FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Schmitt, LM Cook, EH Sweeney, JA Mosconi, MW AF Schmitt, Lauren M. Cook, Edwin H. Sweeney, John A. Mosconi, Matthew W. TI Saccadic eye movement abnormalities in autism spectrum disorder indicate dysfunctions in cerebellum and brainstem SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder (ASD); Sensorimotor; Eye movement; Saccade; Cerebellum; Brainstem ID DIAGNOSTIC OBSERVATION SCHEDULE; CAUDAL FASTIGIAL NUCLEUS; HIGH-FUNCTIONING AUTISM; BURST NEURONS; SUPERIOR COLLICULUS; OCULOMOTOR REGION; REPETITIVE BEHAVIOR; INFANTILE-AUTISM; VISUAL-ATTENTION; MACAQUE MONKEYS AB Background: Individuals with autism spectrum disorder (ASD) show atypical scan paths during social interaction and when viewing faces, and recent evidence suggests that they also show abnormal saccadic eye movement dynamics and accuracy when viewing less complex and non-social stimuli. Eye movements are a uniquely promising target for studies of ASD as their spatial and temporal characteristics can be measured precisely and the brain circuits supporting them are well-defined. Control of saccade metrics is supported by discrete circuits within the cerebellum and brainstem two brain regions implicated in magnetic resonance (MR) morphometry and histopathological studies of ASD. The functional integrity of these distinct brain systems can be examined by evaluating different parameters of visually-guided saccades. Methods: A total of 65 participants with ASD and 43 healthy controls, matched on age (between 6 and 44-years-old), gender and nonverbal IQ made saccades to peripheral targets. To examine the influence of attentional processes, blocked gap and overlap trials were presented. We examined saccade latency, accuracy and dynamics, as well as the trial-to-trial variability of participants' performance. Results: Saccades of individuals with ASD were characterized by reduced accuracy, elevated variability in accuracy across trials, and reduced peak velocity and prolonged duration. In addition, their saccades took longer to accelerate to peak velocity, with no alteration in the duration of saccade deceleration. Gap/overlap effects on saccade latencies were similar across groups, suggesting that visual orienting and attention systems are relatively spared in ASD. Age-related changes did not differ across groups. Conclusions: Deficits precisely and consistently directing eye movements suggest impairment in the error-reducing function of the cerebellum in ASD. Atypical increases in the duration of movement acceleration combined with lower peak saccade velocities implicate pontine nuclei, specifically suggesting reduced excitatory activity in burst cells that drive saccades relative to inhibitory activity in omnipause cells that maintain stable fixation. Thus, our findings suggest that both cerebellar and brainstem abnormalities contribute to altered sensorimotor control in ASD. C1 [Schmitt, Lauren M.; Sweeney, John A.; Mosconi, Matthew W.] Univ Texas Southwestern, Ctr Autism & Dev Disabil, Dallas, TX 75390 USA. [Cook, Edwin H.] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA. [Sweeney, John A.] Bond Univ, Ctr Autism Spectrum Disorders, Gold Coast, Qld 4229, Australia. [Mosconi, Matthew W.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Mosconi, Matthew W.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. RP Mosconi, MW (reprint author), Univ Texas Southwestern, Ctr Autism & Dev Disabil, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Matt.Mosconi@UTSouthwestern.edu FU NIH Autism Center of Excellence grant [P50HD055751]; NIH K23 Research Career Development Award [MH092696]; Autism Speaks [4853] FX This work was supported by NIH Autism Center of Excellence grant P50HD055751 (EHC, JAS, MWM), NIH K23 Research Career Development Award MH092696 (MWM) and an Autism Speaks grant 4853 (MWM). 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Autism PD SEP 16 PY 2014 VL 5 AR 47 DI 10.1186/2040-2392-5-47 PG 13 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AS2JG UT WOS:000344105400001 PM 25400899 ER PT J AU Lukoshe, A Hokken-Koelega, AC van der Lugt, A White, T AF Lukoshe, Akvile Hokken-Koelega, Anita C. van der Lugt, Aad White, Tonya TI Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; AUTISM SPECTRUM DISORDERS; MAGNETIC-RESONANCE IMAGES; GROWTH-HORMONE TREATMENT; MENTAL-RETARDATION; HUMAN BRAIN; GENETIC SUBTYPES; GYRIFICATION; MRI; SCHIZOPHRENIA AB Background: Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods: High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age-and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results: Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions: These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development. C1 [Lukoshe, Akvile; Hokken-Koelega, Anita C.] Dutch Growth Res Fdn, Rotterdam, Netherlands. [Lukoshe, Akvile; Hokken-Koelega, Anita C.] Sophia Childrens Univ Hosp, Erasmus Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands. [White, Tonya] Sophia Childrens Univ Hosp, Erasmus Med Ctr Rotterdam, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [van der Lugt, Aad; White, Tonya] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. RP Lukoshe, A (reprint author), Dutch Growth Res Fdn, Rotterdam, Netherlands. EM a.lukose@kindengroei.nl FU Foundation for Prader-Willi Research; Dutch Growth Research Foundation FX This study was financially supported by the Foundation for Prader-Willi Research and Dutch Growth Research 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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Asperger Syndrome (AS); Oxytocin receptor (OXTR); Haplotype analysis ID SINGLE-NUCLEOTIDE POLYMORPHISMS; AUTISTIC TRAITS; SOCIAL-BEHAVIOR; POPULATION; DISORDER; TWIN; PREVALENCE; EXPRESSION; STABILITY; CHILDREN AB Background: Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods: The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results: There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs22684 90-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions: This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS. C1 [Di Napoli, Agnese; Warrier, Varun; Baron-Cohen, Simon; Chakrabarti, Bhismadev] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust, CLASS Clin, Cambridge CB21 5EF, England. [Chakrabarti, Bhismadev] Univ Reading, Sch Psychol & Clin Language Sci, Ctr Integrat Neurosci & Neurodynam, Reading RG6 6AL, Berks, England. RP Di Napoli, A (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. EM agnesedinapoli@outlook.com; sb205@cam.ac.uk FU Target Autism Genome; Nancy Lurie Marks (NLM) Family Foundation; Autism Research Trust; Medical Research Council United Kingdom; Wellcome Trust Sanger Centre; Max Planck Institute for Psycholinguistics; Nehru Trust for Cambridge University; St John's College Cambridge; Cambridge Commonwealth Trust FX This study was funded by project grants to SBC from Target Autism Genome, the Nancy Lurie Marks (NLM) Family Foundation, the Autism Research Trust, the Medical Research Council United Kingdom, the Wellcome Trust Sanger Centre, and the Max Planck Institute for Psycholinguistics. BC was funded by the Medical Research Council United Kingdom. VW was funded by the Nehru Trust for Cambridge University, St John's College Cambridge, and the Cambridge Commonwealth Trust, and this work was submitted in part fulfilment of the degree of MPhil at Cambridge University by VW. The study was undertaken in association with the National Institute of Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC) East of England (EoE). We are thankful to Robert Plomin, Frank Dudbridge, Lindsey Kent and Ian Craig for discussions, and to Laura Murphy, Jon Breidbord, Allen Chan, Sylvia Lakatosova, Sally Wheelwright, Carrie Allison, Uma Mallya, Alex Politt, and the late Leena Peltonen for support at different stages of the project. Simon Fisher provided part funding for the project. 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Autism PD SEP 16 PY 2014 VL 5 AR 48 DI 10.1186/2040-2392-5-48 PG 7 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AS2JH UT WOS:000344105700001 PM 25264479 ER PT J AU Burrage, LC Nagamani, SCS Campeau, PM Lee, BH AF Burrage, Lindsay C. Nagamani, Sandesh C. S. Campeau, Philippe M. Lee, Brendan H. TI Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders SO HUMAN MOLECULAR GENETICS LA English DT Article ID SYRUP-URINE-DISEASE; ALPHA-KETO-ACIDS; DOMINO LIVER-TRANSPLANTATION; BRAIN ENERGY-METABOLISM; UREA CYCLE DISORDERS; OXIDATIVE STRESS; INBORN-ERRORS; RAT-BRAIN; BIOCHEMICAL BASIS; IN-VITRO AB Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysiology of both rare inborn errors of metabolism and the more common multifactorial diseases. Although deficiency of the branched-chain ketoacid dehydrogenase(BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. In recent years, the discovery of improved leucine tolerance after liver transplantation has resulted in a new therapeutic strategy for this disorder. Likewise, targeting the regulation of the BCKDC activity may be an alternative potential treatment strategy for MSUD. The regulation of the BCKDC by the branched-chain ketoacid dehydrogenase kinase has also been implicated in a new inborn error of metabolism characterized by autism, intellectual disability and seizures. Finally, there is a growing body of literature implicating BCAA metabolism in more common disorders such as the metabolic syndrome, cancer and hepatic disease. This review surveys the knowledge acquired on the topic over the past 50 years and focuses on recent developments in the field of BCAA metabolism. C1 [Burrage, Lindsay C.; Nagamani, Sandesh C. S.; Lee, Brendan H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Campeau, Philippe M.] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Lee, Brendan H.] Howard Hughes Med Inst, Houston, TX 77030 USA. RP Lee, BH (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM blee@bcm.edu FU ACMG Foundation/Genzyme Biochemical Genetics Fellowship; Clinical Scientist Development Award by the Doris Duke Charitable Foundation; O'Malley Foundation Research Fellowship; NIH [DK92921]; Baylor College of Medicine General Clinical Research Center [RR00188]; BCM Intellectual and Developmental Disabilities Research Center [HD024064]; Eunice Kennedy Shriver National Institute Of Child Health & Human Development; Urea Cycle Disorders Research Consortium a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN) [U54 HD061221]; NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS); NICHD FX L.C.B. is supported by the ACMG Foundation/Genzyme Biochemical Genetics Fellowship. S.C.S.N. is supported by the Clinical Scientist Development Award by the Doris Duke Charitable Foundation. P.M.C. was supported by the O'Malley Foundation Research Fellowship. This work was supported by the NIH (DK92921 to B.L.), Baylor College of Medicine General Clinical Research Center (RR00188), the BCM Intellectual and Developmental Disabilities Research Center (HD024064) from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development and the Urea Cycle Disorders Research Consortium (U54 HD061221, a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS) and the NICHD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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Priori, Silvia Pessia, Mauro TI Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype SO HUMAN MOLECULAR GENETICS LA English DT Article ID ANDERSEN-TAWIL-SYNDROME; GAIN-OF-FUNCTION; KCNJ2 MUTATION; POTASSIUM CHANNELS; MEGALENCEPHALIC LEUKOENCEPHALOPATHY; ATRIAL-FIBRILLATION; K+ CHANNELS; CELLS; BRAIN; CHOLESTEROL AB Short QT3 syndrome (SQT3S) is a cardiac disorder characterized by a high risk of mortality and associated with mutations in Kir2.1 (KCNJ2) channels. The molecular mechanisms leading to channel dysfunction, cardiac rhythm disturbances and neurodevelopmental disorders, potentially associated with SQT3S, remain incompletely understood. Here, we report on monozygotic twins displaying a short QT interval on electrocardiogram recordings and autism-epilepsy phenotype. Genetic screening identified a novel KCNJ2 variant in Kir2.1 that (i) enhanced the channel's surface expression and stability at the plasma membrane, (ii) reduced protein ubiquitylation and degradation, (iii) altered protein compartmentalization in lipid rafts by targeting more channels to cholesterol-poor domains and (iv) reduced interactions with caveolin 2. Importantly, our study reveals novel physiological mechanisms concerning wild-type Kir2.1 channel processing by the cell, such as binding to both caveolin 1 and 2, protein degradation through the ubiquitin-proteasome pathway; in addition, it uncovers a potential multifunctional site that controls Kir2.1 surface expression, protein half-life and partitioning to lipid rafts. The reported mechanisms emerge as crucial also for proper astrocyte function, suggesting the need for a neuropsychiatric evaluation in patients with SQT3S and offering new opportunities for disease management. C1 [Ambrosini, Elena; Brignone, Maria S.; Lanciotti, Angela] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Sicca, Federico; Moro, Francesca; Valvo, Giulia; Guerrini, Renzo] IRCCS Stella Maris Fdn, Clin Neurophysiol Lab, Dept Dev Neurosci, Pisa, Italy. [Marchese, Maria; Santorelli, Filippo M.] IRCCS Stella Maris Fdn, Mol Med Lab, Pisa, Italy. [D'Adamo, Maria C.; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro] Univ Perugia, Fac Med, Sect Physiol & Biochem, Dept Expt Med, I-06100 Perugia, Italy. [Pieroni, Stefania; Servillo, Giuseppe] Univ Perugia, Fac Med, Dept Expt Med, I-06100 Perugia, Italy. [Catacuzzeno, Luigi; Franciolini, Fabio] Univ Perugia, Dept Chem Biol & Biotechnol, I-06100 Perugia, Italy. [Napolitano, Carlo; Ruan, Yanfei; Priori, Silvia] IRCCS Salvatore Maugeri Fdn, Pavia, Italy. [Molinari, Paola] Ist Super Sanita, Dept Pharmacol, I-00161 Rome, Italy. [Grottesi, Alessandro] CASPUR, Computat Med & Biol Grp, Rome, Italy. [Guerrini, Renzo] Univ Florence, Childrens Hosp A Meyer, Pediat Neurol Unit & Labs, Florence, Italy. RP Ambrosini, E (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM elena.ambrosini@iss.it RI Catacuzzeno, Luigi/M-4637-2014 FU Telethon grant [GGP11188]; MIUR-PRIN [20108WT59Y_004]; COMPAGNIA di San Paolo (Turin) 'Programma Neuroscienze'; Ministero della Salute [GR-2009-1580433]; Fondazione Cassa di Risparmio di Perugia; Telethon grants [GGP11141, GGP06007]; Fondation Leducq Award [08CVD01]; Fondazione Veronesi Award on inherited arrhythmogenic diseases FX This work was supported by Telethon grant (GGP11188), MIUR-PRIN (20108WT59Y_004), COMPAGNIA di San Paolo (Turin) 'Programma Neuroscienze', Ministero della Salute (GR-2009-1580433) and Fondazione Cassa di Risparmio di Perugia, Telethon grants GGP11141 and GGP06007 (to S. G. P.), Fondation Leducq Award 08CVD01 (to S. G. 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Mol. Genet. PD SEP 15 PY 2014 VL 23 IS 18 BP 4875 EP 4886 DI 10.1093/hmg/ddu201 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AQ9OF UT WOS:000343184400011 PM 24794859 ER PT J AU Oginsky, MF Cui, NR Zhong, WW Johnson, CM Jiang, C AF Oginsky, Max F. Cui, Ningren Zhong, Weiwei Johnson, Christopher M. Jiang, Chun TI Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE acetylcholine; nicotinic acetylcholine receptor; compensatory mechanisms; locus coeruleus; Mecp2; Rett syndrome ID NICOTINIC ACETYLCHOLINE-RECEPTORS; LOCUS-COERULEUS NEURONS; FACILITATES INHIBITORY TRANSMISSION; SINGLE-CHANNEL PROPERTIES; MECP2-NULL MICE; SYNAPTIC-TRANSMISSION; SUBSTANTIA-GELATINOSA; TYROSINE-HYDROXYLASE; CO2 CHEMOSENSITIVITY; GABAERGIC NEURONS AB Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post-and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of alpha(3)-, alpha(4)-, alpha(7)-, and beta(3)-subunits and an increase in the alpha(5)- and alpha(6)-subunits in the mutant mice. The alpha(5)-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABA(A)-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons. C1 [Oginsky, Max F.; Cui, Ningren; Zhong, Weiwei; Johnson, Christopher M.; Jiang, Chun] Georgia State Univ, Dept Biol, Atlanta, GA 30302 USA. RP Jiang, C (reprint author), Georgia State Univ, Dept Biol, 100 Piedmont Ave, Atlanta, GA 30302 USA. EM cjiang@gsu.edu FU National Institute of Neurological Disorders and Stroke [NS-073875] FX This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-073875. 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TI Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Ca-2 waves; DISC1; IP3; mGluR5; persistent activity; prefrontal cortex ID DEPENDENT PROTEIN-KINASE; SPATIAL WORKING-MEMORY; POTASSIUM CHANNEL; BIPOLAR DISORDER; RHESUS-MONKEYS; PSYCHIATRIC-ILLNESS; CANDIDATE GENE; CAG REPEAT; DISC1; BRAIN AB Background: Disrupted in schizophrenia 1 (DISC1) is a protein implicated in schizophrenia, bipolar disorder, major depressive disorder, and autism. To date, most of research examining DISC1 function has focused on its role in neurodevelopment, despite its presence throughout life. DISC1 also regulates cyclic adenosine monophosphate (cAMP) signaling by increasing type 4 phosphodiesterase catabolism of cAMP when cAMP concentrations are high. In this study, we tested the hypothesis that DISC1, through its regulation of cAMP, modulates I-SK and I-TRPC channel-mediated ionic currents that we have shown previously to regulate the activity of mature prefrontal cortical pyramidal neurons. Methods: We used patch-clamp recordings in prefrontal cortical slices from adult rats in which DISC1 function was reduced in vivo by short hairpin RNA viral knockdown or in vitro by dialysis of DISC1 antibodies. Results: We found that DISC1 disruption resulted in an increase of metabotropic glutamate receptor-induced intracellular calcium (Ca2+) waves, small-conductance K+ (SK)-mediated hyperpolarization and a decrease of transient receptor potential C (TRPC)-mediated sustained depolarization. Consistent with a role for DISC1 in regulation of cAMP signaling, forskolin-induced cAMP production also increased intracellular Ca2+ waves, I-SK and decreased I-TRPC. Lastly, inhibiting cAMP generation with guanfacine, an alpha 2A-noradrenergic agonist, normalized the function of SK and TRPC channels. Conclusions: Based on our findings, we propose that diminished DISC1 function, such as occurs in some mental disorders, can lead to the disruption of normal patterns of prefrontal cortex activity through the loss of cAMP regulation of metabotropic glutamate receptor-mediated intracellular Ca2+ waves, SK and TRPC channel activity. C1 [El-Hassar, Lynda; Duque, Alvaro; Arnsten, Amy F. T.; Yeckel, Mark F.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Simen, Arthur A.; Patel, Kiran D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Kaczmarek, Leonard K.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. [Arnsten, Amy F. T.; Yeckel, Mark F.] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. RP El-Hassar, L (reprint author), Yale Univ, Sch Med, Dept Neurobiol, SHMB 436,333 Cedar St, New Haven, CT 06510 USA. EM lynda.elhassar@yale.edu FU National Institute on Alcohol Abuse and Alcoholism [1RL1AA017536]; National Institute of Mental Health [RO1-MH067830, P50-MH068789]; National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award (AFTA); National Institutes of Health [DC 01919]; Kavli Foundation FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism 1RL1AA017536 (AFTA and MFY); Kavli Foundation, National Institute of Mental Health RO1-MH067830 and P50-MH068789 (AFTA and MFY); National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award (AFTA); and National Institutes of Health Grant DC 01919 (LKK). 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Psychiatry PD SEP 15 PY 2014 VL 76 IS 6 BP 476 EP 485 DI 10.1016/j.biopsych.2013.12.019 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AN8WT UT WOS:000340887100011 PM 24560582 ER PT J AU Komulainen, E Zdrojewska, J Freemantle, E Mohammad, H Kulesskaya, N Deshpande, P Marchisella, F Mysore, R Hollos, P Michelsen, KA Magard, M Rauvala, H James, P Coffey, ET AF Komulainen, Emilia Zdrojewska, Justyna Freemantle, Erika Mohammad, Hasan Kulesskaya, Natalia Deshpande, Prasannakumar Marchisella, Francesca Mysore, Raghavendra Hollos, Patrik Michelsen, Kimmo A. Magard, Mats Rauvala, Heikki James, Peter Coffey, Eleanor T. TI JNK1 controls dendritic field size in L2/3 and L5 of the motor cortex, constrains soma size, and influences fine motor coordination SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE JNK; dendrite; motor cortex; MAP2; microtubules; cytoskeleton; schizophrenia; behavior ID MICROTUBULE-ASSOCIATED PROTEIN-2; N-TERMINAL KINASE; SYNAPTIC INTEGRATION; PREFRONTAL CORTEX; MOLECULAR-BASIS; PHOSPHORYLATION; NEURONS; SCHIZOPHRENIA; MAP2; ARBORIZATION AB Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia, and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that JNK1 regulates the dendritic field of L2/3 and L5 pyramidal neurons of the mouse motor cortex (M1), the main excitatory pathway controlling voluntary movement. In Jnk1-/- mice, basal dendrite branching of L5 pyramidal neurons is increased in M1, as is cell soma size, whereas in L2/3, dendritic arborization is decreased. We show that JNK1 phosphorylates rat HMVV-MAP2 on T1619, T1622, and T1625 (Uniprot P15146) corresponding to mouse T1617, T1620, T1623, to create a binding motif, that is critical for MAP2 interaction with and stabilization of microtubules, and dendrite growth control. Targeted expression in M1 of GFP-HMVW-MAP2 that is pseudo-phosphorylated on T1619, T1622, and T1625 increases dendrite complexity in L2/3 indicating that JNK1 phosphorylation of HMVV-MAP2 regulates the dendritic field. Consistent with the morphological changes observed in L2/3 and L5, Jnk1-/mice exhibit deficits in limb placement and motor coordination, while stride length is reduced in older animals. In summary, JNK1 phosphorylates HMVV-MAP2 to increase its stabilization of microtubules while at the same time controlling dendrite fields in the main excitatory pathway of M1. Moreover, JNK1 contributes to normal functioning of fine motor coordination. We report for the first time, a quantitative Sholl analysis of dendrite architecture, and of motor behavior in Jnk1-/- mice. Our results illustrate the molecular and behavioral consequences of interrupted JNK1 signaling and provide new ground for mechanistic understanding of those prevalent neuropyschiatric disorders where genetic disruption of the JNK pathway is central. C1 [Komulainen, Emilia; Zdrojewska, Justyna; Freemantle, Erika; Mohammad, Hasan; Deshpande, Prasannakumar; Marchisella, Francesca; Mysore, Raghavendra; Hollos, Patrik; Coffey, Eleanor T.] Abo Akad Univ, Turku Ctr Biotechnol, FIN-20520 Turku, Finland. [Komulainen, Emilia; Zdrojewska, Justyna; Freemantle, Erika; Mohammad, Hasan; Deshpande, Prasannakumar; Marchisella, Francesca; Mysore, Raghavendra; Hollos, Patrik; Coffey, Eleanor T.] Univ Turku, FIN-20520 Turku, Finland. [Kulesskaya, Natalia; Rauvala, Heikki] Univ Helsinki, Ctr Neurosci, Helsinki, Finland. [Michelsen, Kimmo A.] Abo Akad Univ, Dept Biosci, FIN-20520 Turku, Finland. [Magard, Mats; James, Peter] Lund Univ, Inst Immune Technol, Medicon Village, Lund, Sweden. RP Coffey, ET (reprint author), Abo Akad Univ, Turku Ctr Biotechnol, Tykistokatu 6, FIN-20520 Turku, Finland. EM ecoffey@btk.fi FU Academy of Finland [255537, 218125, 125860]; Sigrid Juselius Foundation; FP7 Marie Curie ITN r'BIRTH; Abo Akademi University; Finnish Graduate School of Neuroscience; Turku Graduate School of Biomedical Sciences; CIMO FX This work was supported by grants to Eleanor Coffey from the Academy of Finland (no. 255537; no. 218125, no. 125860), the Sigrid Juselius Foundation, and the FP7 Marie Curie ITN r'BIRTH We acknowledge Abo Akademi University for supporting Eleanor Coffey, the Finnish Graduate School of Neuroscience for support to Emilia Komulainen and Justyna Zdrojewska, and Turku Graduate School of Biomedical Sciences for support to Prasannakumar Deshpande. We acknowledge CIMO for a grant to Raghavendra. Mysore, We thank Elli Oksanen lair technical assistance with molecular cloning. We are grateful to the Cell Imaging Core at Turku Center for Biotechnology for providing imaging devices. 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Importantly, maternal environmental insults can adversely impact subsequent offspring behavior and have been linked with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (AHDH). It is unknown if maternal obesity significantly alters offspring sociability, a key ASD feature, and if altering maternal diet will provide an efficacious intervention paradigm for behavioral deficits. Here we investigated the impact of maternal high fat diet (HFD) and maternal dietary intervention during lactation on offspring behavior and brain inflammation in mice. We found that maternal HFD increased anxiety and decreased sociability in female offspring. Additionally, female offspring from HFD-fed dams also exhibited increased brain IL-1 beta and TNF alpha and microglial activation. Importantly, maternal dietary intervention during lactation was sufficient to alleviate social deficits and brain inflammation. Maternal obesity during gestation alone was sufficient to increase hyperactivity in male offspring, a phenotype that was not ameliorated by dietary intervention. These data suggest that maternal HFD acts as a prenatal/perinatal insult that significantly impacts offspring behavior and inflammation and that dietary intervention during lactation may be an easily translatable, efficacious intervention to offset some of these manifestations. C1 [Kang, Silvia S.; Kurti, Aishe; Fryer, John D.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Fryer, John D.] Mayo Grad Sch, Neurobiol Dis Program, Rochester, MN 55905 USA. [Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Psychiat & Behav Neurosci, Portland, OR 97239 USA. [Fair, Damien A.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. RP Fryer, JD (reprint author), Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM fryer.john@mayo.edu FU Mayo Foundation; GHR Foundation; Mayo Clinic Center for Individualized Medicine; Mayo Clinic Gerstner Family Career Development Award; National Institutes of Health/National Institute of Mental Health (NIH/NIMH) [R03 MH103632]; NIH/NIMH [R00 MH091238, R01 MH096773] FX We would like to thank Chris Fulcher for technical support. Funding sources for JDF: Mayo Foundation, GHR Foundation, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Gerstner Family Career Development Award. Funding sources for SSK: National Institutes of Health/National Institute of Mental Health (NIH/NIMH) R03 MH103632. Funding sources for DAF: NIH/NIMH R00 MH091238 and R01 MH096773. 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V33, P257, DOI 10.1038/ijo.2008.268 NR 84 TC 1 Z9 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD SEP 12 PY 2014 VL 11 AR 156 DI 10.1186/s12974-014-0156-9 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AQ3LZ UT WOS:000342696700001 PM 25212412 ER PT J AU Chen, JL Yu, SY Fu, YM Li, XH AF Chen, Jianling Yu, Shunying Fu, Yingmei Li, Xiaohong TI Synaptic proteins and receptors defects in autism spectrum disorders SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE autism spectrum disorders; synaptic protein; GABA; PSD-95; SHANK3; TAOK2 ID COPY-NUMBER VARIATION; GEPHYRIN-DEFICIENT MICE; NEUROLIGIN GENES NLGN3; OF-FUNCTION MUTATIONS; DE-NOVO; SUSCEPTIBILITY GENE; MENTAL-RETARDATION; INHIBITORY SYNAPSES; WILLIAMS-SYNDROME; MULTIPLE GENES AB Recent studies have found that hundreds of genetic variants, including common and rare variants, rare and de novo mutations, and common polymorphisms contribute to the occurrence of autism spectrum disorders (ASDs). The mutations in a number of genes such as neurexin, neuroligin, postsynaptic density protein 95, SH3, and multiple ankyrin repeat domains 3 (SHANK3), synapsin, gephyrin, cadherin, and protocadherin, thousand-and-one-amino acid 2 kinase, and contactin, have been shown to play important roles in the development and function of synapses. In addition, synaptic receptors, such as gamma-aminobutyric acid receptors and glutamate receptors, have also been associated with ASDs. This review will primarily focus on the defects of synaptic proteins and receptors associated with ASDs and their roles in the pathogenesis of ASDs via synaptic pathways. C1 [Chen, Jianling; Yu, Shunying; Fu, Yingmei] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Shanghai 200030, Peoples R China. [Li, Xiaohong] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA. RP Yu, SY (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, 600 Wanping Nan Rd, Shanghai 200030, Peoples R China. EM yushuny@gmail.com FU Shanghai Jiao Tong University K.C. Wong Medical Fellowship Fund; National Basic Research Program 973 of China [2012CB 517900] FX The author gratefully acknowledges the support of Shanghai Jiao Tong University K.C. Wong Medical Fellowship Fund and the National Basic Research Program 973 of China (Grant No. 2012CB 517900). 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Cell. Neurosci. PD SEP 11 PY 2014 VL 8 AR 276 DI 10.3389/fncel.2014.00276 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AS7WU UT WOS:000344463400001 PM 25309321 ER PT J AU Pedersen, CA Chang, SWC Williams, CL AF Pedersen, Cort A. Chang, Steven W. C. Williams, Christina L. TI Evolutionary perspectives on the role of oxytocin in human social behavior, social cognition and psychopathology SO BRAIN RESEARCH LA English DT Editorial Material ID MATERNAL AGGRESSIVE-BEHAVIOR; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; RANDOMIZED CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDERS; ANXIETY-RELATED BEHAVIOR; FEMALE HOUSE MICE; INTRANASAL OXYTOCIN; HUMAN BRAIN; INCREASES TRUST; RHESUS-MONKEYS C1 [Pedersen, Cort A.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Chang, Steven W. C.] Levine Sci Res Ctr, Ctr Cognit Neurosci, Durham, NC USA. [Williams, Christina L.] Duke Univ, Dept Psychol & Brain Sci, Durham, NC USA. RP Pedersen, CA (reprint author), Univ N Carolina, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. 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PD SEP 11 PY 2014 VL 1580 SI SI BP 1 EP 7 DI 10.1016/j.brainres.2014.07.033 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100001 PM 25091638 ER PT J AU Febo, M Ferris, CF AF Febo, Marcelo Ferris, Craig F. TI Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats SO BRAIN RESEARCH LA English DT Article DE Functional MRI; BOLD fMRI; Rat; Awake rat imaging; Oxytocin; Vasopressin; Maternal rat; Maternal attachment; Fear; Anxiety; Aggression; Aggressive behavior; Autism; Addiction ID ANTERIOR CINGULATE CORTEX; NUCLEUS BASALIS MAGNOCELLULARIS; MESSENGER-RIBONUCLEIC-ACID; AUTISM SPECTRUM DISORDERS; MIDBRAIN DOPAMINE NEURONS; GAMMA-AMINOBUTYRIC-ACID; V1A RECEPTOR ANTAGONIST; OLFACTORY-BULB REMOVAL; CENTRAL-NERVOUS-SYSTEM; MATERNAL-BEHAVIOR AB Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2014 Elsevier B.V. All rights reserved. C1 [Febo, Marcelo] Univ Florida, McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32611 USA. [Ferris, Craig F.] Northeastern Univ, Ctr Translat Neuroimaging, Boston, MA 02115 USA. [Ferris, Craig F.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Ferris, Craig F.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Febo, M (reprint author), Univ Florida, McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32611 USA. EM c.ferris@neu.edu FU NIH [DA019946] FX Support was provided in part by NIH grant DA019946. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Health. The NIH and NIDA had no 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 article for publication. The authors have no financial, commercial or personal conflict of interest to report. 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Although OT-based therapies are currently being evaluated as remedies for social deficits in neuropsychiatric disorders, precisely how OT regulates complex social processes remains largely unknown. Here we describe how a non-human primate model can be used to understand the mechanisms by which OT regulates social cognition and thereby inform its clinical application in humans. We focus primarily on recent advances in our understanding of OT-mediated social cognition in rhesus macaques (Macaca mulatta), supplemented by discussion of recent work in humans, other primates, and rodents. Together, these studies endorse the hypothesis that OT promotes social exploration both by amplifying social motivation and by attenuating social vigilance. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2013 Elsevier B.V. All rights reserved. C1 [Chang, Steve W. C.] Yale Univ, Dept Psychol, New Haven, CT 06511 USA. [Chang, Steve W. 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The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an indirect peripheral mechanism. And third, the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior, there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not always "pro-social" and others suggest effects on social behaviors are due to a more general anxiolytic effect. In this critique, we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery, and to discuss intranasal OT effects on social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature. This article is part of a Special Issue entitled Oxytocin and Social Behav. Published by Elsevier B.V. C1 [Evans, Simon L.] Univ Sussex, Sch Psychol, Brighton BN1 9QG, E Sussex, England. [Dal Monte, Olga; Noble, Pamela; Averbeck, Bruno B.] NIMH, Lab Neuropsychol, NIH, Bethesda, MD USA. 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PD SEP 11 PY 2014 VL 1580 SI SI BP 69 EP 77 DI 10.1016/j.brainres.2013.11.008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100005 PM 24239931 ER PT J AU Pedersen, CA AF Pedersen, Cort A. TI Schizophrenia and alcohol dependence: Diverse clinical effects of oxytocin and their evolutionary origins SO BRAIN RESEARCH LA English DT Article DE Oxytocin; Schizophrenia; Social cognition; Alcohol withdrawal; Alcohol dependence; Treatment ID RECEPTOR MESSENGER-RNA; INCREASES EXTRACELLULAR DOPAMINE; ADJUNCTIVE INTRANASAL OXYTOCIN; OBSESSIVE-COMPULSIVE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; VOLES MICROTUS-OCHROGASTER; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; PITUITARY-ADRENAL AXIS; FEMALE PRAIRIE VOLES AB Beginning in 1979 with the first report that central administration of oxytocin stimulates maternal behavior in virgin rats, decades of animal research and more recent human studies have demonstrated that oxytocin has many pro-social effects. These many findings suggest that oxytocin may be an effective treatment for social deficits that are hallmark features of disorders such as autism and schizophrenia. Effects in preclinical animal models also imply that oxytocin may be an efficacious pharmacotherapy in a wide range of psychiatric disorders including psychoses and addictions. To date, 3 small clinical trials found that daily intranasal oxytocin treatment for 2-8 weeks significantly reduced psychotic symptoms in schizophrenia. Two of these trials also found improvement in social cognition or neurocognition, areas in which patients have significant deficiencies that do not respond to conventional antipsychotic treatment and contribute to disability. In another small trial, intranasal oxytocin potently blocked alcohol withdrawal. After reviewing the rationale for these trials, they are described in more detail. Questions are then asked followed by discussions of the large gaps in our knowledge about brain oxytocin systems in humans. The hope is to highlight important directions for future investigations of the role of oxytocin in the pathophysiology of psychotic disorders and addictions and to extend clinical research in these areas. Heretofore unrecognized roles for which oxytocin may have been selected during the evolution of placental mammalian maternal-infant and other social attachments are considered as possible origins of oxytocin antipsychotic and antiaddiction effects. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2014 Published by Elsevier B.V. C1 Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Pedersen, CA (reprint author), Univ N Carolina, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. 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AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD SEP 11 PY 2014 VL 1580 SI SI BP 102 EP 123 DI 10.1016/j.brainres.2014.01.050 PG 22 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100007 PM 24508579 ER PT J AU Kanat, M Heinrichs, M Domes, G AF Kanat, Manuela Heinrichs, Markus Domes, Gregor TI Oxytocin and the social brain: Neural mechanisms and perspectives in human research SO BRAIN RESEARCH LA English DT Article DE Functional imaging; Oxytocin; Brain activity; Social behavior; Social cognition ID AUTISM SPECTRUM DISORDERS; MATERNAL LOVE WITHDRAWAL; MENSTRUAL-CYCLE PHASE; ADULT HUMAN BRAIN; INTRANASAL OXYTOCIN; SEX-DIFFERENCES; AMYGDALA ACTIVATION; FACIAL EXPRESSIONS; MODULATES AMYGDALA; ANXIETY DISORDER AB The present paper summarizes functional imaging studies investigating the effects of intranasal oxytocin (OT) on brain responses to social stimuli. We aim to integrate previous research, point to unresolved issues and highlight perspectives for future studies. The studies so far have focused on identifying neural circuits underlying social information processing which are particularly sensitive to modulations by exogenous OT. Most consistently, stimulus-related responses of the amygdala and associated areas within the prefrontal and temporal cortices have been found to be modulated by OT administration. However, there are a number of unresolved issues related to the possible role of sex differences and hormonal status, genetic variability, and individual differences in socio-cognitive functioning. Future studies focusing on these open questions are expected to contribute to a more nuanced understanding of the role of the central OT system in humans and may provide the basis for novel treatment approaches for mental disorders characterized by social deficits. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kanat, Manuela; Heinrichs, Markus; Domes, Gregor] Univ Freiburg, Dept Psychol, Lab Biol & Personal Psychol, D-79104 Freiburg, Germany. [Kanat, Manuela; Heinrichs, Markus; Domes, Gregor] Univ Freiburg, Univ Med Ctr, Freiburg Brain Imaging Ctr, D-79106 Freiburg, Germany. RP Domes, G (reprint author), Univ Freiburg, Dept Psychol, Lab Biol & Personal Psychol, Stefan Meier Str 8, D-79104 Freiburg, Germany. EM domes@psychologie.uni-freiburg.de RI Domes, Gregor/J-3369-2013 OI Domes, Gregor/0000-0001-5908-4374 FU Deutsche Forschungsgemeinschaft [DFG 1312/2-1] FX We gratefully acknowledge the valuable discussion with Dr. Frances S. Chen. Preparation of the manuscript was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG 1312/2-1). 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PD SEP 11 PY 2014 VL 1580 SI SI BP 160 EP 171 DI 10.1016/j.brainres.2013.11.003 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100012 PM 24216134 ER PT J AU Anagnostou, E Soorya, L Brian, J Dupuis, A Mankad, D Smile, S Jacob, S AF Anagnostou, Eudokia Soorya, Latha Brian, Jessica Dupuis, Annie Mankad, Deepali Smile, Sharon Jacob, Suma TI Intranasal oxytocin in the treatment of autism spectrum disorders: A review of literature and early safety and efficacy data in youth SO BRAIN RESEARCH LA English DT Review DE Autism; Oxytocin; Clinical trial; Social cognition; Social function ID RECEPTOR GENE OXTR; OBSESSIVE-COMPULSIVE SCALE; HIGH-FUNCTIONING AUTISM; SOCIAL COGNITION; JAPANESE POPULATION; REVISED VERSION; HUMAN BRAIN; VASOPRESSIN; BEHAVIOR; MICE AB Background: There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Methods: Fifteen children and adolescents with verbal IQs >= 70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Results: Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocip. Conclusions: This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2014 Elsevier B.V. All rights reserved. C1 [Anagnostou, Eudokia; Brian, Jessica; Mankad, Deepali; Smile, Sharon] Univ Toronto, Bloorview Res Inst, Toronto, ON M4G 1R8, Canada. [Soorya, Latha] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60610 USA. [Dupuis, Annie] Univ Toronto, Hosp Sick Children, Dalla Lana Sch Publ Hlth, Toronto, ON M5G 1X8, Canada. [Jacob, Suma] Univ Minnesota, Dept Psychiat & Pediat, Minneapolis, MN 55455 USA. 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TI Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders SO BRAIN RESEARCH LA English DT Article DE Oxytocin; Vasopressin; Autism; Prader-Willi; Williams; Fragile X ID FRAGILE-X-SYNDROME; PRADER-WILLI-SYNDROME; AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION PROTEIN; GENOME MICROARRAY ANALYSIS; LONG-TERM POTENTIATION; WHOLE-BLOOD SEROTONIN; FMR1 KNOCKOUT MOUSE; SOCIAL-BEHAVIOR; 1ST-DEGREE RELATIVES AB Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide hormones found in many mammalian species, including humans. Dysregulation of these neuropeptides have been associated with changes in behavior, especially social interactions. We review how the OT and AVP systems have been investigated in Autism Spectrum Disorder (ASD), Prader-Willi Syndrome (PWS), Williams Syndrome (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders (NDD) are marked by social deficits. While PWS, WS and FXS have identified genetic mutations, ASD stems from multiple genes with complex interactions. Animal models of NDD are invaluable for studying the role and relatedness of OT and AVP in the developing brain. We present data from a FXS mouse model affecting the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP staining cells in some brain regions. Reviewing the research about OT and AVP in these NDD suggests that altered OT pathways may be downstream from different etiological factors and perturbations in development. This has implications for ongoing studies of the therapeutic application of OT in NDD. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2014 Published by Elsevier B.V. C1 [Francis, S. M.; Levin-Decanini, T.; Jacob, S.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Sagar, A.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. 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NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD SEP 11 PY 2014 VL 1580 SI SI BP 199 EP 218 DI 10.1016/j.brainres.2014.01.021 PG 20 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100016 PM 24462936 ER PT J AU Kim, S Soeken, TA Cromer, SJ Martinez, SR Hardy, LR Strathearn, L AF Kim, Sohye Soeken, Timothy A. Cromer, Sara J. Martinez, Sheila R. Hardy, Leah R. Strathearn, Lane TI Oxytocin and postpartum depression: Delivering on what's known and what's not SO BRAIN RESEARCH LA English DT Article DE Postpartum depression; Oxytocin; Treatment; Maternal caregiving; Infant ID RANDOMIZED-CONTROLLED-TRIAL; PITUITARY-ADRENAL AXIS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CORTICOTROPIN-RELEASING HORMONE; AUTISM SPECTRUM DISORDERS; RECEPTOR-ALPHA EXPRESSION; MOTHER-CHILD-RELATIONSHIP; INFANT-FEEDING OUTCOMES; SOCIAL ANXIETY DISORDER; VENTRAL TEGMENTAL AREA AB The role of oxytocin in the treatment of postpartum depression has been a topic of growing interest. This subject carries important implications, given that postpartum depression can have detrimental effects on both the mother and her infant, with lifelong consequences for infant socioemotional and cognitive development. In recent years, oxytocin has received attention for its potential role in many neuropsychiatric conditions beyond its well-described functions in childbirth and lactation. In the present review, we present available data on the clinical characteristics and neuroendocrine foundations of postpartum depression. We outline current treatment modalities and their limitations, and proceed to evaluate the potential role of oxytocin in the treatment of postpartum depression. The aim of the present review is twofold: (a) to bring together evidence from animal and human research concerning the role of oxytocin in postpartum depression, and (b) to highlight areas that deserve further research in order to bring a fuller understanding of oxytocin's therapeutic potential. This article is part of a Special Issue entitled Oxytocin and Social Behav. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kim, Sohye; Soeken, Timothy A.; Cromer, Sara J.; Martinez, Sheila R.; Hardy, Leah R.; Strathearn, Lane] Baylor Coll Med, Houston, TX 77030 USA. [Kim, Sohye; Martinez, Sheila R.; Hardy, Leah R.; Strathearn, Lane] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Attachment & Neurodev Lab, Houston, TX 77030 USA. [Kim, Sohye; Strathearn, Lane] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Strathearn, Lane] Texas Childrens Hosp, Meyer Ctr Dev Pediat, Houston, TX 77054 USA. RP Strathearn, L (reprint author), Baylor Coll Med, Texas Childrens Hosp, Dept Pediat, Attachmen & Neurodev Lab,Childrens Nutr Res Ctr, 1100 Bates St,Suite 4004 B, Houston, TX 77030 USA. EM lanes@bcm.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD065819]; National Institute on Drug Abuse [R01DA026437] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD065819]; and the National Institute on Drug Abuse [R01DA026437]. The content is solely the responsibility of the authors and does not necessarily represent the official views of these institutes or the National Institutes of Health. 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PD SEP 11 PY 2014 VL 1580 SI SI BP 219 EP 232 DI 10.1016/j.brainres.2013.11.009 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AQ1MS UT WOS:000342546100017 PM 24239932 ER PT J AU Duzyj, CM Paidas, MJ Jebailey, L Huang, JS Barnea, ER AF Duzyj, Christina M. Paidas, Michael J. Jebailey, Lellean Huang, Jing Shun Barnea, Eytan R. TI PreImplantation factor (PIF*) promotes embryotrophic and neuroprotective decidual genes: effect negated by epidermal growth factor SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Embryogenesis; Neural development; Preimplantation factor (PIF); Neural disease; Uterine environment ID QUINONE REDUCTASE-ACTIVITY; 1ST TRIMESTER; INTERACTING PROTEIN; MULTIPLE-SCLEROSIS; EMBRYO DEVELOPMENT; CEREBRAL-CORTEX; CELL-LINES; EXPRESSION; DIFFERENTIATION; TISSUES AB Background: Intimate embryo-maternal interaction is paramount for pregnancy success post-implantation. The embryo follows a specific developmental timeline starting with neural system, dependent on endogenous and decidual factors. Beyond altered genetics/epigenetics, post-natal diseases may initiate at prenatal/neonatal, post-natal period, or through a continuum. Preimplantation factor (PIF) secreted by viable embryos promotes implantation and trophoblast invasion. Synthetic PIF reverses neuroinflammation in non-pregnant models. PIF targets embryo proteins that protect against oxidative stress and protein misfolding. We report of PIF's embryotrophic role and potential to prevent developmental disorders by regulating uterine milieu at implantation and first trimester. Methods: PIF's effect on human implantation (human endometrial stromal cells (HESC)) and first-trimester decidua cultures (FTDC) was examined, by global gene expression (Affymetrix), disease-biomarkers ranking (GeneGo), neuro-specific genes (Ingenuity) and proteins (mass-spectrometry). PIF co-cultured epidermal growth factor (EGF) in both HESC and FTDC (Affymetrix) was evaluated. Results: In HESC, PIF promotes neural differentiation and transmission genes (TLX2, EPHA10) while inhibiting retinoic acid receptor gene, which arrests growth. PIF promotes axon guidance and downregulates EGF-dependent neuroregulin signaling. In FTDC, PIF promotes bone morphogenetic protein pathway (SMAD1, 53-fold) and axonal guidance genes (EPH5) while inhibiting PPP2R2C, negative cell-growth regulator, involved in Alzheimer's and amyotrophic lateral sclerosis. In HESC, PIF affects angiotensin via beta-arrestin, transforming growth factor-beta (TGF-beta), notch, BMP, and wingless-int (WNT) signaling pathways that promote neurogenesis involved in childhood neurodevelopmental diseases-autism and also affected epithelial-mesenchymal transition involved in neuromuscular disorders. In FTDC, PIF upregulates neural development and hormone signaling, while downregulating genes protecting against xenobiotic response leading to connective tissue disorders. In both HESC and FTDC, PIF affects neural development and transmission pathways. In HESC interactome, PIF promotes FUS gene, which controls genome integrity, while in FTDC, PIF upregulates STAT3 critical transcription signal. EGF abolished PIF's effect on HESC, decreasing metalloproteinase and prolactin receptor genes, thereby interfering with decidualization, while in FTDC, EGF co-cultured with PIF reduced ZHX2, gene that regulates neural AFP secretion. Conclusions: PIF promotes decidual trophic genes and proteins to regulate neural development. By regulating the uterine milieu, PIF may decrease embryo vulnerability to post-natal neurodevelopmental disorders. Examination of PIF-based intervention strategies used during embryogenesis to improve pregnancy prognosis and reduce post-natal vulnerability is clearly in order. C1 [Duzyj, Christina M.; Paidas, Michael J.] Yale Univ, Sch Med, Yale Women & Childrens Ctr Blood Disorders, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA. [Jebailey, Lellean] GeneGo Inc, Carlsbad, CA 92008 USA. [Huang, Jing Shun] Ohio State Univ, Dept Obstet & Gynecol, Reprod Biol Unit, Columbus, OH 43210 USA. [Barnea, Eytan R.] Soc Invest Early Pregnancy, Cherry Hill, NJ 08003 USA. [Barnea, Eytan R.] BioIncept LLC PIF Proprietary, Cherry Hill, NJ 08003 USA. RP Barnea, ER (reprint author), Soc Invest Early Pregnancy, 1697 Lark Lane, Cherry Hill, NJ 08003 USA. EM Barnea@earlypregnancy.org FU BioIncept, LLC; National Institutes of Health [5R01HD056123-02] FX This work was supported through an unrestricted grant by BioIncept, LLC (MJP) and National Institutes of Health (grant number 5R01HD056123-02) (SJH). 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Single-cell whole-genome sequencing (WGS) in >200 single cells, including >160 neurons from three normal and two pathological human brains, sensitively identified germline trisomy of chromosome 18 but found most (>= 95%) neurons in normal brain tissue to be euploid. Analysis of a patient with hemimegalencephaly (HMG) due to a somatic CNV of chromosome 1q found unexpected tetrasomy 1q in similar to 20% of neurons, suggesting that CNVs in a minority of cells can cause widespread brain dysfunction. Single-cell analysis identified large (>1 Mb) clonal CNVs in lymphoblasts and in single neurons from normal human brain tissue, suggesting that some CNVs occur during neurogenesis. Many neurons contained one or more large candidate private CNVs, including one at chromosome 15q13.2-13.3, a site of duplication in neuropsychiatric conditions. Large private and clonal somatic CNVs occur in normal and diseased human brains. C1 [Cai, Xuyu; Evrony, Gilad D.; Lehmann, Hillel S.; Elhosary, Princess C.; Mehta, Bhaven K.; Poduri, Annapurna; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. [Cai, Xuyu; Evrony, Gilad D.; Lehmann, Hillel S.; Elhosary, Princess C.; Mehta, Bhaven K.; Poduri, Annapurna; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Cai, Xuyu; Evrony, Gilad D.; Lehmann, Hillel S.; Elhosary, Princess C.; Mehta, Bhaven K.; Poduri, Annapurna; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Cai, Xuyu; Evrony, Gilad D.; Lehmann, Hillel S.; Elhosary, Princess C.; Mehta, Bhaven K.; Poduri, Annapurna; Walsh, Christopher A.] Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Cai, Xuyu; Evrony, Gilad D.; Walsh, Christopher A.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. [Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Poduri, Annapurna] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Walsh, CA (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu FU NIGMS [T32GM007726]; NIH MSTP grant [T32GM007753]; Louis Lange III Scholarship in Translational Research; NINDS [R01NS079277, R01NS035129]; NIMH [1RC2MH089952]; Manton Center for Orphan Disease Research FX X. C. was supported by the NIGMS (T32GM007726) and was a Stuart H. Q. and Victoria Quan Fellow in Neuroscience. G. D. E. was supported by NIH MSTP grant T32GM007753 and by the Louis Lange III Scholarship in Translational Research. C. A. W. was supported by the NINDS (R01NS079277 and R01NS035129), the NIMH (1RC2MH089952), and the Manton Center for Orphan Disease Research. C. A. W. is a Distinguished Investigator of the Paul G. Allen Family Foundation and is an Investigator of the Howard Hughes Medical Institute. 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T-brain-1 (TBR1), a critical neuron-specific transcription factor for forebrain development, has been recognized as a high-confidence risk gene for autism spectrum disorders. Here, we show that in addition to its role in brain development, Tbr1 responds to neuronal activation and further modulates the Grin2b expression in adult brains and mature neurons. The expression levels of Tbr1 were investigated using both immunostaining and quantitative reverse transcription polymerase chain reaction (RT-PCR) analyses. We found that the mRNA and protein expression levels of Tbr1 are induced by excitatory synaptic transmission driven by bicuculline or glutamate treatment in cultured mature neurons. The upregulation of Tbr1 expression requires the activation of both alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. Furthermore, behavioral training triggers Tbr1 induction in the adult mouse brain. The elevation of Tbr1 expression is associated with Grin2b upregulation in both mature neurons and adult brains. Using Tbr1-deficient neurons, we further demonstrated that TBR1 is required for the induction of Grin2b upon neuronal activation. Taken together with the previous studies showing that TBR1 binds the Grin2b promoter and controls expression of luciferase reporter driven by Grin2b promoter, the evidence suggests that TBR1 directly controls Grin2b expression in mature neurons. We also found that the addition of the calcium/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93, but not the calcium-dependent phosphatase calcineurin antagonist cyclosporin A, to cultured mature neurons noticeably inhibited Tbr1 induction, indicating that neuronal activation upregulates Tbr1 expression in a CaMKII-dependent manner. In conclusion, our study suggests that Tbr1 plays an important role in adult mouse brains in response to neuronal activation to modulate the activity-regulated gene transcription required for neural plasticity. C1 [Chuang, Hsiu-Chun; Hsueh, Yi-Ping] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan. [Chuang, Hsiu-Chun; Huang, Tzyy-Nan; Hsueh, Yi-Ping] Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan. RP Hsueh, YP (reprint author), Acad Sinica, Inst Mol Biol, 128 Acad Rd,Sect 2, Taipei 11529, Taiwan. EM yph@gate.sinica.edu.tw FU Academia Sinica [AS-103-TP-B05]; Ministry of Science and Technology (MOST) [102-2321-B-001-029, 102-2321-B-001.054, 103-2321-B-001-002, 103-2321-B-001-018] FX We thank Profs. John Rubenstein and Robert Hevner for the Tbr1+/- mice, the Genomic Core of the Institute of Molecular Biology, Academia Sinica, for the technical assistance and members of the Hsueh lab for relabeling samples for the blind test. This work was supported by grants from the Academia Sinica (AS-103-TP-B05 to Yi-Ping Hsueh) and the Ministry of Science and Technology (MOST 102-2321-B-001-029, 102-2321-B-001.054, 103-2321-B-001-002, and 103-2321-B-001-018 to Yi-Ping Hsueh). 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Cell. Neurosci. PD SEP 10 PY 2014 VL 8 AR 280 DI 10.3389/fncel.2014.00280 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AS7XC UT WOS:000344464100001 PM 25309323 ER PT J AU Xu, X Miller, EC Pozzo-Miller, L AF Xu, Xin Miller, Eric C. Pozzo-Miller, Lucas TI Dendritic spine dysgenesis in Rett syndrome SO FRONTIERS IN NEUROANATOMY LA English DT Review DE MeCP2; BDNF; excitatory synapse; spine density; hippocampus; organotypic slice cultures,TrkB; autism spectrum disorder ID MECP2 MUTANT MICE; GROWTH-FACTOR-I; NEUROTROPHIC FACTOR EXPRESSION; ACTIVITY-DEPENDENT SECRETION; CPG-BINDING PROTEIN-2; HIPPOCAMPAL-NEURONS; MOUSE MODEL; SYNAPTIC PLASTICITY; PYRAMIDAL NEURONS; CEREBRAL-CORTEX AB Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (Rh). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in Rh individuals and Mecp2based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in Rh and other MECP2-associated neurodevelopmental disorders. C1 [Xu, Xin; Miller, Eric C.; Pozzo-Miller, Lucas] Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr, Birmingham, AL 35294 USA. RP Pozzo-Miller, L (reprint author), Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr, SHEL-1002,1825 Univ Blvd, Birmingham, AL 35294 USA. EM lucaspm@uab.edu FU NIH [NS-065027, HD-074418] FX This work was supported by NIH grants NS-065027 and HD-074418 (to Lucas Pozzo-Miller). We are indebted to Chris Chapleau, Wei Li, and Mary Phillips for thoughtful discussions. 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PD SEP 10 PY 2014 VL 312 IS 10 BP 991 EP 991 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AO5LF UT WOS:000341385600004 ER PT J AU Laugeray, A Herzine, A Perche, O Richard, O Menuet, A Mazaud-Guittot, S Lesne, L Briault, S Jegou, B Pichon, J Montecot-Dubourg, C Mortaud, S AF Laugeray, Anthony Herzine, Ameziane Perche, Olivier Richard, Olivier Menuet, Arnaud Mazaud-Guittot, Severine Lesne, Laurianne Briault, Sylvain Jegou, Bernard Pichon, Jacques Montecot-Dubourg, Celine Mortaud, Stephane TI Perinatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 50th Congress of the European-Societies-of-Toxicology CY SEP 07-10, 2014 CL Edinburgh, SCOTLAND SP European Soc Toxicol, British Toxicol Soc, Soc Toxicol DE Glufosinate ammonium; Autistic Spectrum Disorders; Perinatal exposure neurodevelopment; Mice C1 [Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Richard, Olivier; Menuet, Arnaud; Briault, Sylvain; Pichon, Jacques; Montecot-Dubourg, Celine; Mortaud, Stephane] CNRS, UMR7355, F-45071 Orleans, France. 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Pillai, Anilkumar TI Dysregulation of estrogen receptor beta (ER beta), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects SO MOLECULAR AUTISM LA English DT Article DE Aromatase; Autism; Estrogen; Receptor; Sex ID NEUROPSYCHIATRIC DISORDERS; TRANSCRIPTIONAL ACTIVATION; CO-REPRESSORS; BRAIN; BEHAVIOR; ANXIETY; GENE; MICE; EXPRESSION; STEROIDS AB Background: Autism spectrum disorders (ASD) are much more common in males than in females. Molecular alterations within the estrogen receptor (ER) signaling pathway may contribute to the sex difference in ASD, but the extent of such abnormalities in the brain is not known. Methods: Postmortem middle frontal gyrus tissues (13 ASD and 13 control subjects) were used. The protein levels were examined by western blotting. The gene expression was determined by qRT-PCR. Results: Gene expression analysis identified a 35% decrease in ER beta mRNA expression in the middle frontal gyrus of ASD subjects. In addition, a 38% reduction in aromatase (CYP19A1) mRNA expression was observed in ASD subjects. We also found significant decreases in ER co-activators that included a 34% decrease in SRC-1, a 77% decrease in CBP, and a 52% decrease in P/CAF mRNA levels in ASD subjects relative to controls. There were no differences in the mRNA levels of TIF-2, AIB-1 (ER co-activators), ER co-repressors (SMRT and nCoR) and ERa in the middle frontal gyrus of ASD subjects as compared to controls. We observed significant correlations between ER beta, CYP19A1, and co-activators in the study subjects. Immunoblot analysis further confirmed the changes in ER beta and aromatase at the protein level in the control and ASD subjects. Conclusions: These results, for the first time, provide the evidence of the dysregulation of ER beta and co-factors in the brain of subjects with ASD. C1 [Crider, Amanda; Ahmed, Anthony O.; Pillai, Anilkumar] Georgia Regents Univ, Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. [Thakkar, Roshni] Georgia Regents Univ, Med Coll Georgia, Dept Neurosci & Regenerat Med, Augusta, GA 30912 USA. RP Pillai, A (reprint author), Georgia Regents Univ, Med Coll Georgia, Dept Psychiat & Hlth Behav, 997 St Sebastian Way, Augusta, GA 30912 USA. EM apillai@gru.edu FU NIH [HHSN275200900011C, NO1-HD-9-0011] FX The authors would like to thank Diya Peter for her technical assistance. Human postmortem samples were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD, USA. The Bank is funded by NIH Contract No. #HHSN275200900011C, Ref. No. NO1-HD-9-0011. 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Marwick, Helen Heron, Jon Golding, Jean Gillberg, Christopher Wilson, Philip TI Association between parent-infant interactions in infancy and disruptive behaviour disorders at age seven: a nested, case-control ALSPAC study SO BMC PEDIATRICS LA English DT Article DE ALSPAC; Disruptive behaviour disorders; Parent-infant interactions; Mellow Parenting Observation System ID CONDUCT DISORDER; ANTISOCIAL-BEHAVIOR; CONTROLLED-TRIAL; CHILD; RISK; PSYCHOPATHOLOGY; COHORT; BOYS; INTERVENTION AB Background: Effective early intervention to prevent oppositional/conduct disorders requires early identification of children at risk. Patterns of parent-child interaction may predict oppositional/conduct disorders but large community-based prospective studies are needed to evaluate this possibility. Methods: We sought to examine whether the Mellow Parenting Observational System (MPOS) used to assess parent-infant interactions at one year was associated with psychopathology at age 7. The MPOS assesses positive and negative interactions between parent and child. It examines six dimensions: anticipation of child's needs, responsiveness, autonomy, cooperation, containment of child distress, and control/conflict; these are summed to produce measures of total positive and negative interactions. We examined videos from the Avon Longitudinal Study of Parents and Children (ALSPAC) sub-cohort who attended the 'Children in Focus' clinic at one year of age. Our sample comprised 180 videos of parent-infant interaction: 60 from infants who received a psychiatric diagnostic categorisation at seven years and 120 randomly selected controls who were group-matched on sex. Results: A negative association between positive interactions and oppositional/conduct disorders was found. With the exception of pervasive developmental disorders (autism), an increase of one positive interaction per minute predicted a 15% (95% CI: 4% to 26%) reduction in the odds of the infant being case diagnosed. There was no statistically significant relationship between negative parenting interactions and oppositional/conduct disorders, although negative interactions were rarely observed in this setting. Conclusions: The Mellow Parenting Observation System, specifically low scores for positive parenting interactions (such as Responsiveness which encompasses parental warmth towards the infant), predicted later psychiatric diagnostic categorisation of oppositional/conduct disorders. C1 [Puckering, Christine; Gillberg, Christopher] Univ Glasgow, RHSC Yorkhill, Inst Hlth & Wellbeing, Glasgow G3 8SJ, Lanark, Scotland. [Allely, Clare S.] Univ Salford, Sch Hlth Sci, Salford M6 6PU, Lancs, England. [Doolin, Orla; Purves, David; McConnachie, Alex; Johnson, Paul C. 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This project was specifically funded by small grants from the Yorkhill Children's Foundation, the Gillberg Neuropsychiatry Centre and the Waterloo Foundation. This article is the work of the authors, and Philip Wilson will serve as guarantor for the contents of this article. 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Immunol. PD SEP 5 PY 2014 VL 5 AR 427 DI 10.3389/fimmu.2014.00427 PG 18 WC Immunology SC Immunology GA CI0QH UT WOS:000354442100002 PM 25250028 ER PT J AU Horlin, C Falkmer, M Parsons, R Albrecht, MA Falkmer, T AF Horlin, Chiara Falkmer, Marita Parsons, Richard Albrecht, Matthew A. Falkmer, Torbjorn TI The Cost of Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID BEHAVIORAL TREATMENT; MEDIATION ANALYSIS; CHILDREN; INTERVENTION; DIAGNOSIS; FAMILIES; PARENTS; ADOS; AGE AB Objective: A diagnosis of an autism spectrum disorders is usually associated with substantial lifetime costs to an individual, their family and the community. However, there remains an elusive factor in any cost-benefit analysis of ASD diagnosis, namely the cost of not obtaining a diagnosis. Given the infeasibility of estimating the costs of a population that, by its nature, is inaccessible, the current study compares expenses between families whose children received a formal ASD diagnosis immediately upon suspecting developmental atypicality and seeking advice, with families that experienced a delay between first suspicion and formal diagnosis. Design: A register based questionnaire study covering all families with a child with ASD in Western Australia. Participants: Families with one or more children diagnosed with an ASD, totalling 521 children diagnosed with an ASD; 317 records were able to be included in the final analysis. Results: The median family cost of ASD was estimated to be AUD $ 34,900 per annum with almost 90% of the sum ($ 29,200) due to loss of income from employment. For each additional symptom reported, approximately $ 1,400 cost for the family per annum was added. While there was little direct influence on costs associated with a delay in the diagnosis, the delay was associated with a modest increase in the number of ASD symptoms, indirectly impacting the cost of ASD. Conclusions: A delay in diagnosis was associated with an indirect increased financial burden to families. Early and appropriate access to early intervention is known to improve a child's long-term outcomes and reduce lifetime costs to the individual, family and society. Consequently, a per symptom dollar value may assist in allocation of individualised funding amounts for interventions rather than a nominal amount allocated to all children below a certain age, regardless of symptom presentation, as is the case in Western Australia. C1 [Horlin, Chiara; Falkmer, Marita; Parsons, Richard; Falkmer, Torbjorn] Curtin Univ, Sch Occupat Therapy & Social Work, Perth, WA 6845, Australia. [Falkmer, Marita] Jonkoping Univ, Inst Disabil Res, Sch Educ & Commun, CHILD Programme, Jonkoping, Sweden. [Albrecht, Matthew A.] Curtin Univ, Sch Psychol, CHIRI, Perth, WA 6845, Australia. [Falkmer, Torbjorn] Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci IMH, Linkoping, Sweden. [Falkmer, Torbjorn] Pain & Rehabil Ctr, Linkoping, Sweden. [Falkmer, Torbjorn] La Trobe Univ, Sch Occupat Therapy, Melbourne, Vic, Australia. RP Falkmer, T (reprint author), Curtin Univ, Sch Occupat Therapy & Social Work, Perth, WA 6845, Australia. EM T.Falkmer@curtin.edu.au FU Department of Social Services (DSS); Australian Government's Cooperative Research Centres Program; DSS [RES-HEA-CRD-TB-50940] FX This study was funded by the Department of Social Services (DSS), formerly the Department of Families, Housing, Community Services and Indigenous Affairs (FaHCSIA), with in-kind support of the Autism CRC, established and supported under the Australian Government's Cooperative Research Centres Program. The research was also conducted in collaboration with Disabilities Services Commission Western Australia (DSC). DSS had no active role in the design, implementation, data collection, analysis or interpretation of the study. DSC collaborated with the authors and assisted in data collection by in-kind contribution of its employee's time in some aspects of the study. Writing of the report and the decision to submit this manuscript were solely the role and responsibility of the authors. However, approval to submit this study for publication was sought from CRC Living with Autism Spectrum Disorders, DSS and DSC. All researchers are independent from both DSS and DSC and take full responsibility for the integrity of the data and the accuracy of the analyses. (DSS grant number - RES-HEA-CRD-TB-50940 http://www.dss.gov.au/) CR Australian Government, 2013, HELP CHILDR AUT Consulting SE, 2007, SYNERGIES EC CONSULT FENSKE EC, 1985, ANAL INTERVEN DEVEL, V5, P49, DOI 10.1016/S0270-4684(85)80005-7 Ganz M, 2006, THE COSTS OF AUTISM, P475 Ganz ML, 2007, ARCH PEDIAT ADOL MED, V161, P343, DOI 10.1001/archpedi.161.4.343 Harris SL, 2000, J AUTISM DEV DISORD, V30, P137, DOI 10.1023/A:1005459606120 Hartley SL, 2010, J FAM PSYCHOL, V24, P449, DOI 10.1037/a0019847 Hayes AF, 2009, COMMUN MONOGR, V76, P408, DOI 10.1080/03637750903310360 Keenan M, 2010, J APPL RES INTELLECT, V23, P390, DOI 10.1111/j.1468-3148.2010.00555.x Le Couteur A, 2008, J AUTISM DEV DISORD, V38, P362, DOI 10.1007/s10803-007-0403-3 LOVAAS OI, 1987, J CONSULT CLIN PSYCH, V55, P3, DOI 10.1037/0022-006X.55.1.3 MacKinnon DP, 2007, ANNU REV PSYCHOL, V58, P593, DOI 10.1146/annurev.psych.58.110405.085542 Matson JL, 2008, RES DEV DISABIL, V29, P537, DOI 10.1016/j.ridd.2007.09.006 MCEACHIN JJ, 1993, AM J MENT RETARD, V97, P359 Montes G, 2008, PEDIATRICS, V121, pE821, DOI 10.1542/peds.2007-1594 Parish SL, 2012, INTELLECT DEV DISAB, V50, P441, DOI 10.1352/1934-9556-50.06.441 Phelps KW, 2009, J INTELLECT DEV DIS, V34, P27, DOI 10.1080/13668250802690930 Remington B, 2007, AM J MENT RETARD, V112, P418, DOI 10.1352/0895-8017(2007)112[418:EIBIOF]2.0.CO;2 Rogers SJ, 1996, J AUTISM DEV DISORD, V26, P243, DOI 10.1007/BF02172020 SHARPE D. 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TI A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors SO ENVIRONMENTAL HEALTH LA English DT Article DE Autism; Temporal trends; Air pollution; Mercury; Vaccines; Organophosphates; PBDEs ID MERCURY CONCENTRATIONS; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; SPECTRUM DISORDERS; AIR-POLLUTION; AMBIENT AIR; LOS-ANGELES; EXPOSURE; CHILDREN; ALUMINUM AB Background: The prevalence of diagnosed autism has increased rapidly over the last several decades among U.S. children. Environmental factors are thought to be driving this increase and a list of the top ten suspected environmental toxins was published recently. Methods: Temporal trends in autism for birth years 1970-2005 were derived from a combination of data from the California Department of Developmental Services (CDDS) and the United States Individuals with Disabilities Education Act (IDEA). Temporal trends in suspected toxins were derived from data compiled during an extensive literature survey. Toxin and autism trends were compared by visual inspection and computed correlation coefficients. Using IDEA data, autism prevalence vs. birth year trends were calculated independently from snapshots of data from the most recent annual report, and by tracking prevalence at a constant age over many years of reports. The ratio of the snapshot: tracking trend slopes was used to estimate the "real" fraction of the increase in autism. Results: The CDDS and IDEA data sets are qualitatively consistent in suggesting a strong increase in autism prevalence over recent decades. The quantitative comparison of IDEA snapshot and constant-age tracking trend slopes suggests that similar to 75-80% of the tracked increase in autism since 1988 is due to an actual increase in the disorder rather than to changing diagnostic criteria. Most of the suspected environmental toxins examined have flat or decreasing temporal trends that correlate poorly to the rise in autism. Some, including lead, organochlorine pesticides and vehicular emissions, have strongly decreasing trends. Among the suspected toxins surveyed, polybrominated diphenyl ethers, aluminum adjuvants, and the herbicide glyphosate have increasing trends that correlate positively to the rise in autism. Conclusions: Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s. In contrast, children's exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame. Environmental factors with increasing temporal trends can help suggest hypotheses for drivers of autism that merit further investigation. C1 Univ Colorado, Inst Arct & Alpine Res, Boulder, CO 80309 USA. RP Nevison, CD (reprint author), Univ Colorado, Inst Arct & Alpine Res, Boulder, CO 80309 USA. 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Health PD SEP 5 PY 2014 VL 13 AR 73 DI 10.1186/1476-069X-13-73 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AP4KC UT WOS:000342044600001 PM 25189402 ER PT J AU Camacho, J Ejaz, E Ariza, J Noctor, SC Martinez-Cerdeno, V AF Camacho, Jasmin Ejaz, Ehsan Ariza, Jeanelle Noctor, Stephen C. Martinez-Cerdeno, Veronica TI RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls SO NEUROSCIENCE LETTERS LA English DT Article DE Autism; Reelin; Superior temporal cortex; Layer I; Cajal-Retzius cells; Postmortem ID REELIN-IMMUNOREACTIVE NEURONS; CAJAL-RETZIUS CELL; NEOCORTEX; MOUSE; SCHIZOPHRENIA; CORTEX; INTERNEURONS; LOCALIZATION; HIPPOCAMPUS; POPULATION AB Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Camacho, Jasmin; Ejaz, Ehsan; Ariza, Jeanelle; Martinez-Cerdeno, Veronica] Shriners Hosp Children Northern Calif, Inst Pediat Regenerat Med, Sacramento, CA USA. [Martinez-Cerdeno, Veronica] Univ Calif Davis, Dept Pathol & Lab Med, Sch Med, Sacramento, CA USA. [Noctor, Stephen C.] Univ Calif Davis, Dept Psychiat, Sch Med, Sacramento, CA USA. [Noctor, Stephen C.; Martinez-Cerdeno, Veronica] Univ Calif Davis, MIND Inst, Sacramento, CA USA. 