, Tarun; Certel, Sarah J.] Univ Montana, Neurosci Grad Program, Missoula, MT 59812 USA. [Fan, Chia-Yu] Ind Technol Res Inst, Biomed Technol & Device Res Labs, Hsinchu 31040, Taiwan. [Fan, Chia-Yu; Chiang, Ann-Shyn] Natl Tsing Hua Univ, Brain Res Ctr, Hsinchu 30013, Taiwan. RP Certel, SJ (reprint author), Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. EM sarah.certel@umontana.edu FU Ministry of Science and Technology of Taiwan; Ministry of Education of Taiwan; National Institutes of Health Center of Biomedical Research Excellence [P20RR015583]; University of Montana Research Grant Program FX Supported by grants from the Ministry of Science and Technology of Taiwan and Ministry of Education of Taiwan to A.-S.C., and the National Institutes of Health Center of Biomedical Research Excellence grant P20RR015583 and the University of Montana Research Grant Program to S.J.C. 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Open PD NOV 15 PY 2014 VL 3 IS 11 BP 1011 EP 1019 DI 10.1242/bio.20149092 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AZ2ZR UT WOS:000348098200001 PM 25305037 ER PT J AU Zhu, B Chen, CS Xue, G Lei, XM Li, J Moyzis, RK Dong, Q Lin, CD AF Zhu, Bi Chen, Chuansheng Xue, Gui Lei, Xuemei Li, Jin Moyzis, Robert K. Dong, Qi Lin, Chongde TI The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence SO NEUROIMAGE LA English DT Article DE Gamma-aminobutyric acid receptor subunit beta-1 gene; GABRB1; Thalamus volume; Intelligence; Sex differences ID GENOME-WIDE ASSOCIATION; RECEPTOR SUBUNIT GENES; SUBCORTICAL VOLUMES; ALCOHOL DEPENDENCE; BRAIN VOLUMES; BIPOLAR DISORDER; SCHIZOPHRENIA; AUTISM; 1ST-EPISODE; ADOLESCENTS AB The GABRB1 gene encodes the beta 1 subunit of the gamma-aminobutyric acid A receptor (GABA A receptor), which is responsible for mediating inhibitory neurotransmission in the thalamus. Potential relationships between the GABRB1 gene, thalamus volume, and intelligence have been suggested by previous clinical studies, but have not been directly examined among nonclinical samples. The current study collected structural MRI, genetic, and behavioral data from 316 healthy Chinese adults (including 187 females and 129 males), and examined associations between GABRB1 variants, thalamus volume, and intelligence (measured by the Wechsler Adult Intelligence Scale Revised). After controlling for intracranial volume, sex, and age, GABRB1 genetic polymorphism at the SNP rs7435958 had the strongest association with thalamus volume (p = 0.002 and 0.00008 for left and right thalamus volumes, respectively), with GG homozygotes having smaller bilateral thalamus volumes than the other genotypes. Furthermore, there were positive correlations between bilateral thalamus volumes and intelligence, especially for GABRB1 rs7435958 GG female homozygotes (r's = 0.31 and 0.29, p < 0.01, for the correlations of intelligence with left and right thalamus volumes, respectively). This study provides the first evidence for the involvement of the GABRB1 gene in the thalamus structure and their interactive effects on intelligence. Future studies of the thalamus-intelligence associations should consider genetic factors as potential moderators. (C) 2014 Elsevier Inc. All rights reserved. C1 [Zhu, Bi; Xue, Gui; Lei, Xuemei; Li, Jin; Dong, Qi; Lin, Chongde] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Zhu, Bi; Xue, Gui; Lei, Xuemei; Li, Jin; Dong, Qi; Lin, Chongde] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China. [Zhu, Bi; Xue, Gui; Lei, Xuemei; Li, Jin; Dong, Qi; Lin, Chongde] Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China. [Chen, Chuansheng] Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA. [Moyzis, Robert K.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. [Moyzis, Robert K.] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA USA. RP Zhu, B (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. EM psyzhubi@gmail.com; cschen@uci.edu FU National Natural Science Foundation of China [31130025, 31221003, 31200850]; Fundamental Research Funds for the Central Universities [2013YB27]; 11 Project of the Ministry of Education of China [B07008] FX This study was supported by the National Natural Science Foundation of China (31130025, 31221003, and 31200850), the Fundamental Research Funds for the Central Universities (2013YB27), and the 111 Project of the Ministry of Education of China (B07008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All authors contributed to and have approved the final manuscript. 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Lal, Dennis Lebon, Sebastien Hildebrand, Michael S. Dahl, Hans-Henrik M. Regan, Brigid M. Feucht, Martha Steinboeck, Hannelore Neophytou, Birgit Ronen, Gabriel M. Roche, Laurian Gruber-Sedlmayr, Ursula Geldner, Julia Haberlandt, Edda Hoffmann, Per Herms, Stefan Gieger, Christian Waldenberger, Melanie Franke, Andre Wittig, Michael Schoch, Susanne Becker, Albert J. Hahn, Andreas Maennik, Katrin Toliat, Mohammad R. Winterer, Georg Lerche, Holger Nuernberg, Peter Mefford, Heather Scheffer, Ingrid E. Berkovic, Samuel F. Beckmann, Jacques S. Sander, Thomas Jacquemont, Sebastien Reymond, Alexandre Zimprich, Fritz Neubauer, Bernd A. CA 16P11 2 European Consortium EPICURE Consortium EuroEPINOMICS Consortium TI 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy SO HUMAN MOLECULAR GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; BENIGN PARTIAL EPILEPSY; IDIOPATHIC GENERALIZED EPILEPSY; CHILDHOOD FOCAL EPILEPSIES; PSEUDO-LENNOX-SYNDROME; COPY NUMBER VARIANTS; CENTROTEMPORAL SPIKES; RECURRENT MICRODELETIONS; 15Q13.3 MICRODELETIONS; 16P13.11 PREDISPOSE AB Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 x 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 3 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE. C1 [Reinthaler, Eva M.; Zimprich, Fritz] Med Univ Vienna, Dept Neurol, A-1090 Vienna, Austria. [Feucht, Martha] Med Univ Vienna, Dept Pediat, A-1090 Vienna, Austria. [Lal, Dennis; Toliat, Mohammad R.; Nuernberg, Peter; Sander, Thomas] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany. [Lal, Dennis; Nuernberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. [Lal, Dennis; Hahn, Andreas; Neubauer, Bernd A.] Univ Med Fac Giessen & Marburg, Dept Neuropediat, Giessen, Germany. [Lebon, Sebastien] Univ Lausanne Hosp, Unit Pediat Neurol & Neurorehabil, Dept Pediat, Lausanne, Switzerland. [Beckmann, Jacques S.; Jacquemont, Sebastien] Univ Lausanne Hosp, Serv Med Genet, Lausanne, Switzerland. [Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Regan, Brigid M.; Scheffer, Ingrid E.; Berkovic, Samuel F.] Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic, Australia. [Neophytou, Birgit] St Anna Childrens Hosp, Dept Neuropediat, A-1090 Vienna, Austria. [Ronen, Gabriel M.; Roche, Laurian] McMaster Univ, Dept Pediat, Hamilton, ON, Canada. [Gruber-Sedlmayr, Ursula] Med Univ Graz, Dept Pediat, Graz, Austria. [Geldner, Julia] Hosp SMZ Sud Kaiser Franz Josef Spital, Dept Pediat, Vienna, Austria. [Haberlandt, Edda] Med Univ Innsbruck, Dept Pediat, A-6020 Innsbruck, Austria. [Hoffmann, Per; Herms, Stefan] Univ Bonn, Inst Human Genet, Bonn, Germany. [Hoffmann, Per; Herms, Stefan] Univ Basel, Univ Hosp, Div Med Genet, Basel, Switzerland. [Hoffmann, Per; Herms, Stefan] Univ Basel, Dept Biomed, Basel, Switzerland. [Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth GmbH, Inst Genet Epidemiol, Neuherberg, Germany. [Waldenberger, Melanie] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany. [Franke, Andre; Wittig, Michael] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Schoch, Susanne; Becker, Albert J.] Univ Bonn Med Ctr, Dept Neuropathol, Bonn, Germany. [Maennik, Katrin; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland. [Maennik, Katrin] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Winterer, Georg] Charite, ECRC, D-13353 Berlin, Germany. [Lerche, Holger] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Tubingen, Germany. [Mefford, Heather] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [Beckmann, Jacques S.] Swiss Inst Bioinformat, Lausanne, Switzerland. [Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Florey Inst, Melbourne, Vic, Australia. [Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Dept Pediat, Melbourne, Vic, Australia. RP Zimprich, F (reprint author), Med Univ Vienna, Dept Neurol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM friedrich.zimprich@meduniwien.ac.at RI Becker, Albert/F-6248-2012; Scheffer, Ingrid/G-1668-2013; Beckmann, Jacques/A-9772-2008; sanlaville, damien/M-4716-2014 OI Scheffer, Ingrid/0000-0002-2311-2174; Beckmann, Jacques/0000-0002-9741-1900; sanlaville, damien/0000-0001-9939-2849 FU Austrian science fund [FWF 1643-B09]; German Research Foundation (DFG) within EuroEPINOMICS network within EURO-CORES framework of the European Science Foundation (ESF) [DFG Ne 416/5-1, DFG SA434/5-1, DFG Le1030/11-1]; European Community [LSHM-CT-2006-037315]; Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research; State of Bavaria; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; DFG as part of the priority program SPP1226: 'Nicotine-Molecular and physiological effects in CNS' [Wi1316/9-1]; Swiss Scientific Exchange NMS Program; bourse de releve academique de la Faculte de Biologie et Medecine de l'Universite de Lausanne; Leenaards Foundation Prize; Simons Foundation Autism Research Initiative [SFARI274424]; Swiss National Science Foundation (SNSF); specific SNSF Sinergia grant; National Health and Medical Research Council [628952, 466671, 1006110, 546493] FX This work was supported by the Austrian science fund (FWF 1643-B09 to F.Z.) and the German Research Foundation (DFG) within the EuroEPINOMICS network within the EURO-CORES framework of the European Science Foundation (ESF) (DFG Ne 416/5-1 to B.N.), (DFG SA434/5-1 to T. S.) and (DFG Le1030/11-1 to H. L.). The study was further supported by grants from the European Community (FP6 Integrated Project EPICURE, grant LSHM-CT-2006-037315 to T. S.). The PopGen biobank (grant to A. F.) 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. G. W. (Wi1316/9-1) providing control data is funded by the DFG as part of the priority program SPP1226: 'Nicotine-Molecular and physiological effects in CNS'. K. M. is a grantee of a scholarship from the Swiss Scientific Exchange NMS Program and S.J. is recipient of a 'bourse de releve academique de la Faculte de Biologie et Medecine de l'Universite de Lausanne'. This work is also supported by the Leenaards Foundation Prize (S.J. and A.R.), the Simons Foundation Autism Research Initiative (SFARI274424 to A. R.), the Swiss National Science Foundation (SNSF) (A. R.) and a specific SNSF Sinergia grant (A. R.). For the Australian cohort the study was supported by a National Health and Medical Research Council Program Grant (628952) to S. F. B and I. E. S, an Australia Fellowship (466671) to S. F. B, a Practitioner Fellowship (1006110) to I. E. S and a Postdoctoral Training Fellowship (546493) to M. S. H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Mol. Genet. PD NOV 15 PY 2014 VL 23 IS 22 BP 6069 EP 6080 DI 10.1093/hmg/ddu306 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AT1CY UT WOS:000344671900019 PM 24939913 ER PT J AU Howard, LM Molyneaux, E Dennis, CL Rochat, T Stein, A Milgrom, J AF Howard, Louise M. Molyneaux, Emma Dennis, Cindy-Lee Rochat, Tamsen Stein, Alan Milgrom, Jeannette TI Perinatal mental health 1 Non-psychotic mental disorders in the perinatal period SO LANCET LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; POSTNATAL-DEPRESSION-SCALE; POSTTRAUMATIC-STRESS-DISORDER; MIDDLE-INCOME COUNTRIES; SEROTONIN REUPTAKE INHIBITORS; PRENATAL ANTIDEPRESSANT EXPOSURE; CORTICOTROPIN-RELEASING HORMONE; OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; AUTISM SPECTRUM DISORDERS AB Mental disorders are among the most common morbidities of pregnancy and the postnatal period, and can have adverse effects on the mother, her child, and family. This Series paper summarises the evidence about epidemiology, risk factors, identification, and interventions for non-psychotic mental disorders. Although the phenomenology and risk factors for perinatal mental disorders are largely similar to those for the disorders at other times, treatment considerations differ during pregnancy and breastfeeding. Most randomised controlled trials have examined psychosocial and psychological interventions for postnatal depression, with evidence for effectiveness in treating and preventing the disorder. Few high-quality studies exist on the effectiveness or safety of pharmacological treatments in the perinatal period, despite quite high prescription rates. General principles of prescribing of drugs in the perinatal period are provided, but individual risk-benefit analyses are needed for decisions about treatment. C1 [Howard, Louise M.; Molyneaux, Emma] Kings Coll London, Hlth Serv, London SE5 8AF, England. [Howard, Louise M.; Molyneaux, Emma] Kings Coll London, Populat Res Dept, Inst Psychiat Psychol & Neurosci, London SE5 8AF, England. [Dennis, Cindy-Lee] Univ Toronto, Toronto, ON, Canada. [Dennis, Cindy-Lee] Womens Coll, Res Inst, Toronto, ON, Canada. [Rochat, Tamsen] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Durban, South Africa. [Stein, Alan] Univ Oxford, Dept Psychiat, Oxford, England. [Stein, Alan] Univ Witwatersrand, Sch Publ Hlth, MRC Wits Rural Publ Hlth & Hlth Transit Res Unit, Johannesburg, South Africa. [Milgrom, Jeannette] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, VA, Australia. RP Howard, LM (reprint author), Kings Coll London, Hlth Serv, London SE5 8AF, England. EM louise.howard@kcl.ac.uk FU ad; Chair of the National Institute for Health and Care Excellence; Chief Investigator of an National Institute of Health Research (NIHR) Programme [RP-RP-DG-1108-10012]; NIHR [NIHR-RP-R3-12-011]; Tommy's baby charity; NIHR Mental Health Biomedical Research Centre at the South London; Maudsley UK National Health Service (NHS) Foundation Trust and King's College London; Medical Research Council; Grand Challenges Canada [0063-03]; Wellcome Trust [097410/Z/11/Z, 090139]; National Institute of Health [1R01HD074267-01]; Barclay Foundation; Department of Education (UK) FX LMH is Chair of the National Institute for Health and Care Excellence (update) guideline on Antenatal and Postnatal Mental Health, and Chief Investigator of an National Institute of Health Research (NIHR) Programme Grant for Applied Research on the effectiveness of perinatal mental health services (RP-RP-DG-1108-10012) which also supports JM. LMH receives funding from an NIHR Research Professorship on maternal mental health (NIHR-RP-R3-12-011), and a grant from Tommy's baby charity (with the support of a corporate social responsibility grant from Johnson and Johnson) on antipsychotics in pregnancy. LMH is also supported by the NIHR Mental Health Biomedical Research Centre at the South London and Maudsley UK National Health Service (NHS) Foundation Trust and King's College London. The views expressed are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health. EM is supported by a Medical Research Council PhD Studentship and Tommy's baby charity. TR receives salary support from Grand Challenges Canada (Grant Number 0063-03), the Wellcome Trust (Grant Number 097410/Z/11/Z) and National Institute of Health (1R01HD074267-01). AS has received many grants in relation to parental perinatal health and child development including from the Wellcome Trust (090139), Medical Research Council UK, Barclay Foundation, Grand Challenges (Canada), and The Department of Education (UK). We declare no other competing interests. 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1788 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA AT7KX UT WOS:000345116400029 PM 25455248 ER PT J AU Clemmensen, L van Os, J Skovgaard, AM Vaever, M Blijd-Hoogewys, EMA Bartels-Velthuis, AA Jeppesen, P AF Clemmensen, Lars van Os, Jim Skovgaard, Anne Mette Vaever, Mette Blijd-Hoogewys, Els M. A. Bartels-Velthuis, Agna A. Jeppesen, Pia TI Hyper-Theory-of-Mind in Children with Psychotic Experiences SO PLOS ONE LA English DT Article ID PERSECUTORY DELUSIONS; NORMAL ADULTS; SCHIZOPHRENIA; AUTISM; SYMPTOMS; DEFICITS; SCHIZOTYPY; DISORDERS; METAANALYSIS; RELIABILITY AB Background: Alterations in Theory-of-Mind (ToM) are associated with psychotic disorder. In addition, studies in children have documented that alterations in ToM are associated with Psychotic Experiences (PE). Our aim was to examine associations between an exaggerated type of ToM (HyperToM) and PE in children. Children with this type of alteration in ToM infer mental states when none are obviously suggested, and predict behaviour on the basis of these erroneous beliefs. Individuals with HyperToM do not appear to have a conceptual deficit (i.e. lack of representational abilities), but rather they apply their theory of the minds of others in an incorrect or biased way. Method: Hypotheses were tested in two studies with two independent samples: (i) a general population sample of 1630 Danish children aged 11-12 years, (ii) a population-based sample of 259 Dutch children aged 12-13 years, pertaining to a case-control sampling frame of children with auditory verbal hallucinations. Multinomial regression analyses were carried out to investigate the associations between PE and ToM and HyperToM respectively. Analyses were adjusted for gender and proxy measures of general intelligence. Results: Low ToM score was significantly associated with PE in sample I (OR = 1.6 95% CI 1.1-2.3 chi(2) (4) = 12.42 p = 0.010), but not in sample II (OR = 0.9 95% CI 0.5-1.8 x 2 (3) = 7.13 p = 0.816). HyperToM was significantly associated with PE both in sample I (OR = 1.8, 95% CI 1.2-2.7 chi(2) (3) = 10.11 p = 0.006) and II (OR = 4.6, 95% CI 1.3-16.2 chi(2) (2) = 7.56 p = 0.018). HyperToM was associated particularly with paranoid delusions in both sample I (OR = 2.0, 95% CI: 1.1-3.7% chi(2) (4) = 9.93 p = 0.021) and II (OR = 6.2 95% CI: 1.7-23.6% chi(2) (4) = 9.90 p = 0.044). Conclusion: Specific alterations in ToM may be associated with specific types of psychotic experiences. HyperToM may index risk for developing psychosis and paranoid delusions in particular. C1 [Clemmensen, Lars; Jeppesen, Pia] Mental Hlth Serv, Child & Adolescent Mental Hlth Ctr, Copenhagen, Denmark. [van Os, Jim] Maastricht Univ, Med Ctr, Dept Psychiat & Psychol, Maastricht, Netherlands. [Skovgaard, Anne Mette] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [Vaever, Mette] Univ Copenhagen, Dept Psychol, Copenhagen, Denmark. [Blijd-Hoogewys, Els M. A.] INTER PSY Groningen, Groningen, Netherlands. [Bartels-Velthuis, Agna A.] Univ Groningen, Univ Med Ctr Groningen, Univ Ctr Psychiat Groningen, Groningen Triadegebouw, Netherlands. RP Clemmensen, L (reprint author), Mental Hlth Serv, Child & Adolescent Mental Hlth Ctr, Copenhagen, Denmark. EM lars.clemmensen@regionh.dk FU Tryg Foundation [J.nr.7-10-0189, J.nr.7-11-0341]; Lundbeck Foundation [j. nr. R54-A5843] FX AMS recieved funding for CCC2000 from Tryg Foundation (J.nr.7-10-0189 and J.nr.7-11-0341) (http://www.trygfonden.dk/Om-TrygFonden/In-English), and Lundbeck Foundation (j. nr. R54-A5843) (http://www.lundbeck.com/global/corporate-responsib/stakeholders/the-lun dbeck-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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Previous linkage studies, genome-wide association studies, controlled expression analyses and animal models support an association with both schizophrenia and autism spectrum disorders, both of which share a substantial portion of genetic risks. Methods: We sequenced the protein-encoding areas of the PTPRA gene for single nucleotide polymorphisms or small insertions/deletions (InDel) in 382 schizophrenia patients. To validate their association with the disorders, rare (minor allele frequency, <1%), missense mutations as well as one InDel in the 39UTR region were then genotyped in another independent sample set comprising 944 schizophrenia patients, 336 autism spectrum disorders patients, and 912 healthy controls. Results: Eight rare mutations, including 3 novel variants, were identified during the mutation-screening phase. In the following association analysis, L59P, one of the two missense mutations, was only observed among patients of schizophrenia. Additionally, a novel duplication in the 3'UTR region, 174620_174623dupTGAT, was predicted to be located within a Musashi Binding Element. Major Conclusions: No evidence was seen for the association of rare, missense mutations in the PTPRA gene with schizophrenia or autism spectrum disorders; however, we did find some rare variants with possibly damaging effects that may increase the susceptibility of carriers to the disorders. C1 [Xing, Jingrui; Wang, Chenyao; Kimura, Hiroki; Takasaki, Yuto; Kunimoto, Shohko; Yoshimi, Akira; Nakamura, Yukako; Koide, Takayoshi; Banno, Masahiro; Kushima, Itaru; Uno, Yota; Okada, Takashi; Aleksic, Branko; Ozaki, Norio] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan. [Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. RP Aleksic, B (reprint author), Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan. EM branko@med.nagoya-u.ac.jp RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labor and Welfare of Japan; Ministry of Education, Science, Sports and Culture of Japan FX Funding for this study was provided by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan; Grant-in-Aid for "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; Grant-in-Aid for Scientific Research on Innovative Areas, "Glial assembly: a new regulatory machinery of brain function and disorders''; and Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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CA DDD Study Homozygosity Mapping Collaborative UK10K Consortium Autism Sequencing Consortium TI Synaptic, transcriptional and chromatin genes disrupted in autism SO NATURE LA English DT Article ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; SPECTRUM DISORDERS; NEURODEVELOPMENTAL DISORDERS; FRAMEWORK; NETWORK; RISK; SCHIZOPHRENIA; EXPRESSION; DISCOVERY AB The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones. C1 [De Rubeis, Silvia; Goldberg, Arthur P.; Poultney, Christopher S.; Kou, Yan; Fu, Shih-Chen; Brownfeld, Jessica M.; Cai, Jinlu; Kolevzon, Alexander; Reichenberg, Abraham; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [De Rubeis, Silvia; Goldberg, Arthur P.; Poultney, Christopher S.; Kou, Yan; Fromer, Menachem; Fu, Shih-Chen; Brownfeld, Jessica M.; Cai, Jinlu; Kolevzon, Alexander; Purcell, Shaun; Reichenberg, Abraham; Skiar, Pamela; Buxbaum, Joseph D.] Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. [He, Xin; Cicek, A. Ercument; Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Goldberg, Arthur P.; Fromer, Menachem; Skiar, Pamela; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Samocha, Kaitlin; Fromer, Menachem; Kosmicki, Jack; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Liu, Li; Lei, Jing; Schafer, Chad; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Walker, Susan; Marshall, Christian R.; Rajagopalan, Deepthi; Tammimies, Kristiina; Yuen, Ryan K. C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Program Genet & Genome Biol, Toronto, ON M5G 0A4, Canada. [Singh, Tarjinder; Crooks, Lucy; Rehnstrom, Karola; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Aleksic, Branko; Ozaki, Norio; UK10K Consortium] Nagoya Univ, Sch Med, Dept Psychiat, Nagoya, Aichi 4668550, Japan. [Biscaldi, Monica] Univ Med Ctr Freiburg, Dept Child & Adolescent Psychiat Psychotherapy &, D-79106 Freiburg, Germany. [Biscaldi, Monica] Ctr Mental Disorders, D-79106 Freiburg, Germany. [Bolton, Patrick F.; Curran, Sarah R.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child Psychiat, London SE5 8AF, England. [Bolton, Patrick F.; Curran, Sarah R.] Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London SE5 8AF, England. [Campbell, Nicholas G.; Crawford, Emily L.; Sutcliffe, James S.] Vanderbilt Univ, Sch Med, Vanderbilt Brain Inst, Nashville, TN 37212 USA. [Campbell, Nicholas G.; Crawford, Emily L.; Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. [Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Santiago De Compostela 15706, Spain. [Carracedo, Angel] Galician Fdn Genom Med SERGAS, Santiago De Compostela 15706, Spain. [Carracedo, Angel] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia. [Chahrour, Maria H.; Hill, R. Sean; Yu, Timothy W.; Walsh, Christopher A.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chahrour, Maria H.; Hill, R. Sean; Yu, Timothy W.; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Chiocchetti, Andreas G.; Duketis, Eftichia; Sachse, Michael; Freitag, Christine M.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Coon, Hilary] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. [Coon, Hilary] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA. [Dawson, Geraldine] Duke Univ, Duke Inst Brain Sci, Durham, NC 27708 USA. [Fernandez, Bridget A.] Mem Univ Newfoundland, Disciplines Genet & Med, St John, NF A1B 3V6, Canada. [Gallagher, Louise; Gill, Michael] Trin Coll Dublin, Sch Med, Dept Psychiat, Dublin 8, Ireland. [Geller, Evan; Lin, Chiao-Feng; Valladares, Otto; Wang, Li-San; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Guter, Stephen J.; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. [Ionita-Laza, Iuliana] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Gonzalez, Patricia Jimenez] Hosp Nacl de Ninos Dr Saenz Herrera, CCSS, Child Dev & Behav Unit, San Jose, Costa Rica. [Kilpinen, Helena] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. [Klauck, Sabine M.] German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany. [Kolevzon, Alexander] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Lee, Irene; Skuse, David] UCL, Inst Child Hlth, London WC1N 1EH, England. [Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, SF-33100 Tampere, Finland. [Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [McInnes, Alison L.] Kaiser Permanente, Dept Psychiat, San Francisco, CA 94118 USA. [Neale, Benjamin; Stevens, Christine; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Owen, Michael J.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales. [Owen, Michael J.] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF24 4HQ, S Glam, Wales. [Parellada, Mara] Univ Complutense, Hosp Gen Univ Gregorio Maranon, Child & Adolescent Psychiat Dept, IiSGM,CIBERSAM, E-28040 Madrid, Spain. [Parr, Jeremy R.] Newcastle Univ, Sch Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Puura, Kaija] Tampere Univ, Dept Child Psychiat, Tampere 33521, Finland. [Puura, Kaija] Tampere Univ Hosp, Tampere 33521, Finland. [Reichenberg, Abraham] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Sabo, Aniko] Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA. [Sanders, Stephan J.; Weiss, Lauren A.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Schulte-Ruether, Martin] Univ Hosp RWTH Aachen, JARA Brain Translat Med, Translat Brain Med Psychiat & Neurol, Dept Child & Adolescent Psychiat Psychosomat Psyc, D-52056 Aachen, Germany. [Skuse, David] Great Ormond St Hosp Sick Children, Natl Hlth Serv Fdn Trust, Dept Child & Adolescent Mental Hlth, London WC1N 3JH, England. [Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Offord Ctr Child Studies, Hamilton, ON L8S 4K1, Canada. [Voran, Annette] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, D-66424 Homburg, Germany. [Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Lehner, Thomas] NIMH, NIH, Bethesda, MD 20892 USA. [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FI-00014 Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Skiar, Pamela; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Zwick, Michael E.; Cutler, David J.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, 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 mjdaly@broadinstitute.org; joseph.buxbaum@mssm.edu RI Scherer, Stephen /B-3785-2013; Yuen, Ryan/J-4876-2012; Aleksic, Branko/G-1540-2011; Breen, Gerome/A-5540-2010; Ozaki, Norio/M-8908-2014; Sutcliffe, James/C-1348-2012; Liu, Li/G-1897-2015 OI Scherer, Stephen /0000-0002-8326-1999; Aleksic, Branko/0000-0001-8982-4580; Breen, Gerome/0000-0003-2053-1792; Ozaki, Norio/0000-0002-7360-4898; Sutcliffe, James/0000-0001-5200-6007; FU National Institutes of Health (NIH) [U01MH100233, U01MH100209, U01MH100229, U01MH100239]; NIH grants [R01MH089208, U54 HG003067]; NIH [R01 MH089482, R37 MH057881, R01 MH061009, UL1TR000445, P50 HD055751, MH089482, NIH RO1 MH083565, RC2MH089952, NIMH MH095034, MH077139, 5UL1 RR024975, P30 HD15052]; Charles and Ann Schlaifer Memorial Fund; UK National Institute for Health Research (NIHR) Senior Investigator award; NIHR Biomedical Research Centre in Mental Health at the South London&Maudsley Hospital; Maria Jose Jove Foundation; Strategic Action from Health Carlos III Institute (FEDER) [FIS PI13/01136]; [HICF-1009-003]; [WT098051]; [WT091310] FX This work was supported by National Institutes of Health (NIH) grants U01MH100233, U01MH100209, U01MH100229 and U01MH100239 to the Autism Sequencing Consortium. Sequencing at Broad Institute was supported by NIH grants R01MH089208 (M.J.D.) and new sequencing by U54 HG003067 (S. Gabriel, E. Lander). Other funding includes NIH R01 MH089482, R37 MH057881 (B. D. and K. R.), R01 MH061009 (J.S.S.), UL1TR000445 (NCAT to VUMC); P50 HD055751 (E. H. C.); MH089482 (J.S.S.), NIH RO1 MH083565 and RC2MH089952 (C. A. W.), NIMH MH095034 (P. S), MH077139 (P.F. Sullivan); 5UL1 RR024975 and P30 HD15052. The DDD Study is funded by HICF-1009-003 and WT098051. UK10K is funded by WT091310. We also acknowledge The National Children's Research Foundation, Our Lady's Children's Hospital, Crumlin; The Meath Foundation; AMNCH, Tallaght; The Health Research Board, Ireland and Autism Speaks, U. S. A. C. A. W. is an Investigator of the Howard Hughes Medical Institute. S.D.R., A.P.G., C.S.P., Y.K. and S.-C.F. are Seaver fellows, supported by the Seaver foundation. A. P. G. is also supported by the Charles and Ann Schlaifer Memorial Fund. P. F. B. is supported by a UK National Institute for Health Research (NIHR) Senior Investigator award and the NIHR Biomedical Research Centre in Mental Health at the South London&Maudsley Hospital. A. C. is supported by Maria Jose Jove Foundation and the grant FIS PI13/01136 of the Strategic Action from Health Carlos III Institute (FEDER). This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. We acknowledge the assistance of D. Hall and his team at National Database for Autism Research. We thank Jian Feng for providing a list of targets of both RBFOX1 and H3K4me3. We thank M. Potter for data coordination; K. Moore and J. Reichert for technical assistance; and, S. Lindsay for helping with molecular validation. We acknowledge the clinicians and organizations that contributed to samples used in this study. Finally, we are grateful to the many families whose participation made this study possible. 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Wigler, Michael TI The contribution of de novo coding mutations to autism spectrum disorder SO NATURE LA English DT Article ID COPY-NUMBER VARIATION; INTELLECTUAL DISABILITY; STRUCTURAL VARIATION; INHERITED DISEASE; PATERNAL AGE; SCHIZOPHRENIA; NETWORK; RISK; EVOLUTION; RESOURCE AB Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females. C1 [Iossifov, Ivan; Ronemus, Michael; Levy, Dan; Yamrom, Boris; Lee, Yoon-ha; Grabowska, Ewa; Dalkic, Ertugrul; Wang, Zihua; Marks, Steven; Andrews, Peter; Leotta, Anthony; Kendall, Jude; Hakker, Inessa; Rosenbaum, Julie; Ma, Beicong; Rodgers, Linda; Troge, Jennifer; Narzisi, Giuseppe; Yoon, Seungtai; Schatz, Michael C.; McCombie, W. Richard; Wigler, Michael] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [O'Roak, Brian J.; Krumm, Niklas; Stessman, Holly A.; Witherspoon, Kali T.; Vives, Laura; Patterson, Karynne E.; Smith, Joshua D.; Paeper, Bryan; Nickerson, Deborah A.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [O'Roak, Brian J.] Oregon Hlth & Sci Univ, Portland, OR 97208 USA. [Sanders, Stephan J.; Dea, Jeanselle; Mandell, Jeffrey D.; Walker, Michael F.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. [Sanders, Stephan J.; Dong, Shan; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Dong, Shan; Wei, Liping] Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. [Gonzalez, Luis E.; Murtha, Michael T.; Sullivan, Catherine A.; Waqar, Zainulabedin; State, Matthew W.] Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA. [Mane, Shrikant M.] Yale Univ, Ctr Child Study, Yale Ctr Genom Anal, New Haven, CT 06520 USA. [Wei, Liping] Natl Inst Biol Sci, Beijing 102206, Peoples R China. [Grabowska, Ewa; Narzisi, Giuseppe] New York Genome Ctr, New York, NY 10013 USA. [Dalkic, Ertugrul] Bulent Ecevit Univ, Sch Med, Dept Med Biol, TR-67600 Zonguldak, Turkey. [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA. [State, Matthew W.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. RP Shendure, J (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM shendure@uw.edu; eee@gs.washington.edu; matthew.state@ucsf.edu; wigler@cshl.edu FU Simons Foundation Autism Research Initiative grants [SF191889, M144095 R11154, SF235988]; Howard Hughes Medical Institute (International Student Research Fellowship); Canadian Institutes of Health Research (Doctoral Foreign Study Award); NHLBI [HL-102923, HL-102924, HL-102925, HL-102926, HL-103010] FX Simons Foundation Autism Research Initiative grants to E.E.E. (SF191889), M.W.S. (M144095 R11154) and M.W. (SF235988) supported this work. Additional support was provided by the Howard Hughes Medical Institute (International Student Research Fellowship to S.J.S.) and the Canadian Institutes of Health Research (Doctoral Foreign Study Award to A.J.W.). E.E.E. is an Investigator of the Howard Hughes Medical Institute. We thank all the families at the participating SSC sites, as well as the principal investigators (A. L. Beaudet, R. Bernier, J. Constantino, E. H. Cook Jr, E. Fombonne, D. Geschwind, D. E. Grice, A. Klin, D. H. Ledbetter, C. Lord, C. L. Martin, D. M. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. W. State, W. Stone, J. S. Sutcliffe, C. A. Walsh and E. Wijsman) and the coordinators and staff at the SSC sites for the recruitment and comprehensive assessment of simplex families; the SFARI staff for facilitating access to the SSC; and the Rutgers University Cell and DNA Repository (RUCDR) for accessing biomaterials. We would also like to thank the CSHL Woodbury Sequencing Center, the Genome Institute at the Washington University School of Medicine, and Yale Center for Genomic Analysis (in particular J. Overton) for generating sequencing data; E. Antoniou and E. Ghiban for their assistance in data production at CSHL; and T. Brooks-Boone, N. Wright-Davis and M. Wojciechowski for their help in administering the project at Yale. The NHLBI GO Exome Sequencing Project and its ongoing studies produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). 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Sauls, Bethany L. Morales, Anna A. Kilgard, Michael P. Ploski, Jonathan E. TI Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE autism; learning; memory; valproic acid; amygdala; emotion; Pavlovian fear conditioning ID PRIMARY AUDITORY-CORTEX; FRAGILE-X-SYNDROME; PRENATAL EXPOSURE; SPECTRUM DISORDERS; ANIMAL-MODEL; HISTONE DEACETYLASES; ANTIEPILEPTIC DRUGS; SYNAPTIC PLASTICITY; GENE-EXPRESSION; SOCIAL-BEHAVIOR AB Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning. 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PD NOV 12 PY 2014 VL 8 DI 10.3389/fnbeh.2014.00387 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AZ0HD UT WOS:000347925800001 PM 25429264 ER PT J AU Zhou, WZ Ye, AY Sun, ZK Tian, HH Pu, TZ Wu, YY Wang, DD Zhao, MZ Lu, SJ Yang, CH Wei, LP AF Zhou, Wei-Zhen Ye, Adam Yongxin Sun, Zhong-Kai Tian, Hope Huiping Pu, Tad Zhengzhang Wu, Yu-Yu Wang, Dan-Dan Zhao, Ming-Zhen Lu, Shu-Juan Yang, Chang-Hong Wei, Liping TI Statistical analysis of twenty years (1993 to 2012) of data from mainland China's first intervention center for children with autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Diagnosis; Intervention; Parental age; China ID PERINATAL RISK-FACTORS; REPUBLIC-OF-CHINA; PARENTAL AGE; PATERNAL AGE; INFANTILE-AUTISM; DIAGNOSIS; IDENTIFICATION; POPULATION; PROVISION; SERVICE AB Background: Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and interaction, and restrictive and repetitive patterns of behavior, interests or activities. This study aimed to analyze trends in ASD diagnosis and intervention in 20 years of data from the Beijing Stars and Rain Education Institute for Autism (SR), the first autism intervention center in mainland China, and from a recent survey of members of the Heart Alliance, an industry association of autism intervention centers in China. Methods: We analyzed the registration data at the SR from 1993 to 2012 for a total of 2,222 children who had a parent-reported diagnosis of ASD and 612 of 'autistic tendencies'. Most of the children who were the primary focus of our analyses were age six and under. We also analyzed results of a survey we conducted in 2013 of 100 member centers of the Heart Alliance. Generalized Estimating Equations, multiple linear regression and the Mann-Whitney test were used for data analysis. Statistically significant findings are reported here. Results: The number of hospitals where SR children received their diagnosis increased from several in the early 1990s to 276 at present. The proportion of 'autistic tendencies' diagnosis increased 2.04-fold from 1998 to 2012 and was higher for children diagnosed at a younger age. The mean age at first diagnosis of ASD or 'autistic tendencies' decreased by 0.27 years every decade. A higher level of parental education was statistically significantly associated with an earlier diagnosis of the child. The mean parental age at childbirth increased by about 1.48 years per decade, and the mean maternal age was 1.40 and 2.10 years higher than that in the national population censuses of 2000 and 2010, respectively. At the time of the survey 3,957 children with ASD were being trained at the 100 autism intervention centers. Ninety-seven of these centers opened after the year 2000. Economically underdeveloped regions are still underserved. Conclusions: This study revealed encouraging trends and remaining challenges in ASD diagnosis and intervention among children at the SR over the past 20 years and the 100 autism intervention centers in China at present. C1 [Zhou, Wei-Zhen; Lu, Shu-Juan; Wei, Liping] Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. [Ye, Adam Yongxin; Wang, Dan-Dan; Zhao, Ming-Zhen; Yang, Chang-Hong; Wei, Liping] Natl Inst Biol Sci, Beijing 102206, Peoples R China. [Sun, Zhong-Kai; Tian, Hope Huiping] Beijing Stars & Rain Educ Inst Autism, Beijing 100121, Peoples R China. [Pu, Tad Zhengzhang] Shanghai Pkwy Hlth, Shanghai 201206, Peoples R China. [Wu, Yu-Yu] Yuning Psychiat Clin, Taipei 10664, Taiwan. RP Wei, LP (reprint author), Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. EM weilp@mail.cbi.pku.edu.cn FU Natural Science Foundation of China [31025014]; Ministry of Science and Technology of China [2012CB837600] FX The authors thank Drs. Yu Shyr, Jinzhu Jia and Xianjin Xie for their suggestions on statistical analysis. This work was supported by Natural Science Foundation of China (No. 31025014) and Ministry of Science and Technology of China (No. 2012CB837600). The funders had no role in study design, data collection, data analysis, manuscript preparation or publication decisions. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th American Psychiatric Association, 2013, DIAGN STAT MAN MENT [Anonymous], 2010, 6 NATL CENSUS DATA [Anonymous], 2003, RES PRACT PERS SEVER, V28, P16 [Anonymous], 2000, 5 NATL CENSUS DATA Blumberg SJ, 2013, NATL HLTH STAT REPOR, V1-11 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 CDC (Cent. Dis. 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C1 [Xu, Junyu; Kam, Chuen; Xia, Jun] Hong Kong Univ Sci & Technol, Div Biomed Engn, Div Life Sci, Kowloon 100044, Hong Kong, Peoples R China. [Xu, Junyu; Kam, Chuen; Xia, Jun] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Kowloon 100044, Hong Kong, Peoples R China. [Xu, Junyu; Luo, Jian-hong] Zhejiang Univ, Sch Med, Minist Hlth,Dept Neurobiol, Zhejiang Prov Key Lab Neurobiol,Key Lab Med Neuro, Hangzhou 310058, Zhejiang, Peoples R China. RP Xia, J (reprint author), Hong Kong Univ Sci & Technol, Div Biomed Engn, Div Life Sci, Kowloon 100044, Hong Kong, Peoples R China. EM jxia@ust.hk FU Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China [663310, 663613, HKUST10/CRF/12R, CUHK2/CRF/11G, T13-607/12R, AoE/M-05/12]; National Natural Science Foundation of China [91232303, 81201008]; National Key Basic Research Program of China [2013CB530900, 2010CB912002]; Zhejiang Provincial Natural Science Foundation of China [LY12C09001] FX This work was supported in part by the Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China (Grants 663310, 663613, HKUST10/CRF/12R, CUHK2/CRF/11G, T13-607/12R, and AoE/M-05/12), the National Natural Science Foundation of China (Grants 91232303 and 81201008), the National Key Basic Research Program of China (Grants 2013CB530900 and 2010CB912002), and the Zhejiang Provincial Natural Science Foundation of China (Grants LY12C09001). We thank W. Tung, C. He, and P. Ieong for their technical assistance; Dr. Ann M. Craig (University of British Columbia, Vancouver, BC, Canada) for providing the CFP-tagged neurexin1 beta and YFP-tagged neuroligin1 constructs; and Dr. D. Chang (The Hong Kong University of Science and Technology) for providing the pECFPC3 vector. 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While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. C1 [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress, Dept Med, Los Angeles, CA 90095 USA. [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Mayer, Emeran A.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biobehav Sci, Div Digest Dis, Los Angeles, CA 90095 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA. [Mazmanian, Sarkis K.] CALTECH, Dept Biol & Biol Engn, Pasadena, CA 91125 USA. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Dept Anat & Neurosci, Cork, Ireland. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland. [Tillisch, Kirsten] Vet Adm Greater Los Angeles Healthcare Syst, Div Integrat Med, Dept Med, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, CHS 42-210,MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant [R01 DK048351, P30 DK041301]; National Institutes of Health/National Institute of Mental Health Grant [R01 MH100556]; Simons Foundation SFARI Program; Howard Hughes Medical Institute; Autism Speaks FX This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK048351 to E. A. M., Grant P30 DK041301, National Institutes of Health/National Institute of Mental Health Grant R01 MH100556 to S. K. M., Autism Speaks to S. K. M., Simons Foundation SFARI Program to S. K. M., and Howard Hughes Medical Institute to R. K. 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Neurosci. PD NOV 12 PY 2014 VL 34 IS 46 BP 15490 EP 15496 DI 10.1523/JNEUROSCI.3299-14.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AT9AU UT WOS:000345220900037 PM 25392516 ER PT J AU Biagi, E Candela, M Centanni, M Consolandi, C Rampelli, S Turroni, S Severgnini, M Peano, C Ghezzo, A Scurti, M Salvioli, S Franceschi, C Brigidi, P AF Biagi, Elena Candela, Marco Centanni, Manuela Consolandi, Clarissa Rampelli, Simone Turroni, Silvia Severgnini, Marco Peano, Clelia Ghezzo, Alessandro Scurti, Maria Salvioli, Stefano Franceschi, Claudio Brigidi, Patrizia TI Gut Microbiome in Down Syndrome SO PLOS ONE LA English DT Article ID ABERRANT BEHAVIOR CHECKLIST; AUTISM SPECTRUM DISORDER; PHYLOGENETIC MICROARRAY; CHILDREN; PERSPECTIVES; LONGEVITY; BACTERIA AB Background: Premature aging seriously compromises the health status of Down Syndrome (DS) persons. Since human aging has been associated with a deterioration of the gut microbiota (GM)-host mutualism, here we investigated the composition of GM in DS. Methods: The observational study presented involved 17 adult DS persons. We characterized the GM structure by 454 pyrosequencing of the V4 region of the 16S rRNA gene. DS microbiome was compared with that of age-matched healthy non-trisomic adults enrolled in the same geographic area. Results and Conclusions: The dominant GM fraction of DS persons showed an overall mutualistic immune-modulatory layout, comparable to that of healthy controls. This makes GM a possible factor counteracting the genetic determined acceleration of immune senescence in DS persons. However, we also found detectable signatures specific for DS among subdominant GM components, such as the increase of Parasporobacterium and Sutterella. In particular, the abundance of this last microorganism significantly correlated with the Aberrant Behavior Checklist (ABC) total score, allowing us to hypothesize a possible role for this microbial genus in behavioral features in DS. C1 [Biagi, Elena; Candela, Marco; Centanni, Manuela; Rampelli, Simone; Turroni, Silvia; Brigidi, Patrizia] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. [Consolandi, Clarissa; Severgnini, Marco; Peano, Clelia] Italian Natl Res Council, Inst Biomed Technol, Milan, Italy. [Ghezzo, Alessandro; Scurti, Maria; Salvioli, Stefano; Franceschi, Claudio] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy. [Scurti, Maria; Salvioli, Stefano; Franceschi, Claudio] Univ Bologna, Interdept Ctr L Galvani CIG, Bologna, Italy. RP Candela, M (reprint author), Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. EM marco.candela@unibo.it FU European Union's Seventh Framework Programme (FP7) (IDEAL) [259679]; Italian Ministry of Health, Progetto Ricerca Finalizzata FX The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement n. 259679 (IDEAL), and the Italian Ministry of Health, Progetto Ricerca Finalizzata 2008, convenzione 35: ''An integrated approach to identify functional, biochemical and genetic markers for diagnostic and prognostic purposes in the elderly, in the centenarians and in people with dementia, Alzheimer's disease, mild cognitive impairment'' to CF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CR Adams J. 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Sperry, Jantzen Ngo, Amy Ghochani, Yasmin Laks, Dan R. Lopez-Aranda, Manuel Silva, Alcino J. Kornblum, Harley I. TI Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells SO STEM CELL REPORTS LA English DT Article ID SPECTRUM DISORDERS; SELF-RENEWAL; CHILDREN; NEUROGENESIS; INFECTION; REVEALS; NUMBER; CORTEX; LEADS AB A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. C1 [Le Belle, Janel E.; Ngo, Amy; Laks, Dan R.; Lopez-Aranda, Manuel; Silva, Alcino J.; Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, NPI Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Le Belle, Janel E.; Ngo, Amy; Laks, Dan R.; Lopez-Aranda, Manuel; Silva, Alcino J.; Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sperry, Jantzen; Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Ghochani, Yasmin; Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. [Laks, Dan R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Lopez-Aranda, Manuel; Silva, Alcino J.] Univ Calif Los Angeles, David Geffen Sch Med, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA. [Lopez-Aranda, Manuel; Silva, Alcino J.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Kornblum, Harley I.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Kornblum, HI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, NPI Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. EM harley@ucla.edu FU Miriam and Sheldon G. Adelson Medical Research Foundation; Cure Autism Now Fellowship; Autism Speaks Basic and Clinical grant; Autism Speaks Environmental Sciences grant; Center for Autism Research and Treatment (CART) Pilot Grant [06LEB2008]; NIH [MH65756, CA-16042, AI-28697]; JCCC; UCLA AIDS Institute; David Geffen School of Medicine at UCLA; UCLA Chancellor's Office; NIH/NICHD [P50-HD-055784] FX This work was supported by the following grants and awards: Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to H.I.K.); Cure Autism Now Fellowship (to J.E.L.); Autism Speaks Basic and Clinical grant (to H.I.K.); Autism Speaks Environmental Sciences grant (to J.E.L.); Center for Autism Research and Treatment (CART) Pilot Grant Award #06LEB2008, which is supported by NIH/NICHD grant P50-HD-055784 (to J.E.L.); and NIH grant MH65756 (to H.I.K.). Flow cytometry and cell sorting was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and the Center for AIDS Research Flow Cytometry Core Facility, which is supported by NIH awards CA-16042 and AI-28697, the JCCC, the UCLA AIDS Institute, the David Geffen School of Medicine at UCLA, and the UCLA Chancellor's Office. 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PD NOV 11 PY 2014 VL 3 IS 5 BP 725 EP 734 DI 10.1016/j.stemcr.2014.09.004 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AT7LP UT WOS:000345118600005 PM 25418720 ER PT J AU Dinalankara, DMR Miles, JH Yao, G AF Dinalankara, Dinalankara M. R. Miles, Judith H. Yao, Gang TI rPLR: an imaging system for measuring pupillary light reflex at a distance SO APPLIED OPTICS LA English DT Article ID DYNAMIC PUPILLOMETRY; PARKINSONS-DISEASE; ALZHEIMERS; CHILDREN; AUTISM; HEAD; SIZE AB Pupillary light reflex (PLR) is a simple noninvasive neurological test that can reveal a great amount of information of the neural system. We report here a novel imaging system for measuring PLR without using any restraints to limit the subject's movement. Our system incorporates a tracking component that can locate the subject's eye position and redirect the pupillary imaging component to follow the subject's movement. This system can measure PLR, at a distance from the subject, with high spatial resolution (<50 mu m) and temporal resolution (120 Hz). Because this new PLR device can accommodate the subject's movement, it is well positioned to test in young children and other people who have difficulty remaining voluntarily still during tests. (C) 2014 Optical Society of America C1 [Dinalankara, Dinalankara M. R.; Yao, Gang] Univ Missouri, Dept Bioengn, Columbia, MO 65211 USA. [Miles, Judith H.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO 65211 USA. RP Yao, G (reprint author), Univ Missouri, Dept Bioengn, Columbia, MO 65211 USA. EM yaog@missouri.edu RI yao, gang/E-8025-2015 OI yao, gang/0000-0002-2763-8667 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [R21-HD075971]; Coulter Translational Partnership at University of Missouri FX s This work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under grant R21-HD075971, and the Coulter Translational Partnership at University of Missouri. CR Ashburner J, 2008, AM J OCCUP THER, V62, P564 Barbur J. L., 2004, THE VISUAL NEUROSCIE, V2, P641 Barbur J. 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Optics PD NOV 10 PY 2014 VL 53 IS 32 BP 7787 EP 7795 DI 10.1364/AO.53.007787 PG 9 WC Optics SC Optics GA AT7GF UT WOS:000345104100026 PM 25403005 ER PT J AU Orekhova, EV Elsabbagh, M Jones, EJH Dawson, G Charman, T Johnson, MH AF Orekhova, Elena V. Elsabbagh, Mayada Jones, Emily J. H. Dawson, Geraldine Charman, Tony Johnson, Mark H. CA BASIS Team TI EEG hyper-connectivity in high-risk infants is associated with later autism SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; EEG; Connectivity; Alpha; Infants; Siblings ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDER; WHITE-MATTER; BRAIN CONNECTIVITY; CINGULATE CORTEX; FRONTAL-CORTEX; YOUNG-CHILDREN; ALPHA-ACTIVITY; COHERENCE; NETWORKS AB Background: It has been previously reported that structural and functional brain connectivity in individuals with autism spectrum disorders (ASD) is atypical and may vary with age. However, to date, no measures of functional connectivity measured within the first 2 years have specifically associated with a later ASD diagnosis. Methods: In the present study, we analyzed functional brain connectivity in 14-month-old infants at high and low familial risk for ASD using electroencephalography (EEG). EEG was recorded while infants attended to videos. Connectivity was assessed using debiased weighted phase lag index (dbWPLI). At 36 months, the high-risk infants were assessed for symptoms of ASD. Results: As a group, high-risk infants who were later diagnosed with ASD demonstrated elevated phase-lagged alpha-range connectivity as compared to both low-risk infants and high-risk infants who did not go on to ASD. Hyper-connectivity was most prominent over frontal and central areas. The degree of hyper-connectivity at 14 months strongly correlated with the severity of restricted and repetitive behaviors in participants with ASD at 3 years. These effects were not attributable to differences in behavior during the EEG session or to differences in spectral power. Conclusions: The results suggest that early hyper-connectivity in the alpha frequency range is an important feature of the ASD neurophysiological phenotype. C1 [Orekhova, Elena V.; Jones, Emily J. H.; Johnson, Mark H.] Univ London, Sch Psychol, Ctr Brain & Cognit Dev, London WC1E 7HX, England. [Elsabbagh, Mayada] McGill Univ, Dept Psychiat, Montreal, PQ H3A 1A1, Canada. [Dawson, Geraldine] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Charman, Tony] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, London SE5 8AF, England. RP Orekhova, EV (reprint author), Univ London, Sch Psychol, Ctr Brain & Cognit Dev, Henry Welcome Bldg, London WC1E 7HX, England. EM orekhova.elena.v@gmail.com FU UK Medical Research Council [G0701484]; Autism Speaks [1292]; BASIS funding consortium led by Autistica; EU-AIMS, the Innovative Medicines Initiative Joint Undertaking [115300]; European Union FX We are very grateful for the enormous contributions BASIS families have made towards this study. This work was supported by the UK Medical Research Council (G0701484), Autism Speaks (#1292), the BASIS funding consortium led by Autistica (www.basisnetwork.org), and EU-AIMS, 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) and EFPIA companies' in-kind contribution. 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Neurodev. Disord. PD NOV 7 PY 2014 VL 6 AR 40 DI 10.1186/1866-1955-6-40 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW1DX UT WOS:000346031800001 PM 25400705 ER PT J AU Bambini, V Zanatta, G Nunes, GD de Melo, GM Michels, M Fontes-Dutra, M Freire, VN Riesgo, R Gottfried, C AF Bambini-Junior, Victorio Zanatta, Geancarlo Nunes, Gustavo Della Flora de Melo, Gabriela Mueller Michels, Marcus Fontes-Dutra, Mellanie Freire, Valder Nogueira Riesgo, Rudimar Gottfried, Carmem TI Resveratrol prevents social deficits in animal model of autism induced by valproic acid SO NEUROSCIENCE LETTERS LA English DT Article DE Autism spectrum disorder; Valproate; Resveratrol; Animal model; Behavior ID SPECTRUM DISORDERS; PRENATAL EXPOSURE; PHYSIOLOGY; BEHAVIOR AB Autism spectrum disorders (ASD) involve a complex interplay of both genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). Considering the neuroprotective, antioxidant and anti-inflammatory effects of resveratrol (RSV), we investigated the influence of prenatal RSV treatment on social behaviors of a rodent model of autism induced by prenatal exposure to VPA. In the three-chambered apparatus test, the VPA group showed a reduced place preference conditioned by conspecific and no preference between exploring a wire-cage or a rat enclosed inside a wire cage, revealing sociability impairments. Prenatal administration of RSV prevented the VPA-induced social impairments evaluated in this study. A bioinformatics analysis was used to discard possible molecular interactions between VPA and RSV during administration. The interaction energy between RSV and VPA is weak and highly unstable, suggesting cellular effects instead of a single chemical process. In summary, the present study highlights a promising experimental strategy to evaluate new molecular targets possibly involved in the etiology of autism and developmental alterations implicated in neural and behavioral impairments in ASD. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Bambini-Junior, Victorio; Zanatta, Geancarlo; Nunes, Gustavo Della Flora; de Melo, Gabriela Mueller; Michels, Marcus; Fontes-Dutra, Mellanie; Gottfried, Carmem] Univ Fed Rio Grande do Sul, Inst Hlth Basic Sci, Res Grp Neuroglial Plast, Dept Biochem, BR-90035003 Porto Alegre, RS, Brazil. [Bambini-Junior, Victorio; Zanatta, Geancarlo; Nunes, Gustavo Della Flora; de Melo, Gabriela Mueller; Michels, Marcus; Fontes-Dutra, Mellanie; Riesgo, Rudimar; Gottfried, Carmem] Univ Fed Rio Grande do Sul, Translat Res Grp Autism Spectrum Disorders GETTA, BR-90035003 Porto Alegre, RS, Brazil. [Riesgo, Rudimar] Univ Fed Rio Grande do Sul, Child Neurol Unit, HCPA, Clin Hosp Porto Alegre, BR-90035003 Porto Alegre, RS, Brazil. [Freire, Valder Nogueira] Univ Fed Ceara, Dept Phys, Fortaleza, Ceara, Brazil. RP Bambini, V (reprint author), Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, Rua Ramiro Barcelos 2600 Anexo, BR-90035003 Porto Alegre, RS, Brazil. EM victoriobambini@gmail.com FU National Counsel of Technological and Scientific Development (CNPq); Coordination for the Improvement of Higher Education Personnel (CAPES); FINEP and INCT-EN National Institute of Science and Technology for Excitotoxicity and Neuroprotection FX This work was supported by the National Counsel of Technological and Scientific Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), FINEP and INCT-EN National Institute of Science and Technology for Excitotoxicity and Neuroprotection. Special thanks to Janine MacKenzie for the careful English review. We would also like to thank Fluxome (Stenlose, Denmark) for the generous gift of resveratrol. 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Lett. PD NOV 7 PY 2014 VL 583 BP 176 EP 181 DI 10.1016/j.neulet.2014.09.039 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AU4TM UT WOS:000345604300033 PM 25263788 ER PT J AU West, PR Amaral, DG Bais, P Smith, AM Egnash, LA Ross, ME Palmer, JA Fontaine, BR Conard, KR Corbett, BA Cezar, GG Donley, ELR Burrier, RE AF West, Paul R. Amaral, David G. Bais, Preeti Smith, Alan M. Egnash, Laura A. Ross, Mark E. Palmer, Jessica A. Fontaine, Burr R. Conard, Kevin R. Corbett, Blythe A. Cezar, Gabriela G. Donley, Elizabeth L. R. Burrier, Robert E. TI Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children SO PLOS ONE LA English DT Article ID OXIDATIVE STRESS; AMINO-ACIDS; MITOCHONDRIAL; ABNORMALITIES; SPECTROMETRY; PERFORMANCE; ALIGNMENT; PROFILES; DATABASE; MARKERS AB Background: The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. Objectives: To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment. Methods: Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD. Results: A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set. Conclusions: This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations. C1 [West, Paul R.; Smith, Alan M.; Egnash, Laura A.; Ross, Mark E.; Palmer, Jessica A.; Fontaine, Burr R.; Conard, Kevin R.; Cezar, Gabriela G.; Donley, Elizabeth L. R.; Burrier, Robert E.] Stemina Biomarker Discovery, Madison, WI 53719 USA. [Amaral, David G.] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Bais, Preeti] Univ Connecticut, Ctr Hlth, Jackson Lab Genom Med, Farmington, CT USA. [Corbett, Blythe A.] Vanderbilt Univ, Dept Psychiat Psychol & Kennedy Ctr, Nashville, TN 37235 USA. RP West, PR (reprint author), Stemina Biomarker Discovery, Madison, WI 53719 USA. EM pwest@stemina.com FU Stemina FX Stemina funded this study. The funder provided support in the form of salaries for authors (PRW, LAE, AMS, MER, JAP, BRF, KRC, GGC, ELRD, and REB), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Yesim Barmada, M. Michael Richardson, Gale A. Lopez, Oscar L. Sweet, Robert A. Kamboh, M. Ilyas Feingold, Eleanor TI A Rare Duplication on Chromosome 16p11.2 Is Identified in Patients with Psychosis in Alzheimer's Disease SO PLOS ONE LA English DT Article ID COPY NUMBER VARIATION; MENTAL-RETARDATION; SEIZURE DISORDER; DOWN-REGULATION; SCHIZOPHRENIA; RISK; MICRODELETION; DELETIONS; AUTISM; ASSOCIATION AB Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis. C1 [Zheng, Xiaojing; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Demirci, F. Yesim; Barmada, M. Michael; Kamboh, M. Ilyas; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Richardson, Gale A.; Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Kamboh, M. Ilyas] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Richardson, Gale A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zheng, Xiaojing] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Zheng, XJ (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. EM xiaojinz@email.unc.edu FU National Institute on Aging [AG030653, AG041718, AG005133, AG027224]; NanoString award; NIMH Grant [T32 MH015169] FX This study was supported by the National Institute on Aging grants AG030653, AG041718 (MIK), AG005133 (OLL), and AG027224 (RAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs or the United States Government. Funding for experimental validation was provided by NanoString award. This work was conducted in partial fulfillment of requirements for the first author's doctoral degree, supported by NIMH Grant T32 MH015169 (G.A.R., Program Director). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices. Results: Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes. Conclusions: Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such that the preferred food choices were switched on when either the mGluR3-AC5 pathway was inactive or the mGluR1 pathway was active, whereas the preferred food-choices were switched off when mGluR1 or its downstream pathway was suppressed. These results identify the AC5 and mGluR system in the dorsal striatum as molecular on/off switches to direct decisions on behavioral preferences for cue-oriented options. C1 [Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Han, Pyung-Lim] Ewha Womans Univ, Dept Brain & Cognit Sci, Seoul 120750, South Korea. [Kim, Kyoung-Shim] Korea Res Inst Biosci & Biotechnol, Lab Anim Ctr, Taejon, South Korea. [Han, Pyung-Lim] Ewha Womans Univ, Brain Dis Res Inst, Seoul 120750, South Korea. [Han, Pyung-Lim] Ewha Womans Univ, Dept Chem & Nano Sci, Seoul 120750, South Korea. RP Han, PL (reprint author), Ewha Womans Univ, Dept Brain & Cognit Sci, 11-1 Daehyun Dong, Seoul 120750, South Korea. EM plhan@ewha.ac.kr FU Ministry of Science, ICT and Future Planning, Republic of Korea [2012R1A2A1A03010177] FX This research was supported by a grant (2012R1A2A1A03010177) from the Ministry of Science, ICT and Future Planning, Republic of Korea. 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TI Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE autism; schizophrenia; birth size; parent-of-origin; genomic imprinting; copy number ID BECKWITH-WIEDEMANN-SYNDROME; SILVER-RUSSELL-SYNDROME; SOCIAL BRAIN; SPECTRUM DISORDERS; NEUROPSYCHIATRIC DISORDERS; MISSING HERITABILITY; LIFE-HISTORY; FETAL-GROWTH; DISEASE; WEIGHT AB Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark's roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean +/- 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory. C1 [Byars, Sean G.; Boomsma, Jacobus J.] Univ Copenhagen, Dept Biol, Ctr Social Evolut, Copenhagen, Denmark. [Stearns, Stephen C.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA. RP Boomsma, JJ (reprint author), Univ Copenhagen, Dept Biol, Ctr Social Evolut, Copenhagen, Denmark. EM sean.byars@unimelb.edu.au; jjboomsma@bio.ku.dk RI Boomsma, Jacobus/M-2785-2014 OI Boomsma, Jacobus/0000-0002-3598-1609 FU Danish National Research Foundation [DNRF57]; Marie Curie International Incoming Fellowship [FP7-PEOPLE-2010-IIF-276565] FX The Centre for Social Evolution and its Evolutionary Medicine programme are funded by the Danish National Research Foundation (DNRF57). S. G. B. was also funded by a Marie Curie International Incoming Fellowship FP7-PEOPLE-2010-IIF-276565. 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R. Soc. B-Biol. Sci. PD NOV 7 PY 2014 VL 281 IS 1794 DI 10.1098/rspb.2014.0604 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA AP2RT UT WOS:000341922700002 PM 25232142 ER PT J AU Brown, JA Sherrod, SD Goodwin, CR Brewer, B Yang, LJ Garbett, KA Li, DY McLean, JA Wikswo, JP Mirnics, K AF Brown, Jacquelyn A. Sherrod, Stacy D. Goodwin, Cody R. Brewer, Bryson Yang, Lijie Garbett, Krassimira A. Li, Deyu McLean, John A. Wikswo, John P. Mirnics, Karoly TI Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE glycerophospholipid; immune activation; interleukin; kynurenine; metabolomics; microfluidics; ultra-performance liquid chromatography; ion mobility; mass spectrometry ID MATERNAL INFLUENZA INFECTION; FETAL-BRAIN DEVELOPMENT; KYNURENINE PATHWAY; ALZHEIMERS-DISEASE; THERAPEUTIC STRATEGY; NEURITE OUTGROWTH; IMMUNE ACTIVATION; BIPOLAR DISORDER; GENE-EXPRESSION; SCHIZOPHRENIA AB Background: Maternal immune activation and subsequent interleukin-6 (IL-6) induction disrupt normal brain development and predispose the offspring to developing autism and schizophrenia. While several proteins have been identified as having some link to these developmental disorders, their prevalence is still small and their causative role, if any, is not well understood. However, understanding the metabolic consequences of environmental predisposing factors could shed light on disorders such as autism and schizophrenia. Methods: To gain a better understanding of the metabolic consequences of IL-6 exposure on developing central nervous system (CNS) cells, we separately exposed developing neuron and astroglia cultures to IL-6 for 2 hours while collecting effluent from our gravity-fed microfluidic chambers. By coupling microfluidic technologies to ultra-performance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS), we were able to characterize the metabolic response of these CNS cells to a narrow window of IL-6 exposure. Results: Our results revealed that 1) the use of this technology, due to its superb media volume: cell volume ratio, is ideally suited for analysis of cell-type-specific exometabolome signatures; 2) developing neurons have low secretory activity at baseline, while astroglia show strong metabolic activity; 3) both neurons and astroglia respond to IL-6 exposure in a cell type-specific fashion; 4) the astroglial response to IL-6 stimulation is predominantly characterized by increased levels of metabolites, while neurons mostly depress their metabolic activity; and 5) disturbances in glycerophospholipid metabolism and tryptophan/kynurenine metabolite secretion are two putative mechanisms by which IL-6 affects the developing nervous system. Conclusions: Our findings are potentially critical for understanding the mechanism by which IL-6 disrupts brain function, and they provide information about the molecular cascade that links maternal immune activation to developmental brain disorders. C1 [Brown, Jacquelyn A.; Garbett, Krassimira A.; Mirnics, Karoly] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37232 USA. [Brown, Jacquelyn A.; Sherrod, Stacy D.; Goodwin, Cody R.; Li, Deyu; McLean, John A.; Wikswo, John P.; Mirnics, Karoly] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Nashville, TN 37235 USA. [Sherrod, Stacy D.; Wikswo, John P.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA. [Goodwin, Cody R.; McLean, John A.] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA. [Brewer, Bryson; Yang, Lijie; Li, Deyu] Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Mirnics, Karoly] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37203 USA. [Mirnics, Karoly] Univ Szeged, Dept Psychiat, H-6725 Szeged, Hungary. RP Wikswo, JP (reprint author), Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, 6809 Stevenson Ctr, Nashville, TN 37235 USA. EM john.wikswo@vanderbilt.edu; karoly.mirnics@vanderbilt.edu RI Li, Deyu/D-2938-2012 OI Li, Deyu/0000-0001-8364-0924 FU National Institutes of Health [R01 MH079299, UH2 TR000491, P30 HD15052]; Vanderbilt University Discovery Grant; Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE); Vanderbilt Institute of Chemical Biology; [2T32MH065215-11] FX This work and the preparation of the manuscript were supported in part by grants from the National Institutes of Health: R01 MH079299 (NIMH) to KM, UH2 TR000491 (NCATS and the NIH Common Fund) to JPW, and P30 HD15052 (NICHD) awarded to the Vanderbilt Kennedy Center for Research on Human Development; JAB is supported by 2T32MH065215-11 (NIMH). A portion of the work was also funded by a Vanderbilt University Discovery Grant to JPW. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies and organizations. The funding agencies and organizations had no role in the design, collection, analysis, and interpretation of data, nor were they involved in the writing of the manuscript and the decision to submit it for publication. We appreciate the support of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) and the Vanderbilt Institute of Chemical Biology, and thank Allison Price of VIIBRE for editing and providing valuable comments on the manuscript. 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Neuroinflamm. PD NOV 6 PY 2014 VL 11 AR 183 DI 10.1186/s12974-014-0183-6 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AW1DI UT WOS:000346030400001 PM 25374324 ER PT J AU Gamazon, ER Cox, NJ Davis, LK AF Gamazon, Eric R. Cox, Nancy J. Davis, Lea K. TI Structural Architecture of SNP Effects on Complex Traits SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY-NUMBER VARIATIONS; DE-NOVO MUTATIONS; GENOME-WIDE ASSOCIATION; GENOTYPING DATA; GENETIC-BASIS; AUTISM; POPULATION; VARIANTS; LOCI; SUSCEPTIBILITY AB Despite the discovery of copy-number variation (CNV) across the genome nearly 10 years ago, current SNP-based analysis methodologies continue to collapse the homozygous (i.e., A/A), hemizygous (i.e., A/0), and duplicative (i.e., A/A/A) genotype states, treating the genotype variable as irreducible or unaltered by other colocalizing forms of genetic (e.g., structural) variation. Our understanding of common, genome-wide CNVs suggests that the canonical genotype construct might belie the enormous complexity of the genome. Here we present multiple analyses of several phenotypes and provide methods supporting a conceptual shift that embraces the structural dimension of genotype. We comprehensively investigate the impact of the structural dimension of genotype on (1) GWAS methods, (2) interpretation of rare LOF variants, (3) characterization of genomic architecture, and (4) implications for snapping loci involved in complex disease. Taken together, these results argue for the inclusion of a structural dimension and suggest that some portion of the "missing" heritability might be recovered through integration of the structural dimension of SNP effects on complex traits. C1 [Gamazon, Eric R.; Cox, Nancy J.; Davis, Lea K.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. RP Davis, LK (reprint author), Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM lea.k.davis@gmail.com FU Conte Center for Computational Neuropsychiatric Genomics [NIH P50MH94267]; National Center for Advancing Translational Sciences of the NIH [KL2TR000431]; [R01 MH090937]; [U01 HG005773]; [P60 DK20595]; [U19 GM61393]; [P50 HD055751] FX L.K.D. wishes to acknowledge posthumously, with deep gratitude and profound thanks, the intellectual contributions to this study provided by George Stephen Karatheodoris whose generous perspective on science is here honored. We wish to thank Dr. Mathew Barber for discussions regarding the statistical analysis described in this manuscript and Dr. Jeffrey MacDonald (The Centre for Applied Genomics) for assistance with specialized DGV data requests. This study makes use of data generated by the Wellcome Trust Case Control Consortium, funding for which was provided by the Wellcome Trust under award 076113. The WTCCC bears no responsibility for the further analysis or interpretation of these data, over and above that published by the Consortium. We acknowledge the International Obsessive-Compulsive Foundation Genetics Consortium (IOCDFGC; Steering Committee: Pino Alonso, Paul Arnold, Helena Brentani, Danielle Cath, Eske Derks, Gregory Hanna, James Knowles, Carol Mathews, Dennis Murphy, Gerry Nestadt, David Pauls, Jeremiah Scharf, Evelyn Stewart, Michael Wagner, Danielle Posthuma, Susanne Walitza, and Yin Yao) and the Tourette Syndrome Association International Consortium for Genetics (TSAICG; Steering Committee: Jeremiah Scharf, Carol Mathews, Benjamin Neale, Nelson Freimer, Nancy Cox, Giovanni Coppola, Danielle Posthuma, David Pauls) for use of the TS and OCD GWAS data. This work was funded in part by the Conte Center for Computational Neuropsychiatric Genomics (NIH P50MH94267). We wish to acknowledge additional support for this study provided by R01 MH090937, U01 HG005773, P60 DK20595, U19 GM61393, P50 HD055751, and the National Center for Advancing Translational Sciences of the NIH under Award Number KL2TR000431 (L.K.D.). 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Bourque, Guillaume Ernst, Carl TI Molecular Convergence of Neurodevelopmental Disorders SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIATION; INTELLECTUAL DISABILITY; DIAGNOSTIC BOUNDARIES; DEVELOPMENTAL DELAY; GENETIC-VARIATION; DNA METHYLATION; HUMAN GENOME; CELLS; COMPLEX AB Neurodevelopmental disorders (NDDs) are caused by mutations in diverse genes involved in different cellular functions, although there can be crosstalk, or convergence, between molecular pathways affected by different NDDs. To assess molecular convergence, we generated human neural progenitor cell models of 9q34 deletion syndrome, caused by haploinsufficiency of EHMT1, and 18q21 deletion syndrome, caused by haploinsufficiency of TCF4. Using next-generation RNA sequencing, methylation sequencing, chromatin immunoprecipitation sequencing, and whole-genome miRNA analysis, we identified several levels of convergence. We found mRNA and miRNA expression patterns that were more characteristic of differentiating cells than of proliferating cells, and we identified CpG clusters that had similar methylation states in both models of reduced gene dosage. There was significant overlap of gene targets of TCF4 and EHMT1, whereby 8.3% of TCF4 gene targets and 4.2% of EHMT1 gene targets were identical. These data suggest that 18q21 and 9q34 deletion syndromes show significant molecular convergence but distinct expression and methylation profiles. Common intersection points might highlight the most salient features of disease and provide avenues for similar treatments for NDDs caused by different genetic mutations. C1 [Chen, Elizabeth S.; Gigek, Carolina O.; Diallo, Alpha B.; Maussion, Gilles; Chen, Gary G.; Vaillancourt, Kathryn; Crapper, Liam; Poujol, Raphael; Ernst, Carl] McGill Univ, Dept Psychiat, Montreal, PQ H4H 1R3, Canada. [Chen, Elizabeth S.; Gigek, Carolina O.; Diallo, Alpha B.; Maussion, Gilles; Chen, Gary G.; Vaillancourt, Kathryn; Lopez, Juan P.; Crapper, Liam; Poujol, Raphael; Ernst, Carl] Douglas Hosp, Res Inst, McGill Grp Suicide Studies, Montreal, PQ H4H 1R3, Canada. [Rosenfeld, Jill A.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA. [Lopez, Juan P.; Bourque, Guillaume; Ernst, Carl] McGill Univ, Dept Human Genet, Montreal, PQ H4H 1R3, Canada. [Shaffer, Lisa G.] Genet Vet Sci Inc, Paw Print Genet, Spokane, WA 99202 USA. [Bourque, Guillaume] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Bourque, Guillaume] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. RP Ernst, C (reprint author), McGill Univ, Dept Psychiat, Montreal, PQ H4H 1R3, Canada. EM carl.ernst@mcgill.ca RI Gigek, Carolina/B-3767-2014; Chen, Elizabeth/G-1598-2012 OI Chen, Elizabeth/0000-0002-3573-0164 FU Scottish Rite Charitable Foundation; Banting Foundation; Canada Research Chairs program; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico scholarship; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; Canadian Institute of Health Research; Fonds de Recherche de Quebec Sante FX This work was funded by a grant from the Scottish Rite Charitable Foundation and the Banting Foundation to C.E., who is supported by the Canada Research Chairs program. C.O.G. is supported by a Conselho Nacional de Desenvolvimento Cientifico e Tecnologico scholarship, E.S.C. is supported by a fellowship from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, K.V. and J.P.L. are supported by the Canadian Institute of Health Research, and L.C. is supported by the Fonds de Recherche de Quebec Sante. We are grateful to Maria Antonietta Davoli and Naguib Mechawar for help and advice on performing fluorescent microscopy and microscopy analysis. 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CA Go-T2D Consortium TI A Novel Test for Recessive Contributions to Complex Diseases Implicates Bardet-Biedl Syndrome Gene BBS10 in Idiopathic Type 2 Diabetes and Obesity SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ALZHEIMERS-DISEASE; VARIANTS; ASSOCIATION; DISRUPTION; CILIOPATHY; MUTATIONS; AUTISM; GWAS AB Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing approaches when the variant influences disease risk in a recessive manner on simulated data. We then applied our method to 1,791 Finnish individuals with type 2 diabetes (T2D) and 2,657 matched control subjects. In BBS10, we discovered a rare variant (c.1189A>G [p.Ile397Val]; rs202042386) that confers risk of T2D in a recessive state (p = 1.38 x 10(-6)) and would be missed by conventional methods. Testing of this variant in an established in vivo zebrafish model confirmed the variant to be pathogenic. Taken together, these data suggest that RAFT can effectively reveal rare recessive contributions to complex diseases overlooked by conventional association tests. C1 [Lim, Elaine T.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. [Lim, Elaine T.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Lim, Elaine T.; Chan, Yingleong; Altshuler, David M.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lim, Elaine T.; Chan, Yingleong; Altshuler, David M.; Raychaudhuri, Soumya; Fannick, Jason; Hirschhorn, Joel N.; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Liu, Yangfan P.; Madsen, Erik; Katsanis, Nicholas] Duke Univ, Med Ctr, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Tiinamaija, Tuomi] Univ Helsinki, Cent Hosp, Dept Internal Med Diabetol, Helsinki 00029, Finland. [Tiinamaija, Tuomi] Univ Helsinki, Folkhalsan Res Ctr, Inst Diabet Genet, FIN-00014 Helsinki, Finland. [Tiinamaija, Tuomi] Univ Helsinki, Res Program Diabet & Obes, FIN-00014 Helsinki, Finland. [Karajamaki, AnnMari] Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa 65130, Finland. [Karajamaki, AnnMari] Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa 65100, Finland. [Altshuler, David M.; Fannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol,Dept Med, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Ctr Musculoskeletal Res, Inst Inflammat & Repair, Arthrit Res UK Epidemiol Unit, Manchester M13 9PT, Lancs, England. [Groop, Leif] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Groop, Leif] Lund Univ, Skane Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, S-20502 Malmo, Sweden. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Lim, ET (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. EM tengting.lim@childrens.harvard.edu; mjdaly@atgu.mgh.harvard.edu FU NIH [R37GM04360, R01HD04260, R01DK072301, R01DK075972]; Lung GO Sequencing Project [HL-102923]; WHI Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010] FX The Botnia PPP and Direva studies are supported by grants from Academy of Finland and the Juselius and Folkhalsan Foundations. The in vivo functional study is supported by NIH grants R37GM04360, R01HD04260, R01DK072301, and R01DK075972 (N.K.). The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010). Finally, the authors would also like to thank anonymous reviewers 1 and 2 for their words of encouragement and insightful, detailed feedback, which have helped improve this manuscript substantially. 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Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes) with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes). When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition. C1 [Solyst, James A.] Emory Univ, Neurosci Grad Program, Atlanta, GA 30322 USA. [Solyst, James A.; Buffalo, Elizabeth A.] Univ Washington, Seattle, WA 98195 USA. [Solyst, James A.] Washington Natl Primate Res Ctr, Atlanta, GA USA. [Solyst, James A.; Buffalo, Elizabeth A.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Buffalo, Elizabeth A.] Ctr Translat Social Neurosci, Atlanta, GA USA. RP Solyst, JA (reprint author), Univ Arizona, Life Sci North Room 327, Tucson, AZ 85724 USA. EM jsolyst@email.arizona.edu FU NIH [R01MH093807, R01MH080007]; National Center for Research Resources [P51RR165]; Office of Research Infrastructure Programs [ODP51OD11132, P50MH100023] FX We thank Lisa Parr, Ph.D. for providing photos of monkeys from the Yerkes National Primate Research Field Station and support for obtaining photos of monkeys from the Caribbean Primate Research Center. We also thank Megan Jutras for animal training, Kelly Morrisroe for helping to identify characteristics of the monkey photos and Seth Koenig for providing MATLAB code replicating the Itti et al. (1998) saliency map. Funding provided by: NIH Grant R01MH093807, NIH Grant R01MH080007, National Center for Research Resources P51RR165, Office of Research Infrastructure Programs/ODP51OD11132, P50MH100023. 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Neurosci. PD NOV 5 PY 2014 VL 8 DI 10.3389/fnins.2014.00354 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AW9EH UT WOS:000346559800001 PM 25414633 ER PT J AU Mergy, MA Gowrishankar, R Gresch, PJ Gantz, SC Williams, J Davis, GL Wheeler, CA Stanwood, GD Hahn, MK Blakely, RD AF Mergy, Marc A. Gowrishankar, Raajaram Gresch, Paul J. Gantz, Stephanie C. Williams, John Davis, Gwynne L. Wheeler, C. Austin Stanwood, Gregg D. Hahn, Maureen K. Blakely, Randy D. TI The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dopamine; transporter; transgenic; mouse; polymorphism ID DEFICIT-HYPERACTIVITY-DISORDER; HUMAN DOPAMINE TRANSPORTER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDER; SEQUENCE VARIATION; SYNAPTIC CURRENTS; REWARD CIRCUITRY; BIPOLAR DISORDER; ANIMAL-MODELS; MICE LACKING AB Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant- evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. C1 [Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. [Hahn, Maureen K.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Blakely, Randy D.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37232 USA. 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Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2014 VL 111 IS 44 BP E4779 EP E4788 DI 10.1073/pnas.1417294111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS2CY UT WOS:000344088100010 PM 25331903 ER PT J AU Lindsay, WR Carson, D O'Brien, G Holland, AJ Taylor, JL Wheeler, JR Steptoe, L AF Lindsay, William R. Carson, Derek O'Brien, Gregory Holland, Anthony J. Taylor, John L. Wheeler, Jessica Ruth Steptoe, Lesley TI A Comparison of Referrals With and Without Autism Spectrum Disorder to Forensic Intellectual Disability Services SO PSYCHIATRY PSYCHOLOGY AND LAW LA English DT Article DE offending; intellectual disability; autism spectrum; Asperger's ID ASPERGERS-SYNDROME; OFFENDERS; BEHAVIOR; PREVALENCE; COMMUNITY; VARIABLES; VIOLENCE; ADULTS; HEALTH AB Although some authors have suggested that there are higher rates of people with Autism Spectrum Disorder (ASD) in forensic and offending groups, systematic studies have not supported the hypothesis. The present study reviewed 477 referrals made to forensic intellectual disability (ID) services in one calendar year. It was found that 10% of referrals had ASD, a figure similar to the general population of people with ID. Those with ASD had similar patterns of offending to those without but they showed a lower prevalence of contact sexual offences and fewer had been previously charged. We concluded that there is no persuasive evidence that ASD is a risk factor for offending or for any particular type of offending. C1 [Lindsay, William R.; Carson, Derek; Steptoe, Lesley] Univ Abertay Dundee, Dundee, Scotland. [Lindsay, William R.] Deakin Univ, Melbourne, Vic, Australia. [Holland, Anthony J.; Wheeler, Jessica Ruth] Univ Cambridge, Cambridge, England. [O'Brien, Gregory; Taylor, John L.] Northumbria Univ, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. [O'Brien, Gregory] Univ Queensland, Brisbane, Qld, Australia. [Lindsay, William R.] Danshell Healthcare, York, N Yorkshire, England. 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Training Educators of Students With Autism Spectrum Disorder SO TEACHER EDUCATION AND SPECIAL EDUCATION LA English DT Article C1 [Marder, Tamara; deBettencourt, Laurie] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Marder, T (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0888-4064 EI 1944-4931 J9 TEACH EDUC SPEC EDUC JI Teach. Educ. Spec. Educ. PD NOV PY 2014 VL 37 IS 4 BP 363 EP 363 DI 10.1177/0888406414551893 PG 1 WC Education & Educational Research SC Education & Educational Research GA CI3MO UT WOS:000354652100006 ER PT J AU Markwick, L Smith, C Mick, D AF Markwick, Laura Smith, Charlene Mick, Diane TI Functional Behavioral Analysis and Social Scripting for the Older Patient with Schizophrenia: a Staff Development Program SO Issues in Mental Health Nursing LA English DT Article ID CHALLENGING BEHAVIORS; MANAGEMENT; AUTISM; ADULTS; DISABILITIES; DISORDER AB Executive functioning is the ability to plan, strategize, organize, and focus on details. Impaired executive functioning plays a significant role in behavior disturbances. Lack of inhibition, impaired abstract reasoning, thought perseverance, rigidity in routine, and lack of insight disrupt social skills and daily life. Autism and schizophrenia present some similar behaviors, including impaired executive functioning, often resulting in pharmacological management as many healthcare professionals receive limited training in executive functioning. Non-pharmacological tools used in autism for behavior management include functional behavioral analysis and social scripting, which help to identify causes of behavior and teach more appropriate behavioral responses. Described here is an educational program for healthcare workers in a long-term care skilled nursing facility, to help them understand the basis for behaviors in individuals with impaired executive function, to use these same tools for behavioral modification techniques, and to help patients learn more appropriate social skills. 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Health Nurs. PD NOV PY 2014 VL 35 IS 11 BP 883 EP 890 DI 10.3109/01612840.2014.897777 PG 8 WC Nursing; Psychiatry SC Nursing; Psychiatry GA CG4HR UT WOS:000353246700010 PM 25353301 ER PT J AU Ikematsu, Y Mizutani, M Tozaka, H Mori, S Egawa, K Endo, M Yokouchi, M AF Ikematsu, Yuko Mizutani, Masako Tozaka, Hiroaki Mori, Sachiko Egawa, Koji Endo, Midori Yokouchi, Mitsuko TI Nursing students with special educational needs in Japan SO NURSE EDUCATION IN PRACTICE LA English DT Article DE Nursing students; Special educational needs; Developmental disorders; Japan ID AUTISM SPECTRUM; COLLEGE; DISABILITIES; DYSLEXIA AB Aim: To reveal the prevalence of nursing students with special educational needs in Japan. Method: A mail survey of 833 nursing programs was conducted. Nurse educators were asked to report on their program's profiles and the number of extremely difficult students who belonged to the March 2011 class of graduates. They were also asked to fill a modified questionnaire developed by the Ministry of Education, Culture, Sports, Science and Technology about each extremely difficult student. Results: Among the 14,325 students enrolled the class of 2011, 146 students (1.02%) were identified as having one or more special educational needs for "listening," "speaking," "reading," "writing," "math," "reasoning," "inattentiveness," "hyperactivity/impulsivity," or "social interaction/restricted interests." The most prevalent need was "social interaction/restricted interests," followed by "listening" and "inattentiveness." These students had the most difficulty participating in "nursing care for patients during clinical practicum." Conclusion: The proportion of nursing students with special educational needs is small but may have a large impact on the clinical practicum. Evaluation and support systems at multiple levels, including entrance examinations, course placement, and special educational programs, are warranted. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Ikematsu, Yuko; Tozaka, Hiroaki; Yokouchi, Mitsuko] Nagoya Univ, Grad Sch Med, Dept Nursing, Nagoya, Aichi 4618673, Japan. [Egawa, Koji] Kobe City Coll Nursing, Kobe, Hyogo, Japan. [Endo, Midori] Yamanashi Prefectural Univ, Sch Nursing, Yamanashi, Japan. RP Ikematsu, Y (reprint author), Nagoya Univ, Grad Sch Med, Dept Nursing, Higashi Ku, 1-1-20 Daiko Minami, Nagoya, Aichi 4618673, Japan. EM ikematsu@met.nagoya-u.ac.jp; my@mvi.biglobe.ne.jp; tozaka@met.nagoya-u.ac.jp; mori@met.nagoya-u.ac.jp; egawa@tr.kobe-ccn.ac.jp; midorie@yamanashi-ken.ac.jp; yokouchi@met.nagoya-u.ac.jp FU Japan Society for the Promotion of Science [21659496] FX This study was supported by the Japan Society for the Promotion of Science (Exploratory Research Program #21659496). 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Jacob, S. Crawley, J. N. Silverman, J. L. Larke, R. H. Sahagun, E. Puhger, K. R. Pride, M. C. Mendoza, S. P. TI Long-term exposure to intranasal oxytocin in a mouse autism model SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID PLUS TF/J MOUSE; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; MALE PRAIRIE VOLES; BTBR-T+TF/J MICE; SPECTRUM DISORDERS; MICROTUS-OCHROGASTER; ALLOPARENTAL BEHAVIOR; PARTNER PREFERENCES; RECEPTOR SYSTEM AB Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N = 94) were administered 0.8 IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT. C1 [Bales, K. L.; Larke, R. H.; Sahagun, E.; Mendoza, S. P.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Bales, K. L.; Larke, R. H.; Sahagun, E.; Mendoza, S. P.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Solomon, M.; Crawley, J. N.; Silverman, J. L.; Puhger, K. R.; Pride, M. C.] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Solomon, M.; Crawley, J. N.; Silverman, J. L.; Puhger, K. R.; Pride, M. C.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Jacob, S.] Univ Minnesota, Dept Psychiat & Pediat, Minneapolis, MN USA. RP Bales, KL (reprint author), Univ Calif Davis, Dept Psychol, 135 Young Hall, Davis, CA 95616 USA. EM klbales@ucdavis.edu FU MIND Institute IDDRC Core E [HD079125-01]; [HD071998]; [OD P51OD01107] FX This research was funded by HD071998 to KLB, MS, SJ and SPM; OD P51OD01107 to the California National Primate Research Center; HD079125-01 MIND Institute IDDRC Core E to JLS, KRP and JNC. 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Psychiatr. PD NOV PY 2014 VL 4 AR e480 DI 10.1038/tp.2014.117 PG 10 WC Psychiatry SC Psychiatry GA CB7RU UT WOS:000349825900004 PM 25386957 ER PT J AU Dachtler, J Glasper, J Cohen, RN Ivorra, JL Swiffen, DJ Jackson, AJ Harte, MK Rodgers, RJ Clapcote, SJ AF Dachtler, J. Glasper, J. Cohen, R. N. Ivorra, J. L. Swiffen, D. J. Jackson, A. J. Harte, M. K. Rodgers, R. J. Clapcote, S. J. TI Deletion of alpha-neurexin II results in autism-related behaviors in mice SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID COPY NUMBER VARIATION; DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; SYNAPSE FORMATION; GENES; ANXIETY; SCHIZOPHRENIA; NEUROLIGIN-1; HIPPOCAMPUS; DYSFUNCTION AB Autism is a common and frequently disabling neurodevelopmental disorder with a strong genetic basis. Human genetic studies have discovered mutations disrupting exons of the NRXN2 gene, which encodes the synaptic adhesion protein a-neurexin II (Nrxn2a), in two unrelated individuals with autism, but a causal link between NRXN2 and the disorder remains unclear. To begin to test the hypothesis that Nrxn2a deficiency contributes to the symptoms of autism, we employed Nrxn2a knockout (KO) mice that genetically model Nrxn2a deficiency in vivo. We report that Nrxn2a KO mice displayed deficits in sociability and social memory when exposed to novel conspecifics. In tests of exploratory activity, Nrxn2a KO mice displayed an anxiety-like phenotype in comparison with wild-type littermates, with thigmotaxis in an open field, less time spent in the open arms of an elevated plus maze, more time spent in the enclosure of an emergence test and less time spent exploring novel objects. However, Nrxn2a KO mice did not exhibit any obvious changes in prepulse inhibition or in passive avoidance learning. Real-time PCR analysis of the frontal cortex and hippocampus revealed significant decreases in the mRNA levels of genes encoding proteins involved in both excitatory and inhibitory transmission. Quantification of protein expression revealed that Munc18-1, encoded by Stxbp1, was significantly decreased in the hippocampus of Nrxn2a KO mice, which is suggestive of deficiencies in presynaptic vesicular release. Our findings demonstrate a causal role for the loss of Nrxn2a in the genesis of autism-related behaviors in mice. C1 [Dachtler, J.; Cohen, R. N.; Ivorra, J. L.; Swiffen, D. J.; Jackson, A. J.; Clapcote, S. J.] Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. [Glasper, J.; Harte, M. K.] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. [Rodgers, R. J.] Univ Leeds, Inst Psychol Sci, Leeds, W Yorkshire, England. RP Dachtler, J (reprint author), Univ Leeds, Sch Biomed Sci, Garstang Bldg,Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England. EM j.dachtler@leeds.ac.uk FU Medical Research Council (UK) grant [G0900625]; University of Leeds Wellcome Trust ISSF (UK) Fellowship; British Pharmacological Society (UK) grant; Royal Society (UK) grant [RG130316] FX This work was supported by a Medical Research Council (UK) grant (G0900625) to SJC and RJR, a University of Leeds Wellcome Trust ISSF (UK) Fellowship, a British Pharmacological Society (UK) grant and a Royal Society (UK) grant (RG130316) to JD. 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The identified metabolite biomarkers belong to pathways that have important functions in central nervous system physiology. Biomarkers of response to fluoxetine in the normally functioning brain of juvenile nonhuman primates may aid in finding predictors of response to treatment in young psychiatric populations and in progress toward the realization of a precision medicine approach in the area of neurodevelopmental disorders. C1 [He, Y.; Turck, C. W.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, D-80804 Munich, Germany. [Hogrefe, C. E.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Grapov, D.; Palazoglu, M.; Fiehn, O.] Univ Calif Davis, NIH West Coast Metabol Ctr, Davis, CA 95616 USA. [Golub, M. S.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. RP Turck, CW (reprint author), Max Planck Inst Psychiat, Dept Translat Res Psychiat, Kraepelinstr 2, D-80804 Munich, Germany. EM turck@psych.mpg.de; msgolub@ucdavis.edu FU NIH [HD065826, OD011107]; WCMC [U24 DK097154]; Max Planck Society FX Supported by NIH grants HD065826, HD065826 (supplement) (MSG PI), OD011107 (Harris Lewin, PI), WCMC funding U24 DK097154 (OF PI) and the Max Planck Society (CWT PI). 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Psychiatr. PD NOV PY 2014 VL 4 AR e478 DI 10.1038/tp.2014.116 PG 9 WC Psychiatry SC Psychiatry GA CB7RU UT WOS:000349825900002 PM 25369145 ER PT J AU Pagan, C Delorme, R Callebert, J Goubran-Botros, H Amsellem, F Drouot, X Boudebesse, C Le Dudal, K Ngo-Nguyen, N Laouamri, H Gillberg, C Leboyer, M Bourgeron, T Launay, JM AF Pagan, C. Delorme, R. Callebert, J. Goubran-Botros, H. Amsellem, F. Drouot, X. Boudebesse, C. Le Dudal, K. Ngo-Nguyen, N. Laouamri, H. Gillberg, C. Leboyer, M. Bourgeron, T. Launay, J-M TI The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; CONTROLLED-RELEASE MELATONIN; WHOLE-BLOOD SEROTONIN; 1ST-DEGREE RELATIVES; SOCIAL-BEHAVIOR; YOUNG-ADULTS; CHILDREN; OXYTOCIN; ENZYME; 6-SULPHATOXYMELATONIN AB Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex-and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. C1 [Pagan, C.; Callebert, J.; Launay, J-M] Univ Hosp Lariboisiere, AP HP, INSERM, Dept Biochem,U942,Serv Biochim & Biol Mol, F-75010 Paris, France. [Pagan, C.; Callebert, J.; Launay, J-M] Univ Paris 05, Paris, France. [Pagan, C.; Delorme, R.; Goubran-Botros, H.; Bourgeron, T.] Inst Pasteur, CNRS, URA 2182, Paris, France. [Pagan, C.; Delorme, R.; Amsellem, F.; Drouot, X.; Boudebesse, C.; Le Dudal, K.; Ngo-Nguyen, N.; Laouamri, H.; Leboyer, M.; Bourgeron, T.; Launay, J-M] Fdn FondaMental, Creteil, France. [Delorme, R.; Amsellem, F.] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. [Drouot, X.; Boudebesse, C.; Leboyer, M.] Univ Paris Diderot, Paris, France. [Boudebesse, C.] Univ Paris Est Creteil, Univ Hosp Henri Mondor, AP HP, Dept Psychiat, Creteil, France. [Le Dudal, K.] Hop Henri Mondor, AP HP, INSERM, CIC 1430, F-94010 Creteil, France. [Gillberg, C.] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Gillberg, C.] UCL, Inst Child Hlth, London, England. RP Launay, JM (reprint author), Univ Hosp Lariboisiere, AP HP, INSERM, Dept Biochem,U942,Serv Biochim & Biol Mol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM jean-marie.launay@lrb.aphp.fr FU Institut Pasteur, CNRS, INSERM, AP-HP, University Paris Diderot; Bettencourt-Schueller foundation; Orange foundation; FondaMental foundation; Conny-Maeva foundation; Cognacq-Jay foundation; ANR (SynDivAutism); Neuron-ERANET (EUHF-AUTISM) FX We thank the patients and their families, and the controls who accepted to participate in this study. The Clinical Investigation Centers of Robert-Debre and Henri Mondor Hospitals obtained and processed blood samples, the Hematology departments from both hospitals (Dr MF Hurtaud and Professor M Imbert) performed platelet counts. Dr E Gayat provided help with statistics. This work was supported by the Institut Pasteur, CNRS, INSERM, AP-HP, University Paris Diderot, the Bettencourt-Schueller foundation, the Orange foundation, the FondaMental foundation, the Conny-Maeva foundation, the Cognacq-Jay foundation, the ANR (SynDivAutism) and the Neuron-ERANET (EUHF-AUTISM). 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Psychiatr. PD NOV PY 2014 VL 4 AR e479 DI 10.1038/tp.2014.120 PG 8 WC Psychiatry SC Psychiatry GA CB7RU UT WOS:000349825900003 PM 25386956 ER PT J AU Okoshi, Y Tanuma, N Miyata, R Hayashi, M AF Okoshi, Yumi Tanuma, Naoyuki Miyata, Rie Hayashi, Masaharu TI Melatonin alterations and brain acetylcholine lesions in sleep disorders in Cockayne syndrome SO BRAIN & DEVELOPMENT LA English DT Article DE Cockayne syndrome; Sleep disorders; Melatonin; Immunohistochemistry; Hypothalamus; Acetylcholine ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; AUTISM SPECTRUM DISORDERS; EYE-MOVEMENT SLEEP; XERODERMA-PIGMENTOSUM; DOWN-SYNDROME; YOUNG-ADULTS; DONEPEZIL; CHILDREN; 6-SULPHATOXYMELATONIN; ASSOCIATIONS AB Background: Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. Objective: The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. Methods: We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. Results: Sleep wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. Conclusions: AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. C1 [Okoshi, Yumi; Miyata, Rie; Hayashi, Masaharu] Tokyo Metropolitan Inst Med Sci, Dept Brain Dev & Neural Regenerat, Tokyo 1568506, Japan. [Okoshi, Yumi] Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido 060, Japan. [Okoshi, Yumi; Tanuma, Naoyuki] Tokyo Metropolitan Fuchu Med Ctr Disabled, Dept Pediat, Tokyo, Japan. RP Hayashi, M (reprint author), Tokyo Metropolitan Inst Med Sci, Dept Brain Dev & Neural Regenerat, Setagaya Ku, 2-1-6 Kamikitazawa, Tokyo 1568506, Japan. 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PD NOV PY 2014 VL 36 IS 10 BP 907 EP 913 DI 10.1016/j.braindev.2014.01.004 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CA8WR UT WOS:000349202100011 PM 24503446 ER PT J AU Roche, L Sigafoos, J Lancioni, GE O'Reilly, MF Schlosser, RW Stevens, M van der Meer, L Achmadi, D Kagohara, D James, R Carnett, A Hodis, F Green, VA Sutherland, D Lang, R Rispoli, M Machalicek, W Marschik, PB AF Roche, Laura Sigafoos, Jeff Lancioni, Giulio E. O'Reilly, Mark F. Schlosser, Ralf W. Stevens, Michelle van der Meer, Larah Achmadi, Donna Kagohara, Debora James, Ruth Carnett, Amarie Hodis, Flaviu Green, Vanessa A. Sutherland, Dean Lang, Russell Rispoli, Mandy Machalicek, Wendy Marschik, Peter B. TI An evaluation of speech production in two boys with neurodevelopmental disorders who received communication intervention with a speech-generating device SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Augmentative and alternative communication; Speech-generating device; Natural speech production; Neurodevelopmental disorders; Severe communication impairment ID ALTERNATIVE COMMUNICATION; DEVELOPMENTAL-DISABILITIES; AUTISM; INDIVIDUALS; CHILDREN; OUTPUT AB Background: Children with neurodevelopmental disorders often present with little or no speech. Augmentative and alternative communication (AAC) aims to promote functional communication using non-speech modes, but it might also influence natural speech production. Method: To investigate this possibility, we provided AAC intervention to two boys with neurodevelopmental disorders and severe communication impairment. Intervention focused on teaching the boys to use a tablet computer-based speech-generating device (SGD) to request preferred stimuli. During SGD intervention, both boys began to utter relevant single words. In an effort to induce more speech, and investigate the relation between SGD availability and natural speech production, the SGD was removed during some requesting opportunities. Results: With intervention, both participants learned to use the SGD to request preferred stimuli. After learning to use the SGD, both participants began to respond more frequently with natural speech when the SGD was removed. Conclusion: The results suggest that a rehabilitation program involving initial SGD intervention, followed by subsequent withdrawal of the SGD, might increase the frequency of natural speech production in some children with neurodevelopmental disorders. This effect could be an example of response generalization. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Roche, Laura; Sigafoos, Jeff; Stevens, Michelle; van der Meer, Larah; Achmadi, Donna; Kagohara, Debora; James, Ruth; Carnett, Amarie; Hodis, Flaviu; Green, Vanessa A.] Victoria Univ Wellington, Sch Educ, Wellington, 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. [Schlosser, Ralf W.] Northeastern Univ, Dept Speech Language Pathol & Audiol, Boston, MA 02115 USA. [Sutherland, Dean] Univ Canterbury, Coll Educ, Sch Hlth Sci, Christchurch 1, New Zealand. [Lang, Russell] SW Texas State Univ, Clin Autism Res Evaluat & Support, San Marcos, TX 78666 USA. [Rispoli, Mandy] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. [Machalicek, Wendy] Univ Oregon, Dept Special Educ & Clin Sci, Eugene, OR 97403 USA. [Marschik, Peter B.] Med Univ Graz, Ctr Physiol Med, Inst Physiol, Res Unit iDN Interdisciplinary Dev Neurosci, Graz, Austria. RP Sigafoos, J (reprint author), Victoria Univ Wellington, Sch Educ, POB 17-310,Karori 6147, Wellington, New Zealand. EM jeff.sigafoos@vuw.ac.nz FU New Zealand Government through the Marsden Fund Council [10-VUW-071]; Victoria University of Wellington, The University of Canterbury; New Zealand Institute of Language, Brain Behaviour FX Support for this research was provided by the New Zealand Government through the Marsden Fund Council, administered by the Royal Society of New Zealand (Grant Number 10-VUW-071); and by Victoria University of Wellington, The University of Canterbury, and The New Zealand Institute of Language, Brain & Behaviour. 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Walitza, S. Gruenblatt, E. TI Prenatal stress increases the striatal and hippocampal expression of correlating c-FOS and serotonin transporters in murine offspring SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Prenatal stress; Immediate early genes; Serotonin transporter; Hippocampus; Striatum; Mouse ID GENE-EXPRESSION; FEMALE RATS; BRAIN; PREGNANCY; EXPOSURE; SUSCEPTIBILITY; SCHIZOPHRENIA; ANXIETY; AUTISM; 5-HT AB Prenatal stress (PS) is a known risk factor for several psychiatric diagnoses, including schizophrenia, attention deficit hyperactivity disorder, autism, anxiety, and depression which have been associated with serotonin transporter (SERT) dysregulation. Moreover, long-term effects in animal models associate with higher levels of immediate early genes, e.g. c-FOS (up-regulated in response to neuronal activity), in the brain of PS offspring. We therefore quantified the expression of both protein related mRNAs in adolescent BALB/c mice subjected to mild auditory stress on two separate days in mid gestation. SERT and c-FOS consistently correlated in most brain regions of PS mice and controls. Moreover, two-way ANOVAs revealed concomitantly increased levels of proteins, as well as of FOSL1 and FOSL2 mRNA, especially in the striatum and hippocampus of the PS offspring. Sex affected only and less consistently mRNA expression, yet interacted with PS, demonstrating that glucocorticoid receptor mRNA expression decreased in PS males but increased in PS females compared to the respective controls. This first finding of a correlation between SERT and c-FOS protein expression affected by PS, together with related mRNAs, may be considered a new target for behavioral and treatment studies in offspring. (C) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Bielas, H.; Walitza, S.; Gruenblatt, E.] Univ Zurich, Univ Clin Child Psychiat, CH-8032 Zurich, Switzerland. [Bielas, H.; Walitza, S.; Gruenblatt, E.] Univ Zurich, Univ Clin Adolescent Psychiat, CH-8032 Zurich, Switzerland. [Walitza, S.; Gruenblatt, E.] Univ Zurich, Neurosci Ctr Zurich, CH-8006 Zurich, Switzerland. [Walitza, S.; Gruenblatt, E.] Swiss Fed Inst Technol, Zurich, Switzerland. [Arck, P.] Univ Med Ctr Hamburg, Lab Expt Fetomaternal Med, Hamburg, Germany. [Bielas, H.] Univ Childrens Hosp Zurich, Dept Psychosomat & Psychiat, Zurich, Switzerland. [Bruenahl, C. A.] Univ Med Ctr Hamburg, Dept Psychosomat Med & Psychotherapy, Hamburg, Germany. RP Bielas, H (reprint author), Univ Childrens Hosp, Dept Psychosomat & Psychiat, Steinwiesstr 75, CH-8032 Zurich, Switzerland. EM hannes.bielas@kispi.uzh.ch FU Boehringer Ingelheim Foundation; German Research Foundation [AR232/17-1] FX The work presented herein was facilitated by grants provided to Hannes Bielas by the Boehringer Ingelheim Foundation and by the German Research Foundation to P.A. (AR232/17-1). We would like to thank Dr. Molinari for his helpful comments on statistical analysis. A special thanks also goes to Miss Miryame Hofmann for her technical assistance. CR Adamec R, 2006, BEHAV BRAIN RES, V170, P126, DOI 10.1016/j.bbr.2006.02.012 Ago Y, 2011, PSYCHOPHARMACOLOGY, V217, P377, DOI 10.1007/s00213-011-2293-5 Bethea CL, 2013, PROG NEURO-PSYCHOPH, V44, P143, DOI 10.1016/j.pnpbp.2013.01.013 Beversdorf DQ, 2005, J AUTISM DEV DISORD, V35, P471, DOI 10.1007/s10803-005-5037-8 Bock J, 2014, FRONT NEUROSCI-SWITZ, V8, DOI 10.3389/fnins.2014.00011 Browne CA, 2011, NEUROPHARMACOLOGY, V60, P683, DOI 10.1016/j.neuropharm.2010.11.020 Buss C, 2011, STRESS, V14, P665, DOI 10.3109/10253890.2011.623250 Chervoneva I, 2006, ANAL BIOCHEM, V348, P198, DOI 10.1016/j.ab.2005.10.042 Clavarino AM, 2010, J ATTEN DISORD, V13, P658, DOI 10.1177/1087054709347203 Gill RK, 2011, AM J PHYSIOL-GASTR L, V300, pG627, DOI 10.1152/ajpgi.00563.2010 Gutierrez-Mecinas M, 2011, P NATL ACAD SCI USA, V108, P13806, DOI 10.1073/pnas.1104383108 Huang YJ, 2012, BMC NEUROSCI, V13, DOI 10.1186/1471-2202-13-22 Jones KL, 2010, INT J DEV NEUROSCI, V28, P529, DOI 10.1016/j.ijdevneu.2010.05.002 Khashan AS, 2008, ARCH GEN PSYCHIAT, V65, P146, DOI 10.1001/archgenpsychiatry.2007.20 Kinney DK, 2008, J AUTISM DEV DISORD, V38, P481, DOI 10.1007/s10803-007-0414-0 Koenig JI, 2002, NEUROPSYCHOPHARMACOL, V27, P309 Mairesse J., 2012, INT J NEUROPSYCHOPH, P1 Malynn S, 2013, NEUROCHEM RES, V38, P694, DOI 10.1007/s11064-012-0967-y Morgan CP, 2011, J NEUROSCI, V31, P11748, DOI 10.1523/JNEUROSCI.1887-11.2011 Mueller BR, 2008, J NEUROSCI, V28, P9055, DOI 10.1523/JNEUROSCI.1424-08.2008 Mychasiuk R, 2011, DEV NEUROSCI-BASEL, V33, P531, DOI 10.1159/000335524 Paternain L, 2012, NEUROENDOCRINOLOGY, V96, P249, DOI 10.1159/000341684 Pincus-Knackstedt MK, 2006, J IMMUNOL, V177, P8484 Raikkonen K, 2011, STRESS, V14, P590, DOI 10.3109/10253890.2011.602147 Sierksma ASR, 2012, NEUROCHEM INT, V61, P697, DOI 10.1016/j.neuint.2012.06.022 Simon AR, 2005, CELL BIOCHEM BIOPHYS, V42, P263, DOI 10.1385/CBB:42:3:263 Sullivan PF, 2006, AM J MED GENET B, V141B, P261, DOI 10.1002/ajmg.b.30272 Tobe I, 2005, NEUROSCIENCE, V134, P387, DOI 10.1016/j.neuroscience.2005.04.023 Vandesompele J, 2002, GENOME BIOL, V3, DOI 10.1186/gb-2002-3-7-research0034 Viltart O, 2006, PSYCHONEUROENDOCRINO, V31, P769, DOI 10.1016/j.psyneuen.2006.02.007 Warren BL, 2011, J NEUROSCI, V31, P10347, DOI 10.1523/JNEUROSCI.1470-11.2011 Weinstock M, 2008, NEUROSCI BIOBEHAV R, V32, P1073, DOI 10.1016/j.neubiorev.2008.03.002 Weinstock M, 2011, STRESS, V14, P604, DOI 10.3109/10253890.2011.588294 Zouhairi N, 2012, ACTA HISTOCHEM, V114, P525, DOI 10.1016/j.acthis.2011.09.006 Zucchi FCR, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056967 Zuena AR, 2008, PLOS ONE, V3, DOI 10.1371/journal.pone.0002170 NR 36 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 EI 1873-474X J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD NOV PY 2014 VL 38 BP 30 EP 35 DI 10.1016/j.ijdevneu.2014.07.006 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA AY6FN UT WOS:000347662800005 PM 25102410 ER PT J AU Valleau, JC Sullivan, EL AF Valleau, Jeanette C. Sullivan, Elinor L. TI The impact of leptin on perinatal development and psychopathology SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE Pregnancy; Inflammation; Obesity; Neurodevelopment; Behavioral regulation; Mental health disorders ID CORD BLOOD LEPTIN; OB GENE-EXPRESSION; POSTTRAUMATIC-STRESS-DISORDER; PITUITARY-ADRENAL AXIS; ANXIETY-LIKE BEHAVIOR; DIET-INDUCED OBESITY; C-REACTIVE PROTEIN; BODY-MASS INDEX; SERUM LEPTIN; PLASMA LEPTIN AB Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as anti-psychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naive populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including autism spectrum disorders and Rhett disorder. Further, studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations. (C) 2014 Elsevier B.V. All rights reserved. C1 [Valleau, Jeanette C.; Sullivan, Elinor L.] Oregon Natl Primate Res Ctr, Div Diabet Obes & Metab, Beaverton, OR USA. [Sullivan, Elinor L.] Univ Portland, Dept Biol, Portland, OR 97203 USA. RP Sullivan, EL (reprint author), Univ Portland, 5000 N Willamette Blvd, Portland, OR 97203 USA. EM sullivae@up.edu FU Murdock Charitable Trust, Murdock College Research Program for Life Science [2011273:HVP]; Oregon Clinical and Translational Research Institute (OCTRI) from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) [UL1TR000128]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institute of Health (NIH) [R01 DK079194] FX This publication was supported by the Murdock Charitable Trust, Murdock College Research Program for Life Science, grant number 2011273:HVP, Oregon Clinical and Translational Research Institute (OCTRI), grant number (UL1TR000128) from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) and grant number R01 DK079194 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institute of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Trust. 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Chem. Neuroanat. PD NOV PY 2014 VL 61-62 BP 221 EP 232 DI 10.1016/j.jchemneu.2014.05.001 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AY7LN UT WOS:000347741800025 PM 24862904 ER PT J AU Kasari, C Siller, M Huynh, LN Shih, W Swanson, M Hellemann, GS Sugar, CA AF Kasari, Connie Siller, Michael Huynh, Linh N. Shih, Wendy Swanson, Meghan Hellemann, Gerhard S. Sugar, Catherine A. TI Randomized controlled trial of parental responsiveness intervention for toddlers at high risk for autism SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Early intervention; Parental responsiveness; Autism spectrum disorder; High risk infants ID SPECTRUM DISORDERS; JOINT ATTENTION; CHILDREN; COMMUNICATION; BEHAVIORS; PLAY AB This study tested the effects of a parent-mediated intervention on parental responsiveness with their toddlers at high risk for an autism spectrum disorder (ASD). Participants included caregivers and their 66 toddlers at high risk for ASD. Caregivers were randomized to 12 sessions of an individualized parent education intervention aimed at improving parental responsiveness or to a monitoring control group involving 4 sessions of behavioral support. Parental responsiveness and child outcomes were measured at three time points: at beginning and end of the 3-month treatment and at 12-months post-study entry. Parental responsiveness improved significantly in the treatment group but not the control group. However, parental responsiveness was not fully maintained at follow up. There were no treatment effects on child outcomes of joint attention or language. Children in both groups made significant developmental gains in cognition and language skills over one year. These results support parental responsiveness as an important intervention target given its general association with child outcomes in the extant literature; however, additional supports are likely needed to fully maintain the treatment effect and to affect child outcomes. Published by Elsevier Inc. C1 [Kasari, Connie; Huynh, Linh N.; Shih, Wendy; Hellemann, Gerhard S.; Sugar, Catherine A.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Siller, Michael; Swanson, Meghan] CUNY Hunter Coll, New York, NY 10021 USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90095 USA. 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PD NOV PY 2014 VL 37 IS 4 BP 711 EP 721 DI 10.1016/j.infbeh.2014.08.007 PG 11 WC Psychology, Developmental SC Psychology GA AZ1RZ UT WOS:000348016800026 PM 25260191 ER PT J AU Jones, S AF Jones, Sharon TI Maternal cradling bias and early communicative interactions: Implications for early identification of children at risk SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Maternal cradling bias; Early communication development; Infant maternal interactions ID FUSIFORM FACE AREA; AUTISM SPECTRUM DISORDERS; FULL-TERM NEWBORNS; CORPUS-CALLOSUM; LANGUAGE-ACQUISITION; YOUNG-CHILDREN; HUMAN INFANTS; SELECTIVE ATTENTION; BRAIN; SPEECH C1 Northeastern State Univ, Tahlequah, OK 74464 USA. RP Jones, S (reprint author), Northeastern State Univ, 800 N Vinita, Tahlequah, OK 74464 USA. 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Dev. PD NOV PY 2014 VL 37 IS 4 BP 722 EP 728 DI 10.1016/j.infbeh.2014.08.008 PG 7 WC Psychology, Developmental SC Psychology GA AZ1RZ UT WOS:000348016800027 PM 25260192 ER PT J AU Yassa, HA AF Yassa, Heba A. TI Autism: A form of lead and mercury toxicity SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Autism; Heavy metals; Autistic symptoms; Chelating agents ID SPECTRUM DISORDERS; RISK-FACTORS; CHILDREN; ASSOCIATION; MEASLES; MUMPS AB Aim: Autism is a developmental disability characterized by severe deficits in social interaction and communication. The definite cause of autism is still unknown. The aim of this study is to find out the relation between exposure to Lead and/or mercury as heavy metals and autistic symptoms, dealing with the heavy metals with chelating agents can improve the autististic symptoms. Method: Blood and hair samples were obtained from 45 children from Upper Egypt with autism between the ages of 2 and 10 years and 45 children served as controls in the same age range, after taken an informed consent and fill a questionnaire to assess the risk factors. The samples were analyzed blindly for lead and mercury by using atomic absorption and ICP-MS. Data from the two groups were compared, then follow up of the autistic children after treatment with chelating agents were done. Results: The results obtained showed significant difference among the two groups, there was high level of mercury and lead among those kids with autism. Significant decline in the blood level of lead and mercury with the use of DMSA as a chelating agent. In addition, there was decline in the autistic symptoms with the decrease in the lead and mercury level in blood. Conclusion: Lead and mercury considered as one of the main causes of autism. Environmental exposure as well as defect in heavy metal metabolism is responsible for the high level of heavy metals. Detoxification by chelating agents had great role in improvement of those kids. (C) 2014 Elsevier B.V. All rights reserved. C1 Assiut Univ, Fac Med, Forens Med & Clin Toxicol Dept, Asyut, Egypt. RP Yassa, HA (reprint author), Assiut Univ, Fac Med, Forens Med & Clin Toxicol Dept, Asyut, Egypt. 