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TI LOSS OF GLUTAMIC ACID DECARBOXYLASE (GAD67) IN GPR88-EXPRESSING NEURONS INDUCES LEARNING AND SOCIAL BEHAVIOR DEFICITS IN MICE SO NEUROSCIENCE LA English DT Article DE striatum; GABA; glutamic acid decarboxylase; learning; social behavior; conditional knockout ID FRAGILE-X-SYNDROME; GAMMA-AMINOBUTYRIC-ACID; BASAL GANGLIA; GABA SYNTHESIS; MOUSE MODEL; REPETITIVE BEHAVIOR; WATER MAZE; AUTISM; INHIBITION; STRIATUM AB GABA is the neurotransmitter of striatal projection neurons, however the contribution of the striatal GABAergic output to behavior is not well understood. We assessed motor function, spatial learning, social behavior, olfactory and object recognition preferences in mice lacking the GABA-synthesizing enzyme glutamic acid decarboxylase, Gad67, in neurons expressing the protein Gpr88, an orphan G-protein-coupled receptor primarily expressed in the striatum. Gad67-deficient mice show no impairments in motor coordination and balance, but exhibit enhanced locomotor activity and stereotypic grooming behavior. Furthermore, Gad67-deficient mice show impairments in spatial learning, social behavior, olfactory preferences, and they prefer a familiar compared to a novel object in the object recognition test. These findings provide original evidence that striate! Gad67 expression is involved in the modulation of learning and social behavior. Some of the behavioral abnormalities observed in Gad67-deficient mice are reminiscent of Autism-spectrum-disorder (ASD) deficits, suggesting that abnormal striatal GABAergic output may contribute to behavioral deficits in ASD. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Zhang, K.; Hill, K.; Labak, S.; Blatt, G. J.; Soghomonian, J. -J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. 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P. Marino, S. Abuadili, A. J. Valdes Signoriello, G. Attena, F. TI Is it reasonable to abandon obligatory vaccinations in Italy? A 2013 survey SO EUROSURVEILLANCE LA English DT Article ID MANDATORY VACCINATIONS; CHILDHOOD VACCINATION; IMMUNIZATION STATUS; PARENTS; VACCINES; CHILDREN; BELIEFS; RISK; ASSOCIATION; THIMEROSAL AB In Italy, infant vaccinations are mandatory for four infectious diseases: diphtheria, polio, tetanus and hepatitis B. In the past, there was widespread apprehension in Italy that doing away with obligatory vaccinations would reduce the coverage rate, but the possibility of making vaccinations optional has recently become more popular. The objectives of this study were to investigate parental willingness to vaccinate their children if those vaccinations were no longer mandatory and to evaluate the variables influencing this intention. We conducted face-to-face structured interviews with 1,039 parents at public health vaccination centres in four cities of the Campania region of southern Italy. Most respondents (91.9%) said that they would certainly (69.4%) or probably (22.5%) vaccinate their children if vaccinations were not mandatory. The belief that vaccinations are effective and safe was positively associated with willingness to vaccinate their children, whereas having heard that autism is a possible adverse reaction to vaccination was inversely associated with willingness to vaccinate. Nevertheless, in the context of the relatively low 2012* vaccination coverage rates in Campania (under the national standard of 95%), our results suggest that eliminating mandatory vaccinations is likely to lead to current coverage rates decreasing to unacceptably low levels, significantly below 90%. C1 [Pelullo, C. P.; Marino, S.; Abuadili, A. J. Valdes] Univ Naples 2, Sch Hyg & Prevent Med, Naples, Italy. [Signoriello, G.] Univ Naples 2, Med Stat Unit, Naples, Italy. [Attena, F.] Univ Naples 2, Dept Expt Med, Naples, Italy. RP Pelullo, CP (reprint author), Univ Naples 2, Sch Hyg & Prevent Med, Naples, Italy. EM francesco.attena@unina2.it CR [Anonymous], PIAN NAZ PREV VACC 2 [Anonymous], 2014, AD MANT EROG LEA ATT [Anonymous], 2012, REP SULL VACC ANN 20 Benin AL, 2006, PEDIATRICS, V117, P1532, DOI 10.1542/peds.2005-1728 Colgrove J, 2005, HEALTH AFFAIR, V24, P729, DOI 10.1377/hlthaff.24.3.729 Guellin BG, 2000, PEDIATRICS, V106, P1097 Gust D, 2005, AM J HEALTH BEHAV, V29, P81 Gust Deborah A, 2004, Pediatrics, V114, pe16 Haverkate M, 2012, EURO SURVEILL, V17 Jones A. 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Still, no direct comparison of both disorders has been performed to identify differences and commonalities in brain structure. In this voxel based morphometry study, 34 patients with autism spectrum disorder, 21 patients with schizophrenia and 26 typically developed control subjects were included to identify global and regional brain volume alterations. No global gray matter or white matter differences were found between groups. In regional data, patients with autism spectrum disorder compared to typically developed control subjects showed smaller gray matter volume in the amygdala, insula, and anterior medial prefrontal cortex. Compared to patients with schizophrenia, patients with autism spectrum disorder displayed smaller gray matter volume in the left insula. Disorder specific positive correlations were found between mentalizing ability and left amygdala volume in autism spectrum disorder, and hallucinatory behavior and insula volume in schizophrenia. Results suggest the involvement of social brain areas in both disorders. Further studies are needed to replicate these findings and to quantify the amount of distinct and overlapping neural correlates in autism spectrum disorder and schizophrenia. C1 [Radeloff, Daniel; Ciaramidaro, Angela; Siniatchkin, Michael; Hainz, Daniela; Schlitt, Sabine; Poustka, Fritz; Boelte, Sven; Freitag, Christine Margarete] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany. [Weber, Bernhard; Walter, Henrik] Goethe Univ Frankfurt, Dept Psychiat Psychosomat & Psychotherapy, D-60054 Frankfurt, Germany. [Boelte, Sven] Karolinska Inst KIND, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Walter, Henrik] Charite, Dept Psychiat & Psychotherapy, Div Mind & Brain Res, D-13353 Berlin, Germany. [Weber, Bernhard] Univ Basel, Psychiat Univ Clin, Basel, Switzerland. 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Opposits, Gabor Aranyi, Csaba Berenyi, Ervin Emri, Miklos TI Voxel-Wise Motion Artifacts in Population-Level Whole-Brain Connectivity Analysis of Resting-State fMRI SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; GLOBAL SIGNAL REGRESSION; FUNCTIONAL CONNECTIVITY; CEREBRAL-CORTEX; SUBJECT MOTION; HEAD MOTION; MRI; REGISTRATION; NETWORKS; IMPACT AB Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that "resting-state'' fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences and preserves real neuronal differences, as demonstrated by the autism-related comparisons. C1 [Spisak, Tamas; Kis, Sandor A.; Opposits, Gabor; Aranyi, Csaba; Emri, Miklos] Univ Debrecen, Med & Hlth Sci Ctr, Dept Nucl Med, Debrecen, Hungary. [Jakab, Andras] Med Univ Vienna, Dept Radiol, Vienna, Austria. [Berenyi, Ervin] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biomed Lab & Imaging Sci, Debrecen, Hungary. RP Spisak, T (reprint author), Univ Debrecen, Med & Hlth Sci Ctr, Dept Nucl Med, Debrecen, Hungary. EM tspisak@pet.dote.hu FU European Union; European Social Fund through project "Supercomputer, the national virtual lab'' [TAMOP-4.2.2.C-11/1/KONV-2012-0010]; State of Hungary - European Social Fund through project "Basic and applied research to assist the development of speech for the deaf" [TAMOP 4.2.2.C-11/1/KONV]; State of Hungary through the National Brain Research Program [KTIA_13_NAP-A-II/3]; European Commission, 7th European Community Framework Programme, Marie Curie IEF Research grant FABRIC - "exploring the Formation and Adaptation of the Brain Connectome'' [2012-PIEF-GA-33003]; State of Hungary - European Social Fund 'National Excellence Program' [TAMOP-4.2.4.A/2-11/1-2012-0001] FX The study was partially supported by the European Union and the European Social Fund through project "Supercomputer, the national virtual lab'' (grant. no.: TAMOP-4.2.2.C-11/1/KONV-2012-0010). The work was supported by the European Union and the State of Hungary, co-financed by the European Social Fund through project "Basic and applied research to assist the development of speech for the deaf'' (TAMOP 4.2.2.C-11/1/KONV). The project was supported by the State of Hungary through the National Brain Research Program ("Charting the normal and pathological macro-scale brain connectome by in vivo neuroimaging'', KTIA_13_NAP-A-II/3). T. S. was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. A.J. was supported by the European Commission, 7th European Community Framework Programme, Marie Curie IEF Research grant FABRIC - "exploring the Formation and Adaptation of the Brain Connectome'', 2012-PIEF-GA-33003. 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 domain is compromised in the autism spectrum disorders (ASDs), including Asperger's syndrome (AS) (DSM-V). However, the few available reports of social cognition skills in adults with AS have largely neglected the effects of contextual factors. Moreover, previous studies on this population have also failed to simultaneously (a) assess multiple social cognition domains, (b) examine executive functions, (c) follow strict sample selection criteria, and (d) acknowledge the cognitive heterogeneity typical of the disorder. The study presently reviewed (Baez et al., 2012), addressed all these aspects in order to establish the basis of social cognition deficits in adult AS patients. Specifically, we assessed the performance of AS adults in multiple social cognition tasks with different context-processing requirements. The results suggest that social cognition deficits in AS imply a reduced ability to implicitly encode and integrate contextual cues needed to access social meaning. Nevertheless, the patients' performance was normal when explicit social information was presented or when the situation could be navigated with abstract rules. Here, we review the results of our study and other relevant data, and discuss their implications for the diagnosis and treatment of AS and other neuropsychiatric conditions (e.g., schizophrenia, bipolar disorder, frontotemporal dementia). Finally, we analyze previous results in the light of a current neurocognitive model of social-context processing. C1 [Baez, Sandra; Ibanez, Agustin] Favaloro Univ, Inst Cognit Neurol INECO, Buenos Aires, DF, Argentina. [Baez, Sandra; Ibanez, Agustin] Favaloro Univ, Inst Neurosci, Buenos Aires, DF, Argentina. [Baez, Sandra; Ibanez, Agustin] Diego Port Univ, UIFCoN, Santiago, Chile. [Baez, Sandra; Ibanez, Agustin] Consejo Nacl Invest Cient & Tecn, Natl Sci & Tech Res Council, RA-1033 Buenos Aires, DF, Argentina. [Ibanez, Agustin] Univ Autonoma Caribe, Barranquilla, Colombia. 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Neurosci. PD SEP 3 PY 2014 VL 8 AR 270 DI 10.3389/fnins.2014.00270 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AW8LZ UT WOS:000346515000001 PM 25232301 ER PT J AU Koh, JY Lim, JS Byun, HR Yoo, MH AF Koh, Jae-Young Lim, Joon Seo Byun, Hyae-Ran Yoo, Min-Heui TI Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients SO MOLECULAR BRAIN LA English DT Review DE Autism spectrum disorder (ASD); Zinc; Metalloprotease; Brain-derived neurotrophic factor (BDNF) ID FRAGILE-X-SYNDROME; NEUROTROPHIC FACTOR; MENTAL-RETARDATION; SERUM-LEVELS; MUTANT MICE; MATRIX-METALLOPROTEINASE; FUNCTIONAL CONNECTIVITY; ESSENTIAL MINERALS; SYNAPTIC VESICLES; DELETION SYNDROME AB Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo-or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up-and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies. C1 [Koh, Jae-Young; Lim, Joon Seo; Byun, Hyae-Ran; Yoo, Min-Heui] Univ Ulsan, Coll Med, Asan Inst Life Sci, Neural Injury Res Lab, Seoul, South Korea. [Koh, Jae-Young] Univ Ulsan, Coll Med, Dept Neurol, Seoul 138736, South Korea. RP Koh, JY (reprint author), Univ Ulsan, Coll Med, Asan Inst Life Sci, Neural Injury Res Lab, Seoul, South Korea. EM jkko@amc.seoul.kr RI Koh, Jae-Young/C-9014-2011 OI Koh, Jae-Young/0000-0002-4318-495X FU National Research Foundation of Korea [NRF: 2005-0093836]; Korean Health Technology R&D Project, Ministry of Health Welfare [KHIDI: A0920420]; Asan Institute for Life Sciences [2014-193] FX This work was supported by the following grants: the National Research Foundation of Korea (NRF: 2005-0093836); the Korean Health Technology R&D Project, Ministry of Health & Welfare (KHIDI: A0920420); the Asan Institute for Life Sciences (2014-193). We thank Dr. Eunjoon Kim at KAIST for kindly providing Shank2-knockout mice for our analyses. 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Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS) led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage. C1 [Rideau Batista Novais, Aline; Cavalier, Melanie; Boubal, Mathilde; Guiramand, Janique; Cohen-Solal, Catherine; Ferreira, Marie-Celeste de Jesus; Cambonie, Gilles; Vignes, Michel; Barbanel, Gerard] Univ Montpellier 2, Univ Montpellier 1, CNRS, Lab IBMM UMR Inst Biomol Max Mousseron 5247, Montpellier, France. [Rideau Batista Novais, Aline; Boubal, Mathilde; Cambonie, Gilles] Montpellier Univ Hosp, Neonatal Intens Care Unit, Montpellier, France. [Crouzin, Nadine] Aix Marseille Univ, CNRS, Lab NICN Neurobiol Interact Cellulaires & Neuroph, Marseille, France. RP Barbanel, G (reprint author), Univ Montpellier 2, Univ Montpellier 1, CNRS, Lab IBMM UMR Inst Biomol Max Mousseron 5247, Montpellier, France. EM gerard.barbanel@univ-montp2.fr FU Ministere de l'Enseignement Superieur et de la Recherche; Centre National de la Recherche Scientifique; University of Montpellier 2; Groupe d'Etudes de Neonatalogie-Languedoc Roussillon FX ARBN was the recipient of a fellowship from the "Ministere de l'Enseignement Superieur et de la Recherche". This work was supported in part by the Centre National de la Recherche Scientifique and University of Montpellier 2 and with the financial support of Groupe d'Etudes de Neonatalogie-Languedoc Roussillon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of a-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. Methods/Design: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. Discussion: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and a-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. C1 [de Diego-Otero, Yolanda; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes; Garcia-Guirado, Francisco; Perez-Costillas, Lucia] Hosp Reg Univ Malaga, Hosp Civil, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Salud Mental, Malaga 29009, Spain. [Calvo-Medina, Rocio] Hosp Reg Univ Malaga, Unidad Gest Clin Pediat, Malaga 29009, Spain. [del Arco-Herrera, Ignacio] Infobiotic, Malaga 29018, Spain. [Fernandez-Carvajal, Isabel] Univ Valladolid, CSIC, IBGM, Unidad Genet Mol Enfermedad, Valladolid 47003, Spain. [Ferrando-Lucas, Teresa] Hosp Quiron, Serv Neuropediat, Madrid 28223, Spain. [Caballero-Andaluz, Rafaela] Univ Seville, Fac Med, Dept Psiquiat, E-41009 Seville, Spain. [Perez-Costillas, Lucia] Univ Malaga, Fac Med, Dept Psiquiat, Malaga 29010, Spain. [de Diego-Otero, Yolanda] Hosp Reg Univ Malaga, Hosp Civil, Lab Invest, Unidad Gest Clin Salud Mental, Malaga 29009, Spain. RP de Diego-Otero, Y (reprint author), Hosp Reg Univ Malaga, Hosp Civil, Inst Invest Biomed Malaga IBIMA, Unidad Gest Clin Salud Mental, Pabellon 2 Bajo,Plaza Hosp Civil S-N, Malaga 29009, Spain. EM yolanda.diego.exts@juntadeandalucia.es FU Spanish Ministry of Health, Research Funds from FEDER-EU [TRA152, EC10-191, EC11-434]; Health Department of the Andalusian Regional Government [PI09-0507]; Economic Innovation and Science Regional Government [CTS546, P10-CTS-05704]; Jerome Lejeune Foundation (Paris, France); Servicio Andaluz de Salud. Consejeria de Salud. Junta de Andalucia; Fragile X Syndrome Association in Andalucia; Fragile X Syndrome Association in Madrid; Fragile X Syndrome Association in Extremadura; Spanish Federation of Fragile X Syndrome; Spanish Federation for Rare Diseases (FEDER); University Regional Hospital in Malaga FX The trial protocol is approved and funded by the Spanish Ministry of Health, Research Funds from FEDER-EU (TRA152, EC10-191 and EC11-434), the Health Department of the Andalusian Regional Government (PI09-0507), the Economic Innovation and Science Regional Government (CTS546 and P10-CTS-05704) and the Jerome Lejeune Foundation (Paris, France). YDDO is the recipient of a Nicolas Monarde contract from the Servicio Andaluz de Salud. Consejeria de Salud. Junta de Andalucia. We deeply thank the all the patients and their families for their participation. The authors wish to thank the following for their support: the Fragile X Syndrome Association in Andalucia, the Fragile X Syndrome Association in Madrid, the Fragile X Syndrome Association in Extremadura, the Spanish Federation of Fragile X Syndrome, the Spanish Federation for Rare Diseases (FEDER) and the University Regional Hospital in Malaga for their support. We thank DWE Ramsden for revising the manuscript. 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Rosoklija, Gorazd Sosunov, Alexander Sonders, Mark S. Kanter, Ellen Castagna, Candace Yamamoto, Ai Yue, Zhenyu Arancio, Ottavio Peterson, Bradley S. Champagne, Frances Dwork, Andrew J. Goldman, James Sulzer, David TI Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits SO NEURON LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; SUPERIOR TEMPORAL SULCUS; NEUROPSYCHIATRIC DISORDERS; FUNCTIONAL CONNECTIVITY; HIPPOCAMPAL-NEURONS; DENDRITIC SPINES; MOUSE MODELS; AUTOPHAGY; BRAIN; MICE AB Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/- ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASDlike behaviors and spine pruning defects in Tsc2+/ mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2+/- : Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR. C1 [Tang, Guomei; Kuo, Sheng-Han; Sonders, Mark S.; Kanter, Ellen; Castagna, Candace; Yamamoto, Ai; Sulzer, David] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Gudsnuk, Kathryn; Champagne, Frances] Columbia Univ, Med Ctr, Dept Psychol, New York, NY 10032 USA. [Cotrina, Marisa L.; Sosunov, Alexander; Arancio, Ottavio; Dwork, Andrew J.; Goldman, James] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Rosoklija, Gorazd; Peterson, Bradley S.; Dwork, Andrew J.; Sulzer, David] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA. [Sulzer, David] Columbia Univ, Med Ctr, Dept Pharmacol, New York, NY 10032 USA. [Yue, Zhenyu] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurol, New York, NY 10029 USA. [Yue, Zhenyu] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY 10029 USA. [Cotrina, Marisa L.] Univ Rochester, Ctr Translat Neuromed, Rochester, NY 14642 USA. [Rosoklija, Gorazd; Peterson, Bradley S.; Dwork, Andrew J.; Sulzer, David] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Sulzer, D (reprint author), Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. EM ds43@columbia.edu FU Simons Foundation; DOD TSCRP [TS110056]; Parkinson's Disease Foundation from NIMH [K01MH096956]; JPB Foundation from NIMH [K01MH096956]; AHA; NIMH [MH64168]; NIH [DP2OD001674-01, NS049442] FX This study was supported by the Simons Foundation. Additional support for D.S. is from DOD TSCRP (TS110056) and the Parkinson's Disease and JPB Foundations, for G.T. from NIMH (K01MH096956), for M.L.C. from AHA, for A.J.D. from NIMH (MH64168), for F.C. from NIH (DP2OD001674-01), for O.A. from NIH (NS049442). We thank the Autism Tissue Portal, Harvard Brain Bank, and Maryland NICHD Brain & Tissue Bank for kindly providing us brain tissues for the present study. We thank Ana Maria Cuervo for reagents and valuable advice. 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M. Carver, Leslie J. TI Effect of Familiarity on Reward Anticipation in Children with and without Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID EVENT-RELATED POTENTIALS; STIMULUS-PRECEDING NEGATIVITY; FUSIFORM FACE AREA; TYPICAL DEVELOPMENT; FACIAL EXPRESSIONS; YOUNG-CHILDREN; RECOGNITION; PERCEPTION; ATTACHMENT; PUNISHMENT AB Background: Previous research on the reward system in autism spectrum disorders (ASD) suggests that children with ASD anticipate and process social rewards differently than typically developing (TD) children-but has focused on the reward value of unfamiliar face stimuli. Children with ASD process faces differently than their TD peers. Previous research has focused on face processing of unfamiliar faces, but less is known about how children with ASD process familiar faces. The current study investigated how children with ASD anticipate rewards accompanied by familiar versus unfamiliar faces. Methods: The stimulus preceding negativity (SPN) of the event-related potential (ERP) was utilized to measure reward anticipation. Participants were 6- to 10-year-olds with (N = 14) and without (N = 14) ASD. Children were presented with rewards accompanied by incidental face or non-face stimuli that were either familiar (caregivers) or unfamiliar. All non-face stimuli were composed of scrambled face elements in the shape of arrows, controlling for visual properties. Results: No significant differences between familiar versus unfamiliar faces were found for either group. When collapsing across familiarity, TD children showed larger reward anticipation to face versus non-face stimuli, whereas children with ASD did not show differential responses to these stimulus types. Magnitude of reward anticipation to faces was significantly correlated with behavioral measures of social impairment in the ASD group. 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Hum. Neurosci. PD SEP 2 PY 2014 VL 8 AR 680 DI 10.3389/fnhum.2014.00680 PG 16 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AO4FL UT WOS:000341291500003 PM 25228875 ER PT J AU Mulder, AM Cashin, A AF Mulder, Ann M. Cashin, Andrew TI The Need to Support Students with Autism at University SO Issues in Mental Health Nursing LA English DT Article ID SPECTRUM DISORDERS; POSTSECONDARY EDUCATION; ASPERGER-SYNDROME; HIGH-SCHOOL; POPULATION; PREVALENCE; DISABILITIES; TRANSITION AB Publicity surrounds the increased prevalence of autism. However, in contrast to support in primary and secondary schools, there exists little focus on supporting students with autism at university. Mental health nurses are well placed to facilitate support programmes for students with autism who have the capacity for higher education. This article examines the international literature around the support needs for these students and discusses opportunities that exist to support these students, their families, and higher education staff. Research is urgently needed to evaluate the success of such interventions, particularly in light of the low participation rates in study and work for people with autism. C1 [Mulder, Ann M.; Cashin, Andrew] So Cross Univ, Sch Hlth & Human Sci, Lismore, NSW 2480, Australia. RP Mulder, AM (reprint author), So Cross Univ, Sch Hlth & Human Sci, Lismore, NSW 2480, Australia. 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[Jemel, B.] Hop Riviere des Prairies, Res Ctr, Cognit Neurosci & Electrophysiol Lab, Montreal, PQ, Canada. [Jemel, B.] Univ Montreal, Sch Orthophony & Audiol, Montreal, PQ, Canada. [Godbout, R.] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2014 VL 23 SU 1 SI SI MA 211 BP 52 EP 52 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB9OG UT WOS:000349960600122 ER PT J AU Baker, E Richdale, A AF Baker, E. Richdale, A. TI Sleep patterns in adults with a diagnosis of high-functioning autism spectrum disorder: a preliminary analysis SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 22nd Congress of the European-Sleep-Research-Society CY SEP 16-20, 2014 CL Tallinn, ESTONIA SP European Sleep Res Soc C1 [Baker, E.; Richdale, A.] La Trobe Univ, Olga Tennison Autism Res Ctr, Bundoora, Vic, Australia. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2014 VL 23 SU 1 SI SI MA P737 BP 230 EP 230 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB9OG UT WOS:000349960600624 ER PT J AU Baker, E Richdale, A AF Baker, E. Richdale, A. TI Chronic sleep reduction and psychopathology symptoms in adults with high-functioning autism spectrum disorder SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 22nd Congress of the European-Sleep-Research-Society CY SEP 16-20, 2014 CL Tallinn, ESTONIA SP European Sleep Res Soc C1 [Baker, E.; Richdale, A.] La Trobe Univ, Olga Tennison Autism Res Ctr, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2014 VL 23 SU 1 SI SI MA P745 BP 232 EP 232 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB9OG UT WOS:000349960600632 ER PT J AU Andujar, MA Sanchez, MDG De Leon, CM Ramos, I Marquez, A AF Aguilar Andujar, M. Guerrero Sanchez, M. D. Menendez De Leon, C. Ramos, I. Marquez, A. TI Sleep characteristics in children with autism spectrum disorder SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 22nd Congress of the European-Sleep-Research-Society CY SEP 16-20, 2014 CL Tallinn, ESTONIA SP European Sleep Res Soc C1 [Guerrero Sanchez, M. D.; Menendez De Leon, C.; Ramos, I.; Marquez, A.] HUVM, Seville, Spain. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2014 VL 23 SU 1 SI SI MA P1029 BP 326 EP 326 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CB9OG UT WOS:000349960600911 ER PT J AU Agran, M AF Agran, Martin TI Facilitated Communication: A House Divided SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Editorial Material ID AUTISM C1 [Agran, Martin] Univ Wyoming, Laramie, WY 82071 USA. RP Agran, M (reprint author), Univ Wyoming, Dept 3374, 1000 E Univ Ave, Laramie, WY 82071 USA. EM magran@uwyo.edu CR Broderick AA, 2001, J ASSOC PERS SEVERE, V26, P13, DOI 10.2511/rpsd.26.1.13 Cardinal D., 2014, RES PRACTICE PERSONS, V36 GREEN G, 1994, J ASSOC PERS SEVERE, V19, P151 HALLE JW, 1994, J ASSOC PERS SEVERE, V19, P149 Mostert M. P., 2014, RES PRACTICE PERSONS, V36 Mostert MP, 2010, EXCEPTIONALITY, V18, P1, DOI 10.1080/09362830903462409 Sheehan CM, 1996, MENT RETARD, V34, P94 SIMPSON RL, 1995, J SPEC EDUC, V28, P424 Singer G., 2014, RES PRACTICE PERSONS, V36 Travers J., 2014, RES PRACTICE PERSONS, V36 WHEELER DL, 1993, MENT RETARD, V31, P49 NR 11 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1540-7969 EI 2169-2408 J9 RES PRACT PERS SEV D JI Res. Pract. Pers. Sev. Disabil. PD SEP PY 2014 VL 39 IS 3 SI SI BP 175 EP 177 DI 10.1177/1540796914558830 PG 3 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300001 ER PT J AU Singer, GHS Horner, RH Dunlap, G Wang, MA AF Singer, George H. S. Horner, Robert H. Dunlap, Glen Wang, Mian TI Standards of Proof: TASH, Facilitated Communication, and the Science-Based Practices Movement SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE science based practices; research methods; values; facilitated communication ID SPECIAL-EDUCATION; SUPPORT; AUTISM; PERSPECTIVES; PARENTS; COMPETENCE; AUTHORSHIP; CHILDREN; IMPACT AB TASH's historic commitment to advocacy and science has enabled it to be a trusted voice for people with severe disabilities and their families. We review recent developments in the controversy over facilitated communication (FC) in light of major contextual continuities and changes in the past two decades. A series of scholarly reviews of the literature on controlled experiments have established a preponderance of evidence that FC is not reliably an expression from the individual who receives facilitation. Evidence indicates that the facilitator is the usual source of the text. We discuss the standards of proof of efficacy that must apply before an intervention should be endorsed by a national organization that aims to have a major impact on policy and practices. The need for controlled experiments in evaluation interventions is discussed. The central concern in establishing efficacy of a practice is to rule out other plausible explanations for an outcome. The main concern in establishing effectiveness is replication under real-world conditions. The science-based practices movement has been taken up by most of the helping professions contributing to the education and support of people with severe disabilities. The movement aims to identify practices and catalog them in terms of the trustworthiness of the evidence supporting them. The movement has led to establishing standards for determining when an intervention can be said to be efficacious. We urge TASH to join this movement and, in light of a commitment to science-based practices, argue that it should withdraw its stated endorsement of FC, which is not supported by science-based research. C1 [Singer, George H. S.; Wang, Mian] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Horner, Robert H.] Univ Oregon, Eugene, OR 97403 USA. [Dunlap, Glen] Univ Nevada, Reno, NV 89557 USA. [Dunlap, Glen] Univ S Florida, Tampa Bay, FL USA. RP Singer, GHS (reprint author), Univ Calif Santa Barbara, Gevertz Grad Sch Educ, Santa Barbara, CA 93106 USA. EM singer@education.ucsb.edu CR Ainbinder JG, 1998, J PEDIATR PSYCHOL, V23, P99, DOI 10.1093/jpepsy/23.2.99 Behavior Analysis Association of Michigan, 2014, BAAM SCI WATCH FAC C Biklen D., 2005, AUTISM MYTH PERSON A Biklen D., 1993, SPECIAL ED SERIES Biklen D., 1997, CONTESTED WORDS CONT Brassier L. L., 2001, FAMILYS LIFE UNRAVEL Broderick AA, 2001, J ASSOC PERS SEVERE, V26, P13, DOI 10.2511/rpsd.26.1.13 Calculator S., 1992, TOP LANG DISORD, V12, P9 Cardinal DN, 1996, MENT RETARD, V34, P231 Cho S.-J., 2003, FOCUS AUTISM OTHER D, V18, P9, DOI [10.1177/108835760301800103, DOI 10.1177/108835760301800103] Cook BG, 2013, EXCEPT CHILDREN, V79, P135 Crossley R., 1997, CONTESTED WRODS CONT, P209 Felce D., 1994, BRIT J LEARN DISABIL, V22, P122, DOI 10.1111/j.1468-3156.1994.tb00133.x Fox L, 1997, J ASSOC PERS SEVERE, V22, P198 Gangarosa EJ, 1998, LANCET, V351, P356, DOI 10.1016/S0140-6736(97)04334-1 Ganz JB, 2012, J AUTISM DEV DISORD, V42, P60, DOI 10.1007/s10803-011-1212-2 Greydanus DE, 2012, PEDIATR CLIN N AM, V59, P1, DOI 10.1016/j.pcl.2011.10.004 HALLE JW, 1994, J ASSOC PERS SEVERE, V19, P149 Hamer S., 2005, ACHIEVING EVIDENCE B Horner RH, 2005, EXCEPT CHILDREN, V71, P165 International Society for Augmentative and Alternative Communication, ISAAC POS S IN PRESS JACOBSON JW, 1995, AM PSYCHOL, V50, P750, DOI 10.1037//0003-066X.50.9.750 Kliewer C, 2006, AM EDUC RES J, V43, P163, DOI 10.3102/00028312043002163 Koegel LK, 1999, J ASSOC PERS SEVERE, V24, P174, DOI 10.2511/rpsd.24.3.174 Lucyshyn JM, 1995, J ASSOC PERS SEVERE, V20, P16 Maul CA, 2009, TOP EARLY CHILD SPEC, V29, P155, DOI 10.1177/0271121408328516 Mirenda P, 2003, TOP LANG DISORD, V23, P271 Mostert MP, 2001, J AUTISM DEV DISORD, V31, P287, DOI 10.1023/A:1010795219886 Mostert MP, 2010, EXCEPTIONALITY, V18, P31, DOI 10.1080/09362830903462524 National Autism Center, 2009, NAT STAND REP NAT ST National Research Council, 2002, MINORITY STUDENTS SP Odom SL, 2005, EXCEPT CHILDREN, V71, P137 OFFIT PA, 2012, BRIT MED J, V344, DOI DOI 10.1136/BMJ Offit Paul, 2008, AUTISMS FALSE PROPHE Perini S., 2010, PSICOTERAPIA COGNITI, V16, P103 Probst P, 2005, Z KLIN PSYCH PSYCHIA, V53, P93 Rubin S, 2001, DISABIL SOC, V16, P415 SABIN LA, 1993, J ASSOC PERS SEVERE, V18, P200 Saloviita T, 2014, AUGMENT ALTERN COMM, V30, P213, DOI 10.3109/07434618.2014.927529 Schiavo P., 2005, GIORNALE ITALIANO DI, V5, P3 Schlosser R, AUGMENTATIV IN PRESS Singer GHS, 1999, J EARLY INTERVENTION, V22, P217 Smith MJ, 2010, PEDIATRICS, V125, P1134, DOI 10.1542/peds.2009-2489 Snell M. E., 2010, INSTRUCTION STUDENTS Wang M, 2004, RES PRACT PERS SEV D, V29, P144, DOI 10.2511/rpsd.29.2.144 Wang M, 2007, J POSIT BEHAV INTERV, V9, P38 Wegner DM, 2003, J PERS SOC PSYCHOL, V85, P5, DOI 10.1037/0022-3514.85.1.5 Wehrenfennig A., 2008, PSICOLOGIA CLIN SVIL, V12, P437 Wennberg J E, 1984, Health Aff (Millwood), V3, P6, DOI 10.1377/hlthaff.3.2.6 West SG, 2010, PSYCHOL METHODS, V15, P18, DOI 10.1037/a0015917 What Works Clearinghouse, 2014, WWC PROC STAND HDB NR 51 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1540-7969 EI 2169-2408 J9 RES PRACT PERS SEV D JI Res. Pract. Pers. Sev. Disabil. PD SEP PY 2014 VL 39 IS 3 SI SI BP 178 EP 188 DI 10.1177/1540796914558831 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300002 ER PT J AU Cardinal, DN Falvey, MA AF Cardinal, Donald N. Falvey, Mary A. TI The Maturing of Facilitated Communication: A Means Toward Independent Communication SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE facilitated communication; multivariate analysis; severe disabilities; facilitated communication ID AUTHORSHIP; AUTISM; INDIVIDUALS; PERSPECTIVE; GRAMMAR; LEXICON AB Facilitated communication (FC) can be a successful means for people to learn to communicate effectively and independently. The preponderance of peer-reviewed articles supports FC as a useful tool for developing communication skills. While there has been a chasm of difference in qualitative versus quantitative studies on FC, researchers have produced a body of current literature confirming the method. Many people with significant intellectual disabilities, through the use of FC, have been able to demonstrate their ability to successfully communicate. We, as a profession, now need to respond with collaborative scholarship. In addition, revised position statements must be developed reflecting the past research findings and encouraging future research. C1 [Cardinal, Donald N.] Chapman Univ, Coll Educ Studies, Orange, CA 92866 USA. [Falvey, Mary A.] Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. RP Cardinal, DN (reprint author), Chapman Univ, Coll Educ Studies, One Univ Dr, Orange, CA 92866 USA. 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Pract. Pers. Sev. Disabil. PD SEP PY 2014 VL 39 IS 3 SI SI BP 189 EP 194 DI 10.1177/1540796914555581 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300003 ER PT J AU Travers, JC Tincani, MJ Lang, R AF Travers, Jason C. Tincani, Matt J. Lang, Russell TI Facilitated Communication Denies People With Disabilities Their Voice SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE Facilitated Communication; pseudoscience; autism; developmental disabilities; augmentative and alternative communication ID AUTISM; SYSTEM; SAY AB Facilitated Communication (FC) has been rebranded as "supported typing" and repackaged as rapid prompting method, but remains a disproven intervention for people with disabilities. Despite the absence of supportive evidence and abundant evidence that facilitators always author the messages, FC has experienced resurgence in popularity among families, professionals, and advocacy groups. Strategic marketing, confirmation bias, pseudoscience, anti-science, and fallacy explain this troubling renewal. We briefly discuss each of these and contrast the method with authentic augmentative and alternative communication to illustrate differences in values and practices. Our intention is to persuade readers to resist or abandon FC in favor of validated methods and to encourage advocacy organizations to advance agendas that emphasize genuine self-expression by people with disabilities. C1 [Travers, Jason C.] Univ Kansas, Lawrence, KS 66045 USA. [Tincani, Matt J.] Temple Univ, Philadelphia, PA 19122 USA. [Lang, Russell] Texas State Univ, San Marcos, TX USA. RP Travers, JC (reprint author), Univ Kansas, Joseph R Pearson Hall,Rm 521,1122 West Campus Rd, Lawrence, KS 66045 USA. 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Pract. Pers. Sev. Disabil. PD SEP PY 2014 VL 39 IS 3 SI SI BP 195 EP 202 DI 10.1177/1540796914556778 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300004 ER PT J AU Mostert, MP AF Mostert, Mark P. TI An Activist Approach to Debunking FC SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE facilitated communication; autism; special education ID FACILITATED COMMUNICATION; META-ANALYSIS; AUTISM; CHILDREN; SCIENCE AB Facilitated Communication (FC), a controversial educational intervention touted for persons with autism and other non-communicative conditions, has reemerged as a viable educational option despite a number of earlier empirical studies that unequivocally identified the facilitator as the author of any communication and not the client. Several intersecting vectors including a current dearth of new empirical studies debunking the practice, the proliferation of questionable research favorable to FC, and the increased acceptance by academic journals of the legitimacy of FC have fueled this resurgence. I suggest a series of activist approaches to counter the acceptance of FC as legitimate educational practice. C1 [Mostert, Mark P.] Regent Univ, Virginia Beach, VA 23454 USA. RP Mostert, MP (reprint author), Regent Univ, Sch Educ, 1000 Univ Dr, Virginia Beach, VA 23454 USA. 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PD SEP PY 2014 VL 39 IS 3 SI SI BP 203 EP 210 DI 10.1177/1540796914556779 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300005 ER PT J AU Domire, SC Wolfe, P AF Domire, Sarah C. Wolfe, Pamela TI Effects of Video Prompting Techniques on Teaching Daily Living Skills to Children With Autism Spectrum Disorders: A Review SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Review DE autism; technology; video-based instruction; video prompting; daily living skills ID SINGLE-SUBJECT RESEARCH; DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITY; ERROR-CORRECTION; STUDENTS; INDIVIDUALS; INSTRUCTION; TECHNOLOGY; SELF; INTERVENTION AB Video-based instruction is becoming a common intervention in today's classrooms. Previous research has focused primarily on video modeling techniques that required the student to watch an entire video of the task before attempting to complete the task independently. Video prompting is a form of video instruction that breaks down target skills into steps that are then performed directly after viewing each clip. The present review examined studies using video prompting techniques to teach functional and daily living skills to individuals with autism spectrum disorders (ASD). The focus of the review was on evaluation of the effectiveness of video prompting and the factors that affect student attention to the video, retention of target behavior, production of target behavior, and motivation. Results showed that video prompting was an effective intervention for teaching a wide array of target skills and that students with ASD were able to generalize and maintain the acquired skills. Video prompting was also shown to be more effective than both static picture prompts and video modeling techniques in terms of percentage of correct independent responding. Suggestions for practice and future research are discussed. C1 [Domire, Sarah C.; Wolfe, Pamela] Penn State Univ, University Pk, PA 16802 USA. RP Domire, SC (reprint author), Penn State Univ, 219 CEDAR Bldg, University Pk, PA 16802 USA. 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Pract. Pers. Sev. Disabil. PD SEP PY 2014 VL 39 IS 3 SI SI BP 211 EP 226 DI 10.1177/1540796914555578 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300006 ER PT J AU Kurth, JA Morningstar, ME Kozleski, EB AF Kurth, Jennifer A. Morningstar, Mary E. Kozleski, Elizabeth B. TI The Persistence of Highly Restrictive Special Education Placements for Students With Low-Incidence Disabilities SO RESEARCH AND PRACTICE FOR PERSONS WITH SEVERE DISABILITIES LA English DT Article DE inclusive education; low-incidence disabilities; severe disabilities; instruction ID SIGNIFICANT COGNITIVE DISABILITIES; INTELLECTUAL DISABILITIES; LEARNING-DISABILITIES; INCLUSION; ADOLESCENTS; AUTISM; IMPACT; INSTRUCTION; SETTINGS; CHILDREN AB The purpose of this study is to analyze the Least Restrictive Environment (LRE) data that states and U. S. territories report from the Office of Special Education Programs (OSEP) and discuss the status of the most restrictive special education placement settings for students with disabilities. In this analysis, we found that (a) states do not set rigorous improvement goals to reduce restrictive placements, (b) the percentage of students with disabilities placed in restrictive placements have remained essentially unchanged over the past decade, and (c) students with low-incidence (severe) disabilities are disproportionally placed in restrictive placements. These results suggest that segregated educational experiences continue for thousands of students with disabilities in spite of evidence that shows that opportunities to learn and develop are enhanced in more inclusive educational settings. C1 [Kurth, Jennifer A.] Univ Kansas, Lawrence, KS 66045 USA. [Morningstar, Mary E.] Univ Kansas, Dept Special Educ, Lawrence, KS 66045 USA. 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PD SEP PY 2014 VL 39 IS 3 SI SI BP 227 EP 239 DI 10.1177/1540796914555580 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CB7HK UT WOS:000349797300007 ER PT J AU Ahmed, SS Unland, T Slaven, JE Nitu, ME Rigby, MR AF Ahmed, Sheikh Sohail Unland, Tamara Slaven, James E. Nitu, Mara E. Rigby, Mark R. TI Successful Use of Intravenous Dexmedetomidine for Magnetic Resonance Imaging Sedation in Autistic Children SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE autistic spectrum disorders; conscious sedation; dexmedetomidine; magnetic resonance imaging; pediatrics ID PEDIATRIC-PATIENTS; CHLORAL HYDRATE; DEVELOPMENTAL DISORDERS; DOSE DEXMEDETOMIDINE; SPECTRUM DISORDERS; SAFE SEDATION; DOUBLE-BLIND; MANAGEMENT; MRI; PROPOFOL AB Objectives Autism and autism spectrum disorders (A/ASD) represent a family of neurodevelopmental conditions that are associated with overactive, difficult-to-control behaviors. Sedating these patients for magnetic resonance imaging (MRI) poses challenges. Children with A/ASD were examined against clinical controls to determine the effectiveness and safety of intravenous (IV) dexmedetomidine for deep sedation. Methods The quality assurance data on all of the children who received IV dexmedetomidine sedation for MRI between July 2007 and December 2012 were reviewed. Patients in both groups were sedated by an intensivist-based team with a standard plan of 2 g/kg IV dexmedetomidine administered for 10 minutes followed by an infusion of 1 gkg(-1)hour(-1). The amount of IV dexmedetomidine was titrated to the deep level of sedation. A total of 56 patients in the A/ASD group and 107 in the control group were sedated with no reported sedation failures. Sedation parameters were compared between the A/ASD and control groups using analysis of covariance models, controlling for age, sex, and weight. Results Children in the A/ASD group were predominantly male (73%) and older (6.1 0.3 years) than children in the control group (56%; 5.0 +/- 0.2 years; P < 0.05 for both). Procedure time was significantly shorter for patients in the A/ASD group than in control patients (34.6 +/- 2.4 vs 44.3 +/- 1.6 minutes; P < 0.05). The A/ASD and control groups required a similar IV bolus of dexmedetomidine (2.6 g/kg +/- 0.1 vs 2.4 g/kg +/- 0.10; P = 0.29), with a significantly lower infusion dose in the A/ASD group (0.74 g/kg +/- 0.05 vs 0.89 g/kg +/- 0.03; P < 0.05). Heart rates were similar in the A/ASD group and the control group (67.0 beats per minute +/- 1.6 vs 69.3 +/- 1.1 beats per minute; P = 0.250). There were no complications. Recovery time was approximately 7 minutes longer in the A/ASD group than in the control group, but this was nonsignificant (101.2 +/- 3.5 minutes vs 94.2 +/- 2.4 minutes; P = 0.12). Analyses were performed using analysis of covariance methods and generalized linear models to control for age, sex, and weight. Conclusions Children with A/ASD can be successfully sedated for MRIs with IV dexmedetomidine without complications. C1 [Ahmed, Sheikh Sohail] Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Indiana Univ Hlth, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. RP Ahmed, SS (reprint author), Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Indiana Univ Hlth, 705 Riley Hosp Dr,RI 2117, Indianapolis, IN 46202 USA. 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PD SEP PY 2014 VL 107 IS 9 BP 559 EP 564 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CA6VK UT WOS:000349053700005 PM 25188619 ER PT J AU Mikeska, T Craig, JM AF Mikeska, Thomas Craig, Jeffrey M. TI DNA Methylation Biomarkers: Cancer and Beyond SO Genes LA English DT Review DE cancer; diabetes; obesity; smoking; stress; autism; schizophrenia; bipolar disorder; depression; environmental factors ID EPIGENOME-WIDE ASSOCIATION; MGMT PROMOTER METHYLATION; GLUCOCORTICOID-RECEPTOR GENE; POLYMERASE-CHAIN-REACTION; POSTTRAUMATIC-STRESS-DISORDER; DEPENDENT PROBE AMPLIFICATION; PRADER-WILLI-SYNDROME; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; CHRONIC LYMPHOCYTIC-LEUKEMIA; CARDIOVASCULAR-DISEASE RISK AB Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient's response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease. C1 [Mikeska, Thomas] Genet Technol Ltd, Fitzroy, Vic 3065, Australia. [Craig, Jeffrey M.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Craig, Jeffrey M.] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia. RP Craig, JM (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. EM thomas.mikeska@gtglabs.com; jeff.craig@mcri.edu.au RI Mikeska, Thomas/B-4876-2008 OI Mikeska, Thomas/0000-0003-1318-0859 FU Murdoch Childrens Research Institute (MCRI); National Health and Medical Research Council; National Institutes of Health; Australian Twin Registry; Victorian Government's Operational Infrastructure Support Program FX Jeffrey M. Craig is supported by the Murdoch Childrens Research Institute (MCRI), the National Health and Medical Research Council, the National Institutes of Health, and the Australian Twin Registry. This work was supported by the Victorian Government's Operational Infrastructure Support Program. 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Research in this area, however, is relatively unexplored. This study developed and tested a video intervention to teach healthy eating to adults with DD. A 5-segment educational video, an accompanying workbook, and a facilitator guide were developed to teach basic healthy eating concepts to adults with DD. Twelve adults with DD took part in a 5-week educational program led by trained facilitators using the materials created. Pre- and posttests were used to measure knowledge gained from participating in the intervention. Seventy-five percent (n = 9) of participants improved their knowledge scores, 8% (n = 1) maintained residue knowledge, and 17% (n = 2) had a decrease in their score. Video instructions can be an effective intervention modality to increase knowledge in adults with DD about healthy eating. 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Indeed, the United States as a whole is said to be displaying an empathy deficit. When and why does empathy break down, and what predicts whether people will exert effort to experience empathy in challenging contexts? Across 7 studies, we found that people who held a malleable mindset about empathy (believing empathy can be developed) expended greater empathic effort in challenging contexts than did people who held a fixed theory (believing empathy cannot be developed). Specifically, a malleable theory of empathy whether measured or experimentally induced promoted (a) more self-reported effort to feel empathy when it is challenging (Study 1); (b) more empathically effortful responses to a person with conflicting views on personally important sociopolitical issues (Studies 2-4); (c) more time spent listening to the emotional personal story of a racial outgroup member (Study 5); and (d) greater willingness to help cancer patients in effortful, face-to-face ways (Study 6). 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[Teng, C.] Far Eastern Mem Hosp, Dept Med, Div Oncol & Hematol, New Taipei City, Taiwan. NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2014 VL 25 SU 4 MA 1372P DI 10.1093/annonc/mdu352.4 PG 1 WC Oncology SC Oncology GA AX4KG UT WOS:000346901000393 ER PT J AU Bosse, KR Shukla, AR Pawel, B Chikwava, KR Santi, M Tooke, L Castagna, K Biegel, JA Bagatell, R AF Bosse, Kristopher R. Shukla, Aseem R. Pawel, Bruce Chikwava, Kudakwashe R. Santi, Mariarita Tooke, Laura Castagna, Katherine Biegel, Jaclyn A. Bagatell, Rochelle TI Malignant rhabdoid tumor of the bladder and ganglioglioma in a 14 year-old male with a germline 22q11.2 deletion SO CANCER GENETICS LA English DT Article DE Rhabdoid; SMARCB1; distal 22q11.2 syndrome ID ATYPICAL TERATOID/RHABDOID TUMOR; OF-THE-LITERATURE; SWI/SNF COMPLEX; MUTATIONS; DISORDER; CANCER; SMARCB1/INI1; GENE; INI1 AB Malignant rhabdoid tumors (MRTs) are rare pediatric malignancies characterized by clinically aggressive lesions that typically show loss of SMARCB1 expression. We herein describe a case of a malignant rhabdoid tumor of the bladder in a 14-year-old male with an autism spectrum disorder and a de novo 3 Mb germline deletion in chromosome band 22q11.2 that included the SMARCB1 gene. The malignancy developed in the setting of chronic hematuria (>2 years) following the occurrence of two other lesions: a central nervous system ganglioglioma and an intraoral dermoid cyst. MRTs of the bladder are exceedingly rare, and this patient is the oldest child reported with this tumor to date. This case adds to the growing body of literature regarding the recently described, phenotypically diverse, distal 22q11.2 syndrome. Furthermore, this is the first reported case in which an MRT of the bladder appears to have developed from a pre-existing bladder lesion. Finally, this case further supports a rhabdoid tumorigenesis model in which heterozygous loss of SMARCB1 predisposes to initial tumor formation with intact SMARCB1 expression, with subsequent inactivation of the other SMARCB1 allele, which results in transformation into more malignant lesions. C1 [Bosse, Kristopher R.; Bagatell, Rochelle] Univ Penn, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Bosse, Kristopher R.; Shukla, Aseem R.; Pawel, Bruce; Chikwava, Kudakwashe R.; Santi, Mariarita; Tooke, Laura; Castagna, Katherine; Biegel, Jaclyn A.; Bagatell, Rochelle] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shukla, Aseem R.] Univ Penn, Childrens Hosp Philadelphia, Div Urol, Philadelphia, PA 19104 USA. [Pawel, Bruce; Chikwava, Kudakwashe R.; Santi, Mariarita; Tooke, Laura; Castagna, Katherine; Biegel, Jaclyn A.] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Bosse, Kristopher R.; Biegel, Jaclyn A.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Bagatell, R (reprint author), Univ Penn, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. 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PD SEP PY 2014 VL 207 IS 9 SI SI BP 415 EP 419 DI 10.1016/j.cancergen.2014.05.007 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AX3DB UT WOS:000346819600013 PM 25018128 ER PT J AU Martin, L Sample, H Gregg, M Wood, C AF Martin, Loren Sample, Hannah Gregg, Michael Wood, Caleb TI Validation of operant social motivation paradigms using BTBR T+tf/J and C57BL/6J inbred mouse strains SO BRAIN AND BEHAVIOR LA English DT Article DE Autism; behavior; mouse; open field; progressive ratio; three-chamber task; valence ID T PLUS TF/J; REPETITIVE BEHAVIOR; UNUSUAL REPERTOIRE; AUTISM; MICE; MODEL; VOCALIZATIONS; PHENOTYPES; RELEVANT AB Background: As purported causal factors are identified for autism spectrum disorder (ASD), new assays are needed to better phenotype animal models designed to explore these factors. With recent evidence suggesting that deficits in social motivation are at the core of ASD behavior, the development of quantitative measures of social motivation is particularly important. The goal of our study was to develop and validate novel assays to quantitatively measure social motivation in mice. Methods: In order to test the validity of our paradigms, we compared the BTBR strain, with documented social deficits, to the prosocial C57BL/6J strain. Two novel conditioning paradigms were developed that allowed the test mouse to control access to a social partner. In the social motivation task, the test mice lever pressed for a social reward. The reward contingency was set on a progressive ratio of reinforcement and the number of lever presses achieved in the final trial of a testing session (breakpoint) was used as an index of social motivation. In the valence comparison task, motivation for a food reward was compared to a social reward. We also explored activity, social affiliation, and preference for social novelty through a series of tasks using an ANY-Maze video-tracking system in an open-field arena. Results: BTBR mice had significantly lower breakpoints in the social motivation paradigm than C57BL/6J mice. However, the valence comparison task revealed that BTBR mice also made significantly fewer lever presses for a food reward. Conclusions: The results of the conditioning paradigms suggest that the BTBR strain has an overall deficit in motivated behavior. Furthermore, the results of the open-field observations may suggest that social differences in the BTBR strain are anxiety induced. C1 [Martin, Loren; Sample, Hannah; Gregg, Michael; Wood, Caleb] Azusa Pacific Univ, Dept Grad Psychol, Azusa, CA 91702 USA. RP Martin, L (reprint author), Azusa Pacific Univ, Dept Grad Psychol, 901 E Alosta Ave, Azusa, CA 91702 USA. EM lamartin@apu.edu FU Faculty Research Council at Azusa Pacific University; Faculty for Undergraduate Neuroscience and San Diego Instruments FX We thank the Faculty Research Council at Azusa Pacific University for internal grant support. We also thank Faculty for Undergraduate Neuroscience and San Diego Instruments for grant support in the form of an equipment loan of the ANY-Maze system. 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PD SEP PY 2014 VL 4 IS 5 BP 754 EP 764 DI 10.1002/brb3.273 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AX5NW UT WOS:000346974400014 PM 25328850 ER PT J AU Xiang, AH Wang, X Martinez, MP Getahun, D Page, KA Buchanan, TA Curry, ES Coleman, KJ AF Xiang, A. H. Wang, X. Martinez, M. P. Getahun, D. Page, K. A. Buchanan, T. A. Curry, E. S. Coleman, K. J. TI Gestational diabetes mellitus and risk for autism in offspring SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Xiang, A. H.; Wang, X.; Martinez, M. P.; Getahun, D.; Coleman, K. J.] Kaiser Permanente So Calif, Pasadena, CA 91101 USA. [Page, K. A.; Buchanan, T. A.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Curry, E. S.] Kaiser Permanente Fontana Med Ctr, Fontana, CA USA. NR 0 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2014 VL 57 SU 1 MA 156 BP S72 EP S73 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AS6PX UT WOS:000344386100156 ER PT J AU Wu, P Teot, L Murdoch, G Monaghan-Nichols, AP McFadden, K AF Wu, Peter Teot, Lisa Murdoch, Geoffrey Monaghan-Nichols, A. Paula McFadden, Kathryn TI Neuropathology of 22q11 Deletion Syndrome in an Infant SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE 22q11 deletion syndrome; cortex; interstitial neurons; neuropathology; subplate; velocardiofacial syndrome ID MOUSE MODEL; GENES; MRI AB The 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and one of the chromosomal conditions most associated with psychosis and autism spectrum disorder. To date, only 2 neuropathologic studies of 22q11DS have been reported. 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C1 [Wu, Peter] Univ Pittsburgh, Dietrich Sch Arts & Sci, Pittsburgh, PA 15260 USA. [Teot, Lisa] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Murdoch, Geoffrey] Univ Pittsburgh, Sch Med, Div Neuropathol, Pittsburgh, PA 15213 USA. [Monaghan-Nichols, A. Paula; McFadden, Kathryn] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA. RP McFadden, K (reprint author), Univ Pittsburgh, Sch Med, Dept Neurobiol, 6065 BST 3,3501 Fifth Ave, Pittsburgh, PA 15213 USA. 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TI Diagnostic Challenges and Educational Planning in Autism SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD SEP PY 2014 VL 29 IS 6 SI SI MA B-43 PG 1 WC Psychology, Clinical; Psychology SC Psychology GA AU9CW UT WOS:000345890200138 ER PT J AU DiCowden, M Miller, S Brumer, C Fernandez, V AF DiCowden, M. Miller, S. Brumer, C. Fernandez, V TI Using the International Classification of Functioning to Track Functional Improvement: A 9-Year Longitudinal Study of an Adolescent with Severe Autism SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD SEP PY 2014 VL 29 IS 6 SI SI MA C-62 PG 1 WC Psychology, Clinical; Psychology SC Psychology GA AU9CW UT WOS:000345890200249 ER PT J AU Wellmann, KA Varlinskaya, EI Mooney, SM AF Wellmann, Kristen A. Varlinskaya, Elena I. Mooney, Sandra M. TI D-Cycloserine ameliorates social alterations that result from prenatal exposure to valproic acid SO BRAIN RESEARCH BULLETIN LA English DT Article DE Adolescence; Autism; Prenatal; Rat; Social behavior; Ultrasonic vocalization ID AUTISM SPECTRUM DISORDERS; ANXIETY DISORDER; ULTRASONIC VOCALIZATIONS; IMPROVES SOCIABILITY; REPEATED RESTRAINT; PARTIAL AGONIST; ANIMAL-MODEL; ADULT RATS; MICE; BEHAVIOR AB Prenatal exposure to valproic acid (VPA) alters rodent social interactions in a dose-dependent way: exposure to a high dose of VPA (>500 mg/kg) mid-gestation decreases social interactions whereas a moderate dose of VPA (350 mg/kg) increases peer-directed social behavior. The moderate dose also decreases expression of the mRNA for serine in amygdala and orbitofrontal cortex. In this study, we examined whether D-cycloserine could ameliorate VPA-induced alterations in ultrasonic vocalizations (USVs), social interactions, and locomotor activity. Pregnant Sprague Dawley rats were given intraperintoneal injections of VPA (200 mg/kg each) on gestational days 12, 12.5 and 13; controls were injected with saline. Offspring received a subcutaneous injection of saline or D-cycloserine (32 or 64 mg/kg) either acutely (1 h prior to testing) or repeatedly (once per day for four days). Social interactions were assessed during late adolescence, and USVs were recorded concomitantly. Male and female rats that were exposed to VPA demonstrated more locomotor activity than control animals during habituation to the testing chamber. VPA-exposed males showed increased play fighting. D-Cycloserine normalized the VPA-induced increase in play fighting in males and also increased social motivation in females. When the pair contained a VPA-exposed rat, significantly fewer USVs were emitted and 16% of the vocalizations were of a novel waveform. These effects were not seen in pairs containing VPA-exposed animals that were treated with D-cycloserine. Overall, these findings are consistent with data from other laboratories suggesting that D-cycloserine may be a promising pharmacotherapeutic compound for improving social behavior disorders. (C) 2014 Elsevier Inc. All rights reserved. C1 [Wellmann, Kristen A.; Mooney, Sandra M.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Varlinskaya, Elena I.] SUNY Binghamton, Dept Psychol, Ctr Dev & Behav Neurosci, Binghamton, NY 13902 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Baltimore, MD 21201 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Binghamton, NY 13902 USA. [Varlinskaya, Elena I.; Mooney, Sandra M.] Dev Exposure Alcohol Res Ctr, Syracuse, NY 13210 USA. RP Mooney, SM (reprint author), Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. EM kwellmann@peds.umaryland.edu; varlinsk@binghamton.edu; smooney@peds.umaryland.edu FU Autism Speaks [4946]; National Institute of Alcohol Abuse and Alcoholism [AA018693, AA0178231] FX The authors thank Celina Tran and Nathan Nguyen for technical assistance and Dr. Jeffery Burgdorf for advice regarding the USV data. This research was supported by Autism Speaks (4946 to SMM) and the National Institute of Alcohol Abuse and Alcoholism (AA018693 and AA0178231 to SMM). 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Bull. PD SEP PY 2014 VL 108 BP 1 EP 9 DI 10.1016/j.brainresbull.2014.08.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AU2UC UT WOS:000345471900001 PM 25130667 ER PT J AU Limeres-Posse, J Castano-Novoa, P Abeleira-Pazos, M Ramos-Barbosa, I AF Limeres-Posse, Jacobo Castano-Novoa, Patricia Abeleira-Pazos, Maite Ramos-Barbosa, Isabel TI Behavioural aspects of patients with Autism Spectrum Disorders (ASD) that affect their dental management SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Dentistry; autism; ASD; behavior management ID CARIES EXPERIENCE; CHILDREN; ADOLESCENTS; ADULTS AB Dental treatment in patients with Autism Spectrum Disorders (ASD) can be complicated due to the presence of behavioral alterations. In this group, there are no specific behavioral profiles that allow dentist to anticipate the attitude that a patient will show during a visit. Thus, behavioral attitudes have been described that vary from total permissiveness and collaboration during even bloody procedures, to the absolute impossibility in conducting a simple oral examination. There is no effective behavioral management technique for all ASD patients. Prior information, such as the type of ASD or the presence of certain concurrent pathologies can help predict the patient's likely behavior. Therefore, gathering all the information in a preliminary interview with the parents/guardians of the patient is recommended. Knowing these factors will allow individualized behavioral management strategies to be designed and facilitates the planning of dental treatment. C1 [Limeres-Posse, Jacobo; Castano-Novoa, Patricia; Abeleira-Pazos, Maite; Ramos-Barbosa, Isabel] Univ Santiago de Compostela, Sch Med & Dent, Grp Invest Odontol Medicoquirurg OMEQUI, Santiago De Compostela, Spain. 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Bucal PD SEP PY 2014 VL 19 IS 5 BP E467 EP E472 DI 10.4317/medoral.19566 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AU1HO UT WOS:000345371900007 PM 24608219 ER PT J AU Machuca-Portillo, G Cabrerizo-Merino, C Cutando-Soriano, A Gimenez-Prats, MJ Silvestre-Donat, FJ Tomas-Carmona, I AF Machuca-Portillo, Guillermo Cabrerizo-Merino, Carmen Cutando-Soriano, Antonio Gimenez-Prats, Maria-Jose Silvestre-Donat, Farncisco-Javier Tomas-Carmona, Inmaculada TI Consensus Report of the XI Congress of the Spanish Society of Odontology for the Handicapped and Special Patients SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Autism; cardiovascular diseases; cerebral palsy; dental implants; disabled patients; haematological disorders; hospital dentistry AB This article summarizes the findings of consensus of the XI congress of the SEOEME. All of these conclusions are referring to the review articles responsible to the general rapporteurs in order to bringing up to date knowledge with regard to the use of implants in patients medically compromised and with special needs and, in the dental management of autism and cerebral palsy, in the dental treatment of patients with genetic and adquired haematological disorders, the dental implications of cardiovascular disease and hospital dentistry. C1 [Machuca-Portillo, Guillermo] Univ Seville, Fac Odontol, E-41009 Seville, Spain. [Cabrerizo-Merino, Carmen] Univ Odontol Clin, Fac Med, Murcia, Spain. [Cutando-Soriano, Antonio] Univ Granada, Fac Odontol, E-18071 Granada, Spain. [Gimenez-Prats, Maria-Jose] Hosp Nen Deu, Barcelona, Spain. [Silvestre-Donat, Farncisco-Javier] Univ Valencia, Fac Odontol, E-46003 Valencia, Spain. [Tomas-Carmona, Inmaculada] Univ Santiago de Compostela, Fac Med & Odontol, Santiago De Compostela, Spain. 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Bucal PD SEP PY 2014 VL 19 IS 5 BP E495 EP E499 DI 10.4317/medoral.19569 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AU1HO UT WOS:000345371900012 PM 24608224 ER PT J AU Hester, MS Danzer, SC AF Hester, Michael S. Danzer, Steve C. TI Hippocampal granule cell pathology in epilepsy - A possible structural basis for comorbidities of epilepsy? SO EPILEPSY & BEHAVIOR LA English DT Review DE Epilepsy; mTOR; Neurogenesis; Disc1; Reelin; Schizophrenia; Autism ID TEMPORAL-LOBE EPILEPSY; ADULT DENTATE GYRUS; SEIZURE-INDUCED NEUROGENESIS; TUBEROUS SCLEROSIS COMPLEX; AUTISM SPECTRUM DISORDERS; NEWLY GENERATED NEURONS; HILAR BASAL DENDRITES; TRANSLATION REPRESSOR 4E-BP2; ENHANCED SYNAPTIC PLASTICITY; PILOCARPINE-INDUCED SEIZURES AB Temporal lobe epilepsy in both animals and humans is characterized by abnormally integrated hippocampal dentate granule cells. Among other abnormalities, these cells make axonal connections with inappropriate targets, grow dendrites in the wrong direction, and migrate to ectopic locations. These changes promote the formation of recurrent excitatory circuits, leading to the appealing hypothesis that these abnormal cells may by epileptogenic. While this hypothesis has been the subject of intense study, less attention has been paid to the possibility that abnormal granule cells in the epileptic brain may also contribute to comorbidities associated with the disease. Epilepsy is associated with a variety of general findings, such as memory disturbances and cognitive dysfunction, and is often comorbid with a number of other conditions, including schizophrenia and autism. Interestingly, recent studies implicate disruption of common genes and gene pathways in all three diseases. Moreover, while neuropsychiatric conditions are associated with changes in a variety of brain regions, granule cell abnormalities in temporal lobe epilepsy appear to be phenocopies of granule cell deficits produced by genetic mouse models of autism and schizophrenia, suggesting that granule cell dysmorphogenesis may be a common factor uniting these seemingly diverse diseases. Disruption of common signaling pathways regulating granule cell neurogenesis may begin to provide mechanistic insight into the cooccurrence of temporal lobe epilepsy and cognitive and behavioral disorders. (C) 2014 Elsevier Inc. All rights reserved. C1 [Hester, Michael S.; Danzer, Steve C.] Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, Cincinnati, OH 45229 USA. [Danzer, Steve C.] Univ Cincinnati, Dept Anesthesia, Cincinnati, OH 45267 USA. [Danzer, Steve C.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45267 USA. [Hester, Michael S.; Danzer, Steve C.] Cincinnati Childrens Hosp Med Ctr, Mol & Dev Biol Grad Program, Cincinnati, OH 45229 USA. RP Danzer, SC (reprint author), 3333 Burnet Ave,ML 2001, Cincinnati, OH 45229 USA. EM steve.danzer@cchmc.org FU National Institute of Neurological Disorders and Stroke [R01NS065020, R01NS062806] FX This work was supported by the National Institute of Neurological Disorders and Stroke (SCD, Award Numbers R01NS065020 and R01NS062806). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Special thanks to Victor Santos, Dr. Candi LaSarge, and Dr. Brian Murphy for help with Figs. 2, 5, and 6, respectively. We would also like to thank Keri Kaeding for useful comments on earlier versions of this manuscript. 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PD SEP PY 2014 VL 38 SI SI BP 105 EP 116 DI 10.1016/j.yebeh.2013.12.022 PG 12 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AT9FJ UT WOS:000345233000016 PM 24468242 ER PT J AU Sivapalan, S Aitchison, KJ AF Sivapalan, Sudhakar Aitchison, Katherine J. TI Neurological Structure Variations in Individuals with Autism Spectrum Disorder: a Review SO KLINIK PSIKOFARMAKOLOJI BULTENI-BULLETIN OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review DE autism spectrum disorder; neuroimaging; brain; MRI; CT; review ID CORTICAL THICKNESS; HEAD CIRCUMFERENCE; BRAIN ENLARGEMENT; CORPUS-CALLOSUM; ADULTS; CHILDREN; MRI; FEATURES; VOLUME; SIZE AB Autism spectrum disorder is a neurodevelopmental disorder that is characterized by impairments in social communication and social interactions along with repetitive, stereotyped behaviors and interests. The spectrum is quite broad, and the pathophysiology appears to be related to a number of factors. A common theme is that the disorder is one of impaired brain development. Neuroimaging studies offer a way to investigate impaired brain development by considering structural differences between those with autism and those without. Areas of focus include neuroanatomical regions that correlate with the clinically recognizable features of autism. In this review of structural studies, volumetric variation in terms of grey and white matter and total brain volume and in terms of neurological structures (e.g. frontal lobe, parietal cortex, amygdala, etc.) is discussed. Although a few trends have been noted, much of the literature demonstrates heterogeneity in the reported findings, which likely reflects the heterogeneity of the clinical presentation of this disorder. Further studies will need to correlate these structural findings with functional data and look to better understand the underlying molecular and genetic processes. C1 [Sivapalan, Sudhakar] Univ Alberta, Dept Psychiat, Edmonton, AB T6G 2B7, Canada. [Aitchison, Katherine J.] Univ Alberta, Dept Psychiat, Alberta Centennial Addict & Mental Hlth Res Chair, Edmonton, AB T6G 2E1, Canada. [Aitchison, Katherine J.] Univ Alberta, Dept Med Genet, Alberta Centennial Addict & Mental Hlth Res Chair, Edmonton, AB T6G 2E1, Canada. RP Sivapalan, S (reprint author), Univ Alberta, Dept Psychiat, Walter Mackenzie Hlth Sci Ctr 1E1, 8440 112 St NW, Edmonton, AB T6G 2B7, Canada. EM sivapala@ualberta.ca FU Government of Alberta FX Dr. Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair funded by the Government of Alberta. 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Psikofarmakol. Bul. PD SEP PY 2014 VL 24 IS 3 BP 268 EP 275 DI 10.5455/bcp.20140903110206 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AT7HY UT WOS:000345108400012 ER PT J AU Basil, P Li, Q Dempster, EL Mill, J Sham, PC Wong, CCY McAlonan, GM AF Basil, P. Li, Q. Dempster, E. L. Mill, J. Sham, P-C Wong, C. C. Y. McAlonan, G. M. TI Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID CPG-BINDING-PROTEIN; DNA METHYLATION; GENE-EXPRESSION; RETT-SYNDROME; L1 RETROTRANSPOSITION; BIPOLAR DISORDER; MUS-MUSCULUS; MECP2; SCHIZOPHRENIA; AUTISM AB Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI: C caused significant global DNA hypomethylation (t = 2.44, P = 0.019, PolyI: C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t = 3.32, P = 0.002; PolyI: C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment. C1 [Basil, P.; Li, Q.; Sham, P-C; McAlonan, G. M.] Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China. [Dempster, E. L.; Mill, J.] Univ Exeter, Univ Exeter Med Sch, Exeter, Devon, England. [Mill, J.; Wong, C. C. Y.] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Sham, P-C] Univ Hong Kong, Ctr Genom Sci, Pokfulam, Hong Kong, Peoples R China. [McAlonan, G. M.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London SE5 8AF, England. RP McAlonan, GM (reprint author), Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, De Crespigny Pk,Denmark Hill, London SE5 8AF, England. EM grainne.mcalonan@kcl.ac.uk RI Wong, Chloe/B-3679-2012 OI Wong, Chloe/0000-0003-4886-8506 FU Post Graduate Scholarship, HKU; Graduate Research Exchange Scheme, Faculty of Medicine, HKU; Hong Kong Universities General Research Fund [GRF_HKU 774710M]; ZEE Foundation, Hong Kong FX We thank members of the Psychiatric Epigenetic group for Infrastructural support for aspects of the study at Social, Genetic and Developmental Psychiatry, Department of Forensic and Neurodevelopmental Sciences, Kings College London and Statistical Genetics group, Department of Psychiatry, The University of Hong Kong (HKU). PB is supported by a Post Graduate Scholarship, HKU and the Graduate Research Exchange Scheme, Faculty of Medicine, HKU. The experimental work was supported by Hong Kong Universities General Research Fund award GRF_HKU 774710M. We also acknowledge ZEE Foundation, Hong Kong for their financial support. GM is a member of the EU-AIMS consortium. 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TI DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; ENVIRONMENTAL-FACTORS; INCREASED PREVALENCE; SYNAPTIC FUNCTION; MICROGLIA; NEURONS; ROLES; AGE; CONNECTIVITY AB Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by dysfunction in social interaction, communication and stereotypic behavior. Genetic and environmental factors have been implicated in the development of ASD, but the molecular mechanisms underlying their interaction are not clear. Epigenetic modifications have been suggested as molecular mechanism that can mediate the interaction between the environment and the genome to produce adaptive or maladaptive behaviors. Here, using the Illumina 450 K methylation array we have determined the existence of many dysregulated CpGs in two cortical regions, Brodmann area 10 (BA10) and Brodmann area 24 (BA24), of individuals who had ASD. In BA10 we found a very significant enrichment for genomic areas responsible for immune functions among the hypomethylated CpGs, whereas genes related to synaptic membrane were enriched among hypermethylated CpGs. By comparing our methylome data with previously published transcriptome data, and by performing real-time PCR on selected genes that were dysregulated in our study, we show that hypomethylated genes are often overexpressed, and that there is an inverse correlation between gene expression and DNA methylation within the individuals. Among these genes there were C1Q, C3, ITGB2 (C3R), TNF-alpha, IRF8 and SPI1, which have recently been implicated in synaptic pruning and microglial cell specification. Finally, we determined the epigenetic dysregulation of the gene HDAC4, and we confirm that the locus encompassing C11orf21/TSPAN32 has multiple hypomethylated CpGs in the autistic brain, as previously demonstrated. Our data suggest a possible role for epigenetic processes in the etiology of ASD. C1 [Nardone, S.; Sams, D. Sharan; Reuveni, E.; Getselter, D.; Oron, O.; Karpuj, M.; Elliott, E.] Bar Ilan Univ, Fac Med, IL-13215 Safed, Israel. RP Elliott, E (reprint author), Bar Ilan Univ, Fac Med, Hanrietta Sold 8, IL-13215 Safed, Israel. EM evan.elliott@biu.ac.il FU ISRAEL SCIENCE FOUNDATION [1047/12]; National Institute of Psychobiology in Israel FX We thank Dr Nili Avidan from the Genomics Core Facility of The Rappaport Family Institute for Research in the Medical Sciences (Haifa, IL, USA) for the preliminary analysis of the Illumina 450K methylation array. In addition, we thank Professor Itzhak Haviv from the Bar Ilan University Faculty of Medicine (Safed, IL, USA) for his informative discussion which improved the quality of this work. We thank the Autism Tissue Program, the Harvard Brain Tissue Resource Center and Oxford University for the control and autism tissues used in this project. This research was supported by the ISRAEL SCIENCE FOUNDATION (grant No. 1047/12) and the National Institute of Psychobiology in Israel. 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Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-related pathways. However, the regulatory role and targets of Auts2 are not well known. Here, by using ChIP-seq (chromatin immunoprecipitation followed by deep sequencing) and RNA-seq on mouse embryonic day 16.5 forebrains, we elucidated the gene regulatory networks of Auts2. We find that the majority of promoters bound by Auts2 belong to genes highly expressed in the developing forebrain, suggesting that Auts2 is involved in transcriptional activation. Auts2 non-promoter-bound regions significantly overlap developing brain-associated enhancer marks and are located near genes involved in neurodevelopment. Auts2-marked sequences are enriched for binding site motifs of neurodevelopmental transcription factors, including Pitx3 and TCF3. In addition, we characterized two functional brain enhancers marked by Auts2 near NRXN1 and ATP2B2, both ASD-implicated genes. Our results implicate Auts2 as an active regulator of important neurodevelopmental genes and pathways and identify novel genomic regions that could be associated with ASD and other neurodevelopmental diseases. C1 [Oksenberg, N.; Eckalbar, W. L.; Nishizaki, S.; Murphy, K.; Birnbaum, R. Y.; Ahituv, N.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. [Oksenberg, N.; Haliburton, G. D. E.; Eckalbar, W. L.; Nishizaki, S.; Murphy, K.; Pollard, K. S.; Birnbaum, R. Y.; Ahituv, N.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. [Haliburton, G. D. E.; Pollard, K. S.] Gladstone Inst, San Francisco, CA USA. [Oren, I.; Birnbaum, R. Y.] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [Pollard, K. S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94158 USA. RP Ahituv, N (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, 1550 4th St,Rock Hall,RH584C, San Francisco, CA 94158 USA. EM ramonb@bgu.ac.il; nadav.ahituv@ucsf.edu FU Simons Foundation, SFARI [256769]; National Institute of Neurological Disorders and Stroke [1R01NS079231]; German-Israel Foundation [I-2360-203]; Career Integration grant (CIG) [630849]; National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK090382]; National Human Genome Research Institute [R01HG005058, R01HG006768]; National Institute of Child and Human Development [R01HD059862]; National Institute of General Medical Sciences [GM61390]; NHLBI [HL098179]; J David Gladstone Institutes FX We would like to thank Megan Laurance for her assistance with IPA and Mariel Mckenzie Finucane with her assistance with statistics. This work was supported by a grant from the Simons Foundation, SFARI no. 256769, the National Institute of Neurological Disorders and Stroke grant number 1R01NS079231 and German-Israel Foundation grant number I-2360-203. RYB is supported in part by the Career Integration grant (CIG) number 630849. NA is also supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases grant number 1R01DK090382, the National Human Genome Research Institute grant numbers R01HG005058 and R01HG006768, the National Institute of Child and Human Development grant number R01HD059862, and the National Institute of General Medical Sciences grant number GM61390. KSP and GDEH are also supported by NHLBI grant number HL098179, a gift from the San Simeon Fund, and institutional funds from the J David Gladstone Institutes. 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Self-reported data on ASD dimensions social and communication difficulties (ASDsc), and repetitive and restricted behavior and interests (ASDr), and ADHD dimensions inattention (IA), and hyperactivity/impulsivity (HI) were assessed in a community sample of 17 770 adult Swedish twins. Phenotypic, genetic and environmental associations between disorder dimensions were examined in a multivariate model, accounting for sex differences. ASDr showed the strongest associations with IA and HI in both sexes (r(p) 0.33 to 0.40). ASDsc also correlated moderately with IA (females r(p) 0.29 and males r(p) 0.35) but only modestly with HI (females r(p) 0.17 and males r(p) 0.20). Genetic correlations ranged from 0.22 to 0.64 and were strongest between ASDr and IA and HI. Sex differences were virtually absent. The ASDr dimension (reflecting restricted, repetitive and stereotyped patterns of behavior, interests and activities) showed the strongest association with dimensions of ADHD, on a phenotypic, genetic and environmental level. This study opens new avenues for molecular genetic research. As our findings demonstrated that genetic overlap between disorders is dimension-specific, future gene-finding studies on psychiatric comorbidity should focus on carefully selected genetically related dimensions of disorders. C1 [Polderman, T. J. C.; Posthuma, D.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. [Hoekstra, R. A.] Open Univ, Fac Sci, Dept Life Hlth & Chem Sci, Milton Keynes MK7 6AA, Bucks, England. [Posthuma, D.] Vrije Univ Amsterdam Med Ctr, Dept Complex Trait Genet, Amsterdam, Netherlands. [Larsson, H.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Polderman, TJC (reprint author), Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Neurosci Campus Amsterdam,De Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM tinca.polderman@vu.nl FU Netherlands Organization for Scientific research (NWO Brain Cognition) [433-09-228]; Neuroscience Campus Amsterdam; Swedish research council FX We thank the participants of STAGE. TJCP and DP would like to acknowledge financial support from the Netherlands Organization for Scientific research (NWO Brain & Cognition: 433-09-228), and the Neuroscience Campus Amsterdam. HL would like to acknowledge financial support from the Swedish research council. 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PD SEP PY 2014 VL 4 AR e435 DI 10.1038/tp.2014.84 PG 7 WC Psychiatry SC Psychiatry GA AT3HS UT WOS:000344827000005 PM 25180574 ER PT J AU Natsubori, T Inoue, H Abe, O Takano, Y Iwashiro, N Aoki, Y Koike, S Yahata, N Katsura, M Gonoi, W Sasaki, H Takao, H Kasai, K Yamasue, H AF Natsubori, Tatsunobu Inoue, Hideyuki Abe, Osamu Takano, Yosuke Iwashiro, Norichika Aoki, Yuta Koike, Shinsuke Yahata, Noriaki Katsura, Masaki Gonoi, Wataru Sasaki, Hiroki Takao, Hidemasa Kasai, Kiyoto Yamasue, Hidenori TI Reduced Frontal Glutamate plus Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE anterior cingulate cortex; at-risk mental state; biomarkers; frontal lobe; magnetic resonance imaging; neurochemical abnormality ID MAGNETIC-RESONANCE-SPECTROSCOPY; GRAY-MATTER VOLUME; AUTISM SPECTRUM DISORDERS; CHILDHOOD-ONSET SCHIZOPHRENIA; ANTERIOR CINGULATE CORTEX; NMDA RECEPTOR SUBUNITS; TWIN PAIRS DISCORDANT; H-1 MR SPECTROSCOPY; PREFRONTAL CORTEX; TEMPORAL-LOBE AB Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy (H-1 MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in 1H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent 1H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in 1H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia. C1 [Natsubori, Tatsunobu; Inoue, Hideyuki; Takano, Yosuke; Iwashiro, Norichika; Aoki, Yuta; Koike, Shinsuke; Yahata, Noriaki; Kasai, Kiyoto; Yamasue, Hidenori] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138655, Japan. [Abe, Osamu; Katsura, Masaki; Gonoi, Wataru; Sasaki, Hiroki; Takao, Hidemasa] Univ Tokyo, Grad Sch Med, Dept Radiol, Tokyo 1138655, Japan. [Abe, Osamu] Nihon Univ, Sch Med, Dept Radiol, 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 Ministry of Education, Culture, Sports, Science and Technology (MEXT); KAKENHI [22689034, 20591378, 21249064]; Global Center of Excellence (COE) Program "Comprehensive Center of Education and Research for Chemical Biology of the Diseases"; Health and Labour Sciences Research Grants for Comprehensive Research on Disability, Health and Welfare [H22-seishin-ippan-015] FX "Development of biomarker candidates for social behavior" project carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology (MEXT); KAKENHI (22689034 to H.Y., 20591378 to N.Y., 21249064 to K. K.); Global Center of Excellence (COE) Program "Comprehensive Center of Education and Research for Chemical Biology of the Diseases" (to N.Y.); Health and Labour Sciences Research Grants for Comprehensive Research on Disability, Health and Welfare (H22-seishin-ippan-015 to K.K.). 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Bull. PD SEP PY 2014 VL 40 IS 5 BP 1128 EP 1139 DI 10.1093/schbul/sbt124 PG 12 WC Psychiatry SC Psychiatry GA AT0ET UT WOS:000344610800023 PM 24023251 ER PT J AU LaGasse, AB AF LaGasse, A. Blythe TI Effects of a Music Therapy Group Intervention on Enhancing Social Skills in Children with Autism SO JOURNAL OF MUSIC THERAPY LA English DT Article DE autism spectrum disorder; group intervention; music therapy; social skills ID SPECTRUM DISORDERS; RESPONSIVENESS; BEHAVIORS; PROFILE; SPEECH; ADULTS; SONG AB Background: Research indicates that music therapy can improve social behaviors and joint attention in children with Autism Spectrum Disorder (ASD); however, more research on the use of music therapy interventions for social skills is needed to determine the impact of group music therapy. Objective: To examine the effects of a music therapy group intervention on eye gaze, joint attention, and communication in children with ASD. Method: Seventeen children, ages 6 to 9, with a diagnosis of ASD were randomly assigned to the music therapy group (MTG) or the no-music social skills group (SSG). Children participated in ten 50-minute group sessions over a period of 5 weeks. All group sessions were designed to target social skills. The Social Responsiveness Scale (SRS), the Autism Treatment Evaluation Checklist (ATEC), and video analysis of sessions were used to evaluate changes in social behavior. Results: There were significant between-group differences for joint attention with peers and eye gaze towards persons, with participants in the MTG demonstrating greater gains. There were no significant between-group differences for initiation of communication, response to communication, or social withdraw/behaviors. There was a significant interaction between time and group for SRS scores, with improvements for the MTG but not the SSG. Scores on the ATEC did not differ over time between the MTG and SSG. Conclusions: The results of this study support further research on the use of music therapy group interventions for social skills in children with ASD. Statistical results demonstrate initial support for the use of music therapy social groups to develop joint attention. C1 [LaGasse, A. Blythe] Colorado State Univ, Ft Collins, CO 80523 USA. RP LaGasse, AB (reprint author), 1778 Campus Delivery, Ft Collins, CO 80524 USA. 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PD FAL PY 2014 VL 51 IS 3 BP 250 EP 275 DI 10.1093/jmt/thu012 PG 26 WC Music; Rehabilitation SC Music; Rehabilitation GA AS3KU UT WOS:000344177300004 PM 25053766 ER PT J AU Anitha, A Thanseem, I Nakamura, K Vasu, MM Yamada, K Ueki, T Iwayama, Y Toyota, T Tsuchiya, KJ Iwata, Y Suzuki, K Sugiyama, T Tsujii, M Yoshikawa, T Mori, N AF Anitha, Ayyappan Thanseem, Ismail Nakamura, Kazuhiko Vasu, Mahesh M. Yamada, Kazuo Ueki, Takatoshi Iwayama, Yoshimi Toyota, Tomoko Tsuchiya, Kenji J. Iwata, Yasuhide Suzuki, Katsuaki Sugiyama, Toshiro Tsujii, Masatsugu Yoshikawa, Takeo Mori, Norio TI Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; ANTERIOR CINGULATE CORTEX; HIGH-FUNCTIONING AUTISM; RISK GENE; SCHIZOPHRENIA-PATIENTS; SPECTRUM DISORDERS; PSYCHOSIS VARIANT; SOCIAL COGNITION; REVISED VERSION; WORKING-MEMORY AB Background: In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism. Methods: We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition. Results: We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001). Limitations: Study limitations include our small sample size of postmortem brains. Conclusion: Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism. C1 [Anitha, Ayyappan; Tsuchiya, Kenji J.; Tsujii, Masatsugu; Mori, Norio] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan. [Thanseem, Ismail; Vasu, Mahesh M.; Iwata, Yasuhide; Suzuki, Katsuaki; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat, Hamamatsu, Shizuoka 4313192, Japan. [Nakamura, Kazuhiko] Hirosaki Univ, Sch Med, Dept Psychiat, Hirosaki, Aomori 036, Japan. [Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Yoshikawa, Takeo] RIKEN Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama, Japan. [Ueki, Takatoshi] Hamamatsu Univ Sch Med, Dept Anat, Hamamatsu, Shizuoka 4313192, Japan. [Sugiyama, Toshiro] Hamamatsu Univ Sch Med, Dept Child & Adolescent Psychiat, Hamamatsu, Shizuoka 4313192, Japan. [Tsujii, Masatsugu] Chukyo Univ, Fac Sociol, Toyota, Japan. RP Nakamura, K (reprint author), Hirosaki Univ, Sch Med, Dept Psychiat, 5 Zaifu Cho, Hirosaki, Aomori 0368562, Japan. EM nakakazu@cc.hirosaki-u.ac.jp FU National Institute of Mental Health [1U24MH081810]; PHS grant [R24 MH 068855]; Ministry of Education, Culture, Sports, Science, and Technology, Japan; Takeda Science Foundation, Japan; Strategic Research Program for Brain Sciences (Integrated research on neuropsychiatric disorders) FX We gratefully acknowledge the resources provided by the AGRE Consortium and the participating AGRE families. The AGRE is a program of Autism Speaks and is supported in part by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (P.I.). We thank Dr. Jane Pickett, Director of Brain Resources and Data, ATP, for facilitating brain tissue collection. Human tissue was obtained from the NICHD BTB for Developmental Disorders at the University of Maryland. Tissue samples were also provided by the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH 068855. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (A.A., K.N.), the Takeda Science Foundation, Japan (K.S.), and partly by the Strategic Research Program for Brain Sciences (Integrated research on neuropsychiatric disorders). We thank Tae Takahashi and Mika Oyaizu for technical assistance. 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Psychiatry Neurosci. PD SEP PY 2014 VL 39 IS 5 BP 294 EP 303 DI 10.1503/jpn.130126 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AS9PJ UT WOS:000344574000003 PM 24866414 ER PT J AU Valles, A Martens, GJM De Weerd, P Poelmans, G Aschrafi, A AF Valles, Astrid Martens, Gerard J. M. De Weerd, Peter Poelmans, Geert Aschrafi, Armaz TI MicroRNA-137 regulates a glucocorticoid receptor-dependent signalling network: implications for the etiology of schizophrenia SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; AUTISM SPECTRUM DISORDERS; ALZHEIMERS-DISEASE; MOUSE MODEL; ENVIRONMENTAL ENRICHMENT; SYNAPTIC PLASTICITY; INTELLECTUAL DISABILITY; TARGET PREDICTION; AMYLOID-BETA; EXPRESSION AB Background: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting miR-137 targets may provide insights into the biological processes underlying schizophrenia. Methods: We first used bioinformatics tools to obtain and analyze predicted human and mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex after environmental enrichment (EE), a neuronal plasticity model that induces upregulation of several predicted miR-137 targets. Subsequently, expression changes of these predicted targets were examined through loss of miR-137 function experiments in rat cortical neurons. Finally, we conducted bioinformatics and literature analyses to examine the targets that were upregulated upon miR-137 downregulation. Results: Predicted human and mouse miR-137 targets were enriched in neuronal processes, such as axon guidance, neuritogenesis and neurotransmission. The miR-137 levels were significantly downregulated after EE, and we identified 5 novel miR-137 targets through loss of miR-137 function experiments. These targets fit into a glucocorticoid receptor-dependent signalling network that also includes 3 known miR-137 targets with genome-wide significant association with schizophrenia. Limitations: The bioinformatics analyses involved predicted human and mouse miR-137 targets owing to lack of information on predicted rat miR-137 targets, whereas follow-up experiments were performed with rats. Furthermore, indirect effects in the loss of miR-137 function experiments cannot be excluded. Conclusion: We have identified a miR-137-regulated protein network that contributes to our understanding of the molecular basis of schizophrenia and provides clues for future research into psychopharmacological treatments for schizophrenia. C1 [Valles, Astrid; De Weerd, Peter] Maastricht Univ, Fac Psychol & Neurosci, Dept Neurocognit, Maastricht, Netherlands. [Valles, Astrid; Martens, Gerard J. M.; Poelmans, Geert] Radboud Univ Nijmegen, NCMLS, Dept Mol Anim Physiol, Donders Inst Brain Cognit & Behav, NL-6525 AJ Nijmegen, Netherlands. [De Weerd, Peter; Poelmans, Geert; Aschrafi, Armaz] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Poelmans, Geert] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands. [Aschrafi, Armaz] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neuroinformat, NL-6525 AJ Nijmegen, Netherlands. RP Aschrafi, A (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neuroinformat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands. EM a.aschrafi@donders.ru.nl RI Martens, Gerard/D-1925-2010 FU VICI grant from the Netherlands Foundation of Scientific Research (NWO) [453_04_002]; Dutch Top Institute Pharma grant [T5-209]; Donders Center for Neuroscience fellowship award of the Radboud University Nijmegen Medical Centre; FP7-Marie Curie International Reintegration Grant FX We thank Laurens Kirkels, Mahshid Gazorpak, Aron Kos and Nikkie Olde Loohuis for technical assistance. This work was supported by VICI grant 453_04_002 from the Netherlands Foundation of Scientific Research (NWO) to P. De Weerd, a Dutch Top Institute Pharma grant (T5-209) to G.J.M Martens, and the Donders Center for Neuroscience fellowship award of the Radboud University Nijmegen Medical Centre and the FP7-Marie Curie International Reintegration Grant to A. Aschrafi. 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Psychiatry Neurosci. PD SEP PY 2014 VL 39 IS 5 BP 312 EP 320 DI 10.1503/jpn.130269 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AS9PJ UT WOS:000344574000005 PM 24866554 ER PT J AU Buha, N Gligorovic, M Maksic, J AF Buha, Natasa Gligorovic, Milica Maksic, Jasmina TI Challenging Behavior: Behavioral Phenotypes of Some Genetic Syndromes SO SRPSKI ARHIV ZA CELOKUPNO LEKARSTVO LA Serbian DT Review DE genetic syndromes; mental retardation; behavioral phenotype; challenging behavior ID PRADER-WILLI-SYNDROME; FRAGILE-X-SYNDROME; ANGELMAN-SYNDROME; PSYCHIATRIC-DISORDERS; MENTAL-RETARDATION; DOWNS-SYNDROME; CHILDREN; MALES; AUTISM AB Challenging behavior in individuals with mental retardation (MR) is relatively frequent, and represents a significant obstacle to adaptive skills. The frequency of specific forms and manifestations of challenging behavior can depend on a variety of personal and environmental factors. There are several prominent theoretical models regarding the etiology of challenging behavior and psychopathology in persons with MR: behavioral, developmental, socio-cultural and biological. The biological model emphasizes the physiological, biochemical and genetic factors as the potential source of challenging behavior. The progress in the field of genetics and neuroscience has opened the opportunity to study and discover the neurobiological basis of phenotypic characteristics. Genetic syndromes associated with MR can be followed by a specific set of problems and disorders which constitutes their behavioral phenotype. The aim of this paper was to present challenging behaviors that manifest in the most frequently studied syndromes: Down syndrome, Fragile X syndrome, Williams syndrome, Prader-Willi syndrome and Angelman syndrome. The concept of behavioral phenotype implies a higher probability of manifesting specific developmental characteristics and specific behaviors in individuals with a certain genetic syndrome. Although the specific set of (possible) problems and disorders is distinctive for the described genetic syndromes, the connection between genetics and behavior should be viewed through probabilistic dimension. The probabilistic concept takes into consideration the possibility of intra-syndrome variability in the occurrence, intensity and time onset of behavioral characteristics, at which the higher variability the lower is the specificity of the genetic syndrome. Identifying the specific pattern of behavior can be most important for the process of early diagnosis and prognosis. In addition, having knowledge about behavioral phenotype can be a landmark in the creation of targeted treatment strategies for individuals with a specific genetic syndrome. 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Ark. Celok. Lek. PD SEP-OCT PY 2014 VL 142 IS 9-10 BP 621 EP 627 DI 10.2298/SARH1410621B PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AS5JH UT WOS:000344306900019 ER PT J AU Eyal, G Fitzgerald, D Gillis-Buck, E Hart, B Lappe, MD Navon, D Richardson, SS AF Eyal, Gil Fitzgerald, Des Gillis-Buck, Eva Hart, Brendan Lappe, Martine D. Navon, Daniel Richardson, Sarah S. TI New modes of understanding and acting on human difference in autism research, advocacy and care: Introduction to a Special Issue of BioSocieties Introduction SO BIOSOCIETIES LA English DT Editorial Material DE autism; geneticization; looping; biosociality AB The papers collected in this special issue examine specific instances of autism research, treatment and advocacy. Their shared aim is to explore not the causes, but the manifold biosocial consequences and theoretical implications of the recent expansion of the autism spectrum. Three such implications are singled out in the introduction as common threads running through all the papers. First, the extent to which developments in the field of autism research, treatment and advocacy pose a challenge to theories of 'biomedicalization' and 'geneticization'. Second, the intimate connection between autism's recalcitrance to be pinned down and explained and its enormous biosocial productivity. Third, the need to broaden Hacking's (1998, 2006) concept of 'looping' to make sense of the 'moving target' that is autism. C1 [Eyal, Gil] Columbia Univ, Dept Sociol, New York, NY 10027 USA. [Fitzgerald, Des] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England. [Gillis-Buck, Eva] UCSF Sch Med, San Francisco, CA 94117 USA. [Hart, Brendan] Columbia Univ, Dept Sociomed Sci, New York, NY 10027 USA. [Lappe, Martine D.] Univ Calif Los Angeles, Inst Soc & Genet, Los Angeles, CA 90095 USA. [Navon, Daniel] Harvard Univ, Cambridge, MA 02138 USA. [Richardson, Sarah S.] Harvard Univ, Ctr Sci, Dept Hist Sci, Cambridge, MA 02138 USA. [Richardson, Sarah S.] Harvard Univ, Ctr Sci, Studies Women Gender & Sexual Program, Cambridge, MA 02138 USA. RP Eyal, G (reprint author), Columbia Univ, Dept Sociol, MC9649,606 W 122nd St, New York, NY 10027 USA. 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While much literature has commented on the positive hopes and expectations that surround technoscientific projects, fewer have focused on less promissory visions - and, in particular, on the presence of uncertainty and ambiguity among working scientists. This article shows how autism neuroscientists actually talk about their research in ambivalent, entangled registers of both promising hope and deflated uncertainty. The article locates the dynamic between these in an 'intermediate terrain' of autism research - in which autism is both 'present' as an epidemiological and social force, but also 'ambiguous' as a (not yet) well-defined clinical and scientific object. It argues that neuroscientists work through this terrain by drawing not only on a discourse of unalloyed hope and promise, but by entangling their research within a more complex register of 'structured ambivalence', which includes languages of uncertainty, deflation and low expectation. As well as showing the novelty of research within autism's 'intermediate terrain', this adds to a growing literature on the 'sociology of low expectations', and analyses the presence of such feelings among scientific researchers particularly. C1 Kings Coll London, Dept Social Sci Hlth & Med, London, England. RP Fitzgerald, D (reprint author), Kings Coll London, Dept Social Sci Hlth & Med, D11 East Wing,Strand Campus, London, England. 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TI Autism as a biomedical platform for sex differences research SO BIOSOCIETIES LA English DT Article DE autism; Asperger's Syndrome; biomedical platform; gender; sex differences; translational research ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; ASPERGERS-SYNDROME; SAVANT SYNDROME; GENDER; BRAIN; MATH; EPIDEMIOLOGY; STEREOTYPES; PERFORMANCE AB Autism has become a 'biomedical platform' for sex differences research in fields such as genetics, endocrinology and neuroscience. Increasingly, researchers in these fields pose the male prevalence of autism as a model for investigating sex differences in the brain, and offer basic research on sex differences in the brain as a resource for understanding the etiology of autism. The use of autism as a biomedical platform for sex differences research obscures empirical and interpretive contestations surrounding claims about the male prevalence of autism. We argue that the uncritical use of this research platform across many fields stands to distort scientific research on autism and contribute to harmful gender stereotypes. C1 [Richardson, Sarah S.] Harvard Univ, Dept Hist Sci, Cambridge, MA 02138 USA. [Gillis-Buck, Eva M.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Richardson, SS (reprint author), Harvard Univ, Dept Hist Sci, Sci Ctr 371, Cambridge, MA 02138 USA. 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A., 2010, ISLANDS GENIUS BOUNT Treffert DA, 2009, PHILOS T R SOC B, V364, P1351, DOI 10.1098/rstb.2008.0326 United States National Science Foundation, 2012, DOCT REC US U 2012 Weiss L., 2012, SEX SPECIFIC DISSECT Werling D., 2012, INVESTIGATION SEX DI Whitby PJS, 2009, EDUC TRAIN DEV DISAB, V44, P551 Whitby P.J.S., 2009, BEHAVIOUR, V19, P3 Whiteley P, 2010, AUTISM INSIGHTS, V2, P17 Wing L, 2005, J AUTISM DEV DISORD, V35, P197, DOI 10.1007/s10803-005-1998-x WING L, 1981, PSYCHOL MED, V11, P115 NR 104 TC 0 Z9 0 PU PALGRAVE MACMILLAN LTD PI BASINGSTOKE PA BRUNEL RD BLDG, HOUNDMILLS, BASINGSTOKE RG21 6XS, HANTS, ENGLAND SN 1745-8552 EI 1745-8560 J9 BIOSOCIETIES JI BioSocieties PD SEP PY 2014 VL 9 IS 3 SI SI BP 262 EP 283 DI 10.1057/biosoc.2014.17 PG 22 WC Social Sciences, Biomedical SC Biomedical Social Sciences GA AS4CU UT WOS:000344221800003 ER PT J AU Hart, B AF Hart, Brendan TI Autism parents & neurodiversity: Radical translation, joint embodiment and the prosthetic environment SO BIOSOCIETIES LA English DT Article DE autism; looping; classifications; disability; patient advocacy ID CHILDREN; DISABILITY; SPECTRUM; SERVICES; KINSHIP; GENDER AB It has become increasingly common to view and discuss autism as a form of difference, rather than a disorder. Moreover, the autism spectrum has generated new possibilities for personhood and social inclusion. These developments have typically been ascribed to the recent work of autistic autobiographers and autistic self-advocates associated with the neurodiversity movement, who are providing a sort of linguistic infrastructure to support autistic personhood. Drawing on historical and ethnographic research, this article makes the complementary and analogous claim that parents of autistic children have used autism therapies to create a technical infrastructure to support autistic personhood. The article follows an earlier genealogical thread to argue that parents have used the techniques and technologies of behavioral therapies (sometimes said to be incommensurable with neurodiversity's philosophy) in ways that have actually helped establish this autism-as-difference view. They have done so by translating their child's behaviors and utterances and engaging in forms of 'joint embodiment' with her to create enabling 'prosthetic environments' where her unique personhood can be recognized. Through an ethnographic focus on 'prosaic technologies' and the politics of everyday practice, the article also provides a thicker and more grounded account of what Ian Hacking calls the "looping effect of human kinds". C1 [Hart, Brendan] Columbia Univ, Dept Sociomed Sci, New York, NY 10027 USA. RP Hart, B (reprint author), Columbia Univ, Dept Sociomed Sci, 5th Floor,722 W 168th St, New York, NY 10027 USA. 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TI Taking care: Anticipation, extraction and the politics of temporality in autism science SO BIOSOCIETIES LA English DT Article DE autism; research; care; ethics; participation; science ID REPRODUCTIVE WORK; CLINICAL-TRIALS; MOTHER-BLAME; PERSPECTIVE; ENVIRONMENT; DISABILITY; LIFE; BIOMEDICINE; EXPERIENCE; EMERGENCE AB Research on autism has increased significantly over the past several decades. This upsurge parallels the steep rise in autism diagnoses. Together, these conditions have increased the number of people occupying the social role of research participants, including investigators, analysts and subjects. Simultaneously, addressing scientific questions about autism now involves new research efforts including prospective enriched-risk cohort studies exploring the environmental and genetic causes of autism during pregnancy and early child development. Rather than one-time donations, these studies require extended commitments on the part of all those involved in the research. This article draws on ethnographic observations of research practices and interviews with investigators, study staff and participants to examine the emergent relationships between research and care in this area of autism science. I introduce the notion of 'taking care' to describe the forms of anticipatory labor and mutual extraction involved in longitudinal research. Through tracing three modes of taking care across practices of study design, data collection and participation, I argue that research and care become intimately intertwined and mutually constructed during the research process. These findings reflect how processes of taking and giving are constitutive of research participation for all those engaged in the research enterprise. This article considers the relationships between these practices and new forms of community and sociality related to biomedical science. C1 Univ Calif Los Angeles, Inst Soc & Genet, Los Angeles, CA 90095 USA. 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This argument is explored by examining the intersection of a rare genetic disorder - 22q13 Deletion/Phelan-McDermid Syndrome (PMS) - with the much broader but genetically heterogeneous category of autism. We show that a 'genomically designated' classification such as PMS thrives as an object of research and social mobilization by virtue of its capacity to interface with, rather than supplant, the existing psychiatric diagnosis of autism. Autism genetics thus functions as a 'trading zone' (Galison, 1997) that allows for the exchange of knowledge, biomedical objects and resources despite incommensurable ends and frameworks of understanding. C1 [Navon, Daniel] Harvard Univ, Cambridge, MA 02138 USA. [Eyal, Gil] Columbia Univ, Dept Sociol, New York, NY 10027 USA. RP Navon, D (reprint author), Harvard Univ, 1730 Cambridge St,S410, Cambridge, MA 02138 USA. 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IASSIDD (www.iassidd.org) is the leading global organisation for researchers and research centres that seek to improve the understanding of and improve the lives of people with intellectual or developmental disabilities, their families and those who support them. The paper and the recommendations it contains have been developed through an iterative process led by IASSIDD's Families Special Interest Research Group (SIRG). During this process, all members of the Families SIRG and all members of IASSIDD's ruling council have had the opportunity to comment on drafts of this paper. The final Position Paper was adopted by the Council of IASSIDD on 9 July 2012. C1 Univ Lancaster, Div Hlth Res, Lancaster, Devon, England. RP Emerson, E (reprint author), Univ Lancaster, Div Hlth Res, Lancaster, Devon, England. 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Appl. Res. Intellect. Disabil. PD SEP PY 2014 VL 27 IS 5 BP 420 EP 430 DI 10.1111/jar.12078 PG 11 WC Psychology, Educational; Rehabilitation SC Psychology; Rehabilitation GA AR9AY UT WOS:000343864300002 ER PT J AU Penketh, V Hare, DJ Flood, A Walker, S AF Penketh, Victoria Hare, Dougal Julian Flood, Andrea Walker, Samantha TI Attachment in Adults with Intellectual Disabilities: Preliminary Investigation of the Psychometric Properties of the Manchester Attachment Scale-Third Party Observational Measure SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE adults; assessment; attachment theory; intellectual disability ID AUTISM SPECTRUM DISORDER; MENTAL-RETARDATION; DOWN-SYNDROME; CHALLENGING BEHAVIOR; CHILDREN; PEOPLE; PERSONALITY; SENSITIVITY; HEALTH; MODEL AB Background The Manchester Attachment Scale-Third party observational measure (MAST) was developed to assess secure attachment style for adults with intellectual disabilities. The psychometric properties of the MAST were examined. Materials and Methods Professional carers (N = 40) completed the MAST and measures related to the construct of attachment theory [Edward Zigler-Yale Personality Questionnaire (EZPQ), Emotional Rating Scale (ERS) and the Learning Disability Casemix Scale (LDCS)] regarding individuals with an intellectual disability (N = 57). Individuals with an intellectual disability (N = 14) completed the Self-report Assessment of Attachment Security (SRAAS). Results The MAST was found to have good internal consistency, test-retest reliability and convergent validity. MAST scores were negatively correlated with level of intellectual disability and challenging behaviour (CB) as measured by LDCS. Conclusions Support was provided for the reliability and validity of the MAST and a relationship between attachment security, level of intellectual disability and CB. 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Here we relate behavioral, psycholinguistic, cognitive (memory/executive), and graphomotor measures to spelling skills in school-age girls with ADHD (n = 30) and an age-matched group of typically developed spellers (TYPSP, n = 35). When subdividing the ADHD group into those with poor (ADHDPSP, n = 19) and typical spelling (ADHDTYPSP, n = 11), the two subgroups did not differ with regard to inattentive or hyperactive-impulsive symptom severity according to parent or teacher ratings. Both ADHD subgroups also had equally severe difficulties in graphomotor control-handwriting and (parent ratings of) written expression as compared to the TYPSP group. In contrast, ADHDPSP had problems relative to ADHDTYPSP and TYPSP on phonological and orthographic recoding (choice tasks) and verbal memory (digit span) and were more likely to make commissions on a continuous performance task (CPT). 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Mental disorders may present in a special way in patients with autism spectrum disorders. For instance, depression may produce irritability, aggressive behavior, and change of rituals. Autism spectrum disorders have common features with many other mental disorders, such as schizophrenia and obsessive-compulsive disorders. Our article offers a review of clinical and historical particularities that may help clinicians establish appropriate diagnosis. In this article we focus on clinical features, differential diagnosis, and comorbidity in adult people with autism spectrum disorders. A subsequent article will deal with diagnostic work-up and therapeutic aspects of autism in adult patients. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Murad, Ayman; Fritsch, Aurelie; Bizet, Eric; Schaal, Christian] Ctr Hosp Rouffach, F-68000 Colmar, France. RP Murad, A (reprint author), Ctr Hosp Rouffach, Espace Autismes 68,13 Rue Charles Sandherr, F-68000 Colmar, France. 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Med.-Psychol. PD SEP PY 2014 VL 172 IS 7 BP 577 EP 586 DI 10.1016/j.amp.2014.07.010 PG 10 WC Pharmacology & Pharmacy; Psychiatry; Psychology; Psychology, Multidisciplinary SC Pharmacology & Pharmacy; Psychiatry; Psychology GA AR1YD UT WOS:000343379600018 ER PT J AU Murad, A Fritsch, A Bizet, E Schaal, C AF Murad, Ayman Fritsch, Aurelie Bizet, Eric Schaal, Christian TI Autism in adulthood: Diagnostic work-up and therapeutic issues SO ANNALES MEDICO-PSYCHOLOGIQUES LA French DT Article DE Asperger's syndrome; Autism; Autism spectrum disorders; Invasive developmental disorders; Social skills training ID SPECTRUM DISORDERS; MELATONIN; OXYTOCIN; BEHAVIOR AB Diagnostic assessment of autism spectrum disorders includes psychiatric examination, semi-structured interviews as well as standardized tools. Work-up should allow to establish diagnosis and comorbidities and to evaluate the patient's skills and difficulties. Assessment should offer suggestions about the help that may be proposed to patients in the personal and social fields. In this article, we present the way our team carry on diagnostic assessment. Afterwards, we give a synopsis about the support mental health professionals can propose to adult patients with autism spectrum disorders. The main forms of support are fitting out patient's environment, emotion (especially anger and anxiety) management, social skills training, and medication. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Murad, Ayman; Fritsch, Aurelie; Bizet, Eric; Schaal, Christian] Ctr Hosp Rouffach, F-68000 Colmar, France. RP Murad, A (reprint author), Ctr Hosp Rouffach, Espace Autismes 68,13 Rue Charles Sandherr, F-68000 Colmar, France. 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Med.-Psychol. PD SEP PY 2014 VL 172 IS 7 BP 587 EP 594 DI 10.1016/j.amp.2014.07.011 PG 8 WC Pharmacology & Pharmacy; Psychiatry; Psychology; Psychology, Multidisciplinary SC Pharmacology & Pharmacy; Psychiatry; Psychology GA AR1YD UT WOS:000343379600019 ER PT J AU Meltzer, LJ Mindell, JA AF Meltzer, Lisa J. Mindell, Jodi A. TI Systematic Review and Meta-Analysis of Behavioral Interventions for Pediatric Insomnia SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Review DE bedtime problems; behavioral insomnia of childhood; behavioral treatment; insomnia; night wakings; pediatric insomnia; treatment ID RANDOMIZED CONTROLLED-TRIAL; SCHOOL-AGED CHILDREN; INFANT SLEEP PROBLEMS; AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; INTERNET-BASED INTERVENTION; SELF-HARM BEHAVIORS; 1ST 3 YEARS; YOUNG-CHILDREN; NIGHT WAKINGS AB Objective To evaluate and quantify the evidence for behavioral interventions for pediatric insomnia. Methods Meta-analysis of 16 controlled trials and qualitative analysis of 12 within-subject studies were conducted (total n = 2,560). Results Meta-analysis found significant effects for four specified sleep outcomes: sleep-onset latency, number of night wakings, and duration of night wakings, and sleep efficiency, with small to large effect sizes across the controlled clinical trials involving typical children. No significant effects were found for the two studies conducted with special needs populations. Finally, within-subjects studies demonstrated significant effects for all sleep outcomes with large effect sizes. Risk of bias assessment and GRADE ratings of the quality of the evidence are described. Conclusion Moderate-level evidence supports behavioral interventions for pediatric insomnia in young children. However, low evidence for children, adolescents, and those with special needs (due to a lack of studies that met inclusion criteria) highlights the need for future research. 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TI Surface-based morphometry of the cortical architecture of autism spectrum disorders: volume, thickness, area, and gyrification SO NEUROPSYCHOLOGIA LA English DT Article DE Autism spectrum disorder; Surface-based morphometry; Freesurfer; Social brain; Neuroanatomy ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; MIRROR NEURON DYSFUNCTION; VOXEL-BASED MORPHOMETRY; EMBEDDED FIGURES TASK; AGE-RELATED-CHANGES; BRAIN SIZE; FUNCTIONAL CONNECTIVITY; MINICOLUMNAR PATHOLOGY; GEOMETRICALLY ACCURATE AB Structural neuroimaging studies of autism spectrum disorder (ASD) have uncovered widespread neuroanatomical abnormalities, which may have a significant impact on brain function, connectivity, and on behavioral symptoms of autism. The findings of previous structural MRI studies have largely been distributed across several brain areas, with limited consistency. The current study examined neuroanatomical abnormalities by comparing surface-based measures of cortical morphology (CT: cortical thickness, CSA: cortical surface area, CV: cortical volume, and GI: gyrification index) in 55 high-functioning children and adults with ASD to 60 age-and-IQ-matched typically developing (TD) peers. A few brain areas, the fusiform gyrus (FG), middle temporal gyrus (MTG), and inferior frontal gyrus (IFG), emerged to be primarily different in their morphology between the two groups. Compared to TD participants, ASD participants had significantly smaller CV in left MTG, reduced CSA in bilateral MTG and FG, reduced GI in left supramarginal gyrus, and significantly increased CT in the pars opercularis of the IFG. As a function of age, ASD participants had significant reductions in: CT in the pars opercularis, CSA of the left rostral middle frontal gyrus, and GI for left supramarginal gyrus. Thus, alterations in cortical morphology in ASD were seen primarily in regions that are considered part of the social brain. Overall, these findings point to: neuroanatomical alterations in social brain areas, developmental differences in neuroanatomy, and the need to study neuroanatomy at multiple levels in order to better characterize the cortical architecture of ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Libero, Lauren E.; DeRamus, Thomas P.; Kana, Rajesh K.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Deshpande, Hrishikesh D.] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL 35294 USA. RP Kana, RK (reprint author), Univ Alabama Birmingham, Dept Psychol, CIRC 235G,1719 6th Ave South, Birmingham, AL 35294 USA. EM rkana@uab.edu FU UAB Department of Psychology funds FX This research was supported by the UAB Department of Psychology funds to R.K. The authors would like to thank Heather Wadsworth, Adrian Lazarescu, and Dr. Lawrence Ver Hoef for their help in different aspects of data collection. 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Pellicano, Elizabeth TI The Cambridge Face Memory Test for Children (CFMT-C): A new tool for measuring face recognition skills in childhood SO NEUROPSYCHOLOGIA LA English DT Article DE Face recognition; Face memory; Development; Children; Inversion effect ID DEVELOPMENTAL PROSOPAGNOSIA; IDENTITY RECOGNITION; MOTHERS FACE; AUTISM; PERCEPTION; INDIVIDUALS; INFORMATION; EXPERTISE; ABILITY; ADULTS AB Face recognition ability follows a lengthy developmental course, not reaching maturity until well into adulthood. Valid and reliable assessments of face recognition memory ability are necessary to examine patterns of ability and disability in face processing, yet there is a dearth of such assessments for children. We modified a well-known test of face memory in adults, the Cambridge Face Memory Test (Duchaine & Nakayama, 2006, Neuropsychologia, 44,576-585), to make it developmentally appropriate for children. To establish its utility, we administered either the upright or inverted versions of the computerised Cambridge Face Memory Test - Children (CFMT-C) to 401 children aged between 5 and 12 years. Our results show that the CFMT-C is sufficiently sensitive to demonstrate age-related gains in the recognition of unfamiliar upright and inverted faces, does not suffer from ceiling or floor effects, generates robust inversion effects, and is capable of detecting difficulties in face memory in children diagnosed with autism. Together, these findings indicate that the CFMT-C constitutes a new valid assessment tool for children's face recognition skills. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Croydon, Abigail; Pellicano, Elizabeth] Univ London, Inst Educ, Ctr Res Autism & Educ CRAE, London WC1N 1AZ, England. [Pimperton, Hannah] UCL, Inst Cognit Neurosci, London, England. [Ewing, Louise] Birkbeck, Dept Psychol Sci, London, England. [Ewing, Louise; Pellicano, Elizabeth] Univ Western Australia, Sch Psychol, Perth, WA 6009, Australia. [Duchaine, Brad C.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. RP Pellicano, E (reprint author), Inst Educ, Ctr Res Autism & Educ, Dept Psychol & Human Dev, 25 Woburn Sq, London WC1H 0AA, England. EM l.pellicano@ioe.ac.uk FU Clothworkers' Foundation; Pears Foundation FX This paper is in memory of Dr Andy Calder, a mentor and friend, whose dedication to the highest quality scientific research in face processing was unsurpassed. We are very grateful to the children, families and school staff who kindly took part in this research. Thanks also to Laura Dixon, Louise Edgington, Marlene Flogel, Emma Jaquet, Lydia King, Elena Klaric, Catherine Manning, Romina Palermo, Gill Rhodes, Erica Salomone, Martin Thirkettle and Ellie Wilson for help with data collection and to Marc Stears for comments on a previous version of this manuscript. 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This coding is compromised in autism and the broader autism phenotype, suggesting that atypical adaptive coding of faces may be an endophenotype for autism. Here we investigate the nature of this atypicality, asking whether adaptive face-coding mechanisms are fundamentally altered, or simply less responsive to experience, in autism. We measured adaptive coding, using face identity aftereffects, in cognitively able children and adolescents with autism and neurotypical age- and ability-matched participants. We asked whether these aftereffects increase with adaptor identity strength as in neurotypical populations, or whether they show a different pattern indicating a more fundamental alteration in face-coding mechanisms. As expected, face identity aftereffects were reduced in the autism group, but they nevertheless increased with adaptor strength, like those of our neurotypical participants, consistent with norm-based coding of face identity. Moreover, their aftereffects correlated positively with face recognition ability, consistent with an intact functional role for adaptive coding in face recognition ability. We conclude that adaptive norm-based face-coding mechanisms are basically intact in autism, but are less readily calibrated by experience. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rhodes, Gillian; Ewing, Louise; Jeffery, Linda; Avard, Eleni; Taylor, Libby] Univ Western Australia, Sch Psychol, ARC Ctr Excellence Cognit & Its Disorders, Crawley, WA 6009, Australia. RP Rhodes, G (reprint author), Univ Western Australia, Sch Psychol, ARC Ctr Excellence Cognit & Its Disorders, 35 Stirling Highway, Crawley, WA 6009, Australia. EM gillian.rhodes@uwa.edu.au FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; ARC [DP0877379, DP130102300] FX This research was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Professorial Fellowship to Rhodes (DP0877379) and an ARC Discovery Outstanding Researcher Award to Rhodes (DP130102300). We thank Mayu Nishimura and Daphne Maurer for co-creating the Robbers Game used in the Identity Aftereffects task, Ainsley Read for assistance designing testing protocols and assistance with testing, and Nichola Burton, Francis Caulfield and Samantha Bank for assistance with testing. Ethical approval was granted by the Human Research Ethics Committee of the University of Western Australia. 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Health PD FAL PY 2014 VL 34 IS 4 BP 193 EP 201 DI 10.3928/15394492-20141006-04 PG 9 WC Rehabilitation SC Rehabilitation GA AR1PO UT WOS:000343357300004 PM 25347757 ER PT J AU Lim, JH Seo, EJ Kim, YM Cho, HJ Lee, JO Cheon, CK Yoo, HW AF Lim, Ji-Hun Seo, Eul-Ju Kim, Yoo-Mi Cho, Hyun-Ju Lee, Jin-Ok Cheon, Chong Kun Yoo, Han-Wook TI A de novo Microdeletion of ANKRD11 Gene in a Korean Patient with KBG Syndrome SO ANNALS OF LABORATORY MEDICINE LA English DT Article DE KBG syndrome; ANKRD11; Array CGH; 16q24.3 microdeletion ID MUTATIONS; DELETION AB KBG syndrome is a very rare genetic disorder characterized by macrodontia of upper central incisors, global developmental delay, distinctive craniofacial features, short stature, and skeletal anomalies. Ankyrin repeat domain 11 gene (ANKRD11) has recently been identified as a causal factor of this syndrome. We describe a 6-yr-old Korean boy with features of KBG syndrome. The patient had a short stature, macrodontia, dysmorphic facial features, speech and motor delay with intellectual disability, and partial seizures as indicated by the electroencephalogram, but he was neither autistic nor had autism spectrum disorders. Using-high-resolution oligonucleotide array comparative genomic hybridization, we identified a heterozygous 240-kb deletion at 16q24.3 corresponding to ANKRD11. This patient provided additional evidence on the influence of ANKRD11 in KBG syndrome and suggested that deletion limited to ANKRD11 is unlikely to cause autism. C1 [Lim, Ji-Hun; Seo, Eul-Ju; Kim, Yoo-Mi; Cho, Hyun-Ju; Yoo, Han-Wook] Univ Ulsan, Coll Med, Ctr Med Genet, Seoul, South Korea. [Lim, Ji-Hun; Seo, Eul-Ju] Univ Ulsan, Coll Med, Dept Lab Med, Seoul, South Korea. [Kim, Yoo-Mi; Yoo, Han-Wook] Univ Ulsan, Coll Med, Dept Pediat, Seoul, South Korea. [Kim, Yoo-Mi; Yoo, Han-Wook] Asan Med Ctr, Seoul 138736, South Korea. [Lim, Ji-Hun] Univ Ulsan, Coll Med, Ulsan Univ Hosp, Dept Lab Med, Ulsan 680749, South Korea. [Lee, Jin-Ok] Asan Med Ctr, Asan Inst Life Sci, Seoul 138736, South Korea. [Cheon, Chong Kun] Pusan Natl Univ, Childrens Hosp, Dept Pediat, Pusan, South Korea. RP Seo, EJ (reprint author), Asan Med Ctr, Dept Lab Med, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea. 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J. Mol. Sci. PD SEP PY 2014 VL 15 IS 9 BP 15924 EP 15950 DI 10.3390/ijms150915924 PG 27 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA AQ8UN UT WOS:000343109700062 PM 25207602 ER PT J AU Deriziotis, P O'Roak, BJ Graham, SA Estruch, SB Dimitropoulou, D Bernier, RA Gerdts, J Shendure, J Eichler, EE Fisher, SE AF Deriziotis, Pelagia O'Roak, Brian J. Graham, Sarah A. Estruch, Sara B. Dimitropoulou, Danai Bernier, Raphael A. Gerdts, Jennifer Shendure, Jay Eichler, Evan E. Fisher, Simon E. TI De novo TBR1 mutations in sporadic autism disrupt protein functions SO NATURE COMMUNICATIONS LA English DT Article ID ULNAR-MAMMARY SYNDROME; HOLT-ORAM SYNDROME; LANGUAGE DISORDER; SPECTRUM DISORDERS; SEVERE SPEECH; TRANSCRIPTION FACTOR; PROJECTION NEURONS; CEREBRAL-CORTEX; HUMAN TBX3; GENE AB Next-generation sequencing recently revealed that recurrent disruptive mutations in a few genes may account for 1% of sporadic autism cases. Coupling these novel genetic data to empirical assays of protein function can illuminate crucial molecular networks. Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism. De novo truncating and missense mutations disrupt multiple aspects of TBR1 function, including subcellular localization, interactions with co-regulators and transcriptional repression. Missense mutations inherited from unaffected parents did not disturb function in our assays. We show that TBR1 homodimerizes, that it interacts with FOXP2, a transcription factor implicated in speech/language disorders, and that this interaction is disrupted by pathogenic mutations affecting either protein. These findings support the hypothesis that de novo mutations in sporadic autism have severe functional consequences. Moreover, they uncover neurogenetic mechanisms that bridge different neurodevelopmental disorders involving language deficits. C1 [Deriziotis, Pelagia; Graham, Sarah A.; Estruch, Sara B.; Dimitropoulou, Danai; Fisher, Simon E.] Max Planck Inst Psycholinguist, Language & Genet Dept, NL-6525 XD Nijmegen, Netherlands. [O'Roak, Brian J.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [O'Roak, Brian J.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Bernier, Raphael A.; Gerdts, Jennifer] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Fisher, Simon E.] Donders Inst Brain Cognit & Behav, NL-6525 EN Nijmegen, Netherlands. RP Fisher, SE (reprint author), Max Planck Inst Psycholinguist, Language & Genet Dept, Wundtlaan 1, NL-6525 XD Nijmegen, Netherlands. EM simon.fisher@mpi.nl RI Fisher, Simon/E-9130-2012; Derizioti, Pelagia/C-3857-2015 OI Fisher, Simon/0000-0002-3132-1996; Derizioti, Pelagia/0000-0001-5544-8345 FU Max Planck Society; Simons Foundation Autism Research Initiative [SFARI 303241]; NIH [MH101221] FX We wish to thank Arianna Vino and Flavia Bianca Cristian for technical assistance. This work was supported by the Max Planck Society and a grant from the Simons Foundation Autism Research Initiative (SFARI 303241 to E. E. E.) and NIH (MH101221 to E. E. E.). We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, 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, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the SSC population data set described in this study (https://ordering.base.sfari.org/similar to browse_collection/archive[ssc_v13]/ui:view) by applying at https://base.sfari.org. 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Chow, Carolyn Congdon, Eliza Jalbrzikowski, Maria Bearden, Carrie E. TI Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE functional MRI; resting state; velocardiofacial syndrome; dysconnectivity ID RESTING-STATE NETWORKS; FUNCTIONAL CONNECTIVITY; DIAGNOSTIC INTERVIEW; BRAIN-DYSFUNCTION; AUTISTIC TRAITS; SCHIZOPHRENIA; DISORDERS; INDIVIDUALS; SPECTRUM; DEFICITS AB 22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a 'developmental-disconnection' hypothesis of symptom development in this disorder. C1 [Schreiner, Matthew J.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Interdept Neurosci Program, Los Angeles, CA 90095 USA. [Schreiner, Matthew J.; Chow, Carolyn; Congdon, Eliza; Jalbrzikowski, Maria; Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Karlsgodt, Katherine H.] Feinstein Inst Med Res, Dept Psychiat, Manhasset, NY 11030 USA. [Karlsgodt, Katherine H.] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA. [Uddin, Lucina Q.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Jalbrzikowski, Maria; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Bearden, CE (reprint author), 300 Med Plaza,Suite 2267, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 FU National Institute of Mental Health [R01 MH085953]; NIH/NICHD [P50-HD-055784]; Neuroimaging Training Program fellowship [T32 T90DA022768]; UL1 Coordinating Center Grant [UL1 -DE019580, PL1MH083271]; [K01M8092288] FX This study was supported by grants from the National Institute of Mental Health R01 MH085953 to CEO.); NIH/NICHD (grant P50-HD-055784 Pilot Project Grant to C.E.B.); Neuroimaging Training Program fellowship (T32 T90DA022768 to M.J.S.), UL1 Coordinating Center Grant (UL1 -DE019580 and PL1MH083271 to R.B.) and K01M8092288 (to L.Q.U.). 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PD SEP PY 2014 VL 9 IS 9 BP 1261 EP 1267 DI 10.1093/scan/nst114 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IH UT WOS:000342985600002 PM 23912681 ER PT J AU Gong, PY Liu, JT Li, S Zhou, XL AF Gong, Pingyuan Liu, Jinting Li, She Zhou, Xiaolin TI Dopamine beta-hydroxylase gene modulates individuals' empathic ability SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE dopamine beta-hydroxylase; DBH; -1021C/T; polymorphism; empathy ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; PARKINSONS-DISEASE; EMOTIONAL EMPATHY; DBH LOCUS; SCHIZOPHRENIA; ADULTS; NOREPINEPHRINE; POLYMORPHISM AB Dopamine beta-hydroxylase (DBH), an enzyme that converts dopamine to norepinephrine, has broad influences on social functions. In this study, we examined to what extent two polymorphisms (-1021C/T and a 19 bp insertion/deletion) in DBH gene modulate individuals' empathic perception and response, which were measured, respectively, by reading the mind in the eyes test and the empathic concern subscale of interpersonal reactivity index. Results showed that polymorphism at -1021C/T, but not the 19 bp insertion/deletion, accounts for 2.3% variance of empathic perception and 1.4% variance of empathic response. Individuals with the CC genotype, which is associated with higher DBH activity, manifested greater empathic ability than those with CT/TT genotypes. These findings demonstrate the importance of DBH -1021C/T as a genetic basis of empathy and in predicting individual differences in social and affective processing. C1 [Gong, Pingyuan; Liu, Jinting; Zhou, Xiaolin] Peking Univ, Ctr Brain & Cognit Sci, Beijing 100871, Peoples R China. [Gong, Pingyuan; Li, She] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. [Gong, Pingyuan; Li, She] Henan Univ Sci & Technol, Lab Med Mol Biol, Luoyang 471003, Peoples R China. [Zhou, Xiaolin] Minist Educ, Key Lab Machine Percept, Beijing 100871, Peoples R China. [Zhou, Xiaolin] Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China. RP Zhou, XL (reprint author), Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. EM xz104@pku.edu.cn FU National Basic Research Program of China (973 Program) [2010CB833904]; China Postdoctoral Science Foundation [2013M530002]; Natural Science Foundation of China [30110972, 91232708] FX This study was supported by grants from National Basic Research Program of China (973 Program: 2010CB833904), China Postdoctoral Science Foundation (2013M530002), Natural Science Foundation of China (30110972, 91232708), and China Postdoctoral Science Foundation (2013M530002). 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PD SEP PY 2014 VL 9 IS 9 BP 1341 EP 1345 DI 10.1093/scan/nst122 PG 5 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IH UT WOS:000342985600012 PM 23988761 ER PT J AU Robertson, CE Thomas, C Kravitz, DJ Wallace, GL Baron-Cohen, S Martin, A Baker, CI AF Robertson, Caroline E. Thomas, Cibu Kravitz, Dwight J. Wallace, Gregory L. Baron-Cohen, Simon Martin, Alex Baker, Chris I. TI Global motion perception deficits in autism are reflected as early as primary visual cortex SO BRAIN LA English DT Article DE autism; motion; fMRI; vision; global perception ID SPECTRUM DISORDERS; AREA MT; COORDINATE SYSTEM; DECISION-MAKING; PARIETAL CORTEX; STRIATE CORTEX; NEURAL BASIS; HUMAN BRAIN; CHILDREN; MECHANISM AB Individuals with autism are often characterized as 'seeing the trees, but not the forest'-attuned to individual details in the visual world at the expense of the global percept they compose. Here, we tested the extent to which global processing deficits in autism reflect impairments in (i) primary visual processing; or (ii) decision-formation, using an archetypal example of global perception, coherent motion perception. In an event-related functional MRI experiment, 43 intelligence quotient and age-matched male participants (21 with autism, age range 15-27 years) performed a series of coherent motion perception judgements in which the amount of local motion signals available to be integrated into a global percept was varied by controlling stimulus viewing duration (0.2 or 0.6 s) and the proportion of dots moving in the correct direction (coherence: 4%, 15%, 30%, 50%, or 75%). Both typical participants and those with autism evidenced the same basic pattern of accuracy in judging the direction of motion, with performance decreasing with reduced coherence and shorter viewing durations. Critically, these effects were exaggerated in autism: despite equal performance at the long duration, performance was more strongly reduced by shortening viewing duration in autism (P<0.015) and decreasing stimulus coherence (P<0.008). To assess the neural correlates of these effects we focused on the responses of primary visual cortex and the middle temporal area, critical in the early visual processing of motion signals, as well as a region in the intraparietal sulcus thought to be involved in perceptual decision-making. The behavioural results were mirrored in both primary visual cortex and the middle temporal area, with a greater reduction in response at short, compared with long, viewing durations in autism compared with controls (both P<0.018). In contrast, there was no difference between the groups in the intraparietal sulcus (P>0.574). These findings suggest that reduced global motion perception in autism is driven by an atypical response early in visual processing and may reflect a fundamental perturbation in neural circuitry. C1 [Robertson, Caroline E.; Thomas, Cibu; Kravitz, Dwight J.; Wallace, Gregory L.; Martin, Alex; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Robertson, Caroline E.; Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge CB2 8AH, England. [Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust, CLASS Clin, Peterborough, England. RP Robertson, CE (reprint author), Harvard Soc Fellows, 78 Mt Auburn St, Cambridge, MA 02138 USA. EM carolinerobertson@fas.harvard.edu FU NIH-Cambridge Fellowship; MRC; Autism Research Trust; Wellcome Trust; Intramural Research Program of the National Institute of Mental Health [1-ZIA-MH002893-07, 1-ZIA-MH002920-04]; NIH Combined Neuroscience Institutional Review Board FX This work was supported by the Intramural Research Program of the National Institute of Mental Health under grant numbers 1-ZIA-MH002893-07 and 1-ZIA-MH002920-04. Ethics approval for this study was granted by the NIH Combined Neuroscience Institutional Review Board under protocol number 10-M-0027. We gratefully acknowledge the Gates-Cambridge Trust and the NIH-Cambridge Fellowship (C.E.R.). S.B-C. was supported by the MRC, the Autism Research Trust, and the Wellcome Trust during the period of this work. We declare no competing financial interests. 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M. TI Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion SO BRAIN LA English DT Article DE autistic spectrum disorder; impulsivity and inhibition disorders ID EVENT-RELATED FMRI; SPECTRUM DISORDERS; BEHAVIORAL-INHIBITION; REPETITIVE BEHAVIORS; NEURONAL RESPONSES; HEALTHY-VOLUNTEERS; ASPERGERS-SYNDROME; STOP-SIGNAL; HUMAN-BRAIN; HUMANS AB It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. C1 [Daly, Eileen; Ecker, Christine; Deeley, Quinton; Craig, Michael; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Gudbrandsen, Maria; Toal, Fiona; Murphy, Declan G. M.] Kings Coll London, Sackler Inst Translat Neurodev, Dept Forens & Neurodev Sci, Inst Psychiat, London WC2R 2LS, England. [Hallahan, Brian] Natl Univ Ireland, Dept Psychiat, Galway, Ireland. [Brammer, Michael; Giampietro, Vincent] Kings Coll London, Dept Neuroimaging, Inst Psychiat, London WC2R 2LS, England. [Lamar, Melissa] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Page, Lisa] Sussex Partnership NHS Fdn Trust, Brighton & Sussex Med Sch, Brighton, E Sussex, England. [Schmitz, Nicole] UCL, Dementia Res Unit, Inst Neurol, London WC1E 6BT, England. [Cleare, Anthony] Kings Coll London, Dept Psychol Med, Inst Psychiat, London WC2R 2LS, England. [Robertson, Dene] South London & Maudsley NHS Fdn, Behav & Dev Clin Acad Grp, London, England. [Rubia, Katya] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London WC2R 2LS, England. RP Daly, E (reprint author), IOP, Box 50,DeCrespigny Pk, London SE5 8AF, England. EM eileen.daly@kcl.ac.uk RI Ecker, Christine/E-5194-2010 FU Health Foundation; MRC UK AIMS [G0400061]; Innovative Medicines Initiative Joint Undertaking from the EU [115300]; Biomedical Research Centre for Mental Health-CD Cluster-Developmental Disorders, National Institute for Health Research (NIHR) at South London and Maudsley NHS Foundation Trust and King's College London; Dr Mortimer and Theresa Sackler Foundation; Autism Speaks FX The Health Foundation and the MRC UK AIMS (G0400061) sponsored the study. We would also like to acknowledge the EU-AIMS (supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, which includes financial contributions from the EU Seventh Framework Programme (FP7/2007-2013) the Biomedical Research Centre for Mental Health-CD Cluster-Developmental Disorders, National Institute for Health Research (NIHR) at South London and Maudsley NHS Foundation Trust and King's College London, The Dr Mortimer and Theresa Sackler Foundation and Autism Speaks. 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D., 1996, ANN CHILD DEV, V12, P119 Zelazo PD, 2006, NAT PROTOC, V1, P297, DOI 10.1038/nprot.2006.46 Zmyj N., 2011, BIENN M SOC RES CHIL NR 73 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-3920 EI 1467-8624 J9 CHILD DEV JI Child Dev. PD SEP-OCT PY 2014 VL 85 IS 5 BP 1777 EP 1794 DI 10.1111/cdev.12237 PG 18 WC Psychology, Educational; Psychology, Developmental SC Psychology GA AQ5CF UT WOS:000342820100002 PM 24605760 ER PT J AU Berry, R Firth, G Leeming, C Sharma, V AF Berry, Ruth Firth, Graham Leeming, Catherine Sharma, Vishal TI Clinical Psychologists' Views of Intensive Interaction as an Intervention in Learning Disability Services SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Intensive Interaction; Psychology; Therapeutic; Learning Disabilities; Inclusion; Development AB Intensive Interaction was initially developed in the 1980s as an educational approach for developing social communication and engagement with people with severe or profound intellectual disabilities and/or autism. Intensive Interaction has subsequently been adopted by a range of practitioners and professionals working in learning disability services and has a broad multi-disciplinary acceptance, being recommended in a number of UK governmental guidance documents. Despite this, there has been limited work on developing a deeper psychological understanding of the approach. This study utilises a qualitative description/thematic analysis approach to explore how clinical psychologists conceptualise the approach with regard to currently accepted psychological theories, as well as looking at other factors that influence their adoption and advocacy. The sample deliberately consisted of eight NHS (National Health Service) clinical psychologists known to be using or advocating the use of Intensive Interaction with people with a learning disability. The results of this study indicate that although the participants referred to some theories that might explain the beneficial outcomes of Intensive Interaction, these theories were rarely explicitly or clearly referenced, resulting in the authors having to attribute specific theoretical positions on the basis of inductive analysis of the participants' responses. Moreover, the participants provided varying views on how Intensive Interaction might be conceptualised, highlighting the lack of a generally accepted, psychologically framed definition of the approach. In conclusion, it was felt that further research is required to develop a specifically psychological understanding of Intensive Interaction alongside the formation of a Special Interest Group, which might have this task as one of its aims. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Berry, Ruth; Firth, Graham; Leeming, Catherine; Sharma, Vishal] St Marys Hosp, Leeds & York Partnership NHS Fdn Trust, Learning Disabil Psychol Serv, Leeds LS12 3QE, W Yorkshire, England. RP Firth, G (reprint author), St Marys Hosp, Leeds & York Partnership NHS Fdn Trust, Learning Disabil Psychol Serv, Greenhill Rd, Leeds LS12 3QE, W Yorkshire, England. EM graham.firth@nhs.net CR Ainsworth M. 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N., 2000, INTERPERSONAL WORLD Vygotsky Lev Semyonovitch, 1978, MIND SOC DEV HIGHER Watson J, 1997, BRIT J SPECIAL ED, V24, P80, DOI 10.1111/1467-8527.00020 Watson T., 2006, BRIT J LEARN DISABIL, V34, P103, DOI 10.1111/j.1468-3156.2005.00374.x Zeedyk S., 2009, BRIT J LEARN DISABIL, V37, P186 Zeedyk S., 2009, EUROPEAN J SPECIAL N, V24, P119 NR 33 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1063-3995 EI 1099-0879 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD SEP-OCT PY 2014 VL 21 IS 5 BP 403 EP 410 DI 10.1002/cpp.1846 PG 8 WC Psychology, Clinical SC Psychology GA AQ6DG UT WOS:000342897900003 PM 23696471 ER PT J AU D'Alessandro, G Cremonesi, I Alkhamis, N Piana, G AF D'Alessandro, G. Cremonesi, I. Alkhamis, N. Piana, G. TI Correlation between oral health in disabled children and depressive symptoms in their mothers SO EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY LA English DT Article DE Disabled children; Major depression risk; Mothers of disabled children; Son/daughter oral health ID POSTNATAL DEPRESSION; MATERNAL DEPRESSION; MENTAL-RETARDATION; DENTAL-CARIES; AUTISM; PARENTS; STRESS; FAMILIES; SCALE; INTERVENTION AB Aim The aim of this study was to evaluate the presence and degree of depressive symptoms in mothers of disabled children and to assess the correlation between maternal major depression risk and son/daughter oral health. Materials and methods A prospective study was conducted in 51 disabled children and their 51 mothers. In children dmft/DMFT values, food and/or sugar-sweetened consumption levels and daily tooth brushing frequency were evaluated. Depressive maternal symptoms were Measured by EDPS questionnaire: the questionnaire scores were converted into positive predictive values (PPV) that represented the risk of falling into major depression. A regression analysis was performed on the variables (statical significance was set at p value <= 0.05). Results Children (8.68 +/- 3.98 years old) average dmft/DMFT was 2.7 Fifty three percent of the mothers (38.37 +/- 6.04 years) were at risk for depression (PPV>60%), while depressive symptoms were already present in 25% of the subjects (PPV=100%). Discussion and conclusion Mothers of disabled Children are more likely to fall into major depression compared to mothers of healthy children. For each mother-child couple the correlation between different variables was evaluated: there was a statistically significant Correlation between children's dmft/ DMFT values and mothers' depression risk. The risk of maternal depression was statistically correlated to prevalence of caries and sugar consumption in children. C1 [D'Alessandro, G.; Cremonesi, I.; Alkhamis, N.; Piana, G.] Univ Bologna, Alma Mater Studiorum, Sch Dent, Dept Biomed & Neuromotor Sci DIBINEM,Dent Speci, Bologna, Italy. RP D'Alessandro, G (reprint author), Univ Bologna, Alma Mater Studiorum, Sch Dent, Dept Biomed & Neuromotor Sci DIBINEM,Dent Speci, Bologna, Italy. 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J. Paediatr. Dent. PD SEP PY 2014 VL 15 IS 3 BP 303 EP 308 PG 6 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA AQ5VI UT WOS:000342876300010 PM 25306149 ER PT J AU Mielnik, CA Horsfall, W Ramsey, AJ AF Mielnik, C. A. Horsfall, W. Ramsey, A. J. TI Diazepam improves aspects of social behaviour and neuron activation in NMDA receptor-deficient mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Antipsychotic; benzodiazepine; GABA; glutamate; neural substrate; NMDA; social behaviour ID VASOPRESSIN RECEPTOR; NEGATIVE SYMPTOMS; TASKS RELEVANT; GENETIC MODEL; SCHIZOPHRENIA; EXPRESSION; AUTISM; HYPOFUNCTION; SOCIABILITY; AMYGDALA AB NR1 knockdown (NR1KD) mice are genetically modified to express low levels of the NR1 subunit of N-methyl-d-aspartate (NMDA) receptors, and show deficits in affiliative social behaviour. In this study, we determined which brain regions were selectively activated in response to social stimulation and asked whether differences in neuronal activation could be observed in mice with reduced sociability. Furthermore, we aimed to determine whether brain activation patterns correlated with the amelioration of social deficits through pharmacological intervention. The cingulate cortex, lateral septal nuclei, hypothalamus, thalamus and amygdala showed an increase in c-Fos immunoreactivity that was selective for exposure to social stimuli. NR1KD mice displayed a reduction in social behaviour and a reduction in c-Fos immunoreactivity in the cingulate cortex and septal nuclei. Acute clozapine did not significantly alter sociability; however, diazepam treatment did increase sociability and neuronal activation in the lateral septal region. This study has identified the lateral septal region as a neural substrate of social behaviour and the GABA system as a potential therapeutic target for social dysfunction. C1 [Mielnik, C. A.; Horsfall, W.; Ramsey, A. J.