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Toxicol. Pharmacol. PD NOV PY 2014 VL 38 IS 3 BP 1016 EP 1024 DI 10.1016/j.etap.2014.10.005 PG 9 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA AY3XI UT WOS:000347512400036 PM 25461563 ER PT J AU Martin, M AF Martin, Mary TI Moving on the spectrum: Dance/movement therapy as a potential early intervention tool for children with Autism Spectrum Disorders SO ARTS IN PSYCHOTHERAPY LA English DT Article DE Dance/movement therapy; Autism Spectrum Disorder; Early intervention; Motor; Social Communication ID JOINT ATTENTION; YOUNG-CHILDREN; COMMUNICATION DEVELOPMENT; DEVELOPMENTAL DISORDERS; LANGUAGE-DEVELOPMENT; MOTOR COORDINATION; SOCIAL BEHAVIORS; MIRROR NEURONS; PRETEND PLAY; ACTION GOALS AB The rising number of Autism Spectrum Disorder (ASD) diagnoses, in addition to the ability to recognize the disorder early, has led to much interest in early intervention tools. This theoretical work examines how dance/movement therapy (DMT) might be applied to address the early developmental connections between social and communication challenges and early motor maturation in young children diagnosed with ASDs. As a foundation for this discussion, literature pertaining to the early relationship of motor challenges and social/communication deficits is reviewed. A theoretical framework is proposed that promotes the integration and early development of these two realms based on DMT interventions and principles in children at high risk for or diagnosed with an ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 Naropa Univ, Boulder, CO 80302 USA. RP Martin, M (reprint author), Naropa Univ, Boulder, CO 80302 USA. 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Konar, Amit TI Eye movement sequence analysis using electrooculogram to assist autistic children SO BIOMEDICAL SIGNAL PROCESSING AND CONTROL LA English DT Article DE Autism; Hjorth Parameters; Electrooculogram; Ensemble classifier; Eye movement analysis ID EOG; CLASSIFICATION; ALGORITHMS; ENSEMBLES; SYSTEMS; DISEASE AB The present work proposes a system for assistance of Autistic children by analysis of eye movements. Autism is a disease characterized by abnormal eye movements and an inability to follow a pattern of object movement in different directions. Eye movement data is recorded from normal individuals over a period of five days using an Electrooculogram signal acquisition system developed in the laboratory. Hjorth Parameters are used as signal features. Eye movement directions in response to a visual stimulus for tracking an object are classified using ensemble classifiers based on bagging and adaptive boosting algorithms. Maximum classification accuracies of 83.09%, 90.27%, 80.75% and 92.27% were achieved on Hjorth Parameters as features using Bagging Ensemble classifier while tracking four different sequences. The individuals are trained by repeated tracking of the sequences such that there is an improvement in tracking over time. The system is designed to measure the tracking accuracy of following four different sequences of movement of an object in different directions as shown in a cue in a predetermined interval of time. The average tracking accuracy over ten normal subjects considering all the four sequence stimuli improves from 78.64% to 90.96% in five days which is accompanied with a decrease in staring errors from 6.36% to 1.29%. This would enable convenient detection of eye fixations/staring errors in Autistic people along with the provision of gradual improvements when the tracking sequences are not followed in 50% of the cases through consequent training. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Banerjee, Anwesha; Tibarewala, D. N.] Jadavpur Univ, Sch Biosci & Engn, Kolkata 700032, W Bengal, India. [Pal, Monalisa; Datta, Shreyasi; Konar, Amit] Jadavpur Univ, Dept Elect & Telecommun Engn, Kolkata 700032, W Bengal, India. RP Banerjee, A (reprint author), Jadavpur Univ, Sch Biosci & Engn, Raja SC Mullick Rd, Kolkata 700032, W Bengal, India. EM anwesha.banerjee@ymail.com; monalisap90@gmail.com; shreyasidatta@gmail.com; biomed.ju@gmail.com; konaramit@yahoo.co.in FU Jadavpur University; Council of Scientific and Industrial Research (CSIR), India FX This work is supported by Jadavpur University and Council of Scientific and Industrial Research (CSIR), India. 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Control PD NOV PY 2014 VL 14 BP 134 EP 140 DI 10.1016/j.bspc.2014.07.010 PG 7 WC Engineering, Biomedical; Medical Laboratory Technology SC Engineering; Medical Laboratory Technology GA AX6FW UT WOS:000347019500012 ER PT J AU Aoki, Y Yahata, N Watanabe, T Takano, Y Kawakubo, Y Kuwabara, H Iwashiro, N Natsubori, T Inoue, H Suga, M Takao, H Sasaki, H Gonoi, W Kunimatsu, A Kasai, K Yamasue, H AF Aoki, Yuta Yahata, Noriaki Watanabe, Takamitsu Takano, Yosuke Kawakubo, Yuki Kuwabara, Hitoshi Iwashiro, Norichika Natsubori, Tatsunobu Inoue, Hideyuki Suga, Motomu Takao, Hidemasa Sasaki, Hiroki Gonoi, Wataru Kunimatsu, Akira Kasai, Kiyoto Yamasue, Hidenori TI Oxytocin improves behavioural and neural deficits in inferring others' social emotions in autism SO BRAIN LA English DT Article DE empathy; mentalizing; neuropeptide; perspective taking; theory of mind ID HIGH-FUNCTIONING AUTISM; RANDOMIZED CONTROLLED-TRIAL; HEALTHY CAUCASIAN ADULTS; INFERIOR FRONTAL GYRUS; EXTENDED LIMBIC SYSTEM; INTRANASAL OXYTOCIN; SPECTRUM DISORDERS; ASPERGER-SYNDROME; PROSOCIAL BEHAVIOR; BRAIN RESPONSES AB Recent studies have suggested oxytocin's therapeutic effects on deficits in social communication and interaction in autism spectrum disorder through improvement of emotion recognition with direct emotional cues, such as facial expression and voice prosody. Although difficulty in understanding of others' social emotions and beliefs under conditions without direct emotional cues also plays an important role in autism spectrum disorder, no study has examined the potential effect of oxytocin on this difficulty. Here, we sequentially conducted both a case-control study and a clinical trial to investigate the potential effects of oxytocin on this difficulty at behavioural and neural levels measured using functional magnetic resonance imaging during a psychological task. This task was modified from the Sally-Anne Task, a well-known first-order false belief task. The task was optimized for investigation of the abilities to infer another person's social emotions and beliefs distinctively so as to test the hypothesis that oxytocin improves deficit in inferring others' social emotions rather than beliefs, under conditions without direct emotional cues. In the case-control study, 17 males with autism spectrum disorder showed significant behavioural deficits in inferring others' social emotions (P = 0.018) but not in inferring others' beliefs (P = 0.064) compared with 17 typically developing demographically-matched male participants. They also showed significantly less activity in the right anterior insula and posterior superior temporal sulcus during inferring others' social emotions, and in the dorsomedial prefrontal cortex during inferring others' beliefs compared with the typically developing participants (P < 0.001 and cluster size > 10 voxels). Then, to investigate potential effects of oxytocin on these behavioural and neural deficits, we conducted a double-blind placebo-controlled crossover within-subject trial for single-dose intranasal administration of 24 IU oxytocin in an independent group of 20 males with autism spectrum disorder. Behaviourally, oxytocin significantly increased the correct rate in inferring others' social emotions (P = 0.043, one-tail). At the neural level, the peptide significantly enhanced the originally-diminished brain activity in the right anterior insula during inferring others' social emotions (P = 0.004), but not in the dorsomedial prefrontal cortex during inferring others' beliefs (P = 0.858). The present findings suggest that oxytocin enhances the ability to understand others' social emotions that have also required second-order false belief rather than first-order false beliefs under conditions without direct emotional cues in autism spectrum disorder at both the behaviour and neural levels. C1 [Aoki, Yuta; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Inoue, Hideyuki; Suga, Motomu; Kasai, Kiyoto; Yamasue, Hidenori] Univ Tokyo, Sch Med, Dept Neuropsychiat, Bunkyo Ku, Tokyo 1138655, Japan. [Watanabe, Takamitsu] Univ Tokyo, Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1138655, Japan. [Kawakubo, Yuki; Kuwabara, Hitoshi] Univ Tokyo, Sch Med, Dept Child Neuropsychiat, Bunkyo Ku, Tokyo 1138655, Japan. [Takao, Hidemasa; Sasaki, Hiroki; Gonoi, Wataru; Kunimatsu, Akira] Univ Tokyo, Sch Med, Dept Radiol, Bunkyo Ku, Tokyo 1138655, Japan. [Yamasue, Hidenori] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo, Japan. RP Yamasue, H (reprint author), Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM yamasue-tky@umin.ac.jp FU KAKENHI [22689034, 20591378]; Global Centre of Excellence Program; Japan Society for the Promotion of Science Research Foundation for Young Scientists [222882] FX A part of this study is a result of the 'Development of biomarker candidates for social behavior' project under the Strategic Research Program for Brain Sciences by the MEXT. We acknowledge the supports provided by KAKENHI (22689034 to H.Y.; 20591378 to N.Y.), the Global Centre of Excellence Program (N.Y.), and a grant from the Japan Society for the Promotion of Science Research Foundation for Young Scientists (222882 to T.W). 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TI Findings and Implications of Developmental Screening for High-Risk Children Referred to a Tertiary Developmental Disability Center SO JOURNAL OF PEDIATRIC HEALTH CARE LA English DT Article DE Development; screening; autism spectrum disorders ID AUTISM SPECTRUM DISORDERS; MODIFIED CHECKLIST; YOUNG-CHILDREN; BEHAVIORAL TREATMENT; PRIMARY-CARE; DIAGNOSIS; TODDLERS; IDENTIFICATION; SURVEILLANCE; INFANTS AB Introduction: The primary goal of this article is to describe an intake process and results of screening for developmental and autism spectrum disorders in children referred to a tertiary center. A secondary analysis of abnormal screening results, demographic variables, and parental concerns of autism was conducted, along with a correlation analysis between developmental and autism-specific screening tools. Methods: A total of 379 children younger than 6 years were "prescreened'' with the Ages and Stages Questionnaire-3 and the Modified Checklist for Autism in Toddlers or the Social Communication Questionnaire. Medical records were reviewed to identify demographic variables and parental primary concerns. Results: In approximately 11% of participants who screened positive for autism, no parental concerns of autism were present. Medium effect size correlations were found between the failed autism screening tools and delays in two domains on the Ages and Stages Questionnaire-3. Discussion: Clinical implications are addressed concerning diligent use of developmental and autism-specific rating scales to identify children at risk. C1 [Mathews, Therese L.] Munroe Meyer Inst, Omaha, NE 68198 USA. [King, Melissa Lynne] Univ Nebraska Med Ctr, Munroe Meyer Inst, Omaha, NE USA. [Kupzyk, Kevin A.] Munroe Meyer Inst, Coll Nursing, Omaha, NE 68198 USA. 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Health Care PD NOV-DEC PY 2014 VL 28 IS 6 BP 507 EP 515 DI 10.1016/j.pedhc.2014.03.002 PG 9 WC Health Policy & Services; Nursing; Pediatrics SC Health Care Sciences & Services; Nursing; Pediatrics GA AW8ZH UT WOS:000346547200015 PM 24793986 ER PT J AU Berry, AD Garzon, DL Mack, P Kanwischer, KZ Beck, DG AF Berry, Anita D. Garzon, Dawn Lee Mack, Patricia Kanwischer, Katelyn Z. Beck, Deborah Guzzo TI Implementing an Early Childhood Developmental Screening and Surveillance Program in Primary Care Settings: Lessons Learned From a Project in Illinois SO JOURNAL OF PEDIATRIC HEALTH CARE LA English DT Article DE Developmental screening; developmental surveillance ID MEDICAL HOME; DISORDERS; ALGORITHM; CHILDREN; AUTISM AB Enhancing Developmentally Oriented Primary Care (EDOPC) is a project with a goal to increase the financing and delivery of preventive developmental services for children birth to age 3 years in the state of Illinois. Primary care providers have more opportunities to screen and observe infants and toddlers than any other professional, because they see them up to 13 times in the first 3 years of life for well-child visits. The project focused on using a 1-hour, on-site training for primary care providers and their entire office staff as the method of increasing knowledge, focusing on intent to change practice and implementation of routine early childhood developmental screening. Although many primary care providers routinely use only developmental surveillance in their practices, clinical practice guidelines recommend routine use of standardized developmental screening, using validated developmental screening tools. This article includes lessons learned and recommendations based on clinical practice guidelines and experiences of the team members during implementation of the EDOPC project. Primary care providers are critical to this process because children with developmental disorders have the best long-term outcomes and opportunities for improved family functioning with early detection, diagnosis, and treatment. C1 [Berry, Anita D.; Mack, Patricia; Kanwischer, Katelyn Z.; Beck, Deborah Guzzo] Advocate Childrens Hosp, Hlth Steps Young Children Program, Downers Grove, IL 60515 USA. [Berry, Anita D.; Mack, Patricia; Beck, Deborah Guzzo] Advocate Childrens Hosp, Enhancing Dev Oriented Primary Care Project, Downers Grove, IL 60515 USA. [Garzon, Dawn Lee] Univ Missouri, Coll Nursing, St Louis, MO 63121 USA. RP Berry, AD (reprint author), Advocate Childrens Hosp, 3075 Highland Pkwy, Downers Grove, IL 60515 USA. EM anita.berry@advocatehealth.com FU Advocate Health Care; Advocate Charitable Foundation; Illinois Department of Healthcare and Family Services; Michael Reese Health Trust; Illinois Children's Healthcare Foundation; W. Clement and Jesse V. Stone Foundation; Irving B. Harris Foundation FX We thank Barbara Giloth, Advocate Health Care, Advocate Charitable Foundation, for her assistance in developing the EDOPC project and for securing grant support. We thank Scott Allen, Juanona Brewster, and Rachel Sacks, Illinois Chapter, American Academy of Pediatrics, for their collegiality and assistance in the development and implementation of the EDOPC project. We also thank the Illinois Department of Healthcare and Family Services, Michael Reese Health Trust, Illinois Children's Healthcare Foundation, W. Clement and Jesse V. Stone Foundation, and Irving B. Harris Foundation for core funding for the project. 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TI Interaction of Participant Characteristics and Type of AAC With Individuals With ASD: A Meta-Analysis SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE AAC; augmentative and alternative communication; ASD; autism spectrum disorders; meta-analysis; PECS; speech; SGDs ID EXCHANGE COMMUNICATION-SYSTEM; AUTISM SPECTRUM DISORDERS; SINGLE-SUBJECT RESEARCH; SYNTHETIC SPEECH OUTPUT; YOUNG-CHILDREN; DEVELOPMENTAL-DISABILITIES; ALTERNATIVE COMMUNICATION; FUNCTIONAL COMMUNICATION; CONFIDENCE-INTERVALS; AGED CHILDREN AB Individuals with autism spectrum disorders (ASD) and complex communication needs often rely on augmentative and alternative communication (AAC) as a means of functional communication. This meta-analysis investigated how individual characteristics moderate effectiveness of three types of aided AAC: the Picture Exchange Communication System (PECS), speech-generating devices (SGDs), and other picture-based AAC. Effectiveness was measured via the Improvement Rate Difference. Results indicated that AAC has small to moderate effects on speech outcomes, and that SGDs appear to be most effective when considering any outcome measure with individuals with ASD without comorbid intellectual/developmental disorders (IDD). PECS appears to be most effective when considering any outcome measure with individuals with ASD and IDD. SGDs and PECS were the most effective type of AAC for preschoolers, when aggregating across outcome measures. No difference was found between systems for elementary-aged and older individuals. C1 [Ganz, Jennifer B.; Goodwyn, Fara D.; Boles, Margot B.; Davis, John L.] Texas A&M Univ, College Stn, TX 77843 USA. [Mason, Rose A.] Univ Kansas, Lawrence, KS 66045 USA. RP Ganz, JB (reprint author), Texas A&M Univ, 4225 TAMU, College Stn, TX 77843 USA. 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L, 2001, J POSIT BEHAV INTERV, V3, P194, DOI 10.1177/109830070100300401 YAMAMOTO J., 2006, JAPANESE J SPECIAL E, V43, P485 NR 73 TC 0 Z9 0 PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES PI WASHINGTON PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA SN 1944-7515 EI 1944-7558 J9 AJIDD-AM J INTELLECT JI AJIDD-Am. J. Intellect. Dev. Disabil. PD NOV PY 2014 VL 119 IS 6 BP 516 EP 535 DI 10.1352/1944-7558-119.6.516 PG 20 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AW2OO UT WOS:000346128100003 PM 25354122 ER PT J AU Levin, DS Volkert, VM Piazza, CC AF Levin, Darren S. Volkert, Valerie M. Piazza, Cathleen C. TI A Multi-Component Treatment to Reduce Packing in Children With Feeding and Autism Spectrum Disorders SO BEHAVIOR MODIFICATION LA English DT Article DE autism; chaser; feeding disorder; packing; re-distribution; swallow facilitation ID FLIPPED SPOON; FOOD SELECTIVITY; DECREASE PACKING; INDUCTION; REFUSAL AB Despite the high prevalence and potential negative consequences of feeding disorders in children with autism spectrum disorder (ASD), there are surprisingly few studies that examine the efficacy of treatment exclusively with these children. Children with feeding disorders also frequently exhibit packing (holding or pocketing food without swallowing). Investigators have evaluated procedures in the general pediatric population to treat packing, and some have shown that procedures need to be combined to form an effective treatment. Although investigators have evaluated the efficacy of re-distribution, swallow facilitation, and a chaser, these procedures have not been evaluated specifically with children with ASD. Prior to the current investigation, we successfully used nonremoval procedures to increase acceptance of pureed foods and liquids and decrease the inappropriate mealtime behavior of two children diagnosed with ASD and feeding problems; however, in each case, packing emerged during initial treatment. We then used different combinations of re-distribution, swallow facilitation, and chaser treatments to decrease packing for both children. C1 [Levin, Darren S.] Univ Nebraska Med Ctr, Behav Pediat Dept, Omaha, NE 68198 USA. [Levin, Darren S.] Univ Nebraska Med Ctr, Pediat Feeding Disorders Program, Omaha, NE 68198 USA. [Volkert, Valerie M.; Piazza, Cathleen C.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. 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PD NOV PY 2014 VL 38 IS 6 BP 940 EP 963 DI 10.1177/0145445514550683 PG 24 WC Psychology, Clinical SC Psychology GA AW0YH UT WOS:000346016700007 PM 25271069 ER PT J AU Collins, A Lockton, E Adams, C AF Collins, Anna Lockton, Elaine Adams, Catherine TI Metapragmatic explicitation ability in children with typical language development: Development and validation of a novel clinical assessment SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article DE Metapragmatic awareness; Assessment; Reliability; Social Communication Disorder; Specific language impairment; Children ID COMMUNICATION INTERVENTION PROJECT; RANDOMIZED CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDER; PRAGMATIC DIFFICULTIES; COMPREHENSION; IMPAIRMENT; KNOWLEDGE; SKILLS AB Purpose: Speech-language practitioners recognise the importance of metapragmatic (MP) ability (the ability to explicitly reflect on pragmatic rules) in therapy for children with pragmatic and social communication difficulties. There is inconclusive evidence in the literature regarding both the development of metapragmatic ability in children with typical language and the expected levels of explicitation (reflection on. pragmatic behaviours) in children's metapragmatic descriptions. The main purposes of this study were to investigate the reliability of a novel task of metapragmatic awareness (the Assessment of Metapragmatics or AMP) and to investigate typical developmental trends of metapragmatic ability and metapragmatic explicitation using the AMP task. Main results: Analysis of pooled data from 40 children with typical language development aged between six and eleven years and 48 children with communication impairments indicated that the AMP task had satisfactory internal consistency and inter-rater reliability. For children with typical language development, there was no relationship between gender and metapragmatic ability as measured by AMP. There was a linear relationship between age and AMP task scores and between age and explicitation. The scoring system used in the AMP task was sensitive to age-related changes in metapragmatic ability in a normative sample. The sophistication of metapragmatic awareness (explicitation) also increased with age. At age six years, children demonstrated metapragmatic awareness in their responses to 74% of AMP stimuli items; this increased to 95% of AMP items at ages 10-11 years. Conclusions: The AMP is a reliable measure of development in MP explicitation for children with satisfactory face validity in terms of acceptability to communication professionals and to child participants. From age six, children have some awareness of pragmatic acts and can identify and relate linguistic cues or pragmatic rules in atypical interactions of the type depicted in the AMP. The AMP task solicited significantly increased frequency of use of higher levels of MP explication beyond seven years of age in children with typical language development. Learning outcomes: Readers will explain the development, reliability and structure of a novel task that measures the ability of a child to understand and explain pragmatic rules. Readers will also identify age related changes in this ability in a sample of typically developing child participants. (C) 2014 Elsevier Inc. All rights reserved. C1 [Collins, Anna; Lockton, Elaine; Adams, Catherine] Univ Manchester, Sch Psychol Sci, Manchester M13 9PL, Lancs, England. RP Lockton, E (reprint author), Univ Manchester, Sch Psychol Sci, Ellen Wilkinson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England. EM elaine.lockton@manchester.ac.uk FU ESRC [RES-00022-2223, RES-000-22-2223] FX The original research was supported by ESRC Grant (RES-00022-2223) to Adams and Lockton (reference number: RES-000-22-2223). 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Pediatr. Nurs. PD NOV-DEC PY 2014 VL 29 IS 6 BP 596 EP 605 DI 10.1016/j.pedn.2014.03.023 PG 10 WC Nursing; Pediatrics SC Nursing; Pediatrics GA AW4AU UT WOS:000346224800013 PM 24709526 ER PT J AU Johnson, N Bree, O Lalley, EE Rettler, K Grande, P Gani, MO Ahamed, SI AF Johnson, Norah Bree, Octavia Lalley, Erin E. Rettler, Kelly Grande, Pam Gani, Md O. Ahamed, Sheikh I. TI Effect of a Social Script iPad Application for Children With Autism Going to Imaging SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Article DE Autism spectrum disorder; iPad app; Anxiety; Social script; Imaging ID SPECTRUM DISORDERS; DEVELOPMENTAL-DISABILITIES; INDIVIDUALS; STORIES; INJURY; HEALTH AB This randomized controlled trial feasibility study tested the effectiveness of an iPad (R) application (app) social script intervention for children with autism spectrum disorder (ASD) going to imaging and their parent (n = 32 parent/child dyads). Parents of the children exposed to the app = 16) had lower state anxiety compared to the parents whose children were not exposed to the app = 16) (effect size 0.33). Children exposed to the app had fewer externalized challenging behaviors than the control group (effect size 0.56). The results demonstrate feasibility and efficacy of the intervention. Further study of the iPad app is warranted. (C) 2014 Elsevier Inc. All rights reserved. C1 [Johnson, Norah; Bree, Octavia] Marquette Univ, Coll Nursing, Milwaukee, WI 53233 USA. [Lalley, Erin E.] Pk Nicollet Clin Gastroenterol, Minneapolis, MN USA. [Rettler, Kelly] Childrens Hosp Wisconsin, Child Life Dept, Milwaukee, WI 53201 USA. [Grande, Pam] Childrens Hosp Wisconsin, Dept Imaging, Milwaukee, WI 53201 USA. [Gani, Md O.; Ahamed, Sheikh I.] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53233 USA. RP Johnson, N (reprint author), Marquette Univ, Coll Nursing, Milwaukee, WI 53233 USA. 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PD NOV-DEC PY 2014 VL 29 IS 6 BP 651 EP 659 DI 10.1016/j.pedn.2014.04.007 PG 9 WC Nursing; Pediatrics SC Nursing; Pediatrics GA AW4AU UT WOS:000346224800018 PM 24836052 ER PT J AU Kane, GC Johnson, J Majchrzak, A AF Kane, Gerald C. Johnson, Jeremiah Majchrzak, Ann TI Emergent Life Cycle: The Tension Between Knowledge Change and Knowledge Retention in Open Online Coproduction Communities SO MANAGEMENT SCIENCE LA English DT Article DE online communities; peer production; knowledge creation; social media; wiki; longitudinal ID ELECTRONIC NETWORKS; INFORMATION-SYSTEMS; USER COMMUNITIES; ORGANIZATIONS; COMMUNICATION; AUTISM; PARTICIPATION; COLLABORATION; EXPLORATION; TECHNOLOGY AB Online coproduction communities often face a challenge of whether to change or retain the knowledge they have created. Disparate and often conflicting theoretical models have been used to explain how these communities respond to this tension. We conducted a case study of how one online coproduction community-the nine-year history of the Wikipedia article on autism-handles this tension. We find that the nature of the change-retain tension and the community's response to it fluctuates considerably over the life of the community. These changes bear striking similarities to processes associated with traditional software development life cycles, despite the absence of traditional control mechanisms. What initially appear to be conflicts in the extant literature actually describe different roles and production focus at the different stages of development. Disruptive events signal the need for the community to shift production focus, which often involves members joining and leaving the production process, rather than adopting new roles. C1 [Kane, Gerald C.] Boston Coll, Carroll Sch Management, Chestnut Hill, MA 02467 USA. [Johnson, Jeremiah; Majchrzak, Ann] Univ So Calif, Marshall Sch Business, Los Angeles, CA 90089 USA. RP Kane, GC (reprint author), Boston Coll, Carroll Sch Management, Chestnut Hill, MA 02467 USA. EM gerald.kane@bc.edu; johnsonjeremiah@gmail.com; majchrza@usc.edu FU National Science Foundation [1219832, 0953285] FX The authors thank department editor Sandra Slaughter and her review team for constructive comments on an earlier version of the paper. The authors also thank Lily Chen for help with coding, and the National Science Foundation [Grants 1219832, 0953285] for generous funding of this research. 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The autism susceptibility candidate 2 (AUTS2) gene has been reported to be associated with autism, suicide, alcohol consumption, and heroin dependence. We hypothesized that AUTS2 might be associated with SCZ. In the present study, three polymorphisms (rs6943555, rs7459368, and rs9886351) in the AUTS2 gene were genotyped in 410 patients with SCZ and 435 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forced PCR-RFLP methods. We detected an association between SCZ and the rs6943555 genotype distribution (odds ratio (OR) = 1.363, 95% confidence interval (CI): 0.848-2.191, p = 0.001). The association remained significant after adjusting for gender, and a significant effect (p = 0.001) was observed among the females. In the present study, rs6943555 was determined to be associated with female SCZ. Our results confirm previous reports which have suggested that rs6943555 might elucidate the pathogenesis of schizophrenia and play an important role in its etiology. C1 [Zhang, Bao; Xu, Yue-Hong; Wei, Shu-Guang; Zhang, Hong-Bo; Fu, Dong-Ke; Feng, Zu-Fei; Guan, Fang-Lin; Zhu, Yong-Sheng; Li, Sheng-Bin] Xi An Jiao Tong Univ, Coll Forens Sci, Hlth Sci Ctr, Xian 710061, Peoples R China. RP Li, SB (reprint author), Xi An Jiao Tong Univ, Coll Forens Sci, Hlth Sci Ctr, Xian 710061, Peoples R China. EM zhangbao_814@mail.xjtu.edu.cn; yueyuehong921@stu.xjtu.edu.cn; weisg@mail.xjtu.edu.cn; zhanghb@mail.xjtu.edu.cn; fdk.1991.02.07@stu.xjtu.edu.cn; zufeifeng@mail.xjtu.edu.cn; fanglingguan@mail.xjtu.edu.cn; zys3000@mail.xjtu.edu.cn; shbinlee@mail.xjtu.edu.cn FU National Natural Science Foundation of China [31301949]; National Science Foundation for Post-Doctoral Scientists of China [2013M532056]; National Science Foundation for Post-Doctoral Scientists of Shanxi FX This work was supported by the National Natural Science Foundation of China (Grant No. 31301949), the National Science Foundation for Post-Doctoral Scientists of China (Grant No. 2013M532056), and the National Science Foundation for Post-Doctoral Scientists of Shanxi. 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Hansel, Christian TI Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism SO NATURE COMMUNICATIONS LA English DT Article ID CLIMBING FIBER INNERVATION; TERM SYNAPTIC DEPRESSION; X MENTAL-RETARDATION; GAMMA MUTANT MICE; PURKINJE-CELLS; VESTIBULOOCULAR REFLEX; SPECTRUM DISORDERS; ANGELMAN SYNDROME; PROXIMAL 15Q; CHILDREN AB A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning-a form of cerebellum-dependent motor learning-is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres-a model for activity-dependent synaptic pruning-is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism. C1 [Piochon, Claire; Grasselli, Giorgio; Titley, Heather K.; Wan, Vivian; Simmons, Dana H.; Eissa, Tahra; Hansel, Christian] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. [Kloth, Alexander D.; Cherskov, Adriana; Wang, Samuel S. -H.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Kloth, Alexander D.; Cherskov, Adriana; Wang, Samuel S. -H.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA. [Nakayama, Hisako; Hashimoto, Kouichi] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Neurophysiol, Hiroshima 7348551, Japan. [Nakatani, Jin] Shiga Univ Med Sci, Otsu, Shiga 5202192, Japan. [Miyazaki, Taisuke; Watanabe, Masahiko] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan. [Takumi, Toru] RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Kano, Masanobu] Univ Tokyo, Grad Sch Med, Dept Neurophysiol, Tokyo 1130033, Japan. RP Hansel, C (reprint author), Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. EM chansel@bsd.uchicago.edu FU Ministry of Education, Culture, Sports, Science and Technology in Japan [25242077, 23111005, 25123716, 25117006, 2420007, 25000015]; Ministry's Strategic Research Program for Brain Sciences; CREST from the Japanese Science and Technology Agency; MEXT, Japan; Global COE Program; Nancy Lurie Marks Family Foundation; National Institutes of Health [NS045193, F31 MH098651]; Simons Foundation [SFARI 221582, SFARI 203507, SFARI 311232]; Brain Research Foundation [BRF SG 2011-07] FX We would like to thank E.H. Cook and P.Mason for helpful suggestions and for critically reading the manuscript. This work was supported by Ministry of Education, Culture, Sports, Science and Technology in Japan Grants-in-Aid for Scientific Research (25242077 and 23111005 to T.T.; 25123716 and 25117006 to K.H.; 2420007 to M.W.; 25000015 to M.K.), and the Ministry's Strategic Research Program for Brain Sciences (M.K.), CREST from the Japanese Science and Technology Agency (T.T.), MEXT, Japan (M.K.), the Global COE Program (M.K.), a grant from the Nancy Lurie Marks Family Foundation (S.S.-H.W.), National Institutes of Health grants NS045193 (S.S.-H.W.) and F31 MH098651 (A.K.), Simons Foundation grants SFARI 221582 (S.S.- H.W.), SFARI 203507 and SFARI 311232 (C.H.), and a grant from the Brain Research Foundation BRF SG 2011-07 (C.H.). 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Commun. PD NOV PY 2014 VL 5 AR 5586 DI 10.1038/ncomms6586 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW1XK UT WOS:000346081800001 PM 25418414 ER PT J AU Thompson, R Kerr, M Glynn, M Linehan, C AF Thompson, Rose Kerr, Mike Glynn, Mike Linehan, Christine TI Caring for a family member with intellectual disability and epilepsy: Practical, social and emotional perspectives SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE Intellectual disability; Family support; Life-long care burden; Co-morbidity ID CHILDREN; PARENTS; PEOPLE; POPULATION; PREVALENCE; CAREGIVERS; CARERS; AUTISM; BURDEN; ADULTS AB Purpose: To examine the caregiving impact of those who support a family member with intellectual disability and epilepsy. Methods: An online, qualitative international survey was conducted via the auspices of the International Bureau of Epilepsy with various stakeholders who support individuals who have intellectual disability and epilepsy. Qualitative comments were analyzed from respondents who identified themselves as family members (n = 48; 36%) who referred specifically to the impact of supporting a family member with these combined disabilities. Results: Four main domains, which were comprised of ten themes, were derived from the qualitative data using Braun and Clarke's qualitative framework. These domains comprised (1) practical concerns, (2) disrupted family dynamics, (3) emotional burden and (4) positive experiences. In combination these themes illustrate the pervasive impact on family life for those supporting an individual with complex needs. Financial concerns, coordination and responsibility of care, diverted attention from other family members and social isolation all contributed a significant burden of care for family members. Positive aspects were, however, also cited including the closeness of the family unit and a fostering of altruistic behavior. Conclusion: The study provides an insight into an under-researched area. The burden of caring for a family member across the lifespan has a largely negative and pervasive impact. Targeted service provision could contribute to an amelioration of the challenges faced by these families. (C) 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Thompson, Rose] Queen Mary Univ London, WHO Collaborat Ctr Mental Hlth Serv Dev, Barts & London Sch Med, Unit Social & Community Psychiat,Newham Ctr Menta, London, England. [Kerr, Mike] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Glynn, Mike] Epilepsy Ireland, Dublin, Ireland. [Linehan, Christine] Univ Coll Dublin, Sch Psychol, Dublin 4, Ireland. [Linehan, Christine] Univ Kent, Tizard Ctr, Canterbury, Kent, England. [Linehan, Christine] Trinity Coll Dublin, Sch Social Work & Social Policy, Dublin, Ireland. RP Linehan, C (reprint author), Univ Coll Dublin, Sch Psychol, F208 Newman Bldg, Dublin 4, Ireland. EM christine.linehan@ucd.ie FU International League against Epilepsy's Commission on Neuropsychobiology; International Bureau of Epilepsy (IBE) FX The authors would like to acknowledge the support of the International League against Epilepsy's Commission on Neuropsychobiology, the International Bureau of Epilepsy (IBE) and all the IBE and caregiver organizations who participated in this survey. 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Secondary endpoint was to correlate the results with cognitive function. Methods: Benton Facial Recognition Test (BFRT) and Ekman&Friesen series were performed for FIR and FER respectively in 23 controls, 20 IGE and 19 MTLE patients. Eye movements were recorded by a Hi-Speed eye-tracker system. Neuropsychological tools explored cognitive function. Results: Correct FIR rate was 78% in controls, 70.7% in IGE and 67.4% (p = 0.009) in MTLE patients. FER hits reached 82.7% in controls, 74.3% in IGE (p = 0.006) and 73.4% in MTLE (p = 0.002) groups. ICE patients failed in disgust (p = 0.005) and MTLE ones in fear (p = 0.009) and disgust (p = 0.03). FER correlated with neuropsychological scores, particularly verbal fluency (r = 0.542, p < 0.001). Eye-tracking revealed that controls scanned faces more diffusely than IGE and MTLE patients for FIR, who tended to top facial areas. A longer scanning of the top facial area was found in the three groups for FER. Gap between top and bottom facial region fixation time decreased in MTLE patients, with more but shorter fixations in bottom facial region. However, none of these findings were statistically significant. Conclusion: FIR was impaired in MTLE patients, and FER in both IGE and MTLE, particularly for fear and disgust. Although not statistically significant, those with impaired FER tended to perform more diffuse eye-tracking over the faces and have cognitive dysfunction. (C) 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Gomez-Ibanez, Asier; Viteri, Cesar] Univ Navarra Clin, Dept Neurol & Neurosurg, Pamplona, Spain. [Urrestarazu, Elena] Univ Navarra Clin, Serv Neurophisiol, Pamplona, Spain. RP Gomez-Ibanez, A (reprint author), Western Univ, Epilepsy Program, 339 Windermere Rd, London, ON N6G 2V4, Canada. EM asiergomez81@gmail.com FU Basque Country government [BFI-2010-43]; Advanced Program Training in Epilepsy at Clinica Universidad de Navarra (Pamplona, Spain) FX Asier Gomez-Ibanez was supported by the Aid Program for Education and Training of Research Staff (BFI-2010-43) grant from the Basque Country government to perform this study and an Advanced Program Training in Epilepsy at Clinica Universidad de Navarra (Pamplona, Spain). The authors would like to thank the following for their help in designing and technical issues while conducting this study: Maria Asuncion Pastor, Gonzalo Arrondo, Miguel Valencia and Javier Aramendia. 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Sharer, Elizabeth A. Bargh, John A. Pineda, Jaime A. TI Modulations of mirroring activity by desire for social connection and relevance of movement SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE mirror neurons; empathy; affiliation; social cognition; emotion; goals ID AUTISM SPECTRUM DISORDERS; BEHAVIORAL MIMICRY; EMOTIONAL EMPATHY; NEGATIVE AFFECT; NEURON SYSTEM; RESPONSES; POTENTIALS; MECHANISMS; IMPACT; EEG AB Mirroring neurons fire both when an individual moves and observes another move in kind. This simulation of others' movements is thought to effortlessly and ubiquitously support empathetic connection and social understanding. However, at times this could be maladaptive. How could a boxer mirror a losing opponent's expressions of fatigue, feeling his weariness, precisely when strength is required? Clearly, the boxer must emotionally disconnect from his opponent and those expressions of fatigue must become irrelevant and not mirrored. But, movements that inform of his opponent's intentions to deliver an incoming blow are quite relevant and still should require mirroring. We tested these dimensions of emotional connectedness and relevance of movement in an electroencephalography experiment, where participants' desires to socially connect with a confederate were manipulated. Before manipulation, all participants mirrored the confederate's purely kinematic (a hand opening and closing) and goal-directed (a hand opening and closing around a token that the participant desired) hand movements. After manipulation, unfairly treated subjects ceased to mirror the purely kinematic movements but continued to mirror goal-relevant movements. Those treated fairly continued to mirror all movements. The results suggest that social mirroring can be adaptive in order to meet the demands of a varied social environment. C1 [Aragon, Oriana R.; Sharer, Elizabeth A.; Bargh, John A.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Pineda, Jaime A.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. RP Aragon, OR (reprint author), 205 Fairview Rd, Westbrook, CT 06498 USA. EM oriana.aragon@yale.edu FU Yale University, Psychology Department, Graduate Dissertation Research Fund FX The authors would like to thank Gregory McCarthy for the support in laboratory resources. They would also like to thank Andre Morales, Erica Reetz and Ah Joo Shin for assisting in the running of the study. This work was supported by the Yale University, Psychology Department, Graduate Dissertation Research Fund. 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Cogn. Affect. Neurosci. PD NOV PY 2014 VL 9 IS 11 BP 1762 EP 1769 DI 10.1093/scan/nst172 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AU8LA UT WOS:000345846800015 PM 24194581 ER PT J AU Takara, K Kondo, T AF Takara, Kiyoharu Kondo, Tsuyoshi TI Autism spectrum disorder among first-visit depressed adult patients: diagnostic clues from backgrounds and past history SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Interpersonal friction; Bullied experience; Psychotic-like experiences; Age under 32 years ID PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGERS SYNDROME; FOLLOW-UP; PSYCHIATRIC COMORBIDITY; FUNCTIONING AUTISM; CLINICAL-FEATURES; SCHOOL REFUSAL; RISK-FACTORS; CHILDREN; EPIDEMIOLOGY AB Objective: The present study aimed to extract discriminating indicators for diagnosis of autism spectrum disorder (ASD) from personal backgrounds and past history among depressed adult outpatients. Methods: Subjects were 430 depressed adults, consisting of patients with ASD (n=70) and those without ASD (n=360). Group comparison and discriminant analysis was conducted with regard to backgrounds (age, gender, education, marriage, living alone, physical diseases and family history of mood disorders) and past history (school non-attendance, bullied experience, psychotic-like experiences, conduct problems, suicide-related behaviors and interpersonal friction). Results: Six discriminating indicators (interpersonal friction, bullied experience, psychotic-like experiences, age under 32 years, school non-attendance and university educational level) were identified by stepwise discriminant analysis (P<.001). Absence of the first 4 indicators almost excluded ASD diagnosis with the highest negative predictive value (98%) and the least negative likelihood ratio (0.11) whereas one or more out of these 4 indicators showed low positive predictive value (32%) despite high sensitivity (93%). Conclusions: The abovementioned 4 indicators may be useful clues to cover possible ASD subjects among depressed adults although further detailed ASD focused diagnostic procedure is absolutely necessary to specify true ASD subjects. Meanwhile, absence of these 4 indicators is probably helpful to rule out ASD diagnosis. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). C1 [Takara, Kiyoharu; Kondo, Tsuyoshi] Univ Ryukyus, Dept Neuropsychiat, Grad Sch Med, Nishihara, Okinawa 9030215, Japan. RP Takara, K (reprint author), Univ Ryukyus, Dept Neuropsychiat, Grad Sch Med, 207 Uehara, Nishihara, Okinawa 9030215, Japan. 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Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 737 EP 742 DI 10.1016/j.genhosppsych.2014.08.004 PG 6 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400034 PM 25217491 ER PT J AU Stern, JE Luke, B Hornstein, MD Cabral, H Gopal, D Diop, H Kotelchuck, M AF Stern, Judy E. Luke, Barbara Hornstein, Mark D. Cabral, Howard Gopal, Daksha Diop, Hafsatou Kotelchuck, Milton TI The effect of father's age in fertile, subfertile, and assisted reproductive technology pregnancies: A population based cohort study SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Paternal age; Maternal age; Subfertility; ART; IVF; Preterm delivery; Birthweight ID PATERNAL AGE; MATERNAL AGE; SEMEN QUALITY; BIRTH-DEFECTS; DNA-DAMAGE; SPERM; ASSOCIATION; INFERTILITY; OUTCOMES; AUTISM AB To compare ages of mothers and of fathers at delivery in couples who are fertile, subfertile, and subfertile treated with assisted reproductive technology (ART) and to characterize birth outcomes in the ART population according to paternal age. Live birth deliveries in Massachusetts between July, 2004 and December, 2008 were identified from vital records and categorized by maternal fertility status and treatment as ART, subfertile or fertile. The ART births were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database to obtain cycle-specific treatment data. Parental ages were obtained from birth certificates. Age of mothers and fathers were compared using ANOVA for continuous measures and chi (2) for categories. Risks of prematurity (< 37 weeks), low birthweight (< 2,500 g), and low birthweight z-score (small for gestatational age, SGA) were modeled using logistic regression by categories of paternal age as adjusted odds ratios and 95 % CI. The study population included 9,092 ART, 6,238 subfertile, and 318,816 fertile deliveries. Paternal ages in the ART and subfertile groups were similar and differed significantly from those of the fertile group. Maternal age in the ART and subfertile groups averaged 5-6 years older than their fertile counterparts and fathers averaged 4-5 years older with twice as many being older than 37. The risks for prematurity, low birthweight and SGA did not increase with increasing paternal age. Fathers in ART- treated and subfertile couples are older than in their fertile counterparts. Older paternal age was not assoicated with increased risk for prematurity, low birthweight, or SGA. C1 [Stern, Judy E.] Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH 03755 USA. [Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA. [Hornstein, Mark D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gopal, Daksha] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Diop, Hafsatou] Massachusetts Dept Publ Hlth, Boston, MA USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Stern, JE (reprint author), Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH 03755 USA. EM judy.e.stern@dartmouth.edu FU [R01HD064595]; [R01HD067270] FX This work was supported by R01HD064595 and R01HD067270. The views expressed in this article are those of the authors and do not necessarily represent the official view of the National Institutes of Health. 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Assist. Reprod. Genet. PD NOV PY 2014 VL 31 IS 11 BP 1437 EP 1444 DI 10.1007/s10815-014-0327-8 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA AU1UR UT WOS:000345406000006 PM 25193289 ER PT J AU Fuertes-Gonzalez, MC Silvestre, FJ AF Fuertes-Gonzalez, Maria-Cristina Silvestre, Francisco-Javier TI Oral health in a group of patients with Rett syndrome in the regions of Valencia and Murcia (Spain): A case-control study SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Rett syndrome; oral habits; bruxism; caries ID AUTISM SPECTRUM DISORDER; MUTATIONS; CHILDREN; MECP2 AB Objectives: Rett syndrome (RS) is a rare disease with oral manifestations that have not been described in detail or in a standardized manner in the literature. The present study describes the oral health of the population with RS in two Spanish regions, following the protocol of the World Health Organization for conducting common oral health surveys. Study Design: A prospective, observational case-control study was carried out, involving a group of patients with RS (n(1)=41) and a mean age of 13.37 +/- 3.19 years, and an age-and gender-matched control group without RS (n(0)=82). The data referred to oral health and habits were recorded by means of a questionnaire and oral examination was used to document caries indicators (prevalence of caries, df(t), df(s), DMF(T), DMF(S) and indices referred to dental loss, morbidity, restoration), the Community Periodontal Index (CPI), and the most characteristic oral manifestations. Results: The most frequent oral habit in the patients with RS was diurnal bruxism, followed by stereotyped tongue movements and oral breathing. The caries scores were lower in the RS population than in the control group, but patients with RS showed greater periodontal alterations and a greater prevalence of drooling, dental wear, high-arched palate and anterior open bite. Conclusions: The population with RS exhibits characteristic and early oral habits and alterations, and periodontal problems that are more notorious than caries disease, so that our efforts should focus on the diagnosis and early correction of the parafunctional habits, promoting restorative treatment, and providing instructions on correct oral hygiene. C1 [Fuertes-Gonzalez, Maria-Cristina] Red Cross Special Patients Dent Clin, Valencia, Spain. [Fuertes-Gonzalez, Maria-Cristina; Silvestre, Francisco-Javier] Univ Valencia, Dept Stomatol, E-46003 Valencia, Spain. [Silvestre, Francisco-Javier] Dr Peset Univ Hosp Valencia, Stomatol Unit, Valencia, Spain. RP Silvestre, FJ (reprint author), Hosp Univ Dr Peset Consultas Externas, Unidad Estomatol, C Juan de Garay S-N, Valencia 46017, Spain. 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Bucal PD NOV PY 2014 VL 19 IS 6 BP E598 EP E604 DI 10.4317/medoral.19743 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AU1HX UT WOS:000345372800011 PM 25350594 ER PT J AU Takuma, K Hara, Y Kataoka, S Kawanai, T Maeda, Y Watanabe, R Takano, E Hayata-Takano, A Hashimoto, H Ago, Y Matsuda, T AF Takuma, Kazuhiro Hara, Yuta Kataoka, Shunsuke Kawanai, Takuya Maeda, Yuko Watanabe, Ryo Takano, Erika Hayata-Takano, Atsuko Hashimoto, Hitoshi Ago, Yukio Matsuda, Toshio TI Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Autism spectrum disorders; Valproic acid; Sodium butyrate; Histone deacetylase; Dendritic spines; Hippocampus ID METHAMPHETAMINE-INDUCED IMPAIRMENT; ALZHEIMERS-DISEASE; RAT MODEL; HISTONE ACETYLATION; BEHAVIORAL DEFICITS; MEMORY FORMATION; HDAC INHIBITORS; MICE; MECHANISMS; CHROMATIN AB We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with WA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes. Mice given prenatal exposure to VPA exhibited novel object recognition deficits at 9 weeks of age, and that the impairment was blocked by chronic (5-week) treatment with WA (30 mg/kg/d, i.p.) or sodium butyrate (1.2 g/kg/d, i.p.) starting at 4 weeks of age. In agreement with the behavioral findings, the mice prenatally exposed to VPA showed a decrease in dendritic spine density in the hippocampal CM region, and the spine loss was attenuated by chronic treatment with sodium butyrate or VPA. Furthermore, acute treatment with sodium butyrate, but not VPA, significantly increased acetylation of histone H3 in the hippocampus at 30 mm, suggesting the difference in the mechanism for the effects of chronic VPA and sodium butyrate. These findings suggest that prenatal VPA-induced cognitive dysfunction is associated with changes in hippocampal dendritic spine morphology. (C) 2014 Elsevier Inc. All rights reserved. C1 [Takuma, Kazuhiro; Hara, Yuta; Kataoka, Shunsuke; Kawanai, Takuya; Maeda, Yuko; Watanabe, Ryo; Takano, Erika; Ago, Yukio; Matsuda, Toshio] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, Suita, Osaka 5650871, Japan. [Hashimoto, Hitoshi] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Mol Neuropharmacol, Suita, Osaka 5650871, Japan. [Hayata-Takano, Atsuko; Hashimoto, Hitoshi] Chiba Univ, Hamamatsu Univ Sch Med, Kanazawa Univ, United Grad Sch Child Dev,Osaka Univ, Suita, Osaka 5650871, Japan. [Hayata-Takano, Atsuko; Hashimoto, Hitoshi] Univ Fukui, Suita, Osaka 5650871, Japan. RP Matsuda, T (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. EM matsuda@phs.osaka-u.ac.jp RI Hashimoto, Hitoshi/D-1209-2010 OI Hashimoto, Hitoshi/0000-0001-6548-4016 FU Funding Program for Next Generation World-Leading Researchers - Japan Society for the Promotion of Science (JSPS); [25460099]; [13J05359]; [11J03070]; [26-6142]; [13J05377] FX A part of this work was supported by Grants in Aid for Scientific Research (C) (25460099) and Grand-in-Aid for JSPS Fellows (13J05359, 11J03070, 26-6142, 13J05377), and the Funding Program for Next Generation World-Leading Researchers granted by the Japan Society for the Promotion of Science (JSPS) (H.H). 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PD NOV PY 2014 VL 126 BP 43 EP 49 DI 10.1016/j.pbb.2014.08.013 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA AU2TU UT WOS:000345471200006 PM 25240644 ER PT J AU Kocsis, B Lee, P Deth, R AF Kocsis, Bernat Lee, Peia Deth, Richard TI Enhancement of gamma activity after selective activation of dopamine D4 receptors in freely moving rats and in a neurodevelopmental model of schizophrenia SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Oscillatory networks; D4R; Interneurons; In vivo; ADHD; Autism; NMDA receptor; MAM-treatment ID DEFICIT HYPERACTIVITY DISORDER; IMPROVES COGNITIVE PERFORMANCE; AUTISM SPECTRUM DISORDER; PREFRONTAL CORTEX; NMDA RECEPTORS; BAND RESPONSES; OSCILLATIONS; INTERNEURONS; ASSOCIATION; NEURONS AB Dopamine D4 receptor (D4R) mechanisms have been implicated in several psychiatric diseases, including schizophrenia, attention-deficit hyperactivity disorder (ADHD), and autism, which are characterized by cognitive deficits. The cellular mechanisms are poorly understood but impaired neuronal synchronization within cortical networks in the gamma frequency band has been proposed to contribute to these deficits. A D4R polymorphism was recently linked to variations in gamma power in both normal and ADHD subjects, and D4R activation was shown to enhance kainate-induced gamma oscillations in brain slices in vitro. The goal of this study was to investigate the effect of D4R activation on gamma oscillations in freely moving rats during natural behavior. Field potentials were recorded in the frontal, prefrontal, parietal, and occipital cortex and hippocampus. Gamma power was assessed before and after subcutaneous injection of a D4R agonist, A-412997, in several doses between 0.3 and 10.0 mg/kg. The experiments were also repeated in a neurodevelopmental model of schizophrenia, in which rats are prenatally treated with methylazoxymethanol (MAM). We found that the D4R agonist increased gamma power in all regions at short latency and lasted for similar to 2 h, both in normal and MAM-treated rats. The effect was dose dependent indicated by the significant difference between the effects after 3 and 10 mg/kg in pair-wise comparison, whereas 0.3 and 1.0 mg/kg injections were ineffective. This study demonstrates the involvement of D4R in cortical gamma oscillations in vivo and identifies this receptor as potential target for pharmacological treatment of cognitive deficits. C1 [Kocsis, Bernat; Lee, Peia] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Deth, Richard] Northeastern Univ, Boston, MA 02115 USA. RP Kocsis, B (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. EM bkocsis@hms.harvard.edu FU [MH087777]; [HL95491] FX This study was supported by MH087777, HL95491. 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PD NOV-DEC PY 2014 VL 85 IS 6 BP 2218 EP 2231 DI 10.1111/cdev.12262 PG 14 WC Psychology, Educational; Psychology, Developmental SC Psychology GA AU0EH UT WOS:000345295800009 PM 24978128 ER PT J AU Fink, E Begeer, S Hunt, C de Rosnay, M AF Fink, Elian Begeer, Sander Hunt, Caroline de Rosnay, Marc TI False-Belief Understanding and Social Preference Over the First 2 Years of School: A Longitudinal Study SO CHILD DEVELOPMENT LA English DT Article ID HIGH-FUNCTIONING AUTISM; PEER ACCEPTANCE; INDIVIDUAL-DIFFERENCES; SOCIOMETRIC STATUS; EMOTION KNOWLEDGE; EARLY-CHILDHOOD; FAUX PAS; MIND; CHILDREN; BEHAVIOR AB The role of false belief in establishing children's social relationships during the transition to school was examined and compared to other social cognitive constructs. One hundred and fourteen 5-year-olds were recruited during their 1st year of school (Time 1); 106 children were retained 1year later. 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TI Self-referential memory in autism spectrum disorder and typical development: Exploring the ownership effect SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Autism spectrum disorder; Recognition memory; Ownership; Self-reference effect; Self-awareness ID CONSCIOUSNESS; RECOGNITION; COGNITION; DEFICITS; CHILDREN; ADULTS; MIND AB Owned objects occupy a privileged cognitive processing status and are viewed almost as extensions of the self. It has been demonstrated that items over which a sense of ownership is felt will be better remembered than other items (an example of the "self-reference effect"). As autism spectrum disorder (ASD) is characterised by an a typical self-concept, people with ASD may not demonstrate this "ownership effect". Two experiments were conducted which replicate and extend Cunningham, Turk, MacDonald, and Macrae (2008). 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Cogn. PD NOV PY 2014 VL 30 BP 133 EP 141 DI 10.1016/j.concog.2014.08.023 PG 9 WC Psychology, Experimental SC Psychology GA AT8PP UT WOS:000345195100011 PM 25286242 ER PT J AU Basten, M van der Ende, J Tiemeier, H Althoff, RR Rijlaarsdam, J Jaddoe, VWV Hofman, A Hudziak, JJ Verhulst, FC White, T AF Basten, Maartje van der Ende, Jan Tiemeier, Henning Althoff, Robert R. Rijlaarsdam, Jolien Jaddoe, Vincent W. V. Hofman, Albert Hudziak, James J. Verhulst, Frank C. White, Tonya TI Nonverbal intelligence in young children with dysregulation: the Generation R Study SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE CBCL-dysregulation profile; Nonverbal intelligence; Childhood; Neurodevelopment; General population ID JUVENILE BIPOLAR DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; LONG-TERM OUTCOMES; BEHAVIOR CHECKLIST; TEST MOTIVATION; LOW IQ; CHILDHOOD; PHENOTYPE; ADHD; PSYCHOPATHOLOGY AB Children meeting the Child Behavior Checklist Dysregulation Profile (CBCL-DP) suffer from high levels of co-occurring internalizing and externalizing problems. Little is known about the cognitive abilities of these children with CBCL-DP. We examined the relationship between CBCL-DP and nonverbal intelligence. Parents of 6,131 children from a population-based birth cohort, aged 5 through 7 years, reported problem behavior on the CBCL/1.5-5. The CBCL-DP was derived using latent profile analysis on the CBCL/1.5-5 syndrome scales. Nonverbal intelligence was assessed using the Snijders Oomen Nonverbal Intelligence Test 2.5-7-Revised. We examined the relationship between CBCL-DP and nonverbal intelligence using linear regression. Analyses were adjusted for parental intelligence, parental psychiatric symptoms, socio-economic status, and perinatal factors. In a subsample with diagnostic interview data, we tested if the results were independent of the presence of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorders (ASD). The results showed that children meeting the CBCL-DP (n = 110, 1.8 %) had a 11.0 point lower nonverbal intelligence level than children without problems and 7.2-7.3 points lower nonverbal intelligence level than children meeting other profiles of problem behavior (all p values < 0.001). After adjustment for covariates, children with CBCL-DP scored 8.3 points lower than children without problems (p < 0.001). The presence of ADHD or ASD did not account for the lower nonverbal intelligence in children with CBCL-DP. In conclusion, we found that children with CBCL-DP have a considerable lower nonverbal intelligence score. The CBCL-DP and nonverbal intelligence may share a common neurodevelopmental etiology. C1 [Basten, Maartje; van der Ende, Jan; Tiemeier, Henning; Althoff, Robert R.; Rijlaarsdam, Jolien; Hudziak, James J.; Verhulst, Frank C.; White, Tonya] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat Psychol, NL-3000 CB Rotterdam, Netherlands. [Basten, Maartje; Rijlaarsdam, Jolien; Jaddoe, Vincent W. V.] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands. [Tiemeier, Henning; Jaddoe, Vincent W. V.; Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. [Althoff, Robert R.; Hudziak, James J.] Univ Vermont, Vermont Ctr Children Youth & Families, Burlington, VT USA. [Jaddoe, Vincent W. V.] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat, NL-3000 CB Rotterdam, Netherlands. [White, Tonya] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. RP van der Ende, J (reprint author), Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands. EM jan.vanderende@erasmusmc.nl FU Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development (ZonMw); NWO ZonMw TOP project [91211021]; NIMH [MH082116] FX The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trom-bosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of general practitioners, hospitals, midwives and pharmacies in Rotterdam. The first phase of the Generation R Study is made possible by financial support from: Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, and the Netherlands Organization for Health Research and Development (ZonMw). In addition, this study is supported through NWO ZonMw TOP project number 91211021 (Dr. White). Finally, this research was also supported by NIMH grant MH082116 (Dr. Althoff). 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Child Adolesc. Psych. PD NOV PY 2014 VL 23 IS 11 BP 1061 EP 1070 DI 10.1007/s00787-014-0551-x PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AT6UY UT WOS:000345076000006 PM 24802760 ER PT J AU Beuker, KT Schjolberg, S Lie, KK Swinkels, S Rommelse, NNJ Buitelaar, JK AF Beuker, Karin T. Schjolberg, Synnve Lie, Kari Kveim Swinkels, Sophie Rommelse, Nanda N. J. Buitelaar, Jan K. TI ESAT and M-CHAT as screening instruments for autism spectrum disorders at 18 months in the general population: issues of overlap and association with clinical referrals SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE ASD; M-CHAT; ESAT; Early screening; Development; Infants ID TRAITS QUESTIONNAIRE ESAT; MODIFIED CHECKLIST; PRIMARY-CARE; EARLY INTERVENTION; NORWEGIAN MOTHER; PARENTS CONCERNS; YOUNG-CHILDREN; TODDLERS; COHORT; DIAGNOSIS AB The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in very young children. The aim of this study was to explore proportions of children that screened positive on the ESAT or the M-CHAT and to investigate if screening positive on the ESAT and M-CHAT is associated with clinical referral by 18 months and other aspects of children's development, health, and behavior. In this study, the mothers of 12,948 18-month-old children returned a questionnaire consisting of items from the ESAT and M-CHAT, plus questions about clinical and developmental characteristics. The M-CHAT identified more screen-positive children than the ESAT, but the ESAT was associated with more clinical referrals and tended to identify more children with medical, language, and behavioral problems. A post hoc analysis of combining the two instruments found this to be more effective than the individual instruments alone in identifying children referred to clinical services at 18 months. Further analysis at the level of single items is warranted to improve these screening instruments. C1 [Beuker, Karin T.; Swinkels, Sophie; Rommelse, Nanda N. J.] Radboud Univ Nijmegen Med Ctr, Nijmegen Ctr Evidence Based Practice, Dept Psychiat 966, NL-6500 HB Nijmegen, Netherlands. [Beuker, Karin T.; Swinkels, Sophie; Rommelse, Nanda N. J.; Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Schjolberg, Synnve] Norwegian Inst Publ Hlth, Div Mental Hlth, Oslo, Norway. [Lie, Kari Kveim] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Buitelaar, Jan K.] Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Nijmegen Ctr Evidence Based Practice, Nijmegen, Netherlands. RP Beuker, KT (reprint author), Radboud Univ Nijmegen Med Ctr, Nijmegen Ctr Evidence Based Practice, Dept Psychiat 966, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM Karin.Beuker@radboudumc.nl FU Norwegian Ministry of Health; Ministry of Education and Research; NIH/NIEHS [N01-ES-75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1] FX The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (Contract No. N01-ES-75558), NIH/NINDS (Grant No. 1 UO1 NS 047537-01 and Grant No. 2 UO1 NS 047537-06A1). 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S, 2006, STAT METHODS RATER A NR 47 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD NOV PY 2014 VL 23 IS 11 BP 1081 EP 1091 DI 10.1007/s00787-014-0561-8 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AT6UY UT WOS:000345076000008 PM 24867341 ER PT J AU Kuteykin-Teplyakov, K Maldonado, R AF Kuteykin-Teplyakov, Konstantin Maldonado, Rafael TI Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Social behavior; Proteomics; N-Methyl-3; 4-methylenedioxyam-phetramine; Oxytocin; 5-HT1A receptor ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SOCIAL BRAIN; OXYTOCIN; ECSTASY; RECEPTOR; EXPRESSION; RESPONSES; HUMANS; RATS; HIPPOCAMPUS AB Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3, 4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3 mg/kg) has differential effects on mouse social behavior. In some animals, MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability. Both WAY-100635, a selective antagonist of 5-HT1A receptor, and L-368899, a selective oxytocin receptor antagonist, abolish prosocial effects of MDMA. Differential quantitative analysis of brain proteome by isobaric tag for relative and absolute quantification technology (iTRAQ) revealed 21 specific proteins that were highly correlated with sociability, and allowed to distinguish between entactogenic prosocial and hyperlocomotor effects of MDMA on proteome level. Our data suggest particular relevance of neurotransmission mediated by GABA B receptor, as well as proteins involved in energy maintenance for MDMA-induced sociability. Functional association network for differentially expressed proteins in cerebral cortex, hippocampus and amygdala were identified. These results provide new information for understanding the neurobiological substrate of sociability and may help to discover new therapeutic approaches to modulate social behavior in patients suffering from social fear and low sociability. (C) 2014 Elsevier B.V. and ECNP. All rights reserved. C1 [Kuteykin-Teplyakov, Konstantin; Maldonado, Rafael] Univ Pompeu Fabra, Neuropharmacol Lab, Barcelona 08003, Spain. RP Kuteykin-Teplyakov, K (reprint author), Univ Pompeu Fabra, Dept Nat Sci & Hlth, Neuropharmacol Lab, Carrer Dr Aiguader 88, Barcelona 08003, Spain. EM konstantin.kuteykin@upf.edu FU Spanish "Ministerio de Ciencia e Innovacion" [SAF2011-29864]; Spanish "Instituto de Salud Carlos III" [RD06/0001/0001, RD06/0001/1004]; Spanish "Plan Nacional sobre Drogas" [PNSD 2009/026]; Catalan Government [5GR2009-00131]; ICREA Foundation; European Commission [MC-2010-274950] FX This work was supported by the Spanish "Ministerio de Ciencia e Innovacion" (SAF2011-29864); Spanish "Instituto de Salud Carlos III" (RETICS - Red de Trastornos Adictivos - Redes Tematicas de Investigacion Cooperativa en Salud: #RD06/0001/0001, #RD06/0001/1004); Spanish "Plan Nacional sobre Drogas" (PNSD #2009/026); the Catalan Government (5GR2009-00131); and the ICREA Foundation (ICREA Academia-2008). KK-T was supported by a Marie Curie Intra-European Fellowship from the European Commission (MC-2010-274950). These institutions had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. 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Although there is no single identifiable cause for autism, roles for genetic and environmental factors have been implicated in autism. Extensive evidence suggests increased oxidative stress and mitochondrial dysfunction in autism. In this study, we examined whether bisphenol A (BPA) is an environmental risk factor for autism by studying its effects on oxidative stress and mitochondrial function in the lymphoblasts. When lymphoblastoid cells from autistic subjects and age-matched unaffected sibling controls were exposed to SPA, there was an increase in the generation of reactive oxygen species (ROS) and a decrease in mitochondrial membrane potential in both groups. A further subdivision of the control group into two subgroups unaffected nontwin siblings and twin siblings showed significantly higher ROS levels without any exposure to BPA in the unaffected twin siblings compared to the unaffected nontwin siblings. ROS levels were also significantly higher in the autism vs the unaffected nontwin siblings group. The effect of BPA on three important mtDNA genes NADH dehydrogenase 1, NADH dehydrogenase 4, and cytochrome b-was analyzed to observe any changes in the mitochondria after BPA exposure. SPA induced a significant increase in the mtDNA copy number in the lymphoblasts from the unaffected siblings group and in the unaffected twin siblings group vs the unaffected nontwin siblings. In all three genes, the mtDNA increase was seen in 70% of the subjects. These results suggest that SPA exposure results in increased oxidative stress and mitochondrial dysfunction in the autistic subjects as well as the age-matched sibling control subjects, particularly unaffected twin siblings. Therefore, BPA may act as an environmental risk factor for autism in genetically susceptible children by inducing oxidative stress and mitochondrial dysfunction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kaur, Kulbir; Chauhan, Ved; Gu, Feng; Chauhan, Abha] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA. [Kaur, Kulbir] CUNY, Grad Ctr, Biol Neurosci Grad Program, New York, NY 10016 USA. [Kaur, Kulbir] Ctr Dev Neurosci & Dev Disabil, Staten Isl, NY 10314 USA. RP Chauhan, A (reprint author), New York State Inst Basic Res Dev Disabil, Dept Neurochem, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM abha.chauhan@opwdd.ny.gov FU NYS Institute for Basic Research in Developmental Disabilities; Autism Research Institute, Autism Collaboration; CUNY Graduate Center/CSI-CDNDD Program FX This work was supported in part by funds from the NYS Institute for Basic Research in Developmental Disabilities, Autism Research Institute, Autism Collaboration, and CUNY Graduate Center/CSI-CDNDD Program. 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Biol. Med. PD NOV PY 2014 VL 76 BP 25 EP 33 DI 10.1016/j.freeradbiomed.2014.07.030 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AT9NW UT WOS:000345254800003 PM 25101517 ER PT J AU Mazurek, MO Handen, BL Wodka, EL Nowinski, L Butter, E Engelhardt, CR AF Mazurek, Micah O. Handen, Benjamin L. Wodka, Ericka L. Nowinski, Lisa Butter, Eric Engelhardt, Christopher R. TI Age at First Autism Spectrum Disorder Diagnosis: The Role of Birth Cohort, Demographic Factors, and Clinical Features SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism; autism spectrum disorder; diagnosis; early diagnosis; delayed diagnosis ID CHILDREN; SAMPLE; TIME AB Objective: This study sought to identify factors that may be associated with delays in autism spectrum disorder (ASD) diagnosis, including birth cohort, sociodemographic characteristics, and clinical features. Methods: Participants included 1716 children and adolescents with ASD enrolled in the Autism Speaks Autism Treatment Network (AS-ATN) between the years 2008 and 2011. Data were collected at enrollment using AS-ATN parent- and clinician-report forms and standardized measures of I.Q., ASD symptoms, adaptive function, and psychiatric symptoms. Results: Age at first ASD diagnosis was positively correlated with current age, suggesting a birth cohort effect. Sociodemographic and clinical features were also associated with age at diagnosis, even after controlling for current age. Hierarchical linear regression results showed that older current age, lower socioeconomic status (SES), higher I.Q. score, and lower levels of autism symptoms were associated with later age at initial diagnosis. There was also a significant interaction between current age and I.Q., with higher functioning children being diagnosed at younger ages than in previous years. Conclusions: Early diagnosis of ASD is critically important for improving access to interventions; however, many children experience diagnostic delays. In this sample, children from the most recent birth cohorts were diagnosed earlier, suggesting that early signs of ASD are being increasingly recognized. However, socioeconomic barriers to diagnosis still seem to exist. Children with less severe ASD symptoms and with higher I.Q. are also diagnosed at later ages. Efforts are still needed to reduce diagnostic disparities for families of low SES and to improve early recognition of more subtle symptoms. C1 [Mazurek, Micah O.; Engelhardt, Christopher R.] Univ Missouri, Dept Hlth Psychol, Columbia, MO 65211 USA. [Mazurek, Micah O.; Engelhardt, Christopher R.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO 65211 USA. [Handen, Benjamin L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Wodka, Ericka L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Wodka, Ericka L.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA. [Nowinski, Lisa] MassGen Hosp Children, Lurie Ctr Autism, Boston, MA USA. [Nowinski, Lisa] Harvard Univ, Sch Med, Boston, MA USA. [Butter, Eric] Ohio State Univ, Nationwide Childrens Hosp, Dept Pediat, Columbus, OH 43210 USA. [Butter, Eric] Ohio State Univ, Nationwide Childrens Hosp, Dept Psychol, Columbus, OH 43210 USA. RP Mazurek, MO (reprint author), Univ Missouri, Dept Hlth Psychol, 205 Portland St, Columbia, MO 65211 USA. EM mazurekm@missouri.edu FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054] 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 were collected as part of the AS-Am Further support came from a cooperative agreement (UA3 MC 11054) from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to the Massachusetts General Hospital. The views expressed in this publication do not necessarily reflect the views of the AS-ATN. CR Achenbach TM, 2001, MANUAL ASEBA SCH AGE Aman MG, 2005, J CHILD ADOL PSYCHOP, V15, P116, DOI 10.1089/cap.2005.15.116 American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2013, DIAGN STAT MAN MENT Charman T, 2005, J CHILD PSYCHOL PSYC, V46, P500, DOI 10.1111/j.1469-7610.2004.00377.x Daniels AM, 2011, J AUTISM DEV DISORD, V41, P110, DOI 10.1007/s10803-010-1031-x Daniels AM, 2014, AUTISM, V18, P583, DOI 10.1177/1362361313480277 Elliot C. 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Dev. Behav. Pediatr. PD NOV-DEC PY 2014 VL 35 IS 9 BP 561 EP 569 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AT7HN UT WOS:000345107400001 PM 25211371 ER PT J AU Larru, B Offit, P AF Larru, Beatriz Offit, Paul TI Communicating vaccine science to the public SO JOURNAL OF INFECTION LA English DT Article DE Vaccine; Communication; Social media ID AUTISM AB Communicating science to the public is not always a straightforward process. In the case of vaccines, fear and lack of knowledge makes it even more challenging. We present some suggestions on how to defend the methods and fruits of scientific investigation to the public: 1) stand up for science, even if it not an easy task, 2) remember that no venue it too small, 3) don't let bad information go unchallenged, 4) don't assume other people are doing it, they are not and 5) remember that scientist have a responsibility to the public. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Larru, Beatriz; Offit, Paul] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. RP Larru, B (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, 3615 Civ Ctr Blvd,ARC Suite 1202, Philadelphia, PA 19104 USA. EM LarruB@email.chop.edu; offit@email.chop.edul CR Armstrong GL, 2001, PEDIATRICS, V108, P1123, DOI 10.1542/peds.108.5.1123 Offit MD, 2013, DO YOU BELIEVE MAGIC, VHarperCollins Offit P. A, 2011, DEADLY CHOICES ANTIV Offit PA, 2011, VACCINES YOUR CHILD Plotkin MD, 2008, VACCINES Taylor B, 1999, LANCET, V353, P2026, DOI 10.1016/S0140-6736(99)01239-8 Wakefield AJ, 1999, LANCET, V354, P949, DOI 10.1016/S0140-6736(05)75696-8 NR 7 TC 0 Z9 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD NOV PY 2014 VL 69 SU 1 BP S2 EP S4 DI 10.1016/j.jinf.2014.07.009 PG 3 WC Infectious Diseases SC Infectious Diseases GA AT4UD UT WOS:000344937400002 PM 25264164 ER PT J AU Price, AMH Coates, C Symeonides, C Hiscock, H Smith, L York, E Hennel, S AF Price, Anna M. H. Coates, Cathy Symeonides, Christos Hiscock, Harriet Smith, Libby York, Elissa Hennel, Sabine TI Chocolate frogs do not increase completion of parent survey: Randomised study SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH LA English DT Article DE incentive; parent survey; randomised control trial; response rate AB Four months into a year-long, national survey assessing parents' experiences of a child's diagnosis of autism spectrum disorder, our response fraction was only 23%. We aimed to determine whether including a chocolate incentive in the postal survey would increase the response fraction. Families enrolled between 15 March and 25 May 2012 were randomised to receive a chocolate frog versus no chocolate frog. Both groups received a written reminder and replacement survey 2 weeks after the survey was posted and up to two telephone reminders thereafter. We analysed the effect of the incentive using (2) tests for the categorical response variable and t-tests for the continuous reminder and length of response variables at the end of (i) randomisation and (ii) the study (1November 2012). A total of 137 families were randomised in the 6-week period. Parents who received an incentive were more likely to return a completed survey in the 6 weeks than those who did not (21% vs. 6%, P=0.009). This effect faded by the end of the study (53% vs. 42%, P=0.4). There were no differences between groups at either follow-up in the number of reminders that parents received or the number of days it took parents to return the survey. Including a chocolate-based incentive does not significantly increase response rate in a postal survey over and above standard reminder techniques like posting follow-up survey packs or phoning families. C1 [Price, Anna M. H.; Symeonides, Christos; Hiscock, Harriet; Smith, Libby; York, Elissa] Royal Childrens Hosp, Murdoch Childrens Res Inst, Ctr Community Child Hlth, Melbourne, Vic, Australia. [Symeonides, Christos] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Hennel, Sabine] Monash Childrens Hosp, Victorian Paediat Rehabil Serv & Dev Med Unit, Melbourne, Vic, Australia. [Coates, Cathy] Latrobe Reg Hosp, Traralgon, Vic, Australia. RP Price, AMH (reprint author), Royal Childrens Hosp, Ctr Community Child Hlth, Flemington Rd, Parkville, Vic 3052, Australia. EM anna.price@mcri.edu.au FU Scobie and Claire Mackinnon Trust; Southern Health; NHMRC Population Health Capacity Building Grant [436914]; NHMRC Career Development Award [607351]; Murdoch Childrens Research Institute (MCRI); Victorian Government's Operational Infrastructure Support Program FX This study was funded by the Scobie and Claire Mackinnon Trust and Southern Health. AP was supported by NHMRC Population Health Capacity Building Grant #436914 and HH by NHMRC Career Development Award 607351. The Murdoch Childrens Research Institute (MCRI) administered the grants and provided infrastructural support to its staff but played no role in the conduct or analysis of the trial. MCRI research is supported by the Victorian Government's Operational Infrastructure Support Program. CR Brennan M, 2009, PUBLIC OPIN QUART, V73, P368, DOI 10.1093/poq/nfp030 Edwards PJ, 2009, COCHRANE DB SYST REV, DOI 10.1002/14651858.MR000008.pub4 Gendall P, 2005, P ANZMAC 2005 C 5 7 Heussler H, 2012, SLEEP MED, V14, P189 Hiscock H, 2011, MED J AUSTRALIA, V194, P392 Hiscock H, 2012, J PAEDIATR CHILD H, V48, P6, DOI 10.1111/j.1440-1754.2010.01772.x Rudolph S, 2009, J PAEDIATR CHILD H, V45, P704, DOI 10.1111/j.1440-1754.2009.01598.x NR 7 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1034-4810 EI 1440-1754 J9 J PAEDIATR CHILD H JI J. Paediatr. Child Health PD NOV PY 2014 VL 50 IS 11 BP 866 EP 868 DI 10.1111/jpc.12606 PG 3 WC Pediatrics SC Pediatrics GA AU0OK UT WOS:000345322500006 PM 24925605 ER PT J AU Shaukat, F Fatima, A Zehra, N Hussein, MAG Ismail, O AF Shaukat, Farah Fatima, Ambreen Zehra, Nosheen Hussein, Mohammed Amirali Ghulam Ismail, Ozair TI Assessment of knowledge about childhood autism among medical students from private and public universities in Karachi SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION LA English DT Article DE Autism; Pervasive developmental disorder; Medical university students ID DISORDERS; NIGERIA AB Objective: To Assess the knowledge about childhood autism among fourth year medical students in public and private medical universities of a metropolitan city. Methods: The cross-sectional descriptive study was conducted in Karachi from January to August 2012. Two medical universities - one each from public and private sectors - were selected using non-probability convenience sampling technique. Fourth year medical students present at the time of data collection were included in the study. Data collection was done by Knowledge About Childhood Autism Among Health Worker questionnaire from fourth year medical students. Data was analysed using SPS5 20. Results: Of the 157 students in the study, 62(39.6%) were males and 95(60.4%) were females; 84(43.5%) were from public medical university and 73(46.5%) were from private university. Total mean score obtained out of the maximum 25 was 12.30 +/- 4.71. The mean score obtained by public medical students was 12.40 +/- 4.69 and 12.1 +/- 4.76 by those of private university. Conclusion: The scores reflected shortcoming in knowledge about childhood autism among the study population. In order to bridge knowledge deficit, awareness-generation activities must be held more frequently. C1 [Shaukat, Farah; Fatima, Ambreen; Hussein, Mohammed Amirali Ghulam; Ismail, Ozair] Ziauddin Univ, Karachi, Pakistan. [Zehra, Nosheen] Ziauddin Univ, Dept Community Hlth Sci, Karachi, Pakistan. RP Shaukat, F (reprint author), Ziauddin Univ, Karachi, Pakistan. 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Intriguingly, our recent results from an entirely different line of reasoning and experiments also show that applying cathodal stimulation (suppressing) at the left anterior temporal lobe together with anodal stimulation (facilitating) at the right anterior temporal lobe, by transcranial direct current stimulation (tDCS), can induce some autistic-like cognitive abilities in otherwise normal adults. If we could briefly induce autistic like cognitive abilities in healthy individuals, it follows that we might be able to mitigate some autistic traits by reversing the above stimulation protocol, in an attempt to restore the typical dominance of the left anterior temporal lobe. Accordingly, we hypothesize that at least some autistic traits can be mitigated, by applying anodal stimulation (facilitating) at the left anterior temporal lobe together with cathodal stimulation (suppressing) at the right anterior temporal lobe. Our hypothesis is supported by strong convergent evidence that autistic symptoms can emerge and later reverse due to the onset and subsequent recovery of various temporal lobe (predominantly the left) pathologies. It is also consistent with evidence that the temporal lobes (especially the left) are a conceptual hub, critical for extracting meaning from lower level sensory information to form a coherent representation, and that a deficit in the temporal lobes underlies autistic traits. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chi, Richard P.] Creat Cap, Sydney, NSW, Australia. [Snyder, Allan W.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. RP Snyder, AW (reprint author), Univ Sydney, Sydney Med Sch, Med Fdn Bldg K25, Sydney, NSW 2006, Australia. 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Hypotheses PD NOV PY 2014 VL 83 IS 5 BP 614 EP 618 DI 10.1016/j.mehy.2014.08.002 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8KG UT WOS:000345181700020 PM 25227333 ER PT J AU Pujol, J Macia, D Blanco-Hinojo, L Martinez-Vilavella, G Sunyer, J de la Torre, R Caixas, A Martin-Santos, R Deus, J Harrison, BJ AF Pujol, Jesus Macia, Didac Blanco-Hinojo, Laura Martinez-Vilavella, Gerard Sunyer, Jordi de la Torre, Rafael Caixas, Assumpta Martin-Santos, Rocio Deus, Joan Harrison, Ben J. TI Does motion-related brain functional connectivity reflect both artifacts and genuine neural activity? SO NEUROIMAGE LA English DT Article DE fMRI; Resting-state; Brain networks; Sensorimotor cortex; Default mode network; Head motion ID ABERRANT BEHAVIOR CHECKLIST; AUTISM-SPECTRUM DISORDER; DOWN-SYNDROME; DEFAULT NETWORK; HEAD MOTION; IMPACT; MRI; RELEVANCE; CHILDREN; DISEASE AB Imaging research on functional connectivity is uniquely contributing to characterize the functional organization of the human brain. Functional connectivity measurements, however, may be significantly influenced by head motion that occurs during image acquisition. The identification of how motion influences such measurements is therefore highly relevant to the interpretation of a study's results. We have mapped the effect of head motion on functional connectivity in six different populations representing a wide range of potential influences of motion on functional connectivity. Group-level voxel-wise maps of the correlation between a summary head motion measurement and functional connectivity degree were estimated in 80 young adults, 71 children, 53 older adults, 20 patients with Down syndrome, 24 with Prader-Willi syndrome and 20 with Williams syndrome. In highly compliant young adults, motion correlated with functional connectivity measurements showing a system-specific anatomy involving the sensorimotor cortex, visual areas and default mode network. Further characterization was strongly indicative of these changes expressing genuine neural activity related to motion, as opposed to pure motion artifact. In the populations with larger head motion, results were more indicative of widespread artifacts, but showing notably distinct spatial distribution patterns. Group-level regression of motion effects was efficient in removing both generalized changes and changes putatively related to neural activity. Overall, this study endorses a relatively simple approach for mapping distinct effects of head motion on functional connectivity. Importantly, our findings support the intriguing hypothesis that a component of motion-related changes may reflect system-specific neural activity. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pujol, Jesus; Macia, Didac; Blanco-Hinojo, Laura; Martinez-Vilavella, Gerard; Deus, Joan] Hosp Mar, CRC Mar, MRI Res Unit, Barcelona 08003, Spain. [Pujol, Jesus] CIBERSAM G21, Barcelona, Spain. [Blanco-Hinojo, Laura; de la Torre, Rafael] Hosp Mar, Dept Magnet Resonance, Barcelona 08003, Spain. [Sunyer, Jordi] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Sunyer, Jordi] UFP, Barcelona, Spain. [de la Torre, Rafael] CIBER Fisiopatol Obesidad & Nutr CIBEROBN, S De Compostela, Spain. [Caixas, Assumpta] Univ Autonoma Barcelona, Hosp Sabadell, Inst Univ Parc Tauli, Diabet Endocrinol & Nutr Dept, E-08193 Barcelona, Spain. [Martin-Santos, Rocio] Univ Barcelona, Hosp Clin, CIBERSAM, Clin Inst Neurosci,Dept Psychiat & Clin Psychobio, Barcelona, Spain. [Deus, Joan] Autonomous Univ Barcelona, Dept Clin & Hlth Psychol, Barcelona, Spain. [Harrison, Ben J.] Univ Melbourne, Melbourne Neuropsychiatry Ctr, Dept Psychiat, Melbourne, Vic, Australia. RP Pujol, J (reprint author), Hosp Mar, CRC Mar, Dept Magnet Resonance, Passeig Maritim 25-29, Barcelona 08003, Spain. EM jpujol@crccorp.es RI Deus Yela, Joan/F-3652-2011; Sunyer, J/G-6909-2014 OI Sunyer, J/0000-0002-2602-4110 FU Spanish Government [SAF2010-19434, PI10/00940, PI11/00744]; European Community [268479]; PFIS grant from the Carlos III Health Institute [FI10/00387]; National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Award [628509] FX This study was supported in part by the Spanish Government (grants SAF2010-19434, PI10/00940 and PI11/00744) and the European Community's Seventh Framework Program (ERC-Advanced grant number 268479). The Agency of University and Research Funding Management of the Catalonia Government participated in the context of Research Groups SGR 2009/1450. Ms. Blanco-Hinojo is supported by the PFIS grant FI10/00387 from the Carlos III Health Institute. Dr. Harrison is supported by a National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Award (I.D. 628509). 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Becker, Stefanie I. Dux, Paul E. TI Implicit false-belief processing in the human brain SO NEUROIMAGE LA English DT Article DE Eye-movements; fMRI; Implicit theory of mind; Social cognition ID TEMPORO-PARIETAL JUNCTION; HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; ASPERGER-SYNDROME; INDIVIDUAL-DIFFERENCES; PREFRONTAL CORTEX; SOCIAL COGNITION; OTHERS BELIEFS; MIND TASKS; ATTENTION AB Eye-movement patterns in 'Sally-Anne' tasks reflect humans' ability to implicitly process the mental states of others, particularly false-beliefs - a key theory of mind (ToM) operation. It has recently been proposed that an efficient ToM system, which operates in the absence of awareness (implicit ToM, iToM), subserves the analysis of belief-like states. This contrasts to consciously available belief processing, performed by the explicit ToM system (eToM). The frontal, temporal and parietal cortices are engaged when humans explicitly 'mentalize' about others' beliefs. However, the neural underpinnings of implicit false-belief processing and the extent to which they draw on networks involved in explicit general-belief processing are unknown. Here, participants watched 'Sally-Anne' movies while fMRI and eye-tracking measures were acquired simultaneously. Participants displayed eye-movements consistent with implicit false-belief processing. After independently localizing the brain areas involved in explicit general-belief processing, only the left anterior superior temporal sulcus and precuneus revealed greater blood-oxygen-level-dependent activity for false-relative to true-belief trials in our iToM paradigm. No such difference was found for the right temporal-parietal junction despite significant activity in this area. These findings fractionate brain regions that are associated with explicit general ToM reasoning and false-belief processing in the absence of awareness. (C) 2014 Elsevier Inc. All rights reserved. C1 [Schneider, Dana; Slaughter, Virginia P.; Becker, Stefanie I.; Dux, Paul E.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Schneider, Dana] Univ Jena, Inst Psychol, D-07743 Jena, Germany. RP Schneider, D (reprint author), Univ Jena, Inst Psychol, Dept Gen Psychol & Cognit Neurosci, Steiger 3,Haus 1, D-07743 Jena, Germany. EM msdanaschneider@gmail.com; paul.e.dux@gmail.com FU University of Queensland; Australian Research Council [DP120103721, DP110100588, DP0986387, FT120100033] FX DS was supported by a The University of Queensland PhD Centennial Scholarship, SIB by an Australian Research Council Discovery Grant and APD Fellowship (DP120103721; DP110100588); and PED by an Australian Research Council Discovery Grant and APD fellowship (DP0986387) and an Australian Research Council Future Fellowship (FT120100033). 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Recent evidences has expanded the concept of coordination, from voluntary movements and orientation of the body to nearly every cerebral function including emotion regulation, social cognition, and time perception. This article aims to review the current evidences supporting the role of the cerebellum in the pathophysiology of psychiatric disorders, including studies using volumetric and/or functional imaging techniques, genetic and molecular studies, and clinical reports. The implication of these findings, their potential use, and future directions are also discussed. C1 Univ Tehran Med Sci, Rouzbeh Hosp, Dept Psychiat, Tehran 1333795914, Iran. RP Shakiba, A (reprint author), Univ Tehran Med Sci, Rouzbeh Hosp, Dept Psychiat, 606 South Kargar Ave, Tehran 1333795914, Iran. 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Clin. PD NOV PY 2014 VL 32 IS 4 BP 1105 EP + DI 10.1016/j.ncl.2014.07.008 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AT8NU UT WOS:000345190600014 PM 25439296 ER PT J AU Song, G Silva, CL Jenkins-Smith, HC AF Song, Geoboo Silva, Carol L. Jenkins-Smith, Hank C. TI Cultural Worldview and Preference for Childhood Vaccination Policy SO POLICY STUDIES JOURNAL LA English DT Article DE childhood vaccination policy; health policy; cultural theory; public opinion ID RISK PERCEPTION; RUBELLA VACCINE; UNITED-STATES; POLITICAL-IDEOLOGY; INTERNET SURVEYS; PERCEIVED RISK; PUBLIC-HEALTH; IMMUNIZATION; MEASLES; AUTISM AB In the face of the reemerging threat of preventable diseases and the simultaneous vaccine risk controversy, what explains variations in Americans' policy preferences regarding childhood vaccinations? Using original data from a recent nationwide Internet survey of 1,213 American adults, this research seeks to explain differing public opinions on childhood vaccination policies and related issues of governance. As Mary Douglas and Aaron Wildavsky's grid-group cultural theory of policy preference formation suggests, cultural biases have a significant impact on the formation of preferences toward various vaccination policies. Hierarchs are in support of mandatory vaccination, oppose religious and philosophical exemption, and believe the government should preside over vaccination-related decisions. Fatalists strike a bold contrast in their opposition to mandatory vaccination policy and support for religious and philosophical exemptions and the role of parents in deciding on vaccinations. Falling between hierarchs and fatalists, egalitarian support for vaccinations is stronger than individualists. C1 [Song, Geoboo] Univ Arkansas, J William Fulbright Coll Arts & Sci, Dept Polit Sci, Fayetteville, AR 72701 USA. [Silva, Carol L.; Jenkins-Smith, Hank C.] Univ Oklahoma, Dept Polit Sci, Norman, OK 73019 USA. [Silva, Carol L.] Univ Oklahoma, Ctr Risk Crisis & Management, Norman, OK 73019 USA. [Jenkins-Smith, Hank C.] Univ Oklahoma, Ctr Energy Secur & Soc, Norman, OK 73019 USA. [Jenkins-Smith, Hank C.] Sandia Natl Labs, Ctr Energy Secur & Soc, Livermore, CA 94550 USA. RP Song, G (reprint author), Univ Arkansas, J William Fulbright Coll Arts & Sci, Dept Polit Sci, Fayetteville, AR 72701 USA. 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J. PD NOV PY 2014 VL 42 IS 4 BP 528 EP 554 DI 10.1111/psj.12076 PG 27 WC Political Science; Public Administration SC Government & Law; Public Administration GA AU0YM UT WOS:000345348100004 ER PT J AU Davis, MC Horan, WP Nurmi, EL Rizzo, S Li, WD Sugar, CA Green, MF AF Davis, Michael C. Horan, William P. Nurmi, Erika L. Rizzo, Shemra Li, Wendy Sugar, Catherine A. Green, Michael F. TI Associations between oxytocin receptor genotypes and social cognitive performance in individuals with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Social cognition; Oxytocin; Oxytocin receptor; Single nucleotide polymorphism ID GENE OXTR; JAPANESE POPULATION; POLYMORPHISM OXTR; 5-HTT GENES; AUTISM; RISK; VARIANTS; BEHAVIOR; SUPPORT; INTELLIGENCE AB Individuals with schizophrenia often show substantial deficits in social cognitive abilities, which are strongly associated with social functioning. To advance our understanding of the genetic variation that is associated with social cognitive deficits in schizophrenia, we genotyped 74 schizophrenia outpatients who completed social cognitive performance measures assessing mentalizing, social perception, and emotional intelligence, as well as clinical symptoms. We assessed seven single nucleotide polymorphisms (SNPs) of the oxytocin receptor (OXTR) previously found to show replicable associations with socio-emotional processes. For one of the seven SNPs, rs2268493, the 'T' allele was significantly associated with poorer performance on a composite social cognition index, as well as specific tests of mentalizing and social perception. None of the SNPs were associated with clinical symptoms. Though the sample size is small, these findings provide initial support for the involvement of genetic variants of the OXTR in social cognitive impairments in schizophrenia. Published by Elsevier B.V. C1 [Davis, Michael C.; Horan, William P.; Nurmi, Erika L.; Li, Wendy; Sugar, Catherine A.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Davis, Michael C.; Horan, William P.] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Rizzo, Shemra; Sugar, Catherine A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. RP Green, MF (reprint author), 11301 Wilshire Blvd Bldg 210A, Los Angeles, CA 90073 USA. EM mgreen@ucla.edu RI Nurmi, Erika/P-4627-2014 OI Nurmi, Erika/0000-0003-4893-8957 FU NIH [MH043292, MH094613-01]; VA Desert Pacific Mental Illness Research, Education, and Clinical Center FX This work was supported by NIH MH043292 to MFG; NIH MH094613-01 to ELN; and the VA Desert Pacific Mental Illness Research, Education, and Clinical Center. 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In order to identify convergent and divergent mechanisms, we investigated facial emotion recognition in SZ, high-functioning ASD (HFASD), and typically developed controls (TD). Different degrees of task difficulty and emotion complexity (face, eyes; basic emotions, complex emotions) were used. Two Benton tests were implemented in order to elicit potentially confounding visuo-perceptual functioning and facial processing. Nineteen participants with paranoid SZ, 22 with HFASD and 20 TD were included, aged between 14 and 33 years. Individuals with SZ were comparable to TD in all obtained emotion recognition measures, but showed reduced basic visuo-perceptual abilities. The HFASD group was impaired in the recognition of basic and complex emotions compared to both, SZ and TD. When facial identity recognition was adjusted for, group differences remained for the recognition of complex emotions only. Our results suggest that there is a SZ subgroup with predominantly paranoid symptoms that does not show problems in face processing and emotion recognition, but visuo-perceptual impairments. They also confirm the notion of a general facial and emotion recognition deficit in HFASD. No shared emotion recognition deficit was found for paranoid SZ and HFASD, emphasizing the differential cognitive underpinnings of both disorders. (C) 2014 Elsevier B.V. All rights reserved. C1 [Sachse, Michael; Schlitt, Sabine; Hainz, Daniela; Ciaramidaro, Angela; Poustka, Fritz; Bolte, Sven; Freitag, Christine M.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany. [Walter, Henrik] Goethe Univ Frankfurt, Dept Psychiat Psychosomat & Psychotherapy, Frankfurt, Germany. [Bolte, Sven] Karolinska Inst KIND, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, Stockholm, Sweden. RP Sachse, M (reprint author), Deutschordenstr 50, D-60528 Frankfurt, Germany. 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We do so by drawing on narrative qualitative interviews and visual practices carried out with seventeen disabled young people in a project funded by the Economic and Social Research Council that took place between 2011 and 2012 in the North East of England. The findings discussed here focus on how medical and societal responses to bodily difference become part of the stories disabled young people tell about their bodies, and influence the way they work with the body as something which remains 'unfinished' and therefore both fixable and flawed. Our conclusion is that a narrative of an unfinished body is produced, as young people manage their bodies as something that is integral to their emerging identity, but also as a potential threat that could undermine and give away their labour in making an 'ordinary' functioning body and life. 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Sci. Med. PD NOV PY 2014 VL 120 BP 76 EP 84 DI 10.1016/j.socscimed.2014.09.012 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AT8JU UT WOS:000345180600009 PM 25226449 ER PT J AU Ha, VS Whittaker, A Whittaker, M Rodger, S AF Vu Song Ha Whittaker, Andrea Whittaker, Maxine Rodger, Sylvia TI Living with autism spectrum disorder in Hanoi, Vietnam SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Autism spectrum disorder; Stigma; Assessment; Children; Vietnam ID INTELLECTUAL DISABILITIES; CHILDREN; CHALLENGES; INCLUSION; FAMILIES; PARENTS; NAM AB There is limited understanding of Autism spectrum disorder (ASD) in Vietnam. This ethnographic study aimed to explore how ASD is represented and managed in the cultural, social and economic contexts of Vietnam, and describe the experiences of families with children with ASD in Hanoi, Vietnam. This study was conducted from 2011 to 2012 in Hanoi and employed a range of methods, including participant observation, in-depth interviews with 27 parents of children with ASD and 17 key informants, and online survey. This study found that within Hanoi, Vietnam, ASD has been culturally and socially constructed as a 'disease', 'karmic demerit' and 'family problem' rather than a life-long developmental disorder that needs support from government Children with ASD and their families experience various forms of stigma and discrimination. There are limitations in assessment and diagnosis of ASD. Parents of children with ASD have little access to services for their children, and the limited political and economic supports exacerbate their difficulties. This study highlights some of the ways in which the understandings and management of ASD vary cross culturally. It also suggests further attention is required to the provision of appropriate public education, low cost interventions and support for family advocacy groups. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Vu Song Ha] Ctr Creat Initiat Hlth & Populat, Hanoi, Vietnam. [Vu Song Ha; Whittaker, Maxine] Univ Queensland, Sch Populat Hlth, Brisbane, Qld 4006, Australia. [Whittaker, Andrea] Monash Univ, Sch Social Sci, Fac Arts, Melbourne, Vic 3800, Australia. [Rodger, Sylvia] Univ Queensland, Sch Hlth & Rehabil Sci, Brisbane, Qld 4072, Australia. RP Ha, VS (reprint author), Ctr Creat Initiat Hlth & Populat, 48,Alley 251-8 Nguyen Khang, Hanoi, Vietnam. EM ha@ccihp.org; andrea.whittaker@monash.edu; m.whittaker@sph.uq.edu.au; s.rodger@uq.edu.au FU Australian government through International Postgraduate Research Scholarships; University of Queensland through UQadvance; Organization for Autism Research through Graduate Student Grants FX This research received support from the Australian government through International Postgraduate Research Scholarships, the University of Queensland through UQadvance, and the Organization for Autism Research through Graduate Student Grants. We also thank colleagues at the Center for Creative Initiatives in Health and Population (CCIHP), Beth Smart and Hanoi Club of parents of children with ASD for their support during fieldwork. Most of all, we thank the parents of children with ASD in Hanoi, and service providers participating in this study for sharing their experiences and views with us. The observations and conclusions herein are those of the authors and do not represent CCIHP, the University of Queensland or the Organization for Autism Research. 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Sci. Med. PD NOV PY 2014 VL 120 BP 278 EP 285 DI 10.1016/j.socscimed.2014.09.038 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AT8JU UT WOS:000345180600032 PM 25262315 ER PT J AU Brick, DJ Nethercott, HE Montesano, S Banuelos, MG Stover, AE Schutte, SS O'Dowd, DK Hagerman, RJ Ono, M Hessl, DR Tassone, F Schwartz, PH AF Brick, David J. Nethercott, Hubert E. Montesano, Samantha Banuelos, Maria G. Stover, Alexander E. Schutte, Soleil Sun O'Dowd, Diane K. Hagerman, Rand J. Ono, Michele Hessl, David R. Tassone, Flora Schwartz, Philip H. TI The Autism Spectrum Disorders Stem Cell Resource at Children's Hospital of Orange County: Implications for Disease Modeling and Drug Discovery SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Induced pluripotent stem cells; Neural stem cell; Neuron; Disease modeling; Differentiation; Autism spectrum disorder ID FRAGILE-X-SYNDROME; DE-NOVO MUTATIONS; NEURAL PROGENITOR CELLS; TREMOR/ATAXIA SYNDROME; INTRANUCLEAR INCLUSIONS; NEURONAL DEVELOPMENT; EXPANDED ALLELES; FMR1 GENE; PREMUTATION; PATIENT AB The autism spectrum disorders (ASDs) comprise a set of neurodevelopmental disorders that are, at best, poorly understood but are the fastest growing developmental disorders in the United States. Because animal models of polygenic disorders such as the ASDs are difficult to validate, the derivation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming offers an alternative strategy for identifying the cellular mechanisms contributing to ASDs and the development of new treatment " options. Access to statistically relevant numbers of ASD patient cell lines, however, is still a limiting factor for the field. We describe a new resource with more than 200 cell lines (fibroblasts, iPSC clones, neural stem cells, glia) from unaffected volunteers and patients with a wide range of clinical ASD diagnoses, including fragile X syndrome. We have shown that both normal and ASD-specific iPSCs can be differentiated toward a neural stem cell phenotype and terminally differentiated into action-potential firing neurons and glia. The ability to evaluate and compare data from a number of different cell lines will facilitate greater insight into the cause or causes and biology of the ASDs and will be extremely useful for uncovering new therapeutic and diagnostic targets. Some drug treatments have already shown promise in reversing the neurobiological abnormalities in iPSC-based models of ASD-associated diseases. The ASD Stem Cell Resource at the Children's Hospital of Orange County will continue expanding its collection and make Wines available on request with the goal of advancing the use of ASD patient cells as disease models by the scientific community. C1 [Brick, David J.; Nethercott, Hubert E.; Montesano, Samantha; Banuelos, Maria G.; Stover, Alexander E.; Schwartz, Philip H.] Childrens Hosp, Cty Res Inst, Ctr Neurosci, Orange, CA 92868 USA. [Brick, David J.; Nethercott, Hubert E.; Montesano, Samantha; Banuelos, Maria G.; Stover, Alexander E.; Schwartz, Philip H.] Childrens Hosp, Cty Res Inst, Ctr Translat Res, Orange, CA 92868 USA. [Schutte, Soleil Sun; O'Dowd, Diane K.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Hagerman, Rand J.; Ono, Michele; Hessl, David R.; Tassone, Flora] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Hagerman, Rand J.; Ono, Michele; Hessl, David R.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. [Tassone, Flora] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA. RP Schwartz, PH (reprint author), Childrens Hosp, Cty Res Inst, 1201 West La Veta Ave, Orange, CA 92868 USA. EM pschwartz@choc.org FU NIH [R01HD059967, R01-NS083009]; Autism Speaks Trailblazer Grant [7379]; Eunice Kennedy Shriver National Institute of Child Health; National Human Neural Stem Cell Resource FX We thank the patients with ASDs and their families for participation in this study. We also thank the unaffected controls at UC Davis, who generously volunteered to be a part of the study. We are extremely grateful to Dr. Lily Ngotran, Andrew Ligsay, and Jonathan Polussa for the coordination of patient recruitment and procurement of patient samples at the Medical Investigation of Neurodevelopmental Disorders Institute. We thank Dr. Jane Pickett of the Autism Tissue Program of Autism Speaks and Dr. Clara Lajonchere of the Autism Genetic Resource Exchange of Autism Speaks for their enthusiasm for the development of this ASD-specific resource. We thank Dr. Atsushi Miyanohara, UC San Diego, for the kind gift of the pHIV7/Syn-EGFP transfer vector. We thank Dr. Omar Khalid, Siranush Herculian, Daniel C. Mendez, Dean R. Perusse, and Matthew Kunicki for tissue culture assistance. This work was funded in part by NIH Grant R01HD059967 and Autism Speaks Trailblazer Grant 7379 to P.N.S., Eunice Kennedy Shriver National Institute of Child Health and Development Grants HD036071 and HD02274 to R.J.H. and F.T., NIH Grant R01-NS083009 to D.K.O., and CHOC Children's continued support of the National Human Neural Stem Cell Resource. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, Autism Speaks, the University of California, Irvine, the University of California, Davis, or CHOC Children's. The National Cancer Institute Preclinical Repository generously supplied basic fibroblast growth factor-2. 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Med. PD NOV PY 2014 VL 3 IS 11 BP 1275 EP 1286 DI 10.5966/sctm.2014-0073 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA AT6OA UT WOS:000345057500013 PM 25273538 ER PT J AU McKinney, CM Nelson, T Scott, JM Heaton, LJ Vaughn, MG Lewis, CW AF McKinney, Christy M. Nelson, Travis Scott, JoAnna M. Heaton, Lisa J. Vaughn, Matthew G. Lewis, Charlotte W. TI Predictors of Unmet Dental Need in Children With Autism Spectrum Disorder: Results From a National Sample SO ACADEMIC PEDIATRICS LA English DT Article DE autism; austim spectrum disorder; autistic disorder; dental; medical home; oral health; unmet need ID HEALTH-CARE NEEDS; MEDICAL HOME; ORAL CARE; PERSPECTIVE; SERVICES; ACCESS AB OBJECTIVE: Unmet dental need in children with autism spectrum disorder (ASD) is common. We tested hypotheses that lacking a medical home or having characteristics of more severe ASD is positively associated with having unmet dental need among children with ASD. METHODS: Using data from the 2009 to 2010 National Survey of Children with Special Health Care Needs, we analyzed 2772 children 5 to 17 years old with ASD. We theorized that unmet dental need would be positively associated with not having a medical home and having characteristics of more severe ASD (eg, parent reported severe ASD, an intellectual disability, communication, or behavior difficulties). Prevalence of unmet dental need was estimated, and unadjusted and adjusted odds ratios, 95% confidence intervals, and P values were computed using survey methods for logistic regression. RESULTS: Nationally, 15.1% of children with ASD had unmet dental need. Among children with ASD, those without a medical home were more apt to have unmet dental need than those with a medical home (adjusted odds ratio, 4.46; 95% confidence interval, 2.59-7.69). Children with ASD with intellectual disability or greater communication or behavioral difficulties had greater odds of unmet dental need than those with ASD without these characteristics. Parent-reported ASD severity was not associated with unmet dental need. CONCLUSIONS: Children with ASD without a medical home and with characteristics suggestive of increased ASD-related difficulties were more apt to have unmet dental need. Pediatricians might use these findings to aid in identifying children with ASD who might not receive all needed dental care. C1 [McKinney, Christy M.; Heaton, Lisa J.] Univ Washington, Dept Oral Hlth Sci, Seattle, WA 98195 USA. [Nelson, Travis; Scott, JoAnna M.] Univ Washington, Dept Pediat Dent, Seattle, WA 98195 USA. [Lewis, Charlotte W.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Vaughn, Matthew G.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP McKinney, CM (reprint author), Univ Washington, Box 357475, Seattle, WA 98195 USA. 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Pediatr. PD NOV-DEC PY 2014 VL 14 IS 6 BP 624 EP 631 PG 8 WC Pediatrics SC Pediatrics GA AT5ES UT WOS:000344966800016 PM 25439161 ER PT J AU Schmidt, RJ Tancredi, DJ Krakowiak, P Hansen, RL Ozonoff, S AF Schmidt, Rebecca J. Tancredi, Daniel J. Krakowiak, Paula Hansen, Robin L. Ozonoff, Sally TI Maternal Intake of Supplemental Iron and Risk of Autism Spectrum Disorder SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE autism; case-control studies; child development; dietary supplements; iron; pregnancy; primary prevention; risk factors ID DIAGNOSTIC INTERVIEW; DEFICIENCY ANEMIA; MOTOR DEVELOPMENT; US ADULTS; CHILDREN; PREGNANCY; FERRITIN; RATS; METABOLISM; EXPRESSION AB Iron deficiency affects 40%-50% of pregnancies. Iron is critical for early neurodevelopmental processes that are dysregulated in autism spectrum disorder (ASD). We examined maternal iron intake in relation to ASD risk in California-born children enrolled in a population-based case-control study (the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study) from 2003 to 2009 with a diagnosis of ASD (n = 520) or typical development (n = 346) that was clinically confirmed using standardized assessments. Mean maternal daily iron intake was quantified on the basis of frequency, dose, and brands of supplements and cereals consumed each month from 3 months before pregnancy through the end of pregnancy and during breastfeeding (the index period), as reported in parental interviews. Mothers of cases were less likely to report taking iron-specific supplements during the index period (adjusted odds ratio = 0.63, 95% confidence interval: 0.44, 0.91), and they had a lower mean daily iron intake (51.7 (standard deviation, 34.0) mg/day) than mothers of controls (57.1 (standard deviation, 36.6) mg/day; P = 0.03). The highest quintile of iron intake during the index period was associated with reduced ASD risk compared with the lowest (adjusted odds ratio = 0.49, 95% confidence interval: 0.29, 0.82), especially during breastfeeding. Low iron intake significantly interacted with advanced maternal age and metabolic conditions; combined exposures were associated with a 5-fold increased ASD risk. Further studies of this link between maternal supplemental iron and ASD are needed to inform ASD prevention strategies. C1 [Schmidt, Rebecca J.; Krakowiak, Paula] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Schmidt, Rebecca J.; Hansen, Robin L.; Ozonoff, Sally] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Sacramento, CA 95817 USA. [Tancredi, Daniel J.; Hansen, Robin L.] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. [Ozonoff, Sally] Univ Calif Davis, Sch Med, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. RP Schmidt, RJ (reprint author), Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, 123 MS1C,1 Shields Ave, Davis, CA 95616 USA. EM rjschmidt@ucdavis.edu FU National Institutes of Health [R01-ES015359, P01-11269, 2K12HD051958-06]; Environmental Protection Agency's Science to Achieve Results (STAR) Program [R-829388, R833292]; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California, Davis FX The Childhood Autism Risks from Genetics and the Environment (CHARGE) Study has been supported by grants R01-ES015359, P01-11269, and 2K12HD051958-06 from the National Institutes of Health; by grants R-829388 and R833292 from the Environmental Protection Agency's Science to Achieve Results (STAR) Program; and by the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California, Davis. 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J. Epidemiol. PD NOV 1 PY 2014 VL 180 IS 9 BP 890 EP 900 DI 10.1093/aje/kwu208 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AT0BD UT WOS:000344600900005 PM 25249546 ER PT J AU Class, QA Rickert, ME Larsson, H Lichtenstein, P D'Onofrio, BM AF Class, Quetzal A. Rickert, Martin E. Larsson, Henrik Lichtenstein, Paul D'Onofrio, Brian M. TI Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID LOW-BIRTH-WEIGHT; INTRAUTERINE GROWTH; MATERNAL SMOKING; ENVIRONMENTAL-INFLUENCES; BEHAVIORAL OUTCOMES; ATTENTION PROBLEMS; MONOZYGOTIC TWINS; BRAIN-DEVELOPMENT; YOUNG ADULTHOOD; GESTATIONAL-AGE AB Background It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. Aims To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. Method We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n=3291773), while controlling for measured and unmeasured confounding. Results In the population, lower birth weight (<= 2500g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight=2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Conclusions Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. C1 [Class, Quetzal A.; Rickert, Martin E.; D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Class, QA (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 East 10th St, Bloomington, IN 47405 USA. EM qaclass@indiana.edu FU National Institute of mental Health [MH094011]; National Institute of Child Health and Development [HD061817]; Swedish Council for Working Life and Social Research; Swedish Research Council (Medicine) FX This study was supported by grants from the National Institute of mental Health (MH094011), National Institute of Child Health and Development (HD061817), the Swedish Council for Working Life and Social Research and the Swedish Research Council (Medicine). 