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada. RP Ramsey, AJ (reprint author), Univ Toronto, Dept Pharmacol & Toxicol, 1 Kings Coll Circle,Rm 4302,Med Sci Bldg, Toronto, ON M5S 1A8, Canada. EM a.ramsey@utoronto.ca CR Anthony TE, 2014, CELL, V156, P522, DOI 10.1016/j.cell.2013.12.040 Baandrup L, 2011, BMC PSYCHIATRY, V11, DOI 10.1186/1471-244X-11-160 Bielsky IF, 2005, NEURON, V47, P503, DOI 10.1016/j.neuron.2005.06.031 BULLITT E, 1990, J COMP NEUROL, V296, P517, DOI 10.1002/cne.902960402 Caldwell HK, 2012, ADV EXP MED BIOL, V739, P187, DOI 10.1007/978-1-4614-1704-0_12 Ciudad A, 2006, PROG NEURO-PSYCHOPH, V30, P1515, DOI 10.1016/j.pnpbp.2006.05.010 CORBETT R, 1995, PSYCHOPHARMACOLOGY, V120, P67, DOI 10.1007/BF02246146 Crawley JN, 2004, MENT RETARD DEV D R, V10, P248, DOI 10.1002/mrdd.20039 Dold M, 2012, COCHRANE DB SYST REV, V11 Duncan GE, 2004, BEHAV BRAIN RES, V153, P507, DOI 10.1016/j.bbr.2004.01.008 Duncan GE, 2009, BRAIN RES, V1265, P186, DOI 10.1016/j.brainres.2009.02.002 Fairless AH, 2011, ANAT REC, V294, P1713, DOI 10.1002/ar.21318 Gandal MJ, 2012, GENES BRAIN BEHAV, V11, P740, DOI 10.1111/j.1601-183X.2012.00816.x Gandal MJ, 2012, TRANSL PSYCHIAT, V2, DOI 10.1038/tp.2012.69 Goodson JL, 2005, HORM BEHAV, V48, P11, DOI 10.1016/j.yhbeh.2005.02.003 Halene TB, 2009, GENES BRAIN BEHAV, V8, P661, DOI 10.1111/j.1601-183X.2009.00504.x Han S, 2014, NEURON, V81, P1282, DOI 10.1016/j.neuron.2014.01.016 Hanks AN, 2013, BEHAV BRAIN RES, V252, P405, DOI 10.1016/j.bbr.2013.06.017 Labrie V, 2008, PSYCHOPHARMACOLOGY, V200, P217, DOI 10.1007/s00213-008-1196-6 Levitt P, 2004, TRENDS NEUROSCI, V27, P400, DOI 10.1016/j.tins.2004.05.008 Lewis DA, 2005, NAT REV NEUROSCI, V6, P312, DOI 10.1038/nrn1648 Mohn AR, 1999, CELL, V98, P427, DOI 10.1016/S0092-8674(00)81972-8 Moy SS, 2007, BEHAV BRAIN RES, V176, P4, DOI 10.1016/j.bbr.2006.07.030 Nadler JJ, 2004, GENES BRAIN BEHAV, V3, P303, DOI 10.1111/j.1601-183X.2004.00071.x Newman SW, 1999, ANN NY ACAD SCI, V877, P242, DOI 10.1111/j.1749-6632.1999.tb09271.x Ophir AG, 2009, BEHAV NEUROSCI, V123, P979, DOI 10.1037/a0016663 Pereira A., 2011, INT J NEUROPSYCHOPH, V15, P1149 Pollack MH, 1999, J CLIN PSYCHIAT, V60, P20 Ramsey AJ, 2009, PROG BRAIN RES, V179, P51, DOI 10.1016/S0079-6123(09)17906-2 Ramsey AJ, 2011, P NATL ACAD SCI USA, V108, P5795, DOI 10.1073/pnas.1012621108 Ramsey AJ, 2008, NEUROPSYCHOPHARMACOL, V33, P2701, DOI 10.1038/sj.npp.1301663 Sandhu KV, 2014, GENES BRAIN BEHAV, V13, P439, DOI 10.1111/gbb.12131 Veenema AH, 2008, PROG BRAIN RES, V170, P261, DOI 10.1016/S0079-6123(08)00422-6 Yizhar O, 2011, NATURE, V477, P171, DOI 10.1038/nature10360 Yizhar O, 2012, BIOL PSYCHIAT, V71, P1075, DOI 10.1016/j.biopsych.2011.12.029 NR 35 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 EI 1601-183X J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD SEP PY 2014 VL 13 IS 7 BP 592 EP 602 DI 10.1111/gbb.12155 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AQ5CY UT WOS:000342823600002 PM 25040071 ER PT J AU Wade, M Hoffmann, TJ Wigg, K Jenkins, JM AF Wade, M. Hoffmann, T. J. Wigg, K. Jenkins, J. M. TI Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Child development; family-based association design; genetic association; oxytocin receptor; social cognition; theory of mind ID FAMILY-BASED ASSOCIATION; YOUNG-CHILDREN; HUMAN-BEHAVIOR; MIND; AUTISM; HUMANS; VASOPRESSIN; BRAIN; POLYMORPHISMS; TEMPERAMENT AB At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self-recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social-cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene (OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio-emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self-recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family-based association design was used to control for population admixture and stratification, and additional non-genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition (P=0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149-rs2254298 was also associated with social cognition (P=0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed. C1 [Wade, M.; Jenkins, J. M.] Univ Toronto, Dept Appl Psychol & Human Dev, Toronto, ON M5S 1V6, Canada. [Hoffmann, T. J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Hoffmann, T. J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Wigg, K.] Toronto Western Res Inst, Genet & Dev Div, Toronto, ON, Canada. RP Jenkins, JM (reprint author), Univ Toronto, Dept Appl Psychol & Human Dev, 252 Bloor St West, Toronto, ON M5S 1V6, Canada. EM jenny.jenkins@utoronto.ca FU Canadian Institutes of Health Research FX We are grateful to the families who give so generously of their time, to the Hamilton and Toronto Public Health Units for facilitating recruitment of the sample, and to Mira Boskovic for project management. The grant 'Transactional processes in emotional and behavioral regulation: individuals in context' was awarded to Jennifer M. Jenkins and Michael Boyle from the Canadian Institutes of Health Research and covered data collection. The study team, beyond the current authors includes: Cathy Barr, Kathy Georgiades, Greg Moran, Tom O'Connor, Michal Perlman, Hildy Ross, Louis Schmidt. A special thank you goes to Cathy Barr for her comments on earlier versions of this manuscript. 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PD SEP PY 2014 VL 13 IS 7 BP 603 EP 610 DI 10.1111/gbb.12148 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AQ5CY UT WOS:000342823600003 PM 24916666 ER PT J AU Timimi, S AF Timimi, S. TI Children's behaviour problems: a NICE mess SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Editorial Material ID DISORDER; AUTISM AB The potential harms of medicalisation are well known. A good illustration comes from the medicalisation of children's behaviour problems. National Institute for health and Clinical Excellence (NICE) guidelines on conditions such as Attention Deficit Hyperactivity Disorder (ADHD), Autistic Spectrum Disorder (ASD) and Conduct Disorder (CD) reflect how attempts to regulate medical practice in this area has spawned guidelines based more on wish fulfilment (that getting kids to behave themselves can be accomplished by simple technological interventions that exist independent of context) than scientific evidence. In this perspective piece, I explain why these NICE guidelines are more a reflection of cultural confusion about how to deal with children, than the outcome of sound scientific understanding in this area. C1 [Timimi, S.] Lincolnshire Partnership NHSFT, Child Serv, Lincoln, England. [Timimi, S.] Lincolnshire Partnership NHSFT, Family Serv, Lincoln, England. RP Timimi, S (reprint author), Lincolnshire Partnership NHSFT, Child Serv, Lincoln, England. 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PD SEP PY 2014 VL 68 IS 9 BP 1053 EP 1055 DI 10.1111/ijcp.12442 PG 3 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA AQ4XV UT WOS:000342805700003 PM 25196181 ER PT J AU Radley, KC Jenson, WR Clark, E Hood, JA Nicholas, P AF Radley, Keith C. Jenson, William R. Clark, Elaine Hood, Julia A. Nicholas, Peter TI Using a Multimedia Social Skills Intervention to Increase Social Engagement of Young Children With Autism Spectrum Disorder SO INTERVENTION IN SCHOOL AND CLINIC LA English DT Article DE social; skills; early intervention; intervention(s); autism; disabilities; preschool; early childhood ID METAANALYSIS; PROGRAMS AB Children with autism spectrum disorder (ASD) display impairments in social interactions and communication that appear at early ages. Fewer social engagements of children with ASD with peers often lead to long-term negative outcomes, such as social isolation and restricted language and cognitive skills. Although there is a clear need for social skills training for children with ASD, evidence-based practices are often not implemented for young children in school settings. The authors describe the Superheroes Social Skills program, a social skills intervention that combines multiple evidence-based practices, for use with young children with ASD. A case example is provided to describe the implementation and utility of the program for addressing social engagement skills of children with ASD and peers. Results of the case example suggest that the intervention contributed to greater engagement of children with ASD with peers during a free-play period. C1 [Radley, Keith C.] Univ So Mississippi, Hattiesburg, MS 39406 USA. [Jenson, William R.; Clark, Elaine; Hood, Julia A.] Univ Utah, Salt Lake City, UT USA. [Nicholas, Peter] Carmen B Pingree Ctr Children Autism, Salt Lake City, UT USA. 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PD SEP PY 2014 VL 50 IS 1 BP 22 EP 28 DI 10.1177/1053451214532350 PG 7 WC Education, Special SC Education & Educational Research GA AQ4TK UT WOS:000342792400004 ER PT J AU Lillvis, DF Kirkland, A Frick, A AF Lillvis, Denise F. Kirkland, Anna Frick, Anna TI Power and Persuasion in the Vaccine Debates: An Analysis of Political Efforts and Outcomes in the United States, 1998-2012 SO MILBANK QUARTERLY LA English DT Article DE child; health legislation; United States; vaccination ID SCHOOL IMMUNIZATION REQUIREMENTS; NONMEDICAL EXEMPTIONS; AUTISM; POLICIES; CONTROVERSY; MERCURY AB From 2011 to 2013, immunization proponents won significant legislative victories that tightened philosophical exemptions in Washington, Oregon, and California. Highlighting data on the high rates of unvaccinated children and subsequent, preventable infectious disease outbreaks has proven to be quite compelling to state lawmakers, especially when combined with physician expert testimony. Even vigorous protest from vaccine-critical organizations failed to defeat recent legislative wins when other political conditions were favorable. Our research suggests that immunization proponents have not been as active as they could be, and that much of the energy in pressing for new policies over the past 15 years has been on the vaccine-critical side of the aisle. ContextThis article examines trends in state-level childhood vaccine policies in the United States from 1998 to 2012 and explains the trajectories for both vaccine-critical and proimmunization legislative efforts. Successful mobilization by vaccine critics during the height of the autism and thimerosal scares (roughly 1998 to 2003) yielded a few state-level expansions for the most permissive type of exemption from vaccine mandates for public school attendance, those based on personal beliefs. Vaccine-critical positions, however, have largely become discredited. How has vaccine critics' ability to advance preferred policies and prevent the passage of unfavorable legislation changed over time? MethodsWe created a unique data set of childhood vaccine bills (n = 636), introduced from 1998 to 2012 across the 50 state legislatures, and coded them by type of effort (exemption, mandate, mercury ban, and information policies) and outcome. We then mapped out the trends in vaccine policies over time. In order to contextualize the trends we identified, we also reviewed numerous primary sources and conducted interviews with stakeholders. FindingsIn general, we found that vaccine critics' legislative success has begun to wane. In only 20 bills in our data set were vaccine critics able to change policy in their preferred direction via the legislative process. Only 5 of those wins were significant (such as obtaining a new philosophical exemption to vaccine mandates), and the last of these was in 2007. Critics were more successful at preventing passage of proimmunization legislation, such as mandates for the human papillomavirus (HPV) vaccine. ConclusionsRecent legislation in California, Oregon, and Washington that tightened philosophical exemptions by means of informational requirements suggests that vaccine politics may be entering another phase, one in which immunization supporters may be able to counter increasing opt-out rates, particularly in states with recent outbreaks and politicians favoring science-based policies. C1 [Lillvis, Denise F.] Univ Michigan, Dept Hlth Management & Policy, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Lillvis, Denise F.] Univ Michigan, Dept Polit Sci, Ann Arbor, MI 48109 USA. [Lillvis, Denise F.; Frick, Anna] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Lillvis, DF (reprint author), Univ Michigan, Dept Hlth Management & Policy, Sch Publ Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM dlillvis@umich.edu CR Abiola SE, 2013, J HEALTH POLIT POLIC, V38, P645, DOI 10.1215/03616878-2208567 Adams M., 2012, NATURAL NEWS 1024 Advisory Commission on Childhood Vaccines (ACCV), 2002, 51 M ADV COMM CHILDH American Academy of Pediatrics (AAP) and the United States Public Health Service (USPHS), 1999, PEDIATRICS, V104, P568 Baker JP, 2008, AM J PUBLIC HEALTH, V98, P244, DOI 10.2105/AJPH.2007.113159 Bernard S, 2001, MED HYPOTHESES, V56, P462, DOI 10.1054/mehy.2000.1281 Blank NR, 2013, HEALTH AFFAIR, V32, P1282, DOI 10.1377/hlthaff.2013.0239 Boushey G, WORKING PAPER Colgrove J, 2010, NEW ENGL J MED, V363, P785, DOI 10.1056/NEJMsr1003547 Colgrove J., 2006, STATE IMMUNITY POLIT Freed GL, 2010, PEDIATRICS, V125, P654, DOI 10.1542/peds.2009-1962 Heffter E., 2011, SEATTLE TIMES Institute of Medicine, 2004, IMM SAF REV VACC AUT Institute of Medicine, 2001, THIM CONT VACC NEUR Kirkland A, 2012, SOC STUD SCI, V42, P237, DOI 10.1177/0306312711435832 Kirkland A, 2012, J HEALTH POLIT POLIC, V37, P69, DOI 10.1215/03616878-1496020 Krehbiel Keith, 1998, PIVOTAL POLITICS THE Nelson KB, 2003, PEDIATRICS, V111, P674, DOI 10.1542/peds.111.3.674 Oliver TR, 2006, ANNU REV PUBL HEALTH, V27, P195, DOI 10.1146/annurev.publhealth.25.101802.123126 Omer SB, 2006, JAMA-J AM MED ASSOC, V296, P1757, DOI 10.1001/jama.296.14.1757 Omer SB, 2009, NEW ENGL J MED, V360, P1981, DOI 10.1056/NEJMsa0806477 Oregonians for Healthy Children, 2013, OR HIGH RAT VACC EX Ostrum C., 2011, SEATTLE TIMES Pollan Michael, 2009, FOOD RULES EATERS MA Richardson D., 2009, 2009 NAT VACC INF CT Richardson D., 2012, NVIC ADVOCACY TEAM N Rota JS, 2001, AM J PUBLIC HEALTH, V91, P645, DOI 10.2105/AJPH.91.4.645 Salmon DA, 2005, AM J PUBLIC HEALTH, V95, P436, DOI 10.2105/AJPH.2004.046201 Salmon DA, 2006, LANCET, V367, P436, DOI 10.1016/S0140-6736(06)68144-0 Shipan CR, 2006, AM J POLIT SCI, V50, P825, DOI 10.1111/j.1540-5907.2006.00218.x UNEP News Centre, 2013, MIN CONV AGR NAT GLO US Food and Drug Administration (FDA), THIM VACC Vannice KS, 2011, PEDIATRICS, V127, pS120, DOI 10.1542/peds.2010-1722R Wakefield AJ, 1998, LANCET, V351, P637, DOI 10.1016/S0140-6736(97)11096-0 NR 34 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-378X EI 1468-0009 J9 MILBANK Q JI Milbank Q. PD SEP PY 2014 VL 92 IS 3 BP 475 EP 508 DI 10.1111/1468-0009.12075 PG 34 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AQ4HS UT WOS:000342755200012 PM 25199897 ER PT J AU Orosco, LA Ross, AP Cates, SL Scott, SE Wu, D Sohn, J Pleasure, D Pleasure, SJ Adamopoulos, IE Zarbalis, KS AF Orosco, Lori A. Ross, Adam P. Cates, Staci L. Scott, Sean E. Wu, Dennis Sohn, Jiho Pleasure, David Pleasure, Samuel J. Adamopoulos, Iannis E. Zarbalis, Konstantinos S. TI Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology SO NATURE COMMUNICATIONS LA English DT Article ID DE-NOVO MUTATIONS; INTERMEDIATE PROGENITOR CELLS; FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; MESSENGER-RNAS; STEM-CELLS; DEVELOPING NEOCORTEX; NERVOUS-SYSTEM; NEURON NUMBER; RADIAL GLIA AB Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neuro-developmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs. C1 [Orosco, Lori A.; Ross, Adam P.; Cates, Staci L.; Scott, Sean E.] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [Orosco, Lori A.; Ross, Adam P.; Cates, Staci L.; Scott, Sean E.; Wu, Dennis; Sohn, Jiho; Pleasure, David; Adamopoulos, Iannis E.; Zarbalis, Konstantinos S.] Shriners Hosp Children, Inst Pediat Regenerat Med, Sacramento, CA 95817 USA. [Wu, Dennis; Adamopoulos, Iannis E.] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Dept Internal Med, Davis, CA 95616 USA. [Pleasure, David] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Pleasure, David] Univ Calif Davis, Dept Pediat, Sacramento, CA 95817 USA. [Pleasure, Samuel J.] Univ Calif San Francisco, UCSF Inst Regenerat Med, Dept Neurol, Program Neurosci,Sandler Neurosci Ctr, San Francisco, CA 94158 USA. [Pleasure, Samuel J.] Univ Calif San Francisco, UCSF Inst Regenerat Med, Dept Neurol, Sandler Neurosci Ctr,Program Dev & Stem Cell Biol, San Francisco, CA 94158 USA. RP Zarbalis, KS (reprint author), Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. EM kzarbalis@ucdavis.edu FU Shriners Hospitals for Children, NICHD [R21HD67855]; Simons Foundation [286567]; Nancy Lurie Marks Family Foundation; Shriners Hospital for Children Postdoctoral Fellowship Grant; NIH [U01HG004085]; CSD Consortium [U01HG004080]; KOMP Repository at UC Davis and CHORI [U42RR024244]; SFARI [286567] FX This study was funded by Shriners Hospitals for Children, NICHD R21HD67855 to KSZ, the Simons Foundation with SFARI 286567 to KSZ, and the Nancy Lurie Marks Family Foundation to KSZ as well as a Shriners Hospital for Children Postdoctoral Fellowship Grant to LAO. We would particularly like to thank Drs Matthew State and Michael Wigler for helpful advice and sharing data with us before publication. We would like to thank Drs Leah Krubitzer, Stephen Noctor and Veronica Martinez Cerdeno for support and helpful discussions during the course of this project as well as Katie Yerocostas and Danielle Brill-Lehn for technical assistance. NIH grants to Velocigene at Regeneron Inc. (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8,500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244). For more information or to obtain KOMP products go to www.komp.org or email service@komp.org. 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Commun. PD SEP PY 2014 VL 5 AR 4692 DI 10.1038/ncomms5692 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ5HO UT WOS:000342838800002 PM 25198012 ER PT J AU St Pourcain, B Cents, RAM Whitehouse, AJO Haworth, CMA Davis, OSP O'Reilly, PF Roulstone, S Wren, Y Ang, QW Velders, FP Evans, DM Kemp, JP Warrington, NM Miller, L Timpson, NJ Ring, SM Verhulst, FC Hofman, A Rivadeneira, F Meaburn, EL Price, TS Dale, PS Pillas, D Yliherva, A Rodriguez, A Golding, J Jaddoe, VWV Jarvelin, MR Plomin, R Pennell, CE Tiemeier, H Smith, GD AF St Pourcain, Beate Cents, Rolieke A. M. Whitehouse, Andrew J. O. Haworth, Claire M. A. Davis, Oliver S. P. O'Reilly, Paul F. Roulstone, Susan Wren, Yvonne Ang, Qi W. Velders, Fleur P. Evans, David M. Kemp, John P. Warrington, Nicole M. Miller, Laura Timpson, Nicholas J. Ring, Susan M. Verhulst, Frank C. Hofman, Albert Rivadeneira, Fernando Meaburn, Emma L. Price, Thomas S. Dale, Philip S. Pillas, Demetris Yliherva, Anneli Rodriguez, Alina Golding, Jean Jaddoe, Vincent W. V. Jarvelin, Marjo-Riitta Plomin, Robert Pennell, Craig E. Tiemeier, Henning Smith, George Davey TI Common variation near ROBO2 is associated with expressive vocabulary in infancy SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; LANGUAGE-DEVELOPMENT SURVEY; AXON-GUIDANCE RECEPTORS; GENE-EXPRESSION; MIDLINE; AUTISM; TOOL; CHROMOSOME-3; ENHANCERS; GENOTYPES AB Twin studies suggest that expressive vocabulary at similar to 24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15-18 months, 'one-word stage', N-Total = 8,889) and a later (24-30 months, 'two-word stage', N-Total = 10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P = 1.3 x 10(-8)) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h(5-18-months)(2) = 0.13, meta-GCTA h(24-30-months)(2) = 0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h(24-months)(2) = 0.20). C1 [St Pourcain, Beate; Evans, David M.; Kemp, John P.; Timpson, Nicholas J.; Ring, Susan M.; Smith, George Davey] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [St Pourcain, Beate] Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England. [St Pourcain, Beate] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TU, Avon, England. [Cents, Rolieke A. M.; Velders, Fleur P.; Jaddoe, Vincent W. V.] Erasmus MC Univ, Med Ctr, Generat R Study Grp, NL-3000 CA Rotterdam, Netherlands. [Cents, Rolieke A. M.; Velders, Fleur P.; Verhulst, Frank C.; Tiemeier, Henning] Erasmus MC Univ, Med Ctr, Dept Child & Adolescent Psychiat Psychol, NL-3000 CB Rotterdam, Netherlands. [Whitehouse, Andrew J. O.] Univ Western Australia, Ctr Child Hlth Res, Telethon Kids Inst, Subiaco, WA 6008, Australia. [Haworth, Claire M. A.] Univ Warwick, Dept Psychol, Coventry CV4 7AL, W Midlands, England. [Haworth, Claire M. A.; Davis, Oliver S. P.; O'Reilly, Paul F.; Plomin, Robert] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, MRC, London SE5 8AF, England. [Davis, Oliver S. P.] UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London WC1E 6BT, England. [O'Reilly, Paul F.; Pillas, Demetris; Rodriguez, Alina; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ctr Environm & Hlth, Dept Epidemiol & Biostat,MRC,Publ Hlth England, London W2 1PG, England. [Roulstone, Susan; Wren, Yvonne] Univ W England, Frenchay Hosp, Bristol Speech & Language Therapy Res Unit, Bristol BS16 1LE, Avon, England. [Ang, Qi W.; Warrington, Nicole M.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Subiaco, WA 6008, Australia. [Evans, David M.; Kemp, John P.; Miller, Laura; Timpson, Nicholas J.; Ring, Susan M.; Golding, Jean; Smith, George Davey] Univ Bristol, Sch Social & Community Med, Bristol BS8 2PS, Avon, England. [Evans, David M.; Kemp, John P.; Warrington, Nicole M.] Univ Queensland, Translat Res Inst, Diamantina Inst, Woolloongabba, Qld 4102, Australia. [Hofman, Albert; Rivadeneira, Fernando; Jaddoe, Vincent W. V.; Tiemeier, Henning] Erasmus MC Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Rivadeneira, Fernando] Erasmus MC Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Meaburn, Emma L.] Univ London, Dept Psychol Sci, London WC1E 7HX, England. [Price, Thomas S.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Dale, Philip S.] Univ New Mexico, Dept Speech & Hearing Sci, Albuquerque, NM 87131 USA. [Yliherva, Anneli] Univ Oulu, Fac Humanities, Child Language Res Ctr, Oulu 90014, Finland. [Rodriguez, Alina] Mid Sweden Univ, Dept Psychol, Mittuniv, S-83125 Ostersund, Sweden. [Jaddoe, Vincent W. V.] Erasmus MC Univ, Med Ctr, Dept Pediat, NL-3000 CB Rotterdam, Netherlands. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, FI-90220 Oulu, Finland. [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children & Young People & Families, FI-90101 Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FI-90014 Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, FI-90014 Oulu, Finland. RP St Pourcain, B (reprint author), Univ Bristol, MRC, Integrat Epidemiol Unit, Oakfield House,15-23 Oakfield Grove, Bristol BS8 2BN, Avon, England. EM Beate.StPourcain@bristol.ac.uk RI Price, Thomas/B-7372-2008; Dale, Philip/A-2254-2009; Warrington, Nicole/P-4868-2014 OI Price, Thomas/0000-0001-7356-2109; Dale, Philip/0000-0002-7697-8510; Warrington, Nicole/0000-0003-4195-775X FU UK Medical Research Council; Wellcome Trust [092731]; Medical Research Council Integrative Epidemiology Unit [MC_UU_12013/1-9]; Medical Research Council New Investigator Award [MRCG0800582]; Autism Speaks [7132]; Wellcome Trust 4-year PhD studentship [WT083431MA]; 23andMe FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for ALSPAC. ALSPAC GWAS data were generated by the Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using funding from 23andMe. This work was also supported by the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/1-9). D.M.E. is supported by a Medical Research Council New Investigator Award (MRCG0800582 to D.M.E.). J.P.K. is funded by a Wellcome Trust 4-year PhD studentship (WT083431MA). B.S.P. is supported by an Autism Speaks grant (7132). This publication is the work of the authors and they will serve as guarantors for the contents of this paper. 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PD SEP PY 2014 VL 5 AR 4831 DI 10.1038/ncomms5831 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ6ND UT WOS:000342929300002 PM 25226531 ER PT J AU Wang, CJ Chung, BC Yan, HD Wang, HG Lee, SY Pitt, GS AF Wang, Chaojian Chung, Ben C. Yan, Haidun Wang, Hong-Gang Lee, Seok-Yong Pitt, Geoffrey S. TI Structural analyses of Ca2+/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation SO NATURE COMMUNICATIONS LA English DT Article ID GATED SODIUM-CHANNEL; DE-NOVO MUTATIONS; INHERITED CARDIAC-ARRHYTHMIA; FACTOR HOMOLOGOUS FACTORS; SOLUTION NMR STRUCTURE; EF-HAND DOMAIN; CRYSTAL-STRUCTURE; NEURONAL EXCITABILITY; FAST INACTIVATION; BRUGADA SYNDROME AB Ca2+ regulates voltage-gated Na+ (Na-V) channels, and perturbed Ca2+ regulation of Na-V function is associated with epilepsy syndromes, autism and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca2+ affects Na-V channel function. Here we report the crystal structures of two ternary complexes of a human Na-V cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor and Ca2+ /calmodulin (Ca2+ /CaM). These structures rule out direct binding of Ca2+ to the Na-V CTD and uncover new contacts between CaM and the Na-V CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca2+ could regulate Na-V channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by Na-V channel mutations. C1 [Wang, Chaojian; Chung, Ben C.; Yan, Haidun; Wang, Hong-Gang; Lee, Seok-Yong; Pitt, Geoffrey S.] Duke Univ, Med Ctr, Dept Med, Ion Channel Res Unit, Durham, NC 27710 USA. [Wang, Chaojian; Yan, Haidun; Wang, Hong-Gang; Pitt, Geoffrey S.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Chung, Ben C.; Lee, Seok-Yong] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Pitt, Geoffrey S.] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. RP Lee, SY (reprint author), Duke Univ, Med Ctr, Dept Med, Ion Channel Res Unit, 2 Genome Court, Durham, NC 27710 USA. EM sylee@biochem.duke.edu; geoffrey.pitt@duke.edu FU NHLBI [R01 HL71165, HL113136]; American Heart Association Established Investigator Award; Duke University Medical Center; Basil O'Connor Starter Scholar Research Award from the March of Dimes foundation [5-FY10-473]; N.I.H. Director's New Innovator Award [1 DP2 OD008380-01] FX Data for this study were collected at beam lines NE-CAT ID 24-C and SER-CAT BM22/ID22 and at the Advanced Photon Source and the Duke X-ray Crystallography Facility. We thank R. Brennan, M. Schumacher and P. Zhou for providing access to their ITC machines; C. Pemble for help with remote data collection. This work was supported by NHLBI R01 HL71165 and HL113136 (G. S. P.) and American Heart Association Established Investigator Award (G. S. P.); start-up funds from the Duke University Medical Center (S.-Y.L.), the Basil O'Connor Starter Scholar Research Award 5-FY10-473 from the March of Dimes foundation (S.-Y.L.), the N.I.H. Director's New Innovator Award 1 DP2 OD008380-01 (S.-Y.L.). S.-Y.L. is a McKnight Scholar, Klingenstein fellow, Alfred P. Sloan Research fellow, Mallinckrodt Scholar and Whitehead Scholar. 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Commun. PD SEP PY 2014 VL 5 AR 4896 DI 10.1038/ncomms5896 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ7HP UT WOS:000342983700003 PM 25232683 ER PT J AU Godman, M Nagatsu, M Salmela, M AF Godman, Marion Nagatsu, Michiru Salmela, Mikko TI The Social Motivation Hypothesis for Prosocial Behavior SO PHILOSOPHY OF THE SOCIAL SCIENCES LA English DT Article DE social motivation; pro-social behavior; fellow-feeling; social norms; team reasoning ID INTERPERSONAL SYNCHRONY; YOUNG-CHILDREN; JOINT ACTION; COOPERATION; IMITATION; AUTISM; EXPECTATIONS; ATTACHMENTS; AFFILIATION; PERCEPTION AB Existing economic models of prosociality have been rather silent in terms of proximate psychological mechanisms. We nevertheless identify the psychologically most informed accounts and offer a critical discussion of their hypotheses for the proximate psychological explanations. 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Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR)/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk), which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc) as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem/progenitor cells, suggesting that the role of Unk in neurogenesis may be conserved in mammals. C1 [Avet-Rochex, Amelie; Carvajal, Nancy; Christoforou, Christina P.; Maierbrugger, Katja T.; Hobbs, Carl; Lalli, Giovanna; Cagin, Umut; Bateman, Joseph M.] Kings Coll London, Wolfson Ctr Age Related Dis, London, England. [Yeung, Kelvin; Plachot, Cedric; McNeill, Helen] Lunenfeld Tanenbaum Res Ctr, Toronto, ON, Canada. RP Avet-Rochex, A (reprint author), Univ Lyon 1, CNRS, Ctr Genet & Physiol Mol & Cellulaire, UMR 5534, F-69622 Villeurbanne, France. EM joseph_matthew.bateman@kcl.ac.uk RI McNeill, Helen/E-4579-2013 OI McNeill, Helen/0000-0003-1126-5154 FU King's College London; Wellcome Trust [WT088460MA, WT089622MA]; Canadian Institutes of Health Research [FRN 102656, 97933] FX The work was funded by King's College London, The Wellcome Trust (WT088460MA and WT089622MA, http://www.wellcome.ac.uk/) and the Canadian Institutes of Health Research (FRN 102656 and 97933, http://www.cihr-irsc.gc.ca/e/193.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Nava, Caroline Polge, Anne Gauthier, Julie Huguet, Guillaume Lumbroso, Serge Giuliano, Fabienne Stordeur, Coline Depienne, Christel Mouzaf, Kevin Pinto, Dalila Howe, Jennifer Lemiere, Nathalie Durand, Christelle M. Guibert, Jessica Ey, Elodie Toro, Roberto Peyre, Hugo Mathieu, Alexandre Amsellem, Frederique Rastam, Maria Gillberg, I. Carina Rappold, Gudrun A. Holt, Richard Monaco, Anthony P. Maestrini, Elena Galan, Pilar Heron, Delphine Jacquette, Aurelia Afenjar, Alexandra Rastetter, Agnes Brice, Alexis Devillard, Francoise Assouline, Brigitte Laffargue, Fanny Lespinasse, James Chiesa, Jean Rivier, Francois Bonneau, Dominique Regnault, Beatrice Zelenika, Diana Delepine, Marc Lathrop, Mark Sanlaville, Damien Schluth-Bolard, Caroline Edery, Patrick Perrin, Laurence Tabet, Anne Claude Schmeisser, Michael J. Boeckers, Tobias M. Coleman, Mary Sato, Daisuke Szatmari, Peter Scherer, Stephen W. Rouleau, Guy A. Betancur, Catalina Leboyer, Marion Gillberg, Christopher Delorme, Richard Bourgeron, Thomas TI Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments SO PLOS GENETICS LA English DT Article ID DE-NOVO MUTATIONS; COPY NUMBER VARIATION; SCAFFOLDING PROTEIN SHANK3; 22Q13 DELETION SYNDROME; SYNAPTIC-TRANSMISSION; DIAGNOSTIC INTERVIEW; MUTANT MICE; GENE; BEHAVIORS; REARRANGEMENTS AB SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in similar to 1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice. C1 [Leblond, Claire S.; Huguet, Guillaume; Stordeur, Coline; Lemiere, Nathalie; Durand, Christelle M.; Guibert, Jessica; Ey, Elodie; Toro, Roberto; Mathieu, Alexandre; Amsellem, Frederique; Delorme, Richard; Bourgeron, Thomas] Inst Pasteur, Human Genet & Cognit Funct Unit, Paris, France. [Leblond, Claire S.; Huguet, Guillaume; Stordeur, Coline; Lemiere, Nathalie; Durand, Christelle M.; Guibert, Jessica; Ey, Elodie; Toro, Roberto; Mathieu, Alexandre; Delorme, Richard; Bourgeron, Thomas] Inst Pasteur, CNRS UMR Genes Synapses & Cognit 3571, Paris, France. [Leblond, Claire S.; Huguet, Guillaume; Stordeur, Coline; Lemiere, Nathalie; Durand, Christelle M.; Guibert, Jessica; Ey, Elodie; Toro, Roberto; Mathieu, Alexandre; Delorme, Richard; Bourgeron, Thomas] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Nava, Caroline; Depienne, Christel; Rastetter, Agnes; Brice, Alexis] Hop La Pitie Salpetriere, INSERM CRICM U975, Inst Cerveau & Moelle Epiniere ICM, CNRS CRICM 7225, Paris, France. [Nava, Caroline; Depienne, Christel; Rastetter, Agnes; Brice, Alexis; Betancur, Catalina] Univ Paris 06, Univ Paris 04, Paris, France. [Nava, Caroline; Depienne, Christel; Rastetter, Agnes; Brice, Alexis] UMR S 975, Paris, France. [Polge, Anne; Lumbroso, Serge; Mouzaf, Kevin] CHU Nimes, Biochim Lab, Nimes, France. [Gauthier, Julie] CHU St Justine, Mol Diagnost Lab, Montreal, PQ, Canada. [Gauthier, Julie] CHU St Justine, Div Med Genet, Montreal, PQ, Canada. [Giuliano, Fabienne] Nice Teaching Hosp, Dept Med Genet, Nice, France. [Stordeur, Coline; Amsellem, Frederique; Delorme, Richard] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, Paris, France. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Psychiat, New York, NY 10029 USA. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Genet, New York, NY 10029 USA. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Genom Sci, New York, NY 10029 USA. [Howe, Jennifer; Sato, Daisuke; Szatmari, Peter; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. [Howe, Jennifer; Sato, Daisuke; Szatmari, Peter; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5G 1X8, Canada. [Peyre, Hugo] Ecole Normale Super, CNRS, EHESS, Lab Sci Cognit & Psycholinguist, Paris, France. [Amsellem, Frederique; Leboyer, Marion; Delorme, Richard; Bourgeron, Thomas] FondaMental Fdn, Creteil, France. [Rastam, Maria] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Gillberg, I. Carina; Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Rappold, Gudrun A.] Heidelberg Univ, Dept Human Mol Genet, Heidelberg, Germany. [Holt, Richard; Monaco, Anthony P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. [Galan, Pilar] Univ Paris 13, Nutrit Epidemiol Res Unit, INSERM U557, INRA U1125,CNAM,CRNH IdF, Bobigny, France. [Heron, Delphine; Jacquette, Aurelia; Afenjar, Alexandra] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Unite Fonct Genet Clin, Paris, France. [Heron, Delphine; Jacquette, Aurelia; Afenjar, Alexandra] Ctr Reference Deficiences Intellectuelles Causes, Paris, France. [Heron, Delphine; Jacquette, Aurelia; Afenjar, Alexandra] UPMC, Grp Rech Clin Deficience Intellectuelle & Autisme, Paris, France. [Heron, Delphine; Afenjar, Alexandra] Hop Armand Trousseau, AP HP, Serv Neuropediat, Paris, France. [Devillard, Francoise] Hop Couple Enfant, Dept Genet & Procreat, Grenoble, France. [Assouline, Brigitte] Ctr Ressources Autisme Rhone Alpes, CADIPA, St Egreve, France. [Laffargue, Fanny] Ctr Hosp Univ Estaing, Serv Genet Med, Clermont Ferrand, France. [Lespinasse, James] Ctr Hosp Chambery, Hotel Dieu, UF Genet Chromosom, Chambery, France. [Chiesa, Jean] Hop Caremeau, UF Cytogenet & Genet Med, Nimes, France. [Rivier, Francois] CHRU Montpellier, Neuropediat CR Malad Neuromusculaires, Montpellier, France. [Rivier, Francois] Univ Montpellier 1 & 2, INSERM, U1046, Montpellier, France. [Bonneau, Dominique] LUNAM Univ, INSERM U1083, Angers, France. [Bonneau, Dominique] CNRS UMR 6214, Angers, France. [Bonneau, Dominique] Ctr Hosp Univ, Dept Biochim & Genet, Angers, France. [Regnault, Beatrice] Inst Pasteur, Genopole, Paris, France. [Zelenika, Diana; Delepine, Marc; Lathrop, Mark] Ctr Natl Genotypage, Evry, France. [Sanlaville, Damien; Schluth-Bolard, Caroline; Edery, Patrick] Univ Lyon 1, Hosp Civils Lyon, CHU Lyon,INSERM U1028, Dept Genet,Ctr Rech Neurosci Lyon,CNRS UMR 5292, Bron, France. [Perrin, Laurence; Tabet, Anne Claude] Hop Robert Debre, AP HP, Dept Genet, Cytogenet Unit, F-75019 Paris, France. [Schmeisser, Michael J.; Boeckers, Tobias M.] Univ Ulm, Inst Anat & Cell Biol, D-89069 Ulm, Germany. [Coleman, Mary] Fdn Autism Res, Sarasota, FL USA. [Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Betancur, Catalina] INSERM U1130, Paris, France. [Betancur, Catalina] CNRS UMR 8246, Paris, France. [Leboyer, Marion] INSERM U955, Creteil, France. [Leboyer, Marion] Univ Paris Est, Fac Med, Creteil, France. [Leboyer, Marion] Hop Univ Henri Mondor, AP HP, DHU PePSY, Pole Psychiat & Addictol, Creteil, France. [Gillberg, Christopher] UCL, Inst Child Hlth, London, England. RP Leblond, CS (reprint author), Inst Pasteur, Human Genet & Cognit Funct Unit, Paris, France. EM thomasb@pasteur.fr RI Scherer, Stephen /B-3785-2013; sanlaville, damien/M-4716-2014; Monaco, Anthony/A-4495-2010 OI Scherer, Stephen /0000-0002-8326-1999; sanlaville, damien/0000-0001-9939-2849; Monaco, Anthony/0000-0001-7480-3197 FU Institut Pasteur; CNRS; INSERM; AP-HP; University Paris Diderot; Bettencourt-Schueller foundation; Orange foundation; FondaMental foundation; Conny-Maeva foundation; Cognacq-Jay foundation; ANR [ANR-08-MNPS-037-01 - SynGen]; Neuron-ERANET (EUHF-AUTISM); DFG [BO1718/3-1, 4-1]; Baustein [L.SBN.0081] FX This work was funded 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 (ANR-08-MNPS-037-01 - SynGen), Neuron-ERANET (EUHF-AUTISM), the DFG (BO1718/3-1, 4-1) and Baustein L.SBN.0081. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI Evaluating the Effectiveness of the Self-Administered Interview c for Witnesses with Autism Spectrum Disorder SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID IMPAIRED MEMORY FUNCTIONS; HIGH-FUNCTIONING CHILDREN; SPATIAL WORKING-MEMORY; COGNITIVE INTERVIEW; ASPERGERS-SYNDROME; EYEWITNESS MEMORY; FREE-RECALL; ADULTS; PERCEPTION; ADOLESCENTS AB The widely used evidence-based police interviewing technique, the Cognitive Interview, is not effective for witnesses with autism spectrum disorder (ASD). The present study examined whether a modification of the Cognitive Interview that removes the social element, the Self-Administered Interview((c)), is more useful in facilitating recall by ASD witnesses. One of the main components of the Cognitive Interview is context reinstatement, where the witness follows verbal instructions from the interviewer to mentally recreate the personal and physical context that they experienced during the event. The present findings showed that this procedure is not effective for witnesses with ASD in SAI format in which the social component of its administration is removed. However, the SAI sketch plan component did elicit more correct details from the ASD group, although to a lesser degree than for the comparison group. Theoretical and practical implications of the findings are discussed. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Maras, Katie L.] Univ Bath, Bath BA2 7AY, Avon, England. [Mulcahy, Sue] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Memon, Amina; Picariello, Federica] Univ London, Egham, Surrey, England. [Bowler, Dermot M.] City Univ London, London EC1V 0HB, England. RP Maras, KL (reprint author), Univ Bath, Bath BA2 7AY, Avon, England. 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PD SEP-OCT PY 2014 VL 28 IS 5 BP 693 EP 701 DI 10.1002/acp.3055 PG 9 WC Psychology, Experimental SC Psychology GA AQ3ED UT WOS:000342671200009 ER PT J AU Grados, M Sung, HM Kim, S Srivastava, S AF Grados, Marco Sung, Hyung Mo Kim, Sejin Srivastava, Siddharth TI Genetic Findings in Obsessive-Compulsive Disorder Connect to Brain-Derived Neutrophic Factor and Mammalian Target of Rapamycin Pathways: Implications for Drug Development SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE obsessive-compulsive disorder (OCD); brain-derived neutrophic factor (BDNF); mammalian target of rapamycin (mTOR); FKBP12; GRM5 ID LONG-TERM POTENTIATION; NEUROTROPHIC FACTOR BDNF; TUBEROUS SCLEROSIS COMPLEX; AUTISM SPECTRUM DISORDERS; VAL66MET POLYMORPHISM; SYNAPTIC PLASTICITY; FEAR MEMORY; PREFRONTAL CORTEX; SIGNALING PATHWAY; MUTANT MICE AB Traditional pharmacological approaches to the treatment of obsessive-compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1-MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation and neurogenesis pathways BDNF-mTOR. These pathways are emerging as a promising area of research for the development of neuroprotective pharmaceuticals. Emergent genetic epidemiologic data on OCD and repetitive behaviors may support new approaches for pharmacological discovery. Neuroprotective approaches that take into consideration glutamate-mediated BDNF-mTOR pathways are suggested by OCD susceptibility genes. (C) 2014 Wiley Periodicals, Inc. C1 [Grados, Marco] Johns Hopkins Univ, Sch Med, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA. [Sung, Hyung Mo] CHA Univ, Sch Med, Dept Psychiat, Pocheon Shi, Gyeongghi Do, South Korea. [Kim, Sejin] Yeungnam Univ, Coll Med, Gyongsan 712749, Gyeongbuk, South Korea. [Srivastava, Siddharth] Kennedy Krieger Inst, Baltimore, MD 21287 USA. RP Grados, M (reprint author), Johns Hopkins Univ, Sch Med, Div Child & Adolescent Psychiat, 1800 Orleans St 12th Floor, Baltimore, MD 21287 USA. 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PD SEP 1 PY 2014 VL 4 IS 9 BP 1667 EP 1670 DI 10.1534/g3.114.012849 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AQ1VE UT WOS:000342570600011 PM 24996580 ER PT J AU Hill, DR King, SA Mrachko, AA AF Hill, David R. King, Seth A. Mrachko, Alicia A. TI Students With Autism, Service Dogs, and Public Schools: A Review of State Laws SO JOURNAL OF DISABILITY POLICY STUDIES LA English DT Review DE autism; service dogs; schools; statutes ID CHILDREN; THERAPY; BEHAVIOR; DISABILITIES; DISORDERS; BENEFITS; YOUTH AB Children with autism spectrum disorder (ASD) increasingly receive assistance from service dogs. Nonetheless, confusion surrounding service dogs for students with ASD has precipitated litigation between parents and schools. The purpose of this review was to examine state laws pertaining to the use of service dogs among children with ASD. 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PD SEP PY 2014 VL 25 IS 2 BP 106 EP 116 DI 10.1177/1044207313477204 PG 11 WC Rehabilitation SC Rehabilitation GA AQ1VA UT WOS:000342569800004 ER PT J AU Butean, I Costescu, C Dobrean, A AF Butean, Iulia Costescu, Cristina Dobrean, Anca TI DIFFERENCES BETWEEN EMPATHIC RESPONSES IN CHILDREN WITH AUTISM SPECTRUM DISORDER AND TYPICALLY DEVELOPING CHILDREN SO JOURNAL OF EVIDENCE-BASED PSYCHOTHERAPIES LA English DT Article DE empathic responses; autism spectrum disorder; prosocial behaviors ID BEHAVIOR; EMOTION; TEMPERAMENT; DISTRESS; OTHERS; ADULTS AB Previous studies show that empathy deficits are considered an important barrier for the social development of children diagnosed with autism spectrum disorder (ASD). This study compares the empathic responses between a group of children with ASD and a group of typically developing (TD) children. We included 63 children, out of which 26 had a diagnosis of ASD. We used an empathy task which simulated leg pain and an observational grid to assess four dimensions of empathy: affective responding, behavior activation, verbal empathic initiations and prosocial behaviors. The results showed that children with ASD had a lower performance at the affective responding and behavior activation dimensions, as compared with TD children, but there were no differences between the two groups in verbal empathic initiations and prosocial behaviors. C1 [Butean, Iulia; Costescu, Cristina; Dobrean, Anca] Univ Babes Bolyai, Dept Clin Psychol & Psychotherapy, R-3400 Cluj Napoca, Romania. RP Costescu, C (reprint author), Univ Babes Bolyai, Dept Clin Psychol & Psychotherapy, R-3400 Cluj Napoca, Romania. 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De Jong, Neal Morrissey, Joseph P. TI Adequate Health Insurance for Children with Autism: Parent-Reported Outcomes and Implications for Defining Essential Benefits SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Meeting Abstract C1 [Thomas, Kathleen C.; Williams, Christianna S.; De Jong, Neal; Morrissey, Joseph P.] Univ N Carolina, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD SEP PY 2014 VL 17 SU 1 BP S24 EP S24 PG 1 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA AQ3ZF UT WOS:000342731300047 ER PT J AU Yoshimasu, K Kiyohara, C Takemura, S Nakai, K AF Yoshimasu, Kouichi Kiyohara, Chikako Takemura, Shigeki Nakai, Kunihiko TI A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood SO NEUROTOXICOLOGY LA English DT Review DE Mercury exposure; Autism; ADHD; Thimerosal; Meta-analysis ID THIMEROSAL-CONTAINING VACCINES; DEFICIT HYPERACTIVITY DISORDER; HAZARDOUS AIR-POLLUTANTS; NEURODEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; DEVELOPMENTAL DISORDERS; METHYLMERCURY EXPOSURE; CAUSAL ASSOCIATION; CLINICAL-TRIALS; UNITED-KINGDOM AB Although a measurable number of epidemiological studies have been conducted to clarify the associations between mercury exposure during embryo or early infancy and later incidences of autism spectrum disorders (ASD) or attention-deficit hyperactivity disorder (ADHD), the conclusion still remains unclear. Meta-analysis was conducted for two major exposure sources; i.e., thimerosal vaccines that contain ethylmercury (clinical exposure), and environmental sources, using relevant literature published before April 2014. While thimerosal exposures did not show any material associations with an increased risk of ASD or ADHD (the summary odds ratio (OR) 0.99,95% confidence interval (CI) 0.80-1.24 for ASD; OR 0.91, 95% CI 0.70-1.13 for ADHD/ADD), significant associations were observed for environmental exposures in both ASD (OR 1.66,95% CI 1.14-2.17) and ADHD (OR 1.60,95% CI 1.10-2.33). The summary ORs were similar after excluding studies not adjusted for confounders. Moderate adverse effects were observed only between environmental inorganic or organic mercury exposures and ASD/ADHD. However, these results should be interpreted with caution since the number of epidemiological studies on this issue was limited and still at an early stage. Further studies focused on subjects with genetic vulnerabilities of developmental disorders are warranted for better understanding of the effects of such environmental exposures. (C) 2014 Elsevier Inc. All rights reserved. C1 [Yoshimasu, Kouichi; Takemura, Shigeki] Wakayama Med Univ, Sch Med, Dept Hyg, Wakayama 6410012, Japan. [Kiyohara, Chikako] Kyushu Univ, Grad Sch Med Sci, Dept Prevent Med, Fukuoka, Japan. [Nakai, Kunihiko] Tohoku Univ, Grad Sch Med, Dept Dev & Environm Med, Sendai, Miyagi 980, Japan. RP Yoshimasu, K (reprint author), Wakayama Med Univ, Sch Med, Dept Hyg, 811-1 Kimiidera, Wakayama 6410012, Japan. EM kyoshi@wakayama-med.ac.jp FU Environment Research and Technology Development Fund of the Ministry of the Environment, Japan [5-1451] FX This research was supported by the Environment Research and Technology Development Fund (5-1451) of the Ministry of the Environment, Japan. 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Yoshida, T. Naoe, J. TI THREE CASES OF ALCOHOLISM WITH AUTISM SPECTRUM DISORDER SO ALCOHOL AND ALCOHOLISM LA English DT Meeting Abstract C1 [Tabata, K.; Yoshida, T.; Naoe, J.] Asahikawa Keisenkai Hosp, Med Off, Asahikawa, Hokkaido, Japan. NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD SEP PY 2014 VL 49 SU 1 MA P-4 PG 1 WC Substance Abuse SC Substance Abuse GA AP8TO UT WOS:000342352100005 ER PT J AU Kosho, T Miyake, N Carey, JC AF Kosho, Tomoki Miyake, Noriko Carey, John C. TI Coffin-Siris Syndrome and Related Disorders Involving Components of the BAF (mSWI/SNF) Complex: Historical Review and Recent Advances Using Next Generation Sequencing SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Editorial Material ID CHROMATIN-REMODELING COMPLEX; FORSSMAN-LEHMANN-SYNDROME; DE-NOVO MUTATIONS; NICOLAIDES-BARAITSER SYNDROME; SWI/SNF COMPLEX; INTELLECTUAL DISABILITY; MENTAL-RETARDATION; FAMILIAL SCHWANNOMATOSIS; DYSMORPHIC FEATURES; DISTINCT PHENOTYPE AB This issue of Seminars in Medical Genetics, American Journal of Medical Genetics Part C investigates the human diseases caused by mutations in the BAF complex (also known as the mammalian SWI/SNF complex) genes, particularly focusing on Coffin-Siris syndrome (CSS). CSS is a rare congenital malformation syndrome characterized by developmental delay or intellectual disability (ID), coarse facial appearance, feeding difficulties, frequent infections, and hypoplasia/aplasia of the fifth fingernails and fifth distal phalanges. In 2012, 42 years after the first description of CSS in 1970, five causative genes (SMARCB1, SMARCE1, SMARCA4, ARID1A, ARID1B), all encoding components of the BAF complex, were identified as being responsible for CSS through whole exome sequencing and pathway-based genetic screening. The identification of two additional causative genes (PHF6, SOX11) followed. Mutations in another BAF complex gene (SMARCA2) and (TBC1D24) were found to cause clinically similar conditions with ID, Nicolaides-Baraitser syndrome and DOORS syndrome, respectively. Also, ADNP was found to be mutated in an autism/ID syndrome. Furthermore, there is growing evidences for germline or somatic mutations in the BAF complex genes to be causal for cancer/cancer predisposition syndromes. These discoveries have highlighted the role of the BAF complex in the human development and cancer formation. The biology of BAF is very complicated and much remains unknown. Ongoing research is required to reveal the whole picture of the BAF complex in human development, and will lead to the development of new targeted therapies for related disorders in the future. (c) 2014 Wiley Periodicals, Inc. C1 [Kosho, Tomoki] Shinshu Univ, Sch Med, Shinshu Univ Hosp, Div Clin & Mol Genet, Matsumoto, Nagano 3908621, Japan. [Kosho, Tomoki] Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 3908621, Japan. [Miyake, Noriko] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan. [Carey, John C.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84112 USA. RP Kosho, T (reprint author), Shinshu Univ, Sch Med, Dept Med Genet, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. 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J. Med. Genet. C PD SEP PY 2014 VL 166 IS 3 SI SI BP 241 EP 251 DI 10.1002/ajmg.c.31415 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AP8QG UT WOS:000342343200001 PM 25169878 ER PT J AU Vandeweyer, G Helsmoortel, C Van Dijck, A Vulto-van Silfhout, AT Coe, BP Bernier, R Gerdts, J Rooms, L van den Ende, J Bakshi, M Wilson, M Nordgren, A Hendon, LG Abdulrahman, OA Romano, C De Vries, BBA Kleefstra, T Eichler, EE Van der Aa, N Kooy, RF AF Vandeweyer, Geert Helsmoortel, Celine Van Dijck, Anke Vulto-van Silfhout, Anneke T. Coe, Bradley P. Bernier, Raphael Gerdts, Jennifer Rooms, Liesbeth van den Ende, Jenneke Bakshi, Madhura Wilson, Meredith Nordgren, Ann Hendon, Laura G. Abdulrahman, Omar A. Romano, Corrado de Vries, Bert B. A. Kleefstra, Tjitske Eichler, Evan E. Van der Aa, Nathalie Kooy, R. Frank TI The Transcriptional Regulator ADNP Links the BAF (SWI/SNF) Complexes With Autism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE autism; SWI; SNF; BAF complexes; ADNP ID DEPENDENT NEUROPROTECTIVE PROTEIN; DE-NOVO MUTATIONS; CHROMATIN REMODELING COMPLEX; COFFIN-SIRIS SYNDROME; SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; NEURAL DEVELOPMENT; PEPTIDE; NAP; GENETICS AB Mutations in ADNP were recently identified as a frequent cause of syndromic autism, characterized by deficits in social communication and interaction and restricted, repetitive behavioral patterns. Based on its functional domains, ADNP is a presumed transcription factor. The gene interacts closely with the SWI/SNF complex by direct and experimentally verified binding of its C-terminus to three of its core components. A detailed and systematic clinical assessment of the symptoms observed in our patients allows a detailed comparison with the symptoms observed in other SWI/SNF disorders. While the mutational mechanism of the first 10 patients identified suggested a gain of function mechanism, an 11th patient reported here is predicted haploinsufficient. The latter observation may raise hope for therapy, as addition of NAP, a neuroprotective octapeptide named after the first three amino acids of the sequence NAPVSPIQ, has been reported by others to ameliorate some of the cognitive abnormalities observed in a knockout mouse model. It is concluded that detailed clinical and molecular studies on larger cohorts of patients are necessary to establish a better insight in the genotype phenotype correlation and in the mutational mechanism. (c) 2014 Wiley Periodicals, Inc. C1 [Vandeweyer, Geert; Helsmoortel, Celine; Van Dijck, Anke; van den Ende, Jenneke; Van der Aa, Nathalie; Kooy, R. Frank] Univ Antwerp, Dept Med Genet, B-2650 Edegem, Belgium. [Van Dijck, Anke; van den Ende, Jenneke; Van der Aa, Nathalie] Univ Antwerp Hosp, B-2650 Edegem, Belgium. [Vulto-van Silfhout, Anneke T.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Coe, Bradley P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Bernier, Raphael; Gerdts, Jennifer] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Rooms, Liesbeth] Univ Antwerp Hosp, Dept Med Genet, B-2650 Edegem, Belgium. [Nordgren, Ann] Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, S-10401 Stockholm, Sweden. [Hendon, Laura G.; Abdulrahman, Omar A.] Univ Mississippi, Med Ctr Jackson, University, MS 38677 USA. [Romano, Corrado] IRCCS Assoc Oasi Maria Santissima, Troina, Italy. [de Vries, Bert B. A.; Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav Dept, NL-6525 ED Nijmegen, Netherlands. [de Vries, Bert B. A.; Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands. [Eichler, Evan E.] Univ Washington, Seattle, WA 98195 USA. RP Van der Aa, N (reprint author), Univ Antwerp, Dept Med Genet, Prins Boudewijnlaan 43, B-2650 Edegem, Belgium. EM Nathalie.VanderAa@uza.be; Frank.Kooy@uantwerpen.be RI Romano, Corrado/B-9695-2008 OI Romano, Corrado/0000-0003-1049-0683 FU Dutch Organization for Health Research and Development [917-86-319, 40-00812-98-12109, 907-00-365]; EU [EU-7th-2010-241995]; Simons Foundation Autism Research Initiative award [SFARI191889EE]; NIH [MH101221] FX Grant sponsor: Dutch Organization for Health Research and Development; Grant number: 917-86-319, 40-00812-98-12109, 907-00-365; Grant sponsor: EU; Grant number: EU-7th-2010-241995; Grant sponsor: Simons Foundation Autism Research Initiative award; Grant number: SFARI191889EE; Grant sponsor: NIH; Grant number: MH101221. 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J. Med. Genet. C PD SEP PY 2014 VL 166 IS 3 SI SI BP 315 EP 326 DI 10.1002/ajmg.c.31413 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AP8QG UT WOS:000342343200008 PM 25169753 ER PT J AU Son, EY Crabtree, GR AF Son, Esther Y. Crabtree, Gerald R. TI The Role of BAF (mSWI/SNF) Complexes in Mammalian Neural Development SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE BAF; mammalian SWI; SNF; chromatin remodeling; neural development; microRNA; intellectual disability; Coffin-Siris syndrome; Nicolaides-Baraitser syndrome; autism; schizophrenia ID CHROMATIN-REMODELING COMPLEX; EMBRYONIC STEM-CELLS; PUTATIVE PHEROMONE RECEPTORS; COFFIN-SIRIS SYNDROME; DE-NOVO MUTATIONS; NICOLAIDES-BARAITSER SYNDROME; DOUBLE-POSITIVE THYMOCYTES; TARGET GENE ACTIVATION; CAUSE WEAVER SYNDROME; SWI/SNF COMPLEXES AB The BAF (mammalian SWI/SNF) complexes are a family of multi-subunit ATP-dependent chromatin remodelers that use ATP hydrolysis to alter chromatin structure. Distinct BAF complex compositions are possible through combinatorial assembly of homologous subunit families and can serve non-redundant functions. In mammalian neural development, developmental stage-specific BAF assemblies are found in embryonic stem cells, neural progenitors and postmitotic neurons. In particular, the neural progenitor-specific BAF complexes are essential for controlling the kinetics and mode of neural progenitor cell division, while neuronal BAF function is necessary for the maturation of postmitotic neuronal phenotypes as well as long-term memory formation. The microRNA-mediated mechanism for transitioning from npBAF to nBAF complexes is instructive for the neuronal fate and can even convert fibroblasts into neurons. The high frequency of BAF subunit mutations in neurological disorders underscores the rate-determining role of BAF complexes in neural development, homeostasis, and plasticity. (c) 2014 Wiley Periodicals, Inc. C1 [Son, Esther Y.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Crabtree, Gerald R.] Stanford Univ, Stanford, CA 94305 USA. 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J. Med. Genet. C PD SEP PY 2014 VL 166 IS 3 SI SI BP 333 EP 349 DI 10.1002/ajmg.c.31416 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AP8QG UT WOS:000342343200010 PM 25195934 ER PT J AU Allen, JL Liu, XF Pelkowski, S Palmer, B Conrad, K Oberdorster, G Weston, D Mayer-Proschel, M Cory-Slechta, DA AF Allen, Joshua L. Liu, Xiufang Pelkowski, Sean Palmer, Brian Conrad, Katherine Oberdoerster, Guenter Weston, Douglas Mayer-Proschel, Margot Cory-Slechta, Deborah A. TI Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID DEVELOPMENTAL EXPOSURE; SPECTRUM DISORDER; ISCHEMIC-STROKE; LOS-ANGELES; IN-UTERO; SCHIZOPHRENIA; BRAIN; AUTISM; ENLARGEMENT; STRESS AB BACKGROUND: Air pollution has been associated with adverse neuro-logical and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neuro-developmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. OBJECTIVES: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. METHODS: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. RESULTS: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. CONCLUSIONS: We observed brain region-and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuro-pathology that has been associated with poor neuro-developmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neuro-logical/neuro-developmental outcomes in humans. C1 [Allen, Joshua L.; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdoerster, Guenter; Weston, Douglas; Cory-Slechta, Deborah A.] Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY USA. [Mayer-Proschel, Margot] Univ Rochester, Sch Med, Dept Biochem Genet, Rochester, NY USA. RP Cory-Slechta, DA (reprint author), 601 Elmwood Ave,Box EHSC Room 2-6810, Rochester, NY 14642 USA. EM deborah_cory-slechta@urmc.rochester.edu FU National Institute of Environmental Health Sciences [ES019105, ES019852, ES001247, T32 ES007026] FX This work was supported by National Institute of Environmental Health Sciences grants ES019105 and ES019852 (D.A.C.-S.), ES001247 (G.O., M.M-P., and D.A.C.-S.), and T32 ES007026 (J.L.A. and B.P.). 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Health Perspect. PD SEP PY 2014 VL 122 IS 9 BP 939 EP 945 DI 10.1289/ehp.1307984 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AO9XT UT WOS:000341714600022 PM 24901756 ER PT J AU Potera, C AF Potera, Carol TI Echoes of Autism? Inhaled Ultrafine Particles and Brain Changes in Mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT News Item ID AIR-POLLUTION; DEVELOPMENTAL EXPOSURE; PARTICULATE MATTER; SCHIZOPHRENIA CR Allen JL, 2014, ENVIRON HEALTH PERSP, V122, P939, DOI 10.1289/ehp.1307984 Allen JL, 2014, TOXICOL SCI, V140, P160, DOI 10.1093/toxsci/kfu059 Allen JL, 2013, ENVIRON HEALTH PERSP, V121, P32, DOI [10.1289/ehp.1205505, 10.1289/ehp.121-a32] Baio J., 2014, MMWR SURVEILL SUM S2, V63, P1 Becerra TA, 2013, ENVIRON HEALTH PERSP, V121, P380, DOI 10.1289/ehp.1205827 Movsas TZ, 2013, J PEDIATR-US, V163, P73, DOI 10.1016/j.jpeds.2012.12.084 Pedersen CB, 2004, SCHIZOPHR RES, V66, P83, DOI 10.1016/S0920-9964(03)00062-8 Volk HE, 2013, JAMA PSYCHIAT, V70, P71, DOI 10.1001/jamapsychiatry.2013.266 Volk HE, 2011, ENVIRON HEALTH PERSP, V119, P873, DOI 10.1289/ehp.1002835 Wright IC, 2000, AM J PSYCHIAT, V157, P16 NR 10 TC 0 Z9 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2014 VL 122 IS 9 BP A250 EP A250 DI 10.1289/ehp.122-A250 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AO9XT UT WOS:000341714600010 PM 25181731 ER PT J AU Geier, DA Hooker, BS Kern, JK King, PG Sykes, LK Geier, MR AF Geier, David A. Hooker, Brian S. Kern, Janet K. King, Paul G. Sykes, Lisa K. Geier, Mark R. TI A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE attention deficit; autism; ethylmercury; merthiolate; thiomersal ID HEPATITIS-B VACCINATION; EVENT REPORTING SYSTEM; SAFETY DATALINK; INFANTS; AUTISM; METHYLMERCURY; ETHYLMERCURY; ASSOCIATION; THIOMERSAL; DATABASES AB A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991-2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis. C1 [Geier, David A.; Kern, Janet K.; Geier, Mark R.] Inst Chron Illnesses Inc, Silver Spring, MD 20905 USA. [Hooker, Brian S.] Simpson Univ, Dept Biol, Redding, CA 96003 USA. [Kern, Janet K.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [King, Paul G.; Sykes, Lisa K.] CoMeD Inc, Silver Spring, MD 20905 USA. RP Geier, MR (reprint author), Inst Chron Illnesses Inc, 14 Redgate Ct, Silver Spring, MD 20905 USA. EM davidallengeier@comcast.net; bhooker@simpsonu.edu; jkern@dfwair.net; paulgkingphd@gmail.com; syklone5@verizon.net; mgeier@comcast.net FU Institute of Chronic Illnesses, Inc.; CoMeD, Inc.; Seltz Foundation; Dwoskin Family Foundation FX This study was supported by the non-profit Institute of Chronic Illnesses, Inc., and the non-profit CoMeD, Inc. This study was also supported the Seltz Foundation and the Dwoskin Family Foundation, but they were not involved in the design and conducting of the study, in the collection analysis, in the interpretation of the data, in the preparation, in the review nor in the approval of the manuscript. 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J. Environ. Res. Public Health PD SEP PY 2014 VL 11 IS 9 BP 9156 EP 9170 DI 10.3390/ijerph110909156 PG 15 WC Environmental Sciences SC Environmental Sciences & Ecology GA AP4DN UT WOS:000342027500033 PM 25198681 ER PT J AU Rauf, NK Anis-ul-Haq Aslam, N Anjum, U AF Rauf, Nelofar Kiran Anis-ul-Haq Aslam, Naeem Anjum, Uzma TI Characteristic Symptoms and Adaptive Behaviors of Children with Autism SO JCPSP-JOURNAL OF THE COLLEGE OF PHYSICIANS AND SURGEONS PAKISTAN LA English DT Article DE Autism; Adaptive behaviors; Characteristic symptoms; Autism spectrum disorder; Special education ID HIGHER FUNCTIONING INDIVIDUALS; SPECTRUM DISORDERS; ALTERNATIVE COMMUNICATION; PARENTING STRESS; DISABILITIES; ABILITIES; TODDLERS; LANGUAGE AB Objective: To determine the characteristic symptoms and adaptive behaviors of children with autism, as well as the distribution of autism severity groups across gender. Study Design: Cross-sectional observational study. Place and Duration of Study: Special Education Schools of Rawalpindi and Islamabad, from September 2011 to January 2012. Methodology: Thirty nine children of either gender, aged 3 - 16 years and enrolled in special education schools, fulfilled the DSM-IV-TR criteria of autism. Among those, were identified as meeting the criteria of autism. The childhood autism rating scale-2 (CARS-2) was used to study the characteristics and severity of symptoms of autism. Later, adaptive behavior scale (school edition: 2) ABS-S: 2, was administered on children (n=21) to formulate the level of adaptive functioning. Results: There were 15 boys and 8 girls with mean age of 10.6 +/- 2.97 years. They showed marked impairment in verbal communication (mean=3.17 +/- 0.90) followed by relating to people (mean=2.75 +/- 0.83) and general impression (mean=2.73 +/- 0.7). Most of the children showed average to below average adaptive behaviors on number and time (n=19, 90.5%), independent functioning (n=17, 81.0%), self direction (n=17, 81.0%), physical development (n=13, 61.9%), responsibility (n=12, 57.1%) and socialization (n=13, 61.9%) as well as poor to very poor adaptive behaviors on pre-vocational skill (n=15, 71.4%), language development (n=13, 61.9%) and economic development (n=13, 61.9%). The frequency of boys with autism was more towards moderate to severely impaired spectrum, without gender differences in any symptom associated with autism. Conclusion: Comprehension of the presentation of characteristic symptoms of children with autism will be helpful in devising the indigenous intervention plans that are congruent with the level of adaptive functioning. C1 [Rauf, Nelofar Kiran; Anis-ul-Haq; Aslam, Naeem] Quaid I Azam Univ, Ctr Excellence, Natl Inst Psychol, Islamabad, Pakistan. [Anjum, Uzma] Natl Univ Modern Languages, Fac Adv Integrated Studies & Res, Islamabad, Pakistan. RP Rauf, NK (reprint author), House 172,St 3b, Judicial Colony, Rawalpindi, Pakistan. 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Coll. Physicians Surg. PD SEP PY 2014 VL 24 IS 9 BP 658 EP 662 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AP8NY UT WOS:000342336900012 PM 25233971 ER PT J AU Damiano, CR Mazefsky, CA White, SW Dichter, GS AF Damiano, Cara R. Mazefsky, Carla A. White, Susan W. Dichter, Gabriel S. TI Future Directions for Research in Autism Spectrum Disorders SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; DRUG DEVELOPMENT; YOUNG-CHILDREN; MOUSE MODELS; PSYCHOSOCIAL INTERVENTIONS; TROPHOBLAST INCLUSIONS; BEHAVIORAL-GENETICS; TRAINING-PROGRAM AB This article suggests future directions for research aimed at improving our understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (a) preclinical models, (b) experimental therapeutics, (c) early identification and intervention, (d) psychiatric comorbidities and the Research Domain Criteria initiative, (e) ecological momentary assessment, (f) neurotechnologies, and (g) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families. C1 [Damiano, Cara R.; Dichter, Gabriel S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Damiano, Cara R.; Dichter, Gabriel S.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Mazefsky, Carla A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [White, Susan W.] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. [Dichter, Gabriel S.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. RP Dichter, GS (reprint author), Univ N Carolina, CB 7255, Chapel Hill, NC 27599 USA. 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Bekhet, Abir Robinson, Karen Rodriguez, Dana TI Attributed Meanings and Strategies to Prevent Challenging Behaviors of Hospitalized Children With Autism: Two Perspectives SO JOURNAL OF PEDIATRIC HEALTH CARE LA English DT Article DE Autism; challenging behaviors; focus groups AB Introduction: Understanding is limited of the meaning attributed to behaviors of children with autism spectrum disorder and strategies used to prevent challenging behaviors in the context of hospitalization. Methods: This qualitative study consisted of two focus groups (n = 10; five mothers and five health care providers [HCPs]). Transcripts were analyzed using the qualitative method of narrative inquiry. Results: The meaning attributed to behaviors by the mothers and the HCPs differed. The mothers attributed behaviors to the child's communication of frustration, hyperactivity, and self-calming. The HCPs attributed challenging behaviors to self-stimulation and child aggression. Strategies to prevent behaviors also differed. Mothers focused on preparation prior to hospitalization and attempts to partner with HCPs. HCPs identified fewer strategies and consulted mothers for strategies to manage challenging behaviors. Discussion: HCP and parent collaboration could lead to strategies to increase supports for children with autism spectrum disorder in the hospital to decrease their frustration and challenging behaviors. C1 [Johnson, Norah L.; Bekhet, Abir; Robinson, Karen; Rodriguez, Dana] Marquette Univ, Coll Nursing, Milwaukee, WI 53201 USA. RP Johnson, NL (reprint author), Marquette Univ, Coll Nursing, Clark Hall 325,POB 1881, Milwaukee, WI 53201 USA. EM norah.johnson@marquette.edu CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bultas MW, 2012, J PEDIATR NURS, V27, P460, DOI 10.1016/j.pedn.2011.05.005 Carbone PS, 2010, J AUTISM DEV DISORD, V40, P317, DOI 10.1007/s10803-009-0874-5 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Gray C., 2010, NEW SOCIAL STORY BOO Holloway I., 2007, NARRATIVE RES NURSIN Kohler-Riessman C., 2008, NARRATIVE METHODS HU Levy SE, 2010, J DEV BEHAV PEDIATR, V31, P267, DOI 10.1097/DBP.0b013e3181d5d03b Lowe K, 2007, J INTELL DISABIL RES, V51, P625, DOI 10.1111/j.1365-2788.2006.00948.x Lubisch N, 2009, PEDIATR NEUROL, V41, P88, DOI 10.1016/j.pediatrneurol.2009.02.006 Scarpinato N, 2010, J SPEC PEDIATR NURS, V15, P244, DOI 10.1111/j.1744-6155.2010.00244.x Searcy E, 2001, JAAPA, V14, P39 Souders Margaret C, 2002, Pediatr Nurs, V28, P555 NR 13 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5245 EI 1532-656X J9 J PEDIATR HEALTH CAR JI J. Pediatr. Health Care PD SEP-OCT PY 2014 VL 28 IS 5 BP 386 EP 393 DI 10.1016/j.pedhc.2013.10.001 PG 8 WC Health Policy & Services; Nursing; Pediatrics SC Health Care Sciences & Services; Nursing; Pediatrics GA AP8SQ UT WOS:000342349600005 PM 24239062 ER PT J AU Thompson, DG Tielsch-Goddard, A AF Thompson, Debbie Gearner Tielsch-Goddard, Anna TI Improving Management of Patients With Autism Spectrum Disorder Having Scheduled Surgery: Optimizing Practice SO JOURNAL OF PEDIATRIC HEALTH CARE LA English DT Article DE Autism; autistic spectrum disorders; presurgical assessment; quality improvement; pediatric; perioperative process ID CHILDREN; INTERVENTION; DIAGNOSIS; CARE AB Introduction: Surgical preparation for children with autism spectrum disorders can be a challenge to perioperative staff because of the unique individual needs and behaviors in this population. Most children with autism function best in predictable, routine environments, and being in the hospital and other health care settings can create a stressful situation. This prospective, descriptive, quality improvement project was conducted to optimize best practices for perioperative staff and better individualize the plan of care for the autistic child and his or her family. Methods: Forty-three patients with a diagnosis of autism or autistic spectrum disorder were seen over 6 months at a suburban pediatric hospital affiliated with a major urban pediatric hospital and had an upcoming scheduled surgery or procedure requiring anesthesia. Caregivers were interviewed before and after surgery to collect information to better help their child cope with their hospital visit. Results: In an evaluation of project outcomes, data were tabulated and summarized and interview data were qualitatively coded for emerging themes to improve the perioperative process for the child. Discussion: Findings showed that staff members were able to recognize potential and actual stressors and help identify individual needs of surgical patients with autism. The families were pleased and appreciative of the individual attention and focus on their child's special needs. Investigators also found increased staff interest in optimizing the surgical experience for autistic children. C1 [Thompson, Debbie Gearner; Tielsch-Goddard, Anna] Childrens Med Ctr Legacy, Perioperat Serv, Plano, TX 75024 USA. RP Thompson, DG (reprint author), Childrens Med Ctr Legacy, Perioperat Serv, 7601 Preston Rd, Plano, TX 75024 USA. 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TI Narcissistic disorder and the failure of symbolisation: A Relational Affective Hypothesis SO MEDICAL HYPOTHESES LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; EMOTIONAL AWARENESS; ALEXITHYMIA; AUTISM; ASYMMETRY; CORTEX; SLEEP; LIMBS; FEEL; SELF AB The psychoanalytic concept of narcissistic disorder is broader than that of Narcissistic Personality Disorder (DSM-5 [1]), underlying a range of Personality Disorders (PD) and their co-morbidities. Existing Mentalisation, Psychoanalytic and Cognitive models, fail to account fully for the emerging evidence of biological, developmental, relational and defensive contributions to narcissistic disorder, nor do they account for the common and variant features of co-morbidities namely Anorexia Nervosa, Somatisation, Substance Misuse and Autistic Spectrum Disorder. Alexithymia and concrete modes of relating are common findings in narcissistic disorder and these co-morbid conditions. Current models do not provide a comprehensive account, on the basis of neuro-scientific and developmental evidence, of how affective feelings come to be represented in words and the association between narcissistic disorders and failures of symbolisation. In this paper I propose an empirically based Relational Affective Hypothesis that narcissistic disorder and its comorbidities represent failures at specific points on a representational function pathway through which subcortical affect and visceral feeling in a relational context become the basis for abstraction and language. The elucidation of this pathway allows investigation of the contribution of biological, social and psychogenic factors in narcissistic disorders. It also brings a new understanding of the neurological underpinning of psychodynamic defences in narcissistic disorders. Research and novel treatment implications are briefly considered. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Mizen, C. S.] Univ Exeter, Sch Psychol, Exeter EX2 5AF, Devon, England. [Mizen, C. S.] Devon Partnership NHS Trust, Wonford House Hosp, Exeter EX2 5AF, Devon, England. RP Mizen, CS (reprint author), Univ Exeter, Sch Psychol, Dryden Rd, Exeter EX2 5AF, Devon, England. 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Hypotheses PD SEP PY 2014 VL 83 IS 3 BP 254 EP 262 DI 10.1016/j.mehy.2014.05.012 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AP7PA UT WOS:000342268000003 PM 24986704 ER PT J AU Kuhn, M Bransfield, R AF Kuhn, Mason Bransfield, Robert TI Divergent opinions of proper Lyme disease diagnosis and implications for children co-morbid with autism spectrum disorder SO MEDICAL HYPOTHESES LA English DT Article ID BORRELIA-BURGDORFERI; SERODIAGNOSIS; ANTIBODIES; IMMUNOBLOT; CRITERIA; PCR AB This paper proposes that some children with an autism spectrum disorder (ASD) in the United States have undiagnosed Lyme disease and different testing criteria used by commercial laboratories may be producing false negative results. Two testing protocols will be evaluated; first, the Centers for Disease Control (CDC) and Infectious Disease Society of America (IDSA) approved two-tiered Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA) followed by an IgM and/or IgG Western Blot test. Second, a clinical diagnosis (flu like symptoms, joint pain, fatigue, neurological symptoms, etc.) possibly followed by a Western Blot with a broader criteria for positive bands [1]. The hypothesis proposes that the former criteria may be producing false negative results for some individuals diagnosed with an ASD. Through an online survey parents of 48 children who have a diagnosis of an ASD and have been diagnosed with Lyme disease were asked to fill out the Autism Treatment Evaluation Checklist (ATEC) before they started antibiotic therapy and after treatment. Of the 48 parents surveyed 45 of them (94%) indicated their child initially tested negative using the two-tiered CDC/IDSA approved test. The parents sought a second physician who diagnosed their child with Lyme disease using the wider range of Western Blot bands. The children were treated with antibiotics and their scores on the ATEC improved. Anecdotal data indicated that some of the children achieved previously unattained developmental milestones after antibiotic therapy began. Protein bands OSP-A and/or OSP-B (Western Blot band 31) and (Western Blot band 34) were found in 44 of 48 patients. These two bands are so specific to Borrelia burgdorferi that they were targeted for use in vaccine trials, yet are not included in the IDSA interpretation of the Western Blot. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kuhn, Mason] Univ No Iowa, Dept Curriculum & Instruct, Cedar Falls, IA 50614 USA. [Bransfield, Robert] Robert Wood Johnson Univ Med & Dent, Sch Med, Camden, NJ 08103 USA. RP Kuhn, M (reprint author), Univ No Iowa, Dept Curriculum & Instruct, 1227 W 27th St, Cedar Falls, IA 50614 USA. 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Hypotheses PD SEP PY 2014 VL 83 IS 3 BP 321 EP 325 DI 10.1016/j.mehy.2014.06.005 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AP7PA UT WOS:000342268000018 PM 24986703 ER PT J AU Oberman, LM Pascual-Leone, A AF Oberman, Lindsay M. Pascual-Leone, Alvaro TI Hyperplasticity in Autism Spectrum Disorder confers protection from Alzheimer's disease SO MEDICAL HYPOTHESES LA English DT Article ID CORTICAL PLASTICITY; STIMULATION; MODEL; GENETICS; CORTEX AB Autism Spectrum Disorders (ASD) currently affects approximately 1% of the population causing grave disability and necessitating a better understanding of the currently enigmatic etiology of these disorders. Recent data suggest that some patients with ASD may have a dysfunction in brain plasticity (specifically data from animal models and human studies suggest a propensity toward excessive amount of plasticity). Plasticity is essential to the establishment and maintenance of brain circuitry; however, too much plasticity may lead to instability of structural connections and compromise of functional systems necessary for cognition and behavior. Multiple lines of evidence suggest that plasticity declines throughout the age-span and may underlie age-related cognitive decline. We hypothesize that individuals whose cortex begins as relatively "hyperplastic" (such as may be seen in ASD) should then be relatively protected from age-related cognitive decline (which we suggest is related to a reduction in plasticity). In the current study, we conducted a multiple linear regression using age and diagnosis as predictor variables in order to evaluate strength of the relationship between age, diagnosis or an interaction of the two factors and the degree of modulation in cortical excitability by transcranial magnetic stimulation as an index of cortical plasticity. Results indicate that across the age-span individuals with ASD show a consistently increased modulation of cortical excitability as compared to typically developing individuals, such that the general slope of decline across the age span is matched across both groups. We have argued that an individual's risk of age-related cognitive decline (and risk for manifesting symptoms of dementia) depends on the individual's starting point and slopes of change in plasticity efficiency over the lifespan. Therefore, our results suggest that individuals with ASD might be relatively protected from age-related cognitive decline and the risk of dementia. (C) 2014 Published by Elsevier Ltd. C1 Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Brain Stimulat & Cognit Training, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pascual-Leone, A (reprint author), Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, 330 Brookline Ave,KS 158, Boston, MA 02215 USA. EM apleone@bidmc.harvard.edu FU National Institutes of Health; National Institute of Mental Health [1R01MH100186]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NCRR); Harvard Catalyst I The Harvard Clinical and Translational Science Center (NCATS NIH) [8KL2TR000168-05]; Harvard Clinical and Translational Science Center [8UL1TR000170-05]; Epilepsy Research Foundation; Simons Foundation; Nancy Lurie Marks Family Foundation; National Institutes of Health [R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758]; Michael J. Fox Foundation; Sidney R. Baer Foundation FX Work on the project is supported by grants from the National Institutes of Health and National Institute of Mental Health (1R01MH100186), and Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH 8KL2TR000168-05) Dr. Oberman is further supported by grants from the Harvard Clinical and Translational Science Center (8UL1TR000170-05), the Epilepsy Research Foundation, the Simons Foundation and the Nancy Lurie Marks Family Foundation. Dr. Pascual-Leone is further supported by grants from the National Institutes of Health (R01HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758), Michael J. Fox Foundation and Sidney R. Baer Foundation. 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Hypotheses PD SEP PY 2014 VL 83 IS 3 BP 337 EP 342 DI 10.1016/j.mehy.2014.06.008 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AP7PA UT WOS:000342268000021 PM 25047996 ER PT J AU Stackpole, EE Akins, MR Fallon, JR AF Stackpole, Emily E. Akins, Michael R. Fallon, Justin R. TI N-myristoylation regulates the axonal distribution of the Fragile X-related protein FXR2P SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE RNA binding proteins; Myristoylation; Fragile X syndrome; FXR2P ID MENTAL-RETARDATION PROTEIN; LIVING HIPPOCAMPAL-NEURONS; KINASE-C SUBSTRATE; MESSENGER-RNA; MOUSE MODEL; FMRP; GRANULES; BINDING; AUTISM; LOCALIZATION AB Fragile X syndrome, the leading cause of inherited intellectual disability and autism, is caused by loss of function of Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that regulates local protein synthesis in the somatodendritic compartment. However, emerging evidence also indicates important roles for FMRP in axonal and presynaptic functions. In particular, FMRP and its homologue FXR2P localize axonally and presynaptically to discrete endogenous structures in the brain termed Fragile X granules (FXGs). FXR2P is a component of all FXGs and is necessary for the axonal and presynaptic localization of FMRP to these structures. We therefore sought to identify and characterize structural features of FXR2P that regulate its axonal localization. Sequence analysis reveals that FXR2P harbors a consensus N-terminal myristoylation sequence (MGXXXS) that is absent in FMRP. Using click chemistry with wild type and an unmyristoylatable G2A mutant we demonstrate that FXR2P is N-myristoylated on glycine 2, establishing it as a lipid-modified RNA binding protein. To-investigate the role of FXR2P N-myristoylation in neurons we generated fluorescently tagged wild type and unmyristoylatable FXR2P (WT and G2A, respectively) and expressed them in primary cortical cultures. Both FXR2P(WT) and FXR2P(G2A) are expressed at equivalent overall levels and are capable of forming FMRP-containing axonal granules. However, FXR2P(WT) granules are largely restricted to proximal axonal segments while granules formed with unmyristoylatable FXR2PG2A are localized throughout the axonal arbor, including in growth cones. These studies indicate that N-terminal myristoylation of the RNA binding protein FXR2P regulates its localization within the axonal arbor. Moreover, since FMRP localization within axonal domains requires its association with FXR2P, these findings suggest that FXR2P lipid modification is a control point for the axonal and presynaptic distribution of FMRP. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stackpole, Emily E.; Akins, Michael R.; Fallon, Justin R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Akins, Michael R.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA. RP Fallon, JR (reprint author), Brown Univ, Dept Neurosci, Box G-LN, Providence, RI 02912 USA. EM Justin_Fallon@brown.edu FU [HD052083]; [MH090237] FX We thank B. McKechnie and C. Schmiedel for technical assistance and E. Morrow for the use of the Neurolucida programs. We also thank T. Hughes for the generous gift of the pBNJ24.6 vector. Grant support: HD052083 to JRF and MH090237 to MRA. 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Med PD SEP PY 2014 VL 20 IS 9 BP 509 EP 518 DI 10.1016/j.molmed.2014.05.002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AP7PP UT WOS:000342269500007 PM 24956966 ER PT J AU Schoen, SA Miller, LJ Sullivan, JC AF Schoen, Sarah A. Miller, Lucy J. Sullivan, Jillian C. TI Measurement in Sensory Modulation: The Sensory Processing Scale Assessment SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE reproducibility of results; sensation disorders; sensory thresholds; somatosensory disorders ID YOUNG-CHILDREN; DEVELOPMENTAL DELAYS; TYPICAL DEVELOPMENT; PRESCHOOL-CHILDREN; OVER-RESPONSIVITY; DAILY-LIFE; AUTISM; DISORDERS; ADHD; DIAGNOSIS AB OBJECTIVE. Sensory modulation issues have a significant impact on participation in daily life. Moreover, understanding phenotypic variation in sensory modulation dysfunction is crucial for research related to defining homogeneous groups and for clinical work in guiding treatment planning. We thus evaluated the new Sensory Processing Scale (SPS) Assessment. METHOD. Research included item development, behavioral scoring system development, test administration, and item analyses to evaluate reliability and validity across sensory domains. RESULTS. Items with adequate reliability (internal reliability >.4) and discriminant validity (p < .01) were retained. Feedback from the expert panel also contributed to decisions about retaining items in the scale. CONCLUSION. The SPS Assessment appears to be a reliable and valid measure of sensory modulation (scale reliability >.90; discrimination between group effect sizes >1.00). This scale has the potential to aid in differential diagnosis of sensory modulation issues. 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J. Occup. Ther. PD SEP-OCT PY 2014 VL 68 IS 5 SI SI BP 522 EP 530 DI 10.5014/ajot.2014.012377 PG 9 WC Rehabilitation SC Rehabilitation GA AO9MB UT WOS:000341678700005 PM 25184464 ER PT J AU Doorenweerd, N Straathof, CS Dumas, EM Spitali, P Ginjaar, IB Wokke, BH Schrans, DG van den Bergen, JC van Zwet, EW Webb, A van Buchem, MA Verschuuren, JJ Hendriksen, JG Niks, EH Kan, HE AF Doorenweerd, Nathalie Straathof, Chiara S. Dumas, Eve M. Spitali, Pietro Ginjaar, Ieke B. Wokke, Beatrijs H. Schrans, Debby G. van den Bergen, Janneke C. van Zwet, Erik W. Webb, Andrew van Buchem, Mark A. Verschuuren, Jan J. Hendriksen, Jos G. Niks, Erik H. Kan, Hermien E. TI Reduced Cerebral Gray Matter and Altered White Matter in Boys with Duchenne Muscular Dystrophy SO ANNALS OF NEUROLOGY LA English DT Article ID AUTISM SPECTRUM DISORDER; CENTRAL-NERVOUS-SYSTEM; BRAIN-DEVELOPMENT; MR-IMAGES; CHILDREN; NEURONS; CORTEX; MALES; DMD; QUESTIONNAIRE AB Objective: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with mutations in the distal part of the DMD gene, predicted to affect expression of shorter protein isoforms. We used quantitative magnetic resonance (MR) imaging to study brain microstructure in DMD. Methods: T1-weighted and diffusion tensor images were obtained on a 3T MR scanner from 30 patients and 22 age-matched controls (age = 8-18 years). All subjects underwent neuropsychological examination. Group comparisons on tissue volume and diffusion tensor imaging parameters were made between DMD patients and controls, and between 2 DMD subgroups that were classified according to predicted Dp140 isoform expression (DMD_Dp140(+) and DMD_Dp140(-)). Results: DMD patients had smaller total brain volume, smaller gray matter volume, lower white matter fractional anisotropy, and higher white matter mean and radial diffusivity than healthy controls. DMD patients also performed worse on neuropsychological examination. Subgroup analyses showed that DMD_Dp140(-) subjects contributed most to the gray matter volume differences and performed worse on information processing. Interpretation: Both gray and white matter is affected in boys with DMD at a whole brain level. Differences between the DMD_Dp140(-) subgroup and controls indicate an important role for the Dp140 dystrophin isoform in cerebral development. C1 [Doorenweerd, Nathalie; Webb, Andrew; van Buchem, Mark A.; Kan, Hermien E.] Leiden Univ, Med Ctr, Dept Radiol, CJ Gorter Ctr High Field MRI, NL-2333 ZA Leiden, Netherlands. [Doorenweerd, Nathalie; Kan, Hermien E.] Leiden Inst Brain & Cognit, Leiden, Netherlands. [Doorenweerd, Nathalie; Straathof, Chiara S.; Dumas, Eve M.; Wokke, Beatrijs H.; van den Bergen, Janneke C.; Verschuuren, Jan J.; Niks, Erik H.] Leiden Univ, Med Ctr, Dept Neurol, NL-2333 ZA Leiden, Netherlands. [Spitali, Pietro] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands. [Ginjaar, Ieke B.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2333 ZA Leiden, Netherlands. [Schrans, Debby G.; Hendriksen, Jos G.] Kempenhaeghe Epilepsy Ctr, Dept Neurol Learning Disabil, Heeze, Netherlands. [van Zwet, Erik W.] Leiden Univ, Med Ctr, Dept Med Stat, NL-2333 ZA Leiden, Netherlands. [Hendriksen, Jos G.] Maastricht Univ, Med Ctr, Dept Neurol, Maastricht, Netherlands. RP Doorenweerd, N (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C-03-Q,Albinusdreef2, NL-2333 ZA Leiden, Netherlands. EM N.Doorenweerd@lumc.nl RI Kan, Hermien/L-2385-2013 OI Kan, Hermien/0000-0002-5772-7177 FU Duchenne Parent Project NL; Gratama Stichting FX The sponsors, Duchenne Parent Project NL and Gratama Stichting, had no role in study design, data collection, data analysis, data interpretation, or writing of the report. 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Neurol. PD SEP PY 2014 VL 76 IS 3 BP 403 EP 411 DI 10.1002/ana.24222 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AP6RG UT WOS:000342204500011 PM 25043804 ER PT J AU Monnier, M Jaunin, L Graz, MB Tolsa, CB Huppi, P Rossignol, AS Barisnikov, K Guex, MF AF Monnier, M. Jaunin, L. Graz, M. Bickle Tolsa, C. Borradori Hueppi, P. Rossignol, A. Sancho Barisnikov, K. Guex, M. Forcada TI Detection of executive function disorders with a standard neurodevelopmental follow-up of premature children SO ARCHIVES DE PEDIATRIE LA French DT Article ID LOW-BIRTH-WEIGHT; SCHOOL-AGED CHILDREN; PRETERM INFANTS; NEUROBEHAVIORAL OUTCOMES; BORN; ATTENTION; METAANALYSIS; MORTALITY; AND/OR AB Introduction. A significant proportion of prematurely born children encounter behavioral difficulties, such as attention deficit or hyperactivity, which could be due to executive function disorders. Aims. To examine whether the standard neurodevelopmental assessment offered to premature children in Switzerland recognizes executive function disorders. Methods. The study population consisted of 49 children born before 29 weeks of gestation who were examined between 5 and 6 years of age with a standard assessment, with additional items to assess executive functioning. Children with severe neurodevelopmental impairment were excluded (mental retardation, cerebral palsy, autism). Standard assessment consisted in the Kaufman Assessment Battery for Children (K-ABC), which comprises three subscales: sequential processes (analysis of sequential information), simultaneous processes (global analysis of visual information), and composite mental processes (CMP) (result of the other two scales), as well as a behavioral evaluation using the standardized Strengths and Difficulties Questionnaire (SDQ). Executive functioning was assessed with tasks evaluating visual attention, divided attention, and digit memory as well as with a specialized questionnaire, the Behavior Rating Index of Executive Functions (BRIEF), which evaluates several aspects of executive function (regulation, attention, flexibility, working memory, etc). Results. Children were divided according to their results on the three K-ABC scales (< or >85), and the different neuropsychological tasks assessing executive function were compared between the groups. The CMP did not differentiate children with executive difficulties, whereas a score < 85 on the sequential processes was significantly associated with worse visual and divided attention. There was a strong correlation between the SDQ and the BRIEF questionnaires. For both questionnaires, children receiving psychotherapy had significantly higher results. Children who presented behavioral problems assessed with the SDQ presented. significantly higher scores on the BRIEF. Conclusion. A detailed analysis of the standard neurodevelopmental assessment allows the identification of executive function disorders in premature children. Children who performed below 85 on the sequential processes of the K-ABC had significantly more attentional difficulties on the neuropsychological tasks and therefore have to be recognized and carefully followed. Emotional regulation had a strong correlation with behavioral difficulties, which were suitably assessed with the SDQ, recognized by the families, and treated. (C) 2014 Published by Elsevier Masson SAS. C1 [Monnier, M.; Jaunin, L.; Graz, M. Bickle; Guex, M. Forcada] CHU Vaudois, Dept Medicochirurg Pediat, Serv Neonatol, Unite Dev, Lausanne, Switzerland. [Tolsa, C. Borradori; Hueppi, P.; Rossignol, A. Sancho] HUG, Dept Pediat, Serv Dev & Croissance, Geneva, Switzerland. [Barisnikov, K.] Univ Geneva, Fac Psychol & Sci Educ, Unite Psychol Clin & Neuropsychol Enfant, Geneva, Switzerland. RP Monnier, M (reprint author), CHU Vaudois, Dept Medicochirurg Pediat, Serv Neonatol, Unite Dev, Lausanne, Switzerland. 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TI Crossing the equator: Ube3a in Idic15 autism and Angelman syndrome SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 18th International Congress of Neuropathology CY SEP 14-18, 2014 CL Rio de Janeiro, BRAZIL C1 [Anderson, M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Cambridge, MA 02138 USA. [Anderson, M.] Harvard Univ, Sch Med, Autism BrainNET, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2014 VL 24 SU 1 SI SI BP 37 EP 37 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AP6CT UT WOS:000342165800142 ER PT J AU Hutsler, J AF Hutsler, J. TI Cortical organization and synaptic culling in individuals with autism SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 18th International Congress of Neuropathology CY SEP 14-18, 2014 CL Rio de Janeiro, BRAZIL C1 [Hutsler, J.] Univ Nevada, Dept Psychol, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2014 VL 24 SU 1 SI SI BP 37 EP 37 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AP6CT UT WOS:000342165800141 ER PT J AU Wisniewski, T AF Wisniewski, T. TI Brain region specific alterations of neuronal number and volume in autism SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 18th International Congress of Neuropathology CY SEP 14-18, 2014 CL Rio de Janeiro, BRAZIL C1 [Wisniewski, T.] NYU, Sch Med, Dept Neurol Psychiat & Pathol, New York, NY 10003 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2014 VL 24 SU 1 SI SI BP 37 EP 37 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AP6CT UT WOS:000342165800140 ER PT J AU Wainer, J Robins, B Amirabdollahian, F Dautenhahn, K AF Wainer, Joshua Robins, Ben Amirabdollahian, Farshid Dautenhahn, Kerstin TI Using the Humanoid Robot KASPAR to Autonomously Play Triadic Games and Facilitate Collaborative Play Among Children With Autism SO IEEE TRANSACTIONS ON AUTONOMOUS MENTAL DEVELOPMENT LA English DT Article DE Autism; autonomous robots; human-robot interaction; humanoid robots; therapeutic robots ID SPECTRUM DISORDERS; JOINT ATTENTION; IMITATION; THERAPY; AGENT AB This paper presents a novel design, implementation, and first evaluation of a triadic, collaborative game involving the humanoid robot, kinesics and synchronization in personal assistant robotics (KASPAR), playing games with pairs of children with autism. Children with autism have impaired social communication and social interaction skills which make it difficult for them to participate in many different forms of social and collaborative play. Our proof-of-concept 10-week, long term study demonstrates how a humanoid robot can be used to foster and support collaborative play among children with autism. In this work, KASPAR operates fully autonomously, and uses information on the state of the game and behavior of the children to engage, motivate, encourage, and advise pairs of children playing an imitation game. Results are presented from a first evaluation study which examined whether having pairs of children with autism play an imitative, collaborative game with a humanoid robot affected the way these children would play the same game without the robot. Our initial evaluation involved six children with autism who each participated in 23 controlled play sessions both with and without the robot, using a specially designed imitation-based collaborative game. In total 78 play sessions were run. Detailed observational analyses of the children's behaviors indicated that different pairs of children with autism showed improved social behaviors in playing with each other after they played as pairs with the robot KASPAR compared to before they did so. These results are encouraging and provide a proof-of-concept of using an autonomously operating robot to encourage collaborative skills among children with autism. C1 [Wainer, Joshua; Robins, Ben; Amirabdollahian, Farshid; Dautenhahn, Kerstin] Univ Hertfordshire, Adapt Syst Res Grp, Sch Comp Sci, Hatfield AL10 9AB, Herts, England. RP Wainer, J (reprint author), Univ Hertfordshire, Adapt Syst Res Grp, Sch Comp Sci, Hatfield AL10 9AB, Herts, England. 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PD SEP PY 2014 VL 6 IS 3 BP 183 EP 199 DI 10.1109/TAMD.2014.2303116 PG 17 WC Computer Science, Artificial Intelligence; Robotics; Neurosciences SC Computer Science; Robotics; Neurosciences & Neurology GA AP5JL UT WOS:000342115400002 ER PT J AU Boucenna, S Anzalone, S Tilmont, E Cohen, D Chetouani, M AF Boucenna, Sofiane Anzalone, Salvatore Tilmont, Elodie Cohen, David Chetouani, Mohamed TI Learning of Social Signatures Through Imitation Game Between a Robot and a Human Partner SO IEEE TRANSACTIONS ON AUTONOMOUS MENTAL DEVELOPMENT LA English DT Article DE Autism spectrum disorder; human-robot interaction; imitation; sensory-motor architecture ID AUTISM SPECTRUM DISORDERS; DEVELOPMENTAL ROBOTICS; ASSISTIVE ROBOTICS; DEPRESSED MOTHERS; COMMUNICATION; CHILDREN; INFANTS; RECOGNITION; DEMONSTRATIONS; INDIVIDUALS AB In this paper, a robot learns different postures by imitating several partners. We assessed the effect of the type of partners, i.e., adults, typically developing (TD) children and children with autism spectrum disorder (ASD), on robot learning during an imitation game. The experimental protocol was divided into two phases: 1) a learning phase, during which the robot produced a random posture and the partner imitated the robot; and 2) a phase in which the roles were reversed and the robot had to imitate the posture of the human partner. Robot learning was based on a sensory-motor architecture whereby neural networks (N.N.) enabled the robot to associate what it did with what it saw. Several metrics (i.e., annotation, the number of neurons needed to learn, and normalized mutual information) were used to show that the partners affected robot learning. The first result obtained was that learning was easier with adults than with both groups of children, indicating a developmental effect. Second, learning was more complex with children with ASD compared to both adults and TD children. Third, learning with the more complex partner first (i.e., children with ASD) enabled learning to be more easily generalized. C1 [Boucenna, Sofiane; Anzalone, Salvatore; Tilmont, Elodie; Chetouani, Mohamed] Univ Paris 06, CNRS, UMR 7222, Inst Syst Intelligents & Robot, Paris, France. [Cohen, David] Univ Paris 06, Grp Hosp Piti SalpAtrire, AP HP, Dept Child & Adolescent Psychiat, Paris, France. RP Boucenna, S (reprint author), Univ Paris 06, CNRS, UMR 7222, Inst Syst Intelligents & Robot, Paris, France. EM sofiane.boucenna@gmail.com; anza-lone@isir.upmc.fr; elodie.tilmont@isir.upmc.fr; david.cohen@psl.aphp.fr; mohamed.chetouani@upmc.fr FU European Commission [288241]; endowment fund "Entreprendre pour aider" FX This work was supported by the European Commission (FP7: MICHELANGELO under Grant 288241) and the endowment fund "Entreprendre pour aider." 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EM ghol7955@med.usyd.edu.au CR D'Onofrio BM, 2014, JAMA PSYCHIAT, V71, P432, DOI 10.1001/jamapsychiatry.2013.4525 Gillberg C, 2006, J AUTISM DEV DISORD, V36, P429, DOI 10.1007/s10803-006-0081-6 Jick H, 2003, EPIDEMIOLOGY, V14, P630, DOI 10.1097/01.EDE.0000082044.88833.c4 Taylor B, 2013, BMJ OPEN NR 4 TC 0 Z9 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2014 VL 71 IS 9 BP 1077 EP 1078 PG 2 WC Psychiatry SC Psychiatry GA AP0SV UT WOS:000341775300015 PM 25188260 ER PT J AU Siegel, M Beresford, CA Bunker, M Verdi, M Vishnevetsky, D Karlsson, C Teer, O Stedman, A Smith, KA AF Siegel, Matthew Beresford, Carol A. Bunker, Madisun Verdi, Mary Vishnevetsky, Donna Karlsson, Cassie Teer, Olivia Stedman, Amy Smith, Kahsi A. TI Preliminary Investigation of Lithium for Mood Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB Objective: Children with autism spectrum disorder (ASD) have higher rates of comorbid psychiatric disorders, including mood disorders, than the general child population. Although children with ASD may experience irritability (aggression, self-injury, and tantrums), a portion also experience symptoms that are typical of a mood disorder, such as euphoria/elevated mood, mania, hypersexuality, paranoia, or decreased need for sleep. Despite lithium's established efficacy in controlling mood disorder symptoms in the neurotypical population, lithium has been rarely studied in children with ASD. Methods: We performed a retrospective chart review of 30 children and adolescents diagnosed with ASD by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria who were prescribed lithium in order to assess target symptoms, safety, and tolerability. Clinical Global Impressions - Improvement (CGI-I) ratings were performed by two board-certified child psychiatrists with expertise in ASD. CGI-I scores were dichotomized into "improved'' (CGI-I score of 1 or 2) or "not improved'' (CGI-I score >= 3). Results: Forty-three percent of patients who received lithium were rated as "improved'' on the CGI-I. Seventy-one percent of patients who had two or more pretreatment mood disorder symptoms were rated as "improved.'' The presence of mania (p = 0.033) or euphoria/elevated mood (p = 0.041) were the pretreatment symptoms significantly associated with an "improved'' rating. The mean lithium blood level was 0.70 mEq/L (SD = 0.26), and the average length of lithium treatment was 29.7 days (SD = 23.9). Forty-seven percent of patients were reported to have at least one side effect, most commonly vomiting (13%), tremor (10%), fatigue (10%), irritability (7%), and enuresis (7%). Conclusions: This preliminary assessment of lithium in children and adolescents with ASD suggests that lithium may be a medication of interest for those who exhibit two or more mood disorder symptoms, particularly mania or euphoria/elevated mood. A relatively high side effect rate merits caution, and these results are limited by the retrospective, uncontrolled study design. Future study of lithium in a prospective trial with treatment-sensitive outcome measures may be indicated. C1 [Siegel, Matthew] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. [Siegel, Matthew; Bunker, Madisun; Verdi, Mary; Teer, Olivia; Stedman, Amy] Spring Harbor Hosp, Westbrook, ME 04092 USA. [Siegel, Matthew; Smith, Kahsi A.] Maine Med Ctr, Res Inst, Scarborough, ME USA. [Beresford, Carol A.; Vishnevetsky, Donna; Karlsson, Cassie] Univ Colorado, Denver, CO 80202 USA. [Beresford, Carol A.] Childrens Hosp, Aurora, CO USA. RP Siegel, M (reprint author), Spring Harbor Hosp, 123 Andover Rd, Westbrook, ME 04092 USA. EM siegem@springharbor.org FU Maine Medical Center Research Institute; Pond Family Foundation FX This work was performed with general support from the Maine Medical Center Research Institute and the Pond Family Foundation. 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PD SEP PY 2014 VL 24 IS 7 BP 399 EP 402 DI 10.1089/cap.2014.0019 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AP6CD UT WOS:000342164200006 PM 25093602 ER PT J AU Henry, CA Nowinski, L Koesterer, K Ferrone, C Spybrook, J Bauman, M AF Henry, Charles A. Nowinski, Lisa Koesterer, Karmen Ferrone, Christine Spybrook, Jessaca Bauman, Margaret TI Low Rates of Depressed Mood and Depression Diagnoses in a Clinic Review of Children and Adolescents with Autistic Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; INFANTILE-AUTISM; SYMPTOMS; BEHAVIOR; ADULTS; CHILDHOOD; ANXIETY AB Objectives: The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. Methods: Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. Results: Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n = 78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. Conclusions: Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder. C1 [Henry, Charles A.; Nowinski, Lisa; Koesterer, Karmen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02445 USA. 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PD SEP PY 2014 VL 24 IS 7 BP 403 EP 406 DI 10.1089/cap.2014.0024 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AP6CD UT WOS:000342164200007 PM 25198799 ER PT J AU Sokolov, AA Erb, M Tatagiba, MS Grodd, W Frackowiak, RSJ Pavlova, MA AF Sokolov, A. A. Erb, M. Tatagiba, M. S. Grodd, W. Frackowiak, R. S. J. Pavlova, M. A. TI Cerebello-temporal Connectivity during Visual Perception of Body Motion SO KLINISCHE NEUROPHYSIOLOGIE LA German DT Article DE cerebellum; biological motion; magnetic resonance imaging (MRI); connectivity; diffusion tensor imaging (DTI) ID BIOLOGICAL MOTION; HUMAN BRAIN; AUTISM; RECOGNITION; PROJECTIONS; HUMANS; SULCUS; ORGANIZATION; INVOLVEMENT; ACTIVATION AB Visual perception of others' movements is of great value for daily life activities, e. g., for safe car driving or non-verbal communication. While the cortical system for visual perception of body motion has been addressed in a number of studies, the contribution of subcortical structures remains largely unclear. Based on lesion findings in neurosurgical patients indicating eloquence of the left lateral cerebellum, by using functional magnetic resonance imaging (fMRI), we could demonstrate that the left lateral cerebellar lobules Crus I and VIIB are involved in visual processing of body motion. Dynamic causal modelling (DCM) suggests a reciprocal effective connectivity between the left lateral cerebellum and the right superior temporal sulcus (STS), the cornerstone of the network for biological motion perception. Diffusion tensor imaging (DTI) provides the first evidence for a direct bidirectional fibre pathway between the cerebellum and STS. These findings open a new window for future neurological and psychiatric research. C1 [Sokolov, A. A.; Frackowiak, R. S. 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Neurophysiol. PD SEP PY 2014 VL 45 IS 3 BP 144 EP 150 DI 10.1055/s-0034-1382071 PG 7 WC Clinical Neurology; Neuroimaging; Physiology SC Neurosciences & Neurology; Physiology GA AP4OI UT WOS:000342056600002 ER PT J AU Fabri, ZN Nagy, P Varga, L AF Fabri, Zsofia Nora Nagy Peter Varga Laszlo TI Production, general characteristics, chemical composition and health benefits of camel milk. Literature review. 2. Lactose, minerals and vitamin contents, health benefits SO MAGYAR ALLATORVOSOK LAPJA LA Hungarian DT Article AB In the second part of a two-part article, the lactose, major and trace minerals and vitamin Contents of camel's milk are reviewed. A detailed comparison is also made between the physicochemical properties of camel milk and those of cow, sheep, goat and human milk. Finally, the health benefits associated with camel milk consumption are thoroughly discussed. Camel milk is higher in sodium and calcium than milks of other species. Furthermore, camel milk is a good source of certain vitamins. For instance, its vitamin C content can be as much as 10 times higher than that of bovine milk. Fresh and fermented camel milks were reported to provide a wide range of potential health benefits to humans, including antihypertensive, hypocholesterolemic, antiviral and hypoglycemic effects. In addition, fermented camel's milk is used in various Asian and African countries to treat tuberculosis and chronic diseases of the gastrointestinal tract. Some recent findings suggest that camel milk, consumed on a regular basis, is capable of reducing autism symptoms. C1 [Fabri, Zsofia Nora; Varga Laszlo] Nyugat Magyarorszagi Egyet, Mezogazdasag & Elelmiszer Tudomanyi Kar, Elelmiszer Tudomanyi Int, H-9200 Mosonmagyarovar, Hungary. [Nagy Peter] Emirates Ind Camel Milk & Prod, Dubai, U Arab Emirates. RP Fabri, ZN (reprint author), Nyugat Magyarorszagi Egyet, Mezogazdasag & Elelmiszer Tudomanyi Kar, Elelmiszer Tudomanyi Int, Lucsony U 15-17, H-9200 Mosonmagyarovar, Hungary. EM VargaL@mtk.nyme.hu NR 0 TC 0 Z9 0 PU MEZOGAZDA KIADO KFT PI BUDAPEST PA PO BOX 16, 1631 BUDAPEST, HUNGARY SN 0025-004X J9 MAGY ALLATORVOSOK JI Magy. Allatorv. Lapja PD SEP PY 2014 VL 136 IS 9 BP 553 EP 557 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA AP4GX UT WOS:000342036300007 ER PT J AU Stocco, A Baizabal-Carvallo, JF AF Stocco, Amber Baizabal-Carvallo, Jose Fidel TI Deep brain stimulation for severe secondary stereotypies SO PARKINSONISM & RELATED DISORDERS LA English DT Letter DE Stereotypies; Deep brain stimulation; Autism; Movement disorders C1 [Stocco, Amber] Texas Childrens Hosp, Baylor Coll Med, Dept Child Neurol, Houston, TX 77030 USA. [Baizabal-Carvallo, Jose Fidel] Baylor Coll Med, Parkinsons Dis Ctr & Movement Disorders Clin, Dept Neurol, Houston, TX 77030 USA. RP Baizabal-Carvallo, JF (reprint author), Baylor Coll Med, Parkinsons Dis Ctr & Movement Disorders Clin, Dept Neurol, Smith Tower,Suite 1801,6550 Fannin, Houston, TX 77030 USA. EM baizabaljf@hotmail.com CR Baup N, 2008, J NEUROSCI, V28, P8785, DOI 10.1523/JNEUROSCI.2384-08.2008 Edwards MJ, 2012, MOVEMENT DISORD, V27, P179, DOI 10.1002/mds.23994 Houdayer E, 2013, MOV DISORD Lai MC, 2014, LANCET, V383, P896, DOI 10.1016/S0140-6736(13)61539-1 Miller JM, 2006, J CHILD NEUROL, V21, P119, DOI 10.2310/7010.2006.00025 NR 5 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD SEP PY 2014 VL 20 IS 9 BP 1035 EP 1036 DI 10.1016/j.parkreldis.2014.06.019 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AP2KF UT WOS:000341900400020 PM 25012696 ER PT J AU Romanelli, M Rhodes, A AF Romanelli, Mark Rhodes, Arthur TI Guanfacine-Induced Lichenoid Drug Eruption in a Child with Autism and Attention Deficit Hyperactivity Disorder SO PEDIATRIC DERMATOLOGY LA English DT Article AB Lichenoid drug eruptions (LDEs) have a variety of medication causes. We report a case of a 5-year-old boy with autism and attention deficit hyperactivity disorder treated with guanfacine who developed pruritic lesions consistent with LDEs. Rechallenge was not attempted. There are several clinical and histopathologic clues that may distinguish LDEs from lichen planus. C1 [Romanelli, Mark; Rhodes, Arthur] Rush Univ, Med Ctr, Dept Dermatol, Chicago, IL 60612 USA. RP Romanelli, M (reprint author), Rush Univ, Med Ctr, Dept Dermatol, 1653 W Congress Pkwy,220 Annex Bldg, Chicago, IL 60612 USA. EM markgromanelli@gmail.com CR Basow DS, 2011, PEDIAT NEONATAL LEXI Black MM, 1986, TXB DERMATOLOGY, P1665 Bolognia JL, 2008, DERMATOLOGY HALEVY S, 1993, J AM ACAD DERMATOL, V29, P249 VANDENHAUTE V, 1989, DERMATOLOGICA, V179, P10 NR 5 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2014 VL 31 IS 5 BP 614 EP 615 DI 10.1111/pde.12197 PG 3 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA AP1FE UT WOS:000341811700020 PM 23869619 ER PT J AU Waltereit, R Banaschewski, T Meyer-Lindenberg, A Poustka, L AF Waltereit, Robert Banaschewski, Tobias Meyer-Lindenberg, Andreas Poustka, Luise TI Interaction of neurodevelopmental pathways and synaptic plasticity in mental retardation, autism spectrum disorder and schizophrenia: Implications for psychiatry SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Review DE developmental psychopathology; genetics; mental retardation; autism spectrum disorder; schizophrenia ID COPY NUMBER VARIATION; TUBEROUS-SCLEROSIS; DEVELOPMENTAL DISORDERS; NEUREXIN SUPERFAMILY; STRUCTURAL VARIATION; ADULT SCHIZOPHRENIA; DNA METHYLATION; SPECIAL NEEDS; PROJECT SNAP; RISK-FACTORS AB Objectives. Schizophrenia (SCZ), autism spectrum disorder (ASD) and mental retardation (MR) are psychiatric disorders with high heritability. They differ in their clinical presentation and in their time course of major symptoms, which predominantly occurs for MR and ASD during childhood and for SCZ during young adult age. Recent findings with focus on the developmental neurobiology of these disorders emphasize shared mechanisms of common origin. These findings propose a continuum of genetic risk factors impacting on synaptic plasticity with MR causing impairments in global cognitive abilities, ASD in social cognition and SCZ in both global and social cognition. Methods. We assess here the historical developments that led to the current disease concepts of the three disorders. We then analyse, based on the functions of genes mutated in two or three of the disorders, selected mechanisms shared in neurodevelopmental pathways and synaptic plasticity. Results. The analysis of the psychopathological constructs supports the existence of three distinct clinical entities but also elaborates important associations. Similarly, there are common mechanisms especially in global and social cognition. Conclusions. We discuss implications from this integrated view on MR, ASD and SCZ for child & adolescent and adult psychiatry in pathophysiology and research perspectives. C1 [Waltereit, Robert; Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany. [Waltereit, Robert; Banaschewski, Tobias; Meyer-Lindenberg, Andreas; Poustka, Luise] Heidelberg Univ, Mannheim Med Fac, Mannheim, Germany. [Banaschewski, Tobias; Poustka, Luise] Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany. [Waltereit, Robert] Univ Saarland, Med Ctr, Dept Psychiat & Psychotherapy, D-66421 Homburg, Germany. RP Waltereit, R (reprint author), Univ Saarland, Med Ctr, Dept Psychiat & Psychotherapy, D-66421 Homburg, Germany. 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Psychiatry PD SEP PY 2014 VL 15 IS 7 BP 507 EP 516 DI 10.3109/15622975.2013.838641 PG 10 WC Psychiatry SC Psychiatry GA AP7CQ UT WOS:000342235800002 PM 24079538 ER PT J AU Chudal, R Gissler, M Sucksdorff, D Lehti, V Suominen, A Hinkka-Yli-Salomaki, S Brown, AS Sourander, A AF Chudal, Roshan Gissler, Mika Sucksdorff, Dan Lehti, Venla Suominen, Auli Hinkka-Yli-Salomaki, Susanna Brown, Alan S. Sourander, Andre TI Parental age and the risk of bipolar disorders SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; epidemiology; parental age; U-shaped ID ADVANCING PATERNAL AGE; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; POPULATION-BASED COHORT; PSYCHIATRIC-DISORDERS; MATERNAL AGE; SCHIZOPHRENIA; BIRTH; PSYCHOSIS; EXPLAIN AB Objectives Studies on the association between parental age and bipolar disorder (BPD) are scarce and with inconsistent findings. The aim of this study was to examine the association of parental age and age difference between parents with risk of BPD in offspring. Methods This nested case-control study identified 1,861 cases of individuals with BPD born in Finland during 1983-1998 and diagnosed by the end of 2008, and 3,643 sex- and date of birth-matched controls from nationwide population-based registers. Conditional logistic regression was used to examine the association adjusting for potential confounding due to age of the other parent, parental psychiatric history, educational level, and place of birth. Results A U-shaped association of unadjusted odds ratios (ORs) for BPD risk was seen in different paternal age categories, with the odds increasing at both ends of the age spectrum. In the adjusted analyses, offspring of fathers aged 50years had a 2.8-fold increased odds [OR=2.84, 95% confidence interval (CI): 1.32-6.12] of BPD as compared to those with fathers aged 30-34years. The odds were increased 1.3-fold (OR=1.35, CI: 1.06-1.72) in fathers aged 20-24years. No significant association was found between maternal age and BPD in the adjusted analyses. Age difference between parents was not associated with BPD. Conclusions The increased risk of BPD in offspring of the youngest and oldest fathers in the study suggests the involvement of different biological and psychosocial factors at the two ends of the paternal age spectrum. These findings may be significant in the context of advancing parental age in recent times. C1 [Chudal, Roshan; Gissler, Mika; Sucksdorff, Dan; Lehti, Venla; Suominen, Auli; Hinkka-Yli-Salomaki, Susanna; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku 20014, Finland. [Gissler, Mika] Nord Sch Publ Hlth, Gothenburg, Sweden. [Gissler, Mika] Natl Inst Hlth & Welf, Helsinki, Finland. [Brown, Alan S.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Brown, Alan S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Sourander, Andre] Turku Univ Hosp, Dept Child Psychiat, FIN-20520 Turku, Finland. [Sourander, Andre] Univ Tromso, Reg Ctr Child & Youth Mental Hlth & Child Welf, Tromso, Norway. RP Sourander, A (reprint author), Univ Turku, Fac Med, Inst Clin Med, Res Ctr Child Psychiat, Lemminkaisenkatu 3 Teutori 3rd Floor, Turku 20014, Finland. EM andsou@utu.fi RI Chudal, Roshan/C-1067-2015 FU NARSAD Independent Investigator Award, USA (AS) [K02 MH065422-10] FX The study was supported by grants from the NARSAD Independent Investigator Award, USA (AS), the Sigrid Juselius Foundation, Finland (AS), and K02 MH065422-10 (ASB). This study was conducted at the University of Turku, Finland and we thank the study investigators and staff at the medical centers involved in this research. 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PD SEP PY 2014 VL 16 IS 6 BP 624 EP 632 DI 10.1111/bdi.12182 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AO8GU UT WOS:000341592700008 PM 24499422 ER PT J AU Sanchez, RP Bartel, CM Brown, E DeRosier, M AF Sanchez, Rebecca Polley Bartel, Chelsea M. Brown, Emily DeRosier, Melissa TI The acceptability and efficacy of an intelligent social tutoring system SO COMPUTERS & EDUCATION LA English DT Article DE Intelligent tutoring system; Educational computer game; eLeaming; Social skills training; Social skills intervention ID HIGH-FUNCTIONING AUTISM; ANTISOCIAL-BEHAVIOR; PEER REJECTION; CHILDREN; SKILLS; SCHOOL; INTERVENTIONS; ADJUSTMENT; METAANALYSIS; PREVENTION AB This study tested the acceptability and efficacy of an innovative intelligent tutoring system (ITS), Adventures Aboard the S.S. GRIN, that translates the evidence-based in-person Social Skills Group Intervention (SSGRIN) into an interactive game-based social tutorial. This randomized controlled pilot trial tested the first half of the social tutorial software for children with social skills challenges. Participating children in grades 3-5 were randomly assigned to immediate treatment (n = 19) or wait-list control (n = 17). User ratings indicated the software was easy to use and well-liked for this audience. The program was also associated with observable changes in social skills and behavior; children who interacted with Adventures Aboard the S.S. GRIN exhibited lower psychosocial distress and higher behavioral and emotional strength at post-test compared to children who did not. This pilot study offers important insights about the feasibility and potential effectiveness of online social skills training and lays the groundwork for future full-scale effectiveness testing. The advantages of using this state-of-the-art approach and its implications for improving social, emotional, and academic outcomes are discussed. (C) 2014 Elsevier Ltd. 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Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10-16) with ASD (N=16), CP/HCU (N=16) and typically developing (TD) controls (N=16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM. C1 [O'Nions, Elizabeth; Sebastian, Catherine L.; McCrory, Eamon; Chantiluke, Kaylita; Happe, Francesca; Viding, Essi] UCL, Dev Risk & Resilience Unit, Clin Educ & Hlth Psychol Res Dept, London WC1H 0AP, England. [Sebastian, Catherine L.] Univ London, Dept Psychol, London WC1E 7HU, England. RP O'Nions, E (reprint author), UCL, Dev Risk & Resilience Unit, Clin Educ & Hlth Psychol Res Dept, 26 Bedford Way, London WC1H 0AP, England. 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Sci. PD SEP PY 2014 VL 17 IS 5 BP 786 EP 796 DI 10.1111/desc.12167 PG 11 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA AO7DG UT WOS:000341511600013 PM 24636205 ER PT J AU Strunk, JA Pickler, R McCain, NL Ameringer, S Myers, BJ AF Strunk, Julie A. Pickler, Rita McCain, Nancy L. Ameringer, Suzanne Myers, Barbara J. TI Managing the Health Care Needs of Adolescents With Autism Spectrum Disorder: The Parents' Experience SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE adolescents' health care; autism spectrum disorder; health care needs; parents; phenomenology ID MEDICAL HOME; UNITED-STATES; CHILDREN; STRESS; MOTHERS; FAMILY; PARTNERSHIPS; BEHAVIORS; SERVICES; FATHERS AB Parents of adolescents with autism spectrum disorder (ASD) experience the challenges of navigating the health care system, locating information about ASD, lacking an understanding of prescribed medications, and experiencing minimal social support from health care providers. The purpose of this phenomenological study was to describe the experiences of parents who manage the health needs of an adolescent with ASD. Qualitative interviews were conducted at a university setting with 12 parents of 10 adolescents with ASD residing in Central Virginia. Data were analyzed using Moustakas' method in which the phenomenologist asks the following questions: What are the individual's experiences and in what context did they experience them? This study maximized credibility using 3 strategies: prolonged engagement, peer debriefing, and member checking. "Parents needing assistance" emerged as the essence of the parents' experiences. Four themes representing the essential challenging elements of the parents' experiences included concern with medications, frustrations with health care services, recognizing secondary health issues, and the need for resources and services. Findings of the current study revealed key factors to be considered in the development and delivery of health care for adolescents with ASD. These include creating and planning interventions for parents, sharing information about resources and services, and collaborating with others in the health care field. Additional research, both qualitative and quantitative, is needed to understand how parents and adolescents with ASD experience this transitional period. C1 [Strunk, Julie A.] James Madison Univ, Dept Nursing, Harrisonburg, VA 22807 USA. [Pickler, Rita] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [McCain, Nancy L.; Ameringer, Suzanne] Virginia Commonwealth Univ, Sch Nursing, Richmond, VA 23284 USA. [Myers, Barbara J.] Virginia Commonwealth Univ, Sch Psychol, Richmond, VA 23284 USA. RP Strunk, JA (reprint author), James Madison Univ, Dept Nursing, MSC 4305,820 Madison Dr, Harrisonburg, VA 22807 USA. 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Syst. Health PD SEP PY 2014 VL 32 IS 3 BP 328 EP 337 DI 10.1037/a0037180 PG 10 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA AP1QF UT WOS:000341845300008 PM 24911770 ER PT J AU Henderson, LB Applegate, CD Wohler, E Sheridan, MB Hoover-Fong, J Batista, DAS AF Henderson, Lindsay B. Applegate, Carolyn D. Wohler, Elizabeth Sheridan, Molly B. Hoover-Fong, Julie Batista, Denise A. S. TI The impact of chromosomal microarray on clinical management: a retrospective analysis SO GENETICS IN MEDICINE LA English DT Article DE autism; clinical management; clinical utility; chromosomal microarray; intellectual disability ID COPY-NUMBER VARIATIONS; DEVELOPMENTAL-DISABILITIES; HUMAN GENOME; DELAY; INDIVIDUALS; CYSTINOSIS; MUTATIONS; ANOMALIES; VARIANTS AB Purpose: Chromosomal microarray has been widely adopted as the first-tier clinical test for individuals with multiple congenital anomalies, developmental delay, intellectual disability, and autism spectrum disorders. Although chromosomal microarray has been extensively shown to provide a higher diagnostic yield than conventional cytogenetic methods, some health insurers refuse to provide coverage for this test, claiming that it is experimental and does not affect patients' clinical management. Methods: We retrospectively reviewed the electronic medical records of all patients who had abnormal chromosomal microarray findings reported by our laboratory over a 3-year period and quantified the management recommendations made in response to these results. Results: Abnormal chromosomal microarray findings were reported for 12.7% of patients (227/1,780). For patients with clinical follow-up notes available, these results had management implications for 54.5% of patients in the entire abnormal cohort (102/187) and for 42.1% of patients referred for isolated neurodevelopmental disorders (16/38). Recommendations included pharmacological treatment, cancer-related screening or exclusion of screening, contraindications, and referrals for further evaluation. Conclusion: These results empirically demonstrate the clinical utility of chromosomal microarray by providing evidence that management was directly affected for the majority of patients in our cohort with abnormal chromosomal microarray findings. C1 [Henderson, Lindsay B.; Applegate, Carolyn D.; Sheridan, Molly B.; Hoover-Fong, Julie; Batista, Denise A. S.] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Wohler, Elizabeth; Batista, Denise A. S.] Kennedy Krieger Inst, Cytogenet Lab, Baltimore, MD USA. [Batista, Denise A. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Batista, DAS (reprint author), Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM dbatist1@jhmi.edu FU National Institutes of Health [5P30 HD024061-23] FX The authors thank the staff at the Cytogenetics and Microarray Laboratory at the Kennedy Krieger Institute. This work was partially supported by National Institutes of Health grant 5P30 HD024061-23 to the Intellectual and Developmental Disabilities Research Center. 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Med. PD SEP PY 2014 VL 16 IS 9 BP 657 EP 664 DI 10.1038/gim.2014.18 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AP1LG UT WOS:000341830800002 PM 24625444 ER PT J AU Bonarrigo, FA Russo, S Vizziello, P Menni, F Cogliati, F Giorgini, V Monti, F Milani, D AF Bonarrigo, Francesca Andrea Russo, Silvia Vizziello, Paola Menni, Francesca Cogliati, Francesca Giorgini, Valentina Monti, Federico Milani, Donatella TI Think About It: FMR1 Gene Mosaicism SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE fragile X syndrome; intellectual disability; mosaicism ID FRAGILE-X-SYNDROME; CGG REPEAT; FULL MUTATION; NORMAL SIZE; DIAGNOSIS; DELETION; REGION; ALLELE; INSTABILITY; HOTSPOT AB Fragile X syndrome (FXS) is one of the most frequent causes of mental retardation, intellectual disability, and autism. Most cases are the result of an expansion of the CGG trinucleotide repeat in the 5 untranslated region of the FMR1 gene and the subsequent functional loss of the related protein. We describe the case of a 4-year-old boy who clinically presents mild psychomotor delay without any major clinical dysmorphisms. Molecular analysis of the FMR1 gene showed mosaicism in terms of size and methylation, with one normal and 1 fully mutated allele, which is very rare in this syndrome. Physicians should therefore consider a diagnosis of FXS even if the patient's phenotype is mild. Although rare, diagnosing this condition has important consequences for the patient's rehabilitation and the family planning of parents and relatives. C1 [Bonarrigo, Francesca Andrea; Menni, Francesca; Milani, Donatella] Univ Milan, Dept Pathophysiol & Transplantat, Pediat Clin 1, Fdn IRCCS Ca Granda Osped Maggiore Policlin, I-20122 Milan, Italy. [Russo, Silvia; Cogliati, Francesca; Giorgini, Valentina] Ist Auxol Italiano, Cytogenet & Mol Genet Lab, Milan, Italy. [Vizziello, Paola; Monti, Federico] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Child & Adolescent Neuropsychiat UONPIA, Milan, Italy. 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TI Clinical, biochemical and molecular analysis of 13 Japanese patients with beta-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID RHODOCOCCUS-RHODOCHROUS J1; TANDEM MASS-SPECTROMETRY; DIHYDROPYRIMIDINE DEHYDROGENASE; AMINOISOBUTYRIC ACID; ALANINE SYNTHASE; TOXICITY; GENE; DEGRADATION; NITRILASE; URINE AB beta-ureidopropionase (beta UP) deficiency is an autosomal recessive disease characterized by N-carbamyl-beta-amino aciduria. To date, only 16 genetically confirmed patients with beta UP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese beta UP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant beta UP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (a parts per thousand currency sign 1.3 %). Conversely, beta UP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human beta UP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that beta UP deficiency is not as rare as generally considered and screening for beta UP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities. C1 [Nakajima, Yoko; Meijer, Judith; Meinsma, Rutger; Abeling, Nico G. G. M.; Roelofsen, Jeroen; Zoetekouw, Lida; van Kuilenburg, Andre B. P.] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands. [Nakajima, Yoko; Ito, Tetsuya] Nagoya City Univ, Grad Sch Med Sci, Dept Pediat & Neonatol, Nagoya, Aichi 4678601, Japan. [Dobritzsch, Doreen] Uppsala Univ, Dept Chem, BMC, S-75123 Uppsala, Sweden. [Watanabe, Yoriko] Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Kurume, Fukuoka 8300011, Japan. [Watanabe, Yoriko; Tashiro, Kyoko] Kurume Univ, Sch Med, Res Inst Med Mass Spectrometry, Kurume, Fukuoka 8300011, Japan. [Lee, Tomoko; Takeshima, Yasuhiro] Kobe Univ, Dept Pediat, Grad Sch Med, Kobe, Hyogo 6500017, Japan. [Mitsubuchi, Hiroshi] Kumamoto Univ Hosp, Dept Neonatol, Kumamoto 8608556, Japan. [Yoneyama, Akira] Natl Rehabil Ctr Disabled Children, Tokyo 1730037, Japan. [Ohta, Kazuhide] Natl Hosp Org, Dept Pediat, Kanazawa Med Ctr, Kanazawa, Ishikawa 9208650, Japan. [Eto, Kaoru] Tokyo Womens Med Univ, Dept Pediat, Tokyo 1628111, Japan. [Saito, Kayoko] Tokyo Womens Med Univ, Inst Med Genet, Tokyo 1620054, Japan. [Kuhara, Tomiko] Japan Clin Metabol Inst, Kahoku, Ishikawa 9291174, Japan. RP Nakajima, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Pediat & Neonatol, Nagoya, Aichi 4678601, Japan. EM ncu.metabolism@gmail.com CR Assmann B, 2006, NEUROPEDIATRICS, V37, P20, DOI 10.1055/s-2006-923933 Assmann B, 1998, J INHERIT METAB D S2, V21 Begriche K, 2010, FUND CLIN PHARMACOL, V24, P269, DOI 10.1111/j.1472-8206.2009.00765.x DeLano W. 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Inherit. Metab. Dis. PD SEP PY 2014 VL 37 IS 5 BP 801 EP 812 DI 10.1007/s10545-014-9682-y PG 12 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA AP1XE UT WOS:000341864800013 PM 24526388 ER PT J AU Nicolaidis, C Kripke, CC Raymaker, D AF Nicolaidis, Christina Kripke, Clarissa Calliope Raymaker, Dora TI Primary Care for Adults on the Autism Spectrum SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Autism spectrum disorders; Primary care; Adults; Developmental disabilities ID INTELLECTUAL DISABILITIES; SLEEP PROBLEMS; ASPERGER-SYNDROME; YOUNG-ADULTS; DISORDERS; PEOPLE; HEALTH; INDIVIDUALS; CHILDREN; COMMUNITY AB Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults. C1 [Nicolaidis, Christina; Raymaker, Dora] Portland State Univ, Reg Res Inst, Sch Social Work, Portland, OR 97201 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Nicolaidis, Christina] Acad Autism Spectrum Partnership Res & Educ, Portland, OR 97239 USA. [Kripke, Clarissa Calliope] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nicolaidis, Christina; Raymaker, Dora] Acad Autism Spectrum Partnership Res & Educ, Portland, OR 97201 USA. RP Nicolaidis, C (reprint author), Portland State Univ, Reg Res Inst, Sch Social Work, 1600 SW 4th Ave,Suite 900, Portland, OR 97201 USA. EM nicol22@pdx.edu FU National Institute of Mental Health [R34MH092503] FX Many of the recommendations in this article arise from the AASPIRE Healthcare Toolkit Project. Funding for the project was provided by the National Institute of Mental Health (R34MH092503). We would like to thank the many AASPIRE team members and study participants who have contributed to the project. 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PD SEP PY 2014 VL 98 IS 5 BP 1169 EP + DI 10.1016/j.mcna.2014.06.011 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA AO8OO UT WOS:000341614300015 PM 25134878 ER PT J AU Samocha, KE Robinson, EB Sanders, SJ Stevens, C Sabo, A McGrath, LM Kosmicki, JA Rehnstrom, K Mallick, S Kirby, A Wall, DP MacArthur, DG Gabriel, SB DePristo, M Purcell, SM Palotie, A Boerwinkle, E Buxbaum, JD Cook, EH Gibbs, RA Schellenberg, GD Sutcliffe, JS Devlin, B Roeder, K Neale, BM Daly, MJ AF Samocha, Kaitlin E. Robinson, Elise B. Sanders, Stephan J. Stevens, Christine Sabo, Aniko McGrath, Lauren M. Kosmicki, Jack A. Rehnstrom, Karola Mallick, Swapan Kirby, Andrew Wall, Dennis P. MacArthur, Daniel G. Gabriel, Stacey B. DePristo, Mark Purcell, Shaun M. Palotie, Aarno Boerwinkle, Eric Buxbaum, Joseph D. Cook, Edwin H., Jr. Gibbs, Richard A. Schellenberg, Gerard D. Sutcliffe, James S. Devlin, Bernie Roeder, Kathryn Neale, Benjamin M. Daly, Mark J. TI A framework for the interpretation of de novo mutation in human disease SO NATURE GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DNA-SEQUENCING DATA; INTELLECTUAL DISABILITY; GENOME; PATTERNS; GENES; RATES AB Spontaneously arising (de novo) mutations have an important role in medical genetics. For diseases with extensive locus heterogeneity, such as autism spectrum disorders (ASDs), the signal from de novo mutations is distributed across many genes, making it difficult to distinguish disease-relevant mutations from background variation. Here we provide a statistical framework for the analysis of excesses in de novo mutation per gene and gene set by calibrating a model of de novo mutation. We applied this framework to de novo mutations collected from 1,078 ASD family trios, and, whereas we affirmed a significant role for loss-of-function mutations, we found no excess of de novo loss-of-function mutations in cases with IQ above 100, suggesting that the role of de novo mutations in ASDs might reside in fundamental neurodevelopmental processes. We also used our model to identify similar to 1,000 genes that are significantly lacking in functional coding variation in non-ASD samples and are enriched for de novo loss-of-function mutations identified in ASD cases. C1 [Samocha, Kaitlin E.; Robinson, Elise B.; Kosmicki, Jack A.; Kirby, Andrew; MacArthur, Daniel G.; Purcell, Shaun M.; Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Samocha, Kaitlin E.; Robinson, Elise B.; Kosmicki, Jack A.; Kirby, Andrew; MacArthur, Daniel G.; Purcell, Shaun M.; Neale, Benjamin M.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Samocha, Kaitlin E.; Robinson, Elise B.; Stevens, Christine; Kirby, Andrew; MacArthur, Daniel G.; Gabriel, Stacey B.; Purcell, Shaun M.; Neale, Benjamin M.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Samocha, Kaitlin E.; Robinson, Elise B.; Stevens, Christine; Neale, Benjamin M.; Daly, Mark J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Genet & Gen Biol & Biomed Sci, Boston, MA USA. [Sanders, Stephan J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sanders, Stephan J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Sabo, Aniko; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [McGrath, Lauren M.; Purcell, Shaun M.; Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiatr & Neurodev Genet Unit, Boston, MA 02114 USA. [McGrath, Lauren M.; Purcell, Shaun M.; Palotie, Aarno] Harvard Univ, Sch Med, Boston, MA USA. [Kosmicki, Jack A.; Wall, Dennis P.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Kosmicki, Jack A.; Wall, Dennis P.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Rehnstrom, Karola; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Rehnstrom, Karola; Palotie, Aarno] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England. [Mallick, Swapan] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [DePristo, Mark] Synapdx, Lexington, MA USA. [Purcell, Shaun M.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Purcell, Shaun M.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Purcell, Shaun M.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 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. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Pathol & Lab Med, Philadelphia, PA USA. [Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37235 USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Roeder, Kathryn] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM mjdaly@atgu.mgh.harvard.edu RI Sutcliffe, James/C-1348-2012 OI Sutcliffe, James/0000-0001-5200-6007 FU Autism Genetic Resource Exchange (AGRE) Consortium, a program of Autism Speaks [1U24MH081810]; Autism Speaks; Simons Foundation; Autism Consortium; US National Institutes of Health (NIH) [R01MH089208, R01MH089025, R01MH089004, R01MH089175, R01MH089482, P50HD055751, R01MH057881, R01MH061009]; Lung GO Sequencing Project [HL-102923]; Women's Health Initiative (WHI) Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010]; [U54HG003273]; [U54HG003067] FX All data from published studies are available in the respective publications. All newly generated data and computational tools used in this paper will be available online as downloadable material. We have also constructed a website to query genes that provides information on constraint and the de novo mutations found in the specified gene across published studies of de novo mutation. We would like to thank E. Daly and M. Chess for their contributions to data analysis and the construction of the website, respectively. We acknowledge the following resources and families who contributed to them: the National Institute of Mental Health (NIMH) repository (U24MH068457); the Autism Genetic Resource Exchange (AGRE) Consortium, a program of Autism Speaks (1U24MH081810 to C.M. Lajonchere); The Autism Simplex Collection (TASC) (grant from Autism Speaks); the Simons Foundation Autism Research Initiative (SFARI) Simplex Collection (grant from the Simons Foundation); and The Autism Consortium (grant from the Autism Consortium). This work was directly supported by US National Institutes of Health (NIH) grants R01MH089208 (M.J.D.), R01MH089025 (J.D.B.), R01MH089004 (G.D.S.), R01MH089175 (R.A.G.) and R01MH089482 (J.S.S.) and was supported in part by US NIH grants P50HD055751 (E.H.C.), R01MH057881 (B.D.) and R01MH061009 (J.S.S.). We acknowledge partial support from grants U54HG003273 (R.A.G.) and U54HG003067 (E. Lander). We thank T. Lehner (NIMH), A. Felsenfeld (National Human Genome Research Institute) and P. Bender (NIMH) for their support and contribution to the project. E.B., J.D.B., B.D., M.J.D., R.A.G., K. Roeder, A.S., G.D.S. and J.S.S. are lead investigators in the ARRA Autism Sequencing Collaboration (AASC). We would also like to thank the NHLBI GO Exome Sequencing Project (ESP) and its ongoing studies that produced and provided exome variant calls on the web: the Lung GO Sequencing Project (HL-102923), the Women's Health Initiative (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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PD SEP PY 2014 VL 46 IS 9 BP 944 EP + DI 10.1038/ng.3050 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AO8CE UT WOS:000341579400007 PM 25086666 ER PT J AU Lopez-Pison, J Garcia-Jimenez, MC Monge-Gatindo, L Lafuente-Hidalgo, M Perez-Delgado, R Garcia-Oguiza, A Pena-Segura, JL AF Lopez-Pison, J. Garcia-Jimenez, M. C. Monge-Gatindo, L. Lafuente-Hidalgo, M. Perez-Delgado, R. Garcia-Oguiza, A. Pena-Segura, J. L. TI Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006-2010 SO NEUROLOGIA LA Spanish DT Article DE Global developmental delay; Intellectual disability; Microarray comparative genomic hybridisation ID QUALITY-STANDARDS-SUBCOMMITTEE; CHILD-NEUROLOGY-SOCIETY; MENTAL-RETARDATION; NEUROPAEDIATRIC ATTENTION; GENETIC EVALUATION; PRACTICE-COMMITTEE; AMERICAN-ACADEMY; DEMAND AB Introduction: Global developmental delay (GDD) and intellectual disability (ID) are common reasons for consultation in paediatric neurology. Results from aetiological evaluations of children with GDD/ID vary greatly, and consequently, there is no universal consensus regarding which studies should be performed. Material and method: We review our experience with determining aetiological diagnoses for children with GDD/ID who were monitored by the paediatric neurology unit over the 5-year period between 2006 and 2010. Results: During the study period, 995 children with GDD/ID were monitored. An aetiological diagnosis was established for 309 patients (31%), but not in 686 (69%), despite completing numerous tests. A genetic cause was identified in 142 cases (46% of the total aetiologies established), broken down as 118 cases of genetic encephalopathy and 24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile spasms/West syndrome, or visual deficit, but more difficult in cases of autism spectrum disorders. Genetic studies provide an increasing number of aetiological diagnoses, and they are also becoming the first step in diagnostic studies. Array CGH (microarray-based comparative genomic hybridisation) is the genetic test with the highest diagnostic yield in children with unexplained GDD/ID. Discussion: The cost-effectiveness of complementary studies seems to be low if there are no clinically suspected entities. However, even in the absence of treatment, aetiological diagnosis is always important in order to provide genetic counselling and possible prenatal diagnosis, resolve family (and doctors') queries, and halt further diagnostic studies. (C) 2013 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U. All rights reserved. C1 [Lopez-Pison, J.; Monge-Gatindo, L.; Lafuente-Hidalgo, M.; Perez-Delgado, R.; Garcia-Oguiza, A.; Pena-Segura, J. L.] Hosp Univ Miguel Servet, Inst Aragones Ciencias Salud, Unidad Neuropediat, Zaragoza, Spain. [Garcia-Jimenez, M. 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TI In Utero Exposure to Valproic Acid Changes Sleep in Juvenile Rats: A Model for Sleep Disturbances in Autism SO SLEEP LA English DT Article DE autism spectrum disorders; sleep; valproic acid ID CONTROLLED-RELEASE MELATONIN; BASAL FOREBRAIN NEURONS; MESSENGER-RNA LEVELS; EYE-MOVEMENT SLEEP; SPECTRUM DISORDERS; ANIMAL-MODEL; PRENATAL EXPOSURE; TYPICAL DEVELOPMENT; ASPERGERS-DISORDER; FUTURE-DIRECTIONS AB Study Objectives: To determine whether sleep disturbances are found in the valproic acid model of autism spectrum disorders (ASD). Design: Comparative study for sleep behavior, sleep architecture, electroencephalogram (EEG) spectral analysis, and glutamic acid decarboxylase (GAD) 65/67 protein expression in juvenile rats exposed to valproic acid (VPA), sodium salt, or saline in utero. Setting: N/A. Participants: Juvenile (postnatal day 32) male and female Sprague-Dawley rats. Interventions: In utero exposure to either saline or 400 mg/kg VPA administered intraperitoneally to the dams on gestational day 12.5. On postnatal days 22-24, all rats were implanted with transmitters to record EEG and electromyogram (EMG) activity. Measurements and Results: During the light phase, when nocturnal animals are typically quiescent, the VPA-exposed animals spent significantly more time in wake (similar to 35 min) and significantly less time in non-rapid eye movement (NREM) sleep (similar to 26 min) compared to the saline controls. Furthermore, spectral analysis of the EEG reveled that VPA-exposed animals exhibited increased high-frequency activity during wake and rapid eye movement (REM) sleep and reduced theta power across all vigilance states. Interestingly, the gamma-aminobutyric acid (GABA)-ergic system, which modulates the induction and maintenance of sleep states, was also disrupted, with reduced levels of both GAD 65 and GAD67 in the cortical tissue of VPA-exposed animals compared to saline controls. Conclusions: To date, the current animal models of ASD have been underutilized in the investigation of associated sleep disturbances. The VPA animal model recapitulates aspects of sleep disruptions reported clinically, providing a tool to investigate cellular and molecular dysregulation contributing to sleep disruptions in ASD. C1 [Cusmano, Danielle M.; Mong, Jessica A.] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA. [Cusmano, Danielle M.; Mong, Jessica A.] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. RP Cusmano, DM (reprint author), Univ Maryland, Sch Med, 655 W Baltimore St,BRB Room 4-027, Baltimore, MD 21201 USA. EM dcusm001@umaryland.edu FU DOD Research Program [AR080087] FX This was not an industry supported study. Support was provided by a DOD Research Program AR080087 awarded to Dr. Mong. The authors have indicated no financial conflicts of interest. 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characterised by failure to generate and recognize self-reflective, cognitive-based emotions, such as pride, embarrassment and shame. Among this type of emotions, regret and disappointment, as well as their positive counterparts, result from a counterfactual comparison, that is the comparison between an actual value ("what is") and a fictive value ("what might have been"). However, while disappointment is experienced when the obtained outcome is worse than the expected outcome that might have occurred from the same choice, regret occurs when one experiences an outcome that is worse than the outcome of foregone choices. By manipulating a simple gambling task, we examined subjective reports on the intensity of negative and positive emotions in a group of adults with High-Functioning Autism or Asperger syndrome (HFA/AS), and a control group matched for age, gender and educational level. Participants were asked to choose between two lotteries with different levels of risk under two conditions of outcome feedback: (i) Partial, in which only the outcome of the chosen lottery was visible, (ii) Complete, in which the outcomes of the two lotteries were simultaneously visible. By comparing partial and complete conditions, we aimed to investigate the differential effect between disappointment and regret, as well as between their positive counterparts. Relative to the control participants (CP), the group with HFA/AS reported reduced regret and no difference between regret and disappointment, along with a preserved ability to use counterfactual thinking and similar choice behaviour. Difficulties to distinguish the feeling of regret in participants with HFA/AS can be explained by diminished emotional awareness, likely associated with an abnormal fronto-limbic connectivity. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Zalla, Tiziana] Ecole Normale Super, CNRS, Inst Jean Nicod, Dept Etudes Cognit, Paris, France. [Sirigu, Angela] CNRS, Ctr Neurosci Cognit, UMR 5229, Bron, France. [Robic, Suzanne] Univ Lyon 1, CNRS UMR 5292, INSERM U1028, Lyon Neurosci Res Ctr,Brain Dynam & Cognit Team, F-69365 Lyon, France. [Chaste, Pauline; Leboyer, Marion] Univ Paris Est Creteil, AP HP, Henri Mondor Albert Chenevier Hosp,IMRB,Dept Psyc, French Natl Sci Fdn,Fdn FondaMental,INSERM U 955, Creteil, France. [Coricelli, Giorgio] Ecole Normale Super, Dept Etudes Cognit, INSERM U 960, Lab Neurosci Cognit, F-75231 Paris, France. [Coricelli, Giorgio] Univ So Calif, Dept Econ, Los Angeles, CA 90089 USA. RP Zalla, T (reprint author), Ecole Normale Super, CNRS, Inst Jean Nicod, 29 Rue Ulm, Paris, France. EM tiziana.zalla@ens.fr FU Fondation FondaMental; Fondation Orange FX We gratefully acknowledge the commitment of the participants and their families to the pursuit of research in autism. 