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J. Psychiatry PD NOV PY 2014 VL 205 IS 5 BP 355 EP 361 DI 10.1192/bjp.bp.113.143693 PG 7 WC Psychiatry SC Psychiatry GA AT5HD UT WOS:000344973700004 PM 25257067 ER PT J AU Harfterkamp, M Buitelaar, JK Minderaa, RB van de Loo-Neus, G van der Gaag, RJ Hoekstra, PJ AF Harfterkamp, Myriam Buitelaar, Jan K. Minderaa, Ruud B. van de Loo-Neus, Gigi van der Gaag, Rutger-Jan Hoekstra, Pieter J. TI Atomoxetine in Autism Spectrum Disorder: No Effects on Social Functioning; Some Beneficial Effects on Stereotyped Behaviors, Inappropriate Speech, and Fear of Change SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; QUESTIONNAIRE CSBQ; PEDIATRIC-PATIENTS; ANXIETY DISORDER; OPEN-LABEL; CHILDREN; SYMPTOMS; ADOLESCENTS; PLACEBO AB Objective: The objective of this study was to investigate the short-term treatment effects of atomoxetine on autism spectrum disorder (ASD) symptoms in children and adolescents with both ASD and attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 97 patients 6-17 years of age, with ASD and ADHD, were treated with 1.2 mg/kg/day of atomoxetine during an 8 week double-blind placebo-controlled period. Here, we investigated effects on two parent-based secondary outcome measures, the Aberrant Behavior Checklist (ABC) and the Children's Social Behavior Questionnaire (CSBQ). Results: After 8 weeks of double-blind treatment, atomoxetine administration was associated with significant treatment effects on the ABC subscales Hyperactivity, Inappropriate Speech, and Stereotypic Behavior, and on the CSBQ subscale Fear for Changes. Conclusions: Our study results indicate no beneficial effects of atomoxetine on social functioning. However, atomoxetine may ameliorate restricted and stereotyped behaviors and communication. This study has been registered in ClinicalTrials.gov (www.clinicaltrials.gov) under registration number NCT00380692. C1 [Harfterkamp, Myriam; Minderaa, Ruud B.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands. [Buitelaar, Jan K.; van de Loo-Neus, Gigi; van der Gaag, Rutger-Jan] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. RP Harfterkamp, M (reprint author), Univ Med Ctr Groningen, Dept Psychiat, POB 660, NL-9700 AR Groningen, Netherlands. EM maharfterkamp@gmail.com FU Eli Lilly and company FX This study was funded by Eli Lilly and company. CR Adler LA, 2009, DEPRESS ANXIETY, V26, P212, DOI 10.1002/da.20549 AMAN MG, 1985, AM J MENT DEF, V89, P485 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Anagnostou E, 2011, CURR OPIN PEDIATR, V23, P621, DOI 10.1097/MOP.0b013e32834cba3e Arnold LE, 2006, J AM ACAD CHILD PSY, V45, P1196, DOI 10.1097/01.chi.0000231976.28719.2a Dawson G, 2011, CURR OPIN PEDIATR, V23, P616, DOI 10.1097/MOP.0b013e32834cf082 de Bildt A, 2009, J AUTISM DEV DISORD, V39, P1464, DOI 10.1007/s10803-009-0764-x Faries D. 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Child Adolesc. Psychopharmacol. PD NOV 1 PY 2014 VL 24 IS 9 BP 481 EP 485 DI 10.1089/cap.2014.0026 PG 5 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AT5RM UT WOS:000344999600003 PM 25369243 ER PT J AU Lake, JK Weiss, JA Dergal, J Lunsky, Y AF Lake, Johanna K. Weiss, Jonathan A. Dergal, Julie Lunsky, Yona TI Child, Parent, and Service Predictors of Psychotropic Polypharmacy Among Adolescents and Young Adults with an Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; MEDICATION USE; INTELLECTUAL DISABILITY; PSYCHOACTIVE MEDICINES; PSYCHIATRIC-SERVICES; PATTERNS; INDIVIDUALS; PREVALENCE; BEHAVIOR AB Objective: This study examined the child, parent, and service factors associated with polypharmacy in adolescents and young adults with autism spectrum disorders (ASD). Methods: As part of an online survey examining health service utilization patterns among individuals with ASD, parents provided demographic and clinical information pertaining to their child. This included information on current medication use, as well as information on clinical services received, clinical history, and parent well-being. Analyses examined the bivariate association between individual child, parent, and service variables and polypharmacy. Variables significantly associated with polypharmacy were included in a multiple variable logistic regression. Results: Of the 363 participants sampled, similar to 25% were receiving two or more psychotropic drugs concurrently. The patient's psychiatric comorbidity, history of hurting others, therapy use, and parent burden were predictors of polypharmacy. Conclusions: Adolescents and young adults with ASD are a highly medicated population with multiple factors associated with psychotropic polypharmacy. Although there may be circumstances in which polypharmacy is necessary, a richer understanding of what predicts polypharmacy may lead to targeted interventions to better support these individuals and their families. Findings also highlight the need to support families of children with ASD prescribed multiple psychotropic medications. C1 [Lake, Johanna K.; Dergal, Julie; Lunsky, Yona] Ctr Addict & Mental Hlth, Dual Diag Serv, Toronto, ON M5V 2B4, Canada. [Lake, Johanna K.; Lunsky, Yona] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Weiss, Jonathan A.] York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada. RP Lake, JK (reprint author), Ctr Addict & Mental Hlth, Dual Diag Serv, 501 Queen St W, Toronto, ON M5V 2B4, Canada. 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Child Adolesc. Psychopharmacol. PD NOV 1 PY 2014 VL 24 IS 9 BP 486 EP 493 DI 10.1089/cap.2014.0011 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AT5RM UT WOS:000344999600004 PM 25329798 ER PT J AU Zielinski, K Wood, JJ Renno, P Whitham, S Sterling, L AF Zielinski, Kaycie Wood, Jeffrey J. Renno, Patricia Whitham, Siena Sterling, Lindsey TI Examining the Validity of the Columbia Impairment Scale for Assessing Level of Functioning in Youth with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID CHILDREN; ADOLESCENTS; ANXIETY AB Background: Youth with autism spectrum disorder (ASD) exhibit impairment in numerous areas of functioning, most notably in the areas related to social interactions, communication, and behavior at school and at home. Understanding the severity of the impairment in each of the domains associated with areas of functioning is imperative when evaluating the efficacy of an intervention, whether it be medical, therapeutic, or both. Objective: This study sought to examine the convergent and discriminant validity of the Columbia Impairment Scale (CIS) for youth with ASD, and their parents. Methods: A sample of 77 adolescents with ASD and their parents completed the CIS and various other measures that examined mood, anxiety, and behavior. Results: Although there was some evidence of convergent validity for the parent-report CIS, there was inadequate discriminant validity. The child-report version of the CIS yielded generally poor validity indices. Conclusions: There appear to be important limitations when using this measure for youth with ASD. C1 [Zielinski, Kaycie; Wood, Jeffrey J.; Renno, Patricia; Whitham, Siena; Sterling, Lindsey] Univ Calif Los Angeles, Dept Educ, Los Angeles, CA 90095 USA. RP Zielinski, K (reprint author), Univ Calif Los Angeles, 3132A Moore Hall,405 Hilgard Ave, Los Angeles, CA 90095 USA. EM kzielinski@ucla.edu CR Achenbach TM, 2001, MANUAL ASEBA SCH AGE American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th American Psychiatric Association, 2013, DIAGN STAT MAN MENT BIRD HR, 1993, INT J METHOD PSYCH, V3, P167 Chorpita BF, 2005, BEHAV RES THER, V43, P309, DOI 10.1016/j.brat.2004.02.004 Kaat AJ, 2013, J ABNORM CHILD PSYCH, V41, P959, DOI 10.1007/s10802-013-9739-7 Lewandowski LJ, 2009, ASSESSING IMPAIRMENT, P5, DOI 10.1007/978-0-387-87542-2_2 LORD C, 1994, J AUTISM DEV DISORD, V24, P659, DOI 10.1007/BF02172145 Lord C., 2002, AUTISM DIAGNOSTIC OB March J, 1997, MANUAL MULTIDIMENSIO Rapee RM, 2012, J CHILD PSYCHOL PSYC, V53, P454, DOI 10.1111/j.1469-7610.2011.02479.x Research Unit on Pediatric Psychopharmacology Anxiety Study Group, 2002, J AM ACAD CHILD ADOL, V41, P1061, DOI DOI 10.1097/00004583-200209000-00006 Silverman WK, 1996, ALBANO AM ANXIETY DI, V2 Wood JJ, 2009, J CHILD PSYCHOL PSYC, V50, P224, DOI 10.1111/j.1469-7610.2008.01948.x Wood JJ, 2014, BEHAV THER Wood JW, 2002, TLS-TIMES LIT SUPPL, P31 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 NOV 1 PY 2014 VL 24 IS 9 BP 509 EP 512 DI 10.1089/cap.2014.0095 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AT5RM UT WOS:000344999600007 PM 25361233 ER PT J AU Marrus, N Underwood-Riordan, H Randall, F Zhang, Y Constantino, JN AF Marrus, Natasha Underwood-Riordan, Heather Randall, Fellana Zhang, Yi Constantino, John N. TI Lack of Effect of Risperidone on Core Autistic Symptoms: Data from a Longitudinal Study SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; SERIOUS BEHAVIORAL-PROBLEMS; PLACEBO-CONTROLLED TRIAL; SPECTRUM DISORDERS; DOUBLE-BLIND; PEDIATRIC PSYCHOPHARMACOLOGY; PRESCHOOL-CHILDREN; RESEARCH UNITS; RUPP AUTISM; ADOLESCENTS AB Objective: The purpose of this study was to investigate the course of autistic symptoms, using a quantitative measure of core autistic traits, among risperidone-treated children who participated in a 10 year life course longitudinal study. Methods: Parents completed surveys of intervention history, as well as serial symptom severity measurements using the Social Responsiveness Scale (SRS), on their autism spectrum disorder (ASD)-affected children. Fifty participants (out of a total of 184 with full intervention histories) were reported to have been treated with risperidone during the course of the study. Serial SRS scores during risperidone treatment were available for a majority of children whose parents reported a positive effect from risperidone. Results: Two thirds of risperidone-treated children (n=33) were reported by parents to have improved by taking the medication, with the principal effects described being that children were calmer, better focused, and less aggressive. SRS scores of children reported to have responded positively to risperidone did not improve over time. Conclusions: Risperidone's beneficial effect on aggression and other elements of adaptive functioning were not necessarily accompanied by reduction in core ASD symptoms, as serially assessed by the same caregivers who reported improvement in their children. These results reflect the distinction between reduction in core symptom burden and improvement in adaptive functioning. Given the cumulative risks of atypical neuroleptics, the findings underscore the importance of periodic re-evaluation of medication benefit for children with ASD receiving neuroleptic treatment. C1 [Marrus, Natasha; Randall, Fellana; Zhang, Yi; Constantino, John N.] Washington Univ, Dept Psychiat, Div Child & Adolescent Psychiat, St Louis, MO USA. [Underwood-Riordan, Heather] Univ Missouri, Coll Educ, Dept Educ Psychol Res & Evaluat, St Louis, MO 63121 USA. RP Marrus, N (reprint author), 660 South Euclid Ave,Box 8134, St Louis, MO 63110 USA. EM marrusn@psychiatry.wustl.edu FU National Institute of Child Health and Human Development [HD042541]; Intellectual and Developmental Disabilities Research Center at Washington University [NIH/NICHD P30 HD062171]; National Institute of Mental Health [5T32MH100019] FX This work was supported by Grant HD042541 from the National Institute of Child Health and Human Development (J.N.C.), the Intellectual and Developmental Disabilities Research Center at Washington University (NIH/NICHD P30 HD062171 - J.N.C. PI), and Grant 5T32MH100019 from the National Institute of Mental Health (N.M.). CR Achenbach T. M., 1991, INTEGRATIVE GUIDE 19 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Arnold LE, 2003, J AM ACAD CHILD PSY, V42, P1443, DOI 10.1097/01.chi.0000091946.28938.54 Capone GT, 2008, J DEV BEHAV PEDIATR, V29, P106, DOI 10.1097/DBP.0b013e318165c100 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Constantino J. 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Child Adolesc. Psychopharmacol. PD NOV 1 PY 2014 VL 24 IS 9 BP 513 EP 518 DI 10.1089/cap.2014.0055 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AT5RM UT WOS:000344999600008 PM 25361070 ER PT J AU Holt, RJ Chura, LR Lai, MC Suckling, J von dem Hagen, E Calder, AJ Bullmore, ET Baron-Cohen, S Spencer, MD AF Holt, R. J. Chura, L. R. Lai, M. -C. Suckling, J. von dem Hagen, E. Calder, A. J. Bullmore, E. T. Baron-Cohen, S. Spencer, M. D. TI 'Reading the Mind in the Eyes': an fMRI study of adolescents with autism and their siblings SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Autism; emotion recognition; endophenotypes; fMRI ID HIGH-FUNCTIONING AUTISM; SEX-DIFFERENCES; SPECTRUM DISORDERS; ASPERGER-SYNDROME; IMAGING ENDOPHENOTYPE; INFANTILE-AUTISM; NORMAL ADULTS; BRAIN; PHENOTYPE; CHILDREN AB Background. Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endopheno-type for atypical social cognition in ASC. Differences in performance and neural activation on the 'Reading the Mind in the Eyes' task (the Eyes task) have been identified in individuals with ASC in previous studies. Method. Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n=50), their unaffected siblings (n=40) and typically developing controls (n=40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC-control and sibling-control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC-control and sibling-control differences across multiple thresholds. Results. Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups. Conclusions. Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. 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Med. PD NOV PY 2014 VL 44 IS 15 BP 3215 EP 3227 DI 10.1017/S0033291714000233 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AS7YN UT WOS:000344467900007 PM 25065819 ER PT J AU Khandaker, GM Stochl, J Zammit, S Lewis, G Jones, PB AF Khandaker, G. M. Stochl, J. Zammit, S. Lewis, G. Jones, P. B. TI A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence SO PSYCHOLOGICAL MEDICINE LA English DT Article DE autism spectrum disorder; dyslexia; IQ; neurocognitive performance; neurodevelopmental disorder; psychotic experiences ID ALSPAC BIRTH COHORT; AUTISM SPECTRUM DISORDERS; SCHIZOPHRENIFORM DISORDER; SOCIOECONOMIC-STATUS; AGE 12; SYMPTOMS; CHILDREN; ASSOCIATION; METAANALYSIS; ONSET AB Background. Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Method. PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education. Results. Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p<0.0001). The risk of PEs was higher in those with, compared with those without, NDs; the adjusted OR for definite PEs was 1.76 (95% CI 1.11-2.79). IQ (but not working memory) deficit partly explained this association. Conclusions. Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia. C1 [Khandaker, G. M.; Stochl, J.; Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England. [Khandaker, G. M.; Stochl, J.; Jones, P. B.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England. [Khandaker, G. M.; Zammit, S.; Lewis, G.] Univ Bristol, Sch Social & Community Med, Ctr Mental Hlth Addict & Suicide Res, Bristol BS8 1TH, Avon, England. [Zammit, S.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Lewis, G.] UCL, Mental Hlth Sci Unit, London WC1E 6BT, England. RP Khandaker, GM (reprint author), Dept Psychiat, Box 189,Cambridge Biomedical Campus, Cambridge CB2 2QQ, England. 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PD NOV PY 2014 VL 44 IS 15 BP 3229 EP 3238 DI 10.1017/S0033291714000750 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AS7YN UT WOS:000344467900008 PM 25066026 ER PT J AU Kim, BS Lee, J Bang, M Seo, BA Khalid, A Jung, MW Jeon, D AF Kim, Byung Sun Lee, Junghee Bang, Minji Seo, Bo Am Khalid, Arshi Jung, Min Whan Jeon, Daejong TI Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex SO PSYCHOPHARMACOLOGY LA English DT Article DE Serotonin; Dopamine; Anterior cingulate cortex; Empathy; Observational fear; Neural activity; Entropy ID RAT PREFRONTAL CORTEX; CHRONIC-SCHIZOPHRENIC PATIENTS; TEMPORAL-LOBE EPILEPSY; CEREBRAL-CORTEX; ANTIPSYCHOTIC-DRUGS; AUTISTIC DISORDER; NUCLEUS-ACCUMBENS; SPECTRUM DISORDER; PYRAMIDAL NEURONS; 5-HT1A RECEPTORS AB The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known. We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity. An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D-1 receptor antagonist), or haloperidol (DA D-2 receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo. The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment. The current results demonstrated that DA D-2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations. C1 [Kim, Byung Sun; Lee, Junghee; Bang, Minji; Seo, Bo Am; Khalid, Arshi; Jeon, Daejong] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Jung, Min Whan] Korea Adv Inst Sci & Technol, Ctr Synapt Brain Dysfunct, Inst Basic Sci, Taejon 305701, South Korea. [Jung, Min Whan] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. 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Kandeel, Wafaa A. Wakeel, Khaled E. El-Nofely, Aly A. TI Anthropometric assessment of a Middle Eastern group of autistic children SO WORLD JOURNAL OF PEDIATRICS LA English DT Article DE anthropometry; autism spectrum disorders; Egypt; growth ID PERVASIVE DEVELOPMENTAL DISORDERS; HEAD CIRCUMFERENCE; SPECTRUM DISORDERS; GROWTH; BRAIN AB Background: Growth abnormalities are uniquely associated with autism spectrum disorders (ASD); however, the extent to which growth abnormalities are present has hardly been investigated. The current study aims to compare the differences in anthropometric parameters in a group of autistic Egyptian children and the healthy normal population. Methods: We recruited 100 children with ASD from the Outpatient Clinic for "Autistic Children" at the Medical Research Hospital of Excellence, National Research Centre in Cairo, Egypt. They were diagnosed by DSM-IV criteria of the American Psychiatric Association, Autism Diagnostic Interview-Revised, and Childhood Autism Rating Scale. Of these children at age of 3-10 years, 71 were males and 29 females. Eight anthropometric parameters were assessed in view of data of the healthy Egyptians of pertinent sex and age. Results: Weight and body mass index increased because of a significant increase in subcutaneous fat thickness. This tendency with a probable decrease in muscle mass was more evident in male or in older children, likely resulting from sedentary life style and food selectivity. Conclusions: The Z head circumference score and its variance significantly increased especially in males or older children, suggesting the relative overgrowth of the brain in a substantial percentage of Egyptian children with autism. We concluded that increased fat composition in Egyptian autistic children with decreased muscle mass necessitates tailoring a specially designed food supplementation program to ameliorate the severity of autism symptoms. C1 [Meguid, Nagwa A.] Natl Res Ctr, Res Children Special Needs Dept, Cairo, Egypt. [Kandeel, Wafaa A.; Wakeel, Khaled E.; El-Nofely, Aly A.] NRC, Dept Biol Anthropol, Cairo, Egypt. RP Meguid, NA (reprint author), Natl Res Ctr, Res Children Special Needs Dept, Tahrir St, Cairo, Egypt. EM meguidna@yahoo.com FU National Research Centre FX Funding was from the National Research Centre. 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Parents with masculinized 2D:4D ratios, a marker of the organizational effects of T, may have other relevant biological characteristics, in particular exposing their offspring to high T levels in the prenatal environment. This would increase the likelihood of their offspring developing these disorders. MethodsThe present study examined whether parents of offspring with AN (n=34; mean age= 51) and ASD (n=36; mean age=45) differ from control parents (n=40; mean age=43) in 2D:4D ratio, as well as by salivary T levels and its relationships. ResultsOur results revealed that AN and ASD parents (fathers and mothers) have masculinized 2D:4D ratios of the right hand compared to control parents. However, the difference compared to controls was larger in the ASD than the AN group. Furthermore, current salivary T levels were negatively related to the 2D:4D ratio in ASD and AN parents only. ConclusionsOur data partially support the view of high prenatal masculinization as a potential intermediate phenotype to the development of these disorders in their offspring. Am. J. Hum. Biol. 26:863-866, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Romero-Martinez, Angel; Moya-Albiol, Luis] Univ Valencia, Dept Psychobiol, Valencia 46010, Spain. RP Moya-Albiol, L (reprint author), Univ Valencia, Dept Psychobiol, Ave Blasco Ibanez 21, Valencia 46010, Spain. EM luis.moya@uv.es FU Valencia innovation and research program for student researchers (VALi+d) [ACIF/2011/075]; Spanish Ministry of Science [PSI2008-0448/PSIC]; Department for Business, Research and Science of the Regional Government of Valencia Research Groups and Networks of Excellence [PROMETEO/2011/048, ISIC/2013/001, AEST/2013/032] FX Contract grant sponsors: Valencia innovation and research program for student researchers (VALi+d) (ACIF/2011/075), the Spanish Ministry of Science (PSI2008-0448/PSIC), the Department for Business, Research and Science of the Regional Government of Valencia Research Groups and Networks of Excellence (PROMETEO/2011/048; ISIC/2013/001; AEST/2013/032). 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J. Hum. Biol. PD NOV-DEC PY 2014 VL 26 IS 6 BP 863 EP 866 DI 10.1002/ajhb.22597 PG 4 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA AS6IW UT WOS:000344368300019 PM 25130276 ER PT J AU Levenson, D AF Levenson, Deborah TI COMMON GENETIC VARIANTS LINKED WITH LARGE PERCENTAGE OF AUTISM RISK Study finds spontaneous mutations are less-significant risk factors SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article CR Gauglerl T, 2014, NAT GENET, V46, P881, DOI 10.1038/ng.3039 Klei L, 2012, NATURE, V511, P421 NR 2 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV PY 2014 VL 164A IS 11 DI 10.1002/ajmg.a.36817 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA AS3OB UT WOS:000344187200002 ER PT J AU Imbornoni, L Price, ET Andrews, J Meaney, FJ Ciafaloni, E Cunniff, C AF Imbornoni, Lauren Price, Elinora T. Andrews, Jennifer Meaney, F. John Ciafaloni, Emma Cunniff, Christopher TI Diagnostic and Clinical Characteristics of Early-Manifesting Females with Duchenne or Becker Muscular Dystrophy SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE duchenne muscular dystrophy; manifesting heterozygote; dystrophinopathy ID DEFICIT HYPERACTIVITY DISORDER; CARRIERS; MUTATIONS; CHILDREN AB Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up to 40% of heterozygous females, but there are few reports of females who exhibit skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance Tracking and Research Network, a multi-site population-based surveillance network for dystrophinopathy, nine symptomatic female heterozygotes with onset of symptoms prior to age 9 years were identified. The median age at diagnosis was 8.3 years, and the median interval from first symptoms to diagnosis was 1.35 years. Of the nine female heterozygotes, four had a positive family history, seven had intellectual disability and five had at least one mental health disorder. Mental health concerns included attention deficit hyperactivity disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The frequency of intellectual and mental health problems in this group is higher than previously reported for affected males and for symptomatic females. These findings may have implications for diagnosis of early manifesting heterozygotes and for their health supervision. (c) 2014 Wiley Periodicals, Inc. C1 [Imbornoni, Lauren; Price, Elinora T.; Andrews, Jennifer; Meaney, F. John; Cunniff, Christopher] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ 85724 USA. [Ciafaloni, Emma] Univ Rochester, Dept Neurol, Rochester, NY USA. RP Cunniff, C (reprint author), Univ Arizona, Coll Med, Dept Pediat, 1501 N Campbell Ave, Tucson, AZ 85724 USA. 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TI A Terminal 3p26.3 Deletion Is Not Associated With Dysmorphic Features and Intellectual Disability in a Four-Generation Family SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 3p26 deletion syndrome; variable phenotype; genetic counseling ID DISTAL 3P DELETION; MENTAL-RETARDATION; SUBTELOMERIC REARRANGEMENTS; PHENOTYPIC VARIABILITY; DEVELOPMENTAL DELAY; SHORT ARM; PATIENT; GENE; CHROMOSOME-3; KARYOTYPE AB Terminal deletions of the distal part of the short arm of chromosome 3 cause a wide range of phenotypes from normal to dysmorphic including microcephaly, developmental delay and intellectual disability. We studied the clinical consequences of a terminal deletion of the short arm of chromosome 3 in four generations of a family. The index patient is a14-month-old boy with microcephaly, corpus callosum dysgenesis, and minor dysmorphic features. Single Nucleotide Polymorphism (SNP) array analysis detected a duplication on the long arm of chromosome 6. His apparently healthy mother carries the same 6q duplication, but as an unexpected finding a terminal deletion of 2.9Mb of the short arm of chromosome 3 was observed. Further co-segregation analysis in the family for the chromosome 3 deletion showed that with the exception of the sister of the index who has autism, speech delay, and learning problems, family members in four generations of this family are carrier of this 3p deletion and apparently healthy. To our knowledge, this is the first report of a study of this terminal 3p deletion in four generations. In this report, we review the literature on terminal 3p deletions and discuss the importance of molecular testing and reporting of copy number variants to achieve accurate genetic counseling in prenatal and postnatal screening. (c) 2014 Wiley Periodicals, Inc. C1 [Moghadasi, Setareh; van Haeringen, Arie; Gijsbers, Antoinet C. J.; Ruivenkamp, Claudia A. L.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands. 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A PD NOV PY 2014 VL 164A IS 11 BP 2863 EP 2868 DI 10.1002/ajmg.a.36700 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AS3OB UT WOS:000344187200025 PM 25123480 ER PT J AU Srivastava, S Cohen, J Pevsner, J Aradhya, S McKnight, D Butler, E Johnston, M Fatemi, A AF Srivastava, Siddharth Cohen, Julie Pevsner, Jonathan Aradhya, Swaroop McKnight, Dianalee Butler, Elizabeth Johnston, Michael Fatemi, Ali TI A Novel Variant in GABRB2 Associated with Intellectual Disability and Epilepsy SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE epilepsy; intellectual disability; GABRB2; GABA(A) receptor ID CHILDHOOD ABSENCE EPILEPSY; FEBRILE SEIZURES PLUS; RECEPTOR SUBUNIT MUTATIONS; GABA(A) RECEPTOR; GENERALIZED EPILEPSY; GENETIC EPILEPSIES; GAMMA-2-SUBUNIT; TRAFFICKING; FAMILIES; SUBTYPES AB The -aminobutyric acid type A (GABA(A)) receptor is one of the three main classes of receptors activated by GABA, the principal inhibitory neurotransmitter in the central nervous system. Mutations in genes encoding various subunits of this receptor (GABRA1, GABRA2, GABRA4, GABRA5, GABRA6, GABRB1, GABRB3, GABRG1, GABRG2, GABRG3, and GABRD) are implicated in a number of neurological and developmental disorders, including epilepsy and autism. To date, no human genetics studies have implicated mutations in GABRB2, encoding the 2 subunit of the GABA(A) receptor, with neurodevelopmental disorders. Here we present a 12-year-old girl with intellectual disability and epilepsy, who was discovered by whole exome sequencing to have a de novo heterozygous missense variant in exon 4 of GABRB2 (c.236T>C; p.M79T). This variant is likely pathogenic, based on in silico analyses, as well as the fact that it results in the non-conservative substitution of a non-polar amino acid with a polar amino acid at a position that is evolutionarily conserved across multiple species. Our findings underscore the need for further investigation into the mechanisms by which mutations in GABRB2 contribute to neurological and developmental dysfunction. (c) 2014 Wiley Periodicals, Inc. C1 [Srivastava, Siddharth; Cohen, Julie; Pevsner, Jonathan; Johnston, Michael; Fatemi, Ali] Kennedy Krieger Inst, Hugo W Moser Res Inst, Baltimore, MD 21205 USA. [Srivastava, Siddharth; Johnston, Michael; Fatemi, Ali] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Srivastava, Siddharth; Johnston, Michael; Fatemi, Ali] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA. [Aradhya, Swaroop; McKnight, Dianalee; Butler, Elizabeth] GeneDx Lab, Gaithersburg, MD USA. RP Fatemi, A (reprint author), Kennedy Krieger Inst, Hugo W Moser Res Inst, 707 North Broadway,Room 500i, Baltimore, MD 21205 USA. EM fatemi@kennedykrieger.org FU GeneDx Laboratory FX Swaroop Aradhya, Dianalee McKnight, and Elizabeth Butler are paid employees of GeneDx Laboratory. 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J. Med. Genet. A PD NOV PY 2014 VL 164A IS 11 BP 2914 EP 2921 DI 10.1002/ajmg.a.36714 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AS3OB UT WOS:000344187200033 PM 25124326 ER PT J AU Risch, N Hoffmann, TJ Anderson, M Croen, LA Grether, JK Windham, GC AF Risch, Neil Hoffmann, Thomas J. Anderson, Meredith Croen, Lisa A. Grether, Judith K. Windham, Gayle C. TI Familial Recurrence of Autism Spectrum Disorder: Evaluating Genetic and Environmental Contributions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDER; INTER-PREGNANCY INTERVAL; INTERPREGNANCY INTERVAL; EPIDEMIOLOGIC SURVEY; NONVERBAL IQ; TWIN PAIRS; RISK; BIRTH; SCHIZOPHRENIA; POPULATION AB Objective: This study was designed to examine the pattern of familial recurrence of autism spectrum disorder (ASD) in terms of genetic and environmental contributions related to timing of birth. Method: The authors linked California Department of Developmental Services records with state birth certificates to identify all siblings and half siblings of individuals affected with ASD born between 1990 and 2003. A total of 6,616 full siblings, 644 maternal half siblings, and 299 paternal half siblings born after ASD index cases were used to calculate recurrence risks. Control families, identified through matching to cases, were included for comparison (a total of 29,384 siblings). Results: The overall sibling recurrence risk was 10.1%, compared with a prevalence of 0.52% in siblings of controls. The recurrence risk in second-born children was higher (11.5%) than in later-born siblings (7.3%); a similar pattern was observed for maternal half siblings (6.5% for second-born compared with 10% for later-born siblings; 4.8% overall). The recurrence risk was significantly higher for siblings who immediately followed the index case in birth order compared with those later in birth order. The recurrence risk for paternal half siblings (2.3%) was half the overall recurrence risk for maternal half siblings but was similar to that for later-born maternal half siblings. An exponential effect of short interbirth interval was observed, with the recurrence risk reaching 14.4% for an interbirth interval of 18 months or less, compared with 6.8% for an interval of 4 years or more. An identical phenomenon was observed in maternal half siblings. Conclusions: The results support genetic susceptibility in the familial recurrence of ASD along with factors related to timing of birth. C1 [Risch, Neil] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Calif Dept Publ Hlth, Environm Hlth Invest Branch, Richmond, CA USA. RP Risch, N (reprint author), Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. EM rischn@humgen.ucsf.edu FU Institute for Human Genetics, University of California, San Francisco FX Supported by funds from the Institute for Human Genetics, University of California, San Francisco. 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J. Psychiat. PD NOV PY 2014 VL 171 IS 11 BP 1206 EP 1213 DI 10.1176/appi.ajp.2014.13101359 PG 8 WC Psychiatry SC Psychiatry GA AS0LL UT WOS:000343968500014 PM 24969362 ER PT J AU Missault, S Van den Eynde, K Berghe, WV Fransen, E Weeren, A Timmermans, JP Kumar-Singh, S Dedeurwaerdere, S AF Missault, S. Van den Eynde, K. Berghe, W. Vanden Fransen, E. Weeren, A. Timmermans, J. P. Kumar-Singh, S. Dedeurwaerdere, S. TI The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Poly I:C; Maternal immune activation; Neuroinflammation; Schizophrenia; Autism; Locomotion ID PREPULSE INHIBITION; ANIMAL-MODEL; DOPAMINERGIC HYPERFUNCTION; ACTIVATED MICROGLIA; BRAIN-DEVELOPMENT; FETAL-BRAIN; MICE LEADS; SCHIZOPHRENIA; PREGNANCY; RATS AB Background: Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype. Methods: Based on a dose-response study, MIA was induced in pregnant rats by injecting 4 mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-alpha in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n = 14) and weight gain (WG; n = 10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections. Results: Pregnant dams that lost weight following MIA showed increased levels of TNF-alpha compared to controls, unlike dams that gained weight following MIA. Poly I:C WL offspring showed the most severe behavioural outcome. Poly I:C WG offspring, on the other hand, did not show clear behavioural deficits. Most interestingly a reduced sucrose preference indicative of anhedonia was found in Poly I:C WL but not Poly I:C WG offspring compared to controls. Finally, there were no significant differences in microglia activation scores between any of the investigated groups. Conclusions: The individual maternal immune response to MIA is an important determinant of the behavioural outcome in offspring, including negative symptoms such as anhedonia. We failed to find any significant difference in the level of microglia activation between Poly I:C WL, Poly I:C WG and control offspring. (C) 2014 Elsevier Inc. All rights reserved. C1 [Missault, S.; Van den Eynde, K.; Dedeurwaerdere, S.] Univ Antwerp, Fac Med & Hlth Sci, Expt Lab Translat Neurosci & Otolaryngol, B-2610 Antwerp, Belgium. [Berghe, W. Vanden] Univ Antwerp, Fac Pharmaceut Biomed & Vet Sci, Lab Prot Sci Prote & Epigenet Signaling, B-2610 Antwerp, Belgium. [Fransen, E.] Univ Antwerp, StatUA, B-2650 Edegem, Belgium. [Weeren, A.] Univ Antwerp, StatUA, B-2000 Antwerp, Belgium. [Timmermans, J. P.] Univ Antwerp, Fac Pharmaceut Biomed & Vet Sci, Lab Cell Biol & Histol, B-2020 Antwerp, Belgium. [Kumar-Singh, S.] Univ Antwerp, Fac Med & Hlth Sci, Lab Cell Biol & Histol, B-2020 Antwerp, Belgium. RP Dedeurwaerdere, S (reprint author), Univ Antwerp, Fac Med & Hlth Sci, Expt Lab Translat Neurosci & Otolaryngol, Campus Drie Eiken,Univ Pl 1, B-2610 Antwerp, Belgium. EM Stefanie.Dedeurwaerdere@hotmail.com RI Fransen, Erik/C-4102-2015 OI Fransen, Erik/0000-0001-7785-4790 FU Research Foundation Flanders (FWO) [G.0586.12]; Lanceringsproject BOF of the University of Antwerp FX The present study was supported by Research Foundation Flanders (FWO) funding (G.0586.12) and Lanceringsproject BOF of the University of Antwerp. Stephan Missault has a Ph. D. fellowship of the Research Foundation Flanders (MO). We are extremely grateful to Prof. Jean-Michel Rigo, Ajay Palagani, Prof. Rudi D'Hooge, Zsuzsanna Vegh, Isabel Pintelon, Annemie Van Eetveldt, Krystyna Szewczyk, Halima Amhaoul and Joery Goossens for their support and practical assistance during this study. We kindly thank Oto Therapeutics and in particular Prof Van de Heyning for the use of the PPI set-up. We are very grateful to Janssen Pharmaceutica and especially Wilhelmus Drinkenburg for providing the photobeam activity system that was used in this study. 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Psychopathol. PD NOV PY 2014 VL 26 IS 4 BP 889 EP 900 DI 10.1017/S0954579414000522 PN 1 PG 12 WC Psychology, Developmental SC Psychology GA AS2XY UT WOS:000344140900002 PM 24912737 ER PT J AU Lozier, LM Vanmeter, JW Marsh, AA AF Lozier, Leah M. Vanmeter, John W. Marsh, Abigail A. TI Impairments in facial affect recognition associated with autism spectrum disorders: A meta-analysis SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID FUSIFORM FACE AREA; PERVASIVE DEVELOPMENTAL DISORDERS; BIOLOGICAL MOTION PERCEPTION; EMOTION-RECOGNITION; ASPERGERS-SYNDROME; IMPAIRED RECOGNITION; EXPRESSION RECOGNITION; PROCESSING STRATEGIES; SOCIAL COGNITION; AMYGDALA THEORY AB Autism spectrum disorders (ASDs) are characterized by social impairments, including inappropriate responses to affective stimuli and nonverbal cues, which may extend to poor face-emotion recognition. However, the results of empirical studies of face-emotion recognition in individuals with ASD have yielded inconsistent findings that occlude understanding the role of face-emotion recognition deficits in the development of ASD. The goal of this meta-analysis was to address three as-yet unanswered questions. Are ASDs associated with consistent face-emotion recognition deficits? Do deficits generalize across multiple emotional expressions or are they limited to specific emotions? Do age or cognitive intelligence affect the magnitude of identified deficits? The results indicate that ASDs are associated with face-emotion recognition deficits across multiple expressions and that the magnitude of these deficits increases with age and cannot be accounted for by intelligence. 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When infants were 10-28days old, we presented them with an animated macaque avatar displaying a still face followed by lipsmacking or tongue protrusion movements. Using eye tracking technology, we found that macaque infants generally looked equally at the eyes and mouth during gesture presentation, but only lipsmacking-imitators showed significantly more looking at the eyes of the neutral still face. These results suggest that neonatal imitation performance may be an early measure of social attention biases and might potentially facilitate the identification of infants at risk for atypical social development. C1 [Paukner, Annika; Simpson, Elizabeth A.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Dept Hlth & Human Serv, Poolesville, MD USA. [Simpson, Elizabeth A.; Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. 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Sci. PD NOV PY 2014 VL 17 IS 6 BP 833 EP 840 DI 10.1111/desc.12207 PG 8 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA AS5XX UT WOS:000344340900005 PM 24995706 ER PT J AU Henderson, L Powell, A Gaskell, MG Norbury, C AF Henderson, Lisa Powell, Anna Gaskell, M. Gareth Norbury, Courtenay TI Learning and consolidation of new spoken words in autism spectrum disorder SO DEVELOPMENTAL SCIENCE LA English DT Article ID HIGH-FUNCTIONING AUTISM; LEXICAL COMPETITION; LANGUAGE IMPAIRMENT; ASPERGER-SYNDROME; COGNITIVE-STYLE; CHILDREN; SLEEP; MEMORY; SPEECH; ADULTS AB Autism spectrum disorder (ASD) is characterized by rich heterogeneity in vocabulary knowledge and word knowledge that is not well accounted for by current cognitive theories. This study examines whether individual differences in vocabulary knowledge in ASD might be partly explained by a difficulty with consolidating newly learned spoken words and/or integrating them with existing knowledge. Nineteen boys with ASD and 19 typically developing (TD) boys matched on age and vocabulary knowledge showed similar improvements in recognition and recall of novel words (e.g. biscal') 24 hours after training, suggesting an intact ability to consolidate explicit knowledge of new spoken word forms. TD children showed competition effects for existing neighbors (e.g. biscuit') after 24 hours, suggesting that the new words had been integrated with existing knowledge over time. In contrast, children with ASD showed immediate competition effects that were not significant after 24 hours, suggesting a qualitative difference in the time course of lexical integration. These results are considered from the perspective of the dual-memory systems framework. C1 [Henderson, Lisa; Gaskell, M. Gareth] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England. [Powell, Anna; Norbury, Courtenay] Univ London, Dept Psychol, London WC1E 7HU, England. 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Sci. PD NOV PY 2014 VL 17 IS 6 BP 858 EP 871 DI 10.1111/desc.12169 PG 14 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA AS5XX UT WOS:000344340900007 PM 24636285 ER PT J AU Brunsting, NC Sreckovic, MA Lane, KL AF Brunsting, Nelson C. Sreckovic, Melissa A. Lane, Kathleen Lynne TI Special Education Teacher Burnout: A Synthesis of Research from 1979 to 2013 SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article DE teacher burnout; special education; emotional disturbance; role conflict; role ambiguity; Maslach Burnout Inventory ID JOB BURNOUT; EMOTIONAL EXHAUSTION; BEHAVIORAL-DISORDERS; CERTIFIED TEACHERS; SELF-EFFICACY; CHILDREN; AUTISM; MANAGEMENT; ATTRITION; STUDENTS AB Teacher burnout occurs when teachers undergoing stress for long periods of time experience emotional exhaustion, depersonalization, and lack of personal accomplishment (Maslach, 2003). Outcomes associated with burnout include teacher attrition, teacher health issues, and negative student outcomes. Special educators are at high risk for burnout as their working conditions align with many factors associated with burnout. In this review, we updated the literature on special education teacher working conditions by reviewing studies (N = 23) that (a) included a quantitative measure of burnout and (b) focused on special education teachers as participants. An analysis of the studies reviewed provided a clear base of support for the association between burnout and a range of variables from the individual, classroom, school, and district levels. Bronfenbrenner's (1977) Ecological Model supplied the organizational framework for the range of variables. Teacher experience, student disability, role conflict, role ambiguity, and administrative support were particularly salient factors in special education teacher burnout. 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H., 2001, TEACHER ED SPECIAL E, V24, P128, DOI DOI 10.1177/088840640102400207 NR 71 TC 0 Z9 0 PU WEST VIRGINIA UNIV PRESS PI MORGANTOWN PA COMMUNICATIONS BLDG PATTESON DR, PO BOX 6295, MORGANTOWN, WV 26506-6295 USA SN 0748-8491 EI 1934-8924 J9 EDUC TREAT CHILD JI Educ. Treat. Child. PD NOV PY 2014 VL 37 IS 4 BP 681 EP 711 PG 31 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AS0JH UT WOS:000343963100007 ER PT J AU Sanchez-Ortiz, E Cho, W Nazarenko, I Mo, W Chen, J Parada, LF AF Sanchez-Ortiz, Efrain Cho, Woosung Nazarenko, Inga Mo, Wei Chen, Jian Parada, Luis F. TI NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development SO GENES & DEVELOPMENT LA English DT Article DE Neurofibromatosis type 1; cerebellum; granule neuron progenitor; NF1; CNS development; barrel cortex ID AUTISTIC-LIKE BEHAVIOR; NEUROFIBROMATOSIS TYPE-1; MYELOPROLIFERATIVE DISEASE; HIPPOCAMPAL NEUROGENESIS; GLIAL DIFFERENTIATION; SOMATOSENSORY CORTEX; MUTANT MICE; MOUSE MODEL; RHOMBIC LIP; BRAIN AB Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germ line mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1-RAS-ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders. C1 [Sanchez-Ortiz, Efrain; Cho, Woosung; Nazarenko, Inga; Mo, Wei; Chen, Jian; Parada, Luis F.] Univ Texas Southwestern Med Sch, Dept Dev Biol, Dallas, TX 75390 USA. [Sanchez-Ortiz, Efrain; Cho, Woosung; Nazarenko, Inga; Mo, Wei; Chen, Jian; Parada, Luis F.] Univ Texas Southwestern Med Sch, Kent Waldrep Fdn Ctr Res Nerve Growth & Regenerat, Dallas, TX 75390 USA. RP Parada, LF (reprint author), Univ Texas Southwestern Med Sch, Dept Dev Biol, Dallas, TX 75390 USA. EM chenjian2014@suda.edu.cn; luis.parada@utsouthwestern.edu FU National Institutes of Health [P50]; Simons Foundation FX We thank Yuan Zhu for early discussions and sharing of data. We thank Yanjiao Li, Tracey Shipman, and Chen Zhang for technical assistance. We also thank all members of the Parada laboratory for helpful ideas and insightful discussions. This work was supported by National Institutes of Health grant P50 (to L.F.P.) and the Simons Foundation. L.F.P. is an American Cancer Society Research Professor. 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TI A CGG-Repeat Expansion Mutation in ZNF713 Causes FRA7A: Association with Autistic Spectrum Disorder in Two Families SO HUMAN MUTATION LA English DT Article DE autism; folate sensitive; fragile site; CGG repeat; ZNF713 ID FRAGILE-X-SYNDROME; FMR1; ALLELES; MALES AB We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (similar to 450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an un-methylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. 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TI Elevated Burden for Caregivers of Children with Persistent Asthma and a Developmental Disability SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Maternal depression; Parenting confidence; Quality of life; Developmental delay; Chronic condition ID INNER-CITY CHILDREN; QUALITY-OF-LIFE; MATERNAL DEPRESSIVE SYMPTOMS; DEFICIT-HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDER; UNITED-STATES; CHILDHOOD ASTHMA; ANXIETY DISORDERS; MAJOR DEPRESSION; PARENTING STRESS AB To evaluate how having a child with both persistent asthma and a developmental disability (DD) affects caregiver burden and quality of life (QOL). 3-10 year old children with persistent asthma in urban Rochester, NY. Cross-sectional baseline survey (2006-2009). Parent report of autism spectrum disorder or other behavioral disorder requiring medication. 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PD NOV PY 2014 VL 18 IS 9 BP 2080 EP 2088 DI 10.1007/s10995-014-1455-6 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AR9XE UT WOS:000343929300007 PM 24619226 ER PT J AU Kudryavtseva, NN Smagin, DA Kovalenko, IL Vishnivetskaya, GB AF Kudryavtseva, Natalia N. Smagin, Dmitry A. Kovalenko, Irina L. Vishnivetskaya, Galina B. TI Repeated positive fighting experience in male inbred mice SO NATURE PROTOCOLS LA English DT Article ID SOCIAL DEFEAT STRESS; GENE-EXPRESSION; PLUS-MAZE; AGGRESSIVE-BEHAVIOR; SENSORY CONTACT; ANIMAL-MODEL; MOUSE MODEL; DEPRESSION; ANXIETY; SUSCEPTIBILITY AB Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions. 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Mortberg, Ewa Rastam, Maria Stahlberg, Ola Frisen, Louise TI The Brief Obsessive-Compulsive Scale (BOCS): A self-report scale for OCD and obsessive-compulsive related disorders SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Article DE Attention deficit hyperactivity disorder; Autism; Assessment; Compulsive behaviour; Obsessions ID INVENTORY; SYMPTOMS; RELIABILITY; VALIDATION; VALIDITY; PREVALENCE; REVISION; VERSION AB Background: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date. Aim: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population. Method: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS. Results: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's alpha = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha = 0.94). Conclusions: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry. C1 [Bejerot, Susanne; Frisen, Louise] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Edman, Gunnar] TioHundra AB, Dept Psychiat, Nortalje, Sweden. [Anckarsater, Henrik; Gillberg, Christopher; Stahlberg, Ola] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Berglund, Gunilla; Mortberg, Ewa] Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. 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Delahunty, Carol McBrien, Dianne Visootsak, Jeannie Berry-Kravis, Elizabeth TI Fragile X Syndrome: A Review of Associated Medical Problems SO PEDIATRICS LA English DT Article DE fragile X syndrome; otitis media; seizures; strabismus; gastrointestinal; sleep; growth; review ID MITRAL-VALVE-PROLAPSE; MARTIN-BELL SYNDROME; RECURRENT OTITIS-MEDIA; PRESCHOOL-AGE CHILDREN; SLEEP PROBLEMS; PARENT SURVEY; INTELLECTUAL DISABILITY; TYPICAL DEVELOPMENT; MENTAL-RETARDATION; STATUS EPILEPTICUS AB Fragile X syndrome (FXS) is the most common known genetic cause of inherited intellectual disability and the most common known single-gene cause of autism spectrum disorder. It has been reported that a spectrum of medical problems are commonly experienced by people with FXS, such as otitis media, seizures, and gastrointestinal problems. Previous studies examining the prevalence of medical problems related to FXS have been challenging to interpret because of their marked differences in population, setting, and sampling. Through this comprehensive review, we update the literature by reviewing studies that have reported on prominent medical problems associated with FXS. We then compare prevalence results from those studies with results from a large cross-sectional database consisting of data collected by fragile X clinics that specialize in the care of children with FXS and are part of the Fragile X Clinical and Research Consortium. It is vital for pediatricians and other clinicians to be familiar with the medical problems related to FXS so that affected patients may receive proper diagnosis and treatment; improved care may lead to better quality of life for these patients and their families. C1 [Kidd, Sharon A.] Natl Fragile X Fdn, Walnut Creek, CA 94596 USA. [Lachiewicz, Ave] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Lachiewicz, Ave] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Lachiewicz, Ave] Duke Univ, Med Ctr, Dept Behav Sci, Durham, NC 27710 USA. [Barbouth, Deborah] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA. [Blitz, Robin K.] Phoenix Childrens Hosp, Barrow Neurol Inst, Phoenix, AZ USA. [Blitz, Robin K.] Univ Arizona, Coll Med, Dept Pediat, Phoenix, AZ USA. [Delahunty, Carol] Cleveland Clin, Dept Dev & Rehabil Pediat, Cleveland, OH 44106 USA. [McBrien, Dianne] Univ Iowa, Med Ctr, Dept Pediat, Iowa City, IA USA. [Visootsak, Jeannie] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Visootsak, Jeannie] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Berry-Kravis, Elizabeth] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. RP Kidd, SA (reprint author), Natl Fragile X Fdn, 1615 Bonanza St,Suite 202, Walnut Creek, CA 94596 USA. EM sharon@fragilex.org FU Centers for Disease Control and Prevention (CDC) [5U19DD000753-02]; Association of University Centers on Disabilities (AUCD) [5U01DD000231, RTOI 2008-999-03] FX Funded in part by a Centers for Disease Control and Prevention (CDC) cooperative agreement with the Association of University Centers on Disabilities (AUCD) (5U01DD000231), an AUCD cooperative agreement with Dr Ted Brown (RTOI 2008-999-03), and a CDC cooperative agreement with Dr Ted Brown (5U19DD000753-02). 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Howerton, Christopher L. Garner, Joseph P. Hyde, Shellie A. Clark, Catherine L. Hardan, Antonio Y. Penn, Anna A. Parker, Karen J. TI Plasma vasopressin concentrations positively predict cerebrospinal fluid vasopressin concentrations in human neonates SO PEPTIDES LA English DT Article DE Arginine vasopressin; Cerebrospinal fluid; Human neonate; Lumbar puncture; Oxytocin; Plasma ID ARGININE-VASOPRESSIN; OXYTOCIN; BRAIN; RELEASE; IMPACT; CSF AB Central arginine vasopressin (AVP) plays a critical role in mammalian social behavior and has been hypothesized to be a biomarker of certain human neurodevelopmental disorders, including autism. However, opportunities to collect post-mortem brain tissue or cerebrospinal fluid (CSF) from children are extremely limited, and the use of less invasive peripheral assessments (e. g., blood, urine, or saliva) of AVP as a proxy for more invasive central measures has not been well validated. Further, almost nothing is known about AVP biology in very young infants. Therefore in the present study we concomitantly collected basal CSF and plasma samples from N = 20 neonates undergoing clinical sepsis evaluation (all were sepsis negative) and quantified AVP concentrations via well-validated enzyme-immunoassay methodology. Plasma AVP concentrations significantly and positively predicted CSF AVP concentrations (r = 0.73, p = 0.0021), and this relationship persisted when variance attributed to sex, gestational age, and sample collection time was controlled for in the statistical model (r = 0.75, p = 0.0047). These findings provide preliminary support for the use of basal plasma AVP measurement as a proxy for basal brain AVP activity in pediatric populations. Future studies are now required to determine the relationship between behavioral measures and AVP concentrations in both central and peripheral compartments in young infants and older children. (C) 2014 Elsevier Inc. All rights reserved. C1 [Carson, Dean S.; Garner, Joseph P.; Hyde, Shellie A.; Hardan, Antonio Y.; Parker, Karen J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Howerton, Christopher L.; Garner, Joseph P.] Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. [Clark, Catherine L.; Penn, Anna A.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Stanford, CA 94305 USA. [Penn, Anna A.] Childrens Natl Med Ctr, Dept Fetal & Transit Med, Washington, DC 20010 USA. [Penn, Anna A.] Childrens Natl Med Ctr, Dept Neonatol, Washington, DC 20010 USA. [Penn, Anna A.] Childrens Natl Med Ctr, Ctr Res Neurosci, Washington, DC 20010 USA. RP Carson, DS (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, 1201 Welch Rd, Stanford, CA 94305 USA. EM dcarson@stanford.edu; kjparker@stanford.edu FU Autism Speaks Meixner Postdoctoral Fellowship in Translational Research [7895]; Mosbacher Family Fund for Autism Research; Katherine D. McCormick Fund; NIH Director's New Innovator Award [1DP2OD006457]; Center for Brain and Behavior at Lucile Packard Children's Hospital (LPCH); LPCH Autism Center; NIH/NCRR [UL1 RR025744] FX This work was supported by an Autism Speaks Meixner Postdoctoral Fellowship in Translational Research (7895; D. S. C.); the Mosbacher Family Fund for Autism Research (K.J.P.); the Katherine D. McCormick Fund (K.J.P.), NIH Director's New Innovator Award (1DP2OD006457; A. A. P.); Center for Brain and Behavior at Lucile Packard Children's Hospital (LPCH) (to A. A. P., K.J.P., and A.Y.H.), the LPCH Autism Center, and by an NIH/NCRR grant to the Stanford Center for Clinical Informatics (UL1 RR025744). 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On the one hand, people often take on each other's internal states reflexively and outside of awareness. On the other hand, empathy shifts with characteristics of empathizers and situations. These 2 characteristics of empathy can be reconciled by acknowledging the key role of motivation in driving people to avoid or approach engagement with others' emotions. In particular, at least 3 phenomena-suffering, material costs, and interference with competition-motivate people to avoid empathy, and at least 3 phenomena-positive affect, affiliation, and social desirability-motivate them to approach empathy. Would-be empathizers carry out these motives through regulatory strategies including situation selection, attentional modulation, and appraisal, which alter the course of empathic episodes. Interdisciplinary evidence highlights the motivated nature of empathy, and a motivated model holds wide-ranging implications for basic theory, models of psychiatric illness, and intervention efforts to maximize empathy. C1 Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Zaki, J (reprint author), Stanford Univ, Dept Psychol, Jordan Hall Bldg 420, Stanford, CA 94305 USA. 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Bull. PD NOV PY 2014 VL 140 IS 6 BP 1608 EP 1647 DI 10.1037/a0037679 PG 40 WC Psychology; Psychology, Multidisciplinary SC Psychology GA AS6DD UT WOS:000344354000008 PM 25347133 ER PT J AU Lycett, K Mensah, FK Hiscock, H Sciberras, E AF Lycett, Kate Mensah, Fiona K. Hiscock, Harriet Sciberras, Emma TI A prospective study of sleep problems in children with ADHD SO SLEEP MEDICINE LA English DT Article DE Attention-deficit disorder with; hyperactivity; Sleep initiation and maintenance disorder; Child; Longitudinal studies; Risk factors; Sleep disorders ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; STIMULANT MEDICATION; ANXIETY; POPULATION; SCHOOL; ASSOCIATIONS; COMORBIDITY; DEPRESSION; PREVALENCE AB Background: Behavioral sleep problems are common in children with attention-deficit/hyperactivity disorder (ADHD), yet their persistence or otherwise is unknown. We examined behavioral sleep problem trajectories, types of sleep problems experienced, and associated risk/protective factors. Methods: Design: Prospective cohort study. Setting: Twenty-one pediatric practices across Victoria, Australia. Participants: A total of 195 children with ADHD (5-13 years). Outcomes: Sleep problem trajectories classified as never, transient, or persistent on the basis of sleep problem severity measured at baseline, 6, and 12 months. Explanatory variables: Types of sleep problems, internalizing and externalizing comorbidities, ADHD symptom severity and medication use, autism spectrum disorder, caregiver mental health, and sociodemographic factors. Analyses: Multinomial logistic regression models. Results: Sleep problems fluctuated over 12 months, but for 10% of children they persisted. In adjusted analyses, co-occurring internalizing and externalizing comorbidities were a risk factor for persistent (odds ratio (OR) 9.2, 95% confidence interval (CI) 1.6, 53.9, p = 0.01) and transient (OR 3.7, 95% CI 1.5, 8.8, p = 0.003) sleep problems, while greater ADHD symptom severity and poorer caregiver mental health were risk factors for persistent and transient sleep problems, respectively. Conclusions: Sleep problems in children with ADHD are commonly transient, but in a subgroup they are characterized as persistent. Early preventive/intervention strategies should target children at risk of persistent sleep problems. (C) 2014 Elsevier B.V. All rights reserved. C1 [Lycett, Kate] Univ Melbourne, Dept Paediat, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Mensah, Fiona K.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Clin Epidemiol & Biostat Unit, Parkville, Vic 3052, Australia. [Hiscock, Harriet] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Sciberras, Emma] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. RP Lycett, K (reprint author), Univ Melbourne, Dept Paediat, Murdoch Childrens Res Inst, 50 Flemington Rd, Parkville, Vic 3052, Australia. EM kate.lycett@mcri.edu.au FU Australian National Health and Medical Research Council (NHRMC) [607362]; Community Child Health at the Murdoch Childrens Research Institute (MCRI); NHMRC Early Career Fellowships in Population Health [1037159, 1037449]; MCRI Postgraduate Health Scholarship; NHMRC Career Development Award [607351]; Victorian Government's Operational Infrastructure Support Program FX This project is funded by a Project Grant from the Australian National Health and Medical Research Council (NHRMC) (607362) and Community Child Health at the Murdoch Childrens Research Institute (MCRI). Dr Sciberras and Dr Mensah are funded by NHMRC Early Career Fellowships in Population Health (1037159 and 1037449). Ms Lycett is funded by an MCRI Postgraduate Health Scholarship. A/Prof. Hiscock's position is funded by an NHMRC Career Development Award (607351). MCRI is supported by the Victorian Government's Operational Infrastructure Support Program. 