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TI The Broader Autism Phenotype, Social Interaction Anxiety, and Loneliness: Implications for Social Functioning SO CURRENT PSYCHOLOGY LA English DT Article DE Broader autism phenotype; Social interaction anxiety; Loneliness; Social functioning; Personality ID SPECTRUM QUOTIENT AQ; PERSONALITY-DISORDERS; RELIABILITY; POPULATION; SIBLINGS; VERSION; TRAITS; PHOBIA; HEALTH; FAMILY AB Recent research has begun to focus on the subclinical presentation of autistic-like traits in individuals, a construct termed the broader autism phenotype (BAP). The presence of the BAP has been established in both first-degree relatives of individuals with autism as well as in the general population. The current study aimed to examine how self-reported BAP characteristics, social interaction anxiety, and fear of negative evaluation relate to social functioning (specifically, loneliness) in a sample of college students. Results showed that for all subjects, BAP, social interaction anxiety, and fear of negative evaluation did not predict loneliness in a regression model. However, for males these predictors accounted for approximately 48 % of the variance in loneliness scores. Among males, individuals rating themselves as having lower social skills, lower imagination, and higher social interaction anxiety were more likely to also report feeling lonely. These results indicate that the predictors used may function differently among males and females. Although BAP characteristics and social interaction anxiety may not be important correlates of social functioning for females in this sample, they appear to be very important for males' subjective feelings of loneliness. C1 [Lamport, Dustin; Zlomke, Kimberly R.] Univ S Alabama, Dept Psychol, Mobile, AL 36688 USA. RP Zlomke, KR (reprint author), 307 Univ Blvd North,UCOM 1000, Mobile, AL 36688 USA. 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Psychol. PD SEP PY 2014 VL 33 IS 3 BP 246 EP 255 DI 10.1007/s12144-014-9210-0 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AO6AH UT WOS:000341429200002 ER PT J AU Fannemel, M Baroy, T Holmgren, A Rodningen, OK Haugsand, TM Hansen, B Frengen, E Misceo, D AF Fannemel, Madeleine Baroy, Tuva Holmgren, Asbjorn Rodningen, Olaug K. Haugsand, Trine M. Hansen, Borre Frengen, Eirik Misceo, Doriana TI Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a patient with mild intellectual disability and cranio-facial dysmorphisms SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Congenital anomalies; Dysmorphic features; Intellectual disability; USP34; XPO1 or CRM1; 2p15p16.1 Deletion syndrome ID RECOGNIZED MICRODELETION SYNDROME; MB DELETION; 2P15-P16.1; 2P15-16.1; 2P15P16.1; SPECTRUM; FEATURES; REGION AB 2p15p16.1-deletion syndrome was first described in 2007 based on the clinical presentation of two patients. The syndrome is characterized by intellectual disability, autism spectrum disorders, microcephaly, dysmorphic facial features and a variety of congenital organ defects. The precise genotype-phenotype correlation in 2p15-deletion syndrome is not understood. However, greater insight can be obtained by thorough clinical investigation of patients carrying deletions, especially those of small size. We report a 21-year-old male patient with features overlapping the clinical spectrum of the 2p15p16.1-deletion syndrome, such as intellectual disability, dysmorphic facial features, and congenital defects. He carried a 230 kb de novo deletion (chr2:61500346-61733075 bp, hg19), which affects the genes USP34, SNORA70B and XPO1. While there is a lack of functional data on SNORA70B, the involvement of USP34 and XPO1 in the regulation of fundamental developmental processes is well known. We suggest that haploinsufficiency of one or both of these genes is likely to be responsible for the disease in our patient. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Fannemel, Madeleine; Baroy, Tuva; Holmgren, Asbjorn; Rodningen, Olaug K.; Frengen, Eirik; Misceo, Doriana] Univ Oslo, Dept Med Genet, N-0315 Oslo, Norway. [Fannemel, Madeleine; Baroy, Tuva; Holmgren, Asbjorn; Rodningen, Olaug K.; Frengen, Eirik; Misceo, Doriana] Oslo Univ Hosp, Oslo, Norway. [Haugsand, Trine M.; Hansen, Borre] Akershus Univ Hosp, Dept Adult Habilitat, Oslo, Norway. RP Misceo, D (reprint author), Univ Oslo, Dept Med Genet, POB 1036, N-0315 Oslo, Norway. EM uxmafa@ous-hf.no; tuva.baroy@medisin.uio.no; asbjorn.holmgren@medisin.uio.no; uxrdol@ous-hf.no; trine.haugsand@ahus.no; borre.hansen@ahus.no; eirik.frengen@medisin.uio.no; doriana.misceo@medisin.uio.no FU Southeastern Regional Health Authorities [2011071]; Ulleval University Hospital Research Fund (VIRUUS); Anders Jahres fond til vitenskapens fremme FX We would like to thank the family for collaboration and contribution to this project. We are grateful to Dr. William Louch for language revision of the manuscript. This work was supported by a grant from the Southeastern Regional Health Authorities (project no 2011071), Ulleval University Hospital Research Fund (VIRUUS), and DM was supported by "Anders Jahres fond til vitenskapens fremme". 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J. Med. Genet. PD SEP PY 2014 VL 57 IS 9 BP 513 EP 519 DI 10.1016/j.ejmg.2014.05.008 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AO5DS UT WOS:000341363100006 PM 24911659 ER PT J AU Rosello, M Martinez, F Monfort, S Mayo, S Oltra, S Orellana, C AF Rosello, Monica Martinez, Francisco Monfort, Sandra Mayo, Sonia Oltra, Silvestre Orellana, Carmen TI Phenotype profiling of patients with intellectual disability and copy number variations SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE Intellectual disability; Array-CGH; Phenotype; Clinical database ID COMPARATIVE GENOMIC HYBRIDIZATION; CLINICAL DIAGNOSTIC-TEST; MENTAL-RETARDATION; CHROMOSOMAL MICROARRAY; ARRAY-CGH; SUBTELOMERIC REARRANGEMENTS; DEVELOPMENTAL-DISABILITIES; DYSMORPHIC FEATURES; AMERICAN-COLLEGE; IMBALANCES AB Background: Nowadays the microarray technology allows whole-genome analysis with a high resolution and performance for the genetic diagnosis in any patient with intellectual disability or autism spectrum disorder. However in the immediate future, with the development of massive sequencing systems for application at clinical diagnosis, it will be necessary to have clinical criteria to guide studies. Aim: To perform an exhaustive clinical definition of patients with pathogenic copy number variations in order to establish the clinical criteria most suggestive of this kind of genomic rearrangements. Method: We designed and implemented a database to collect 190 different clinical variables (pregnancy, neonatal, facial dysmorphism, congenital anomalies, neurological features and family history) in a series of 246 patients, with developmental delay/intellectual disability. All cases were studied with array comparative genomic hybridization. Results: We have found a pathogenic genomic imbalance in 73 patients. Frequency analysis of all clinical variables showed that growth disorder, abnormalities of hands, low-set ears and hypertelorism are the more frequent features among patients with genomic rearrangements. However other clinical features, such as genital abnormalities and aggressiveness, are more specifically associated with pathogenic copy number variations in spite of their low frequencies in the overall series, yielding higher statistical significance values than other traits. Conclusions: The genotype phenotype comparison may be useful to set in the future the main clinical manifestations associated with deletions, duplications and unbalanced translocations. Theses analyses will improve the clinical indications and protocols to implement genomic arrays in the genetic study of patients with neurodevelopment disorders. (C) 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Rosello, Monica; Martinez, Francisco; Monfort, Sandra; Mayo, Sonia; Oltra, Silvestre; Orellana, Carmen] Hosp Univ & Politecn La Fe, Unidad Genet & Diagnost Prenatal, Valencia 46009, Spain. RP Rosello, M (reprint author), Hosp Univ & Politecn La Fe, Unidad Genet & Diagnost Prenatal, Ave Campanar 21, Valencia 46009, Spain. EM rosello_mpi@gva.es RI Monfort, Sandra/B-2860-2009; Rosello, Monica/B-2319-2009; Orellana, Carmen/B-1925-2009; Oltra, Silvestre/A-2697-2009; Martinez, Francisco/A-2543-2009 OI Rosello, Monica/0000-0001-9234-2953; Orellana, Carmen/0000-0003-4271-5859; Oltra, Silvestre/0000-0001-6863-4382; Martinez, Francisco/0000-0002-0589-2584 FU Instituto de Salud Carlos III [RD09/0076/00021]; Fundacion para la Investigacion del Hospital La Fe/Fundacion Bancaja fellowship; Fundacion Ramon Areces [PI 2009/0093]; National Public Agencies [PI04/0421, PI08/0648]; Autonomics [AP-096/06, AP-138/11] FX This work has been possible thanks to the collaboration of patients and families, the health professionals who referred the patients, the staff of the Genetics Unit of the Hospital Universitari i Politecnic "La Fe" and the aid received through grants of private agencies (Fundacion Ramon Areces PI 2009/0093) and National Public Agencies (PI04/0421, PI08/0648) and Autonomics (AP-096/06, AP-138/11). This study was supported in part by research funding from the "Instituto de Salud Carlos III" grant: "Red de Biobancos Hospitalarios" (RD09/0076/00021). Sonia Mayo was supported by the Fundacion para la Investigacion del Hospital La Fe/Fundacion Bancaja fellowship. 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J. Paediatr. Neurol. PD SEP PY 2014 VL 18 IS 5 BP 558 EP 566 DI 10.1016/j.ejpn.2014.04.010 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AO7SG UT WOS:000341552300002 PM 24815074 ER PT J AU Moses, L Katz, N Weizman, A AF Moses, L. Katz, N. Weizman, A. TI Metabolic profiles in adults with autism spectrum disorder and intellectual disabilities SO EUROPEAN PSYCHIATRY LA English DT Article DE Autism; Intellectual disabilities; Cholesterol; Glucose; Metabolic profile ID SERUM-CHOLESTEROL LEVEL; DOWNS-SYNDROME; ANTIPSYCHOTIC-DRUGS; LIPIDS; LIPOPROTEINS; HYPERCHOLESTEROLEMIA; SCHIZOPHRENIA; HYPERTENSION; ASSOCIATION; ADOLESCENTS AB Introduction: Low levels of blood cholesterol have been found in some children with autism spectrum disorders (ASD). Psychotropic medications, commonly used by people with ASD and people with intellectual disabilities (ID) are frequently associated with altered metabolic profiles. Purpose: We aimed to compare metabolic features of adults with ASD or ID with those of a community-based population. Subjects and methods: Data on blood fasting glucose (FBG), lipid profile, liver enzyme profile, TSH, BMI, medications and diagnoses of 80 adults with ASD, 77 adults with ID and 828 control adults were drawn from medical charts/database. Candidates that used glucose or lipid lowering medications were not included. Results: Total-cholesterol levels of people with ASD and ID were significantly lower than those of the controls (168.3 +/- 32.78, 168.2 +/- 32.91, 185.4 +/- 40.49 mg/dL, respectively, P < 0.001) but after adjusting for gender, age and BMI and using Bonferroni correction, the significance was lost. Compared to controls, ASD and ID had significantly lower FBG (by -14.45 +/- 1.81, -14.58 +/- 1.54 mg/dl, respectively; P < 0.001 for both) and liver enzymes, despite using psychotropic medications. Discussion and conclusion: In contrast to other psychiatric patients receiving similar medications, people with ASD and ID have unaltered lipid profiles and lower glucose and liver enzyme levels compared to a community-based population. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [Moses, L.] Minist Social Affairs & Social Serv, Div Intellectual & Dev Disabil, Hlth Serv, Jerusalem, Israel. [Moses, L.] Maccabi Hlth Serv, South Dist, Israel. [Katz, N.; Weizman, A.] Tel Aviv Univ, Petah Tikva & Sackler Fac Med, Geha Mental Hlth Ctr, IL-69978 Tel Aviv, Israel. [Weizman, A.] Tel Aviv Univ, Sackler Fac Med, Felsenstein Med Res Ctr, Lab Biol Psychiat, Petah Tiqwa, Israel. RP Moses, L (reprint author), Moshav Nir Hen 4, IL-79330 Rehovot, Israel. 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Psychiat. PD SEP PY 2014 VL 29 IS 7 BP 397 EP 401 DI 10.1016/j.eurpsy.2013.05.005 PG 5 WC Psychiatry SC Psychiatry GA AO5OR UT WOS:000341395000001 PM 23849396 ER PT J AU Groskreutz, NC Groskreutz, MP Bloom, SE Slocum, TA AF Groskreutz, Nicole C. Groskreutz, Mark P. Bloom, Sarah E. Slocum, Timothy A. TI Generalization of negatively reinforced mands in children with autism SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; manding; functional communication; negative reinforcement; stimulus generalization ID FUNCTIONAL COMMUNICATION; PROBLEM BEHAVIOR; DEVELOPMENTAL-DISABILITIES AB Each day, people encounter stimuli they find unpleasant. Some children with autism may require systematic instruction to acquire the communication skills necessary to request the termination of such aversive stimuli. We taught 2 school-aged boys with autism a mand (e.g., signing stop) that could be used to escape a variety of aversive stimuli. First, we employed a systematic assessment to identify aversive stimuli to use during training. We then conducted mand training sequentially across those stimuli until sufficient exemplars were trained for generalization to occur to untrained stimuli. For both participants, cross-stimulus generalization was observed after training with 2 stimuli. Participants manded for escape in the presence of aversive stimuli, but almost never manded in the presence of preferred stimuli or when the programmed stimuli were absent. In addition, we found an inverse relation between acquisition of the mand and engagement in problem behavior and evidence of generalization to nontraining contexts. C1 [Groskreutz, Nicole C.; Bloom, Sarah E.; Slocum, Timothy A.] Utah State Univ, Logan, UT 84322 USA. [Groskreutz, Mark P.] So Connecticut State Univ, New Haven, CT USA. RP Slocum, TA (reprint author), Dept Special Educ & Rehabil, 2865 Old Main Hill, Logan, UT 84322 USA. 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PD FAL PY 2014 VL 47 IS 3 BP 560 EP 579 DI 10.1002/jaba.151 PG 20 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100008 PM 25087550 ER PT J AU Rispoli, M Camargo, S Machalicek, W Lang, R Sigafoos, J AF Rispoli, Mandy Camargo, Siglia Machalicek, Wendy Lang, Russell Sigafoos, Jeff TI Functional communication training in the treatment of problem behavior maintained by access to rituals SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; functional communication training; extinction; schedule thinning; resurgence ID AUTISM SPECTRUM DISORDER; OBSESSIVE-COMPULSIVE DISORDER; DIFFERENTIAL REINFORCEMENT; CHALLENGING BEHAVIOR; DEVELOPMENTAL-DISABILITIES; REPETITIVE BEHAVIORS; DESTRUCTIVE BEHAVIOR; ESCAPE BEHAVIOR; EXTINCTION; INTERVENTION AB This study evaluated the assessment and treatment of problem behaviors related to rituals for children with autism. After functional analyses, we used a multiple-probe design to examine the effects of functional communication training (FCT) plus extinction and schedule thinning as a treatment package for problem behavior and appropriate communication for 3 children. Results of the functional analyses suggested that problem behavior was maintained by reinstatement of the interrupted routine for all participants, and the treatment package reduced problem behavior. Generalization across activities was observed for 1 participant. C1 [Rispoli, Mandy; Camargo, Siglia] Texas A&M Univ, College Stn, TX 77843 USA. [Machalicek, Wendy] Univ Oregon, Eugene, OR 97403 USA. [Lang, Russell] Texas State Univ, Clin Autism Res Evaluat & Support, Round Rock, TX 78655 USA. [Sigafoos, Jeff] Victoria Univ Wellington, Wellington, New Zealand. RP Rispoli, M (reprint author), 4225 Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. 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Appl. Behav. Anal. PD FAL PY 2014 VL 47 IS 3 BP 580 EP 593 DI 10.1002/jaba.130 PG 14 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100009 PM 24817482 ER PT J AU Grow, LL Kodak, T Carr, JE AF Grow, Laura L. Kodak, Tiffany Carr, James E. TI A comparison of methods for teaching receptive labeling to children with autism spectrum disorders: A systematic replication SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; conditional discrimination training; receptive language; stimulus control AB Previous research has demonstrated that the conditional-only method (starting with a multiple-stimulus array) is more efficient than the simple-conditional method (progressive incorporation of more stimuli into the array) for teaching receptive labeling to children with autism spectrum disorders (Grow, Carr, Kodak, Jostad, & Kisamore, ). The current study systematically replicated the earlier study by comparing the 2 approaches using progressive prompting with 2 boys with autism. The results showed that the conditional-only method was a more efficient and reliable teaching procedure than the simple-conditional method. The results further call into question the practice of teaching simple discriminations to facilitate acquisition of conditional discriminations. C1 [Grow, Laura L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kodak, Tiffany] Univ Oregon, Eugene, OR 97403 USA. RP Grow, LL (reprint author), Dept Educ & Counselling Psychol & Special Educ, 2125 Main Mall, Vancouver, BC V6T 1Z4, Canada. EM laura.grow@ubc.ca CR DeLeon IG, 1996, J APPL BEHAV ANAL, V29, P519, DOI 10.1901/jaba.1996.29-519 DOYLE PM, 1989, RES DEV DISABIL, V10, P349, DOI 10.1016/0891-4222(89)90036-X Green G., 2001, FOCUS AUTISM OTHER D, V16, P72, DOI 10.1177/108835760101600203 Grow LL, 2011, J APPL BEHAV ANAL, V44, P475, DOI 10.1901/jaba.2011.44-475 Gutierrez A, 2009, RES AUTISM SPECT DIS, V3, P630, DOI 10.1016/j.rasd.2008.12.005 Johnston SS, 2009, AUGMENT ALTERN COMM, V25, P136, DOI 10.1080/07434610902921516 Lovaas O. I., 2003, TEACHING INDIVIDUALS Love JR, 2009, RES AUTISM SPECT DIS, V3, P421, DOI 10.1016/j.rasd.2008.08.008 Martin G. L., 2000, J DEV DISABILITIES, V7, P10 NR 9 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD FAL PY 2014 VL 47 IS 3 BP 600 EP 605 DI 10.1002/jaba.141 PG 6 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100011 PM 24902513 ER PT J AU Ward-Horner, JC Pittenger, A Pace, G Fienup, DM AF Ward-Horner, John C. Pittenger, Alexis Pace, Gary Fienup, Daniel M. TI Effects of reinforcer magnitude and distribution on preference for work schedules SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE preference; choice; autism; concurrent-chains arrangements; reinforcement magnitude ID QUALITY AB When the overall magnitude of reinforcement is matched between 2 alternative work schedules, some students prefer to complete all of their work for continuous access to a reinforcer (continuous work) rather than distributed access to a reinforcer while they work (discontinuous work). We evaluated a student's preference for continuous work by manipulating the overall magnitude of reinforcement associated with continuous work. Preference for continuous work persisted despite a 20% decrease in reinforcer magnitude; however, a 40% decrease in reinforcer magnitude produced a shift in preference to discontinuous work. C1 [Ward-Horner, John C.] Beacon ABA Serv Inc, Milford, MA 01757 USA. [Ward-Horner, John C.; Pittenger, Alexis; Pace, Gary] May Ctr Educ & Neurorehabil, Brockton, MA USA. [Fienup, Daniel M.] CUNY Queens Coll, New York, NY USA. RP Ward-Horner, JC (reprint author), Beacon ABA Serv Inc, 321 Fortune Blvd, Milford, MA 01757 USA. EM wardhornerj@gmail.com CR DeLeon I. G., 2014, J APPL BEHAV ANAL, V47 Fienup DM, 2011, J APPL BEHAV ANAL, V44, P847, DOI 10.1901/jaba.2011.44-847 Fisher WW, 1997, J APPL BEHAV ANAL, V30, P387, DOI 10.1901/jaba.1997.30-387 Hanley GP, 2005, J APPL BEHAV ANAL, V38, P51, DOI 10.1901/jaba.2005.6-04 Hanley GP, 1997, J APPL BEHAV ANAL, V30, P459, DOI 10.1901/jaba.1997.30-459 Hoch H, 2002, J APPL BEHAV ANAL, V35, P171, DOI 10.1901/jaba.2002.35-171 Mace FC, 1996, J APPL BEHAV ANAL, V29, P11, DOI 10.1901/jaba.1996.29-11 Roane HS, 1998, J APPL BEHAV ANAL, V31, P605, DOI 10.1901/jaba.1998.31-605 NR 8 TC 2 Z9 2 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 FAL PY 2014 VL 47 IS 3 BP 623 EP 627 DI 10.1002/jaba.133 PG 5 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100015 PM 24825241 ER PT J AU Roane, HS DeRosa, NM AF Roane, Henry S. DeRosa, Nicole M. TI Reduction of emergent dropping behavior during treatment of elopement SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; dropping; elopement ID RESPONSE-CLASS HIERARCHIES; COMMUNICATION; REINFORCERS; DISORDERS AB Although treatments for elopement (leaving an assigned area or a caregiver without permission) and dropping (falling to the floor) have been reported in the literature, there are no studies that have examined the concurrent treatment of these behaviors. The current investigation reports on the emergence and treatment of dropping during the treatment of elopement. C1 [Roane, Henry S.; DeRosa, Nicole M.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Roane, HS (reprint author), Dept Pediat, 600 E Genesee St,Suite 130, Syracuse, NY 13202 USA. EM roaneh@upstate.edu CR Anderson C, 2012, PEDIATRICS, V130, P870, DOI 10.1542/peds.2012-0762 Betz AM, 2013, J APPL BEHAV ANAL, V46, P219, DOI 10.1002/jaba.23 Bowman LG, 1997, J APPL BEHAV ANAL, V30, P451, DOI 10.1901/jaba.1997.30-451 DeLeon IG, 1996, J APPL BEHAV ANAL, V29, P519, DOI 10.1901/jaba.1996.29-519 DeRosa NM, 2013, J DEV PHYS DISABIL, V25, P119, DOI 10.1007/s10882-012-9312-2 FISHER W, 1992, J APPL BEHAV ANAL, V25, P491, DOI 10.1901/jaba.1992.25-491 FRIMAN PC, 1987, J APPL BEHAV ANAL, V20, P421, DOI 10.1901/jaba.1987.20-421 Hagopian LP, 2003, BEHAV INTERVENT, V18, P291, DOI 10.1002/bin.140 HERBERT EW, 1973, J APPL BEHAV ANAL, V6, P15 Lalli JS, 1995, J APPL BEHAV ANAL, V28, P551, DOI 10.1901/jaba.1995.28-551 Lieving GA, 2004, PSYCHOL REC, V54, P621 Mace FC, 2011, J APPL BEHAV ANAL, V44, P83, DOI 10.1901/jaba.2011.44-83 Richman DM, 1999, J APPL BEHAV ANAL, V32, P269, DOI 10.1901/jaba.1999.32-269 SAJWAJ T, 1972, J APPL BEHAV ANAL, V5, P163, DOI 10.1901/jaba.1972.5-163 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 FAL PY 2014 VL 47 IS 3 BP 633 EP 638 DI 10.1002/jaba.136 PG 6 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100017 PM 24825372 ER PT J AU Brodhead, MT Higbee, TS Pollard, JS Akers, JS Gerencser, KR AF Brodhead, Matthew T. Higbee, Thomas S. Pollard, Joy S. Akers, Jessica S. Gerencser, Kristina R. TI The use of linked activity schedules to teach children with autism to play hide-and-seek SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE activity schedules; autism; social interactions AB Linked activity schedules were used to establish appropriate game play in children with autism during a game of hide-and-seek. All 6 participants demonstrated acquisition of appropriate play skills in the presence of the activity schedules and maintained responding during subsequent phases. When the schedules were removed, responding decreased to baseline levels, demonstrating that the schedules controlled responding. Implications for future research on the use of activity schedules to teach social behavior are discussed. C1 [Brodhead, Matthew T.; Higbee, Thomas S.; Pollard, Joy S.; Akers, Jessica S.; Gerencser, Kristina R.] Utah State Univ, Logan, UT 84332 USA. RP Higbee, TS (reprint author), Utah State Univ, 2865 Old Main Hill, Logan, UT 84332 USA. EM tom.higbee@usu.edu CR Betz A, 2008, J APPL BEHAV ANAL, V41, P237, DOI 10.1901/jaba.2008.41-237 Cooper J. O., 2007, APPL BEHAV ANAL Koyama T, 2011, RES DEV DISABIL, V32, P2235, DOI 10.1016/j.ridd.2011.05.003 MACDUFF GS, 1993, J APPL BEHAV ANAL, V26, P89, DOI 10.1901/jaba.1993.26-89 McClannahan L. E., 1999, ACTIVITY SCHEDULES C NR 5 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD FAL PY 2014 VL 47 IS 3 BP 645 EP 650 DI 10.1002/jaba.145 PG 6 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100019 PM 24905481 ER PT J AU Hoffman, K Falcomata, TS AF Hoffman, Katherine Falcomata, Terry S. TI An evaluation of resurgence of appropriate communication in individuals with autism who exhibit severe problem behavior SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; clinical relapse; mands; problem behavior; resurgence ID EXTINCTION AB We evaluated resurgence of mands exhibited by 3 individuals with autism and histories of problem behavior. The experimental conditions consisted of (a) reinforcement of a mand, (b) extinction, (c) reinforcement of a 2nd mand, and (d) extinction to test for resurgence of the 1st mand. This 4-component sequence was implemented 3 times with each participant, and resurgence occurred during 8 of 9 tests for resurgence. Results are discussed in terms of implications for the prevention of clinical relapse. C1 Univ Texas Austin, Austin, TX 78712 USA. RP Falcomata, TS (reprint author), Univ Texas Austin, Dept Special Educ, 1 Univ Stn D5300, Austin, TX 78712 USA. EM falcomata@mail.utexas.edu CR Bruzek JL, 2009, J EXP ANAL BEHAV, V92, P327, DOI 10.1901/jeab.2009-92-327 EPSTEIN R, 1983, BEHAV ANAL LETT, V3, P391 Lieving GA, 2003, J EXP ANAL BEHAV, V80, P217, DOI 10.1901/jeab.2003.80-217 Lieving GA, 2004, PSYCHOL REC, V54, P621 Reed P, 2006, J EXP ANAL BEHAV, V86, P307, DOI 10.1901/jeab.2006.20-05 Roane HS, 1998, J APPL BEHAV ANAL, V31, P605, DOI 10.1901/jaba.1998.31-605 St Peter Pipkin C., 2010, J APPL BEHAV ANAL, V43, P47, DOI [10.1901/jaba.2010.43-47, DOI 10.1901/JABA.2010.43-47] Volkert VM, 2009, J APPL BEHAV ANAL, V42, P145, DOI 10.1901/jaba.2009.42-145 Wacker DP, 2011, J EXP ANAL BEHAV, V96, P261, DOI 10.1901/jeab.2011.96-261 NR 9 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 FAL PY 2014 VL 47 IS 3 BP 651 EP 656 DI 10.1002/jaba.144 PG 6 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100020 PM 24910326 ER PT J AU Majdalany, LM Wilder, DA Greif, A Mathisen, D Saini, V AF Majdalany, Lina M. Wilder, David A. Greif, Abigail Mathisen, David Saini, Valdeep TI Comparing massed-trial instruction, distributed-trial instruction, and task interspersal to teach tacts to children with autism spectrum disorders SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE discrete-trial instruction; autism spectrum disorders; skill acquisition AB Although massed-trial instruction, distributed-trial instruction, and task interspersal have been shown to be effective methods of teaching skills to children with autism spectrum disorders, they have not been directly compared. In the current study, we taught 6 children to tact shapes of countries using these methods to determine which would result in the quickest acquisition. Five of the 6 participants acquired the targets in the massed-trial condition before the other 2 conditions. C1 Florida Inst Technol, Melbourne, FL 32901 USA. RP Wilder, DA (reprint author), Florida Inst Technol, Sch Behav Anal, 150 West Univ Blvd, Melbourne, FL 32901 USA. EM dawilder@fit.edu CR Bambara L. M., 1993, STRATEGIES TEACHING, P165 Chiara L, 1995, J EARLY INTERVENTION, V19, P203 Sundberg M. L., 2008, VB MAPP VERBAL BEHAV Volkert VM, 2008, J APPL BEHAV ANAL, V41, P335, DOI 10.1901/jaba.2008.41-335 NR 4 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8855 EI 1938-3703 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD FAL PY 2014 VL 47 IS 3 BP 657 EP 662 DI 10.1002/jaba.149 PG 6 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100021 PM 24988891 ER PT J AU Sham, E Smith, T AF Sham, Elyssa Smith, Tristram TI Publication bias in studies of an applied behavior-analytic intervention: An initial analysis SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE publication bias; behavior analysis; single-subject research; autism; pivotal response treatment AB Publication bias arises when studies with favorable results are more likely to be reported than are studies with null findings. If this bias occurs in studies with single-subject experimental designs (SSEDs) on applied behavior-analytic (ABA) interventions, it could lead to exaggerated estimates of intervention effects. Therefore, we conducted an initial test of bias by comparing effect sizes, measured by percentage of nonoverlapping data (PND), in published SSED studies (n=21) and unpublished dissertations (n=10) on 1 well-established intervention for children with autism, pivotal response treatment (PRT). Although published and unpublished studies had similar methodologies, the mean PND in published studies was 22% higher than in unpublished studies, 95% confidence interval (4%, 38%). Even when unpublished studies are included, PRT appeared to be effective (PNDM=62%). Nevertheless, the disparity between published and unpublished studies suggests a need for further assessment of publication bias in the ABA literature. C1 [Sham, Elyssa; Smith, Tristram] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Smith, T (reprint author), Univ Rochester, Div Neurodev & Behav Pediat, Dept Pediat, Med Ctr, 601 Elmwood Ave,Box 671, Rochester, NY 14642 USA. EM Tristram_Smith@URMC.Rochester.edu NR 0 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 FAL PY 2014 VL 47 IS 3 BP 663 EP 678 DI 10.1002/jaba.146 PG 16 WC Psychology, Clinical SC Psychology GA AO7EE UT WOS:000341514100022 PM 24990802 ER PT J AU Uppal, N Wicinski, B Buxbaum, JD Heinsen, H Schmitz, C Hof, PR AF Uppal, Neha Wicinski, Bridget Buxbaum, Joseph D. Heinsen, Helmut Schmitz, Christoph Hof, Patrick R. TI Neuropathology of the Anterior Midcingulate Cortex in Young Children With Autism SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Anterior cingulate cortex; Anterior midcingulate cortex; Autism; Neuropathology; Stereology; von Economo neuron ID VON ECONOMO NEURONS; POSITRON-EMISSION-TOMOGRAPHY; CINGULATE CORTEX; PREFRONTAL CORTEX; PYRAMIDAL NEURONS; CEREBRAL-CORTEX; WHITE-MATTER; SPECTRUM DISORDER; COGNITIVE CONTROL; RHESUS-MONKEY AB The anterior cingulate cortex, which is involved in cognitive and affective functioning, is important in investigating disorders in which individuals exhibit impairments in higher-order functions. In this study, we examined the anterior midcingulate cortex (aMCC) at the cellular level in patients with autism and in controls. We focused our analysis on layer V of the aMCC because it contains von Economo neurons, specialized cells thought to be involved in emotional expression and focused attention. Using a stereologic approach, we determined whether there were neuropathologic changes in von Economo neuron number, pyramidal neuron number, or pyramidal neuron size between diagnostic groups. When the groups were subdivided into young children and adolescents, pyramidal neuron and von Economo neuron numbers positively correlated with autism severity in young children, as measured by the Autism Diagnostic Interview-Revised. Young children with autism also had significantly smaller pyramidal neurons than their matched controls. Because the aMCC is involved in decision-making during uncertain situations, decreased pyramidal neuron size may reflect a potential reduction in the functional connectivity of the aMCC. C1 [Uppal, Neha; Wicinski, Bridget; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Uppal, Neha; Wicinski, Bridget; Buxbaum, Joseph D.; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Uppal, Neha; Buxbaum, Joseph D.; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Uppal, Neha; Buxbaum, Joseph D.; Hof, Patrick R.] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Heinsen, Helmut] Univ Wurzburg, Dept Psychiat, Morphol Brain Res Unit, Wurzburg, Germany. [Schmitz, Christoph] Univ Munich, Dept Neuroanat, Munich, Germany. RP Hof, PR (reprint author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, One Gustave L Levy Pl,Box 1639, New York, NY 10029 USA. EM patrick.hof@mssm.edu FU Seaver Foundation; Autism Speaks (Autism Celloidin Library); James S. McDonnell Foundation; Simons Foundation FX This work was supported by the Seaver Foundation (NU, JDB, PRH), Autism Speaks (Autism Celloidin Library, PRH), the James S. McDonnell Foundation (PRH), and the Simons Foundation (PRH, JDB). 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Neuropathol. Exp. Neurol. PD SEP PY 2014 VL 73 IS 9 BP 891 EP 902 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AO5PW UT WOS:000341398300008 PM 25101703 ER PT J AU Reynolds, LC Inder, TE Neil, JJ Pineda, RG Rogers, CE AF Reynolds, L. C. Inder, T. E. Neil, J. J. Pineda, R. G. Rogers, C. E. TI Maternal obesity and increased risk for autism and developmental delay among very preterm infants SO JOURNAL OF PERINATOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; BODY-MASS INDEX; NEURODEVELOPMENTAL OUTCOMES; MODIFIED CHECKLIST; GESTATIONAL-AGE; DISORDERS; CHILDREN; BORN; PREPREGNANCY; IMPAIRMENT AB OBJECTIVE: Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years. STUDY DESIGN: Maternal/infant dyads (n=62) born <= 30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment. RESULT: Maternal obesity was associated with positive screen for autism (odds ratio = 9.88, P=0.002) and lower composite language scores (beta = -9.36, (confidence interval = -15.11, -3.61), P=0.002). CONCLUSION: Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity. C1 [Reynolds, L. C.; Rogers, C. E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Reynolds, L. C.; Inder, T. E.; Pineda, R. G.; Rogers, C. E.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Inder, T. E.; Neil, J. J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Inder, T. E.; Neil, J. J.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Pineda, R. G.] Washington Univ, Sch Med, Program Occupat Therapy, St Louis, MO 63110 USA. RP Reynolds, LC (reprint author), Washington Univ, Sch Med, Dept Pediat, Campus Box 8116 660 S Euclid Ave, St Louis, MO 63110 USA. EM reynoldsL@wusm.wustl.edu FU National Institute of Health [ROI HD 057098]; Doris Duke Foundation; Washington University Intellectual and Developmental Disabilities Research Center [NIH/NICHD P30 HD062171]; National Center for Advancing Translational Sciences [UL1 TR000448, KL2 TR000450] FX We wish to acknowledge Karen Lukas RN (Washington University School of Medicine), Anthony Barton (Washington University School of Medicine), Jessica Conners (Washington University School of Medicine), Dimitrios Alexopolous MS (Washington University School of Medicine), Joe Ackerman, Jr (Washington University School of Medicine), Claudine Vavasseur MD (National Maternity Hospital, Dublin Ireland) and Han Tjoeng MD (University of Hawaii) who obtained informed consents and conducted patient-oriented responsibilities to support the success of this project. We also wish to thank all the families whose infants participated in this study. This project was supported by the National Institute of Health (ROI HD 057098), the Doris Duke Foundation, the Washington University Intellectual and Developmental Disabilities Research Center (NIH/NICHD P30 HD062171), and the UL1 TR000448, sub award KL2 TR000450 from the National Center for Advancing Translational Sciences. 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Perinatol. PD SEP PY 2014 VL 34 IS 9 BP 688 EP 692 DI 10.1038/jp.2014.80 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA AO5RS UT WOS:000341403600009 PM 24811227 ER PT J AU Daly, MB Pilarski, R Axilbund, JE Buys, SS Crawford, B Friedman, S Garber, JE Horton, C Kaklamani, V Klein, C Kohlmann, W Kurian, A Litton, J Madlensky, L Marcom, PK Merajver, SD Offit, K Pal, T Pasche, B Reiser, G Shannon, KM Swisher, E Voian, NC Weitzel, JN Whelan, A Wiesner, GL Dwyer, MA Kumar, R AF Daly, Mary B. Pilarski, Robert Axilbund, Jennifer E. Buys, Saundra S. Crawford, Beth Friedman, Susan Garber, Judy E. Horton, Carolyn Kaklamani, Virginia Klein, Catherine Kohlmann, Wendy Kurian, Allison Litton, Jennifer Madlensky, Lisa Marcom, P. Kelly Merajver, Sofia D. Offit, Kenneth Pal, Tuya Pasche, Boris Reiser, Gwen Shannon, Kristen Mahoney Swisher, Elizabeth Voian, Nicoleta C. Weitzel, Jeffrey N. Whelan, Alison Wiesner, Georgia L. Dwyer, Mary A. Kumar, Rashmi TI Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 1.2014 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID HAMARTOMA-TUMOR-SYNDROME; RILEY-RUVALCABA-SYNDROME; REVISED DIAGNOSTIC-CRITERIA; AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS DISEASE; GERMLINE PTEN MUTATIONS; SYNDROME PLEASE STAND; COWDEN-SYNDROME; CANCER; GENE AB During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome. C1 [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Pilarski, Robert] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pilarski, Robert] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Axilbund, Jennifer E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Crawford, Beth] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Garber, Judy E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Horton, Carolyn] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Kaklamani, Virginia] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Klein, Catherine] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Kurian, Allison] Stanford Canc Inst, Stanford, CA USA. [Litton, Jennifer] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Madlensky, Lisa] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Marcom, P. Kelly] Duke Canc Inst, Durham, NC USA. [Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Pal, Tuya] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Pasche, Boris] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Reiser, Gwen] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Shannon, Kristen Mahoney] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Swisher, Elizabeth] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Voian, Nicoleta C.] Roswell Pk Canc Inst, Buffalo, NY USA. [Weitzel, Jeffrey N.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Whelan, Alison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Whelan, Alison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Wiesner, Georgia L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. 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Natl. Compr. Cancer Netw. PD SEP PY 2014 VL 12 IS 9 BP 1326 EP 1338 PG 13 WC Oncology SC Oncology GA AO4ZM UT WOS:000341349900011 PM 25190698 ER PT J AU Lewis, S AF Lewis, Sian TI Brain-gut connection in autism? (vol 15, pg 564, 2014) SO NATURE REVIEWS NEUROSCIENCE LA English DT Correction CR LEWIS S, 2014, NATURE REVIEWS NEURO, V15, P564, DOI DOI 10.1038/NRN3806 NR 1 TC 0 Z9 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD SEP PY 2014 VL 15 IS 9 BP 565 EP 565 DI 10.1038/nrn3807 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AO4RR UT WOS:000341329600004 ER PT J AU van Elst, K Bruining, H Birtoli, B Terreaux, C Buitelaar, JK Kas, MJ AF van Elst, Kim Bruining, Hilgo Birtoli, Barbara Terreaux, Christian Buitelaar, Jan K. Kas, Martien J. TI Food for thought: Dietary changes in essential fatty acid ratios and the increase in autism spectrum disorders SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE AA; Autism spectrum disorders; Brain deficiency; Development; DHA; Diet; Docosahexaenoic acid; Humans; Mice; Omega-3; Omega-6; Polyunsaturated fatty acids; PUFA ID ALPHA-LINOLENIC ACID; PROLIFERATOR-ACTIVATED RECEPTORS; RANDOMIZED CONTROLLED-TRIAL; BRAIN DOCOSAHEXAENOIC ACID; LIPID OXIDATION-PRODUCTS; FISH-OIL SUPPLEMENTATION; CENTRAL-NERVOUS-SYSTEM; ARACHIDONIC-ACID; PPAR-ALPHA; IN-VIVO AB The last decades have shown a spectacular and partially unexplained rise in the prevalence of autism spectrum disorders (ASD). This rise in ASD seems to parallel changes in the dietary composition of fatty acids. This change is marked by the replacement of cholesterol by omega-6 (n-6) fatty acids in many of our food products, resulting in a drastically increased ratio of omega-6/omega-3 (n-6/n-3). In this context, we review the available knowledge on the putative role of fatty acids in neurodevelopment and describe how disturbances in n-6/n-3 ratios may contribute to the emergence of ASDs. Both clinical and experimental research is discussed. We argue that a change in the ratio of n-6/n-3, especially during early life, may induce developmental changes in brain connectivity, synaptogenesis, cognition and behavior that are directly related to ASD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [van Elst, Kim; Bruining, Hilgo; Kas, Martien J.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands. [Bruining, Hilgo] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, NL-3584 CG Utrecht, Netherlands. [Birtoli, Barbara; Terreaux, Christian] Vifor Pharma, Glattbrugg, Switzerland. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. RP Kas, MJ (reprint author), Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, Univ Weg 100, NL-3584 CG Utrecht, Netherlands. EM m.j.h.kas@umcutrecht.nl FU Innovative Medicines Initiative Joint Undertaking [115300]; European Union's Seventh Framework Program (FP7); Autism Speaks FX The research of EU-AIMS receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115300, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013), from the EFPIA companies in kind contribution and from Autism Speaks. 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Biobehav. Rev. PD SEP PY 2014 VL 45 BP 369 EP 378 DI 10.1016/j.neubiorev.2014.07.004 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AO6MQ UT WOS:000341466600028 PM 25025657 ER PT J AU Gipson, TT Gerner, G Srivastava, S Poretti, A Vaurio, R Hartman, A Johnston, MV AF Gipson, Tanjala T. Gerner, Gwendolyn Srivastava, Siddharth Poretti, Andrea Vaurio, Rebecca Hartman, Adam Johnston, Michael V. TI Early Neurodevelopmental Screening in Tuberous Sclerosis Complex: A Potential Window of Opportunity SO PEDIATRIC NEUROLOGY LA English DT Article DE development; tuberous sclerosis; vigabatrin; everolimus; sirolimus; cognition; Capute Scales; mTOR inhibitors ID INFANTILE SPASMS; EPILEPSY; ONSET; COUNT; RECOMMENDATIONS; POPULATION; SEVERITY AB BACKGROUND: Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. METHOD: During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. RESULTS: Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. CONCLUSION: Many risk factors have been associated with intellectual disability and/or autism in individuals with tuberous sclerosis complex; however, few data are available regarding practical clinical tools for early identification. In our case series, inclusion of the Capute Scales as a part of routine medical care led to the identification of developmental delays in the first 12 months of life and selection of targeted neurodevelopmental interventions. Development of a risk-based assessment using this approach will be the focus of future studies as it may provide a potential window of opportunity for both research and clinical purposes. In research, it may serve as an objective outcome measure. Clinically, this type of assessment has potential for informing clinical treatment decisions and serving as a prognostic indicator of long-term cognitive and psychiatric outcomes. C1 [Gipson, Tanjala T.; Gerner, Gwendolyn; Johnston, Michael V.] Kennedy Krieger Inst, Tuberous Sclerosis Clin, Baltimore, MD 21205 USA. [Gipson, Tanjala T.; Gerner, Gwendolyn; Srivastava, Siddharth; Johnston, Michael V.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA. [Gipson, Tanjala T.; Gerner, Gwendolyn; Johnston, Michael V.] Kennedy Krieger Inst, Clin Trials Unit, Hugo W Moser Res Inst Inc, Baltimore, MD 21205 USA. [Gipson, Tanjala T.; Johnston, Michael V.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Johnston, Michael V.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Johnston, Michael V.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA. [Poretti, Andrea] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Sect Pediat Neuroradiol,Div Pediat Radiol, Baltimore, MD USA. [Vaurio, Rebecca] Kennedy Krieger Inst, Dept Neuropsychol, Baltimore, MD 21205 USA. [Vaurio, Rebecca] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Hartman, Adam] Johns Hopkins Univ, Sch Med, Dept Neurol, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD 21205 USA. RP Gipson, TT (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, 707 N Broadway, Baltimore, MD 21205 USA. EM tsclinic@kennedykrieger.org FU National Institute of Neurological Disorders and Stroke [2K12NS001696-11A1]; National Institute of Child Health and Human Development [5T32HD007414-18]; Novartis Pharmaceuticals; Novartis FX T.T.G. received grant 2K12NS001696-11A1 from the National Institute of Neurological Disorders and Stroke and G.G. received grant 5T32HD007414-18 from the National Institute of Child Health and Human Development. T.T.G. and M.V.J. are participating as investigators in a clinical trial of everolimus developed and sponsored by Novartis Pharmaceuticals. Funds are provided to Kennedy Krieger Institute by Novartis for research costs associated with this trial. 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Neurol. PD SEP PY 2014 VL 51 IS 3 BP 398 EP 402 DI 10.1016/j.pediatrneurol.2014.04.028 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AO4TT UT WOS:000341335000018 PM 25160545 ER PT J AU Moeschler, JB Shevell, M AF Moeschler, John B. Shevell, Michael TI Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays SO PEDIATRICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; LINKED MENTAL-RETARDATION; COPY NUMBER VARIANTS; MAGNETIC-RESONANCE SPECTROSCOPY; QUALITY-STANDARDS-SUBCOMMITTEE; AUTISM SPECTRUM DISORDERS; CHROMOSOMAL MICROARRAY; MECP2 MUTATIONS; DYSMORPHIC FEATURES; PRACTICE-COMMITTEE AB Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed. 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Park, Sohee TI Social trait judgment and affect recognition from static faces and video vignettes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Affect recognition; Social judgment; Social cognition; Nonverbal behavior; Thin slices ID THIN SLICES; SPECTRUM DISORDERS; NONVERBAL BEHAVIOR; PERCEPTION; COGNITION; AUTISM; INFORMATION; PSYCHOSIS; BRAIN; SCALE AB Social impairment is a core feature of schizophrenia, present from the pre-morbid stage and predictive of outcome, but the etiology of this deficit remains poorly understood. Successful and adaptive social interactions depend on one's ability to make rapid and accurate judgments about others in real time. Our surprising ability to form accurate first impressions from brief exposures, known as "thin slices" of behavior has been studied very extensively in healthy participants. We sought to examine affect and social trait judgment from thin slices of static or video stimuli in order to investigate the ability of schizophrenic individuals to form reliable social impressions of others. 21 individuals with schizophrenia (SZ) and 20 matched healthy participants (HC) were asked to identify emotions and social traits for actors in standardized face stimuli as well as brief video clips. Sound was removed from videos to remove all verbal cues. Clinical symptoms in SZ and delusional ideation in both groups were measured. Results showed a general impairment in affect recognition for both types of stimuli in SZ. However, the two groups did not differ in the judgments of trustworthiness, approachability, attractiveness, and intelligence. Interestingly, in SZ, the severity of positive symptoms was correlated with higher ratings of attractiveness, trustworthiness, and approachability. Finally, increased delusional ideation in SZwas associated with a tendency to rate others as more trustworthy, while the opposite was true for HC. These findings suggest that complex social judgments in SZ are affected by symptomatology. (C) 2014 Elsevier B.V. All rights reserved. C1 [McIntosh, Lindsey G.; Park, Sohee] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Park, Sohee] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA. RP Park, S (reprint author), Vanderbilt Univ, Dept Psychol, 111 21st Ave South,301 Wilson Hall, Nashville, TN 37240 USA. EM sohee.park@vanderbilt.edu FU NIMH [R01MH073028]; NICHD [P30HD15052] FX This work was supported in part by NIMH R01MH073028 and NICHD P30HD15052 to Vanderbilt University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. 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Moore, Susan Kelleher, Eric Hargreaves, April Anderson-Schmidt, Heike Gill, Michael Gallagher, Louise Corvin, Aiden TI The phenotypic manifestations of rare CNVs in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; CNV; Copy number variation; Paternal age; Family history; Phenotype ID COPY NUMBER VARIATION; AUTISM SPECTRUM DISORDERS; DOMAIN CRITERIA RDOC; PATERNAL-AGE; BIPOLAR DISORDER; RISK-FACTOR; GENES; POPULATION; MUTATIONS; MICRODELETIONS AB There is compelling evidence for the role of copy number variants (CNVs) in schizophrenia susceptibility, and it has been estimated that up to 2-3% of schizophrenia cases may carry rare CNVs. Despite evidence that these events are associated with an increased risk across categorical neurodevelopmental disorders, there is limited understanding of the impact of CNVs on the core features of disorders like schizophrenia. Our objective was to evaluate associations between rare CNVs in differentially brain expressed (BE) genes and the core features and clinical correlates of schizophrenia. The sample included 386 cases of Irish ancestry with a diagnosis of schizophrenia, at least one rare CNV impacting any gene, and a core set of phenotypicmeasures. Statistically significant associations between deletions in differentially BE genes were found for family history of mental illness (decreased prevalence of all CNVs and deletions, unadjusted and adjusted) and for paternal age (increase in deletions only, unadjusted, among those with later ages at birth of patient). The strong effect of a lack of a family history on BE genes suggests that CNVs may comprise one pathway to schizophrenia, whereas a positive family history could index other geneticmechanisms that increase schizophrenia vulnerability. To our knowledge, this is the first investigation of the association between genome-wide CNVs and risk factors and sub-phenotypic features of schizophrenia beyond cognitive function. (C) 2014 Elsevier B. V. All rights reserved. C1 [Merikangas, Alison K.; Cormican, Paul; Heron, Elizabeth A.; Anney, Richard J. L.; Moore, Susan; Kelleher, Eric; Hargreaves, April; Gill, Michael; Gallagher, Louise; Corvin, Aiden] Univ Dublin Trinity Coll, Dept Psychiat, Inst Mol Med, Dublin 2, Ireland. [Merikangas, Alison K.; Cormican, Paul; Heron, Elizabeth A.; Anney, Richard J. L.; Moore, Susan; Kelleher, Eric; Hargreaves, April; Gill, Michael; Gallagher, Louise; Corvin, Aiden] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Inst Mol Med, Dublin 2, Ireland. [Segurado, Ricardo] Univ Coll Dublin, Ctr Support & Training Anal & Res, Dublin 4, Ireland. [Anderson-Schmidt, Heike] Univ Gottingen, Dept Psychiat & Psychotherapy, Univ Med Ctr, D-37073 Gottingen, Germany. RP Merikangas, AK (reprint author), Univ Dublin Trinity Coll, Dept Psychiat, Trinity Ctr Hlth Sci, St James Hosp, James St, Dublin 8, Ireland. EM merikana@tcd.ie FU Irish Research Council; Wellcome Trust [072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B]; Wellcome Trust Case Control Consortium 2 project [085475/B/08/Z, 085475/Z/08/Z]; Science Foundation Ireland [08/IN.1/B1916]; National Institute of Mental Health [MH 41953, MH083094]; Meath Foundation (Ireland) FX Funding for this study was provided by the Irish Research Council, the Wellcome Trust, (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B) and Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z) Science Foundation Ireland (08/IN.1/B1916), the National Institute of Mental Health (MH 41953 and MH083094) and the Meath Foundation (Ireland). 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PD SEP PY 2014 VL 158 IS 1-3 BP 270 EP 271 DI 10.1016/j.schres.2014.06.029 PG 2 WC Psychiatry SC Psychiatry GA AO4MW UT WOS:000341314800045 PM 25043265 ER PT J AU Richdale, AL Baker, E Short, M Gradisar, M AF Richdale, Amanda L. Baker, Emma Short, Michelle Gradisar, Michael TI The role of insomnia, pre-sleep arousal and psychopathology symptoms in daytime impairment in adolescents with high-functioning autism spectrum disorder SO SLEEP MEDICINE LA English DT Article DE Autism; Insomnia; Daytime functioning; Anxiety; Arousal; Depression; Adolescence ID ANXIETY DISORDERS; CHILDREN; DISTURBANCES; DEPRESSION; REDUCTION; PARENT AB Objectives: Sleep disturbance and psychopathology are common during adolescence and are highly prevalent in individuals diagnosed with autism spectrum disorder (ASD). The aim of this study was to investigate relationships between sleep disturbance, psychopathology symptoms, and daytime functioning in adolescents with high-functioning autism spectrum disorder (HFASD) compared to typically developing (TD) adolescents. Methods: Twenty-seven adolescents with HFASD and 27 age- and sex-matched TD adolescents completed questionnaires related to sleep, psychopathology and daytime functioning. Participants also completed a 7-day sleep/wake diary. A subsample of HFASD adolescents (55%) and all the TD adolescents wore an actigraphy monitor concurrently with the sleep diary. Results: Adolescents with HFASD had significantly higher scores for depressed mood, anxiety and pre-sleep arousal compared with TD adolescents and poorer daytime functioning. There were more significant correlations between sleep variables and psychopathology variables, and sleep variables and daytime functioning, in the HFASD group than in the TD group. Standard regression found that sleep variables significantly accounted for 57% of the variance in daytime functioning symptoms of insufficient sleep in the HFASD group, while psychopathology variables accounted for 63% of the variance in daytime functioning. Conclusions: Both sleep disturbance and psychopathology are more prevalent in adolescents with HFASD and are major contributors to poor daytime functioning in these individuals. (C) 2014 Published by Elsevier B.V. C1 [Richdale, Amanda L.; Baker, Emma] La Trobe Univ, Olga Tennison Autism Res Ctr, Sch Psychol Sci, Melbourne, Vic, Australia. [Short, Michelle] Univ S Australia, Ctr Sleep Res, Adelaide, SA 5001, Australia. [Gradisar, Michael] Flinders Univ S Australia, Sch Psychol, Adelaide, SA 5001, Australia. RP Richdale, AL (reprint author), La Trobe Univ, Olga Tennison Autism Res Ctr, Sch Psychol Sci, Kingsbury Dr, Bundoora, Vic 3086, Australia. 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PD SEP PY 2014 VL 15 IS 9 BP 1082 EP 1088 DI 10.1016/j.sleep.2014.05.005 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AO6TA UT WOS:000341483200013 PM 24974199 ER PT J AU Angell, AM Solomon, O AF Angell, Amber M. Solomon, Olga TI The social life of health records: Understanding families' experiences of autism SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; African American; Autism; Family perspectives; Health record; Health disparities; Healthcare disparities; Meaningful use ID SPECTRUM DISORDERS; DIAGNOSIS; CHILDREN; CARE; CALIFORNIA; CAPITATION; AGE AB Outside of the epidemiological surveillance studies of autism prevalence, health records of children diagnosed with autism have not been sufficiently examined, yet they provide an important lens for showing how autism diagnosis, services and interventions are negotiated, coordinated and choreographed by families and practitioners across multiple settings. This article provides a multifaceted understanding of these processes from an ethnographic and discourse analytic perspective that reveals structural and interactional phenomena contributing to disparities in autism diagnosis and services. We consider health records as dualistic, material-discursive artifacts that are socio-interactionally co-constructed and variably interpreted, contested and utilized across home, school and clinic contexts. We chronicle several families' experiences of their children's autism diagnoses and interventions and describe ways in which health records are socially constructed, curated and placed in the middle of clinical encounters. We show how the parents in our study draw upon health records' material-discursive properties to display epistemic authority, expertise and knowledge in interactions with healthcare and school professionals involved in authorizing and planning their children's care. We describe how the parents experience the health records' clinical portrayals of their children and themselves, and how the parents' portrayals of their children are tacitly ratified or negated in the health records. The data include health record reviews, narrative interviews with parents and practitioners, and clinical observations. These data were collected between October 2009 and August 2012 as part of a larger study on disparities in autism diagnosis, interventions and services experienced by African American children with autism and their families living in Los Angeles County, California. Our analysis reveals the central role of health records in maintaining continuity of an autism diagnosis, interventions and services. This article contributes to enhanced professional awareness, parent-professional partnerships, and equity in the provision of healthcare and human services related to autism. (C) 2014 The Authors. Published by Elsevier Ltd. C1 [Angell, Amber M.; Solomon, Olga] Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. RP Angell, AM (reprint author), Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. EM aangell@usc.edu; olga.solomon@usc.edu FU grant Autism in Urban Context: Linking Heterogeneity with Health and Service Disparities (NIH/NIMH) [R01 MH089474]; Division of Occupational Science and Occupational Therapy at the USC Herman Ostrow School of Dentistry FX We are deeply grateful to the children and their families who participated in this study. This study was supported by a grant Autism in Urban Context: Linking Heterogeneity with Health and Service Disparities (NIH/NIMH, R01 MH089474, 2009-2012, O. Solomon, P.I.). 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. We thank the members of the Autism in Urban Context research team: Mary Lawlor, ScD, Sharon Cermak, EdD, Marie Poulsen, PhD, Thomas Valente, PhD, Marian Williams, PhD, and Larry Yin, MD; and post-doctoral researchers Kimberly Wilkinson, PhD and Tessa Milman, OTD. We also gratefully acknowledge the support of the Division of Occupational Science and Occupational Therapy at the USC Herman Ostrow School of Dentistry. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bakhtin M. 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PD SEP PY 2014 VL 117 BP 50 EP 57 DI 10.1016/j.socscimed.2014.07.020 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AO6SF UT WOS:000341481100007 PM 25042544 ER PT J AU Fahnehjelm, KT Dahl, S Martin, L Ek, U AF Fahnehjelm, Kristina Tear Dahl, Sara Martin, Lene Ek, Ulla TI Optic nerve hypoplasia in children and adolescents; prevalence, ocular characteristics and behavioural problems SO ACTA OPHTHALMOLOGICA LA English DT Article DE behaviour disc; area optic nerve hypoplasia; prevalence ID DOUBLING TECHNOLOGY PERIMETRY; VISUAL IMPAIRMENT; SWEDISH CHILDREN; RISK-FACTORS; SYSTEM ABNORMALITIES; YOUNG-CHILDREN; DYSPLASIA; SPECTRUM; RAREBIT; REAPPRAISAL AB Purpose: To report prevalence, ocular characteristics and coexisting behavioural problems in children and adolescents with optic nerve hypoplasia (ONH), which is a common cause of visual impairment in children in western countries, often associated with neurological or endocrinological problems and where autism has been reported in severe cases with blindness. Methods: This is a population-based cross-sectional study of patients <20 years of age who had been diagnosed with NH and lived in the county of Stockholm in December 2009. Ophthalmological assessments including fundus photographs with optic disc analyses were made. A questionnaire was used to screen for behaviour and development. Results: The prevalence of ONH in all living children <18 years of age in Stockholm was 17.3/100 000 with a prevalence of visual impairment (<0.3) of 3.9/100 000. In total, 66 patients, median age 9.3 years (0.6-19.4), 36 with bilateral and 30 with unilateral ONH, were included in the current study; 53 were re-examined clinically, group A, and 13 agreed to retrospective analyses of existing medical records, group B. Analyses of the optic discs were made in fundus photographs from 53 patients comparing a semi-automated (Retinal Size Tool) and a manual method (Zeki). There was a strong curvilinear correlation (r(S) = 0.91 p < 0.0001 for both eyes). Behavioural problems were more common (p < 0.05) in bilateral ONII. Conclusion: Optic nerve hypoplasia is a common ocular malformation with a prevalence of 17.3/100 000 children and adolescents <18 years of age in Stockholm. Unilateral ONH seems as common as bilateral. C1 [Fahnehjelm, Kristina Tear] Karolinska Univ Hosp, Dept Clin Neurosci, Karolinska Inst, Stockholm, Sweden. [Fahnehjelm, Kristina Tear] Karolinska Univ Hosp, St Erik Eye Hosp, Dept Paediat Ophthalmol & Strabismus, Stockholm, Sweden. [Dahl, Sara] Karolinska Univ Hosp, Dept Paediat, Stockholm, Sweden. [Martin, Lene] Malardalen Univ, Sch Hlth Care & Social Welf, Eskilstuna, Sweden. [Ek, Ulla] Stockholm Univ, Dept Special Educ, S-10691 Stockholm, Sweden. RP Fahnehjelm, KT (reprint author), Karolinska Univ Hosp, Dept Clin Neuroscienc, Karolinska Inst, Stockholm, Sweden. EM kristina.tear-fahnehjelm@sankterik.se FU Sigvard och Marianne Bernadotte Foundation; Signhild Engkvist Foundation; Samariten Foundation FX This project has been supported by the Sigvard och Marianne Bernadotte Foundation, the Signhild Engkvist Foundation and the Samariten Foundation. 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PD SEP PY 2014 VL 92 IS 6 BP 563 EP 570 DI 10.1111/aos.12270 PG 8 WC Ophthalmology SC Ophthalmology GA AN4VD UT WOS:000340585800033 ER PT J AU Leivonen, S Voutilainen, A Hinkka-Yli-Salomaki, S Timonen-Soivio, L Chudal, R Gissler, M Huttunen, J Sourander, A AF Leivonen, Susanna Voutilainen, Arja Hinkka-Yli-Salomaki, Susanna Timonen-Soivio, Laura Chudal, Roshan Gissler, Mika Huttunen, Jukka Sourander, Andre TI A nationwide register study of the characteristics, incidence and validity of diagnosed Tourette syndrome and other tic disorders SO ACTA PAEDIATRICA LA English DT Article DE Incidence; Register-based study; Tic disorder; Tourette's syndrome; Validation ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; NEURODEVELOPMENTAL DISORDERS; SEVERITY-SCALE; BIRTH COHORT; RISK-FACTORS; SCHIZOPHRENIA; EPIDEMIOLOGY; PREVALENCE; AGE AB Aim: The aim of this study was to describe the characteristics and incidence rates of diagnosed tic disorders in the Finnish Hospital Discharge Register, including changing incidence rates between 1991 and 2010. We also aimed to validate the diagnoses of Tourette's syndrome recorded in the register. Methods: Children born between January 1, 1991 and December 31, 2010, who were diagnosed with tic disorders, were identified from the Finnish Hospital Discharge Register (n = 3003). We studied the validity of the Tourette's syndrome diagnoses by reviewing the medical charts of 88 children born since 1997 and carrying out telephone interviews with 55 of their guardians. Results: The incidence rates of all diagnosed tic disorders increased during the study period. A comorbid diagnosis of hyperkinetic disorder diagnosis was recorded in 28.2% of the children with Tourette's syndrome, and the validity of the register-based Tourette's syndrome diagnosis was approximately 95%. Conclusion: This is the first nationwide study to demonstrate the increasing incidence of all register-based tic disorder diagnoses. The validity of the Tourette's syndrome diagnoses in the Finnish Hospital Discharge Register was good, and the data provided are suitable for use in further register-based studies of tic disorders. C1 [Leivonen, Susanna; Hinkka-Yli-Salomaki, Susanna; Timonen-Soivio, Laura; Chudal, Roshan; Gissler, Mika; Huttunen, Jukka; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku, Finland. [Leivonen, Susanna; Voutilainen, Arja; Timonen-Soivio, Laura] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Leivonen, Susanna; Voutilainen, Arja; Timonen-Soivio, Laura] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Gissler, Mika] Nord Sch Publ Hlth NHV, Gothenburg, Sweden. [Sourander, Andre] Turku Univ Hosp, Dept Child Psychiat, FIN-20520 Turku, Finland. [Sourander, Andre] UiT, RKBU, Tromso, Norway. RP Leivonen, S (reprint author), Univ Turku, Dept Child Psychiat, Kliininen Laitos, Turun 20014, Finland. EM susanna.leivonen@utu.fi RI Chudal, Roshan/C-1067-2015 FU Sigrid Juselius Foundation; Jane and Aatos Erkko Foundation; Academy of Finland FX We are grateful to families who participated in the interview study and the people in Helsinki and Turku University central hospitals and Rovaniemi, Jyvaskyla and Mikkeli central hospitals who did help with the identification of the children and gathering the data. We would also like to thank data manager Juha-Pekka Virtanen and project coordinator Tanja Sarlin and Jarna Lindroos at the Department of child psychiatry, Turku University hospital. The study was funded by Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation and Academy of Finland. On behalf of all authors, the corresponding author states that there is no conflict of interests. 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PD SEP PY 2014 VL 119 IS 5 BP 389 EP 404 DI 10.1352/1944-7558-119.5.389 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AO3XQ UT WOS:000341271000001 PM 25148054 ER PT J AU Totsika, V Hastings, RP Vagenas, D Emerson, E AF Totsika, Vasiliki Hastings, Richard Patrick Vagenas, Dimitrios Emerson, Eric TI Parenting and the Behavior Problems of Young Children With an Intellectual Disability: Concurrent and Longitudinal Relationships in a Population-Based Study SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE intellectual disability; parenting; longitudinal; parent-child relationship ID AUTISM SPECTRUM DISORDER; MATERNAL MENTAL-HEALTH; STONES TRIPLE P; DIFFICULTIES QUESTIONNAIRE; MIDDLE CHILDHOOD; DEVELOPMENTAL-DISABILITY; RELATIONSHIP QUALITY; EMOTIONAL-PROBLEMS; SYMPTOMS; CHAOS AB We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N = 516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more negative relationship with their child. Among children with an ID, discipline, and home atmosphere had no long-term association with behavior problems, whereas relationship quality did: closer relationships were associated with fewer concurrent and later child behavior problems. Increased parent-child conflict was associated with greater concurrent and later behavior problems. Parenting programs in ID could target parent-child relationship quality as a potential mediator of behavioral improvements in children. C1 [Totsika, Vasiliki; Hastings, Richard Patrick] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Vagenas, Dimitrios] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Emerson, Eric] Univ Sydney, Sydney, NSW 2006, Australia. 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J. Intellect. Dev. Disabil. PD SEP PY 2014 VL 119 IS 5 BP 422 EP 435 DI 10.1352/1944-7558-119.5.422 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AO3XQ UT WOS:000341271000003 PM 25148056 ER PT J AU Shire, SY Kasari, C AF Shire, Stephanie Yoshiko Kasari, Connie TI Train the Trainer Effectiveness Trials of Behavioral Intervention for Individuals With Autism: A Systematic Review SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE effectiveness trials; Train-the-Trainer; autism; intervention ID JOINT ATTENTION INTERVENTION; SPECTRUM DISORDERS; PSYCHOSOCIAL INTERVENTIONS; FOLLOW-UP; CHILDREN; PSYCHOTHERAPY; PRESCHOOLERS; PROGRAM; MODEL AB This systematic review examines train the trainer (TTT) effectiveness trials of behavioral interventions for individuals with autism spectrum disorder (ASD). 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R., 2001, EUROPEAN CHILD AND A, V10, p1/12 WEISZ JR, 1992, AM PSYCHOL, V47, P1578, DOI 10.1037/0003-066X.47.12.1578 Weisz JR, 2012, ARCH GEN PSYCHIAT, V69, P274, DOI 10.1001/archgenpsychiatry.2011.147 World Health Organization, 2005, MENTAL HEALTH POLICY NR 34 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 SEP PY 2014 VL 119 IS 5 BP 436 EP 451 DI 10.1352/1944-7558-119.5.436 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AO3XQ UT WOS:000341271000004 PM 25148057 ER PT J AU Lieberman-Betz, RG Yoder, P Stone, WL Nahmias, AS Carter, AS Celimli-Aksoy, S Messinger, DS AF Lieberman-Betz, Rebecca G. Yoder, Paul Stone, Wendy L. Nahmias, Allison S. Carter, Alice S. Celimli-Aksoy, Seniz Messinger, Daniel S. TI An Illustration of Using Multiple Imputation Versus Listwise Deletion Analyses: The Effect of Hanen's "More Than Words'' on Parenting Stress SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE missing data analysis; multiple imputation; autism spectrum disorder; early intervention; parent stress ID AUTISM SPECTRUM DISORDERS; RANDOMIZED CONTROLLED-TRIAL; MISSING-DATA; YOUNG-CHILDREN; 2-YEAR-OLDS STAT; MATERNAL STRESS; SCREENING TOOL; FAMILY STRESS; MENTAL-HEALTH; INTERVENTION AB This investigation illustrates the effects of using different missing data analysis techniques to analyze effects of a parent-implemented treatment on stress in parents of toddlers with autism symptomatology. The analysis approaches yielded similar results when analyzing main effects of the intervention, but different findings for moderation effects. Using listwise deletion, the data supported an iatrogenic effect of Hanen's "More Than Words'' on stress in parents with high levels of pretreatment depressive symptoms. Using multiple imputation, a significant moderated treatment effect with uninterpretable regions of significance did not support an iatrogenic effect of treatment on parenting stress. Results highlight the need for caution in interpreting analyses that do not involve validated methods of handling missing data. C1 [Lieberman-Betz, Rebecca G.; Yoder, Paul] Vanderbilt Univ, Peabody Coll, Dept Special Educ, Nashville, TN USA. [Stone, Wendy L.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. [Nahmias, Allison S.] Vanderbilt Univ, Nashville, TN USA. [Carter, Alice S.] Univ Massachusetts Boston, Dept Psychol, Boston, MA USA. [Celimli-Aksoy, Seniz; Messinger, Daniel S.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. 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PD SEP PY 2014 VL 119 IS 5 BP 472 EP 486 DI 10.1352/1944-7558-119.5.472 PG 15 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AO3XQ UT WOS:000341271000006 PM 25148059 ER PT J AU Ogata, H Ihara, H Murakami, N Gito, M Kido, Y Nagai, T AF Ogata, Hiroyuki Ihara, Hiroshi Murakami, Nobuyuki Gito, Masao Kido, Yasuhiro Nagai, Toshiro TI Autism Spectrum Disorders and Hyperactive/Impulsive Behaviors in Japanese Patients With Prader-Willi Syndrome: A Comparison Between Maternal Uniparental Disomy and Deletion Cases SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Prader-Willi syndrome; chromosome 15q11-13; autism spectrum disorders; maternal uniparental disomy 15 (mUPD); adolescents ID PERVASIVE DEVELOPMENTAL DISORDERS; ABILITIES; CHILDREN AB This study aims to compare maternal uniparental disomy 15 (mUPD) and a paternal deletion of 15q11-13 (DEL) of Prader-Willi syndrome (PWS) in regard to autism spectrum disorders (ASD). Forty-five Japanese individuals with PWS were recruited from a single recruitment center. The participants consisted of 22 children (aged from 6 to 12) and 23 adolescents (aged from 13 to 19). Six children and seven adolescents were confirmed as having mUPD. Sixteen children and 16 adolescents were confirmed as having DEL. Under blindness to the participants' genotypes, a single psychologist carried out behavioral and psychological assessments, including the Wechsler Intelligence Scales, Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), and ADHD-Rating Scale-IV (ADHD-RS-IV). Two comparisons were made: one between mUPD and DEL children and another between mUPD and DEL adolescents. In children, no significant differences were found between mUPD and DEL participants in terms of autistic (PARS childhood, P = 0.657) and impulsive behaviors (ADHD-RS-IV hyperactive/impulsive, P = 0.275). In adolescents, mUPD patients showed significantly more autistic symptomatology (PARS adolescent, P = 0.027) and significantly more impulsive behavior (ADHD-RS-IV hyperactive/impulsive, P = 0.01) than DEL patients. Our findings about Japanese PWS patients were consistent with previous researches from western countries not focused on Asian patients, indicating that mUPD cases would be more prone to ASD than DEL cases, regardless of ethnoregional differences. In addition, our data suggested that the behavioral difference between mUPD and DEL cases in terms of autistic and impulsive symptoms tend to be unrecognizable in their childhood. (C) 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. C1 [Ogata, Hiroyuki; Ihara, Hiroshi; Gito, Masao] Dokkyo Med Univ, Dept Psychiat, Koshigaya Hosp, Koshigaya, Japan. [Murakami, Nobuyuki; Kido, Yasuhiro; Nagai, Toshiro] Dokkyo Med Univ, Dept Pediat, Koshigaya Hosp, Koshigaya, Japan. [Gito, Masao] Ikezawa Hosp, Dept Psychiat, Hanyu, Japan. RP Ihara, H (reprint author), Dokkyo Med Univ, Dept Psychiat, Koshigaya Hosp, Minami Koshigaya 2-1-50, Koshigaya, Japan. EM cotoncb@dokkyomed.ac.jp FU Juntendo Institute of Psychiatry [Heisei 25] FX This research was supported by a grant for Research Support Foundation from the Juntendo Institute of Psychiatry in the financial year 2013 (Heisei 25). 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TI Elevated Maternal C-Reactive Protein and Increased Risk of Schizophrenia in a National Birth Cohort SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; PRENATAL IMMUNE ACTIVATION; INFLUENZA EPIDEMIC; BRAIN-DEVELOPMENT; BIPOLAR DISORDER; ANIMAL-MODELS; EXPOSURE; INFECTION; PREECLAMPSIA; PREGNANCY AB Objective: The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank. Method: A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens. Results: Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. Conclusions: This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders. C1 [Brown, Alan S.] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Med Ctr, New York, NY 10027 USA. 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TI Mediators of the association between parental severe mental illness and offspring neurodevelopmental problems SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Attention deficit hyperactivity disorder; Autism spectrum disorder; Infant; Small for gestational age; Birth weight; Gestational age ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; ADVERSE PREGNANCY OUTCOMES; LOW-BIRTH-WEIGHT; RISK-FACTORS; PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; PRETERM BIRTH; BRAIN-DEVELOPMENT; GESTATIONAL-AGE AB Purpose: Parental severe mental illness (SMI) is associated with an increased risk of offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We conducted a study to examine the extent to which risk of preterm birth, low birth weight, and small for gestational age mediated this association. Methods: We obtained data on offspring born 1992-2001 in Sweden (n = 870,017) through the linkage of multiple population-based registers. We used logistic and Cox regression to assess the associations between parental SMI, adverse pregnancy outcomes, and offspring ASD and ADHD, as well as tested whether adverse pregnancy outcomes served as mediators. Results: After controlling for measured covariates, maternal and paternal SMI were associated with an increased risk for preterm birth, low birth weight, and gestational age, and for offspring ASD and ADHD. These pregnancy outcomes were also associated with an increased risk of ASD and ADHD. We found that pregnancy outcomes did not mediate the association between parental SMI and offspring ASD and ADHD, as there was no substantial change in magnitude of the risk estimates after controlling for pregnancy outcomes. Conclusions: Parental SMI and adverse pregnancy outcomes appear to be independent risk factors for offspring ASD and ADHD. (C) 2014 Elsevier Inc. All rights reserved. C1 [McCoy, Brittany M.; Rickert, Martin E.; Class, Quetzal A.; D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Larsson, Henrik; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP D'Onofrio, BM (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 East 10th St, Bloomington, IN 47405 USA. EM bmdonofr@indiana.edu RI Maattanen, Laura/N-5424-2014 FU National Institute of Child Health and Human Development [HD061817]; National Institute of Mental Health [MH094011]; Swedish council for working life and social research; Swedish Research Council (Medicine); Swedish Society of Medicine FX The study was supported by grants from the National Institute of Child Health and Human Development (HD061817), National Institute of Mental Health (MH094011), the Swedish council for working life and social research, the Swedish Research Council (Medicine), and the Swedish Society of Medicine. 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Psychiatry PD SEP 1 PY 2014 VL 76 IS 5 BP 358 EP 359 DI 10.1016/j.biopsych.2014.07.010 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AN8WQ UT WOS:000340886800005 PM 25103541 ER PT J AU Chini, B Leonzino, M Braida, D Sala, M AF Chini, Bice Leonzino, Marianna Braida, Daniela Sala, Mariaelvina TI Learning About Oxytocin: Pharmacologic and Behavioral Issues SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Animal models; consolidation; flexibility; learning and memory; neuropeptide; neuropsychiatric disorders; oxytocin ID PASSIVE-AVOIDANCE BEHAVIOR; NON-PYRAMIDAL NEURONS; RAT HIPPOCAMPUS; SOCIAL RECOGNITION; ALZHEIMERS-DISEASE; OPPOSITE ACTION; HUMAN-MEMORY; NEUROHYPOPHYSEAL HORMONES; RECEPTOR ANTAGONISTS; VENTRAL HIPPOCAMPUS AB Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptor-deficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted. C1 [Chini, Bice; Leonzino, Marianna; Sala, Mariaelvina] Univ Milan, Natl Res Council, Milan, Italy. [Leonzino, Marianna; Braida, Daniela; Sala, Mariaelvina] Univ Milan, Inst Neurosci, Dipartimento Biotecnol Med & Med Traslaz, Milan, Italy. [Braida, Daniela] Fondazione Ist Ricovero & Cura Carattere Sci Don, Milan, Italy. RP Sala, M (reprint author), Univ Milan, Dipartimento Biotecnol Med & Med Traslaz, I-20129 Milan, Italy. EM mariaelvina.sala@unimi.it FU Telethon Foundation Grant [GGP12207] FX This work was supported by the Telethon Foundation Grant GGP12207 to BC. 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However, most studies investigating striatal differences in autism are cross-sectional, limiting inferences on development. In this study, we set out to 1) investigate striatal development in autism, using a longitudinal design; and 2) examine the relationship between striatal development and repetitive behavior. Methods: We acquired longitudinal structural magnetic resonance imaging scans from 86 individuals (49 children with autism, 37 matched control subjects). Each individual was scanned twice, with a mean scan interval time of 2.4 years. Mean age was 9.9 years at time 1 and 12.3 years at time 2. Striatal structures were traced manually with high reliability. Multivariate analyses of variance were used to investigate differences in brain development between diagnostic groups. To examine the relationship with behavior, correlations between changes in brain volumes and clinical measures were calculated. 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In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. Methods: We used event-related functional magnetic resonance imaging and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12-15; n = 13 with ASD and n = 13 with TYP) and older (ages 16-18; n = 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxelwise univariate and task-related functional connectivity analyses. Results: Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex and the anterior cingulate cortex, bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between dorsolateral prefrontal cortex and parietal cortex (Brodmann areas 9 and 40) was related to task performance in TYP. Conclusions: Adolescents with ASD rely more on reactive cognitive control, involving last-minute conflict detection and control implementation by the anterior cingulate cortex and ventrolateral prefrontal cortex, versus proactive cognitive control requiring processing by dorsolateral prefrontal cortex and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention. C1 [Solomon, Marjorie; Yoon, Jong H.; Ragland, J. Daniel; Niendam, Tara A.; Lesh, Tyler A.; Fairbrother, Wonja; Carter, Cameron S.] Univ Calif, Dept Psychiat & Behav Sci, Davis, CA USA. [Solomon, Marjorie; Fairbrother, Wonja] MIND Inst, Sacramento, CA USA. [Solomon, Marjorie; Yoon, Jong H.; Ragland, J. Daniel; Niendam, Tara A.; Lesh, Tyler A.; Carter, Cameron S.] Univ Calif Davis, Imaging Res Ctr, Sacramento, CA 95817 USA. RP Solomon, M (reprint author), UC Davis Hlth Syst, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM marjorie.solomon@ucdmc.ucdavis.edu FU National Institute of Mental Health [1-K-08 MH074967-01, 2R01 MH059883-05A1, 1R24MH081807, K23MH087708, R01MH084895, K-08]; Building Interdisciplinary Research Careers in Women's Health Award - National Institute of Child Health and Human Development, Office of Research on Women's Health, Office of Dietary Supplements [K12 HD051958]; National Institute of Aging; National Alliance for Research on Schizophrenia and Depression (Atherton Foundation); GlaxoSmithKline FX This work was supported by a K-08 Award from the National Institute of Mental Health (1-K-08 MH074967-01); a Building Interdisciplinary Research Careers in Women's Health Award (K12 HD051958) funded by the National Institute of Child Health and Human Development, Office of Research on Women's Health, Office of Dietary Supplements, and the National Institute of Aging; and a Pilot Award from the National Alliance for Research on Schizophrenia and Depression (Atherton Foundation) to Marjorie Solomon. During the time of the study, Dr. Carter was supported by the National Institute of Mental Health (2R01 MH059883-05A1) and (1R24MH081807). Dr. Niendam was supported by the National Institute of Mental Health (K23MH087708). Dr. Ragland was supported by the National Institute of Mental Health (R01MH084895, Ragland, Principal Investigator).Dr. Carter reports having been a consultant for Pfizer, Merck, Lilly, and Servier. He also has received funding from GlaxoSmithKline. Drs. Solomon, Yoon, Ragland, Niendam, and Lesh and Ms. Fair-brother report no biomedical financial interests or potential conflicts of interest. 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Psychiatry PD SEP 1 PY 2014 VL 76 IS 5 BP 412 EP 421 DI 10.1016/j.biopsych.2013.08.036 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AN8WQ UT WOS:000340886800012 PM 24209777 ER PT J AU Nuske, HJ Vivanti, G Hudry, K Dissanayake, C AF Nuske, Heather J. Vivanti, Giacomo Hudry, Kristelle Dissanayake, Cheryl TI Pupillometry reveals reduced unconscious emotional reactivity in autism SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Autism; Emotion; Pupil dilation; Unconscious; Subliminal; Implicit; Backwards masking; Eye tracking; Autonomic nervous system; Physiological responding; Pupillometry ID FACIAL EXPRESSIONS; SPECTRUM DISORDERS; BACKWARD-MASKING; YOUNG-CHILDREN; CONSCIOUS PERCEPTION; ASPERGER-SYNDROME; NEURAL CIRCUITRY; HUMAN AMYGDALA; PUPIL SIZE; FACE AB Recent theoretical conceptualisations have suggested that emotion processing impairments in autism stem from disruption to the sub-cortical, rapid emotion-processing system. We argue that a clear way to ascertain whether this system is affected in autism is by measuring unconscious emotional reactivity. Using backwards masking, we presented fearful expressions non-consciously (subliminally) as well as consciously (supraliminally), and measured pupillary responses as an index of emotional reactivity in 19 children with autism and 19 typically developing children, aged 2-5 years. The pupillary responses of the children with autism revealed reduced unconscious emotional reactivity, with no group differences on consciously presented emotion. Together, these results indicate a hyporesponsiveness to non-consciously presented emotion suggesting a fundamental difference in emotion processing in autism, which requires consciousness and more time. (C) 2014 Elsevier B.V. All rights reserved. C1 [Nuske, Heather J.; Vivanti, Giacomo; Hudry, Kristelle; Dissanayake, Cheryl] La Trobe Univ, Sch Psychol, Olga Tennison Autism Res Ctr, Melbourne, Vic 3086, Australia. [Vivanti, Giacomo] La Trobe Univ, Victorian Autism Specif Early Learning & Care Ctr, Bundoora, Vic 3086, Australia. RP Dissanayake, C (reprint author), La Trobe Univ, Sch Psychol, Olga Tennison Autism Res Ctr, Melbourne, Vic 3086, Australia. 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W., 1963, PROGRESS BRAIN RESEA, V3, P50, DOI 10.1016/S0079-6123(08)60566-X NR 118 TC 0 Z9 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 2014 VL 101 BP 24 EP 35 DI 10.1016/j.biopsycho.2014.07.003 PG 12 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA AN8FM UT WOS:000340838800005 PM 25017502 ER PT J AU Gabriele, S Sacco, R Cerullo, S Neri, C Urbani, A Tripi, G Malvy, J Barthelemy, C Bonnet-Brilhault, F Persico, AM AF Gabriele, Stefano Sacco, Roberto Cerullo, Sonia Neri, Cristina Urbani, Andrea Tripi, Gabriele Malvy, Joelle Barthelemy, Catherine Bonnet-Brilhault, Frederique Persico, Antonio M. TI Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study SO BIOMARKERS LA English DT Article DE Gut flora; neurotoxicity; organic contaminants; p-cresylsulfate; pervasive developmental disorders ID INTESTINAL PERMEABILITY; DEVELOPMENTAL DISORDERS; PROPIONIC-ACID; CRESYLSULPHATE; BEHAVIOR; DISEASE; ABNORMALITIES; BIOMARKERS; SULFATION; SYMPTOMS AB The aromatic compound p-cresol (4-methylphenol) has been found elevated in the urines of Italian autistic children up to 8 years of age. The present study aims at replicating these initial findings in an ethnically distinct sample and at extending them by measuring also the three components of urinary p-cresol, namely p-cresylsulfate, p-cresylglucuronate and free p-cresol. Total urinary p-cresol, p-cresylsulfate and p-cresylglucuronate were significantly elevated in 33 French autism spectrum disorder (ASD) cases compared with 33 sex-and age-matched controls (p<0.05). This increase was limited to ASD children aged <= 8 years (p<0.01), and not older (p=0.17). Urinary levels of p-cresol and p-cresylsulfate were associated with stereotypic, compulsive/repetitive behaviors (p<0.05), although not with overall autism severity. These results confirm the elevation of urinary p-cresol in a sizable set of small autistic children and spur interest into biomarker roles for p-cresol and p-cresylsulfate in autism. C1 [Gabriele, Stefano; Sacco, Roberto; Cerullo, Sonia; Persico, Antonio M.] Univ Campus Biomed, Unit Child & Adolescent NeuroPsychiat, I-00128 Rome, Italy. [Gabriele, Stefano; Sacco, Roberto; Cerullo, Sonia; Persico, Antonio M.] Univ Campus Biomed, Lab Mol Psychiat & Neurogenet, I-00128 Rome, Italy. [Neri, Cristina; Urbani, Andrea] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. [Neri, Cristina; Urbani, Andrea] IRCCS Fdn S Lucia, Dept Expt Neurosci, Rome, Italy. [Tripi, Gabriele] Univ Palermo, Dept PROSAMI, I-90133 Palermo, Italy. [Tripi, Gabriele] CH Chinon, Childhood Psychiat Serv Neurodev Disorders, Chinon, France. [Malvy, Joelle; Barthelemy, Catherine; Bonnet-Brilhault, Frederique] Univ Tours, Hop Bretonneau, Imagerie & Cerveau INSERM, U930, Tours, 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 s.gabriele@unicampus.it; r.sacco@unicampus.it; a.persico@unicampus.it FU Italian Ministry for University, Scientific Research and Technology [2008BACT54_002]; Italian Ministry of Health (CCM program, progetto NIDA); Fondazione Gaetano e Mafalda Luce (Milan, Italy); Autism Aid ONLUS (Naples, Italy); Autism Speaks (Princeton, NJ); Autism Research Institute (San Diego, CA); European Union (Innovative Medicines Initiative Joint Undertaking, EU-AIMS) [115300] FX This work was financially supported by the Italian Ministry for University, Scientific Research and Technology (n.2008BACT54_002), the Italian Ministry of Health (CCM program 2012, progetto NIDA), the Fondazione Gaetano e Mafalda Luce (Milan, Italy), Autism Aid ONLUS (Naples, Italy), Autism Speaks (Princeton, NJ), the Autism Research Institute (San Diego, CA), and the European Union (Innovative Medicines Initiative Joint Undertaking, EU-AIMS, n. 115300). The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the paper. 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In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations. C1 [Roos, L.; Gronskov, K.; Tumer, Z.] Copenhagen Univ Hosp, Rigshosp, Kennedy Ctr, DK-2600 Glostrup, Denmark. [Fang, M.; Wu, B.; Zhang, J.; Xu, X.] BGI Shenzhen, Dept Mendelian Disorder Res, Shenzhen, Peoples R China. [Dali, C.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Jensen, H.; Christoffersen, N.] Copenhagen Univ Hosp, Rigshosp, Kennedy Ctr, Eye Clin, DK-2600 Glostrup, Denmark. [Xu, R.] BGI Europe, Copenhagen, Denmark. [Harris, P.] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark. [Gronskov, K.] Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark. RP Roos, L (reprint author), Copenhagen Univ Hosp, Rigshosp, Kennedy Ctr, Gl Landevej 7, DK-2600 Glostrup, Denmark. EM laura.kirstine.soenderberg.roos@regionh.dk RI Harris, Pernille/G-7289-2011 OI Harris, Pernille/0000-0002-6806-4903 FU Shenzhen Municipal Government of China [GJHZ20130417140916986] FX The project conformed to the tenets of the Declaration of Helsinki and was approved by the Regional Scientific Ethical Committee for Copenhagen, Denmark. Written informed consent was obtained. This study was supported by the Shenzhen Municipal Government of China (No. GJHZ20130417140916986). 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Weight Disord.-Stud. Anorex. PD SEP PY 2014 VL 19 IS 3 BP 285 EP 293 DI 10.1007/s40519-013-0086-z PG 9 WC Psychiatry SC Psychiatry GA AO2UN UT WOS:000341181600002 PM 24272141 ER PT J AU Diolordi, L del Balzo, V Bernabei, P Vitiello, V Donini, LM AF Diolordi, Laura del Balzo, Valeria Bernabei, Paola Vitiello, Valeria Donini, Lorenzo Maria TI Eating habits and dietary patterns in children with autism SO EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY LA English DT Article DE Eating behavior inventory; Food consumption; Children with autism; Nutrition ID SPECTRUM DISORDERS; BEHAVIOR; BRAIN AB The children with autism have feeding problems such as chewing, preference for the same food that often are responsible for the nutrient imbalance. In this study, we have analyzed the differences in food consumption (food frequency) and eating behavior (CEBI test) between children with autism and their typically developing peers. A statistically significant difference was observed between the two groups for the consumption of milk, yogurt, pulses, rice, and fruit juices (p a parts per thousand currency sign 0,005). We observed a significant difference in the analysis of CEBI results when considering the 6- to 9.5-year-aged subgroup with autism vs control subgroup (103.50 and 110.14, respectively). The advices given by nutritionists have proved crucial to improve eating habits in children with autism, in the follow-up. C1 [Diolordi, Laura; del Balzo, Valeria; Vitiello, Valeria; Donini, Lorenzo Maria] Univ Roma La Sapienza, Dept Expt Med, Res Unit Food Sci & Human Nutr, I-00185 Rome, Italy. [Bernabei, Paola] Univ Roma La Sapienza, Dept Pediat & Pediat Neuropsychiat, I-00185 Rome, Italy. RP del Balzo, V (reprint author), Univ Roma La Sapienza, Dept Expt Med, Res Unit Food Sci & Human Nutr, Ple Aldo Moro 5, I-00185 Rome, Italy. 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Weight Disord.-Stud. Anorex. PD SEP PY 2014 VL 19 IS 3 BP 295 EP 301 DI 10.1007/s40519-014-0137-0 PG 7 WC Psychiatry SC Psychiatry GA AO2UN UT WOS:000341181600003 PM 24981567 ER PT J AU Park, S Park, JE Cho, SC Kim, BN Shin, MS Kim, JW Cho, IH Kim, SA Park, M Park, TW Son, JW Chung, US Yoo, HJ AF Park, Subin Park, Jong-Eun Cho, Soo-Churl Kim, Bung-Nyun Shin, Min-Sup Kim, Jae-Won Cho, In Hee Kim, Soon Ae Park, Mira Park, Tae-Won Son, Jung-Woo Chung, Un-Sun Yoo, Hee Jeong TI No association of the norepinephrine transporter gene (SLC6A2) and cognitive and behavioural phenotypes of patients with autism spectrum disorder SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Autism spectrum disorder; SLC6A2; Haplotype; Phenotype ID DEFICIT HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; ADHD; NET AB We examined the association between the norepinephrine transporter (SLC6A2) gene and autism spectrum disorder (ASD) in a Korean population. In addition, we investigated which phenotypes of ASD are best attributed to the genotype of SLC6A2. A total of 184 subjects with ASD, their 156 unaffected siblings and both biological parents were recruited through university hospitals. We used the Autism Diagnostic Interview-Revised, the Aberrant Behaviour Checklist (ABC), the Child Behaviour Checklist (CBCL), the Stroop Colour-Word Interference Test and the Wisconsin Card Sorting Test (WCST) as quantitative measures of the ASD phenotypes. The associations between the quantitative measures and specific single-nucleotide polymorphisms (SNPs) were tested with linear regression analyses. We did not find any evidence of the over-transmission of either allele of the 10SLC6A2 SNPs in the DFAM test. At an empirical p value < 0.05, findings that were consistent between the linear regression analyses and the QFAM tests were the positive associations between the A allele of rs36020 and attention problems on the CBCL and stereotypical behaviours on the ABC and between the C allele of rs1814270 and the number of trials required to complete the first WCST category. However, these associations did not remain after correction for multiple testing. The study results of this study do not support the association between the SLC6A2 and the diagnosis or phenotype of ASD. However, the study must be replicated in larger populations and with using more genetic markers. C1 [Park, Subin; Cho, Soo-Churl; Kim, Bung-Nyun; Shin, Min-Sup; Kim, Jae-Won] Seoul Natl Univ, Coll Med, Dept Psychiat, Div Child & Adolescent Psychiat, Seoul, South Korea. [Park, Jong-Eun; Yoo, Hee Jeong] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Songnam, Gyeonggi Do, South Korea. [Cho, In Hee] Samsung Child Dev Res Ctr, Dept Psychiat, Songnam, South Korea. [Kim, Soon Ae] Eulji Univ, Dept Pharmacol, Sch Med, Songnam, South Korea. [Park, Mira] Eulji Univ, Dept Prevent Med, Songnam, South Korea. [Park, Tae-Won] Chonbuk Natl Univ Hosp, Dept Psychiat, Jeonju, South Korea. [Son, Jung-Woo] Chungbuk Natl Univ Hosp, Dept Psychiat, Cheongju, South Korea. [Chung, Un-Sun] Kyungpook Natl Univ Hosp, Dept Psychiat, Taegu, South Korea. RP Yoo, HJ (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Songnam, Gyeonggi Do, South Korea. EM hjyoo@snu.ac.kr FU Korea Healthcare Technology R&D project, Ministry of Health & Welfare, Republic of Korea [A120029] FX This work was supported by the Korea Healthcare Technology R&D project, Ministry of Health & Welfare, Republic of Korea [Grant Number A120029]. 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Arch. Psych. Clin. Neurosci. PD SEP PY 2014 VL 264 IS 6 BP 507 EP 515 DI 10.1007/s00406-013-0480-6 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AN8UW UT WOS:000340881500005 PM 24381062 ER PT J AU Soler-Alfonso, C Carvalho, CMB Ge, J Roney, EK Bader, PI Kolodziejska, KE Miller, RM Lupski, JR Stankiewicz, P Cheung, SW Bi, WM Schaaf, CP AF Soler-Alfonso, Claudia Carvalho, Claudia M. B. Ge, Jun Roney, Erin K. Bader, Patricia I. Kolodziejska, Katarzyna E. Miller, Rachel M. Lupski, James R. Stankiewicz, Pawel Cheung, Sau Wai Bi, Weimin Schaaf, Christian P. TI CHRNA7 triplication associated with cognitive impairment and neuropsychiatric phenotypes in a three-generation pedigree SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE dosage sensitivity; copy number variation; cholinergic nervous system; autism spectrum disorder ID COPY NUMBER VARIANTS; GENOME-WIDE ANALYSIS; MENTAL-RETARDATION; 15Q13.3; REARRANGEMENTS; DUPLICATION; RECURRENT; MICRODELETION; MECHANISMS; SCHIZOPHRENIA AB Although deletions of CHRNA7 have been associated with intellectual disability (ID), seizures and neuropsychiatric phenotypes, the pathogenicity of CHRNA7 duplications has been uncertain. We present the first report of CHRNA7 triplication. Three generations of a family affected with various neuropsychiatric phenotypes, including anxiety, bipolar disorder, developmental delay and ID, were studied with array comparative genomic hybridization (aCGH). High-resolution aCGH revealed a 650-kb triplication at chromosome 15q13.3 encompassing the CHRNA7 gene, which encodes the alpha7 subunit of the neuronal nicotinic acetylcholine receptor. A small duplication precedes the triplication at the proximal breakpoint junction, and analysis of the breakpoint indicates that the triplicated segment is in an inverted orientation with respect to the duplication. CHRNA7 triplication appears to occur by a replication-based mechanism that produces inverted triplications embedded within duplications. Co-segregation of the CHRNA7 triplication with neuropsychiatric and cognitive phenotypes provides further evidence for dosage sensitivity of CHRNA7. C1 [Soler-Alfonso, Claudia] Univ Texas Hlth Sci Ctr Houston, Div Med Genet, Dept Pediat, Houston, TX 77030 USA. [Carvalho, Claudia M. B.; Ge, Jun; Roney, Erin K.; Kolodziejska, Katarzyna E.; Lupski, James R.; Stankiewicz, Pawel; Cheung, Sau Wai; Bi, Weimin; Schaaf, Christian P.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Carvalho, Claudia M. B.] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [Bader, Patricia I.; Miller, Rachel M.] Genet Ctr, Parkview Hlth Labs, Ft Wayne, IN USA. [Lupski, James R.] Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA. [Schaaf, Christian P.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. RP Schaaf, CP (reprint author), Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, 1250 Moursund St,Suite 1350, Houston, TX 77030 USA. EM Schaaf@bcm.edu FU Doris Duke Clinical Scientist Development Award; NIH [HD037283]; US National Institute of Neurological Disorders and Stroke [NS058529] FX We are indebted to the family who participated in this study. Dr Schaaf's work is generously supported by the Joan and Stanford Alexander Family. Dr Schaaf is also a recipient of a Doris Duke Clinical Scientist Development Award. NIH grant HD037283 supported Dr Ge's work in the laboratory of Dr Arthur Beaudet. In addition, this work was supported in part by US National Institute of Neurological Disorders and Stroke grant NS058529 to JRL. 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J. Hum. Genet. PD SEP PY 2014 VL 22 IS 9 BP 1071 EP 1076 DI 10.1038/ejhg.2013.302 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AN4SA UT WOS:000340577600004 PM 24424125 ER PT J AU Wang, Y Fang, YD Zhang, FL Xu, M Zhang, JZ Yan, JB Ju, WN Brown, WT Zhong, N AF Wang, Yu Fang, Yudan Zhang, Fengling Xu, Miao Zhang, Jingzhi Yan, Jingbin Ju, Weina Brown, W. Ted Zhong, Nanbert TI Hypermethylation of the enolase gene (ENO2) in autism SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Autism; Neurodevelopment; Gene ENO2; Methylation; Epigenetics ID MECP2 PROMOTER METHYLATION; REVEALS; SCHIZOPHRENIA; EXPRESSION; BIOMARKERS; CORTEX; SERUM AB It has been hypothesized that dysregulation of brain-expressed genes is the major predisposing underlying mechanism for autism. This dysregulation may be mediated by differential methylation of CpG sites within gene promoters, which could be candidate biomarkers and used for early clinical screening of autism. A total of 131 pairs of age- and sex-matched autistic and control subjects were recruited in this study. Peripheral blood cells were analyzed. The first five pairs were randomly applied to array-based genome-wide methylation studies. A neuron-specific gene, ENO2, was found to be hypermethylated in the autistic samples. This difference was validated by bisulfite sequencing PCR (BSP). The differential expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The hypermethylation of ENO2 within the promoter region was confirmed by BSP to be present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2 RNA level in these 19 autistic samples was reduced by about 70 % relative to that in controls. The average level of ENO2 protein expression in the 19 autistic samples (15.18 +/- 3.51 mu g/l) was about half of that in the controls (33.86 +/- 8.16 mu g/l). Conclusion: These findings suggest that reduced ENO2 expression may be a biomarker for a subset of autistic children. C1 [Wang, Yu; Fang, Yudan; Xu, Miao; Zhang, Jingzhi; Yan, Jingbin; Zhong, Nanbert] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Inst Med Genet, Shanghai 200040, Peoples R China. [Wang, Yu; Zhang, Fengling; Zhong, Nanbert] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Inst Children Hlth Care, Shanghai 200040, Peoples R China. [Wang, Yu; Fang, Yudan; Xu, Miao; Zhang, Jingzhi; Yan, Jingbin; Zhong, Nanbert] Minist Hlth, Key Lab Embryo Mol Biol, Shanghai, Peoples R China. [Wang, Yu; Fang, Yudan; Xu, Miao; Zhang, Jingzhi; Yan, Jingbin; Zhong, Nanbert] Shanghai Lab Embryo & Reprod Engn, Shanghai, Peoples R China. [Zhong, Nanbert] Peking Univ, Ctr Med Genet, Beijing 100871, Peoples R China. [Ju, Weina; Brown, W. Ted; Zhong, Nanbert] New York State Inst Basic Res Dev Disabil, New York, NY USA. RP Zhong, N (reprint author), Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Inst Children Hlth Care, 1440 Beijing West Rd, Shanghai 200040, Peoples R China. EM wy_rain@126.com; fangyudan@hotmail.com; zhangfl3985@126.com; xumiao@shhildren.com.cn; zhangjz@shchildren.com.cn; yanjingbin0130@hotmail.com; weina.ju@yahoo.com; ted.brown@opwdd.ny.gov; nanbert.zhong@opwdd.ny.gov FU National "973" program - Chinese Ministry of Science and Technology [2012CB517905]; Shanghai Municipal Department of Science and Technology [2009JC1412600]; Shanghai Municipal Health Bureau [2010Y151]; New York State Office for People with Developmental Disabilities (OPWDD) FX We thank the autism and control children and their parents for making this study feasible. We are extremely grateful to Professors Yitao Zeng and Shuzhen Huang (Shanghai Institute of Medical Genetics) for helpful discussions. This study was supported in part by the National "973" program (2012CB517905) granted from the Chinese Ministry of Science and Technology, and funding from the Shanghai Municipal Department of Science and Technology (2009JC1412600), Shanghai Municipal Health Bureau (2010Y151), and New York State Office for People with Developmental Disabilities (OPWDD). 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Maestripieri, Dario TI Autistic-like and schizotypal traits in a life history perspective: diametrical associations with impulsivity, sensation seeking, and sociosexual behavior SO EVOLUTION AND HUMAN BEHAVIOR LA English DT Article DE Autistic-like traits; Diametrical model; Impulsivity; Life history strategy; Schizotypal traits; Sexual selection; Sociosexuality ID SPECTRUM QUOTIENT AQ; MALE BRAIN THEORY; PHENOTYPIC PLASTICITY; GENERAL-POPULATION; GENETIC-VARIATION; SEX-DIFFERENCES; PERSONALITY; SCHIZOPHRENIA; DISORDER; CREATIVITY AB According to recent theoretical models, autistic-like and schizotypal traits can be regarded as opposite sides of a single continuum of variation in personality and cognition, and may be diametrically associated with individual differences in life history strategies. In this view, schizotypy is a psychological phenotype oriented toward high mating effort and reduced parenting, consistent with a fast life history strategy, whereas autistic-like traits contribute to a slow strategy characterized by reduced mating effort and high parental investment. In this study, we tested the hypothesis that autistic-like and schizotypal traits would be diametrically associated with unrestricted sociosexuality, impulsivity, and sensation seeking (three key behavioral correlates of fast life history strategies in humans) in a sample of 152 young adults (18-38 years). The results were consistent with a diametrical autism-schizotypy axis of individual variation. In line with our hypotheses, autism-schizotypy scores were uniquely associated with individual differences in impulsivity, sensation seeking, and sociosexual behavior, even after controlling for variation in Big Five personality traits. However, we found no significant associations with sociosexual attitude in the present sample. Our findings provide additional support for a life history model of autistic-like and schizotypal traits and demonstrate the heuristic value of this approach in the study of personality and psychopathology. (C) 2014 Elsevier Inc. All rights reserved. C1 [Del Giudice, Marco] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Klimczuk, Amanda C. E.; Maestripieri, Dario] Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA. [Traficonte, Daniel M.] Univ Chicago, Ctr Global Hlth, Chicago, IL 60637 USA. RP Del Giudice, M (reprint author), Univ New Mexico, Dept Psychol, Logan Hall,2001 Redondo Dr NE, Albuquerque, NM 87131 USA. 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Hum. Behav. PD SEP PY 2014 VL 35 IS 5 BP 415 EP 424 DI 10.1016/j.evolhumbehav.2014.05.007 PG 10 WC Psychology, Biological; Behavioral Sciences; Social Sciences, Biomedical SC Psychology; Behavioral Sciences; Biomedical Social Sciences GA AN6EG UT WOS:000340687100009 ER PT J AU Buchanan, R Beckett, RD AF Buchanan, Rachel Beckett, Robert D. TI Assessment of vaccination-related information for consumers available on Facebook (R) SO HEALTH INFORMATION AND LIBRARIES JOURNAL LA English DT Article DE consumer health information; health information needs; information seeking behaviour; social media; social networking ID PERTUSSIS; VACCINES; RUBELLA; AUTISM AB Objectives: To assess the magnitude, interest, purpose and validity of vaccination-related information on Facebook and to determine whether information varies by site viewpoint. Methods: The 10 largest vaccination-focused Facebook (R) pages, groups and places in each category were identified and classified by viewpoint (i.e. anti-, pro-, neutral) and purpose. Number of members, posts per week, likes, comments and shares per post were recorded. Posts were assessed for concordance with CDC and FDA recommendations. Results: Of 30 sites, 43% (n = 13) were anti-vaccination, 7% (n = 2) neutral and 50% (n = 15) pro-vaccination. Most sites were most popular with American users. Median members were similar between anti-vaccination (2703 members, range 337-33 631 members) and pro-vaccination sites (2142 members, range 456-61 565 members, P = 0.262); however, anti-vaccination sites accumulated more posts per week by authors (median 15 vs. 3, P = 0.031) and members (median 33 vs. 1, P < 0.001). Pro-vaccination sites more commonly had commercial purpose (53% [n = 8] vs. 8% [n = 1], P = 0.02). Anti-vaccination sites more commonly gave medical advice (54% [n = 7] vs. 0%, P = 0.004). Overall, 48% (n = 22) of author posts were concordant with regulatory recommendations; concordance was more common on pro-vaccination sites (78% [n = 21] vs. 5% [n = 1], P = 0.0002). Conclusion: Vaccination-related information is prevalent on Facebook regardless of viewpoint; however, anti-vaccination information generates more interest. Anti-vaccination sites were likely to provide medical advice and disagree with regulatory bodies. C1 [Buchanan, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Beckett, Robert D.] Univ Manchester, Coll Pharm, Ft Wayne, IN 46845 USA. RP Beckett, RD (reprint author), Univ Manchester, Coll Pharm, 10627 Diebold Rd, Ft Wayne, IN 46845 USA. 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PD SEP PY 2014 VL 31 IS 3 BP 227 EP 234 DI 10.1111/hir.12073 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA AO2KV UT WOS:000341151500006 PM 25041499 ER PT J AU Micheau, J Vimeney, A Normand, E Mulle, C Riedel, G AF Micheau, Jacques Vimeney, Alice Normand, Elisabeth Mulle, Christophe Riedel, Gernot TI Impaired Hippocampus-Dependent Spatial Flexibility and Sociability Represent Autism-Like Phenotypes in GluK2 Mice SO HIPPOCAMPUS LA English DT Article DE GluK2 KO mice; autism spectrum disorder; social behavior; behavioral flexibility; spatial learning; pattern separation/completion; water maze ID FAMILY-BASED ASSOCIATION; MOSSY FIBER SYNAPSES; GLUTAMATE-RECEPTOR-6 GENE; SPECTRUM DISORDERS; PATTERN SEPARATION; KAINATE RECEPTORS; GLUR6-DEFICIENT MICE; GRIK2 POLYMORPHISMS; BASAL GANGLIA; MEMORY AB Autism is a complex neurodevelopmental disorder with high heritability. grik2 (which encodes the GluK2 subunit of kainate receptors) has been identified as a susceptibility gene in Autism Spectrum Disorders (ASD), but its role in the core and associated symptoms of ASD still remains elusive. We used mice lacking GluK2 (GluK2 KO) to examine their endophenotype with a view to modeling aspects of autism, including social deficits, stereotyped and repetitive behavior and decreased cognitive abilities. Anxiety was recorded in the elevated plus maze, social behavior in a three-chamber apparatus, and cognition in different water maze protocols. Deletion of the GluK2 gene reduced locomotor activity and sociability as indicated by the social interaction task. In addition, GluK2 KO mice learnt to locate a hidden platform in a water maze surrounded by a curtain with hanging cues faster than wild-type mice. They maintained a bias toward the target quadrant when some of these cues were removed, at which point wild-types orthogonalized the behavior and showed no memory. However, GluK2 KO mice were impaired in spatial reversal learning. These behavioral data together with previously published electrophysiology showing severe anomalies in CA3 network activity, suggest a computational shift in this network for enhanced propensity of pattern completion that would explain the loss of behavioral flexibility in GluK2 KO mice. Although a single mutation cannot recapitulate the entire core symptoms of ASD, our data provide evidence for glutamatergic dysfunction underlying a number of social-and cognition-related phenotypes relevant to ASD. (C) 2014 Wiley Periodicals, Inc. C1 [Micheau, Jacques] Univ Bordeaux, INCIA, CNRS, UMR 5287, F-33405 Talence, France. [Vimeney, Alice; Normand, Elisabeth; Mulle, Christophe] Univ Bordeaux, Inst Interdisciplinaire Neurosci, CNRS, UMR 5297, F-33077 Bordeaux, France. [Riedel, Gernot] Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, Scotland. RP Micheau, J (reprint author), Univ Bordeaux, INCIA, CNRS, UMR 5287, Ave Fac, F-33405 Talence, France. 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However, the architecture of the genetic components is still unclear. Genetic studies and subsequent systems biological approaches described converging functional effects of identified genes towards pathways relevant for neuronal signalling. Mouse models suggest an aberrant synaptic plasticity at the neuropathological level, which is believed to be conferred by dysregulation of long-term potentiation or depression of neuronal connections. A central pathway regulating these mechanisms is glutamatergic signalling. Here, we hypothesized that susceptibility genes for ASD are enriched for components of this pathway. To further understand the impact of ASD risk genes on the glutamatergic pathway, we performed a systematic review using the literature database "pubmed" and the "AutismKB" knowledgebase. We provide an overview of the glutamatergic system in typical brain function and development, and summarize findings from linkage, association, copy number variants, and sequencing studies in ASD to provide a comprehensive picture of the glutamatergic landscape of ASD genetics. Genetic variants associated with ASD were enriched in glutamatergic pathways, affecting receptor signalling, metabolism and transport. Furthermore, in genetically modified mouse models for ASD, pharmacological compounds acting on ionotropic or metabotropic receptor activity are able to rescue ASD reminscent phenotypes. We conclude that glutamatergic genetic risk factors for ASD show a complex pattern and further studies are needed to fully understand its mechanisms, before translation of findings into clinical applications and individualized treatment approaches will be possible. C1 [Chiocchetti, Andreas G.; Bour, Hanna S.; Freitag, Christine M.] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. RP Chiocchetti, AG (reprint author), Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Deutschordenstr 50, D-60528 Frankfurt, Germany. 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1081 EP 1106 DI 10.1007/s00702-014-1161-y PG 26 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400002 PM 24493018 ER PT J AU Waltes, R Gfesser, J Haslinger, D Schneider-Momm, K Biscaldi, M Voran, A Freitag, CM Chiocchetti, AG AF Waltes, Regina Gfesser, Johannes Haslinger, Denise Schneider-Momm, Katja Biscaldi, Monica Voran, Anette Freitag, Christine M. Chiocchetti, Andreas G. TI Common EIF4E variants modulate risk for autism spectrum disorders in the high-functioning range SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Association analysis; Transmission disequilibrium testing; Common variant; High-functioning autism; Repetitive behaviour ID FRAGILE-X-SYNDROME; PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; GENETIC-VARIANTS; GERMAN FORM; TRANSLATION; ASSOCIATION; RELIABILITY; BEHAVIORS; MUTATIONS AB The genetic architecture of Autism Spectrum Disorders (ASD) is complex. Common genetic variation has especially been related to high-functioning ASD. In addition, some studies favoured analysis of strictly diagnosed autism individuals, which resulted in more robust findings than the combined analysis of all spectrum individuals. Functional variants modulating EIF4E expression have previously been indicated as risk factors for ASD. Pharmacological modulation of glutamate receptors which regulate EIF4E activity resulted in reduced repetitive behaviours in human and animal studies. Based on these findings, we tested common EIF4E variants for association with overall ASD, with strict autism and with the strict high-functioning autism (strict HFA) subgroup, and their effect on repetitive and/or stereotypic behaviour. We observed over-transmission of rs13109000G in the strict HFA and the strict autism cohort but not in the larger ASD cohort. We report protective effects for the minor allele of rs4699369T on stereotyped and ritualized behaviour in the overall ASD cohort, the strict autism but not in the strict HFA group. In addition, a protective role for rs4699369T and a risk effect of rs12498533G on hand and finger mannerisms was observed. These results need to be replicated in larger ASD and strict autism samples. The predicted impact on transcription through the ASD associated EIF4E variants rs4699369T and rs12498533G as well as the association of the EIF4E interaction partners FMRP and CYFIP1 with ASD point to an mRNA mediated pathomechanism for ASD. C1 [Waltes, Regina; Gfesser, Johannes; Haslinger, Denise; Freitag, Christine M.; Chiocchetti, Andreas G.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, D-60528 Frankfurt, Germany. [Schneider-Momm, Katja; Biscaldi, Monica] Univ Hosp Freiburg, Dept Child & Adolescent Psychiat, D-79104 Freiburg, Germany. [Voran, Anette] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, D-66421 Homburg, Germany. RP Chiocchetti, AG (reprint author), Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, D-60528 Frankfurt, Germany. EM andreas.chiocchetti@kgu.de FU Saarland University [T6 03 10 00-45]; European Union; Bundesministerium fur Bildung und Forschung (ERA-NET NEURON project) [EUHF-AUTISM-01EW1105]; Landes-Offensive zur Entwicklung wissenschaftlich okonomischer Exzellenz (LOEWE): Neuronal Coordination Research Focus Frankfurt (NeFF) FX We thank all patients and their families for taking part in this study. In addition, we thoroughly thank Silvia Lindlar and Hiacynta Jelen for excellent technical assistance and Heiko Zerlaut and Rusico Weber for database management. This work was supported by the Saarland University (T6 03 10 00-45 to C. M. F.), the European Union and the Bundesministerium fur Bildung und Forschung (ERA-NET NEURON project: EUHF-AUTISM-01EW1105 to C. M. F.); and the Landes-Offensive zur Entwicklung wissenschaftlich okonomischer Exzellenz (LOEWE): Neuronal Coordination Research Focus Frankfurt (NeFF to C.M.F.). 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1107 EP 1116 DI 10.1007/s00702-014-1230-2 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400003 PM 24818597 ER PT J AU Taurines, R Segura, M Schecklmann, M Albantakis, L Grunblatt, E Walitza, S Jans, T Lyttwin, B Haberhausen, M Theisen, FM Martin, B Briegel, W Thome, J Schwenck, C Romanos, M Gerlach, M AF Taurines, Regina Segura, Monica Schecklmann, Martin Albantakis, Laura Gruenblatt, Edna Walitza, Susanne Jans, Thomas Lyttwin, Benjamin Haberhausen, Michael Theisen, Frank M. Martin, Berthold Briegel, Wolfgang Thome, Johannes Schwenck, Christina Romanos, Marcel Gerlach, Manfred TI Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Autism spectrum disorder (ASD); Brain-derived neurotrophic factor (BDNF); ADHD; Neurodevelopmental disorders; Peripheral expression ID NEUROTROPHIC FACTOR BDNF; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; GEL-BASED MICROARRAY; MENTAL-RETARDATION; EXECUTIVE DYSFUNCTION; DEPRESSED-PATIENTS; HUMAN PLATELETS; WORKING-MEMORY; SERUM-LEVELS AB Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 +/- A 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 +/- A 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 +/- A 2.2), 15 age- and gender-matched healthy controls (age 12.1 +/- A 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 +/- A 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, eta (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes. C1 [Taurines, Regina; Albantakis, Laura; Jans, Thomas; Lyttwin, Benjamin; Martin, Berthold; Romanos, Marcel; Gerlach, Manfred] Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97080 Wurzburg, Germany. [Segura, Monica] Univ Int Catalunya, Fac Med & Hlth Sci, Barcelona, Spain. [Schecklmann, Martin] Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany. [Gruenblatt, Edna; Walitza, Susanne] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [Haberhausen, Michael] Univ Marburg, Dept Child & Adolescent Psychiat, Marburg, Germany. [Theisen, Frank M.] Herz Jesu Krankenhaus, Dept Child & Adolescent Psychiat, Fulda, Germany. [Briegel, Wolfgang] Leopoldina Hosp, Dept Child & Adolescent Psychiat, Schweinfurt, Germany. [Thome, Johannes] Univ Rostock, Dept Psychiat & Psychotherapy, D-18055 Rostock, Germany. [Thome, Johannes] Swansea Univ, Coll Med, Swansea, W Glam, Wales. [Schwenck, Christina] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, Frankfurt, Germany. RP Taurines, R (reprint author), Univ Wurzburg, Dept Child & Adolescent Psychiat, Fuechsleinstr 15, D-97080 Wurzburg, Germany. EM taurines@kjp.uni-wuerzburg.de FU Actelion; AstraZeneca; Bristol-Meyers Squibb; Ever Neuro Pharma; Janssen-Cilag; Lilly; Lundbeck; Medice Arzneimittel Putter; Merz Pharmaceuticals; Novartis Pharma; Pfizer Pharma; Roche; Servier; Shire; Swiss National Science Foundation (SNF); Deutsche Forschungsgemeinschaft; EU FP7; HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland FX J. T. has obtained financial support (e. g. lecture honoraria, grants for research projects and scientific meetings, advisory-board membership) from Actelion, AstraZeneca, Bristol-Meyers Squibb, Ever Neuro Pharma, Janssen-Cilag, Lilly, Lundbeck, Medice Arzneimittel Putter, Merz Pharmaceuticals, Novartis Pharma, Pfizer Pharma, Roche, Servier, Shire. Some of these companies manufacture drugs used in the treatment of ADHD and ASD. S. W. has received lecture honoraria from Janssen Cilag, AstraZeneca and Eli Lilly in the last 5 years. Her work was partially supported in the last 5 years by the Swiss National Science Foundation (SNF), Deutsche Forschungsgemeinschaft, EU FP7, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland. All other authors have no competing interests. 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TI Elucidating the neurophysiological underpinnings of autism spectrum disorder: new developments SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Autism; Visual event-related potential; Mirror neuron; Connectivity; Transcranial magnetic stimulation; Excitation; Inhibition ID TRANSCRANIAL MAGNETIC STIMULATION; EVENT-RELATED POTENTIALS; FRAGILE-X-SYNDROME; MIRROR NEURON DYSFUNCTION; VISUAL-EVOKED POTENTIALS; HIGH-FUNCTIONING AUTISM; EEG MU-RHYTHM; FACE PERCEPTION; YOUNG-CHILDREN; INTERSTIMULUS VARIANCE AB The study of neurophysiological approaches together with rare and common risk factors for Autism Spectrum Disorder (ASD) allows elucidating the specific underlying neurobiology of ASD. Whereas most neurophysiologically based research in ASD to date has focussed on case-control differences based on the DSM- or ICD-based categorical ASD diagnosis, more recent studies have aimed at studying genetically and/or neurophysiologically defined homogeneous ASD subgroups for specific neuronal biomarkers. This review addresses the neurophysiological investigation of ASD by evoked and event-related potentials, by EEG/MEG connectivity measures such as coherence, and transcranial magnetic stimulation. As an example of classical neurophysiological studies in ASD, we report event-related potential studies which have illustrated which brain areas and processing stages are affected in the visual perception of socially relevant stimuli. However, a paradigm shift has taken place in recent years focussing on how these findings can be tracked down to basic neuronal functions such as deficits in cortico-cortical connectivity and the interaction between brain areas. Disconnectivity, for example, can again be related to genetically induced shifts in the excitation/inhibition balance. Genetic causes of ASD may be grouped by their effects on the brain's system level to identify ASD subgroups which respond differentially to therapeutic interventions. C1 [Luckhardt, C.; Jarczok, T. A.; Bender, S.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, D-60528 Frankfurt, Germany. RP Luckhardt, C (reprint author), Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, Deutschordenstr 50, D-60528 Frankfurt, Germany. EM Christina.Luckhardt@kgu.de FU German Research Foundation DFG (Deutsche Forschungsgemeinschaft) [FR2069/2-1]; LOEWE programme, Neuronal Coordination Research Focus Frankfurt (NeFF) [B1] FX We would like to thank Dr. Susanne Raisig for proofreading our manuscript. This work was supported by grant FR2069/2-1 of the German Research Foundation DFG (Deutsche Forschungsgemeinschaft) to C. M. 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1129 EP 1144 DI 10.1007/s00702-014-1265-4 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400005 PM 25059455 ER PT J AU Ambrosino, S Bos, DJ van Raalten, TR Kobussen, NA van Belle, J Oranje, B Durston, S AF Ambrosino, S. Bos, D. J. van Raalten, T. R. Kobussen, N. A. van Belle, J. Oranje, B. Durston, S. TI Functional connectivity during cognitive control in children with autism spectrum disorder: an independent component analysis SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE ASD; Functional connectivity; ICA; Cognitive control; Rigid behavior ID INHIBITORY CONTROL; FMRI DATA; NETWORK CONNECTIVITY; REPETITIVE BEHAVIOR; DIAGNOSTIC INTERVIEW; RESPONSE-INHIBITION; WORKING-MEMORY; DEFAULT-MODE; MRI DATA; ACTIVATION AB Restrictive and repetitive behavior in autism may be related to deficits in cognitive control. Here, we aimed to assess functional connectivity during a cognitive control task and compare brain network activity and connectivity in children with autism spectrum disorders (ASD) and typically developing children using a multivariate data-driven approach. 19 high-functioning boys with ASD and 19 age-matched typically developing boys were included in this study. Functional magnetic resonance imaging was performed at 3T during the performance of a cognitive control task (go/no-go paradigm). Functional networks were identified using independent component analysis. Network activity and connectivity was compared between groups and correlated with clinical measures of rigid behavior using multivariate analysis of covariance. We found no differences between the groups in task performance or in network activity. Power analysis indicated that, if this were a real difference, it would require nearly 800 subjects to show group differences in network activity using this paradigm. Neither were there correlations between network activity and rigid behavior. Our data do not provide support for the presence of deficits in cognitive control in children with ASD, or the functional networks supporting this ability. C1 [Ambrosino, S.; Bos, D. J.; van Raalten, T. R.; Kobussen, N. A.; van Belle, J.; Oranje, B.; Durston, S.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, NICHE Lab, Dept Psychiat, NL-3584 CX Utrecht, Netherlands. RP Ambrosino, S (reprint author), Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, NICHE Lab, Dept Psychiat, HP A-01-126,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM S.AmbrosinodiBruttopilo-3@umcutrecht.nl FU Hersenstichting Nederland [F2009(1)-17] FX The authors would like to thank all the participants and their families of this study. We wish to thank Juliette Weusten for the assistance with subject recruitment and MRI assessment. This work was financially supported by the Hersenstichting Nederland, grant number F2009(1)-17. 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TI The effect of age, diagnosis, and their interaction on vertex-based measures of cortical thickness and surface area in autism spectrum disorder SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Autism; Neuroanatomy; Cortical thickness; Surface area; Neurodevelopment ID COORDINATE SYSTEM; BRAIN OVERGROWTH; PROGENITOR CELLS; CEREBRAL-CORTEX; MRI; CHILDREN; ADOLESCENCE; ANATOMY; ADULTS; REPRESENTATION AB Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group x age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall. C1 [Ecker, C.; Shahidiani, A.; Feng, Y.; Daly, E.; Murphy, C.; D'Almeida, V.; Gillan, N.; Gudbrandsen, M.; Wichers, R.; Andrews, D.; Murphy, D. G. M.] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London SE5 8AF, England. [Ecker, C.; Shahidiani, A.; Feng, Y.; Daly, E.; Murphy, C.; D'Almeida, V.; Gillan, N.; Gudbrandsen, M.; Wichers, R.; Andrews, D.; Murphy, D. G. M.] Kings Coll London, Inst Psychiat, Sackler Inst Translat Neurodev Sci, London SE5 8AF, England. [Deoni, S.] Brown Univ, Sch Engn, Adv Baby Imaging Lab, Providence, RI 02912 USA. [Williams, S. C.; Van Hemert, L.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, London SE5 8AF, England. RP Ecker, C (reprint author), Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London SE5 8AF, England. EM christine.ecker@kcl.ac.uk RI Williams, Steve/D-6979-2011; Ecker, Christine/E-5194-2010 FU Medical Research Council UK [G0400061, G0800298]; Dr. Mortimer and Theresa Sackler Foundation; EU-AIMS project (European Autism Interventions-a Multicentre Study for developing New Medications) from the Innovative Medicines Initiative Joint Undertaking [115300]; EU; NIHR Biomedical Research Centre for Mental Health at King's College London, Institute of Psychiatry; South London & Maudsley NHS Foundation Trust FX This work was supported (1) by the Medical Research Council UK (G0400061 and G0800298), (2) by the Dr. Mortimer and Theresa Sackler Foundation, (3) by the EU-AIMS project (European Autism Interventions-a Multicentre Study for developing New Medications) receiving support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, which includes financial contributions from the EU Seventh Framework Programme (FP7/2007-2013), (4) by the NIHR Biomedical Research Centre for Mental Health at King's College London, Institute of Psychiatry, and (5) by the South London & Maudsley NHS Foundation Trust. We are also grateful to those who agreed to be scanned and who gave their time so generously to this study. 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1157 EP 1170 DI 10.1007/s00702-014-1207-1 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400007 PM 24752753 ER PT J AU Greimel, E Schulte-Ruther, M Kamp-Becker, I Remschmidt, H Herpertz-Dahlmann, B Konrad, K AF Greimel, Ellen Schulte-Ruether, Martin Kamp-Becker, Inge Remschmidt, Helmut Herpertz-Dahlmann, Beate Konrad, Kerstin TI Impairment in face processing in autism spectrum disorder: a developmental perspective SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Autism spectrum disorder; Development; Age; Face recognition; Emotion ID HIGH-FUNCTIONING ADULTS; FACIAL EXPRESSION; EMOTION RECOGNITION; ASPERGER-SYNDROME; BRAIN ACTIVATION; CHILDREN; PERCEPTION; AMYGDALA; INFORMATION; CHILDHOOD AB Findings on face identity and facial emotion recognition in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about the developmental trajectory of face processing skills in ASD. Taking a developmental perspective, the aim of this study was to extend previous findings on face processing skills in a sample of adolescents and adults with ASD. N = 38 adolescents and adults (13-49 years) with high-functioning ASD and n = 37 typically developing (TD) control subjects matched for age and IQ participated in the study. Moreover, n = 18 TD children between the ages of 8 and 12 were included to address the question whether face processing skills in ASD follow a delayed developmental pattern. Face processing skills were assessed using computerized tasks of face identity recognition (FR) and identification of facial emotions (IFE). ASD subjects showed impaired performance on several parameters of the FR and IFE task compared to TD control adolescents and adults. Whereas TD adolescents and adults outperformed TD children in both tasks, performance in ASD adolescents and adults was similar to the group of TD children. Within the groups of ASD and control adolescents and adults, no age-related changes in performance were found. Our findings corroborate and extend previous studies showing that ASD is characterised by broad impairments in the ability to process faces. These impairments seem to reflect a developmentally delayed pattern that remains stable throughout adolescence and adulthood. C1 [Greimel, Ellen; Schulte-Ruether, Martin; Konrad, Kerstin] Rhein Westfal TH Aachen, Univ Hosp, Dept Child & Adolescent Psychiat, Child Neuropsychol Sect, D-52062 Aachen, Germany. [Greimel, Ellen; Herpertz-Dahlmann, Beate] Rhein Westfal TH Aachen, Univ Hosp, Dept Child & Adolescent Psychiat, D-52062 Aachen, Germany. [Greimel, Ellen] Univ Hosp Munich, Dept Child & Adolescent Psychiat, D-80336 Munich, Germany. [Kamp-Becker, Inge; Remschmidt, Helmut] Univ Hosp Giessen & Marburg, Dept Child & Adolescent Psychiat, Giessen, Germany. RP Greimel, E (reprint author), Univ Hosp Munich, Dept Child & Adolescent Psychiat, Pettenkoferstr 8a, D-80336 Munich, Germany. EM Ellen.Greimel@med.uni-muenchen.de RI Konrad, Kerstin/H-7747-2013 OI Konrad, Kerstin/0000-0001-9039-2615 FU Vifor Pharma; Novartis; Medice FX B. H.-D. receives industry research funding from Vifor Pharma. K. K. received speaking fees from Novartis and Medice. All other authors declare that they have no conflicts of interest. 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SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE ASD; WM; Inhibition; Individual differences ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; N-BACK TASK; DISRUPTIVE BEHAVIOR DISORDERS; LATENT-VARIABLE ANALYSIS; DIAGNOSTIC OBSERVATION SCHEDULE; DEFICIT HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; RESPONSE-INHIBITION; PSYCHIATRIC-DISORDERS AB Findings on working memory (WM) and inhibition in children with autism spectrum disorders (ASD) are contradictory and earlier studies largely ignored individual differences. As WM and inhibition seem to be related, children who experience WM deficits might also experience inhibition deficits. Moreover, these children possibly form a distinct subgroup, differing on other variables, such as cognitive functioning, symptom severity, behavior, and attention deficit hyperactivity disorder (ADHD) characteristics. We studied a large sample of children with and without ASD (8-12 years, IQ > 80) with classic experimental tasks (n-back task, ASD n = 77, control n = 45; stop task, ASD n = 74, control n = 43), and explored individual differences. The ASD group made more errors on the n-back task with increasing WM load, and had longer stop signal reaction times on the stop task when compared with controls. However, only 6 % of the ASD group showed both WM and inhibition deficits, and 71 % showed no deficits. Parents of children with WM and/or inhibition deficits tended to report more conduct problems on the disruptive behavior disorder rating scale. ADHD characteristics did not influence performance. Some children used medication during testing, which seemingly influenced stop task performance, but excluding these data did not change the main findings. Large individual differences in cognitive functioning are present, even within children with ASD with average or above average intelligence. 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1183 EP 1198 DI 10.1007/s00702-014-1225-z PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400009 PM 24796318 ER PT J AU Pankert, A Pankert, K Herpertz-Dahlmann, B Konrad, K Kohls, G AF Pankert, Azarakhsh Pankert, Kilian Herpertz-Dahlmann, Beate Konrad, Kerstin Kohls, Gregor TI Responsivity to familiar versus unfamiliar social reward in children with autism SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Autism spectrum disorders; Social reward; Nonsocial reward; Familiarity; Cognitive control ID FUSIFORM FACE AREA; SPECTRUM DISORDERS; BRAIN PLASTICITY; MONETARY REWARD; JOINT ATTENTION; ROMANTIC LOVE; MOTIVATION; INTERVENTION; DYSFUNCTION; IMPAIRMENT AB In autism spectrum disorders (ASD), social motivation theories suggest that the core social communication problems seen in children with ASD arise from diminished responsiveness to social reward. Although clinical and experimental data support these theories, the extent to which the reward deficit in ASD is unique for social rewards remains unclear. With the present investigation, we aimed to provide insight into the degree to which sociality as well as familiarity of reward incentives impact motivated goal-directed behavior in children with ASD. To do so, we directly compared the influence of familiar versus unfamiliar social reward relative to nonsocial, monetary reward in children with ASD relative to age- and IQ-matched typically developing controls (TDC) using a visual and auditory incentive go/nogo task with reward contingencies for successful response inhibitions. We found that children with ASD responded stronger to visual familiar and unfamiliar social reward as well as to nonsocial, monetary reward than TDC. While the present data are at odds with predictions made by social motivation theories, individual variations beyond clinical diagnosis, such as reward exposure across various social settings, help explain the pattern of results. The findings of this study stress the necessity for additional research on intra-individual as well as environmental factors that contribute to social reward responsiveness in individuals with ASD versus other neuropsychiatric disorders such as ADHD or conduct disorder. C1 [Pankert, Azarakhsh; Pankert, Kilian; Konrad, Kerstin; Kohls, Gregor] Rhein Westfal TH Aachen, Child Neuropsychol Sect, Dept Child & Adolescent Psychiat, D-52074 Aachen, Germany. [Herpertz-Dahlmann, Beate] Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat, D-52074 Aachen, Germany. RP Kohls, G (reprint author), Rhein Westfal TH Aachen, Child Neuropsychol Sect, Dept Child & Adolescent Psychiat, Neuenhofer Weg 21, D-52074 Aachen, Germany. EM gkohls@ukaachen.de RI Konrad, Kerstin/H-7747-2013 OI Konrad, Kerstin/0000-0001-9039-2615 FU German Research Foundation (Deutsche Forschungsgemeinschaft/DFG) [IRTG 1328] FX We would like to thank all young volunteers and their families who participated in this study. We also thank Astrid Putz-Ebert for her help with data collection. This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft/DFG, IRTG 1328). We are also very grateful to two anonymous reviewers for their helpful comments on earlier versions of the manuscript. 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Neural Transm. PD SEP PY 2014 VL 121 IS 9 SI SI BP 1199 EP 1210 DI 10.1007/s00702-014-1210-6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO1TB UT WOS:000341096400010 PM 24728874 ER PT J AU Veness, C Prior, M Eadie, P Bavin, E Reilly, S AF Veness, Carly Prior, Margot Eadie, Patricia Bavin, Edith Reilly, Sheena TI Predicting autism diagnosis by 7 years of age using parent report of infant social communication skills SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH LA English DT Article DE autism; infant; longitudinal study; non-verbal communication; social interaction ID SPECTRUM DISORDERS; EARLY INDICATORS; HOME VIDEOTAPES; 2ND YEAR; CHILDREN; LANGUAGE; LIFE AB Aim: The aim of this study is to identify social communication skills in infancy which predict autism spectrum disorder (ASD) diagnosis by 7 years as compared with children with other developmental difficulties or typical development from within a population sample. Methods: Children with an ASD (n = 41), developmental delay (n = 28), language impairment (n = 47) and typical development (n = 41) were drawn from a large, longitudinal community sample following children from 8 months to 7 years of age, the Early Language in Victoria Study. At 7 years of age, early social communication skills at 8, 12 and 24 months from the Communication and Symbolic Behavior Scales Infant-Toddler Checklist and the MacArthur-Bates Communicative Development Inventory: Words and Gestures were compared between groups and used to predict ASD diagnosis. Results: Significant predictors of ASD diagnosis were found from 8 months, predominantly focused on gesture use and communicative behaviours, such as requesting and joint attention. While comparisons between children with ASD and children with language impairment and typical development revealed differences from 8 months of age, the developmental delay group did not differ significantly from ASD on any measure until 24 months of age. At 24 months, children with ASD had lower Communication and Symbolic Behavior Scales Use of Communication scores as compared with all other groups. Conclusions: The capacity to identify early markers of ASD should facilitate awareness of the risk of an ASD as compared with other developmental problems and point to the need for further developmental assessment, monitoring and provision of early intervention if indicated. C1 [Veness, Carly; Eadie, Patricia; Reilly, Sheena] Royal Childrens Hosp, Murdoch Childrens Res Inst, Hearing Language & Literacy Grp, Melbourne, Vic, Australia. [Prior, Margot] Univ Melbourne, Melbourne, Vic, Australia. [Eadie, Patricia] Univ Melbourne, Dept Audiol & Speech Pathol, Melbourne, Vic, Australia. [Reilly, Sheena] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Bavin, Edith] La Trobe Univ, Sch Psychol Sci, Melbourne, Vic, Australia. RP Reilly, S (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM sheena.reilly@mcri.edu.au FU National Health and Medical Research Council (NHMRC) [1041947, 607407, 1023493]; Victorian Government Operational Infrastructure Support Program; NHMRC [1041892]; Nadia Verrall Memorial Research Grant from Speech Pathology Australia; Syd and Ann Wellard Memorial Trust FX ELVS was supported by the National Health and Medical Research Council (NHMRC) Project Grants (#1041947, #607407 and #1023493) and the Victorian Government Operational Infrastructure Support Program. SR was supported by the NHMRC practitioner fellowship (#1041892). The ELVS Autism study was supported by the Nadia Verrall Memorial Research Grant from Speech Pathology Australia and the Syd and Ann Wellard Memorial Trust as administered by Equity Trustees Limited. The authors would like to acknowledge and thank all participating families and the ELVS research assistants. CR Allen CW, 2007, J AUTISM DEV DISORD, V37, P1272, DOI 10.1007/s10803-006-0279-7 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Australian Bureau of Statistics, 2001, SOC EC IND AR Barbaro J, 2013, AUTISM, V17, P64, DOI 10.1177/1362361312442597 Fenson L, 2007, MACARTHUR BATES COMM Mitchell S, 2006, J DEV BEHAV PEDIATR, V27, pS69, DOI 10.1097/00004703-200604002-00004 Reilly S, 2006, J PAEDIATR CHILD H, V42, P764, DOI 10.1111/j.1440-1754.2006.00974.x Reilly S, 2007, PEDIATRICS, V120, pE1441, DOI 10.1542/peds.2007-0045 Robins DL, 2008, AUTISM, V12, P537, DOI 10.1177/1362361308094502 Rutter M, 2008, SOCIAL COMMUNICATION Semel E., 2006, CLIN EVALUATION LANG, V4th Shumway S, 2009, J SPEECH LANG HEAR R, V52, P1139, DOI 10.1044/1092-4388(2009/07-0280) Stata Statistical Software, 2007, STAT STAT SOFTW VERS Tomblin JB, 1997, J SPEECH LANG HEAR R, V40, P1245 Trillingsgaard A, 2005, EUR CHILD ADOLES PSY, V14, P65, DOI 10.1007/s00787-005-0433-3 Veness C, 2012, AUTISM, V16, P163, DOI 10.1177/1362361311399936 Ventola P, 2007, J AUTISM DEV DISORD, V37, P425, DOI 10.1007/s10803-006-0177-z Watson LR, 2013, AM J SPEECH-LANG PAT, V22, P25, DOI 10.1044/1058-0360(2012/11-0145) Wechsler D, 1999, WECHSLER ABBREVIATED Werner E, 2000, J AUTISM DEV DISORD, V30, P157, DOI 10.1023/A:1005463707029 Werner E, 2005, ARCH GEN PSYCHIAT, V62, P889, DOI 10.1001/archpsyc.62.8.889 Wetherby A. M., 2001, COMMUNICATION SYMBOL Wetherby AM, 2007, J AUTISM DEV DISORD, V37, P960, DOI 10.1007/s10803-006-0237-4 Wetherby AM, 2004, J AUTISM DEV DISORD, V34, P473, DOI 10.1007/s10803-004-2544-y NR 24 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 SEP PY 2014 VL 50 IS 9 BP 693 EP 700 DI 10.1111/jpc.12614 PG 8 WC Pediatrics SC Pediatrics GA AO2HV UT WOS:000341141200007 PM 24909517 ER PT J AU McLean, RL Harrison, AJ Zimak, E Joseph, RM Morrow, EM AF McLean, Rebecca L. Harrison, Ashley Johnson Zimak, Eric Joseph, Robert M. Morrow, Eric M. TI Executive Function in Probands With Autism With Average IQ and Their Unaffected First-Degree Relatives SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism spectrum disorder; executive functioning; adaptive functioning; IQ; pedigree ID TRAUMATIC BRAIN-INJURY; SPECTRUM DISORDERS; COGNITIVE PHENOTYPE; CHILDREN; INDIVIDUALS; PARENTS; IMPAIRMENTS; DYSFUNCTION; CHILDHOOD; PROFILES AB Objective: This study aimed to characterize executive function (EF) in pedigrees of children with autism spectrum disorder (ASD) and average IQ. The authors examined the hypothesis that deficits in EF relate to lower levels of adaptive functioning, and they assessed evidence for a cognitive extended phenotype in unaffected relatives in a large, well-characterized sample. Method: Proband EF was assessed by parent-report questionnaires (Behavior Rating Inventory of Executive Functioning [BRIEF], n = 109) and child neuropsychological tests (Delis-Kaplan Executive Functioning System [D-KEFS], n = 35). EF also was examined in parents (D-KEFS, n = 335) and unaffected siblings (BRIEF, n = 114; D-KEFS, n = 57). Adaptive functioning was assessed by the Vineland Adaptive Behavior Scales-II (n = 155). All data were obtained from the Autism Consortium Clinical Genetics Database. Results: Individuals with ASD showed important EF weaknesses. Multiple regression analyses showed that parent-reported EF deficits were related to profound decreases in adaptive functioning even after controlling for age, IQ and severity of ASD symptoms. Parent-reported EF also was related to adaptive skills in preschoolers. First-degree unaffected relatives did not demonstrate difficulties with EF compared with normative data. Conclusion: In this study, EF impairments do not appear to relate to broad familial risk factors for ASD but may be associated with factors relevant to the expression of ASD in probands. Results support the benefits of EF assessment as a way to identify potential therapeutic targets that could lead to improved adaptive behavior in children with ASD and average IQ. C1 [McLean, Rebecca L.; Morrow, Eric M.] Brown Univ, Sch Med, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, Providence, RI 02912 USA. [McLean, Rebecca L.] Mem Hosp Rhode Isl, Neurodev Ctr, Pawtucket, RI USA. [Harrison, Ashley Johnson; Zimak, Eric] Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, East Providence, RI USA. [Harrison, Ashley Johnson; Zimak, Eric] Brown Univ, Med Sch, Providence, RI 02912 USA. [Joseph, Robert M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Joseph, Robert M.; Morrow, Eric M.] Autism Consortium, Boston, MA USA. [Morrow, Eric M.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. RP Morrow, EM (reprint author), Brown Univ, Mol Med Lab, 70 Ship St, Providence, RI 02912 USA. EM eric_morrow@brown.edu RI Joseph, Roy/D-8530-2015 FU Dr. Morrow's Career Award in Medical Science from the Burroughs Wellcome Fund; National Institutes of Health (NIH) / National Institute of General Medical Sciences (NIGMS) [P20GM103645 01A1]; Autism Consortium; NIMH [1R01MH085143, 1R01MH083565] FX This research was supported by Dr. Morrow's Career Award in Medical Science from the Burroughs Wellcome Fund and the National Institutes of Health (NIH) / National Institute of General Medical Sciences (NIGMS) grant P20GM103645 01A1 : Project Award under Neuroscience COBRE Project. The collection of data and biomaterials comes from the Phenotypic and Genetic Factors in Autism Spectrum Disorders Study. Since 2008, this project has been supported by the Autism Consortium and by NIMH grants (1R01MH085143, principal investigator, Louis M. Kunkel, PhD; 1R01MH083565, principal investigator, Christopher Walsh, MD, PhD) CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT BaronCohen S, 1997, J COGNITIVE NEUROSCI, V9, P548, DOI 10.1162/jocn.1997.9.4.548 Bolte S, 2002, CHILD PSYCHIAT HUM D, V33, P165, DOI 10.1023/A:1020734325815 Delis DC, 2001, DELIS KAPLAN EXECUTI Delorme R, 2007, EUR PSYCHIAT, V22, P32, DOI 10.1016/j.eurpsy.2006.05.002 Duncan AW, 2013, AUTISM Eigsti I. 