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Health PD NOV PY 2014 VL 41 IS 6 BP 808 EP 821 DI 10.1007/s10488-013-0533-1 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AS0UW UT WOS:000343994900011 PM 24389835 ER PT J AU Hall, L Kelley, E AF Hall, Layla Kelley, Elizabeth TI The contribution of epigenetics to understanding genetic factors in autism SO AUTISM LA English DT Article DE autism; autism spectrum disorder; epigenetic; genetic ID X-CHROMOSOME INACTIVATION; CPG-BINDING PROTEIN-2; COPY NUMBER VARIATION; SPECTRUM DISORDERS; RETT-SYNDROME; BRAIN-DEVELOPMENT; NEURODEVELOPMENTAL DISORDERS; MECP2 EXPRESSION; ENVIRONMENTAL-FACTORS; DNA METHYLATION AB Autism spectrum disorder is a grouping of neurodevelopmental disorders characterized by deficits in social communication and language, as well as by repetitive and stereotyped behaviors. While the environment is believed to play a role in the development of autism spectrum disorder, there is now strong evidence for a genetic link to autism. Despite such evidence, studies investigating a potential single-gene cause for autism, although insightful, have been highly inconclusive. A consideration of an epigenetic approach proves to be very promising in clarifying genetic factors involved in autism. The present article is intended to provide a review of key findings pertaining to epigenetics in autism in such a way that a broader audience of individuals who do not have a strong background in genetics may better understand this highly specific and scientific content. Epigenetics refers to non-permanent heritable changes that alter expression of genes without altering the DNA sequence itself and considers the role of environment in this modulation of gene expression. This review provides a brief description of epigenetic processes, highlights evidence in the literature of epigenetic dysregulation in autism, and makes use of noteworthy findings to illustrate how a consideration of epigenetic factors can deepen our understanding of the development of autism. Furthermore, this discussion will present a promising new way for moving forward in the investigation of genetic factors within autism. C1 [Hall, Layla; Kelley, Elizabeth] Queens Univ, Kingston, ON K7L 3N6, Canada. RP Hall, L (reprint author), Queens Univ, Dept Psychol, 62 Arch St, Kingston, ON K7L 3N6, Canada. 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Recently, challenging behaviour has been linked to people with autism spectrum disorders; however, little research has been aimed at exploring staff's experiences of facing such behaviour in services for autism spectrum disorders in particular. A qualitative study using interpretative phenomenological analysis was conducted. This method involves thorough exploration of experiences revealed by individuals. A purposive sample (N = 10) was used. Participants were involved in semi-structured interviews which were later analysed according to the guidelines by Smith and Osborn. Four themes were discovered: intense mental and physical engagement, importance of adaptive coping, ambiguous experience of failure and achievement and destructive emotional reactions. Being exposed to challenging behaviour in services for autism spectrum disorders is a complex multi-component experience. 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This study aimed to develop a valid measure of affectionate behaviour that could be used to investigate and quantify these anecdotal reports and then be used in further intervention research. Using parent and expert focus groups, three measures (Affection for Others Questionnaire, Affection for You Questionnaire and General Affection Questionnaire) were developed with reference to the existing affection literature. The measures were completed by 131 parents of children with a clinician-confirmed diagnosis of Asperger's syndrome. Psychometric assessment of the measures revealed clear factor structures with high internal consistencies and significant concurrent validities. The findings suggest many children with Asperger's syndrome have difficulties with affectionate behaviour that significantly impact their daily functioning and relationships with others, signalling future research needs to develop interventions in this area. Limitations of the research are also discussed. C1 [Sofronoff, Kate; Lee, Jessica; Sheffield, Jeanie; Attwood, Tony] Univ Queensland, St Lucia, Qld 4072, Australia. RP Sofronoff, K (reprint author), Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia. 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Orsmond, Gael I. Coster, Wendy J. Cohn, Ellen S. TI Media use among adolescents with autism spectrum disorder SO AUTISM LA English DT Article DE adolescent; autism spectrum disorder; media use; personal relationships ID PARENTAL MEDIATION; VIDEO GAMES; CHILDREN; TELEVISION; INTERNET; COMMUNICATION; TECHNOLOGY; AGGRESSION; PREVALENCE; BEHAVIOR AB This study explores how adolescents with autism spectrum disorder (ASD) use media, and the factors associated with their media use. A total of 91 adolescents with ASD and their parents completed mail-based surveys. In all, 78% of the adolescents with ASD watched television (approximately 2 h/day), and 98% used computers (approximately 5 h/day) on any given day. They most frequently watched cartoons, played computer or video games that involved shooting, and visited websites that contained information on video games. Adolescents with ASD who watched television with parents reported more positive parent-child relationships. Adolescents with ASD who visited social networking websites or received emails from friends reported more positive friendships. The findings help us understand media-use habits of adolescents with ASD and suggest areas for future research. C1 [Kuo, Melissa H.] Univ Alberta, Edmonton, AB T6G 2G4, Canada. [Orsmond, Gael I.; Coster, Wendy J.; Cohn, Ellen S.] Boston Univ, Boston, MA 02215 USA. RP Kuo, MH (reprint author), Univ Alberta, 2-64 Corbett Hall, Edmonton, AB T6G 2G4, Canada. EM melissa.kuo@ualberta.ca CR Adams E., 2009, FUNDAMENTALS GAME DE, V2nd Anderson DR, 2001, MONOGR SOC RES CHILD, V66, P1, DOI 10.1111/1540-5834.00121 (APA) APA, 2000, DIAGN STAT MAN MENT Barlett CP, 2007, AGGRESSIVE BEHAV, V33, P486, DOI 10.1002/ab.20227 Blais JJ, 2008, J YOUTH ADOLESCENCE, V37, P522, DOI 10.1007/s10964-007-9262-7 BUKOWSKI WM, 1994, J SOC PERS RELAT, V11, P471, DOI 10.1177/0265407594113011 Chandler S, 2007, J AM ACAD CHILD PSY, V46, P1324, DOI 10.1097/chi.0b013e31812f7d8d DORR A, 1989, J BROADCAST ELECTRON, V33, P35 Gullone E, 2005, CLIN PSYCHOL PSYCHOT, V12, P67, DOI 10.1002/cpp.433 Kraut R, 1998, AM PSYCHOL, V53, P1017, DOI 10.1037//0003-066X.53.9.1017 Larson RW, 1999, PSYCHOL BULL, V125, P701, DOI 10.1037//0033-2909.125.6.701 Lecavalier L, 2008, J INTELLECT DEV DIS, V32, P179 Mazurek MO, 2012, J AUTISM DEV DISORD, V42, P1757, DOI 10.1007/s10803-011-1413-8 Nally B, 2000, AUTISM, V4, P331, DOI DOI 10.1177/1362361300004003008 Nathanson AI, 1999, COMMUN RES, V26, P124, DOI 10.1177/009365099026002002 Nathanson AI, 2002, MEDIA PSYCHOL, V4, P207, DOI 10.1207/S1532785XMEP0403_01 Newcomb H, 2004, ENCY TELEVISION Olson CK, 2009, APPL DEV SCI, V13, P188, DOI 10.1080/10888690903288748 O'Riordan M, 2001, Q J EXP PSYCHOL-A, V54, P961, DOI 10.1080/02724980042000543 O'Riordan MA, 2001, J EXP PSYCHOL HUMAN, V27, P719, DOI 10.1037//0096-1523.27.3.719 Orsmond G. 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J., 2010, GENERATION M2 MEDIA Roberts DR, 2004, KIDS MEDIA AM Rutter M., 2003, SCQ SOCIAL COMMUNICA SANG F, 1993, J YOUTH ADOLESCENCE, V22, P531, DOI 10.1007/BF01537714 Shane HC, 2008, J AUTISM DEV DISORD, V38, P1499, DOI 10.1007/s10803-007-0527-5 Sheskin D, 2007, HDB PARAMETRIC NONPA, V4th Shields MK, 2000, FUTURE CHILD, V10, P4, DOI 10.2307/1602687 Valkenburg PM, 2007, DEV PSYCHOL, V43, P267, DOI 10.1037/0012-1649.43.2.267 Willoughby T, 2008, DEV PSYCHOL, V44, P195, DOI 10.1037/0012-1649.44.1.195 Winter-Messiers MA, 2007, REM SPEC EDUC, V28, P140, DOI 10.1177/07419325070280030301 NR 32 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 NOV PY 2014 VL 18 IS 8 BP 914 EP 923 DI 10.1177/1362361313497832 PG 10 WC Psychology, Developmental SC Psychology GA AR9PF UT WOS:000343906200006 PM 24142797 ER PT J AU Suarez, MA Nelson, NW Curtis, AB AF Suarez, Michelle A. Nelson, Nickola W. Curtis, Amy B. TI Longitudinal follow-up of factors associated with food selectivity in children with autism spectrum disorders SO AUTISM LA English DT Article DE autism; food selectivity; sensory over-responsivity; sensory processing disorders; restrictive and repetitive behavior ID REPETITIVE BEHAVIOR; FEEDING PROBLEMS AB The objective of this study was to examine food selectivity in children with autism spectrum disorders longitudinally. Additionally explored were the stability of the relationship between food selectivity and sensory over-responsivity from time 1 to time 2 and the association between food selectivity and restricted and repetitive behavior at time 2. A total of 52 parents of children with autism were surveyed approximately 20 months after completing an initial questionnaire. First and second surveys each contained identical parent-response item to categorize food selectivity level and a scale to measure sensory over-responsivity. A new scale to measure restricted and repetitive behaviors was added at time 2. Results comparing time 1 to time 2 indicated no change in food selectivity level and a stable, significant relationship between food selectivity and sensory over-responsivity. The measure of restrictive and repetitive behavior (time 2) was found to significantly predict membership in the severe food selectivity group. However, when sensory over-responsivity and both restricted and repetitive behaviors were included in the regression model, only sensory over-responsivity significantly predicted severe food selectivity. These results support conclusions about the chronicity of food selectivity in young children with autism and the consistent relationship between food selectivity and sensory over-responsivity. C1 [Suarez, Michelle A.; Nelson, Nickola W.; Curtis, Amy B.] Western Michigan Univ, Kalamazoo, MI 49008 USA. 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Nowell, Kerri P. Kubiszyn, Thomas Goin-Kochel, Robin P. TI Psychotropic medication use among children with autism spectrum disorders within the Simons Simplex Collection: Are core features of autism spectrum disorder related? SO AUTISM LA English DT Article DE autism spectrum disorders; core features; psychotropic medication use; Simons Simplex Collection ID PSYCHIATRIC-DISORDERS; PATTERNS; ADOLESCENTS; PREVALENCE; MANAGEMENT; RISK; PARENTS; YOUTH AB Psychotropic medication use and its relationship to autism spectrum core features were examined in a well-characterized but nonstratified North American sample (N = 1605) of children/adolescents diagnosed with autism spectrum disorders utilizing the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised, from the multisite Simons Simplex Collection. Analyses included (a) prevalence of psychotropic use (overall, and by classes), (b) correlations between prevalence of use and autism spectrum core features, age, and cognitive functioning, and (c) logistic regression to identify whether these factors were predictive of psychotropic use. Results indicated 41.7% ever used one or more classes of psychotropic medications, with attention deficit hyperactivity disorder medications used most. Small but significant correlations between psychotropic medication use and (a) social impairment (p < .001) and (b) repetitive behaviors (p < .001) were found. Overall, however, autism spectrum disorder core features are weakly related to medication use. Older children used more psychotropics (p < .001), and higher cognitive functioning was associated with less overall psychotropic use (p < .001). Logistic regression indicated that use of psychotropics was predicted by repetitive behaviors (both clinician-observed and parent-reported), age, and cognitive ability level. Limitations inherent to the Simons Simplex Collection sample, methodology, and the correlational analyses are discussed. Directions for future research include investigation of factors more influential than core symptoms on psychotropic treatment (e.g. parent perceptions, comorbid symptoms). C1 [Mire, Sarah S.; Nowell, Kerri P.; Kubiszyn, Thomas] Univ Houston, Houston, TX 77044 USA. [Goin-Kochel, Robin P.] Baylor Coll Med, Houston, TX 77030 USA. RP Mire, SS (reprint author), Univ Houston, Dept Educ Psychol, 491 Farish Hall, Houston, TX 77044 USA. EM ssmire@uh.edu CR Aman MG, 2005, J CHILD ADOL PSYCHOP, V15, P116, DOI 10.1089/cap.2005.15.116 Aman MG, 2003, J AUTISM DEV DISORD, V33, P527, DOI 10.1023/A:1025883612879 Brown R. 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Previous research by Reed et al. using static images of the human body shows that people with autism fail to demonstrate this effect. Using a novel task in which adults, adolescents with autism, and typically developing adolescents judged whether walking stick figurescreated from biological motion recordings and shown at seven orientations between 0 degrees and 180 degrees were normal or distorted, this study shows clear effects of stimulus inversion. Reaction times and inverse efficiency increased with orientation for normal but not distorted walkers, and sensitivity declined with rotation from upright for all groups. Notably, the effect of stimulus inversion was equally detrimental to both groups of adolescents suggesting intact configural processing of the body in motion in autism spectrum disorder. C1 [Cleary, Laura; Looney, Kathy; Brady, Nuala] Univ Coll Dublin, Dublin 4, Ireland. [Fitzgerald, Michael] Trinity Coll Dublin, Dublin, Ireland. 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In this pilot study, the feasibility and outcomes of a 6-week acceptance and commitment therapy-based skills training group were evaluated in a special school setting using a quasi-experimental design (acceptance and commitment therapy/school classes as usual). A total of 28 high-functioning students with autism spectrum disorder (aged 13-21 years) were assessed using self- and teacher-ratings at pre- and post-assessment and 2-month follow-up. All participants completed the skills training, and treatment satisfaction was high. Levels of stress, hyperactivity and emotional distress were reduced in the treatment group. The acceptance and commitment therapy group also reported increased prosocial behaviour. These changes were stable or further improved at the 2-month follow-up. Larger studies are needed to further evaluate the benefits of acceptance and commitment therapy for autism spectrum disorder. C1 [Pahnke, Johan; Hirvikoski, Tatja] Karolinska Inst KIND, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, S-11330 Stockholm, Sweden. [Lundgren, Tobias] Stockholm Univ, Stockholm, Sweden. [Hursti, Timo] Uppsala Univ, S-75105 Uppsala, Sweden. RP Hirvikoski, T (reprint author), Karolinska Inst KIND, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, Gavlegatan 22B, S-11330 Stockholm, Sweden. 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Zablotsky, Benjamin Yarger, Heather A. Zimmerman, Andrew Makia, Barraw Lee, Li-Ching TI Sex differences in co-occurring conditions of children with autism spectrum disorders SO AUTISM LA English DT Article DE Autism spectrum disorder; co-occurring conditions; sex ID PERVASIVE DEVELOPMENTAL DISORDERS; PREVALENCE; EPIDEMIOLOGY; DISABILITIES; DIAGNOSIS AB This study investigated differences in co-occurring diagnoses made in females compared to males with autism spectrum disorders in 913 children (746 males and 167 females) living in the United States with a current autism spectrum disorder diagnosis identified via caregiver-reported data from the National Survey of Children's Health 2007. The results indicated that overall, females had significantly fewer reported autism spectrum disorder co-occurring conditions than males. Females, compared to males, with a current autism spectrum disorder diagnosis had lower rates of past learning disorder, current mild learning disorder, and past anxiety diagnoses. Females with a current autism spectrum disorder diagnosis were more likely than males to have been diagnosed with a speech problem in the past, while males with a current autism spectrum disorder diagnosis were more likely than females to have a current diagnosis of a mild learning disability and a past diagnosis of learning disability. In addition, males with a current autism spectrum disorder diagnosis were more likely than females to have two or more co-occurring diagnoses. These findings provide insight into trends in sex differences in autism spectrum disorder co-occurring conditions. C1 [Stacy, Maria E.; Zablotsky, Benjamin; Makia, Barraw; Lee, Li-Ching] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Yarger, Heather A.] Univ Delaware, Newark, DE 19716 USA. [Zimmerman, Andrew] Massachusetts Gen Hosp Children, Boston, MA USA. RP Lee, LC (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Suite E6032, Baltimore, MD 21205 USA. 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Supported employment enables individuals with autism to secure and maintain a paid job in a regular work environment. The objective of this study was to assess the cost-effectiveness of supported employment compared with standard care (day services) for adults with autism in the United Kingdom. Thus, a decision-analytic economic model was developed, which used outcome data from the only trial that has evaluated supported employment for adults with autism in the United Kingdom. The main analysis considered intervention costs, while cost-savings associated with changes in accommodation status and National Health Service and personal social service resource use were examined in secondary analyses. Two outcome measures were used: the number of weeks in employment and the quality-adjusted life year. Supported employment resulted in better outcomes compared with standard care, at an extra cost of 18 pound per additional week in employment or 5600 pound per quality-adjusted life year. 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Wingsiong, Aranda Lunsky, Yona TI Defining crisis in families of individuals with autism spectrum disorders SO AUTISM LA English DT Article DE autism spectrum disorder; crisis; family; qualitative study ID DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITY; BEHAVIOR PROBLEMS; PARENTING STRESS; CHRONIC ILLNESS; MENTAL-HEALTH; CHILDREN; MOTHERS; FATHERS; ADAPTATION AB Parents of children diagnosed with autism spectrum disorder often report higher levels of depression, anxiety, and mental health-related issues. The combination of stressors and family adjustment difficulties can cause distress which may develop into a crisis. Understanding crisis in the family is important to mental health practice since it can serve as a guide in delivering service to at-risk families. This study investigated the subjective experience of crisis in 155 mothers of children diagnosed with autism spectrum disorder. Thematic analysis revealed that crisis is characterized by factors influencing four major areas: demands, internal capabilities, external resources, and subjective appraisal. Understanding what crisis means to families of individuals with autism spectrum disorder can help inform effective preventative and crisis services. C1 [Weiss, Jonathan A.; Wingsiong, Aranda] York Univ, Toronto, ON M3J 1P3, Canada. RP Weiss, JA (reprint author), York Univ, Dept Psychol, 4700 Keele St, Toronto, ON M3J 1P3, Canada. 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Johnson, Ashley L. Spence, Sarah J. Buka, Stephen L. Morrow, Eric M. Triche, Elizabeth W. TI The association between epilepsy and autism symptoms and maladaptive behaviors in children with autism spectrum disorder SO AUTISM LA English DT Article DE autism spectrum disorder; autism symptoms; epilepsy; hyperactivity; intellectual disability ID INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; REPETITIVE BEHAVIOR; INDIVIDUALS; PREVALENCE; CHECKLIST; SEIZURES; SCALE; COMMUNICATION AB Epilepsy is common in children with autism spectrum disorder (ASD) but little is known about how seizures impact the autism phenotype. The association between epilepsy and autism symptoms and associated maladaptive behaviors was examined in 2,645 children with ASD, of whom 139 had epilepsy, from the Simons Simplex Collection. Children with ASD and epilepsy had significantly more autism symptoms and maladaptive behaviors than children without epilepsy. However, after adjusting for IQ, only hyperactivity symptoms remained significantly increased (13% higher) in the epilepsy group. Among children with ASD without co-occurring intellectual disability, children with epilepsy had significantly more irritability (20% higher) and hyperactivity (24% higher) symptoms. This is the largest study to date comparing the autism phenotype in children with ASD with and without epilepsy. Children with ASD and epilepsy showed greater impairment than children without epilepsy, which was mostly explained by the lower IQ of the epilepsy group. These findings have important clinical implications for patients with ASD. C1 [Viscidi, Emma W.; Buka, Stephen L.; Morrow, Eric M.; Triche, Elizabeth W.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Johnson, Ashley L.; Morrow, Eric M.] Emma Pendleton Bradley Hosp, Riverside, CA USA. [Johnson, Ashley L.; Morrow, Eric M.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Spence, Sarah J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Morrow, EM (reprint author), Brown Univ, Dept Mol Biol Cell Biol & Biochem, 70 Ship St, Providence, RI 02912 USA. 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autism spectrum disorder; children; conformity ID JOINT ATTENTION; BEHAVIORS; PRESSURE; CULTURE; ADULTS; AQ AB Perhaps surprisingly, given the importance of conformity as a theoretical construct in social psychology and the profound implications autism has for social function, little research has been done on whether autism is associated with the propensity to conform to a social majority. This study is a modern, child-friendly implementation of the classic Asch conformity studies. The performance of 15 children with autism was compared to that of 15 typically developing children on a line judgement task. Children were matched for age, gender and numeracy and literacy ability. In each trial, the child had to say which of three lines a comparison line matched in length. On some trials, children were misled as to what most people thought the answer was. Children with autism were much less likely to conform in the misleading condition than typically developing children. This finding was replicated using a continuous measure of autism traits, the Autism Quotient questionnaire, which showed that autism traits negatively correlated with likelihood to conform in the typically developing group. This study demonstrates the resistance of children with autism to social pressure. C1 [Yafai, Abdul-Fattah; Verrier, Diarmuid; Reidy, Lisa] Sheffield Hallam Univ, Sheffield S10 2LD, S Yorkshire, England. RP Verrier, D (reprint author), Sheffield Hallam Univ, Sheffield S10 2LD, S Yorkshire, England. 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Teunisse, Jan-Pieter Koot, Hans M. Geurts, Hilde M. TI Verbal fluency in children with autism spectrum disorders: Clustering and switching strategies SO AUTISM LA English DT Article DE autism spectrum disorders; clustering; cognitive flexibility; fluency; switching ID HIGH-FUNCTIONING AUTISM; EXECUTIVE FUNCTIONS; COMMUNICATION DEFICITS; ASPERGER SYNDROME; INDIVIDUALS; ADULTS; SEX; DYSFUNCTION; LANGUAGE; TASK AB This study highlights differences in cognitive strategies in children and adolescents with and without autism spectrum disorders (n = 52) on a verbal fluency task (naming as many words as possible (e.g. animals) within 60 s). The ability to form clusters of words (e.g. farm animals like cow-horse-goat) or to switch between unrelated words (e.g. snake and cat) was analyzed using a coding method that more stringently differentiates between these strategies. Results indicated that children and adolescents with autism spectrum disorders switched less frequently, but produced slightly larger clusters than the comparison group, resulting in equal numbers of total words produced. The currently used measures of cognitive flexibility suggest atypical, but possibly equally efficient, fluency styles used by individuals with autism spectrum disorders. C1 [Begeer, Sander] Univ Sydney, Sydney, NSW 2006, Australia. [Begeer, Sander; Wierda, Marlies; Scheeren, Anke M.; Koot, Hans M.] Vrije Univ Amsterdam, NL-1081 BT Amsterdam, Netherlands. [Begeer, Sander; Wierda, Marlies; Scheeren, Anke M.] Autism Res Amsterdam, Amsterdam, Netherlands. [Teunisse, Jan-Pieter; Geurts, Hilde M.] Dr Leo Kannerhuis Autism Ctr, Amsterdam, Netherlands. [Teunisse, Jan-Pieter] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. [Geurts, Hilde M.] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands. 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Betz, Alison M. Malone, Evadne Henry, Justine E. Chong, Ivy M. TI EFFECTS OF VIDEO MODELING ON TEACHING BIDS FOR JOINT ATTENTION TO CHILDREN WITH AUTISM SO BEHAVIORAL INTERVENTIONS LA English DT Article ID YOUNG-CHILDREN; INTERVENTION; LANGUAGE; BEHAVIORS; PLAY AB The purpose of this study was to evaluate the effects of video modeling to teach children with autism to initiate bids for joint attention. The video model consisted of a child demonstrating three components of a bid for joint attention with an adult conversational partner: orienting toward the object, emitting a vocal statement, and eye gaze shift toward unique objects in the environment. Results indicated that video modeling alone was effective in teaching all components of joint attention for two of the three children, whereas video modeling plus in vivo prompting was effective for the third participant. Further, bids for joint attention did not generalize across novel items for any of the participants. 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Intervent. PD NOV PY 2014 VL 29 IS 4 BP 269 EP 285 DI 10.1002/bin.1398 PG 17 WC Psychology, Clinical SC Psychology GA AS3HB UT WOS:000344167200001 ER PT J AU Dominguez, A Wilder, DA Cheung, K Rey, C AF Dominguez, Alex Wilder, David A. Cheung, Kim Rey, Catalina TI THE USE OF A VERBAL REPRIMAND TO DECREASE RUMINATION IN A CHILD WITH AUTISM SO BEHAVIORAL INTERVENTIONS LA English DT Article ID FUNCTIONAL-ANALYSIS; REINFORCEMENT; INFANT AB After a pre-treatment screening analysis suggested that rumination exhibited by a boy with autism occurred in the absence of social consequences, we evaluated the effect of a verbal reprimand contingent on the target behavior via a reversal design. The reprimand reduced rumination to near-zero levels; we then thinned the reprimand schedule and rumination remained infrequent. Follow-up data collected 6, 12, and 18months after initial treatment suggested that intervention effects were maintained. Copyright (c) 2014 John Wiley & Sons, Ltd. 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PD NOV PY 2014 VL 29 IS 4 BP 339 EP 345 DI 10.1002/bin.1390 PG 7 WC Psychology, Clinical SC Psychology GA AS3HB UT WOS:000344167200006 ER PT J AU Nakako, T Murai, T Ikejiri, M Hashimoto, T Kotani, M Matsumoto, K Manabe, S Ogi, Y Konoike, N Nakamura, K Ikeda, K AF Nakako, Tomokazu Murai, Takeshi Ikejiri, Masaru Hashimoto, Takashi Kotani, Manato Matsumoto, Kenji Manabe, Shoji Ogi, Yuji Konoike, Naho Nakamura, Katsuki Ikeda, Kazuhito TI Effects of lurasidone on ketamine-induced joint visual attention dysfunction as a possible disease model of autism spectrum disorders in common marmosets SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Joint visual attention; Ketamine; Lurasidone; Marmoset; Autism spectrum disorder ID REVERSES MK-801-INDUCED IMPAIRMENT; PREFRONTAL CORTEX; WORKING-MEMORY; COMMUNICATION; CHILDREN; RATS; DOPAMINE; CHIMPANZEES; IMITATION; GLUTAMATE AB Infants with autism have difficulties performing joint visual attention (JVA), defined as following another person's pointing gesture and gaze. Some non-human primates (NHPs) can also perform JVA. Most preclinical research on autism spectrum disorders (ASD) has used rodents as animal models of this social interaction disorder. However, models using rodents fail to capture the complexity of social interactions that are disrupted in ASD. Therefore, JVA impairment in NHPs might be a more useful model of ASD. The aim of this study was to develop an appropriate and convenient ASD model with common marmosets. We first tested whether marmosets were capable of performing JVA. Subsequently, we administered ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, to induce JVA impairment and investigated the effects of lurasidone, a newer antipsychotic agent, on the JVA impairments. An apparatus was constructed using 4 white boxes, which were attached to the corners of a frame. All boxes had a hinged door, and marmosets could easily obtain a reward by pushing the door. An experimenter pointed and gazed at the boxes to inform the marmosets which box contained the reward. Their behavior was scored according to the number of incorrect choices. The JVA score was significantly higher in the cued vs. uncued tasks. Ketamine significantly decreased the JVA score, but lurasidone significantly reversed this effect. These findings suggest that this experimental system could be a useful animal model of neuropsychiatric disorders characterized by NMDA-receptor signaling, including ASD, and that lurasidone might be effective for some aspects of ASD. (C) 2014 Elsevier B.V. All rights reserved. C1 [Nakako, Tomokazu; Murai, Takeshi; Ikejiri, Masaru; Hashimoto, Takashi; Kotani, Manato; Matsumoto, Kenji; Manabe, Shoji; Ogi, Yuji; Ikeda, Kazuhito] Sumitomo Dainippon Pharma Co Ltd, Drug Dev Res Labs, Ikeda Lab, Suita, Osaka 5640053, Japan. [Konoike, Naho; Nakamura, Katsuki] Kyoto Univ, Primate Res Inst, Dept Behav & Brain Sci, Inuyama, Aichi 4848506, Japan. 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Brain Res. PD NOV 1 PY 2014 VL 274 BP 349 EP 354 DI 10.1016/j.bbr.2014.08.032 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AR8WL UT WOS:000343852100042 PM 25169254 ER PT J AU Hastings, RP Petalas, MA AF Hastings, R. P. Petalas, M. A. TI Self-reported behaviour problems and sibling relationship quality by siblings of children with autism spectrum disorder SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE autism spectrum disorder; behaviour problems; maternal depression; sibling relationships; siblings; strengths and difficulties questionnaire ID MENTAL-HEALTH; DIFFICULTIES QUESTIONNAIRE; ADJUSTMENT; PERCEPTIONS; DISABILITY; ANXIETY; STRESS; EXPERIENCES; DEPRESSION; COMPETENCE AB Background There are few published research studies in which siblings of children with autism spectrum disorder (ASD) provide self-reports about their own behavioural and emotional problems and their sibling relationships. Reliance on parent reports may lead to incomplete conclusions about the experiences of siblings themselves. Methods Siblings 7-17 years and their mothers from 94 families of children with ASD were recruited. Mothers reported on family demographics, the behavioural and emotional problems of their child with ASD, and on their own symptoms of depression. Siblings reported on their relationship with their brother or sister with ASD, and siblings 11+ years of age also self-reported on their behavioural and emotional problems. Results Compared with normative British data, siblings reported very slightly elevated levels of behavioural and emotional problems. However, none of the mean differences were statistically significant and all group differences were associated with small or very small effect sizes - the largest being for peer problems (effect size = 0.31). Regression analysis was used to explore family systems relationships, with sibling self-reports predicted by the behaviour problems scores for the child with ASD and by maternal depression. Maternal depression did not emerge as a predictor of siblings' self-reported sibling relationships or their behavioural and emotional problems. Higher levels of behaviour problems in the child with ASD predicted decreased warmth/closeness and increased conflict in the sibling relationship. Conclusions These data support the general findings of recent research in that there was little indication of clinically meaningful elevations in behavioural and emotional problems in siblings of children with ASD. Although further research replication is required, there was some indication that sibling relationships may be at risk where the child with ASD has significant behaviour problems. C1 [Hastings, R. P.] Univ Warwick, Ctr Educ Dev Appraisal & Res, Coventry CV4 7AL, W Midlands, England. [Petalas, M. A.] Mental Healthcare UK, St Asaph, England. RP Hastings, RP (reprint author), Univ Warwick, Ctr Educ Dev Appraisal & Res, Coventry CV4 7AL, W Midlands, England. EM R.Hastings@warwick.ac.uk RI Hastings, Richard/D-9657-2013 OI Hastings, Richard/0000-0002-0495-8270 FU European Social Fund; National Autistic Society; Bangor University FX The research reported in this paper was supported through PhD studentship funding from the European Social Fund, the National Autistic Society and Bangor University. 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PD NOV PY 2014 VL 40 IS 6 BP 833 EP 839 DI 10.1111/cch.12131 PG 7 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA AR8IW UT WOS:000343819800008 PM 24460897 ER PT J AU Thompson, GA McFerran, KS Gold, C AF Thompson, G. A. McFerran, K. S. Gold, C. TI Family-centred music therapy to promote social engagement in young children with severe autism spectrum disorder: a randomized controlled study SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE autism spectrum disorder; family-centred service; music therapy; randomized trials; social relationships ID JOINT ATTENTION; INTERVENTIONS; PARENTS; COMMUNICATION; BEHAVIORS; TRIAL AB Background Limited capacity for social engagement is a core feature of autism spectrum disorder (ASD), often evident early in the child's development. While these skills are difficult to train, there is some evidence that active involvement in music-making provides unique opportunities for social interaction between participants. Family-centred music therapy (FCMT) endeavours to support social engagement between child and parent within active music-making, yet the extent of benefits provided is unknown. Aim This study investigated the impacts of FCMT on social engagement abilities. Methods Twenty-three children (36-60 months) with severe ASD received either 16 weeks of FCMT in addition to their early intervention programmes (n = 12), or their early intervention programme only (n = 11). Change in social engagement was measured with standardized parent-report assessments, parent interviews and clinician observation. Results Intention-to-treat analysis for the Vineland Social Emotional Early Childhood Scale indicated a significant effect in favour of FCMT. Thematic qualitative analysis of the parent interviews showed that the parent-child relationship grew stronger. Conclusion FCMT improves social interactions in the home and community and the parent-child relationship, but not language skills or general social responsiveness. This study provides preliminary support for the use of FCMT to promote social engagement in children with severe ASD. C1 [Thompson, G. A.; McFerran, K. S.] Univ Melbourne, Melbourne Conservatorium Mus, Carlton, Vic 3010, Australia. [Gold, C.] Univ Bergen, Grieg Acad, Mus Therapy Res Ctr, Bergen, Norway. RP Thompson, GA (reprint author), Univ Melbourne, 151 Barry St, Carlton, Vic 3010, Australia. EM graceat@unimelb.edu.au FU University of Melbourne; Victorian Department of Education and Early Childhood Development, Australia FX This study was supported by grants from the University of Melbourne, and the Victorian Department of Education and Early Childhood Development, Australia. 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Hadders-Algra, Mijna TI Dysmorphic features and developmental outcome of 2-year-old children SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID MINOR NEUROLOGICAL DYSFUNCTION; MORPHOLOGICAL ABNORMALITIES; PHYSICAL ANOMALIES; ASSOCIATION; BEHAVIOR; INFANTS; AUTISM; COHORT AB AimThe aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. MethodIn our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39weeks, [range 30-43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. ResultsOf the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference -2.53, 95% confidence interval [CI] -4.23 to -0.83) and fluency score (difference -0.62, 95% CI -1.1 to -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. InterpretationAs dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations. What this paper adds We found that dysmorphic features are associated with minor alterations in neurological development.This finding suggests an early ontogenetic origin of subtle neurological deviations. C1 [Seggers, Jorien; Hadders-Algra, Mijna] Univ Groningen, Univ Med Ctr Groningen, Dept Paediat, Dev Neurol Sect, Groningen, Netherlands. [Haadsma, Maaike L.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Bos, Arend F.] Univ Groningen, Univ Med Ctr Groningen, Dept Paediat, Neonatol Sect, Groningen, Netherlands. [Heineman, Maas Jan; Middelburg, Karin J.] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynaecol, NL-1105 AZ Amsterdam, Netherlands. [Van den Heuvel, Edwin R.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. RP Hadders-Algra, M (reprint author), Univ Med Ctr Groningen, CA85,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM m.hadders-algra@umcg.nl FU University Medical Center Groningen, Groningen, the Netherlands [754510]; Research School of Behavioural and Cognitive Neurosciences, University of Groningen; Cornelia Foundation FX We thank the parents and children who participated in the study. In addition, we thank Jacorina van Hoften, Paul Keating, and Marjolein Jongbloed-Pereboom for their help in collecting the data, Jan Maarten Cobben for training JvH and PK in the clinical morphological examination, and Pamela Schendelaar, Michiel Schrier, Linze Dijkstra, and Loes de Weerd for their technical assistance. The study received financial support from the University Medical Center Groningen, Groningen, the Netherlands (grant number: 754510); the Research School of Behavioural and Cognitive Neurosciences, University of Groningen; and the Cornelia Foundation. CR Achenbach T, 2000, MANUAL ASEBA PRESCHO Bouwstra H, 2006, PEDIATR RES, V60, P334, DOI 10.1203/01.pdr.0000233043.16674.1d Dolk H, 2004, AM J MED GENET C, V125C, P4, DOI 10.1002/ajmg.c.30000 FIRESTONE P, 1983, J AUTISM DEV DISORD, V13, P411, DOI 10.1007/BF01531589 Hadders-Algra M, 2004, CLIN REHABIL, V18, P287, DOI 10.1191/0269215504cr730oa Hadders-Algra M, 2005, MENT RETARD DEV D R, V11, P180, DOI 10.1002/mrdd.20069 Hadders-Algra M, 2002, DEV MED CHILD NEUROL, V44, P561 HADDERSALGRA M, 1992, J LEARN DISABIL, V25, P649 Hall JG, 2003, LANCET, V362, P735, DOI 10.1016/S0140-6736(03)14237-7 Hempel MS., 1993, NEUROLOGICAL EXAMINA Jongbloed-Pereboom M, 2011, FERTIL STERIL, V95, P2283, DOI 10.1016/j.fertnstert.2011.03.034 LARGO RH, 1989, DEV MED CHILD NEUROL, V31, P440 Mandell DS, 2005, PSYCHIAT SERV, V56, P56, DOI 10.1176/appi.ps.56.1.56 Mehes K, 1985, PEDIATR RES, V27, P85 Merks JHM, 2003, AM J MED GENET A, V123A, P211, DOI 10.1002/ajmg.a.20249 Merks JHM, 2008, JAMA-J AM MED ASSOC, V299, P61, DOI 10.1001/jama.2007.66 Merks JHM, 2006, AM J MED GENET A, V140A, P2091, DOI 10.1002/ajmg.a.31355 Middelburg KJ, 2011, FERTIL STERIL, V96, P165, DOI 10.1016/j.fertnstert.2011.04.081 Miles JH, 2000, AM J MED GENET, V91, P245, DOI 10.1002/(SICI)1096-8628(20000410)91:4<245::AID-AJMG1>3.0.CO;2-2 Ruiter SAJ, 2008, NETHERLANDS J PSYCHO, V64, P15 Schendelaar P, 2011, HUM REPROD, V26, P703, DOI 10.1093/humrep/deq377 Seggers J, 2012, EARLY HUM DEV, V88, P823, DOI 10.1016/j.earlhumdev.2012.06.002 Sivkov ST, 2003, PSYCHIATRY, V66, P222, DOI 10.1521/psyc.66.3.222.25163 SOORANILUNSING RJ, 1993, EARLY HUM DEV, V33, P71, DOI 10.1016/0378-3782(93)90174-S Van der Meulen BF, 2004, BAYLEY SCALES INFANT NR 25 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD NOV PY 2014 VL 56 IS 11 BP 1078 EP 1084 DI 10.1111/dmcn.12546 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AR8CM UT WOS:000343803100016 PM 25040419 ER PT J AU Eom, S Fisher, B Dezort, C Berg, AT AF Eom, Soyong Fisher, Breanne Dezort, Catherine Berg, Anne T. TI Routine developmental, autism, behavioral, and psychological screening in epilepsy care settings SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID QUALITY STANDARDS SUBCOMMITTEE; CHILD NEUROLOGY SOCIETY; PRACTICE PARAMETER; MODIFIED CHECKLIST; AMERICAN ACADEMY; AGE; QUESTIONNAIRE; INTERVENTION; TODDLERS; SEIZURE AB AimScreening for cognitive impairment, developmental delay, and neuropsychiatric problems is not always performed in children with epilepsy. The aim of this study was to assess the value of this screening and its validity for determining previously unidentified (actionable') problems in children with epilepsy. MethodNew and existing patients with epilepsy were recruited from a hospital-based epilepsy center. The parent of the child completed screening evaluations for development (Ages and Stages Questionnaire [ASQ], 0-66mo), autism (Modified Checklist for Autism in Toddlers [mCHAT], 16-30mo), social communication (Social Communication Questionnaire [SCQ], 4y), and psychiatric concerns (Strengths and Difficulties Questionnaire [SDQ], 4-17y). ResultsWe screened 236 children overall (136 males [58%], 100 females [42%]; mean age [SD] 6y 7mo [4y 6mo]). Of these, 176 children (75%) had established epilepsy diagnoses and 60 (25%) were patients with new-onset epilepsy. Of those with new-onset disease, 22 (37%) were determined not to have epilepsy. Positive findings by test were 82% (ASQ), 54% (mCHAT), 15%, (SCQ), and 58% (SDQ). Findings were actionable in 46 children (20%): 18% of findings in children with established epilepsy and 23% of findings in patients with new-onset epilepsy. Of the 46 children for whom further referrals were made, the parents of 28 (61%) have pursued further evaluations. InterpretationIn this study, children with existing and new-onset diagnoses of epilepsy had actionable screening findings. These findings support the development of systematic screening of comorbidities for children with epilepsy. What this paper adds Actionable results were found in 20% of children with epilepsy who were screened.Routine screening should be offered to all children with established or new-onset epilepsy.Screening should be done in conjunction with a capacity for referral, in order to interpret and act on the results. This article is commented on by Fodstad and Dunn on pages 1038-1039 of this issue. C1 [Eom, Soyong; Fisher, Breanne; Dezort, Catherine; Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Chicago, IL 60611 USA. [Berg, Anne T.] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. RP Berg, AT (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, 225 E Chicago Ave, Chicago, IL 60611 USA. EM atberg@luriechildrens.org FU Shaw Research Grants in Nursing and Allied Health Professions FX This study was funded by the Shaw Research Grants in Nursing and Allied Health Professions (B Fisher and C Dezort). 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Med. Child Neurol. PD NOV PY 2014 VL 56 IS 11 BP 1100 EP 1105 DI 10.1111/dmcn.12497 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AR8CM UT WOS:000343803100019 PM 24861272 ER PT J AU Bertelsen, B Melchior, L Jensen, LR Groth, C Glenthoj, B Rizzo, R Debes, NM Skov, L Brondum-Nielsen, K Paschou, P Silahtaroglu, A Tumer, Z AF Bertelsen, Birgitte Melchior, Linea Jensen, Lars R. Groth, Camilla Glenthoj, Birte Rizzo, Renata Debes, Nanette Mol Skov, Liselotte Brondum-Nielsen, Karen Paschou, Peristera Silahtaroglu, Asli Tumer, Zeynep TI Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE ADHD; IMMP2L; intronic deletions; OCD; susceptibility gene; Tourette syndrome ID MEMBRANE PEPTIDASE; MITOCHONDRIAL DYSFUNCTION; TRANSLOCATION BREAKPOINT; INNER MEMBRANE; 7Q31; DISORDERS; AUTISM; COMORBIDITIES; ASSOCIATION; CHILDREN AB burette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics, and the, disorder is often accompanied by comorbidities such as attention-deficit hyperactivity-disorder and obsessive compulsive disorder. Tourette syndrome has a complex etiology, but the underlying environmental and genetic factors are largely unknown. IMMP2L (inner mitochondrial membrane peptidase, subunit 2) located on chromosome 7q31 is one of the genes suggested as a susceptibility factor in disease pathogenesis. Through screening of a Danish cohort comprising 188 unrelated Tourette syndrome patients for copy number variations, we identified seven patients with intragenic IMMP2L deletions (3.7%), and this frequency was significantly higher (P = 0.0447) compared with a Danish control cohort (0.9%). Four of the seven deletions identified did not include any known exons of IMMP2L, but were within intron 3. These deletions were found to affect a shorter IMMP2L mRNA species with two alternative 5'-exons (one including the ATG start codon). We showed that both transcripts (long and short) were expressed in several brain regions, with a particularly high expression in cerebellum and hippocampus. The current findings give further evidence for the role of IMMP2L as a susceptibility factor in burette syndrome and suggest that intronic changes in disease susceptibility genes should be investigated further for presence of alternatively spliced exons. C1 [Bertelsen, Birgitte; Melchior, Linea; Brondum-Nielsen, Karen; Tumer, Zeynep] Rigshosp, Copenhagen Univ Hosp, Kennedy Ctr, DK-2600 Glostrup, Denmark. [Jensen, Lars R.] Ernst Moritz Arndt Univ Greifswald, Inst Human Genet, Greifswald, Germany. [Groth, Camilla; Debes, Nanette Mol; Skov, Liselotte] Herlev Univ Hosp, Dept Pediat, Tourette Clin, DK-2730 Herlev, Denmark. [Glenthoj, Birte] Copenhagen Univ Hosp, Ctr Neuropsychiat Schizophrenia Res, Glostrup, Denmark. [Glenthoj, Birte] Copenhagen Univ Hosp, Ctr Clin Intervent & NeuropsychiatSchizophrenia, Psychiat Ctr Glostrup, Glostrup, Denmark. [Rizzo, Renata] Univ Catania, Dept Pediat, Sect Child Neuropsychiat, Catania, Italy. [Brondum-Nielsen, Karen; Silahtaroglu, Asli] Univ Copenhagen, Inst Cellular & Mol Med, Copenhagen, Denmark. [Paschou, Peristera] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece. RP Tumer, Z (reprint author), Rigshosp, Copenhagen Univ Hosp, Kennedy Ctr, DK-2600 Glostrup, Denmark. EM zeynep.tumer@regionh.dk FU Danish Institutional Review Board [H-KA-05118]; Lundbeck Foundation [R24-A2419]; University of Copenhagen FX We thank all the individuals and families for their participation and contribution to this work. We acknowledge the assistance of Judy Grejsen. This study was approved by the Danish Institutional Review Board (H-KA-05118). The study is supported by Lundbeck Foundation (R24-A2419). B B is supported with a fellowship from the University of Copenhagen. 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J. Hum. Genet. PD NOV PY 2014 VL 22 IS 11 BP 1283 EP 1289 DI 10.1038/ejhg.2014.24 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AR8UR UT WOS:000343850200009 PM 24549057 ER PT J AU Hiller, RM Young, RL Weber, N AF Hiller, Rachel M. Young, Robyn L. Weber, Nathan TI Sex Differences in Autism Spectrum Disorder based on DSM-5 Criteria: Evidence from Clinician and Teacher Reporting SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Autism spectrum disorder; Sex differences; Gender; Behaviour presentation; Teacher report ID PERVASIVE DEVELOPMENTAL DISORDERS; CHILDREN; GIRLS; BOYS AB In the absence of intellectual impairment autism spectrum disorder (ASD) is diagnosed both less and later in females. This study used clinician and teacher report to explore sex differences in the behavioural presentation of 69 girls and 69 boys all diagnosed with high-functioning ASD. Evidence from DSM-IV-TR and DSM-5 are presented. Sex differences in teacher concerns were also explored. While no sex differences were found in the broad social criteria presented in the DSM-IV-TR or DSM-5, numerous differences were evident in how boys and girls came to meet each criterion. For example, girls were more likely to show an ability to integrate non-verbal and verbal behaviours, maintain a reciprocal conversation, and be able to initiate, but not maintain friendships. Moreover, girls presented with both less and different restricted interests. Teachers also reported substantially fewer concerns for girls than boys, including for externalising behaviours and social skills. Results suggest girls with ASD may present with a surface-level 'look' different from the 'classic' presentation of ASD, and present as less impaired when in a school setting. Consequently, results provide insight in to why the disorder may be more difficult to detect in cognitively-able girls. 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Abnorm. Child Psychol. PD NOV PY 2014 VL 42 IS 8 BP 1381 EP 1393 DI 10.1007/s10802-014-9881-x PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA AR8IO UT WOS:000343819000011 PM 24882502 ER PT J AU Vivanti, G Trembath, D Dissanayake, C AF Vivanti, Giacomo Trembath, David Dissanayake, Cheryl TI Mechanisms of Imitation Impairment in Autism Spectrum Disorder SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Autism; Imitation; Eye-tracking; Global developmental delay ID JOINT ATTENTION; CHILDREN; IDENTIFICATION; COMMUNICATION; PERFORMANCE; TODDLERS; GAZE AB Individuals with Autism Spectrum Disorders (ASD) have difficulties with imitation, though the nature of these remains unclear. In this study, involving 28 preschoolers with ASD (M age = 48 months; 90 % male), 17 matched children with Global Developmental Delay (GDD group; M age = 44 months; 53 % male) and 17 typically developing children (TD group, M age = 52 months; 65 % male), we found that preschoolers with ASD 1) imitate less frequently than both typically developing children and children with GDD; 2) when they do imitate, their imitation is less accurate than that of TD children but similar to that of children with GDD; 3) unlike participants in both comparison groups, preschoolers with ASD use emulation more often than imitation when copying others' actions; 4) they spend less time looking at the model's face and more time looking at her actions; and 5) attentional, social and executive factors underlie different aspects of imitation difficulties in this population. Implications for developmental models of autism are discussed. C1 [Vivanti, Giacomo; Trembath, David; Dissanayake, Cheryl] La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Melbourne, Vic 3086, Australia. [Vivanti, Giacomo] La Trobe Univ, Victorian Autism Specif Early Learning & Care Ctr, Melbourne, Vic, Australia. [Trembath, David] Griffith Univ, Griffith Hlth Inst, Brisbane, Qld 4111, Australia. RP Vivanti, G (reprint author), La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Bundoora Campus, Melbourne, Vic 3086, Australia. EM g.vivanti@latrobe.edu.au CR APA, 2013, DSM 5 DIAGN STAT MAN BANDURA A, 1961, J ABNORM SOC PSYCH, V63, P311, DOI 10.1037/h0040351 Barbaro J, 2013, AUTISM, V17, P64, DOI 10.1177/1362361312442597 Call J, 2005, ANIM COGN, V8, P151, DOI 10.1007/s10071-004-0237-8 Carpenter M., 1998, MONOGR SOC RES CHILD, V63, P1, DOI DOI 10.2307/1166214 Colombi C., 2011, NEUROPSYCHOLOGY AUTI, P243 Dyckens E. 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Abnorm. Child Psychol. PD NOV PY 2014 VL 42 IS 8 BP 1395 EP 1405 DI 10.1007/s10802-014-9874-9 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA AR8IO UT WOS:000343819000012 PM 24736983 ER PT J AU Hubbard, KL Bandini, LG Folta, SC Wansink, B Must, A AF Hubbard, Kristie L. Bandini, Linda G. Folta, Sara C. Wansink, Brian Must, Aviva TI The Adaptation of a School-based Health Promotion Programme for Youth with Intellectual and Developmental Disabilities: A Community-Engaged Research Process SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE adolescence; developmental disability; health promotion; intellectual disability; nutrition ID QUALITATIVE RESEARCH; PHYSICAL-ACTIVITY; PUBLIC-HEALTH; CHILDREN; ADULTS; PREVALENCE; OBESITY; GUIDELINES; NUTRITION; AUTISM AB BackgroundEvidenced-based health promotion programmes for youth with intellectual and developmental disabilities (I/DD) are notably absent. Barriers include a lack of understanding of how to adapt existing evidence-based programmes to their needs, maximize inclusion and support mutual goals of health and autonomy. MethodsWe undertook a community-engaged process to adapt a school-based nutrition intervention in a residential school for youth with I/DD. Focus groups and interviews with school staff elicited recommendations for adaptation strategies; these were then reviewed by an expert panel. ResultsAdaptations were developed to address needs in three categories: food-related challenges among students, adjusting to change and transition and social environment factors. Choice and heterogeneity were overarching themes across the adaptation categories. ConclusionsFuture research should consider community-engaged approaches for adaptation so that youth with I/DD can participate and benefit from evidence-based health promotion programmes to their maximum potential. 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This manuscript reviews effective interventions based upon functional assessment and appropriate positive behavior supports. Specific interventions for addressing staking behavior by students with ASDs are analyzed and evaluated with suggestions for best practice for instructional procedures. Interventions covered are social skills groups, video modeling, self-management, video feedback, rule governed behavior, scripts, visual supports, counseling, psychopharmacology and reducing the amount of isolating interests and activities while increasing more opportunities for integration. Recommendations for future research are discussed. C1 [Post, Michal; Haymes, Linda; Storey, Keith] Touro Univ, Grad Sch Educ, Vallejo, CA 94592 USA. [Loughrey, Tamara] Loughrey & Associates, Orinda, CA 94563 USA. RP Post, M (reprint author), Touro Univ, Grad Sch Educ, 1310 Club Dr, Vallejo, CA 94592 USA. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2698 EP 2706 DI 10.1007/s10803-012-1712-8 PG 9 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000003 PM 23207743 ER PT J AU Lundstrom, S Forsman, M Larsson, H Kerekes, N Serlachius, E Langstrom, N Lichtenstein, P AF Lundstrom, Sebastian Forsman, Mats Larsson, Henrik Kerekes, Nora Serlachius, Eva Langstrom, Niklas Lichtenstein, Paul TI Childhood Neurodevelopmental Disorders and Violent Criminality: A Sibling Control Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Attention deficit hyperactivity disorder; Neurodevelopmental disorders; Criminality; Familial confounding ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDER; OBSESSIVE-COMPULSIVE DISORDER; NEUROPSYCHIATRIC DISORDERS; PSYCHIATRIC-DISORDERS; TELEPHONE INTERVIEW; TOURETTE-SYNDROME; SUBSTANCE-ABUSE; RISK-FACTORS AB The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all child and adolescent mental health services in Stockholm, we identified 3,391 children, born 1984-1994, with neurodevelopmental disorders, and compared their risk for subsequent violent criminality with matched controls. Individuals with ADHD or TDs were at elevated risk of committing violent crimes, no such association could be seen for ASDs or OCD. ADHD and TDs are risk factors for subsequent violent criminality, while ASDs and OCD are not associated with violent criminality. C1 [Lundstrom, Sebastian; Kerekes, Nora] Univ Gothenburg, Ctr Eth Law & Mental Hlth CELAM, S-43141 Molndal, Sweden. [Lundstrom, Sebastian; Kerekes, Nora; Langstrom, Niklas] Swedish Prison & Probat Serv, R&D Unit, Gothenburg, Sweden. [Lundstrom, Sebastian] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Forsman, Mats; Larsson, Henrik; Langstrom, Niklas; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2707 EP 2716 DI 10.1007/s10803-013-1873-0 PG 10 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000004 PM 23807203 ER PT J AU Woodbury-Smith, M Dein, K AF Woodbury-Smith, Marc Dein, Kalpana TI Autism Spectrum Disorder (ASD) and Unlawful Behaviour: Where Do We Go from Here? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Adulthood; Outcome; Criminal behaviour ID HIGH-FUNCTIONING AUTISM; ASPERGERS-SYNDROME; CRIMINAL RESPONSIBILITY; PSYCHOPATHY; ADULTS; OFFENDERS; EMPATHY AB There exists now a body of research that describes case studies of individuals with autism spectrum disorder (ASD) who have engaged, or are alleged to have engaged, in a range of illegal behaviours, and that attempts to estimate the prevalence of ASD at different stages of the criminal justice process. Taken together, this research does suggest that some individuals with ASD will come into contact with the criminal justice system, but many questions regarding this apparent association remain unanswered. The purpose of this review is to propose a direction for research to address some of these unanswered questions and potentially inform the development of treatments and service provision. C1 [Woodbury-Smith, Marc] McMaster Univ, Dept Psychiat & Behav Neurosci, McMaster Childrens Hosp, Hamilton, ON, Canada. [Dein, Kalpana] Cygnet Hosp, Stevenage, Herts, England. RP Woodbury-Smith, M (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, McMaster Childrens Hosp, Chedoke Campus,Evel Bldg,Room 457, Hamilton, ON, Canada. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2734 EP 2741 DI 10.1007/s10803-014-2216-5 PG 8 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000006 PM 25155337 ER PT J AU Cooper, M Thapar, A Jones, DK AF Cooper, Miriam Thapar, Anita Jones, Derek K. TI White Matter Microstructure Predicts Autistic Traits in Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Diffusion MRI; ADHD; ASD; White matter; Tract-based spatial statistics; RESTORE ID DEFICIT-HYPERACTIVITY DISORDER; DIFFUSION-TENSOR MRI; SPECTRUM DISORDER; FRACTIONAL ANISOTROPY; CORPUS-CALLOSUM; SPATIAL-STATISTICS; ASPERGER-SYNDROME; YOUNG-CHILDREN; COMMUNITY TWIN; ADHD BEHAVIORS AB Traits of autism spectrum disorder (ASD) in children with attention-deficit/hyperactivity disorder (ADHD) have previously been found to index clinical severity. This study examined the association of ASD traits with diffusion parameters in adolescent males with ADHD(n = 17), and also compared WM microstructure relative to controls (n = 17). Significant associations (p < 0.05, corrected) were found between fractional anisotropy/radial diffusivity and ASD trait severity (positive and negative correlations respectively), mostly in the right posterior limb of the internal capsule/corticospinal tract, right cerebellar peduncle and the midbrain. No case-control differences were found for the diffusion parameters investigated. This is the first report of a WM microstructural signature of autistic traits in ADHD. Thus, even in the absence of full disorder, ASD traits may index a distinctive underlying neurobiology in ADHD. C1 [Cooper, Miriam; Thapar, Anita] Cardiff Univ, Sch Med, Child & Adolescent Psychiat Sect, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. [Cooper, Miriam; Thapar, Anita] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales. [Cooper, Miriam; Jones, Derek K.] Cardiff Univ, Sch Psychol, Brain Res Imaging Ctr, Cardiff CF24 4HQ, S Glam, Wales. [Thapar, Anita; Jones, Derek K.] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF24 4HQ, S Glam, Wales. RP Cooper, M (reprint author), Cardiff Univ, Sch Med, Child & Adolescent Psychiat Sect, Inst Psychol Med & Clin Neurosci, Second Floor,Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2742 EP 2754 DI 10.1007/s10803-014-2131-9 PG 13 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000007 PM 24827086 ER PT J AU Lucas, R Norbury, CF AF Lucas, Rebecca Norbury, Courtenay Frazier TI Levels of Text Comprehension in Children with Autism Spectrum Disorders (ASD): The Influence of Language Phenotype SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Language impairment; Sentence processing; Text comprehension ID READING-COMPREHENSION; PSYCHOLINGUISTIC MARKERS; DEVELOPMENTAL DISORDERS; COMMUNICATION DEFICITS; EXECUTIVE FUNCTION; EYE-MOVEMENTS; SIMPLE VIEW; FOLLOW-UP; DIFFICULTIES; IMPAIRMENT AB Many children with autism spectrum disorders (ASD) have reading comprehension difficulties, but the level of processing at which comprehension is most vulnerable and the influence of language phenotype on comprehension skill is currently unclear. We explored comprehension at sentence and passage levels across language phenotypes. Children with ASD and age-appropriate language skills (n = 25) demonstrated similar syntactic and semantic facilitation to typically developing peers. In contrast, few children with ASD and language impairments (n = 25) could read beyond the single word level. Those who could read sentences benefited from semantic coherence, but were less sensitive to syntactic coherence. At the passage level, the strongest predictor of comprehension was vocabulary knowledge. This emphasizes that the intimate relationship between language competence and both decoding skill and comprehension is evident at the sentence, as well as the passage level, for children with ASD. C1 [Lucas, Rebecca; Norbury, Courtenay Frazier] Royal Holloway Univ London, Dept Psychol, Egham TW20 0EX, Surrey, England. RP Lucas, R (reprint author), Royal Holloway Univ London, Dept Psychol, Wolfson Bldg, Egham TW20 0EX, Surrey, England. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2756 EP 2768 DI 10.1007/s10803-014-2133-7 PG 13 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000009 PM 24849254 ER PT J AU Mohammadzaheri, F Koegel, LK Rezaee, M Rafiee, SM AF Mohammadzaheri, Fereshteh Koegel, Lynn Kern Rezaee, Mohammad Rafiee, Seyed Majid TI A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Structured Applied Behavior Analysis (ABA) Intervention for Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Pragmatic skills; Naturalistic approach; Analog approach; Autism; Pivotal response treatment; ABA ID REINFORCER RELATIONSHIPS; SOCIAL COMMUNICATION; LANGUAGE; ACQUISITION; DISORDERS; PROGRAM; PLAY AB Accumulating studies are documenting specific motivational variables that, when combined into a naturalistic teaching paradigm, can positively influence the effectiveness of interventions for children with autism spectrum disorder (ASD). The purpose of this study was to compare two applied behavior analysis (ABA) intervention procedures, a naturalistic approach, pivotal response treatment (PRT) with a structured ABA approach in a school setting. A randomized clinical trial design using two groups of children, matched according to age, sex and mean length of utterance was used to compare the interventions. The data showed that the PRT approach was significantly more effective in improving targeted and un-targeted areas after 3 months of intervention. The results are discussed in terms of variables that produce more rapid improvements in communication for children with ASD. C1 [Mohammadzaheri, Fereshteh; Rezaee, Mohammad] Hamadan Univ Med Sci & Hlth Serv, Fac Rehabil Sci, Hamadan, Iran. [Koegel, Lynn Kern] Univ Calif Santa Barbara, CCS Psychol Dept, Koegel Autism Ctr, Santa Barbara, CA 93106 USA. [Rafiee, Seyed Majid] Inst Cognit Sci Studies, Tehran, Iran. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2769 EP 2777 DI 10.1007/s10803-014-2137-3 PG 9 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000010 PM 24840596 ER PT J AU Ranson, NJ Byrne, MK AF Ranson, Natalia J. Byrne, Mitchell K. TI Promoting Peer Acceptance of Females with Higher-functioning Autism in a Mainstream Education Setting: A Replication and Extension of the Effects of an Autism Anti-Stigma Program SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Female higher-functioning autism; Peer acceptance; Anti-stigma program; Knowledge; Attitudes; Behavioural intentions ID SPECTRUM DISORDERS; CHILDRENS ATTITUDES; ASPERGERS SYNDROME; GENDER; GIRLS; STUDENTS; BEHAVIOR; COMMUNICATION; QUESTIONNAIRE; DISABILITIES AB This study evaluated the effects of an eight-session female higher-functioning autism anti-stigma program on the knowledge, attitudes and behavioural intentions of adolescent girls. Participants were seventh-, eighth- and ninth-grade students (N = 273) in a mainstream school. Two-eighth-grade classes were randomly allocated to the intervention condition. The remaining students were either allocated to the no-intervention peer or no-intervention non-peer condition. The anti-stigma program positively influenced knowledge, attitudes and to a lesser extent behavioural intentions towards peers with higher-functioning autism within the intervention condition. Some degree of attitudinal improvement occurred across all conditions following the program suggesting some spill over effects. Overall, findings provide preliminary evidence supporting the efficacy of an anti-stigma program tailored to support females with higher-functioning autism. C1 [Ranson, Natalia J.; Byrne, Mitchell K.] Univ Wollongong, Dept Psychol, Wollongong, NSW 2522, Australia. RP Byrne, MK (reprint author), Univ Wollongong, Dept Psychol, Northfields Ave, Wollongong, NSW 2522, Australia. 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Thompson, A. CA Pathways ASD Study Team TI Language Impairment and Early Social Competence in Preschoolers with Autism Spectrum Disorders: A Comparison of DSM-5 Profiles SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social competence; Language impairment; DSM-5; Autism spectrum disorders; Longitudinal epidemiology ID DIAGNOSTIC OBSERVATION SCHEDULE; ASPERGER-SYNDROME; JOINT ATTENTION; CHILDREN; INDIVIDUALS; COMMUNICATION; MIND; DIFFICULTIES; ADOLESCENCE; ABILITIES AB Children with autism spectrum disorder (ASD) and structural language impairment (LI) may be at risk of more adverse social-developmental outcomes. We examined trajectories of early social competence (using the Vineland-II) in 330 children aged 2-4 years recently diagnosed with ASD, and compared 3 subgroups classified by: language impairment (ASD/LI); intellectual disability (ASD/ID) and ASD without LI or ID (ASD/alone). Children with ASD/LI were significantly more socially impaired at baseline than the ASD/alone subgroup, and less impaired than those with ASD/ID. Growth in social competence was significantly slower for the ASD/ID group. Many preschool-aged children with ASD/LI at time of diagnosis resembled "late talkers'' who appeared to catch up linguistically. Children with ASD/ID were more severely impaired and continued to lag further behind. C1 [Bennett, T. A.; Georgiades, K.; Janus, M.; Georgiades, S.; Duku, E.; Thompson, A.] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON, Canada. [Bennett, T. A.] McMaster Childrens Hosp, Dept Psychiat & Behav Neurosci, Offord Ctr Child Studies, Hamilton, ON L8S 3Z5, Canada. [Szatmari, P.; Roberts, W.] Univ Toronto, Toronto, ON, Canada. [Hanna, S.] McMaster Univ, Hamilton, ON, Canada. [Bryson, S.; Smith, I. M.] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. [Fombonne, E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mirenda, P.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Volden, J.; Zwaigenbaum, L.] Univ Alberta, Edmonton, AB, Canada. [Waddell, C.] Simon Fraser Univ, Vancouver, BC, Canada. [Vaillancourt, T.] Univ Ottawa, Ottawa, ON, Canada. [Elsabbagh, M.] McGill Univ, Montreal, PQ, Canada. RP Bennett, TA (reprint author), McMaster Childrens Hosp, Dept Psychiat & Behav Neurosci, Offord Ctr Child Studies, Chedoke Site,1200 Main St West, Hamilton, ON L8S 3Z5, Canada. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2797 EP 2808 DI 10.1007/s10803-014-2138-2 PG 12 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000012 PM 24865586 ER PT J AU Speirs, SJ Rinehart, NJ Robinson, SR Tonge, BJ Yelland, GW AF Speirs, Samantha J. Rinehart, Nicole J. Robinson, Stephen R. Tonge, Bruce J. Yelland, Gregory W. TI Efficacy of Cognitive Processes in Young People with High-Functioning Autism Spectrum Disorder Using a Novel Visual Information-Processing Task SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Cognitive processing; Processing efficacy; Subtle Cognitive Impairment Test; Speed of processing ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; LEXICAL ACCESS; WISC-IV; CHILDREN; PERFORMANCE; SPEED; ADHD; SYMPTOMS; ANXIETY; INTELLIGENCE AB Autism spectrum disorders (ASD) are characterised by a unique pattern of preserved abilities and deficits within and across cognitive domains. The Complex Information Processing Theory proposes this pattern reflects an altered capacity to respond to cognitive demands. This study compared how complexity induced by time constraints on processing affect cognitive function in individuals with ASD and typically-developing individuals. On a visual information-processing task, the Subtle Cognitive Impairment Test, both groups exhibited sensitivity to time-constraints. Further, 65 % of individuals with ASD demonstrated deficits in processing efficiency, possibly attributable to the effects of age and clinical comorbidities, like attention deficit hyperactivity disorder. These findings suggest that for some ASD individuals there are significant impairments in processing efficiency, which may have implications for education and interventions. C1 [Speirs, Samantha J.; Tonge, Bruce J.] Monash Univ, Sch Psychol & Psychiat, Clayton, Vic, Australia. [Rinehart, Nicole J.] Deakin Univ, Deakin Child Study Ctr, Sch Psychol, Melbourne, Vic, Australia. [Robinson, Stephen R.; Yelland, Gregory W.] RMIT Univ, Sch Hlth Sci, Bundoora, Vic 3083, Australia. [Yelland, Gregory W.] Monash Univ, Cent Clin Sch, Alfred Ctr, Melbourne, Vic 3004, Australia. RP Yelland, GW (reprint author), RMIT Univ, Sch Hlth Sci, Plenty Rd, Bundoora, Vic 3083, Australia. 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TI A Longitudinal Examination of the Relation Between Parental Expressed Emotion and Externalizing Behaviors in Children and Adolescents with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Expressed emotion; Criticism; Hostility; Emotional overinvolvement; Externalizing behaviors; Parenting ID FOLLOW-UP; QUESTIONNAIRE; STRESS; FAMILY; METAANALYSIS; COMMUNITY; RELAPSE; PDD AB The current study explored the longitudinal relation between parental expressed emotion, a well-established predictor of symptom relapse in various other disorders (e.g., schizophrenia) with externalizing behaviors in 84 children, ages 8-18 (at Time 2), with autism spectrum disorder (ASD). It was found that parental expressed emotion, specifically criticism/hostility at Time 1, significantly related to a change in externalizing behaviors from Time 1 to Time 2, even after controlling for Time 1 family income, ASD symptom severity, parental distress, and parenting practices. That is, higher levels of parental criticism/hostility at Time 1 predicted higher levels of child externalizing behaviors at Time 2. However, the reverse was not found. This finding of a unidirectional relation has important clinical implications. C1 [Bader, Stephanie H.; Barry, Tammy D.] Univ So Mississippi, Hattiesburg, MS 39406 USA. RP Bader, SH (reprint author), Westchester Inst Human Dev, Valhalla, NY 10595 USA. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2820 EP 2831 DI 10.1007/s10803-014-2142-6 PG 12 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000014 PM 24854330 ER PT J AU Shek, DTL Yu, L AF Shek, Daniel Tan Lei Yu, Lu TI Construct Validity of the Chinese Version of the Psycho-Educational Profile-3rd Edition (CPEP-3) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Assessment; Autism spectrum disorder; Chinese; Construct validity; Psycho-Educational Profile-3rd edition; Psychometric properties ID AUTISM SPECTRUM DISORDERS; REPORT FAMILY INVENTORY; PSYCHOMETRIC PROPERTIES; HONG-KONG; CHILDREN AB Objective behavioral assessment of autism spectrum disorder (ASD) in early childhood is essential for guiding appropriate treatment and intervention. In contrast to Western societies, validated measures of ASD are very limited in different Chinese contexts. The present study attempted to examine the construct validity of the Chinese version of Psycho-Educational Profile-3rd edition (CPEP3). The CPEP-3 was administered to a sample of 455 children with ASD and a comparison group of 281 children without ASD. As predicted, older children scored significantly higher than younger children on different subtests of CPEP-3, and there was no gender difference within the autistic group. The construct validity of the CPEP-3 was further supported by the high internal consistency of each subtest as well as the moderate to large correlation coefficients among subtests. In line with the theoretical model, confirmatory factor analysis showed the three-factor model of the Performance test fitted well. In conjunction with the data reported previously, the present findings provided sound evidence for the construct validity of CPEP-3. C1 [Shek, Daniel Tan Lei; Yu, Lu] Hong Kong Polytech Univ, Dept Appl Social Sci, Kowloon, Hong Kong, Peoples R China. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2832 EP 2843 DI 10.1007/s10803-014-2143-5 PG 12 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000015 PM 24838124 ER PT J AU Dickinson, A Jones, M Milne, E AF Dickinson, Abigail Jones, Myles Milne, Elizabeth TI Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic traits; Orientation discrimination; Visual perception ID PRIMARY VISUAL-CORTEX; STRIATE CORTEX; BLOCK DESIGN; PERFORMANCE; SEARCH; PERCEPTION; CHILDREN; EXPERIENCES; FEATURES; ABILITY AB Enhanced low-level perception, although present in individuals with autism, is not seen in individuals with high, but non-clinical, levels of autistic traits (Brock et al. in Percept Lond 40(6): 739. doi: 10.1068/p6953, 2011). This is surprising, as many of the higher-level visual differences found in autism have been shown to correlate with autistic traits in non-clinical samples. Here we measure vertical-oblique and, more difficult, oblique-oblique orientation discrimination thresholds in a non-clinical sample. As predicted, oblique-oblique thresholds provided a more sensitive test of orientation discrimination, and were negatively related to autistic traits (N = 94, r = -. 356, p <. 0001). We conclude that individual differences in orientation discrimination and autistic traits are related, and suggest that both of these factors could be mediated by increased levels of the inhibitory neurotransmitter GABA. C1 [Dickinson, Abigail; Jones, Myles; Milne, Elizabeth] Univ Sheffield, Dept Psychol, Sheffield S10 2TP, S Yorkshire, England. RP Milne, E (reprint author), Univ Sheffield, Dept Psychol, Western Bank, Sheffield S10 2TP, S Yorkshire, England. EM e.milne@sheffield.ac.uk CR Almeida R. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2844 EP 2850 DI 10.1007/s10803-014-2147-1 PG 7 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000016 PM 24870402 ER PT J AU Kerns, CM Kendall, PC Berry, L Souders, MC Franklin, ME Schultz, RT Miller, J Herrington, J AF Kerns, Connor Morrow Kendall, Philip C. Berry, Leandra Souders, Margaret C. Franklin, Martin E. Schultz, Robert T. Miller, Judith Herrington, John TI Traditional and Atypical Presentations of Anxiety in Youth with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Anxiety; Children; Adolescents; Comorbidity; Atypical; Traditional ID PERVASIVE DEVELOPMENTAL DISORDERS; SELF-STATEMENT QUESTIONNAIRE; PSYCHIATRIC-DISORDERS; NEGATIVE AFFECTIVITY; DIAGNOSTIC INTERVIEW; SENSORY-MODULATION; CHILDREN; ADOLESCENTS; SCALE; SYMPTOMS AB We assessed anxiety consistent (i.e., "traditional'') and inconsistent (i.e., "atypical'') with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were explored. Fifty-nine participants (7-17 years, M-age = 10.48 years; IQ > 60) with ASD and parents completed semi-structured interviews, self-and parent-reports. Seventeen percent of youth presented with traditional anxiety, 15 % with atypical anxiety, and 31 % with both. Language ability, anxious cognitions and hypersensitivity predicted traditional anxiety, whereas traditional anxiety and ASD symptoms predicted atypical anxiety. Findings suggest youth with ASD express anxiety in ways similar and dissimilar to DSM definitions. Similarities support the presence of comorbid anxiety disorders in ASD. Whether dissimilarities are unique to ASD requires further examination. C1 [Kerns, Connor Morrow; Berry, Leandra; Souders, Margaret C.; Schultz, Robert T.; Miller, Judith; Herrington, John] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Kerns, Connor Morrow; Kendall, Philip C.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Franklin, Martin E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2851 EP 2861 DI 10.1007/s10803-014-2141-7 PG 11 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000017 PM 24902932 ER PT J AU Ventola, P Friedman, HE Anderson, LC Wolf, JM Oosting, D Foss-Feig, J McDonald, N Volkmar, F Pelphrey, KA AF Ventola, Pamela Friedman, Hannah E. Anderson, Laura C. Wolf, Julie M. Oosting, Devon Foss-Feig, Jennifer McDonald, Nicole Volkmar, Fred Pelphrey, Kevin A. TI Improvements in Social and Adaptive Functioning Following Short-Duration PRT Program: A Clinical Replication SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Pivotal Response Treatment; Intervention; Outcome; Adaptive skills; Social communication skills; Early intervention ID PIVOTAL RESPONSE TREATMENT; MOTIVATING AUTISTIC-CHILDREN; NATURAL-LANGUAGE PARADIGM; YOUNG-CHILDREN; SPECTRUM DISORDERS; BEHAVIOR-THERAPY; PARENTS; SKILLS; INTERVENTION; ACQUISITION AB Pivotal Response Treatment (PRT) is an empirically validated behavioral treatment for individuals with autism spectrum disorders (ASD). The purpose of the current study was to assess the efficacy of PRT for ten cognitively-able preschool-aged children with ASD in the context of a short-duration (4-month) treatment model. Most research on PRT used individual behavioral goals as outcome measures, but the current study utilized standardized assessments of broader-based social communication and adaptive skills. The children made substantial gains; however, magnitude and consistency of response across measures were variable. The results provide additional support for the efficacy of PRT as well as evidence for improvements in higher-order social communication and adaptive skill development within the context of a short-duration PRT model. C1 [Ventola, Pamela; Friedman, Hannah E.; Anderson, Laura C.; Wolf, Julie M.; Oosting, Devon; Foss-Feig, Jennifer; McDonald, Nicole; Volkmar, Fred; Pelphrey, Kevin A.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. RP Ventola, P (reprint author), Yale Univ, Sch Med, Yale Child Study Ctr, 230 South Frontage Rd,207900, New Haven, CT 06520 USA. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2862 EP 2870 DI 10.1007/s10803-014-2145-3 PG 9 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000018 PM 24915928 ER PT J AU Maccari, L Pasini, A Caroli, E Rosa, C Marotta, A Martella, D Fuentes, LJ Casagrande, M AF Maccari, Lisa Pasini, Augusto Caroli, Emanuela Rosa, Caterina Marotta, Andrea Martella, Diana Fuentes, Luis J. Casagrande, Maria TI Visual Search and Emotion: How Children with Autism Spectrum Disorders Scan Emotional Scenes SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Change detection; Change blindness; Flicker task; Visual search; Emotional processing ID HIGH-FUNCTIONING AUTISM; CHANGE BLINDNESS; FACIAL EXPRESSIONS; IMPAIRED RECOGNITION; SOCIAL INFORMATION; ASPERGERS-SYNDROME; PERIPHERAL CUES; YOUNG-CHILDREN; ATTENTION; AMYGDALA AB This study assessed visual search abilities, tested through the flicker task, in children diagnosed with autism spectrum disorders (ASDs). Twenty-two children diagnosed with ASD and 22 matched typically developing (TD) children were told to detect changes in objects of central interest or objects of marginal interest (MI) embedded in either emotion-laden (positive or negative) or neutral real-world pictures. The results showed that emotion-laden pictures equally interfered with performance of both ASD and TD children, slowing down reaction times compared with neutral pictures. Children with ASD were faster than TD children, particularly in detecting changes in MI objects, the most difficult condition. However, their performance was less accurate than performance of TD children just when the pictures were negative. These findings suggest that children with ASD have better visual search abilities than TD children only when the search is particularly difficult and requires strong serial search strategies. The emotional-social impairment that is usually considered as a typical feature of ASD seems to be limited to processing of negative emotional information. C1 [Maccari, Lisa; Caroli, Emanuela; Marotta, Andrea; Casagrande, Maria] Univ Roma La Sapienza, Dipartimento Psicol, I-00185 Rome, Italy. [Pasini, Augusto; Rosa, Caterina] Univ Roma Tor Vergata, Child Neurol & Psychiat Unit, Dept Neurosci, Rome, Italy. [Martella, Diana] Univ Autonoma Chile, Fac Ciencias Jurid & Sociales, Carrera Psicol, Temuco, Chile. [Fuentes, Luis J.] Univ Murcia, Fac Psicol, Murcia, Spain. RP Casagrande, M (reprint author), Univ Roma La Sapienza, Dipartimento Psicol, Via Marsi 78, I-00185 Rome, Italy. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2882 EP 2894 DI 10.1007/s10803-014-2149-z PG 13 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000020 PM 24920285 ER PT J AU Takahashi, J Yasunaga, D Gyoba, J AF Takahashi, Junichi Yasunaga, Daichi Gyoba, Jiro TI Differences in the Efficiency of Pattern Encoding in Relation to Autistic-Like Traits: An Event-Related Potential Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum quotient; Complexity; Encoding efficiency; Event-related potential ID SHORT-TERM-MEMORY; SPATIAL WORKING-MEMORY; SPECTRUM QUOTIENT AQ; GENERAL-POPULATION; VISUAL-SEARCH; INDIVIDUAL-DIFFERENCES; GOODNESS; ADULTS; DISORDERS; DISCRIMINATION AB We examined the effects of complexity on the efficiency of pattern encoding in the general population differing on autism-spectrum quotient (AQ) scores. We compared brain activity (electroencephalography) during a same-different task for High and Low AQ groups. The task was composed of identical comparison and categorical comparison (CC) conditions that presented simple or complex patterns. In the CC condition, the Low AQ showed large P3b amplitudes with simple patterns than with complex patterns, whereas the High AQ showed the same amplitude levels for these patterns. These indicate that, similar to simple patterns, complex patterns are efficiently encoded in the High AQ. Moreover, the High AQ had no impairment in the global pattern encoding compared with the Low AQ. C1 [Takahashi, Junichi] Fukushima Univ, Fac Human Dev & Culture, Fukushima 9601296, Japan. [Yasunaga, Daichi] Kanazawa Univ, Inst Human & Social Sci, Fac Letters, Kanazawa, Ishikawa 9201192, Japan. [Gyoba, Jiro] Tohoku Univ, Grad Sch Arts & Letters, Dept Psychol, Aoba Ku, Sendai, Miyagi 271, Japan. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2895 EP 2907 DI 10.1007/s10803-014-2150-6 PG 13 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000021 PM 24898909 ER PT J AU Williams, DL Mazefsky, CA Walker, JD Minshew, NJ Goldstein, G AF Williams, Diane L. Mazefsky, Carla A. Walker, Jon D. Minshew, Nancy J. Goldstein, Gerald TI Associations Between Conceptual Reasoning, Problem Solving, and Adaptive Ability in High-functioning Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Conceptual reasoning; Problem solving; Adaptive behavior; Cognitive ID DIAGNOSTIC OBSERVATION SCHEDULE; SOCIAL-SKILLS INTERVENTIONS; DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; IMPAIRED MEMORY; YOUNG-ADULTS; CHILDREN; INDIVIDUALS; BEHAVIOR; DYSFUNCTION AB The Abstract thinking is generally highly correlated with problem-solving ability which is predictive of better adaptive functioning. Measures of conceptual reasoning, an ecologically-valid laboratory measure of problem-solving, and a report measure of adaptive functioning in the natural environment, were administered to children and adults with and without autism. The individuals with autism had weaker conceptual reasoning ability than individuals with typical development of similar age and cognitive ability. For the autism group, their flexible thinking scores were significantly correlated with laboratory measures of strategy formation and rule shifting and with reported overall adaptive behavior but not socialization scores. Therefore, in autism, flexibility of thought is potentially more important for adaptive functioning in the natural environment than conceptual reasoning or problem-solving. C1 [Williams, Diane L.] Duquesne Univ, Dept Speech Language Pathol, Pittsburgh, PA 15219 USA. [Mazefsky, Carla A.; Minshew, Nancy J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. 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PD NOV PY 2014 VL 44 IS 11 SI SI BP 2908 EP 2920 DI 10.1007/s10803-014-2190-y PG 13 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000022 PM 25099486 ER PT J AU Murray, AL McKenzie, K Kuenssberg, R O'Donnell, M AF Murray, Aja Louise McKenzie, Karen Kuenssberg, Renate O'Donnell, Michael TI Are We Under-Estimating the Association Between Autism Symptoms?: The Importance of Considering Simultaneous Selection When Using Samples of Individuals Who Meet Diagnostic Criteria for an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Range restriction; Fractionable triad; Simultaneous selection; Sampling ID QUOTIENT-SHORT-FORM; RANGE RESTRICTION; DSM-5 CRITERIA; VALIDITY; POPULATION; TRAITS; AQ; PREVALENCE; VALIDATION; DOMAINS AB The magnitude of symptom inter-correlations in diagnosed individuals has contributed to the evidence that autism spectrum disorders (ASD) is a fractionable disorder. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2921 EP 2930 DI 10.1007/s10803-014-2154-2 PG 10 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000023 PM 24898911 ER PT J AU Logan, SL Carpenter, L Leslie, RS Hunt, KS Garrett-Mayer, E Charles, J Nicholas, JS AF Logan, Sarah L. Carpenter, Laura Leslie, R. Scott Hunt, Kelly S. Garrett-Mayer, Elizabeth Charles, Jane Nicholas, Joyce S. TI Rates and Predictors of Adherence to Psychotropic Medications in Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Psychotropics; Treatment adherence; Public health surveillance; Autism ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POPULATION-BASED SURVEILLANCE; ANTIRETROVIRAL REGIMEN COMPLEXITY; MEDICAID-ENROLLED CHILDREN; PHARMACOLOGICAL-TREATMENT; PHARMACEUTICAL PROMOTION; ETHNIC-DIFFERENCES; BIPOLAR DISORDER; CONTROLLED-TRIAL; DRUG-USE AB Medication adherence in children is poor, particularly among those with chronic or mental health disorders. However, adherence has not been fully assessed in autism spectrum disorders (ASDs). The validated proportion of days covered method was used to quantify adherence to psychotropic medication in Medicaid-eligible children who met diagnostic criteria for ASD between 2000 and 2008 (N = 628). Among children prescribed attention deficit hyperactivity disorder (ADHD) medications, antidepressants, or antipsychotics, 44, 40 and 52 % were adherent respectively. Aggressive behaviors and abnormalities in eating, drinking, and/or sleeping, co-occurring ADHD, and the Medication Regimen Complexity Index were the most significant predictors of adherence rather than demographics or core deficits of ASD. Identifying barriers to adherence in ASD may ultimately lead to improved treatment outcomes. C1 [Logan, Sarah L.; Hunt, Kelly S.; Garrett-Mayer, Elizabeth; Nicholas, Joyce S.] Med Univ S Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC 29425 USA. [Logan, Sarah L.] Med Univ S Carolina, Charleston, SC 29407 USA. [Carpenter, Laura; Charles, Jane] Med Univ S Carolina, Dept Pediat, Coll Med, Charleston, SC 29425 USA. [Leslie, R. Scott] Univ Calif San Diego, San Diego, CA 92093 USA. RP Logan, SL (reprint author), Med Univ S Carolina, 176 Croghan Spur Rd,Ste 104, Charleston, SC 29407 USA. 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TI Brief Report: Parent-Child Sexuality Communication and Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Sexuality; Sexuality education; Parent-child sexuality communication; Puberty; Parents; Adolescence; Adulthood ID ADULTS; ADOLESCENTS; BEHAVIOR AB While considerable research has focused on promoting independence and optimizing quality of life for adolescents and young adult with autism spectrum disorder (ASD), sexual development and sexuality education have been largely neglected. Experts recommend that parents be the primary source of sex education for adolescents with ASD, and that sex education be tailored to a child's developmental level. Prior studies show that parents of youth with ASD are uncertain about how to best communicate about sex and which topics to discuss with their children. In the current study we administered an online survey to 190 parents of adolescents with ASD in order to better understand sexuality communication patterns between parents and adolescents with both low and high functioning ASD. C1 [Holmes, Laura G.; Himle, Michael B.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. RP Himle, MB (reprint author), Univ Utah, Dept Psychol, 380 South 1530 East BEHS 502, Salt Lake City, UT 84112 USA. EM Michael.himle@utah.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Ballan MS, 2012, J AUTISM DEV DISORD, V42, P676, DOI 10.1007/s10803-011-1293-y Beckett M. K., 2009, PEDIATRICS, V125, P34 Byers ES, 2013, AUTISM, V17, P418, DOI 10.1177/1362361311431950 Caterino L. C., 2008, ED TREATMENT CHILDRE, V31, P381 Centers for Disease Control and Prevention, 2014, SURVEILLANCE SUMMARI, V63, P1 Constantino J. 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A., 2010, AM J SEXUALITY ED, V5, P328, DOI DOI 10.1080/15546128.2010.527237 Hardaway E., 2009, TEACHING EXCEPTIONAL, V42, P50 Hellemans H, 2010, SEX DISABIL, V28, P93, DOI 10.1007/s11195-009-9145-9 Hellemans H, 2007, J AUTISM DEV DISORD, V37, P260, DOI 10.1007/s10803-006-0159-1 Koller R, 2000, SEX DISABIL, V18, P125, DOI 10.1023/A:1005567030442 Mehzabin P, 2011, RES AUTISM SPECT DIS, V5, P614, DOI 10.1016/j.rasd.2010.07.006 Nichols S., 2010, SOCIAL WORK MENTAL H, V8, P72 RUBLE LA, 1993, ARCH SEX BEHAV, V22, P229, DOI 10.1007/BF01541768 Sexuality Information and Education Council of the United States, 2012, POS STAT Shattuck PT, 2007, J AUTISM DEV DISORD, V37, P1735, DOI 10.1007/s10803-006-0307-7 Singh J, 2009, J AUTISM DEV DISORD, V39, P788, DOI 10.1007/s10803-008-0685-0 Travers J, 2010, EDUC TRAIN AUTISM DE, V45, P284 VanBourgondien ME, 1997, J AUTISM DEV DISORD, V27, P113, DOI 10.1023/A:1025883622452 NR 23 TC 1 Z9 1 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 NOV PY 2014 VL 44 IS 11 SI SI BP 2964 EP 2970 DI 10.1007/s10803-014-2146-2 PG 7 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000026 PM 24854331 ER PT J AU Fung, LK Libove, RA Phillips, J Haddad, F Hardan, AY AF Fung, Lawrence K. Libove, Robin A. Phillips, Jennifer Haddad, Francois Hardan, Antonio Y. TI Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Pregnenolone; Neurosteroids; Irritability; Open-label trial ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; CHILDREN; TRIAL; SCHIZOPHRENIA; ADOLESCENTS; OLANZAPINE; RECEPTORS; PROTEIN AB The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 +/- 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 +/- 7.4 at baseline to 11.2 +/- 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD. C1 [Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Hardan, Antonio Y.] Stanford Univ, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, Stanford, CA 94305 USA. [Haddad, Francois] Stanford Univ, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA. RP Fung, LK (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, 401 Quarry Rd, Stanford, CA 94305 USA. 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Autism Dev. Disord. PD NOV PY 2014 VL 44 IS 11 SI SI BP 2971 EP 2977 DI 10.1007/s10803-014-2144-4 PG 7 WC Psychology, Developmental SC Psychology GA AR6XK UT WOS:000343724000027 PM 24849255 ER PT J AU Dean, M Kasari, C Shih, W Frankel, F Whitney, R Landa, R Lord, C Orlich, F King, B Harwood, R AF Dean, Michelle Kasari, Connie Shih, Wendy Frankel, Fred Whitney, Rondalyn Landa, Rebecca Lord, Catherine Orlich, Felice King, Bryan Harwood, Robin TI The peer relationships of girls with ASD at school: comparison to boys and girls with and without ASD SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Gender; autism spectrum disorders; inclusion; schools; peer relationships ID SEX-DIFFERENCES; AUTISM; CHILDREN; INVOLVEMENT; CLASSROOMS; DISORDERS AB BackgroundThis study examines the social relationships of elementary school children with high-functioning autism, focusing on how gender relates to social preferences and acceptance, social connections, reciprocal friendships, and rejection. MethodPeer nomination data were analyzed for girls with and without ASD (n=50) and boys with and without ASD (n=50). Girls and boys with ASD were matched by age, gender, and IQ. Each child with ASD was matched by age and gender to a typically developing classmate. ResultsConsistent with typically developing populations, children with ASD preferred, were accepted by, and primarily socialized with same-gender friends. With fewer nominations and social relationships, girls and boys with ASD appear more socially similar to each other than to the same-gender control group. Additionally, girls and boys with ASD showed higher rates of social exclusion than their typically developing peers. However, boys with ASD were more overtly socially excluded compared to girls with ASD, who seemed to be overlooked, rather than rejected. ConclusionsOur data suggest a number of interesting findings in the social relationships of children with ASD in schools. Like typically developing populations, children with ASD identify with their own gender when socializing and choosing friends. But given the social differences between genders, it is likely that girls with ASD are experiencing social challenges that are different from boys with ASD. Therefore, gender is an important environmental factor to consider when planning social skills interventions at school. C1 [Dean, Michelle; Kasari, Connie; Shih, Wendy; Frankel, Fred] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA USA. [Kasari, Connie] Univ Calif Los Angeles, Los Angeles, CA USA. [Whitney, Rondalyn; Landa, Rebecca] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, New York, NY USA. [Orlich, Felice; King, Bryan] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Harwood, Robin] Hlth Resources & Serv Adm, Rockville, MD USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, Semel Inst, NPI 68-229, Los Angeles, CA USA. EM kasari@gseis.ucla.edu FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau [UA3MC11055]; NIMH [5-U54-MH-068172]; HRSA [UA3MC11055] FX This study was funded by grant UA3MC11055 through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau. This study was supported by NIMH 5-U54-MH-068172 and HRSA UA3MC11055, clinical trials number NCT00095420, and the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau grant UA3MC11055. CR *AIR B, 2012, MULT RAND T IN PRESS Bauminger N, 2003, J AUTISM DEV DISORD, V33, P489, DOI 10.1023/A:1025827427901 Blatchford P, 2003, BRIT J DEV PSYCHOL, V21, P481, DOI 10.1348/026151003322535183 Cairns R. B., 1994, LIFELINES RISKS PATH Chamberlain B, 2007, J AUTISM DEV DISORD, V37, P230, DOI 10.1007/s10803-006-0164-4 Dean M, 2013, DISCOURSE STUD, V15, P147, DOI 10.1177/1461445612471472 GOODWIN MH, 2006, HIDDEN LIFE GIRLS Goodwin MH, 2002, HUM DEV, V45, P392, DOI 10.1159/000066260 Hall JA, 2011, J SOC PERS RELAT, V28, P723, DOI 10.1177/0265407510386192 Kasari C, 2011, J AUTISM DEV DISORD, V41, P533, DOI 10.1007/s10803-010-1076-x Lord C., 2002, AUTISM DIAGNOSTIC OB Maccoby E. E., 1999, 2 SEXES GROWING APAR Maccoby EE, 2002, CURR DIR PSYCHOL SCI, V11, P54, DOI 10.1111/1467-8721.00167 Rose AJ, 1999, DEV PSYCHOL, V35, P69, DOI 10.1037/0012-1649.35.1.69 Rose AJ, 2006, PSYCHOL BULL, V132, P98, DOI 10.1037/0033-2909.132.1.98 Rotheram-Fuller E, 2010, J CHILD PSYCHOL PSYC, V51, P1227, DOI 10.1111/j.1469-7610.2010.02289.x RUBIN KH, 2011, SOCIAL PERSONALITY D, P309 Talbot Mary, 2010, LANGUAGE GENDER VOLKMAR FR, 1993, J AUTISM DEV DISORD, V23, P579, DOI 10.1007/BF01046103 NR 19 TC 7 Z9 7 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 NOV PY 2014 VL 55 IS 11 BP 1218 EP 1225 DI 10.1111/jcpp.12242 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AR8KN UT WOS:000343824100005 PM 25039696 ER PT J AU Lancaster, RL Balling, K Hastings, R Lloyd, TJ AF Lancaster, R. L. Balling, K. Hastings, R. Lloyd, T. J. TI Attributions, criticism and warmth in mothers of children with intellectual disability and challenging behaviour: a pilot study SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE behaviour problems; causal attributions; expressed emotion; maternal depression ID ASSESSING EXPRESSED EMOTION; STONES TRIPLE P; DEVELOPMENTAL-DISABILITIES; PARENTAL ATTRIBUTIONS; MENTAL-HEALTH; AUTISM; STAFF; DEPRESSION; STRESS; IMPACT AB BackgroundAssociations between parental expressed emotion (EE) or parental attributions and the problem behaviours of children with intellectual disability (ID) have been explored in ID research. However, a more detailed examination of the attributional model of EE has not been reported. In the present study, we partially replicated and extended research focused on mothers of typically developing children with behaviour problems. MethodsTwenty-seven mothers of children with ID and behaviour problems aged 4-9 years were interviewed about their most problematic behaviours exhibited by their child, and completed a Five Minute Speech Sample. Interview transcripts and speech samples were coded for maternal EE and spontaneous causal attributions regarding the child's behaviour problems. Data were also collected on maternal well-being, and the child's behaviour problems. ResultsMothers typically made attributions that were internal to the child, controllable by the child, personal to the child and stable for the child. Maternal attributions of being able to control the child's behaviour were associated with high maternal criticism and low warmth. Maternal depression was more strongly associated with the child's behaviour problems when mothers were coded as high in criticism or low in warmth. ConclusionsPatterns of maternal attributions about their child's behaviour problems and their consequences for maternal well-being and maternal-child relationships require more research attention. Implications for practice are discussed, including the potential for maternal attributions to be incompatible with the focus of positive behaviour supports offered to families. C1 [Lancaster, R. L.] Child & Family Therapy Serv, Stalybridge SK15 2AU, Cheshire, England. [Lancaster, R. L.; Balling, K.] Wrexham Maelor Hosp, Betsi Cadwaladr Univ Hlth Board, Wrexham, Wales. [Lancaster, R. L.; Hastings, R.; Lloyd, T. J.] Univ Wales Bangor, Bangor, Gwynedd, Wales. RP Lancaster, RL (reprint author), Child & Family Therapy Serv, Waterloo Rd, Stalybridge SK15 2AU, Cheshire, England. EM r.lancaster@nhs.net RI Hastings, Richard/D-9657-2013 OI Hastings, Richard/0000-0002-0495-8270 CR Baker BL, 2003, J INTELL DISABIL RES, V47, P217, DOI 10.1046/j.1365-2788.2003.00484.x Baker JK, 2011, J ABNORM PSYCHOL, V120, P465, DOI 10.1037/a0021900 Barrowclough C, 2003, CLIN PSYCHOL REV, V23, P849, DOI 10.1016/S0272-7358(03)00075-8 Beck A, 2004, J INTELL DISABIL RES, V48, P628, DOI 10.1111/j.1365-2788.2003.00564.x Bolton C, 2003, J CHILD PSYCHOL PSYC, V44, P242, DOI 10.1111/1469-7610.00117 Chavira V, 2000, J CHILD PSYCHOL PSYC, V41, P245, DOI 10.1017/S0021963099005144 Crawford JR, 2001, BRIT J CLIN PSYCHOL, V40, P429, DOI 10.1348/014466501163904 Daley D, 2003, BRIT J CLIN PSYCHOL, V42, P53, DOI 10.1348/014466503762842011 Emerson E, 2003, J INTELL DISABIL RES, V47, P385, DOI 10.1046/j.1365-2788.2003.00498.x Hassall R, 2005, BEHAV COGN PSYCHOTH, V33, P71, DOI 10.1017/S135246580400178X Hastings RP, 2002, J INTELLECT DEV DIS, V27, P149, DOI 10.1080/1366825021000008657 Hastings RP, 2006, AM J MENT RETARD, V111, P48, DOI 10.1352/0895-8017(2006)111[48:MDAEEC]2.0.CO;2 Hastings RP, 2002, AM J MENT RETARD, V107, P222, DOI 10.1352/0895-8017(2002)107<0222:BPOCWA>2.0.CO;2 Hastings RP, 2007, MENT RETARD DEV D R, V13, P339, DOI 10.1002/mrdd.20173 HASTINGS RP, 1994, RES DEV DISABIL, V15, P279, DOI 10.1016/0891-4222(94)90008-6 Jones C, 2003, BRIT J CLIN PSYCHOL, V42, P189, DOI 10.1348/014466503321903599 Katz MR, 2004, PSYCHO-ONCOL, V13, P269, DOI 10.1002/pon.734 Lecavalier L, 2006, J INTELL DISABIL RES, V50, P172, DOI 10.1111/j.1365-2788.2005.00732.x Lloyd T, 2009, J INTELLECT DEV DIS, V34, P104, DOI 10.1080/13668250902862074 MacDonald EE, 2010, J APPL RES INTELLECT, V23, P27, DOI 10.1111/j.1468-3148.2009.00546.x MAGANA AB, 1986, PSYCHIAT RES, V17, P203, DOI 10.1016/0165-1781(86)90049-1 McIntyre LL, 2008, AM J MENT RETARD, V113, P356, DOI 10.1352/2008.113:356-368 Moore E, 1999, BRIT J CLIN PSYCHOL, V38, P345, DOI 10.1348/014466599162953 Munton A.G., 1999, ATTRIBUTIONS ACTION Roberts C, 2006, J CLIN CHILD ADOLESC, V35, P180, DOI 10.1207/s15374424jccp3502_2 Rojahn J, 2001, J AUTISM DEV DISORD, V31, P577, DOI 10.1023/A:1013299028321 Smith LE, 2008, AM J MENT RETARD, V113, P387, DOI 10.1352/2008.113:387-402 Weigel L, 2006, BRIT J CLIN PSYCHOL, V45, P205, DOI 10.1348/014466505X67510 Welsh Assembly Government, 2008, WELSH IND MULT DEPR, V2008 White C, 1998, BRIT J CLIN PSYCHOL, V37, P385 Whittingham K, 2009, J ABNORM CHILD PSYCH, V37, P469, DOI 10.1007/s10802-008-9285-x Whittingham K, 2009, RES AUTISM SPECT DIS, V3, P129, DOI 10.1016/j.rasd.2008.05.002 Woolfson LM, 2011, CHILD CARE HLTH DEV, V37, P184, DOI 10.1111/j.1365-2214.2010.01103.x ZIGMOND AS, 1983, ACTA PSYCHIAT SCAND, V67, P361, DOI 10.1111/j.1600-0447.1983.tb09716.x NR 34 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD NOV PY 2014 VL 58 IS 11 BP 1060 EP 1071 DI 10.1111/jir.12029 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AR8KO UT WOS:000343824200007 PM 23464804 ER PT J AU Redin, C Gerard, B Lauer, J Herenger, Y Muller, J Quartier, A Masurel-Paulet, A Willems, M Lesca, G El-Chehadeh, S Le Gras, S Vicaire, S Philipps, M Dumas, M Geoffroy, V Feger, C Haumesser, N Alembik, Y Barth, M Bonneau, D Colin, E Dollfus, H Doray, B Delrue, MA Drouin-Garraud, V Flori, E Fradin, M Francannet, C Goldenberg, A Lumbroso, S Mathieu-Dramard, M Martin-Coignard, D Lacombe, D Morin, G Polge, A Sukno, S Thauvin-Robinet, C Thevenon, J Doco-Fenzy, M Genevieve, D Sarda, P Edery, P Isidor, B Jost, B Olivier-Faivre, L Mandel, JL Piton, A AF Redin, Claire Gerard, Benedicte Lauer, Julia Herenger, Yvan Muller, Jean Quartier, Angelique Masurel-Paulet, Alice Willems, Marjolaine Lesca, Gaetan El-Chehadeh, Salima Le Gras, Stephanie Vicaire, Serge Philipps, Muriel Dumas, Michael Geoffroy, Veronique Feger, Claire Haumesser, Nicolas Alembik, Yves Barth, Magalie Bonneau, Dominique Colin, Estelle Dollfus, Helene Doray, Berenice Delrue, Marie-Ange Drouin-Garraud, Valerie Flori, Elisabeth Fradin, Melanie Francannet, Christine Goldenberg, Alice Lumbroso, Serge Mathieu-Dramard, Michele Martin-Coignard, Dominique Lacombe, Didier Morin, Gilles Polge, Anne Sukno, Sylvie Thauvin-Robinet, Christel Thevenon, Julien Doco-Fenzy, Martine Genevieve, David Sarda, Pierre Edery, Patrick Isidor, Bertrand Jost, Bernard Olivier-Faivre, Laurence Mandel, Jean-Louis Piton, Amelie TI Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; AUTISM SPECTRUM DISORDERS; LINKED MENTAL-RETARDATION; DE-NOVO MUTATIONS; NEUROLIGIN GENES; DEVELOPMENTAL DELAY; RETT-SYNDROME; FRAGILE-X; DELETION; INDIVIDUALS AB Background Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. Methods We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases. Results We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients' clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders. Conclusions With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism. C1 [Redin, Claire; Muller, Jean; Quartier, Angelique; Haumesser, Nicolas; Mandel, Jean-Louis; Piton, Amelie] Univ Strasbourg, CNRS, Dept Med Translat & Neurogenet,IGBMC, INSERM,UMR 7104,U964, Illkirch Graffenstaden, France. [Redin, Claire; Quartier, Angelique; Haumesser, Nicolas; Mandel, Jean-Louis; Piton, Amelie] Coll France, Chaire Genet Humaine, Illkirch Graffenstaden, France. [Gerard, Benedicte; Lauer, Julia; Herenger, Yvan; Muller, Jean; Mandel, Jean-Louis] Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France. [Masurel-Paulet, Alice; El-Chehadeh, Salima; Thauvin-Robinet, Christel; Thevenon, Julien; Olivier-Faivre, Laurence] CHU Dijon, Hop Enfants, Ctr Genet, Dijon, France. [Masurel-Paulet, Alice; El-Chehadeh, Salima; Thauvin-Robinet, Christel; Thevenon, Julien; Olivier-Faivre, Laurence] CHU Dijon, Hop Enfants, Ctr Reference Anomalies Dev & Syndromes Malformat, Dijon, France. [Willems, Marjolaine; Genevieve, David; Sarda, Pierre] Hop Arnaud de Villeneuve, Ctr Reference Malad Rares Anomalies Dev & Syndrom, Dept Genet Med, Montpellier, France. [Lesca, Gaetan; Edery, Patrick] Hosp Civils Lyon, Dept Genet Med, Bron, France. [Le Gras, Stephanie; Vicaire, Serge; Philipps, Muriel; Dumas, Michael; Feger, Claire; Jost, Bernard] Univ Strasbourg, CNRS, INSERM, IGBMC,UMR 7104,U964, Illkirch Graffenstaden, France. [Geoffroy, Veronique] Univ Strasbourg, CNRS, INSERM, IGBMC,UMR 7104,U964,Plateforme Bioinformat Strasb, Illkirch Graffenstaden, France. [Alembik, Yves; Doray, Berenice; Flori, Elisabeth] CHU Hautepierre, Dept Genet, F-67098 Strasbourg, France. [Barth, Magalie; Bonneau, Dominique; Colin, Estelle] CHU Angers, Dept Biochim & Genet, Angers, France. [Dollfus, Helene] Hop Univ Strasbourg, Fac Med Strasbourg, INSERM, Lab Genet Med,U1112, Strasbourg, France. [Delrue, Marie-Ange; Lacombe, Didier] Univ Bordeaux, Lab MRGM, CHU Bordeaux, Bordeaux, France. [Drouin-Garraud, Valerie; Goldenberg, Alice] CHU Rouen, Dept Genet Med, Rouen, France. [Fradin, Melanie] CHU Rennes, Ctr Reference Anomalies Dev, Serv Genet Med, Rennes, France. [Francannet, Christine] Hop Hotel Dieu, Serv Genet Med, Clermont Ferrand, France. [Polge, Anne] CHU Nimes, Lab Biochim, Nimes, France. [Mathieu-Dramard, Michele; Morin, Gilles] CHU Amiens, Unite Genet Clin, Amiens, France. [Martin-Coignard, Dominique] Ctr Hosp, Serv Genet, Le Mans, France. [Sukno, Sylvie] Grp Hosp, Hop St Vincent de Paul, Serv Neuropediat, Inst Catholique Lillois,Fac Libre Med, Lille, France. [Doco-Fenzy, Martine] CHU Reims, EA3801, Serv Genet, Reims, France. [Isidor, Bertrand] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. RP Piton, A (reprint author), Translat Med & Neurogenet, F-67400 Illkirch Graffenstaden, France. EM jlmandel@igbmc.fr; amelie.piton@igbmc.fr FU Fondation pour la Recherche Medicale; Agence de Biomedecine; Fondation Jerome Lejeune; APLM; CREGEMES FX This study was supported by grants and fellowships from Fondation pour la Recherche Medicale, Agence de Biomedecine and Fondation Jerome Lejeune, APLM and CREGEMES. We thank the students who were involved in this project: Sebastien Kirsch, Audrey Creppy, Ines Bekkour and Grace Gan. We thank Nadege Calmels, Valerie Biancalana, Elsa Nourisson and all other members of the Genetic Diagnostic Laboratory of the Nouvel Hopital Civil (Strasbourg) for their help with patients' DNA sample selection and preparation. We thank Cecile Pizot for the development of VaRank. We thank Damien Sanlaville, Christine Coubes, Delphine Heron, Sophie Naudion, James Lespinasse and Marie-Line Bichon for their contribution to the recruitment of patients, and all medical interns or genetic counsellors who participated in this project. 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Med. Genet. PD NOV PY 2014 VL 51 IS 11 BP 724 EP 736 DI 10.1136/jmedgenet-2014-102554 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AR9ET UT WOS:000343875900003 PM 25167861 ER PT J AU Babbs, C Lloyd, D Pagnamenta, AT Twigg, SRF Green, J McGowan, SJ Mirza, G Naples, R Sharma, VP Volpi, EV Buckle, VJ Wall, SA Knight, SJL Parr, JR Wilkie, AOM AF Babbs, Christian Lloyd, Deborah Pagnamenta, Alistair T. Twigg, Stephen R. F. Green, Joanne McGowan, Simon J. Mirza, Ghazala Naples, Rebecca Sharma, Vikram P. Volpi, Emanuela V. Buckle, Veronica J. Wall, Steven A. Knight, Samantha J. L. Parr, Jeremy R. Wilkie, Andrew O. M. CA IMGSAC TI De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SMITH-MAGENIS-SYNDROME; COPY-NUMBER VARIATION; FUNCTIONAL IMPACT; PEST SEQUENCES; EXPRESSION; RAI1; DUP(17)(P11.2P11.2); PHENOTYPE; INTERVIEW; GENETICS AB Background Autism spectrum disorders (ASDs) are common and have a strong genetic basis, yet the cause of similar to 70-80% ASDs remains unknown. By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints. Methods The rearrangement was characterised using fluorescence in situ hybridisation, Southern blotting, inverse PCR and dideoxy-sequencing. Open reading frames and intron/exon boundaries of the two physically disrupted genes identified, TCF20 and TNRC6B, were sequenced in 342 families (260 multiplex and 82 simplex) ascertained by the International Molecular Genetic Study of Autism Consortium (IMGSAC). Results IMGSAC family screening identified a de novo missense mutation of TCF20 in a single case and significant association of a different missense mutation of TCF20 with ASD in three further families. Through exome sequencing in another project, we independently identified a de novo frameshifting mutation of TCF20 in a woman with ASD and moderate intellectual disability. We did not identify a significant association of TNRC6B mutations with ASD. Conclusions TCF20 encodes a transcriptional coregulator (also termed SPBP) that is structurally and functionally related to RAI1, the critical dosage-sensitive protein implicated in the behavioural phenotypes of the Smith-Magenis and Potocki-Lupski 17p11.2 deletion/duplication syndromes, in which ASD is frequently diagnosed. This study provides the first evidence that mutations in TCF20 are also associated with ASD. C1 [Babbs, Christian; Lloyd, Deborah; Twigg, Stephen R. F.; Green, Joanne; McGowan, Simon J.; Naples, Rebecca; Sharma, Vikram P.; Buckle, Veronica J.; Wilkie, Andrew O. M.] John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. [Babbs, Christian; Pagnamenta, Alistair T.; Knight, Samantha J. L.; Wilkie, Andrew O. M.] NIHR Biomed Res Ctr, Oxford, England. [Pagnamenta, Alistair T.; Mirza, Ghazala; Volpi, Emanuela V.; Knight, Samantha J. L.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 9DU, England. [Sharma, Vikram P.; Wall, Steven A.; Wilkie, Andrew O. M.] John Radcliffe Hosp, Oxford Univ Hosp NHS Trust, Dept Plast & Reconstruct Surg, Craniofacial Unit, Oxford OX3 9DU, England. [Parr, Jeremy R.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Wilkie, AOM (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. EM jeremy.parr@newcastle.ac.uk; andrew.wilkie@imm.ox.ac.uk RI Bailey, Anthony/J-2860-2014 OI Bailey, Anthony/0000-0003-4257-972X FU Wellcome Trust [090532/Z/09/Z, 078666, 093329]; Newlife Foundation for Disabled Children [10-11/04]; Royal College of Surgeons of England; Rosetrees Trust; Blond-McIndoe Research Foundation; Oxford Partnership Comprehensive Biomedical Research Centre; Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme FX This work was funded by the Wellcome Trust (Core Award 090532/Z/09/Z to GM, EVV and SJLK, programme grant 078666 to AOMW, project grant 093329 to AOMW and SRFT), the Newlife Foundation for Disabled Children (10-11/04 to AOMW and SRFT), Royal College of Surgeons of England with support from the Rosetrees Trust and Blond-McIndoe Research Foundation (Research Fellowship to VPS) and the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme (SJLK, JRP and AOMW). 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Wade Shekhar, Anantha TI Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase SO NATURE NEUROSCIENCE LA English DT Article ID AUTISM SPECTRUM DISORDER; NEUROFIBROMATOSIS TYPE-1; SYNAPTIC-TRANSMISSION; BASOLATERAL AMYGDALA; MOUSE MODEL; CHILDREN; MECHANISM; POPULATION; EPILEPSY; COMPLEX AB Children with neurofibromatosis type 1 (NF1) are increasingly recognized as having a high prevalence of social difficulties and autism spectrum disorders (ASDs). We demonstrated a selective social learning deficit in mice with deletion of a single Nf1 allele (Nf1(+/-)), along with greater activation of the mitogen-activated protein kinase pathway in neurons from the amygdala and frontal cortex, structures that are relevant to social behaviors. 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[Molosh, Andrei I.; Johnson, Philip L.; Federici, Lauren M.; Khanna, Rajesh; Zhu, Weiguo; Shekhar, Anantha] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN 46202 USA. [Johnson, Philip L.; Federici, Lauren M.; Bernabe, Cristian] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Spence, John P.; Federici, Lauren M.] Indiana Univ Sch Med, Program Med Neurosci, Indianapolis, IN 46202 USA. [Segu, Zaneer M.; Mechref, Yehia S.] Indiana Univ, METACyt Biochem Anal Ctr, Dept Chem, Bloomington, IN USA. [Khanna, Rajesh; Zhu, Weiguo; Shekhar, Anantha] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. [Goswami, Chirayu; Li, Lang] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Park, Su-Jung; Clapp, D. Wade] Indiana Univ Sch Med, Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA. [Clapp, D. Wade] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Shekhar, Anantha] Indiana Univ Sch Med, Indiana Clin & Translat Sci Inst, Indianapolis, IN 46202 USA. RP Shekhar, A (reprint author), Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. EM ashekhar@iu.edu FU National Center for Advanced Translational Sciences, US National Institutes of Health [UL1RR025761/TR000006, R01 MH52619, MH065702]; [TL1 RR 025759]; [K01AG044466]; [R01 CA74177-06] FX This work was supported by grants from the National Center for Advanced Translational Sciences, US National Institutes of Health UL1RR025761/TR000006, R01 MH52619 and MH065702 (to A.S.), a predoctoral fellowship to J.P.S. (TL1 RR 025759), K01AG044466 (to P.L.J.) and R01 CA74177-06 (to D.W.C.). We thank T. Jacks (Massachusetts Institute of Technology) for providing Nf1+/- mice and J. Chernoff (Fox Chase Cancer Center) for providing Pak1-/- mice. 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Neurosci. PD NOV PY 2014 VL 17 IS 11 BP 1583 EP 1590 DI 10.1038/nn.3822 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AS0LT UT WOS:000343969300024 PM 25242307 ER PT J AU Djukic, A Rose, SA Jankowski, JJ Feldman, JF AF Djukic, Aleksandra Rose, Susan A. Jankowski, Jeffery J. Feldman, Judith F. TI Rett Syndrome: Recognition of Facial Expression and Its Relation to Scanning Patterns SO PEDIATRIC NEUROLOGY LA English DT Article DE Rett syndrome; emotion recognition; visual attention; scanpaths; eye tracking ID 7-MONTH-OLD INFANTS; PRETERM INFANTS; EYE-TRACKING; AUTISM; MEMORY; INDIVIDUALS; EMOTION; FACES; DISCRIMINATION; PERCEPTION AB BACKGROUND: Rett syndrome is a severely disabling neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. Very little is known about its cognitive phenotype and nothing about recognition of emotional expression, a key factor for social interaction and communication. Using eye tracking technology, a technique uniquely suited for studying cognition in this disorder, we examined this ability here. METHODS: Rett syndrome female patients (n = 37; 2-31 years) and a typically developing age- and gender-matched comparison group (n = 34; 2-30 years) were assessed on recognition of three basic emotions (happy, sad, and fear) using six visual paired-comparison problems. Each problem consisted of a 10-second familiarization, in which two identical faces posing one emotion were presented, followed by a 10-second test, in which the familiar emotion was paired with a novel one posed by the same model. Recognition was inferred from preferential looking to the novel target on test. During familiarization, attention was measured by total looking time, number and/or length of fixations, and gaze dispersion across three key facial features (eyes, nose, and mouth). RESULTS: Individuals with Rett syndrome had difficulty recognizing most emotional expressions, unlike the typically developing comparison group. Also, their scanpaths were atypical-less looking, fewer and/or longer fixations, and less time devoted to all facial features (48% versus 72%), particularly the mouth. Significant correlations between looking to critical features and recognition underscored the importance of scanning. CONCLUSIONS: Our results suggest that individuals with Rett syndrome have difficulty reading emotional expressions and that these problems are linked to atypicalities in scanning. C1 [Djukic, Aleksandra] Montefiore Med Ctr, Albert Einstein Coll Med, Rett Syndrome Ctr, Bronx, NY 10467 USA. [Rose, Susan A.; Jankowski, Jeffery J.; Feldman, Judith F.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Dept Pediat, Bronx, NY 10461 USA. [Jankowski, Jeffery J.] CUNY Queensborough Community Coll, Dept Social Sci, New York, NY 11364 USA. RP Rose, SA (reprint author), Albert Einstein Coll Med, Childrens Hosp Montefiore, Dept Pediat, Rm 420,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM susan.rose@einstein.yu.edu FU International Rett Syndrome Foundation [8211] FX This work was supported by grant number #8211 from the International Rett Syndrome Foundation. None of the authors have any financial interests or benefit arising from this work. 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TI Increased Gender Variance in Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE Gender variance; Gender identity; Autism; Attention deficit hyperactivity disorder; Gender dysphoria ID PERVASIVE DEVELOPMENTAL DISORDERS; IDENTITY-DISORDER; BEHAVIOR PROBLEMS; PSYCHIATRIC COMORBIDITY; DIAGNOSTIC INTERVIEW; ADAPTIVE-BEHAVIOR; ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; MANAGEMENT AB Evidence suggests over-representation of autism spectrum disorders (ASDs) and behavioral difficulties among people referred for gender issues, but rates of the wish to be the other gender (gender variance) among different neurodevelopmental disorders are unknown. This chart review study explored rates of gender variance as reported by parents on the Child Behavior Checklist (CBCL) in children with different neurodevelopmental disorders: ASD (N=147, 24 females and 123 males), attention deficit hyperactivity disorder (ADHD; N=126, 38 females and 88 males), or a medical neurodevelopmental disorder (N=116, 57 females and 59 males), were compared with two non-referred groups [control sample (N=165, 61 females and 104 males) and non-referred participants in the CBCL standardization sample (N=1,605, 754 females and 851 males)]. Significantly greater proportions of participants with ASD (5.4%) or ADHD (4.8%) had parent reported gender variance than in the combined medical group (1.7%) or non-referred comparison groups (0-0.7 %). As compared to non-referred comparisons, participants with ASD were 7.59 times more likely to express gender variance; participants with ADHD were 6.64 times more likely to express gender variance. 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PD NOV PY 2014 VL 43 IS 8 BP 1525 EP 1533 DI 10.1007/s10508-014-0285-3 PG 9 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA AR9PW UT WOS:000343907900006 PM 24619651 ER PT J AU Zampini, L Zanchi, P D'Odorico, L AF Zampini, Laura Zanchi, Paola D'Odorico, Laura TI Developing with ring 14 syndrome: A survey in different countries SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE behavioural problems; language development; linear 14q deletions; ring 14 syndrome ID CHROMOSOME; CHILDREN AB This study aimed to assess the communicative skills of children and young adults with ring 14 syndrome and linear 14q deletions, investigating the relationships among their language development and their genetic, clinical, psychomotor and behavioural characteristics. Participants were 36 individuals with chromosome 14 aberrations whose parents completed a questionnaire, specifically developed in five languages, to assess their son's/daughter's development. Data analysis showed that chronological age does not account for the high individual variability found in the participants' skills. The comparison between participants with ring 14 syndrome and participants with 14q linear deletions showed that the former were characterised by a higher occurrence of epilepsy, abnormalities of the retina and autism. The participants with smaller amounts of deleted genetic material were those who had a higher level of language development. Because ring 14 syndrome is a rare genetic disease, the collection of data from a large group of individuals could be helpful to create expectations about the possible developmental outcomes of these children. C1 [Zampini, Laura; Zanchi, Paola; D'Odorico, Laura] Univ Milano Bicocca, Dept Psychol, I-20126 Milan, Italy. 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PD NOV PY 2014 VL 28 IS 11 BP 844 EP 856 DI 10.3109/02699206.2014.911963 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR6DT UT WOS:000343674400004 PM 24779649 ER PT J AU Vaidya, AR Jin, CS Fellows, LK AF Vaidya, Avinash R. Jin, Chenshuo Fellows, Lesley K. TI Eye spy: The predictive value of fixation patterns in detecting subtle and extreme emotions from faces SO COGNITION LA English DT Article DE Emotion; Face perception; Expression; Modeling; Eye-tracking; Fixation ID FACIAL EXPRESSIONS; AMYGDALA DAMAGE; RECOGNITION TASKS; ATTENTION; AUTISM; LANGUAGE; INFORMATION; PERCEPTION; MECHANISM; SELECTION AB Successful social interaction requires recognizing subtle changes in the mental states of others. Deficits in emotion recognition are found in several neurological and psychiatric illnesses, and are often marked by disturbances in gaze patterns to faces, typically interpreted as a failure to fixate on emotionally informative facial features. However, there has been very little research on how fixations inform emotion recognition in healthy people. Here, we asked whether fixations predicted detection of subtle and extreme emotions in faces. We used a simple model to predict emotion detection scores from participants' fixation patterns. The best fit of this model heavily weighted fixations to the eyes in detecting subtle fear, disgust and surprise, with less weight, or zero weight, given to mouth and nose fixations. However, this model could not successfully predict detection of subtle happiness, or extreme emotional expressions, with the exception of fear. These findings argue that detection of most subtle emotions is best served by fixations to the eyes, with some contribution from nose and mouth fixations. In contrast, detection of extreme emotions and subtle happiness appeared to be less dependent on fixation patterns. The results offer a new perspective on some puzzling dissociations in the neuropsychological literature, and a novel analytic approach for the study of eye gaze in social or emotional settings. (C) 2014 Elsevier B.V. All rights reserved. C1 [Vaidya, Avinash R.; Jin, Chenshuo; Fellows, Lesley K.] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. RP Vaidya, AR (reprint author), McGill Univ, Montreal Neurol Inst, Rm 276,3801 Univ St, Montreal, PQ H3A 2B4, Canada. 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Zwaigenbaum, Lonnie Piven, Joseph CA Infant Brain Imaging Study IBIS TI Repetitive Behavior in 12-Month-Olds Later Classified With Autism Spectrum Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; repetitive behavior; motor stereotypies; infant siblings; development ID STEREOTYPED MOVEMENTS; UNAFFECTED SIBLINGS; YOUNG-CHILDREN; FOLLOW-UP; 2ND YEAR; TODDLERS; INFANTS; COMMUNICATION; RISK; LIFE AB Objective: As compared to the utility of early emerging social communicative risk markers for predicting a later diagnosis of autism spectrum disorder (ASD), less is known about the relevance of early patterns of restricted and repetitive behaviors. We examined patterns of stereotyped motor mannerisms and repetitive manipulation of objects in 12-month-olds at high and low risk for developing ASD, all of whom were assessed for ASD at 24 months. Method: Observational coding of repetitive object manipulation and stereotyped motor behaviors in digital recordings of the Communication and Symbolic Behavior Scales was conducted using the Repetitive and Stereotyped Movement Scales for 3 groups of 12-month-olds: low-risk infants (LR, n = 53); high familial-risk infants who did not meet diagnostic criteria for ASD at 24 months (HR-negative, n = 75); and high familial-risk infants who met diagnostic criteria for ASD at 24 months (HR-ASD, n = 30). Results: The HR-ASD group showed significantly more stereotyped motor mannerisms than both the HR-negative group (p =.025) and the LR group (p =.001). The HR-ASD and HR-negative groups demonstrated statistically equivalent repetitive object manipulation scores (p =.431), and both groups showed significantly more repetitive object manipulation than the LR group (p <.040). Combining the motor and object stereotypy scores into a Repetitive and Stereotyped Movement Scales (RSMS) composite yielded a disorder-continuum effect such that each group was significantly different from one another (LR < HR-negative < HR-ASD). Conclusion: These results suggest that targeted assessment of repetitive behavior during infancy may augment early ASD identification efforts. C1 [Elison, Jed T.] Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. [Wolff, Jason J.; Gu, Hongbin; Hazlett, Heather C.; Meadows, Adriane J.; Piven, Joseph] Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Wolff, Jason J.; Reznick, Steven; Gu, Hongbin; Hazlett, Heather C.; Meadows, Adriane J.; Piven, Joseph] Univ N Carolina, Chapel Hill, NC 27599 USA. [Botteron, Kelly N.] Washington Univ, St Louis, MO 63130 USA. [Estes, Annette M.] Univ Washington, Seattle, WA 98195 USA. [Paterson, Sarah J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Zwaigenbaum, Lonnie] Univ Alberta, Edmonton, AB T6G 2R3, Canada. RP Elison, JT (reprint author), Univ Minnesota, Inst Child Dev, 51 East River Pkwy, Minneapolis, MN 55455 USA. EM jtelison@umn.edu FU Infant Brain Imaging Study (IBIS) Network is a National Institutes of Health (NIH); NIH/National Institute of Child Health and Human Development (NICHD) [R01 HD055741, HD055741-S1, P30 HD03110, T32 HD40127]; Autism Speaks; Simons Foundation; NIH/NICHD [5-T32-HD007376] FX The Infant Brain Imaging Study (IBIS) Network is a National Institutes of Health (NIH)-funded Autism Center of Excellence,project and consists of a consortium of 7 universities in the US-and Canada Clinical Sites. University of North Carolina: J. Piven, MD (IBIS Network PI), H.C. Hazlett, PhD, J.C. Chappell, MS; University of Washington, S. Dager, MD, A Estes, PhD, D. Shaw, MD, Washington University:( Botteron, MD, R. McKinstry, MD, PhD, J Constantino, MD, J. Pruett, MD, PhD; Children's Hospital-of Philadelphia: R. Schultz, PhD, S Paterson, PhD; University Of Alberta: L Zwaigenbaum, MD; Data Coordinating Centar, Montreal Neurological Institute: A C. Evans, PhD, DL. Collins, PhD, G.B. Pike, PhD, P. Kostopoulos, PhD, S. Das, BSc, Image Processing, Core, University of Utah: G. Gerig, PhD; University of North Carolina: M. Styner, PhD; Statistical Analysis Core, University of North, Carolina,: H. Gu, PhD; Genetics Analysis Core, University of North Carolina P. Sullivan, MD, F. Wright, PhD.This research was supported, by grants awarded to J.P. from NIH/National Institute of Child Health and Human Development (NICHD) (R01 HD055741, HD055741-S1, P30 HD03110, T32 HD40127) Autism Speaks, and the Simons Foundation. J.T.E. was supported by NIH/NICHD grant 5-T32-HD007376, and aspects of this work contributed to his PhD dissertation while-affiliated with UNC. J.T.E. had full access to the data and takes full responsibility for the integrity and accuracy of the data analysis. 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Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2014 VL 53 IS 11 BP 1216 EP 1224 DI 10.1016/j.jaac.2014.08.004 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AR5JG UT WOS:000343620600010 PM 25440311 ER PT J AU Fitzgerald, KD Liu, YN Reamer, EN Taylor, SF Welsh, RC AF Fitzgerald, Kate D. Liu, Yanni Reamer, Elyse N. Taylor, Stephan F. Welsh, Robert C. TI Atypical Frontal-Striatal-Thalamic Circuit White Matter Development in Pediatric Obsessive-Compulsive Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE development; frontal striatal thalamic circuit; fractional anisotropy; diffusion tensor imaging; obsessive-compulsive disorder ID DIFFUSION-TENSOR; BRAIN; ABNORMALITIES; CHILDREN; ADOLESCENTS; RELIABILITY; VALIDITY; METAANALYSIS; ADULTHOOD; AUTISM AB Objective: Atypical development of frontal striatal thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. Method: To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle, and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Results: Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Conclusions: Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to those in healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth; however, confirmation of these possibilities awaits longitudinal work. C1 [Fitzgerald, Kate D.; Liu, Yanni; Reamer, Elyse N.; Taylor, Stephan F.; Welsh, Robert C.] Univ Michigan, Sch Med, Ann Arbor, MI 48104 USA. RP Fitzgerald, KD (reprint author), Univ Michigan, Dept Psychiat, 4250 Plymouth Rd, Ann Arbor, MI 48104 USA. FU National Institute of Mental Health (NIMH) [K23MH082176]; Dana Foundation; National Institute of Neurological Disorders and Stroke [NSR01-052514]; University of Michigan Medical School Summer Biomedical Research Program FX This study was funded by grants from the National Institute of Mental Health (NIMH; K23MH082176) and the Dana Foundation (K D F), the National Institute of Neurological Disorders and Stroke (NSR01-052514 to R.C.W.), and the University of Michigan Medical School Summer Biomedical Research Program (E.N.R.) 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Peng, Y. Wang, K. He, Y. Xiong, Z. Sun, L. Pan, Q. Long, Z. Zou, X. Li, X. Li, W. Xu, X. Lu, L. Liu, Y. Hu, Y. Tian, D. Long, L. Ou, J. Liu, Y. Li, X. Zhang, L. Pan, Y. Chen, J. Peng, H. Liu, Q. Luo, X. Su, W. Wu, L. Liang, D. Dai, H. Yan, X. Feng, Y. Tang, B. Li, J. Miedzybrodzka, Z. Xia, J. Zhang, Z. Luo, X. Zhang, X. St Clair, D. Zhao, J. Zhang, F. TI Common genetic variants on 1p13.2 associate with risk of autism SO MOLECULAR PSYCHIATRY LA English DT Article DE association fine mapping; autism; common genetic variants; genome-wide association study; human genetics ID DE-NOVO MUTATIONS; LINKED MENTAL-RETARDATION; COPY NUMBER VARIATION; GENOME-WIDE LINKAGE; SPECTRUM DISORDERS; UBIQUITIN; REVEALS; SCAN; ENCODES; COMPLEX AB Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n = 2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P = 4.49 x 10(-8) ), non-synonymous rs6537835 (P = 3.26 x 10(-8)) and rs1877455 (P = 8.70 x 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism. C1 [Xia, K.; Guo, H.; Hu, Z.; Peng, Y.; Xiong, Z.; Pan, Q.; Long, Z.; Li, X.; Li, W.; Xu, X.; Lu, L.; Liu, Y.; Hu, Y.; Tian, D.; Long, L.; Zhang, L.; Pan, Y.; Chen, J.; Peng, H.; Liu, Q.; Su, W.; Wu, L.; Liang, D.; Dai, H.; Yan, X.; Feng, Y.; Tang, B.; Li, J.; Xia, J.; Zhang, Z.; Zhao, J.] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China. [Xia, K.; Guo, H.; Hu, Z.; Peng, Y.; Xiong, Z.] Cent S Univ, Sch Biol Sci & Technol, Changsha 410078, Hunan, Peoples R China. [Guo, H.; St Clair, D.; Zhang, F.] NIMH, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. [Xun, G.; He, Y.; Ou, J.; Liu, Y.; Li, X.; Luo, X.; Zhao, J.] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410078, Hunan, Peoples R China. [Zuo, L.; Luo, X.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Wang, K.; Zhang, X.] State Key Lab Incubation Base Dermatol, Hefei, Anhui, Peoples R China. [Zou, X.] Sun Yat Sen Univ, Hosp 3, Dept Pediat, Guangzhou, Guangdong, Peoples R China. [Yan, X.; Feng, Y.; Tang, B.] Cent S Univ, Xiangya Hosp, Changsha 410078, Hunan, Peoples R China. [Miedzybrodzka, Z.; St Clair, D.] Univ Aberdeen, Royal Cornhill Hosp, Aberdeen, Scotland. [Zhang, F.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA. RP Xia, K (reprint author), Cent S Univ, State Key Lab Med Genet, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China. EM xiakun48@163.com; zhaojingpingcsu@163.com; fzhang20@jhmi.edu RI zhu, caihong/A-1628-2015 FU Autism Genetic Resources Exchange (AGRE); Simons Foundation for Autism Research Initiative (SFARI); National Basic Research Program of China [2012CB517900, 2011CB510002]; National Natural Science Foundation of China [81330027, 81161120544]; National Alliance for Research on Schizophrenia and Depression (NARSAD) [17616]; National Institute of Mental Health, The National Institutes of Health in the United States FX We are grateful to all the children with autism, their families and to the normal controls who participated in this study. We thank Autism Speaks for sharing resources from the Autism Genetic Resources Exchange (AGRE), the Simons Foundation for Autism Research Initiative (SFARI) for providing data from the Simons Simplex Collection (SCC), the NIH GWAS Data Repository (AGP data set: phs000267.v1.p1) and the Contributing Investigator(s) who contributed the phenotype and genotype data from his/her original studies. We also thank Mr Tianzhang Ye, Dr Carlo Colantuoni and Dr Joel E Kleinman for assisting in accessing the brain expression data and Dr Elizabeth Sherman for comments. The research was supported by the National Basic Research Program of China (2012CB517900, 2011CB510002), the National Natural Science Foundation of China (81330027, 81161120544), the National Alliance for Research on Schizophrenia and Depression (NARSAD) Award (17616 to LZ) and Intramural Research Program funding from the National Institute of Mental Health, The National Institutes of Health in the United States. 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Psychiatr. PD NOV PY 2014 VL 19 IS 11 BP 1212 EP 1219 DI 10.1038/mp.2013.146 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AR5ZT UT WOS:000343662300010 PM 24189344 ER PT J AU Nishijo, M Pham, TT Nguyen, ATN Tran, NN Nakagawa, H Hoang, LV Tran, AH Morikawa, Y Ho, MD Kido, T Nguyen, MN Nguyen, HM Nishijo, H AF Nishijo, M. Pham, T. T. Nguyen, A. T. N. Tran, N. N. Nakagawa, H. Hoang, L. V. Tran, A. H. Morikawa, Y. Ho, M. D. Kido, T. Nguyen, M. N. Nguyen, H. M. Nishijo, H. TI 2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam SO MOLECULAR PSYCHIATRY LA English DT Article ID MATERNAL EXPOSURE; DIOXIN EXPOSURE; POLYCHLORINATED-BIPHENYLS; HEAD CIRCUMFERENCE; DEVELOPING BRAIN; PREVALENCE; SPECTRUM; DISORDERS; DIAGNOSIS; INFANTS AB Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (>= 3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)-the toxic equivalents (TEQ) levels >= 17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs). C1 [Nishijo, M.; Nguyen, A. T. N.; Tran, N. N.; Nakagawa, H.] Kanazawa Med Univ, Dept Publ Hlth, Uchinada, Ishikawa 9200293, Japan. [Pham, T. T.; Hoang, L. V.; Tran, A. H.; Nguyen, M. N.; Nguyen, H. M.] Vietnam Mil Med Univ, Biomed & Pharmaceut Res Ctr, Hanoi, Vietnam. [Morikawa, Y.] Kanazawa Med Univ, Sch Nursing, Uchinada, Ishikawa 9200293, Japan. [Ho, M. D.; Kido, T.] Kanazawa Univ, Fac Hlth Sci, Inst Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 9201192, Japan. [Nguyen, M. N.; Nguyen, H. M.; Nishijo, H.] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Syst Emot Sci, Toyama 930, Japan. RP Nishijo, M (reprint author), Kanazawa Med Univ, Dept Publ Hlth, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan. EM ni-koei@kanazawa-med.ac.jp FU JSPS (Japan Society for the Promotion of Science) Asian Core Program and the Japan Society for the Promotion of Science [25305024, 25290005] FX We thank the medical staffs in the Health Department of Da Nang city, Thanh Khe and Son Tra district hospitals and 17 commune health centers of Thanh Khe and Son Tra districts for their enthusiastic collaborations. This work was supported by the JSPS (Japan Society for the Promotion of Science) Asian Core Program and the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (B) (25305024) and (25290005)). None of the founders had role in the study design, sample collection, analysis, interpretation of data, writing the report or decision to submit the manuscript for publication. 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Fourcade, Stephane Pujol, Aurora Artuch-Iriberri, Rafael Molero-Luis, Marta Vidal, August Huertas, Dori Esteller, Manel TI Improvement of the Rett Syndrome Phenotype in a Mecp2 Mouse Model Upon Treatment with Levodopa and a Dopa-Decarboxylase Inhibitor SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID TYROSINE-HYDROXYLASE DEFICIENCY; MEDIUM SPINY NEURONS; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; MICROSCOPY IMAGES; MICE; BRAIN; EXPRESSION; STRIATUM; INCREASE AB Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease is characterized by abnormal motor, respiratory, cognitive impairment, and autistic-like behaviors. No effective treatment of the disorder is available. Mecp2 knockout mice have a range of physiological and neurological abnormalities that resemble the human syndrome and can be used as a model to interrogate new therapies. Herein, we show that the combined administration of Levodopa and a Dopa-decarboxylase inhibitor in RTT mouse models is well tolerated, diminishes RTT-associated symptoms, and increases life span. The amelioration of RTT symptomatology is particularly significant in those features controlled by the dopaminergic pathway in the nigrostratium, such as mobility, tremor, and breathing. Most important, the improvement of the RTT phenotype upon use of the combined treatment is reflected at the cellular level by the development of neuronal dendritic growth. However, much work is required to extend the duration of the benefit of the described preclinical treatment. C1 [Szczesna, Karolina; de la Caridad, Olga; Petazzi, Paolo; Soler, Marta; Roa, Laura; Saez, Mauricio A.; Huertas, Dori; Esteller, Manel] IDIBELL, Bellvitge Biomed Res Inst, PEBC, Barcelona 08908, Catalonia, Spain. [Fourcade, Stephane; Pujol, Aurora] IDIBELL, Bellvitge Biomed Res Inst, Neurometab Dis Lab, Barcelona 08908, Catalonia, Spain. [Fourcade, Stephane; Pujol, Aurora] Univ Barcelona, Inst Neuropathol, Barcelona, Spain. [Fourcade, Stephane; Pujol, Aurora; Artuch-Iriberri, Rafael; Molero-Luis, Marta] ISCIII, CIBERER, Ctr Biomed Res Rare Dis, Madrid, Spain. [Pujol, Aurora; Esteller, Manel] ICREA, Barcelona, Spain. [Artuch-Iriberri, Rafael; Molero-Luis, Marta] Hosp St Joan de Deu, Neurometab Unit, Barcelona, Spain. [Vidal, August] IDIBELL, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Pathol, Barcelona 08908, Catalonia, Spain. [Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Spain. RP Huertas, D (reprint author), IDIBELL, Hosp Duran & Reynals, Bellvitge Biomed Res Inst, PEBC, 3rd Floor,Ave Gran Via 199-203, Barcelona 08908, Catalonia, Spain. EM dhuertas@idibell.cat; mesteller@idibell.cat RI Fourcade, Stephane/N-4508-2014 OI Fourcade, Stephane/0000-0002-8031-5007 FU European Community [PITN-GA-2012-316758- EPITRAIN, PITN-GA-2009-238242-DISCHROM]; ERC [268626-EPINORC]; E-RARE EuroRETT network [PI071327]; GIBER on Rare Diseases (CIBERER) from the Carlos III Health Institute; Fondation Lejeune (France); MINECO [SAF2011-22803, CSD2006-00049]; Cellex Foundation; Botin Foundation; Catalan Association for Rett Syndrome; Health and Science Departments of the Catalan Government (Generalitat de Catalunya) [AGAUR 2009SGR1315, 2009SGR85] FX This study was supported by the European Community's Seventh Framework Program (FP7/2007-2013), under grant agreement PITN-GA-2012-316758- EPITRAIN project and PITN-GA-2009-238242-DISCHROM; ERC grant agreement 268626-EPINORC project; the E-RARE EuroRETT network (PI071327) and the GIBER on Rare Diseases (CIBERER) from the Carlos III Health Institute); the Fondation Lejeune (France); MINECO projects SAF2011-22803, CSD2006-00049; the Cellex Foundation; the Botin Foundation; the Catalan Association for Rett Syndrome; and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) projects AGAUR 2009SGR1315 and 2009SGR85. KS and PP are EPITRAIN Research Fellows; SF is a Miguel Servet Researcher (CP11/00080); and ME and AP are ICREA Research Professors. 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Joffre, Corinne Aubert, Agnes Lemaire-Mayo, Valerie Crusio, Wim E. Laye, Sophie TI Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Dietary enrichment; Fragile X; Gene-environment interactions; Autism; Cytokines; Neurotrophins ID POLYUNSATURATED FATTY-ACIDS; MENTAL-RETARDATION PROTEIN; OMEGA-3; AUTISM; BRAIN; HIPPOCAMPUS; PREMUTATION; CHILDREN; MOUSE; MODEL AB Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to critically influence brain development and functions. Dietary supplementation with n-3 PUFAs has been suggested as a non-pharmacological therapy for a number of developmental disorders, e.g., autistic spectrum disorders (ASD), but human studies so far have led to conflicting results. Furthermore, it has been hypothesized that the therapeutic impact of n-3 PUFAs on these disorders might be explained by their anti-inflammatory properties and their promoting effects on synaptic function and plasticity, but no clear evidence has been produced in this direction. We evaluated the impact of n-3 PUFA dietary supplementation in a mouse model of fragile X syndrome (FXS), i.e., a major developmental disease and the most frequent monogenic cause of ASD. Fmr1-KO and wild-type mice were provided with a diet enriched or not with n-3 PUFAs from weaning until adulthood when they were tested for multiple FXS-like behaviors. The brain expression of several cytokines and of brain-derived neurotrophic factor (BDNF) was concomitantly assessed as inflammatory and synaptic markers. n-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fmr1-KO mice, including alterations in emotionality, social interaction and non-spatial memory, although not their deficits in social recognition and spatial memory. n-3 PUFAs also rescued most of the neuroinflammatory imbalances of KOs, but had a limited impact on their BDNF deficits. These results demonstrate that n-3 PUFAs dietary supplementation, although not a panacea, has a considerable therapeutic value for FXS and potentially for ASD, suggesting a major mediating role of neuroinflammatory mechanisms. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Pietropaolo, Susanna; Goubran, Mina G.; Lemaire-Mayo, Valerie; Crusio, Wim E.] CNRS, UMR 5287, Inst Neurosci Cognit & Integrat Aquitaine, F-33405 Talence, France. [Pietropaolo, Susanna; Goubran, Mina G.; Joffre, Corinne; Aubert, Agnes; Lemaire-Mayo, Valerie; Crusio, Wim E.; Laye, Sophie] Univ Bordeaux, F-33405 Talence, France. [Joffre, Corinne; Aubert, Agnes; Laye, Sophie] UMR INRA 1286, Lab NutriNeurO, F-33076 Bordeaux, France. RP Pietropaolo, S (reprint author), CNRS, UMR 5287, Inst Neurosci Cognit & Integrat Aquitaine, Bat B2 Ave Fac, F-33405 Talence, France. EM susanna.pietropaolo@u-bordeaux.fr RI Crusio, Wim/A-7070-2008 OI Crusio, Wim/0000-0001-6638-202X FU March of Dimes [12-FY05]; CNRS; University of Bordeaux; INRA; Region Aquitaine FX This work was supported by grants from the March of Dimes (12-FY05-1198), CNRS, and the University of Bordeaux to W.E. Crusio, and of the INRA and Region Aquitaine to S. Laye. 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TI A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: Moderation by method and mental health SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Intranasal oxytocin; Cortisol; Mental health; Meta-analysis; Moderation; Stress ID RANDOMIZED CONTROLLED-TRIAL; PITUITARY-ADRENAL AXIS; TEND-AND-BEFRIEND; BRAIN OXYTOCIN; ANXIETY DISORDERS; SOCIAL BEHAVIORS; RECEPTOR-BINDING; PLASMA OXYTOCIN; STRESS-RESPONSE; DOSE-RESPONSE AB Background: A large body of research has examined the acute effects of intranasal oxytocin administration on social cognition and stress-regulation. While progress has been made with respect to understanding the effect of oxytocin administration on social cognition in clinical populations (e.g. autism, schizophrenia), less is known about its impact on the functioning of the hypothalamic-pituitary-adrenal (HPA) axis among individuals with a mental disorder. Method: We conducted a meta-analysis on the acute effect of intranasal oxytocin administration on the cortisol response to laboratory tasks. The search yielded eighteen studies employing a randomized, placebo-controlled design (k = 18, N = 675). Random-effects models and moderator analyses were performed using the metafor package for the statistical program R. Results: The overall effect size estimate was modest and not statistically significant (Hedges G = -0.151, p = 0.11) with moderate heterogeneity in this effect across studies (I-2 = 31%). Controlling for baseline differences in cortisol concentrations, moderation analyses revealed that this effect was larger in response to challenging laboratory tasks that produced a robust stimulation of the HPA-axis (Hedges g = -0.433, 95% CI[-0.841, -0.025]), and in clinical populations relative to healthy controls (Hedges g = -0.742, 95% CI[-1.405, -0.078]). Conclusion: Overall, oxytocin administration showed greater attenuation of the cortisol response to laboratory tasks that strongly activated the HPA-axis, relative to tasks that did not. The effect was more robust among clinical populations, suggesting possible increased sensitivity to oxytocin among those with a clinical diagnosis and concomitant social difficulties. These data support the view that oxytocin may play an important role in HPA dysfunction associated with psychopathology. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cardoso, Christopher; Kingdon, Danielle; Ellenbogen, Mark A.] Concordia Univ, Dept Psychol, Ctr Res Human Dev, Montreal, PQ H4B 1R6, Canada. RP Cardoso, C (reprint author), Concordia Univ, Dept Psychol, Ctr Res Human Dev, Montreal, PQ H4B 1R6, Canada. EM christophercardoso@gmail.com FU Canada Research Chair program (Social Sciences and Humanities Research Council of Canada; SSHRC) [950-213802]; Canadian Institutes of Health Research (CIHR) [12678]; Fonds de recherche du Quebec-Sante (FRQS); SSHRC FX This research was supported by grants to Dr. Ellenbogen from the Canada Research Chair program (supported by the Social Sciences and Humanities Research Council of Canada; SSHRC; 950-213802) and the Canadian Institutes of Health Research (CIHR; 12678). Christopher Cardoso is supported by a scholarship from the Fonds de recherche du Quebec-Sante (FRQS). Danielle Kingdon is supported by a scholarship from SSHRC. 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Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AR1KA UT WOS:000343342900018 PM 25086828 ER PT J AU Szarkowski, A Mood, D Shield, A Wiley, S Yoshinaga-Itano, C AF Szarkowski, Amy Mood, Deborah Shield, Aaron Wiley, Susan Yoshinaga-Itano, Christine TI A Summary of Current Understanding Regarding Children with Autism Spectrum Disorder Who Are Deaf or Hard of Hearing SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Deaf; hard of hearing; autism spectrum disorder; assessment ID COCHLEAR IMPLANTS; LANGUAGE; TODDLERS; FACE AB This article provides a consensus perspective based on the authors' expertise and the limited available literature regarding our understanding of children with an autism spectrum disorder (ASD) who are deaf or hard of hearing (D/HH). The challenges in the accurate identification of an ASD in children who are D/HH, including red flags for a potential ASD and screening and assessment for ASD, are described in this article. Additionally, strategies to guide professionals in their communication about a possible ASD with families and to frame the need for expanding aspects of communication important for this group of children are suggested. C1 [Szarkowski, Amy] Boston Childrens Hosp Waltham, Deaf & Hard Hearing Program, Waltham, MA 02453 USA. [Mood, Deborah] Childrens Hosp Colorado, Child Dev Unit, Aurora, CO USA. [Shield, Aaron] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Szarkowski, Amy] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wiley, Susan] Cincinnati Childrens Hosp Med Ctr, Div Dev & Behav Pediat, Cincinnati, OH 45229 USA. [Yoshinaga-Itano, Christine] Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. 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Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 241 EP 259 DI 10.1055/s-0034-1389097 PG 19 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500001 PM 25321849 ER PT J AU Wiley, S Innis, H AF Wiley, Susan Innis, Heather TI Supporting Families of Children Who Are Deaf or Hard of Hearing with an Autism Spectrum Disorder SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Family support; autism spectrum disorder; deaf/hard of hearing ID EARLY INTERVENTION AB Families of children who are deaf or hard of hearing (Deaf/HH) with an autism spectrum disorder (ASD) experience many frustrations and challenges in the identification of ASD, accessing supports and services to address all of their child's needs, and identifying networking and support opportunities with other families with children with similar needs. Professionals working with families are in a unique position to help navigate the often disconnected systems of services for children who are Deaf/HH and services for children with ASD. This article poses some possible strategies that professionals can implement in practice when working with children who are Deaf/HH with an ASD. C1 [Wiley, Susan; Innis, Heather] Cincinnati Childrens Hosp Med Ctr, Div Dev & Behav Pediat, Cincinnati, OH 45229 USA. RP Wiley, S (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Dev & Behav Pediat, 3333 Burnet Ave ML 4002, Cincinnati, OH 45229 USA. EM susan.wiley@cchmc.org CR Beals K, 2004, INFANT YOUNG CHILD, V17, P284 Centers for Disease Control and Prevention (CDC), 2003, MMWR-MORBID MORTAL W, V52, P981 Muse C, 2013, PEDIATRICS, V131, pE1324, DOI 10.1542/peds.2013-0008 Myck-Wayne J, 2011, AM ANN DEAF, V156, P379 Pimperton H, 2012, ARCH DIS CHILD, V97, P648, DOI 10.1136/archdischild-2011-301501 Roper L, 2003, AUTISM, V7, P245, DOI 10.1177/1362361303007003002 Szymanski CA, 2012, J AUTISM DEV DISORD, V42, P2027, DOI 10.1007/s10803-012-1452-9 Wiley S, 2014, J DEAF STUD DEAF EDU, V19, P40, DOI 10.1093/deafed/ent044 NR 8 TC 1 Z9 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-0478 EI 1098-9056 J9 SEMIN SPEECH LANG JI Semin. Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 260 EP 265 DI 10.1055/s-0034-1389098 PG 6 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500002 PM 25321850 ER PT J AU Carr, J Xu, DX Yoshinaga-Itano, C AF Carr, Jason Xu, Dongxin Yoshinaga-Itano, Christine TI Language ENvironment Analysis Language and Autism Screen and the Child Development Inventory Social Subscale as a Possible Autism Screen for Children Who Are Deaf or Hard of Hearing SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Deaf or hard of hearing; autism; screen; early childhood ID SPECTRUM DISORDERS; YOUNG-CHILDREN; MODIFIED CHECKLIST; FOLLOW-UP; TODDLERS; IMPAIRMENT; DIAGNOSIS; RISK AB The Language ENvironment Analysis Language and Autism Screen (LLAS) is an automated vocal production analysis that has been shown to be a valid screener for autism in hearing children between the ages of 24 to 48 months of age. Although there is reportedly a higher incidence of autism among children who are deaf or hard of hearing, the diagnosis of autism is usually later than that in children with hearing. None of the traditional screening instruments have been used with children with hearing loss. Data about the utility of LLAS with children who are deaf or hard of hearing will be presented and discussed. Though more data will be needed, an LLAS at-risk flag in conjunction with the Social Quotient from the Child Development Inventory holds significant promise for a screen for children who are deaf or hard of hearing. C1 [Xu, Dongxin] LENA Fdn, Boulder, CO USA. [Carr, Jason; Yoshinaga-Itano, Christine] Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. RP Carr, J (reprint author), Univ Colorado, Dept Speech, Campus Box 409, Boulder, CO 80309 USA. EM Jason.P.Carr@Co-lorado.EDU FU Disability Research and Dissemination Center (DRDC) [5U01DD001007]; Association of University Centers on Disabilities; Centers for Disease Control (CDC) and Prevention FX This research was supported by the Disability Research and Dissemination Center (DRDC) through its Cooperative Agreement Number 5U01DD001007, from the Association of University Centers on Disabilities, and from the Centers for Disease Control (CDC) and Prevention. 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PD NOV PY 2014 VL 35 IS 4 BP 266 EP 275 DI 10.1055/s-0034-1389099 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500003 PM 25321851 ER PT J AU Kellogg, EC Thrasher, A Yoshinaga-Itano, C AF Kellogg, Elizabeth Cameron Thrasher, Amy Yoshinaga-Itano, Christine TI Early Predictors of Autism in Young Children Who Are Deaf or Hard of Hearing: Three Longitudinal Case Studies SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Autism; deaf; hard of hearing; children; developmental assessment; screening ID SPECTRUM DISORDERS; COMMUNICATIVE DEVELOPMENT; LANGUAGE-DEVELOPMENT; DIAGNOSIS; BEHAVIOR; SKILLS AB Early assessment data (starting at 9 months) for three children who were deaf or hard. of hearing and later diagnosed with autism spectrum disorder (ASD) were analyzed. The results from the MacArthur-Bates Communicative Development Inventories (CDI) Words and Gestures and the Child Development Inventory were used to develop three profiles of children who were deaf or hard of hearing and had ASD. One child lacked expected skills and language at ages 9 and 14 months. Another child lost skills and language after 17 months. The third child had results usually within or above the average range until 3 years of age. However, his age quotient decreased for MacArthur-Bates CDI: Words and Gestures Words Expressed and the Child Development Inventory: Social to significantly below the normal range. Although it can be difficult to diagnose the co-occurrence of ASD and deafness, there were early warning signs for these children. C1 [Kellogg, Elizabeth Cameron; Thrasher, Amy; Yoshinaga-Itano, Christine] Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. RP Kellogg, EC (reprint author), Univ Colorado, Dept Speech Language & Hearing Sci, 2501 Kittredge Loop Rd,409 UCB, Boulder, CO 80309 USA. EM elizabeth.kellogg@colorado.edu FU Disability Research and Dissemination Center (DRDC) [5U01DD001007]; Association of University Centers on Disabilities; Centers for Disease Control (CDC) and Prevention FX This research was supported by the Disability Research and Dissemination Center (DRDC) through its Cooperative Agreement Number 5U01DD001007, from the Association of University Centers on Disabilities, and from the Centers for Disease Control (CDC) and Prevention. 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Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 276 EP 287 DI 10.1055/s-0034-1389100 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500004 PM 25321852 ER PT J AU Mood, D Shield, A AF Mood, Deborah Shield, Aaron TI Clinical Use of the Autism Diagnostic Observation Schedule-Second Edition with Children Who Are Deaf SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Autism; deaf; ADOS-2; assessment ID SPECTRUM DISORDERS; HEARING-LOSS AB The Autism Diagnostic Observation Schedule Second Edition (ADOS-2) was administered to eight children who are deaf and who are native American Sign Language (ASL) users with previous autism spectrum disorder (ASD) diagnosis. Classification on two different module selection criteria was compared based on: (1) standardized administration rules (signs not counted as equivalent to words) and (2) commonly utilized clinical administration (sign language complexity treated equivalently to spoken language complexity). Differential module selection resulted in discrepant classification in five of the eight cases (63%) and suggests that ADOS-2 via standardized test administration may result in a failure to identify autism among children who are deaf with primary communication in ASL. Two of the eight children (25%) did not exceed the cutoff for an ASD classification on either module administered despite previous ASD diagnosis. Overall results suggest that caution should be used when utilizing the ADOS-2 with children who are deaf who primarily communicate using ASL. C1 [Mood, Deborah] Childrens Hosp Colorado, Child Dev Unit, Aurora, CO 80045 USA. [Shield, Aaron] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Mood, D (reprint author), Childrens Hosp Colorado, Child Dev Unit, 13123 E 16th Ave,Box 140, Aurora, CO 80045 USA. EM Deborah.Mood@childrenscolorado.org FU National Institute on Deafness and other Communication Disorders [1F32 DC0011219] FX We would like to thank Dr. Terry Katz and Dr. Susan Hepburn for their review of an earlier version of this article. Support for this research was provided by a postdoctoral fellowship from the National Institute on Deafness and other Communication Disorders to the second author (Grant #1F32 DC0011219). CR AERA (American Education Research Association) APA and The National Council on Measurement in Education, 1999, STAND ED PSYCH TEST American Psychiatric Association, 2010, DIAGN STAT MAN MENT American Psychiatric Association, 2013, DIAGN STAT MAN MENT Berument SK, 2005, J AUTISM DEV DISORD, V35, P821, DOI 10.1007/s10803-005-0027-4 Centers for Disease Control Prevention (CDC), 2014, MMWR RECOMM REP, V63, P1 Harris M., 1989, 1 LANGUAGE, V9, P81, DOI 10.1177/014272378900902507 Izycky A, 2011, INT M DEAF CHILDR AU JURE R, 1991, DEV MED CHILD NEUROL, V33, P1062 Liddell SK, 2003, GRAMMAR GESTURE MEAN Lord C, 2012, AUTISM DIAGNOSTIC OB, V2 Meinzen-Derr J, 2014, INT J PEDIATR OTORHI, V78, P112, DOI 10.1016/j.ijporl.2013.10.065 Mitchell Ross, 2004, SIGN LANGUAGE STUDIE, V4, P138, DOI DOI 10.1353/SLS.2004.0005 Neidle C, 2000, SYNTAX AM SIGN LANGU Padden C, 1988, INTERACTION MORPHOLO Peterson CC, 2005, CHILD DEV, V76, P502, DOI 10.1111/j.1467-8624.2005.00859.x Roper L, 2003, AUTISM, V7, P245, DOI 10.1177/1362361303007003002 Rosenhall U, 1999, J AUTISM DEV DISORD, V29, P349, DOI 10.1023/A:1023022709710 Scott M, MCHB AUCD WEB FEBR 2 Shield A, 2012, J COMMUN DISORD, V45, P439, DOI 10.1016/j.jcomdis.2012.08.004 Shield A, 2014, SEMIN SPEECH LANG, V35, P241 Swisher V, 2000, DEAF CHILD FAMILY SC, P21 Szarkowski A, 2014, SEMIN SPEECH LANG, V35, P309 Szymanski C., 2008, ODYSSEY NEW DIRECTIO, V9, P10 Szymanski C, THESIS GALLAUDET U W Szymanski CA, 2012, J AUTISM DEV DISORD, V42, P2027, DOI 10.1007/s10803-012-1452-9 Yoshinaga-Itano C, 1998, PEDIATRICS, V102, P1161, DOI 10.1542/peds.102.5.1161 NR 26 TC 3 Z9 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-0478 EI 1098-9056 J9 SEMIN SPEECH LANG JI Semin. Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 288 EP 300 DI 10.1055/s-0034-1389101 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500005 PM 25321853 ER PT J AU Szarkowski, A Flynn, S Clark, T AF Szarkowski, Amy Flynn, Suzanne Clark, Terrell TI Dually Diagnosed: A Retrospective Study of the Process of Diagnosing Autism Spectrum Disorders in Children Who Are Deaf and Hard of Hearing SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE ASD; autism; deaf and hard of hearing; diagnosis; retrospective study ID WILLIAMS-SYNDROME; YOUNG-CHILDREN AB Utilizing a retrospective chart review of 30 children who have been dually diagnosed with hearing loss and autism spectrum disorders (ASDs), this study explores the process of arriving at the diagnosis of ASD in this population. Factors of interest include the age of ASD diagnosis in children who are deaf and hard of hearing, the types of professionals involved in making the diagnosis, and the measures used for assessment. Complications in the diagnostic process are highlighted. C1 [Szarkowski, Amy; Clark, Terrell] Boston Childrens Hosp, Deaf & Hard Hearing Program, Boston, MA USA. [Flynn, Suzanne] Boston Childrens Hosp, Autism Language Program, Boston, MA USA. [Szarkowski, Amy; Clark, Terrell] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Flynn, Suzanne] MIT, Dept Linguist, Cambridge, MA 02139 USA. RP Szarkowski, A (reprint author), Boston Childrens Hosp Waltham, 2nd Floor,West Wing,9 Hope Ave, Waltham, MA 02453 USA. EM Amy.Szarkowski@childrens.harvard.edu CR American Psychiatric Association, 2013, DSM5 AM PSYCH ASS Bauman ML, 2010, NEUROTHERAPEUTICS, V7, P320, DOI 10.1016/j.nurt.2010.06.001 Bellugi U, 1999, NEUROREPORT, V10, P1653, DOI 10.1097/00001756-199906030-00006 Carter JC, 2007, AM J MED GENET B, V144B, P87, DOI 10.1002/ajmg.b.30407 Charman T, 2013, CHILD ADOL MENT H-UK, V18, P52, DOI 10.1111/j.1475-3588.2012.00664.x Falkmer T, 2013, EUR CHILD ADOLES PSY, V22, P329, DOI 10.1007/s00787-013-0375-0 Gearing Robin E, 2006, J Can Acad Child Adolesc Psychiatry, V15, P126 Klein-Tasman BP, 2009, J DEV BEHAV PEDIATR, V30, P289, DOI 10.1097/DBP.0b013e3181ad1f9a Klein-Tasman BP, 2003, DEV NEUROPSYCHOL, V23, P269, DOI 10.1207/S15326942DN231&2_12 Kozlowski AM, 2011, DEV NEUROREHABIL, V14, P72, DOI 10.3109/17518423.2010.539193 Lee H, 2010, AM J MED GENET B, V153B, P1119, DOI 10.1002/ajmg.b.31103 Lord C, 2000, COMM LANG INTERVEN, V9, P11 Matt V, 2013, J ED EVAL HLTH PROF, V10, P12 Meyer-Lindenberg A, 2012, INSIGHTS AUTISM WILL Mishaal RA, 2014, RES AUTISM SPECT DIS, V8, P873, DOI 10.1016/j.rasd.2014.04.001 Mood D, 2014, SEMIN SPEECH LANG, V35, P288, DOI 10.1055/s-0034-1389101 Rosenberg R. R., 2011, AUTISM RES TREAT, V2011, DOI DOI 10.1155/2011/874619 NR 17 TC 1 Z9 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-0478 EI 1098-9056 J9 SEMIN SPEECH LANG JI Semin. Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 301 EP 308 DI 10.1055/s-0034-1389102 PG 8 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500006 PM 25321854 ER PT J AU Shield, A AF Shield, Aaron TI Preliminary Finaings of Similarities and Differences in the Signed and Spoken Language of Children with Autism SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Sign language; autism; language acquisition; echolalia; pronouns ID VISUAL PERSPECTIVE-TAKING; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; PERSONAL PRONOUNS; DEAF-CHILDREN; COMMUNICATION; GESTURE; RECOGNITION; INFORMATION; EMOTIONS AB Approximately 30% of hearing children with autism spectrum disorder (ASD) do not acquire expressive language, and those who do often show impairments related to their social deficits, using language instrumentally rather than socially, with a poor understanding of pragmatics and a tendency toward repetitive content. Linguistic abnormalities can be clinically useful as diagnostic markers of ASD and as targets for intervention. Studies have begun to document how ASD manifests in children who are deaf for whom signed languages are the primary means of communication. Though the underlying disorder is presumed to be the same in children who are deaf and children who hear, the structures of signed and spoken languages differ in key ways. This article describes similarities and differences between the signed and spoken language acquisition of children on the spectrum. Similarities include echolalia, pronoun avoidance, neologisms, and the existence of minimally verbal children. Possible areas of divergence include pronoun reversal, palm reversal, and facial grammar. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Shield, A (reprint author), Boston Univ, Dept Psychol, 64 Cummington Mall, Boston, MA 02215 USA. EM ashield@bu.edu FU National Institute on Deafness and Other Communication Disorders [1F32 DC0011219]; Autism Science Foundation FX The author wishes to thank Lisa Wisman Well and Christine Yoshinaga-Itano for comments on an earlier version of this article. Support for this research was provided by the National Institute on Deafness and Other Communication Disorders (Postdoctoral Fellowship 1F32 DC0011219) and the Autism Science Foundation. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Anderson D, 1998, SIGN LANGUAGE LINGUI, V2, P117 Baker CL, 1983, UNDERSTANDING LANGUA, P27 BARONCOHEN S, 1993, COGNITION EMOTION, V7, P507, DOI 10.1080/02699939308409202 BARTAK L, 1974, J AUTISM CHILD SCHIZ, V4, P217, DOI 10.1007/BF02115227 Bogdashina O., 2005, COMMUNICATION ISSUES Bondy A. S., 1994, FOCUS AUTISTIC BEHAV, V9, P1, DOI DOI 10.1177/108835769400900301 Bonvillian J. 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Speech Lang. PD NOV PY 2014 VL 35 IS 4 BP 309 EP 320 DI 10.1055/s-0034-1389103 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500007 PM 25321855 ER PT J AU Thompson, N Yoshinaga-Itano, C AF Thompson, Nanette Yoshinaga-Itano, Christine TI Enhancing the Development of Infants and Toddlers with Dual Diagnosis of Autism Spectrum Disorder and Deafness SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Autism; deaf; hard of hearing; early intervention; auditory; sign language ID HEARING-LOSS; CHILDREN; INTERVENTION; LANGUAGE; TEACCH AB Children diagnosed with autism spectrum disorder (ASD) are often referred for audiological diagnostic evaluation. This article provides some strategies for preparing children for a successful diagnostic evaluation. Children who are deaf or hard of hearing with a dual diagnosis of ASD may have difficulty learning to demonstrate detection or imitation of the Ling 6 sounds. The Ling 6 sounds are used to determine what a child with a dual diagnosis can hear and discriminate with amplification (hearing aids or cochlear implants). Because children with ASD may not look at the conversational partner and may have difficulty with imitation, adaptive strategies may be necessary to teach these children with dual diagnosis their first words. Strategies for teaching children with dual diagnosis through sign language will also be discussed. C1 [Thompson, Nanette] Univ Hosp, Denver, CO USA. [Yoshinaga-Itano, Christine] Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. RP Yoshinaga-Itano, C (reprint author), Univ Colorado, Dept Speech Language & Hearing Sci, Campus Box 409, Boulder, CO 80309 USA. 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PD NOV PY 2014 VL 35 IS 4 BP 321 EP 330 DI 10.1055/s-0034-1389104 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500008 PM 25321856 ER PT J AU Thrasher, A AF Thrasher, Amy TI Video Modeling for Children with Dual Diagnosis of Deafness or Hard of Hearing and Autism Spectrum Disorder to Promote Peer Interaction SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Autism; deaf; intervention; video modeling; peer interaction ID JOINT ATTENTION; COMMUNICATION; LANGUAGE; SKILLS; PLAY AB This article describes an intervention program offered at the University of Colorado Boulder that supports peer interaction among young children with autism spectrum disorders and their typical peers using a multicomponent approach, including video modeling. Characteristics of autism that may interfere with the development of peer interaction in young children will be discussed. 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PD NOV PY 2014 VL 35 IS 4 BP 331 EP 341 DI 10.1055/s-0034-1389105 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AR1WO UT WOS:000343375500009 PM 25321857 ER PT J AU Seol, KI Song, SH Kim, KL Oh, ST Kim, YT Im, WY Song, DH Cheon, KA AF Seol, Kyeong In Song, Seung Ha Kim, Ka Lim Oh, Seung Taek Kim, Young Tae Im, Woo Young Song, Dong Ho Cheon, Keun-Ah TI A Comparison of Receptive-Expressive Language Profiles between Toddlers with Autism Spectrum Disorder and Developmental Language Delay SO YONSEI MEDICAL JOURNAL LA English DT Article DE Autism spectrum disorder; toddlers; receptive language; expressive language ID EARLY IDENTIFICATION; ASPERGER-SYNDROME; COMPLEX SOUNDS; VIDEO ANALYSIS; HOME VIDEO; CHILDREN; INFANTS; LIFE; RECOGNITION; IMPAIRMENT AB Purpose: It is well known that expressive language impairment is commonly less severe than receptive language impairment in children with autism spectrum disorder (ASD). However, this result is based on experiments in Western countries with Western language scales. This study tries to find whether the result above is applicable for toddlers in a non-Western country; more specifically, in Korea with nonWestern language scales. Materials and Methods: The participants were 166 toddlers aged between 20 months and 50 months who visited the clinic from December 2010 to January 2013. The number of toddlers diagnosed as ASD and developmental language delay (DLD) was 103 and 63, respectively. Language development level was assessed using Sequenced Language Scale for Infants (SELSI), a Korean language scale. Using SELSI, each group was divided into 3 sub-groups. Moreover, the group difference by age was observed by dividing them into three age groups. Chisquare test and linear-by-linear association was used for analysis. Results: Receptive language ability of the DLD group was superior to that of the ASD group in all age groups. However, expressive language ability in both groups showed no difference in all age groups. A greater proportion of expressive dominant type was found in ASD. The 20-29 months group in ASD showed the largest proportion of expressive language dominant type in the three age groups, suggesting that the younger the ASD toddler is, the more severe the receptive language impairment is. Conclusion: These findings suggest that receptive-expressive language characteristics in ASD at earlier age could be useful in the early detection ofASD. C1 [Seol, Kyeong In; Song, Seung Ha; Kim, Ka Lim; Oh, Seung Taek; Song, Dong Ho; Cheon, Keun-Ah] Yonsei Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Coll Med, Seoul 120752, South Korea. [Seol, Kyeong In; Song, Seung Ha; Kim, Ka Lim; Oh, Seung Taek; Song, Dong Ho; Cheon, Keun-Ah] Yonsei Univ, Inst Behav Sci Med, Coll Med, Seoul 120752, South Korea. [Kim, Young Tae] Ewha Womans Univ, Dept Commun Disorder, Seoul, South Korea. [Im, Woo Young] Konyang Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Coll Med, Taejon, South Korea. RP Cheon, KA (reprint author), Yonsei Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Severance Hosp,Coll Med, 50-1 Yonsei Ro, Seoul 120752, South Korea. EM kacheon@yuhs.ac FU Ministry of Health & Welfare, Republic of Korea [HI12C0021, HI12C0245-A120029]; Yonsei University College of Medicine [6-2010-0139] FX This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0021, HI12C0245-A120029).This study was supported by a faculty research grant of Yonsei University College of Medicine for 2010 (6-2010-0139). CR Amaral D., 2011, AUTISM SPECTRUM DISO [Anonymous], 2013, DIAGN STAT MAN MENT Baranek GT, 1999, J AUTISM DEV DISORD, V29, P213, DOI 10.1023/A:1023080005650 Boddaert N, 2004, AM J PSYCHIAT, V161, P2117, DOI 10.1176/appi.ajp.161.11.2117 Boddaert N, 2003, AM J PSYCHIAT, V160, P2057, DOI 10.1176/appi.ajp.160.11.2057 Clifford S, 2007, J AUTISM DEV DISORD, V37, P301, DOI 10.1007/s10803-006-0160-8 Clifford SM, 2008, J AUTISM DEV DISORD, V38, P791, DOI 10.1007/s10803-007-0444-7 De Giacomo A, 1998, EUR CHILD ADOLES PSY, V7, P131 Eaves LC, 2004, J AUTISM DEV DISORD, V34, P367, DOI 10.1023/B:JADD.0000037414.33270.a8 FAY WH, 1977, BRAIN LANG, V4, P396, DOI 10.1016/0093-934X(77)90034-7 Fenson Larry, 1994, Monographs of the Society for Research in Child Development, V59, P1 Grossi D, 2013, J INTELL DISABIL RES, V57, P903, DOI 10.1111/j.1365-2788.2012.01579.x Hudry K, 2010, INT J LANG COMM DIS, V45, P681, DOI 10.3109/13682820903461493 Iverson JM, 2007, J AUTISM DEV DISORD, V37, P158, DOI 10.1007/s10803-006-0339-z Kim YT, 2002, COMMUN SCI DIS, V7, P1 Kjelgaard MM, 2001, LANG COGNITIVE PROC, V16, P287 VENTER A, 1992, J CHILD PSYCHOL PSYC, V33, P489, DOI 10.1111/j.1469-7610.1992.tb00887.x Loukusa S, 2007, J AUTISM DEV DISORD, V37, P1049, DOI 10.1007/s10803-006-0247-2 Luyster RJ, 2008, J AUTISM DEV DISORD, V38, P1426, DOI 10.1007/s10803-007-0510-1 Maestro S, 2001, PSYCHOPATHOLOGY, V34, P147, DOI 10.1159/000049298 Maestro S, 2005, PSYCHOPATHOLOGY, V38, P26, DOI 10.1159/000083967 Mitchell S, 2006, J DEV BEHAV PEDIATR, V27, pS69, DOI 10.1097/00004703-200604002-00004 Osterling JA, 2002, DEV PSYCHOPATHOL, V14, P239 RUTTER M, 1992, SPECIFIC SPEECH AND LANGUAGE DISORDERS IN CHILDREN : CORRELATES, CHARACTERISTICS AND OUTCOMES, P63 Sharp HM, 2008, PEDIATR CLIN N AM, V55, P1159, DOI 10.1016/j.pcl.2008.07.007 Szatmari P, 2009, J CHILD PSYCHOL PSYC, V50, P1459, DOI 10.1111/j.1469-7610.2009.02123.x Tager-Flusberg H., 2005, HDB AUTISM PERVASIVE, P335 Tager-Flusberg H, 2007, PEDIATR CLIN N AM, V54, P469, DOI 10.1016/j.pcl.2007.02.011 Watson LR, 2013, AM J SPEECH-LANG PAT, V22, P25, DOI 10.1044/1058-0360(2012/11-0145) Weismer SE, 2010, J AUTISM DEV DISORD, V40, P1259, DOI 10.1007/s10803-010-0983-1 Zwaigenbaum L, 2013, BEHAV BRAIN RES, V251, P133, DOI 10.1016/j.bbr.2013.04.004 Zwaigenbaum L, 2005, INT J DEV NEUROSCI, V23, P143, DOI 10.1016/j.ijdevneu.2004.05.001 NR 32 TC 1 Z9 1 PU YONSEI UNIV COLL MEDICINE PI SEOUL PA 50-1 YONSEI-RO, SEODAEMUN-GU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 EI 1976-2437 J9 YONSEI MED J JI Yonsei Med. J. PD NOV 1 PY 2014 VL 55 IS 6 BP 1721 EP 1728 DI 10.3349/ymj.2014.55.6.1721 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AR7UL UT WOS:000343785100033 PM 25323912 ER PT J AU von Ehrenstein, OS Aralis, H Cockburn, M Ritz, B AF von Ehrenstein, Ondine S. Aralis, Hilary Cockburn, Myles Ritz, Beate TI In Utero Exposure to Toxic Air Pollutants and Risk of Childhood Autism SO EPIDEMIOLOGY LA English DT Article ID SPECTRUM DISORDERS; LOS-ANGELES; ENVIRONMENTAL-FACTORS; TOLUENE EXPOSURE; PRETERM BIRTH; POLLUTION; CALIFORNIA; CHILDREN; POPULATION; AGE AB Background: Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. Methods: Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. Results: Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. Conclusions: Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations. C1 [von Ehrenstein, Ondine S.] Univ Calif Los Angeles, Dept Community Hlth Sci, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Aralis, Hilary] Univ Calif Los Angeles, Dept Biostat, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Cockburn, Myles] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ritz, Beate] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. RP von Ehrenstein, OS (reprint author), Univ Calif Los Angeles, POB 951772, Los Angeles, CA 90095 USA. EM ovehren@ucla.edu RI Ritz, Beate/E-3043-2015 FU National Institute of Environmental Health Sciences [R21ES022389]; California Center for Population Research, UCLA; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R24HD041022] FX Supported by the National Institute of Environmental Health Sciences R21ES022389 and the California Center for Population Research, UCLA, supported by infrastructure grant R24HD041022 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. 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