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Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2014 VL 53 IS 9 BP 1001 EP 1009 DI 10.1016/j.jaac.2014.05.019 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AO3HW UT WOS:000341221300010 PM 25151423 ER PT J AU Crider, A Pandya, CD Peter, D Ahmed, AO Pillai, A AF Crider, Amanda Pandya, Chirayu D. Peter, Diya Ahmed, Anthony O. Pillai, Anilkumar TI Ubiquitin-proteasome dependent degradation of GABA(A)alpha 1 in autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Autism; GABA(A) receptor; Ubiquitination; SYVN1; Neurons ID ENDOPLASMIC-RETICULUM; RECEPTORS; SYSTEM; PHOSPHORYLATION; EXPRESSION; RETENTION; EPILEPSY; MUTATION; PATHWAY; CORTEX AB Background: Although the neurobiological basis of autism spectrum disorder (ASD) is not fully understood, recent studies have indicated the potential role of GABA(A) receptors in the pathophysiology of ASD. GABA(A) receptors play a crucial role in various neurodevelopmental processes and adult neuroplasticity. However, the mechanism(s) of regulation of GABA(A) receptors in ASD remains poorly understood. Methods: Postmortem middle frontal gyrus tissues (13 ASD and 13 control subjects) were used. In vitro studies were performed in primary cortical neurons at days in vitro (DIV) 14. The protein levels were examined by western blotting. Immunofluorescence studies were employed for cellular localization. The gene expression was determined by RT-PCR array and qRT-PCR. Results: A significant decrease in GABA(A)alpha 1 protein, but not mRNA levels was found in the middle frontal gyrus of ASD subjects indicating a post-translational regulation of GABA(A) receptors in ASD. At the cellular level, treatment with proteasomal inhibitor, MG132, or lactacystin significantly increased GABA(A)alpha 1 protein levels and Lys48-linked polyubiquitination of GABA(A)alpha 1, but reduced proteasome activity in mouse primary cortical neurons (DIV 14 from E16 embryos). Moreover, treatment with betulinic acid, a proteasome activator significantly decreased GABA(A alpha)1 protein levels in cortical neurons indicating the role of polyubiquitination of GABA(A)alpha 1 proteins with their subsequent proteasomal degradation in cortical neurons. Ubiquitination specific RT-PCR array followed by western blot analysis revealed a significant increase in SYVN1, an endoplasmic reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase in the middle frontal gyrus of ASD subjects. In addition, the inhibition of proteasomal activity by MG132 increased the expression of GABA(A)alpha 1 in the ER. The siRNA knockdown of SYVN1 significantly increased GABA(A)alpha 1 protein levels in cortical neurons. Moreover, reduced association between SYVN1 and GABA(A)alpha 1 was found in the middle frontal gyrus of ASD subjects. Conclusions: SYVN1 plays a critical role as an E3 ligase in the ubiquitin proteasome system (UPS)-mediated GABA(A)a1 degradation. Thus, inhibition of the ubiquitin-proteasome-mediated GABA(A)alpha 1 degradation may be an important mechanism for preventing GABA(A)alpha 1 turnover to maintain GABA(A)alpha 1 levels and GABA signaling in ASD. C1 [Crider, Amanda; Pandya, Chirayu D.; Peter, Diya; Pillai, Anilkumar] Georgia Regents Univ, Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. [Ahmed, Anthony O.] Will Cornell Med Coll, Dept Psychiat, White Plains, NY 10605 USA. RP Pillai, A (reprint author), Georgia Regents Univ, Med Coll Georgia, Dept Psychiat & Hlth Behav, 997 St Sebastian Way, Augusta, GA 30912 USA. EM apillai@gru.edu FU NIH [HHSN275200900011C, NO1-HD-9-0011] FX Human postmortem samples were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD, USA. The Bank is funded by NIH Contract No. #HHSN275200900011C, Ref. No. NO1-HD-9-0011. 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Autism PD SEP 1 PY 2014 VL 5 AR 45 DI 10.1186/2040-2392-5-45 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AO2NC UT WOS:000341159500001 PM 25392730 ER PT J AU McDonagh, MS Matthews, A Phillipi, C Romm, J Peterson, K Thakurta, S Guise, JM AF McDonagh, Marian S. Matthews, Annette Phillipi, Carrie Romm, Jillian Peterson, Kim Thakurta, Sujata Guise, Jeanne-Marie TI Depression Drug Treatment Outcomes in Pregnancy and the Postpartum Period A Systematic Review and Meta-analysis SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID SEROTONIN-REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; PERSISTENT PULMONARY-HYPERTENSION; PRENATAL ANTIDEPRESSANT EXPOSURE; AUTISM SPECTRUM DISORDERS; POPULATION-BASED COHORT; MATERNAL DEPRESSION; NEONATAL OUTCOMES; CONGENITAL-MALFORMATIONS; POSTNATAL DEPRESSION AB OBJECTIVE: To evaluate the comparative benefits and harms in both mother and child of antidepressant treatment for depression in pregnant or postpartum women. DATA SOURCES: MEDLINE, the Cochrane Library, CINAHL, Scopus, ClinicalTrials.gov (inception to July 2013), manufacturers, and reference lists. METHODS OF STUDY SELECTION: Two reviewers independently selected studies of pregnant women with depression comparing antidepressants with each other, placebo or no treatment, or nondrug treatments. Studies making comparisons among women taking antidepressants for any reason and those not taking antidepressants (depression status unknown) were used to fill gaps in the evidence. TABULATION, INTEGRATION, AND RESULTS: Dual study data extraction and quality assessment were used. Six randomized controlled trials and 15 observational studies provided evidence. Low-strength evidence suggested neonates of pregnant women with depression taking selective serotonin reuptake inhibitors had higher risk of respiratory distress than did neonates of untreated women (13.9% compared with 7.8%; P<.001) but no difference in risk of neonatal convulsions (0.14% compared with 0.11%; P=.64) or preterm birth (17% compared with 10%; P=.07). Indirect evidence from studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants (depression status unknown) suggested future research should focus on congenital anomalies and autism spectrum and attention deficit disorders in the child. In postpartum depression, low-strength evidence suggested symptom response was not improved when sertraline was added to psychotherapy or when cognitive-behavioral therapy was added to paroxetine. Evidence was insufficient for other outcomes, including depression symptoms, functional capacity, breastfeeding, and infant and child development. A serious limitation is the lack of study populations of exclusively depressed pregnant and postpartum women. CONCLUSION: Evidence about the comparative benefits and harms of pharmacologic treatment of depression in pregnant and postpartum women was largely inadequate to allow informed decisions about treatment. Considering the prevalence of depression, filling this gap is essential. C1 Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Sch Med, Portland, OR 97230 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97230 USA. Oregon Hlth & Sci Univ, Dept Pediat, Sch Med, Portland, OR 97230 USA. Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Sch Med, Portland, OR 97230 USA. Portland Vet Affairs Hosp, Portland, OR USA. RP McDonagh, MS (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97230 USA. 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Gynecol. PD SEP PY 2014 VL 124 IS 3 BP 526 EP 534 DI 10.1097/AOG.0000000000000410 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AO4OV UT WOS:000341320800008 PM 25004304 ER PT J AU Randles, C AF Randles, Clint TI Early Childhood Music Therapy and Autism Spectrum Disorders. SO PSYCHOLOGY OF MUSIC LA English DT Book Review C1 [Randles, Clint] Univ S Florida, Tampa, FL 33620 USA. RP Randles, C (reprint author), Univ S Florida, Tampa, FL 33620 USA. CR KERN P, 2012, EARLY CHILDHOOD MUSI Randles C., 2013, GEN MUSIC TODAY, V27, P48 Randles C., MUSIC MEDIA IN PRESS Randles C, 2012, J AESTHET EDUC, V46, P36 Randles C., J MUSIC TEC IN PRESS NR 5 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0305-7356 EI 1741-3087 J9 PSYCHOL MUSIC JI Psychol. Music PD SEP PY 2014 VL 42 IS 5 BP 766 EP 767 PG 3 WC Psychology, Educational; Psychology, Applied; Music; Psychology, Experimental SC Psychology; Music GA AN6SV UT WOS:000340728400009 ER PT J AU Dickerson, AS Pearson, DA Loveland, KA Rahbar, MH Filipek, PA AF Dickerson, Aisha S. Pearson, Deborah A. Loveland, Katherine A. Rahbar, Mohammad H. Filipek, Pauline A. TI Role of parental occupation in autism spectrum disorder diagnosis and severity SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Diagnosis; Severity; Risk; Occupation; Parents ID INTERGENERATIONAL TRANSMISSION; GENERAL-POPULATION; JAMAICAN CHILDREN; PHENOTYPE; EXPOSURE; LEAD; MATHEMATICIANS; ADOLESCENTS; SIBLINGS; MERCURY AB Some have suggested that parents of children with autism spectrum disorder (ASD) may present with less recognizable autistic-like phenotypic characteristics, leading them to highly systemizing occupations. Using secondary analysis of data from two previous studies of children with ASD, we tested associations between parental occupations and ASD diagnosis and the association of parental occupational characteristics on ASD severity. We found that fathers in healthcare (P < 0.01) and finance (P = 0.03) were more likely to have children with ASD. Additionally, joint effects of parental technical occupations were associated with communication (P < 0.01) and social impairment (P = 0.04). These results support that a "broader phenotype" and possible assortative mating in adults with autistic-like characteristics might contribute to intergenerational transmission and having offspring with greater ASD severity. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Dickerson, Aisha S.; Rahbar, Mohammad H.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX USA. [Dickerson, Aisha S.; Rahbar, Mohammad H.] Univ Texas Houston, Hlth Sci Ctr, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design Core, Houston, TX 77030 USA. [Pearson, Deborah A.; Loveland, Katherine A.] Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Filipek, Pauline A.] Univ Texas Houston, Hlth Sci Ctr, Childrens Learning Inst, Dept Pediat, Houston, TX 77030 USA. [Filipek, Pauline A.] Univ Texas Houston, Hlth Sci Ctr, Div Child & Adolescent Neurol, Houston, TX 77030 USA. RP Dickerson, AS (reprint author), Univ Texas Houston, Hlth Sci Ctr, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design Core, UT Profess Bldg Suite 1100-05, Houston, TX 77030 USA. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 997 EP 1007 DI 10.1016/j.rasd.2014.05.007 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600001 ER PT J AU Gargaro, BA May, T Tonge, BJ Sheppard, DM Bradshaw, JL Rinehart, NJ AF Gargaro, B. A. May, T. Tonge, B. J. Sheppard, D. M. Bradshaw, J. L. Rinehart, N. J. TI Using the DBC-P Hyperactivity Index to screen for ADHD in young people with autism and ADHD: A pilot study SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE ADHD; Autism spectrum disorder; Comorbidity; DBC; Hyperactivity ID PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIOR CHECKLIST; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; CHILDREN; POPULATION; ADOLESCENTS; INSTRUMENT; SYMPTOMS; SAMPLE AB This study aimed to (1) determine preliminary validity of the Developmental Behaviour Checklist-Hyperactivity Index (DBC-HI) as a screening measure of combined-type ADHD in autism and ADHD, and (2) compare emotional-behavioural disturbance using the DBC in autism, ADHD and autism + ADHD. Forty-nine age- and PIQ-matched young people [6-18 years; 12 autism, 13 ADHD, 12 autism + ADHD, 12 typically developing] were recruited. Parents completed the Conners-Revised Rating Scale and DBC. The DBC-HI displayed strong internal consistency and good external validity, reliably measuring combined-type ADHD. The DBC-HI distinguished autism from autism + ADHD with fair sensitivity and specificity. Individuals with autism + ADHD exhibited a more severe profile of emotional-behavioural disturbance than autism or ADHD alone. The DBC may be a useful 'all-in-one' screening tool to (1) identify comorbidity and (2) determine the severity of emotional-behavioural disturbance in autism and/or ADHD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Gargaro, B. A.; Tonge, B. J.; Bradshaw, J. L.] Monash Univ, Sch Psychol & Psychiat, Clayton, Vic 3800, Australia. [May, T.; Rinehart, N. J.] Deakin Univ, Burwood, Vic 3125, Australia. [Sheppard, D. M.] Monash Univ, Monash Univ Accid Res Ctr, Monash Injury Res Inst, Clayton, Vic 3800, Australia. RP May, T (reprint author), Deakin Univ, 221 Burwood Highway, Burwood, Vic 3125, Australia. 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PD SEP PY 2014 VL 8 IS 9 BP 1008 EP 1015 DI 10.1016/j.rasd.2014.05.004 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600002 ER PT J AU Brady, DI Saklofske, DH Schwean, VL Montgomery, JM McCrimmon, AW Thorne, KJ AF Brady, Danielle I. Saklofske, Donald H. Schwean, Vicki L. Montgomery, Janine M. McCrimmon, Adam W. Thorne, Keoma J. TI Cognitive and emotional intelligence in young adults with Autism Spectrum Disorder without an accompanying intellectual or language disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Asperger's syndrome; Autism Spectrum Disorder; Cognitive intelligence; Emotional intelligence; Neuropsychology and young adults ID ASPERGERS SYNDROME; SOCIAL INTELLIGENCE; INDIVIDUALS; HEALTH AB Research in the neurosciences has identified distinctions between neural structures that subserve cognitive intelligence (CI) and those subserving emotional intelligence (EI). This study explored the performance of young adults with Autism Spectrum Disorder (ASD) without an accompanying intellectual or language disorder relative to typically-developing peers, on indices of CI and EI. Both the ASD and age- and sex-matched typically-developing groups exhibited high average cognitive intellectual abilities. In contrast, the ASD group reported lower levels of EI relative to their typically-developing peers, as expected given the social and emotional challenges faced by individuals with ASD. Importantly, cognitive intelligence did not correlate with EI in either group. Taken together, these findings further support the theory of dissociable neural systems underlying CI and EI. These findings also highlight the need to address not only the intellectual aspects of cognition, but also the emotional components to increase understanding of, and improve treatment for individuals on the autism spectrum. This understanding would enhance our ability to assess and support young adults with ASD, and ultimately ease their transition into adulthood. Crown Copyright (C) 2014 Published by Elsevier Ltd. All rights reserved. C1 [Brady, Danielle I.; McCrimmon, Adam W.; Thorne, Keoma J.] Univ Calgary, Div Appl Psychol, Calgary, AB T2N 1N4, Canada. 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PD SEP PY 2014 VL 8 IS 9 BP 1016 EP 1023 DI 10.1016/j.rasd.2014.05.009 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600003 ER PT J AU Adams, HL Matson, JL Jang, J AF Adams, Hilary L. Matson, Johnny L. Jang, Jina TI The relationship between sleep problems and challenging behavior among children and adolescents with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Sleep problems; Challenging behavior ID PERVASIVE DEVELOPMENTAL DISORDER; INTELLECTUAL DISABILITY; MENTAL-RETARDATION; ASPERGERS SYNDROME; PDD-NOS; ADULTS; SYMPTOMS; INFANTS; ASD; RISPERIDONE AB Prior research has indicated fairly consistently that sleep problems appear to worsen ASD core symptomatology. As such, the present study was conducted to examine whether or not sleep problems also exacerbate behavior problems commonly exhibited by children and adolescents with ASD in terms of total, internalizing, and externalizing challenging behavior. Results indicated that presence of sleep problems increased the ratings of challenging behavior across types, as hypothesized. Unexpectedly, degree of sleep problem (i.e., mild versus severe) only affected total and externalizing challenging behavior, whereas ratings of internalizing challenging behavior were not significantly different between mild and severe sleep problem groups. Clinical applications of findings, as well as future directions for additional research on the topic of sleep among individuals with ASD, are discussed. Published by Elsevier Ltd. C1 [Adams, Hilary L.; Matson, Johnny L.; Jang, Jina] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Adams, HL (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1024 EP 1030 DI 10.1016/j.rasd.2014.05.008 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600004 ER PT J AU Rivard, M Terroux, A Mercier, C AF Rivard, Melina Terroux, Amelie Mercier, Celine TI Effectiveness of early behavioral intervention in public and mainstream settings: The case of preschool-age children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Children with autism spectrum disorders; Early behavioral intervention; Intensity; Mainstream day care; Parental coaching; Effectiveness ID PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE EARLY INTERVENTION; YOUNG-CHILDREN; PSYCHOSOCIAL INTERVENTIONS; CHALLENGING BEHAVIOR; MENTAL-RETARDATION; SOCIAL COMPETENCE; PEOPLE; PROGRAM; METAANALYSIS AB Despite the demonstrated positive outcomes of early intensive behavioral intervention (EIBI) among children with autism spectrum disorders (ASD), several challenges to its implementation on a large scale and in community settings remain. In order to maximize the accessibility and cost-effectiveness of its services, a regional public agency serving children with ASD implemented two consecutive programs: a 1 year pre-program for parents (intensive sessions followed by 1 hour per week of individual coaching) and an early behavioral intervention (EBI) program with less than optimal weekly intensity (16-20 hours) delivered in mainstream day care settings. The outcomes of these programs were assessed among 93 children. Their IQ adaptive behavior, and socioaffective competencies were found to have improved after 12 months in the EBI program. Their autism symptoms had also decreased marginally. Although the pre-program did not have observable effects on children's outcomes, their parents reported positive impact on their well-being and family life. These results demonstrate the feasibility and sustainability of offering EBI to large, unselected populations. 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PD SEP PY 2014 VL 8 IS 9 BP 1031 EP 1043 DI 10.1016/j.rasd.2014.05.010 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600005 ER PT J AU Fisher, WW Luczynski, KC Hood, SA Lesser, AD Machado, MA Piazza, CC AF Fisher, Wayne W. Luczynski, Kevin C. Hood, Stephanie A. Lesser, Aaron D. Machado, Mychal A. Piazza, Cathleen C. TI Preliminary findings of a randomized clinical trial of a virtual training program for applied behavior analysis technicians SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Applied behavior analysis; Autism; Behavioral skills training; Early intensive behavioral interventions; Telehealth; Virtual care ID AUTISM SPECTRUM DISORDERS; YOUNG-CHILDREN; INTERVENTIONS; TELEHEALTH AB As the demand for applied behavior analysis (ABA) services for children with an autism spectrum disorder continues to grow, it is critical to develop efficient, effective, and widely accessible procedures for training technicians to implement ABA interventions. One approach would be to develop efficacious training programs that could be delivered over the Internet via a virtual private network (VPN). In the current study, we developed a 40-h virtual training program in which participants completed e-learning modules and also received behavioral skills training over a VPN to implement behavior reduction and skill acquisition protocols in both discrete-trail and play-based formats. This virtual training program was evaluated in a randomized-clinical trial (RCT) using direct-observation measures on the implementation of discrete-trial training and play-based procedures as the primary dependent variables (which were also collected via a VPN). Participants in the treatment group showed robust and statistically significant improvement in their implementation of behavior reduction and acquisition programs under both discrete-trial and play-based formats, and they rated the training as highly socially acceptable. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1044 EP 1054 DI 10.1016/j.rasd.2014.05.002 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600006 ER PT J AU Shih, CH Chiang, MS Wang, SH Chen, CN AF Shih, Ching-Hsiang Chiang, Ming-Shan Wang, Shu-Hui Chen, Chih-Nung TI Teaching two teenagers with autism spectrum disorders to request the continuation of video playback using a touchscreen computer with the function of automatic response to requests SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Touchscreen; ASD; SGD; Communication request ID CONTROLLING ENVIRONMENTAL STIMULATION; FREE WIRELESS MICE; DESIGNATED OCCUPATIONAL ACTIVITIES; FOLLOW SIMPLE INSTRUCTIONS; WII REMOTE CONTROLLER; ASSISTING PEOPLE; DEVELOPMENTAL-DISABILITIES; PHYSICAL-ACTIVITIES; ENABLING PEOPLE; BALANCE BOARDS AB This study used a standard touchscreen computer with a newly developed Communication Request and Automatic Response Assistive Program (CRARAP) software package to evaluate whether two people with autism spectrum disorders (ASDs) would be able to actively perform communication requests to continue their preferred environmental stimulation. The CRARAP software was specifically developed for this study to combine the functions of a standard touchscreen computer with a speech-generating device (SGD) and the feature of automatic response to requests. A multiple probe design across participants was adopted in this study. The results show that both participants significantly improved their target responses in terms of performing the correct alternative communication request during the intervention phase, and retained this effective performance in the maintenance phase. The practical and developmental implications of the findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Shih, Ching-Hsiang; Chiang, Ming-Shan; Wang, Shu-Hui; Chen, Chih-Nung] Natl Dong Hwa Univ, Dept Special Educ, Hualien 970, Taiwan. RP Shih, CH (reprint author), Natl Dong Hwa Univ, Dept Special Educ, Hualien 970, Taiwan. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1055 EP 1061 DI 10.1016/j.rasd.2014.05.014 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600007 ER PT J AU Chuang, IC Tseng, MH Lu, L Shieh, JY Cermak, SA AF Chuang, I-Ching Tseng, Mei-Hui Lu, Lu Shieh, Jeng-Yi Cermak, Sharon A. TI Predictors of the health-related quality of life in preschool children with Autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Health-related quality of life; Caregiver's mental health; Parenting stress; Preschool children with Autism spectrum disorders ID PERVASIVE DEVELOPMENTAL DISORDERS; CEREBRAL-PALSY; PSYCHOMETRIC PROPERTIES; QUESTIONNAIRE CHQ; MENTAL-HEALTH; DETERMINANTS; ASSOCIATIONS; TEMPERAMENT; VALIDATION; CHILDHOOD AB This study was aimed to identify the predictors of health-related quality of life (HRQOL) by considering the caregiver's characteristics such as mental health and parenting stress as well as child characteristics in preschool children with Autism spectrum disorders (ASD). A total of 106 children aged 36-70 months participated in this study. The study indicated that the predictors of HRQOL in children with ASD encompassed not only child but also caregiver characteristics. In particular, good HRQOL on the domains of social and emotional functioning in children with ASD depended upon the caregiver's mental well-being. In summary, the present findings highlight the need for assessment of caregivers' parenting stress and their mental status as well as the predictors of HRQOL in children with ASD. Furthermore, the findings of the study could serve as a guide for clinicians to target at the predictors when providing assessment and intervention for children with ASD to improve their HRQOL. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chuang, I-Ching; Tseng, Mei-Hui] Natl Taiwan Univ, Coll Med, Sch Occupat Therapy, Taipei 10055, Taiwan. [Tseng, Mei-Hui; Lu, Lu; Shieh, Jeng-Yi] Natl Taiwan Univ Hosp, Dept Phys Med & Rehabil, Taipei, Taiwan. [Cermak, Sharon A.] Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. RP Tseng, MH (reprint author), Natl Taiwan Univ, Coll Med, Sch Occupat Therapy, Taipei 10055, Taiwan. 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Di Leone, Antonia Albano, Vincenza Stella, Anna Damato, Concetta TI A microswitch-cluster program to enhance object manipulation and to reduce hand mouthing by three boys with autism spectrum disorders and intellectual disabilities SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Microswitch-cluster; Autism spectrum disorders; Developmental disabilities; Indices of happiness; Quality of life ID SCANNING KEYBOARD EMULATOR; MULTIPLE DISABILITIES; MOTOR DISABILITIES; DEVELOPMENTAL-DISABILITIES; BEHAVIOR; TECHNOLOGY; CHILDREN; ENGAGEMENT; INTERVENTIONS; INDIVIDUALS AB We assessed a microswitch-cluster program to enhance object manipulation and to reduce hand mouthing by three boys with autism spectrum disorders and severe to profound intellectual disabilities. A second goal of the study was to monitor the effect of such program on the indices of happiness of the participants. The study has been carried out according to an ABB(1)AB(1) sequence, where A represented baseline phases, B represented intervention phase in which the adaptive response (i.e. object manipulation) was followed by a contingent positive stimulation irrespective of challenge behavior (i.e. hand mouthing), and B-1 indicated intervention phases in which an adaptive response was followed by a contingent positive stimulation only if it occurred with the simultaneous absence of the challenge behavior. Otherwise, positive stimulation was interrupted if the challenge behavior was exhibited during its supply. Results showed an increasing of the adaptive responses and a decrease of the challenge behavior during intervention phases. All participants spent less time with the exhibition of challenge behavior, during intervention phases, compared to baseline sessions. Finally, the indices of happiness augmented during intervention phases. Clinical, practical and psychological implications of the findings are discussed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stasolla, Fabrizio] Lega Filo dOro Res Ctr, Molfetta, Italy. [Perilli, Viviana] Lega Filo dOro Res Ctr, Lesmo, Italy. [Damiani, Rita; Caffo, Alessandro O.; Di Leone, Antonia; Albano, Vincenza; Stella, Anna; Damato, Concetta] Univ Bari, Dept Educ Sci,Psychol,Commun, I-70121 Bari, Italy. RP Stasolla, F (reprint author), Lega Filo dOro Res Ctr, Molfetta, Italy. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1071 EP 1078 DI 10.1016/j.rasd.2014.05.016 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600009 ER PT J AU Hambly, C Fombonne, E AF Hambly, Catherine Fombonne, Eric TI Factors influencing bilingual expressive vocabulary size in children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Language; Vocabulary; Bilingualism; Child ID LANGUAGE; ENGLISH; TODDLERS; SKILLS AB This study explored bilingual exposure, language, social impairment and cognitive factors that could influence second language (L2) expressive vocabulary size as measured on the MacArthur-Bates Communicative Development Inventories (various languages) in 33 children (mean age = 60 months) diagnosed with ASD. In the 23 children with L2 vocabularies, recent language exposure estimates accounted for 69% of the variation in L2 vocabulary size, and the VABS-II expressive scale score explained an additional 13% of the difference. The complete sample was then subgrouped into three levels of L2 vocabulary size to compare children with no L2 vocabularies (NON-B, n = 10), low L2 word counts (LOW-B, n = 11) and high L2 counts (HIGH-B, n = 12), as determined by a median split procedure. The HIGH-B group had significantly larger L1 vocabularies than both the LOW-B (p = .045) and the NON-B (p = .003) groups, and higher VABS-II expressive scale scores than both the LOW-B (p = .008) and the NON-B (p = .012) groups. Social impairment did not significantly differ across groups and cognitive impairment did not preclude the development of L2 vocabularies. Expressive bilingualism in this population appears related to high levels of recent direct L2 exposure in combination with stronger dominant language abilities. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hambly, Catherine; Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA. RP Hambly, C (reprint author), 14 Gulf Lane, Galveston, TX 77550 USA. EM catherine.hambly@mail.mcgill.ca CR Bedore LM, 2012, BILING-LANG COGN, V15, P616, DOI 10.1017/S1366728912000090 Bialystok E., 2001, BILINGUALISM DEV LAN Bird EKR, 2012, INT J LANG COMM DIS, V47, P52, DOI 10.1111/j.1460-6984.2011.00071.x Bird EKR, 2005, AM J SPEECH-LANG PAT, V14, P187, DOI 10.1044/1058-0360(2005/019) Bornstein M. H., 2006, INT J BILINGUAL, V10, P331, DOI [10.1177/13670069060100030401, DOI 10.1177/13670069060100030401] Brojde CL, 2012, FRONT PSYCHOL, V3, DOI 10.3389/fpsyg.2012.00155 Constantino J. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1079 EP 1089 DI 10.1016/j.rasd.2014.05.013 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600010 ER PT J AU Uono, S Sato, W Toichi, M AF Uono, Shota Sato, Wataru Toichi, Motorni TI Reduced representational momentum for subtle dynamic facial expressions in individuals with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Dynamic facial expression; Representational momentum; Social impairment ID PERVASIVE DEVELOPMENTAL DISORDER; EMOTIONAL EXPRESSIONS; NORMAL-CHILDREN; HUMAN BRAIN; RECOGNITION; PERCEPTION; MOTION; ADOLESCENTS; FACE; IMITATION AB The cognitive mechanisms underlying social communication via emotional facial expressions are crucial for understanding the social impairments experienced by people with autism spectrum disorders (ASD). A recent study (Yoshikawa & Sato, 2008) found that typically developing individuals perceived the last image from a dynamic facial expression to be more emotionally exaggerated than a static facial expression; this perceptual difference is termed representational momentum (RM) for dynamic facial expressions. RM for dynamic facial expressions might be useful for detecting emotion in another's face and for predicting behavior changes. We examined RM for dynamic facial expressions using facial expression stimuli at three levels of emotional intensity (subtle, medium, and extreme) in people with ASD. We predicted that individuals with ASD would show reduced RM for dynamic facial expressions. Eleven individuals with ASD (three with Asperger's disorder and eight with pervasive developmental disorder not otherwise specified) and II IQ-, age- and gender-matched typically developing controls participated in this study. Participants were asked to select an image that matched the final image from dynamic and static facial expressions. Our results revealed that subjectively perceived images were more exaggerated for the dynamic than for the static presentation under all levels of intensity and in both groups. The ASD group, however, perceived a reduced degree of exaggeration for dynamic facial expressions under the subtle intensity condition. As facial expressions are often displayed subtly in daily communications, reduced RM for subtle dynamic facial expressions may prevent individuals with ASD from appropriately interacting with other people as a consequence of their difficulty detecting others' emotions. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Uono, Shota; Toichi, Motorni] Kyoto Univ, Fac Human Hlth Sci, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan. [Sato, Wataru] Kyoto Univ, Primate Res Inst, Hakubi Project, Inuyama, Aichi 4848506, Japan. [Toichi, Motorni] Org Promoting Dev Disorder Res, Sakyo Ku, Kyoto 6068392, Japan. RP Uono, S (reprint author), Kyoto Univ, Fac Human Hlth Sci, Grad Sch Med, Sakyo Ku, 53 Shogoin Kawahara Cho, Kyoto 6068507, Japan. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1090 EP 1099 DI 10.1016/j.rasd.2014.05.018 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600011 ER PT J AU Nordahl-Hansen, A Kaale, A Ulvund, SE AF Nordahl-Hansen, Anders Kaale, Anett Ulvund, Stein Erik TI Language assessment in children with autism spectrum disorder: Concurrent validity between report-based assessments and direct tests SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Language assessment; ASD; Concurrent validity; Reynell Developmental Language Scales; Mullen Scales of Early Learning; Communicative Development Inventory ID COMMUNICATIVE DEVELOPMENT INVENTORIES; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; PREDICTIVE-VALIDITY; JOINT ATTENTION; MULLEN SCALES; COMPREHENSION; ABILITY; PARENT; SKILLS AB Impairments in expressive and receptive language are common in individuals with autism spectrum disorder (ASD). Therefore, the importance of language assessment is emphasized in e.g. DSM-5. Thus, studies addressing the validity of different language measures are important. Parents and preschool teachers of 55 children diagnosed with childhood autism separately filled out the Communicative Development Inventory (CDI), a widely used report-based assessment of language. The children were also tested with the two standardized direct language tests: Reynell Developmental Language Scales (RDLS) and Mullen Scales of Early Learning (MSEL). Concurrent validity across the three measures was investigated. The results suggested very high agreement between the measures, and this was found regardless of whether parents or preschool teachers filled out the CDI. Given the difficulty in testing children with low language levels, as often is the case in young children with ASD, this study shows that several valid measures are available for measuring expressive and receptive language. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Nordahl-Hansen, Anders; Ulvund, Stein Erik] Univ Oslo, Dept Educ, N-0317 Oslo, Norway. [Kaale, Anett] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway. RP Nordahl-Hansen, A (reprint author), Univ Oslo, Dept Educ, POB 1092, N-0317 Oslo, Norway. EM a.j.n.hansen@iped.uio.no CR Akshoomoff N, 2006, CHILD NEUROPSYCHOL, V12, P269, DOI 10.1080/09297040500473714 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bishop SL, 2011, AJIDD-AM J INTELLECT, V116, P331, DOI 10.1352/1944-7558-116.5.331 Bornstein MH, 1998, CHILD DEV, V69, P654, DOI 10.2307/1132196 Burns T. G., 2013, APPL NEUROPSYCHOL, V1, P33 Charman T, 2003, J CHILD LANG, V30, P213, DOI 10.1017/S0305000902005482 Charman T, 2004, J AUTISM DEV DISORD, V34, P59, DOI 10.1023/B:JADD.0000018075.77941.60 Chiat S, 2007, J SPEECH LANG HEAR R, V50, P429, DOI 10.1044/1092-4388(2007/030) De Houwer A, 2005, J CHILD LANG, V32, P735, DOI 10.1017/S0305000905007026 Dockrell J. 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PD SEP PY 2014 VL 8 IS 9 BP 1100 EP 1106 DI 10.1016/j.rasd.2014.05.017 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600012 ER PT J AU King, ML Takeguchi, K Barry, SE Rehfeldt, RA Boyer, VE Mathews, TL AF King, Melissa L. Takeguchi, Kazu Barry, Shaina E. Rehfeldt, Ruth Anne Boyer, Valerie E. Mathews, Therese L. TI Evaluation of the iPad in the acquisition of requesting skills for children with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Requesting skills; iPad (R); Picture-based communication system ID EXCHANGE COMMUNICATION-SYSTEM; VOICE OUTPUT COMMUNICATION; SPEECH-GENERATING DEVICE; DEVELOPMENTAL-DISABILITIES; PECS AB The iPad (R) with the Proloquo2Go (TM) application is designed to function as a speech-generating device (SGD). This study evaluates whether children with autism spectrum disorder (ASD) can acquire requesting skills using the iPad (R) with the Proloquo2Go (TM) application. Participants included three children with ASD between the ages of three and five. A multiple probe design across participants was used. Intervention phases were adapted and modified from the picture exchange communication system (PECS) (Bondy & Frost, 1994; Frost & Bondy, 2002). Results of this study support that children diagnosed with ASD can acquire skills needed to request preferred items using the iPad (R) with the Proloquo2Go (TM) application with training of a picture-based communication system. In addition, vocal requesting increased for the participants during the training phases in comparison to baseline probes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [King, Melissa L.; Takeguchi, Kazu; Barry, Shaina E.; Rehfeldt, Ruth Anne; Boyer, Valerie E.] So Illinois Univ, Carbondale, IL 62901 USA. 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L., 2013, PEDIATRICS, V131, pe1128 NR 29 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 SEP PY 2014 VL 8 IS 9 BP 1107 EP 1120 DI 10.1016/j.rasd.2014.05.011 PG 14 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600013 ER PT J AU Hill, AP Zuckerman, KE Hagen, AD Kriz, DJ Duvall, SW Van Santen, J Nigg, J Fair, D Fombonne, E AF Hill, Alison Presmanes Zuckerman, Katharine E. Hagen, Arlene D. Kriz, Daniel J. Duvall, Susanne W. Van Santen, Jan Nigg, Joel Fair, Damien Fombonne, Eric TI Aggressive behavior problems in children with autism spectrum disorders: Prevalence and correlates in a large clinical sample SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Psychotropic drugs; Aggression; Sleep; Internalizing problems; Attention problems ID CHALLENGING BEHAVIORS; PHYSICAL AGGRESSION; EARLY-CHILDHOOD; INTELLECTUAL DISABILITIES; LANGUAGE IMPAIRMENT; YOUNG-PEOPLE; RISK-FACTORS; TRAJECTORIES; SYMPTOMS; TODDLERS AB Aggressive behavior problems (ABP) are frequent yet poorly understood in children with autism spectrum disorders (ASD) and are likely to co-vary significantly with comorbid problems. We examined the prevalence and sociodemographic correlates of ABP in a clinical sample of children with ASD (N = 400; 2-16.9 years). We also investigated whether children with ABP experience more intensive medical interventions, greater impairments in behavioral functioning, and more severe comorbid problems than children with ASD who do not have ABP. One in four children with ASD had Child Behavior Checklist scores on the Aggressive Behavior scale in the clinical range (T-scores >= 70). Sociodemographic factors (age, gender, parent education, race, ethnicity) were unrelated to ABP status. The presence of ABP was significantly associated with increased use of psychotropic drugs and melatonin, lower cognitive functioning, lower ASD severity, and greater comorbid sleep, internalizing, and attention problems. In multivariate models, sleep, internalizing, and attention problems were most strongly associated with ABP. These comorbid problems may hold promise as targets for treatment to decrease aggressive behavior and proactively identify high-risk profiles for prevention. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hill, Alison Presmanes; Van Santen, Jan] Oregon Hlth & Sci Univ, Dept Pediat, Ctr Spoken Language Understanding, Portland, OR 97239 USA. [Hill, Alison Presmanes; Hagen, Arlene D.; Kriz, Daniel J.; Duvall, Susanne W.; Van Santen, Jan; Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Dept Pediat, Div Gen Pediat, Portland, OR 97239 USA. [Zuckerman, Katharine E.] Oregon Hlth & Sci Univ, Dept Pediat, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97239 USA. [Hagen, Arlene D.; Nigg, Joel; Fair, Damien] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Fair, Damien; Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Hill, AP (reprint author), 3181 Southwest Sam Jackson Pk Rd GH 40, Portland, OR 97239 USA. EM hillali@ohsu.edu CR Achenbach T, 2000, MANUAL ASEBA PRESCHO Achenbach T. 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PD SEP PY 2014 VL 8 IS 9 BP 1121 EP 1133 DI 10.1016/j.rasd.2014.05.006 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600014 ER PT J AU Rahbar, MH Samms-Vaughan, M Dickerson, AS Loveland, KA Ardjomand-Hessabi, M Bressler, J Lee, M Shakespeare-Pellington, S Grove, ML Pearson, DA Boervvinkle, E AF Rahbar, Mohammad H. Samms-Vaughan, Maureen Dickerson, Aisha S. Loveland, Katherine A. Ardjomand-Hessabi, Manouchehr Bressler, Jan Lee, MinJae Shakespeare-Pellington, Sydonnie Grove, Megan L. Pearson, Deborah A. Boervvinkle, Eric TI Role of fruits, grains, and seafood consumption in blood cadmium concentrations of Jamaican children with and without Autism Spectrum Disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Cadmium; Autism Spectrum Disorder; Grains; Fruits; Seafood; Jamaica ID FISH CONSUMPTION; HEAVY-METALS; QUANTILE REGRESSION; CHILDHOOD AUTISM; EXPOSURE; POPULATION; HAIR; LEAD; ACCUMULATION; ENVIRONMENT AB Human exposure to cadmium has adverse effects on the nervous system. Utilizing data from 110 age- and sex-matched case-control pairs (220 children) ages 2-8 years in Kingston, Jamaica, we compared the 75th percentile of blood cadmium concentrations in children with and without Autism Spectrum Disorder (ASD). In both univariable and multivariable Quantile Regression Models that controlled for potential confounding factors, we did not find any significant differences between ASD cases and typically developing (TD) controls with respect to the 75th percentile of blood cadmium concentrations (P > 0.22). However, we found a significantly higher 75th percentile of blood cadmium concentrations in TD Jamaican children who consumed shellfish (lobsters, crabs) (P < 0.05), fried plantain (P < 0.01), and boiled dumpling (P < 0.01). We also observed that children living in Jamaica have an arithmetic mean blood cadmium concentration of 0.16 mu g/L which is similar to that of the children in developed countries and much lower than that of children in developing countries. Although our results do not support an association between blood cadmium concentrations and ASD, to our knowledge, this study is the first to report levels of blood cadmium in TD children as well as those with ASD in Jamaica. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rahbar, Mohammad H.; Dickerson, Aisha S.; Boervvinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX 77030 USA. [Rahbar, Mohammad H.; Lee, MinJae] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Univ Texas Med Sch, Div Clin & Translat Sci, Houston, TX 77030 USA. [Rahbar, Mohammad H.; Dickerson, Aisha S.; Ardjomand-Hessabi, Manouchehr] Univ Texas Hlth Sci Ctr Houston, CCTS, BERD, Houston, TX 77030 USA. [Shakespeare-Pellington, Sydonnie] Univ W Indies, Dept Child & Adolescent Hlth, Kingston 7, Jamaica. [Loveland, Katherine A.; Pearson, Deborah A.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Boervvinkle, Eric] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1134 EP 1145 DI 10.1016/j.rasd.2014.06.002 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600015 ER PT J AU Lacroix, A Guidetti, M Roe, B Reilly, J AF Lacroix, Agnes Guidetti, Michele Roge, Bernadette Reilly, Judy TI Facial emotion recognition in 4-to 8-year-olds with autism spectrum disorder: A developmental trajectory approach SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Emotion recognition; Developmental delay ID CHILDREN; EXPRESSIONS; FACES; PERCEPTION; VOICES; PEOPLE AB The investigation of emotion recognition in autism spectrum disorder (ASD) has both theoretical and practical implications. However, although many studies have examined facial emotion recognition in ASD, some points remain unclear. We therefore studied facial emotion recognition in young children with ASD across a small age range, in order to determine (1) their ability to recognize emotion and (2) the developmental trajectory of this ability. Twenty-two children with ASD aged 4-8 years were compared with typically developing children matched on either chronological age or verbal mental age. We administered three facial emotion tasks: matching, identification, and labeling. Results showed that children with ASD and typically developing children had difficulty with labeling emotions, but not with matching or identifying them. Happiness was the easiest to recognize, and surprise the hardest. The children with ASD did not exhibit delayed onset in the development of facial emotion recognition. To conclude, emotion recognition difficulties in children with ASD primarily concern the recognition of negative emotions and the identification of surprise, as they do in TD groups. This should be taken into account in future research, as well as in the design of future intervention programs. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lacroix, Agnes] Univ Rennes 2, Ctr Rech Psychol Cognit & Commun, EA 1285, F-35000 Rennes, France. [Guidetti, Michele] Univ Toulouse 2, Octogone ECCD, Unite Rech Interdisciplinaire, EA 4156, F-31058 Toulouse 09, France. [Roge, Bernadette] Univ Toulouse 2, Octogone CERPP, Unite Rech Interdisciplinaire ea 4156, F-31058 Toulouse 9, France. [Reilly, Judy] San Diego State Univ, San Diego, CA 92182 USA. RP Lacroix, A (reprint author), Univ Rennes 2, Ctr Rech Psychol Cognit & Commun, EA 1285, Pl Recteur Henri Moal, F-35000 Rennes, France. 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Able, Harriet TI Victimization of students with autism spectrum disorder: A review of prevalence and risk factors SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Review DE Autism; Bullying; Victimization; Risk factors ID PEER VICTIMIZATION; BULLYING EXPERIENCES; YOUNG ADOLESCENTS; GENERAL-EDUCATION; SCHOOL; CHILDREN; INTERVENTION; DISABILITIES; FRIENDSHIP; ASSOCIATION AB Bullying is a serious problem among school-aged youth. Research suggests students with autism spectrum disorder (ASD) are overrepresented as victims within the bullying dynamic. This review synthesizes 21 articles involving prevalence rates of victimization of school-age youth with ASD and factors related to the victimization of youth with ASD. Prevalence studies suggest students with ASD are frequent victims of bullying with victimization rates ranging by study methodology. Studies reporting factors related to the victimization of students with ASD include individual (i.e., characteristics of ASD, social vulnerability, behavior problems, disability, race, academic achievement, and age of student) and contextual (i.e., educational setting, school transportation, parental mental health, parental engagement and confidence, family socioeconomic status, and social support from peers and friendship) factors. Strategies for prevention and intervention are posed. Limitations and directions for future inquiry are addressed. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Sreckovic, Melissa A.; Brunsting, Nelson C.; Able, Harriet] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Sreckovic, MA (reprint author), Peabody Hall 301,CB 3500, Chapel Hill, NC 27599 USA. 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TI Bullying of youth with autism spectrum disorder, intellectual disability, or typical development: Victim and parent perspectives SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Intellectual disability; Bullying; Adolescents; Friendship ID HIGH-FUNCTIONING AUTISM; SOCIAL-SKILLS; ADOLESCENTS; FRIENDSHIP; CHILDREN; PREVALENCE; SCHOOL; LONELINESS; VICTIMIZATION; ADJUSTMENT AB In-depth interviews conducted separately with 13-year-olds with autism spectrum disorder (ASD), intellectual disability (ID), or typical development (TD) and their mothers investigated the experiences of victimization in the form of bullying. Coded constructs from the interviews were utilized to compare groups on the frequency, type, and impact of victimization. Youth with ASD were victimized more frequently than their ID or TO peers, and the groups differed with regard to the type of bullying and the impact it had, with ASD youth faring the worst. Higher internalizing problems and conflict in friendships were found to be significant predictors of victimization, according to both youth- and mother-reports. These predictors were found to be more salient than ASD status alone. Implications for practice are discussed. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Zeedyk, S. M.; Rodriguez, G.; Tipton, L. A.; Blocher, J.] Univ Calif Riverside, Grad Sch Educ, Attn SEARCH Ctr, Riverside, CA 92521 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Zeedyk, SM (reprint author), Univ Calif Riverside, Grad Sch Educ, Attn SEARCH Ctr, Riverside, CA 92521 USA. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1184 EP 1199 DI 10.1016/j.rasd.2014.06.003 PG 16 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600019 ER PT J AU Bardikoff, N McGonigle-Chalmers, M AF Bardikoff, Nicole McGonigle-Chalmers, Margaret TI Testing nonverbal IQ in children with Autism Spectrum Disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE WISC-III; WISC-IV; KABC-II; Nonverbal IQ; Children with Autism; Spectrum Disorders ID HIGH-FUNCTIONING AUTISM; WECHSLER INTELLIGENCE SCALE; PROCESSING SPEED; MATCHING STRATEGIES; ASPERGERS-SYNDROME; WISC-III; PROFILES; IV; INDIVIDUALS; ABILITIES AB 15 high-functioning school aged children with ASD and 15 neurotypically developing age matched controls were assessed using the WISC-IV and the KABC-II in order to assess whether the WISC-IV has rectified problems associated with the WISC-III's undue emphasis on timing measures. No significant group differences were found for the PRI sub-scale of the WISC-IV nor for the nonverbal scale of the KABC-II, but the ASD group scored significantly lower than controls on the Processing Speed Index of the WISC-IV. This supports the need to isolate of timing criteria when IQ testing in populations with ASD, as is now the case with the WISC-IV. However significantly higher scores were obtained for the KABC-II versus the PRI for children with ASD only. The reasons for this are discussed with regard to a possible cultural bias in the Picture Concepts subtest of the WISC-IV. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Bardikoff, Nicole; McGonigle-Chalmers, Margaret] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9QU, Midlothian, Scotland. RP Bardikoff, N (reprint author), Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9QU, Midlothian, Scotland. EM n.bardikoff@ed-alumni.net; 12nb42@queensu.ca CR ALLEN MH, 1991, J AUTISM DEV DISORD, V21, P483, DOI 10.1007/BF02206872 Black DO, 2009, J AUTISM DEV DISORD, V39, P1613, DOI 10.1007/s10803-009-0795-3 Bolte S, 2009, J AUTISM DEV DISORD, V39, P678, DOI 10.1007/s10803-008-0667-2 Burack JA, 2004, J AUTISM DEV DISORD, V34, P65, DOI 10.1023/B:JADD.0000018076.90715.00 Calhoun SL, 2005, PSYCHOL SCHOOLS, V42, P333, DOI 10.1002/pits.20067 Charman T, 2011, PSYCHOL MED, V41, P619, DOI 10.1017/S0033291710000991 Dawson M, 2007, PSYCHOL SCI, V18, P657, DOI 10.1111/j.1467-9280.2007.01954.x Flanagan D. P., 2009, ESSENTIAL WISC 4 ASS Goldstein G, 2008, NEUROPSYCHOLOGY, V22, P301, DOI 10.1037/0894-4105.22.3.301 Goldstein G, 2001, J AUTISM DEV DISORD, V31, P433, DOI 10.1023/A:1010620820786 Green D, 2002, J CHILD PSYCHOL PSYC, V43, P655, DOI 10.1111/1469-7610.00054 Jarrold C, 2004, J AUTISM DEV DISORD, V34, P81, DOI 10.1023/B:JADD.0000018078.82542.ab Kaufman A. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1200 EP 1207 DI 10.1016/j.rasd.2014.06.007 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600020 ER PT J AU Dixon, MR Whiting, SW Rowsey, K Belisly, J AF Dixon, Mark R. Whiting, Seth W. Rowsey, Kyle Belisly, Jordan TI Assessing the relationship between intelligence and the PEAK relational training system SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE ABA therapy; Intelligence quotient; Language; Verbal behavior therapy ID AUTISM SPECTRUM DISORDERS; BEHAVIORAL TREATMENT; CHILDREN; IQ; PREDICTORS AB The Promoting the Emergence of Advanced Knowledge (PEAK) Relational Training System is an assessment and curriculum tool developed for basic and advanced skills using behavior analytic approaches. The current study evaluated the relationship between intelligence (as measured by IQ scores) and performance on the PEAK assessment with children with autism or other developmental and intellectual disabilities. Each child was administered the PEAK assessment from the Direct Training Module. Scores from this assessment were compared to IQ scores for all participants to assess the relationship between the two measures. Results indicated a strong, significant correlation between scores on standardized IQ tests and scores on the PEAK assessment (r= .759, p< .01). The results demonstrated strong convergent validity and indicate that the PEAK may be a useful assessment and curriculum guide for training language and learning skills to individuals with autism and other developmental disabilities. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Dixon, Mark R.; Whiting, Seth W.; Rowsey, Kyle; Belisly, Jordan] So Illinois Univ, Carbondale, IL 62901 USA. 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PD SEP PY 2014 VL 8 IS 9 BP 1208 EP 1213 DI 10.1016/j.rasd.2014.05.005 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600021 ER PT J AU Tomchek, SD Huebner, RA Dunn, W AF Tomchek, Scott D. Huebner, Ruth A. Dunn, Winnie TI Patterns of sensory processing in children with an autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Sensory processing; Assessment ID YOUNG-CHILDREN; ASPERGER SYNDROME; INFANTILE-AUTISM; MOTOR IMPAIRMENT; LEARNING-DISABILITIES; DEVELOPMENTAL DELAY; TYPICAL DEVELOPMENT; ADAPTIVE-BEHAVIOR; ABNORMALITIES; SYMPTOMS AB The literature describing individuals with autism spectrum disorders (ASDs) commonly includes descriptions of differences in sensory processing. The purpose of this study was to describe patterns of sensory processing found in 400 children with an ASD. Exploratory factor analysis identified 6 parsimonious factors: low energy/weak, tactile and movement sensitivity, taste/smell sensitivity, auditory and visual sensitivity, sensory seeking/distractibility, and hypo-responsivity. These factors are consistent with other reports about differences in sensory processing. Findings provide insights about practice and future research. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Tomchek, Scott D.] Univ Louisville, Sch Med, Weisskopf Child Evaluat Ctr, Dept Pediat, Louisville, KY 40202 USA. [Huebner, Ruth A.] Eastern Kentucky Univ, Richmond, KY USA. [Tomchek, Scott D.; Dunn, Winnie] Univ Kansas, Med Ctr, Occupat Therapy Educ Program, Lawrence, KS 66045 USA. RP Tomchek, SD (reprint author), Univ Louisville, Weisskopf Child Evaluat Ctr, Dept Pediat, 571 South Floyd St,Suite 100, Louisville, KY 40202 USA. 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TI Psychometric properties of the SCARED in youth with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Anxiety; Assessment; Validity; Factor analysis ID CHILDRENS ANXIETY SCALE; TEST-RETEST RELIABILITY; EMOTIONAL DISORDERS; DSM-IV; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; CO-MORBIDITY; SCREEN; VALIDITY; ADOLESCENTS AB Children with autism spectrum disorder (ASD) are at increased risk of developing co-occurring anxiety symptoms. However, the assessment of anxiety symptoms in this population is often challenging for researchers and clinicians. This study evaluated the psychometric properties of a questionnaire measure of child anxiety symptoms, the Screen for Child Anxiety Related Emotional Disorders (SCARED), in school-aged children and adolescents with high-functioning ASD. Children and parents recruited for an anxiety treatment study completed the SCARED parent and child versions prior to the start of treatment. Both versions demonstrated factor structures, internal reliability, and score distributions largely consistent with those from typically developing samples (Birmaher et al., 1999). The SCARED showed moderate convergent validity with a structured clinical interview and had good sensitivity and specificity. Differences were explored by child age, gender, and ethnicity. Together, these findings support the use of the SCARED as a valid assessment tool in an ASD population. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Stern, Jessica A.; Blakeley-Smith, Audrey; Reaven, Judy A.; Hepburn, Susan L.] Univ Colorado, Denver Sch Med, Dept Psychiat, Aurora, CO 80045 USA. [Gadgil, Milind S.] Kaiser Permanente Colorado Reg, Hidden Lake Mental Hlth, Arvada, CO 80003 USA. RP Hepburn, SL (reprint author), Univ Colorado, Denver Sch Med, Dept Psychiat, 13121 E 17th Pl,Mailstop C-234, Aurora, CO 80045 USA. EM susan.hepburn@ucdenver.edu CR Achenbach T. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1225 EP 1234 DI 10.1016/j.rasd.2014.06.008 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600023 ER PT J AU Tung, LC Huang, CY Tseng, MH Yen, HC Tsai, YP Lin, YC Chen, KL AF Tung, Li-Chen Huang, Chien-Yu Tseng, Mei-Hui Yen, Hsui-Chen Tsai, Yu-Pei Lin, Yu-Ching Chen, Kuan-Lin TI Correlates of health-related quality of life and the perception of its importance in caregivers of children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Health-related quality of life; Autism; Parenting stress; Behavior problems ID CHILDHOOD AUTISM; PARENTING STRESS; RATING-SCALE; DISORDERS; BEHAVIOR; VERSION; MOTHERS; DISABILITY; VALIDITY; AGE AB This study aims to investigate the correlates of health-related quality of life (HRQOL) and perceptions of the importance of each HRQOL domain in caregivers of children with autism. Eighty-two caregivers completed the World Health Organization Quality of Life and Parenting Stress Index Short Form to respectively measure the caregivers' HRQOL and parenting stress. The Childhood Autism Rating Scale and the Strength and Difficulties Questionnaire were used to respectively assess severity of autism and children's behavior problems. Results revealed that severity of autism, behavior problems, and parenting stress individually had low to moderate associations with HRQOL. However, all variables considered together, only parental distress (parent-related stress) significantly contributed to the four HRQOL domains. In addition, the physical domain was the most important HRQOL domain to caregivers, and environmental domain, the least. Knowledge of the correlates of HRQOL and the importance of each HRQOL domain could serve as guides for clinicians to improve the HRQOL of caregivers of children with autism by targeting parental distress and focusing on the HRQOL domains perceived as most important by caregivers. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Tung, Li-Chen; Yen, Hsui-Chen; Tsai, Yu-Pei] Chi Mei Med Ctr, Dept Phys Med & Rehabil, Tainan 710, Taiwan. [Tung, Li-Chen] Kaohsiung Med Univ, Sch Med, Kaohsiung 807, Taiwan. [Huang, Chien-Yu; Tseng, Mei-Hui] Natl Taiwan Univ, Coll Med, Sch Occupat Therapy, Taipei 100, Taiwan. [Lin, Yu-Ching] Natl Cheng Kung Univ Hosp, Tainan 704, Taiwan. [Chen, Kuan-Lin] Natl Cheng Kung Univ, Coll Med, Sch Occupat Therapy, Tainan 701, Taiwan. RP Chen, KL (reprint author), Natl Cheng Kung Univ, Coll Med, Sch Occupat Therapy, 1 Univ Rd, Tainan 701, Taiwan. 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Autism Spectr. Disord. PD SEP PY 2014 VL 8 IS 9 BP 1235 EP 1242 DI 10.1016/j.rasd.2014.06.010 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600024 ER PT J AU Hill, TL Varela, RE Kamps, JL Niditch, LA AF Hill, Trenesha L. Varela, R. Enrique Kamps, Jodi L. Niditch, Laura A. TI Local processing and social skills in children with Autism Spectrum Disorders: The role of anxiety and cognitive functioning SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Local processing; Anxiety; Social skills; Cognitive functioning ID PERVASIVE DEVELOPMENTAL DISORDERS; WEAK CENTRAL COHERENCE; DIAGNOSTIC INTERVIEW; INDIVIDUALS; ATTENTION; FACES; ASSOCIATION; PERFORMANCE; PRECEDENCE; INVERSION AB The present study examined the relations between anxiety, cognitive functioning, local processing, and social skills in a group of 102 children diagnosed with an Autism Spectrum Disorder. The results indicated that children diagnosed with Asperger's Disorder had significantly higher cognitive functioning and enhanced local processing (i.e., Block Design scores) compared to those diagnosed with Autistic Disorder or PDD-NOS. Regression analyses results showed that anxiety and cognitive functioning moderated the association between local processing and social skills. For children with low cognitive functioning and high anxiety, greater local processing was associated with poorer social skills than those with high cognitive functioning, high anxiety, and greater local processing. For children with high cognitive functioning and high anxiety, enhanced local processing was associated with better social skills than those with high cognitive functioning and reduced local processing. Implications of these findings are discussed. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Hill, Trenesha L.; Varela, R. Enrique; Niditch, Laura A.] Tulane Univ, Dept Psychol, New Orleans, LA 70118 USA. [Kamps, Jodi L.] Childrens Hosp, New Orleans, LA 70118 USA. RP Varela, RE (reprint author), Tulane Univ, Dept Psychol, 2007 Percival Stern Hall,6400 Freret St, New Orleans, LA 70118 USA. 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PD SEP PY 2014 VL 8 IS 9 BP 1243 EP 1251 DI 10.1016/j.rasd.2014.06.005 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AN6GS UT WOS:000340693600025 ER PT J AU Rosqvist, HB AF Rosqvist, Hanna Bertilsdotter TI Becoming an 'Autistic Couple': Narratives of Sexuality and Couplehood Within the Swedish Autistic Self-advocacy Movement SO SEXUALITY AND DISABILITY LA English DT Article DE Couple; Autism; Autistic sexuality; Neurotypical sexuality; Self-advocacy; Sweden ID PARENTAL PERSPECTIVE; ADOLESCENTS; ADULTS; ATTITUDES; KNOWLEDGE; DISORDER AB Research on sexuality and autism is dominated by a sexually deficit view of autism. According to this view, people with autism are considered different from neurotypicals and in need of sexual education that is specially adapted to the social impairments of people with autism. Perspectives on sexuality, couplehood, and autism are gradually changing, and this is partly because of alternative views on autism expressed and advocated within autistic self-advocacy movements. The present paper explores discourses within the Swedish autistic self-advocacy movement of an 'autistic' sexuality and couplehood (sexuality and couplehood on people with autism's own terms). The analysis is based on articles in a Swedish magazine, Empowerment, published between 2002 and 2009 that was produced by and aimed at adults with autism. C1 Umea Univ, Dept Social Work, S-90187 Umea, Sweden. RP Rosqvist, HB (reprint author), Umea Univ, Dept Social Work, S-90187 Umea, Sweden. 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Sandra Nichols, Shana TI Sexual Satisfaction of High-Functioning Adults with Autism Spectrum Disorder SO SEXUALITY AND DISABILITY LA English DT Article DE Sexual satisfaction; Autism spectrum disorder; Sexuality; Asperger syndrome; Canada; United States ID INTERPERSONAL EXCHANGE MODEL; RESPONSE RATES; HELP-SEEKING; QUOTIENT AQ; ADOLESCENTS; SAMPLE; MEN; VALIDATION; VALIDITY; INDIVIDUALS AB This study examined the validity of the Interpersonal Exchange Model of Sexual Satisfaction (IEMSS) as a framework for understanding the sexual satisfaction of 205 adults (77 men and 128 women) with high-functioning autism spectrum disorder (HF-ASD) who were in a romantic relationship of at least 3 months duration. Participants completed an online survey that included a background questionnaire, the IEMSS Questionnaire, and a measure of autism symptoms. The results provide support for the validity of the IEMSS in that all the IEMSS components (relationship satisfaction, balance of sexual rewards and costs, balance of relative sexual rewards and costs, equality of rewards, equality of costs) were significantly associated with sexual satisfaction. Relationship satisfaction and the balance of rewards and costs added over and above the other components. The model was not moderated by gender, relationship duration or extent of autism symptoms. However, participants with more autism symptoms related to social functioning reported lower sexual satisfaction as well as lower scores on all of the IEMSS components. There were few gender differences. These results are discussed in terms of the impact of HF-ASD on adults' experiences of their sexual satisfaction with their partner. C1 [Byers, E. Sandra] Univ New Brunswick, Dept Psychol, Fredericton, NB E3B 5A3, Canada. [Nichols, Shana] ASPIRE Ctr Learning & Dev, Melville, NY USA. 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Weisner, Thomas Singhal, Nidhi TI Adults with autism in India: A mixed-method approach to make meaning of daily routines SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE India; Autism Spectrum Disorders; Disability; Daily routine; Ecocultural ID PARENTING STRESS; SPECTRUM DISORDERS; URBAN INDIA; CHILDREN; PERSPECTIVES; DISABILITY; FAMILIES; LIFE AB Although individuals with Autism Spectrum Disorder (ASD) have been diagnosed in India for over fifty years, virtually nothing is known about the social circumstances of adults, their daily lives, and their families. Where are adults with autism? How do they spend their time? Who are they with, and what are they doing all day? A mixed-method approach was used to obtain information on daily routines of 54 adults with ASD living in New Delhi, India, and about parent levels of stress associated with these routines during a study collected from January through June, 2013. Whether or not they attended a structured setting during the day (59% did so), adults engaged in some 20 activities both inside and outside their home. Contrary to our expectations, most adults were not "hidden" and were out in public at least on occasion. Higher functioning adults were more likely to attend a structured setting, but parents described challenging behaviors, both adult and parent preference, and lack of options as reasons that adults stayed home. The amount of time adults spent outside their home was not associated with parent reported stress, but stress was significantly higher for mothers who were employed. Most families described adaptation to caring for their adult children. A partnership with an Indian nongovernmental organization provided mechanisms to amplify our research findings, making them meaningful to our participants and others. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Daley, Tamara C.] Westat Corp, Durham, NC 27703 USA. [Weisner, Thomas] Univ Calif Los Angeles, Dept Psychiat, Ctr Culture & Hlth, NPI Semel Inst Neurosci, Los Angeles, CA 90024 USA. [Singhal, Nidhi] Act Autism, New Delhi 110025, India. RP Daley, TC (reprint author), Westat Corp, 1009 Slater Rd, Durham, NC 27703 USA. EM TamaraDaley@westat.com FU Foundation for Psychocultural Research [59892]; Robert Lemelson, President (FPR) - Culture, Brain, Development and Mental Health (CBDMH); Action For Autism, New Delhi; FPR FX This project is funded through a grant from the Foundation for Psychocultural Research (Grant #59892), Robert Lemelson, President (FPR) - Culture, Brain, Development and Mental Health (CBDMH) (Tom Weisner, PI; Tamara Daley, Co-PI) and in partnership with Action For Autism, New Delhi (Nidhi Singhal and Merry Barua). FPR-UCLA CBDMH is one of the interdisciplinary programs initiated and funded by the FPR. The RAFIN Adult study was managed by Deepali Taneja, with key assistance from Sachita Suryanarayan. 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PD SEP PY 2014 VL 116 BP 142 EP 149 DI 10.1016/j.socscimed.2014.06.052 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AN6HN UT WOS:000340695700017 PM 24998867 ER PT J AU Delgado, MS Camprubi, C Tumer, Z Martinez, F Mila, M Monk, D AF Delgado, Marta Sanchez Camprubi, Cristina Tuemer, Zeynep Martinez, Francisco Mila, Montserrat Monk, David TI Screening Individuals with Intellectual Disability, Autism and Tourette's Syndrome for KCNK9 Mutations and Aberrant DNA Methylation within the 8q24 Imprinted Cluster SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Imprinting; methylation; KCNK9; autism spectrum disorder; intellectual disability ID MENTAL-RETARDATION; GENE; EXPRESSION; TRAPPC9; UBE3A; IDENTIFICATION; HETEROGENEITY; DEFICIENCY; TRANSCRIPT; DISORDERS AB The phenotype overlap between autism spectrum disorders (ASD) & intellectual disabilities (ID) is mirrored at the genetic level, with common genes being reported mutated in variety of developmental disabilities. However despite widespread genetic screening for mutations, in approximately 40-60% of childhood developmental disorders the genetic cause remains unknown. Several genome-wide linkage screens in ASD have identified a locus mapping to distal 8q. We have recently identified a novel brain-specific imprinted cluster at this location, which contains the reciprocally expressed maternal KCNK9 and paternally expressed non-coding PEG13 transcripts, the latter located within an intron of TRAPPC9. Interestingly, mutations of KCNK9 and TRAPPC9 have been reported in Birk-Barel mental retardation and non-syndromic familial forms of ID, respectively. Here, we report a genetic screen for KCNK9 coding mutations and potential epigenetic aberrations that could result in deregulated imprinting in a cohort of 120 ID, 86 ASD and 86 Tourette syndrome patients. Fifteen of the ID patients had clinical characteristics overlapping with Birk-Barel syndrome. Sequencing of the two coding exons of KCNK9 failed to identify pathologic mutations, with only one variant, rs2615374, being present with allele frequencies similar to those described in dbSNP database. DNA methylation profiling of the KCNK9 and TRAPPC9 promoters, the maternally methylated PEG13 DMR and a long-range enhancer region were normal in all patients. Our findings suggest that mutations of KCNK9 or epigenetic disturbances within the PEG13 imprinted cluster do not significantly contribute to the cause of the developmental disabilities tested in this study. (C) 2014 Wiley Periodicals, Inc. C1 [Delgado, Marta Sanchez; Camprubi, Cristina; Monk, David] Bellvitge Inst Biomed Res IDIBELL, Imprinting & Canc Grp, Canc Epigenet & Biol Program PEBC, Barcelona 08907, Spain. [Tuemer, Zeynep] Rigshosp, Copenhagen Univ Hosp, Kennedy Ctr, Appl Human Mol Genet, Glostrup, Denmark. [Martinez, Francisco] Hosp Univ La Fe, Unitat Genet, Valencia, Spain. [Mila, Montserrat] CIBERER, Barcelona, Spain. RP Monk, D (reprint author), Unidad Genet Med Sistemas Genom SL, Valencia 46980, Spain. EM dmonk@idibell.cat RI Martinez, Francisco/A-2543-2009 OI Martinez, Francisco/0000-0002-0589-2584 FU Spanish Ministerio de Educacion y Ciencia [BFU2011-27658]; Fundacio La Marato de TV3 [101130]; Lundbeck Foundation [R24-A2419] FX Grant sponsor: Spanish Ministerio de Educacion y Ciencia (grant number BFU2011-27658 to DM) and the Fundacio La Marato de TV3 (101130 to DM) and Lundbeck Foundation (R24-A2419 to ZT). 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J. Med. Genet. B PD SEP PY 2014 VL 165 IS 6 BP 472 EP 478 DI 10.1002/ajmg.b.32250 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AN3OF UT WOS:000340497100003 ER PT J AU Rowe, G Nevin, H AF Rowe, Gareth Nevin, Helen TI Bringing 'patient voice' into psychological formulations of in-patients with intellectual disabilities, autism spectrum disorder and severe challenging behaviours: report of a service improvement pilot SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE Autism; challenging behaviour; communication; learning (intellectual) disabilities; nursing; profound and complex learning disabilities ID MENTAL-HEALTH; INDIVIDUALS; PEOPLE; CHOICE; QUESTION; CHILDREN; QUALITY; ADULTS; LIFE; CARE AB This is a report of a service improvement pilot project undertaken at an inpatient autism service for adults with intellectual disabilities and severe challenging behaviours. Within the service, a key facet of the care pathway was the use of a biopsychosocial case formulation. Formulation meetings were led by psychology and involved a full multidisciplinary team and external representation. However, routine invitation of patients was not appropriate due to anxiety and complex communication difficulties. Therefore, the service was looking for alternative ways to incorporate the voices of patients into formulation. This report presents the case studies of four individual patients who were chosen because together they were indicative of the patient profile across the service. The study has demonstrated that it is possible to include patients' voices in their psychological formulation. For those with mild intellectual disabilities and mild autism spectrum disorder, this has been simple and extremely fruitful. 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J. Learn. Disabil. PD SEP PY 2014 VL 42 IS 3 BP 177 EP 184 DI 10.1111/bld.12026 PG 8 WC Education, Special SC Education & Educational Research GA AN4BW UT WOS:000340533600002 ER PT J AU Leonard, HC Hill, EL AF Leonard, Hayley C. Hill, Elisabeth L. TI Review: The impact of motor development on typical and atypical social cognition and language: a systematic review SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Review DE Motor development; social cognition; autism spectrum disorders; developmental coordination disorder; specific language impairment ID SCHOOL-AGED CHILDREN; COORDINATION DISORDER; PRESCHOOL-CHILDREN; KINDERGARTEN-CHILDREN; BEHAVIORAL-PROBLEMS; AUTISM SPECTRUM; ARM MOVEMENTS; IMPAIRMENT; INFANTS; SKILLS AB Background: Motor development allows infants to gain knowledge of the world but its vital role in social development is often ignored. Method: A systematic search for papers investigating the relationship between motor and social skills was conducted, including research in typical development and in Developmental Coordination Disorder, Autism Spectrum Disorders and Specific Language Impairment. Results: The search identified 43 studies, many of which highlighted a significant relationship between motor skills and the development of social cognition, language and social interactions. Conclusions: This complex relationship requires more attention from researchers and practitioners, allowing the development of more tailored intervention techniques for those at risk of motor, social and language difficulties. [GRAPHICS] . C1 [Leonard, Hayley C.; Hill, Elisabeth L.] Univ London, Dept Psychol, London SE14 6NW, England. RP Leonard, HC (reprint author), Univ London, Dept Psychol, London SE14 6NW, England. EM h.leonard@gold.ac.uk FU British Academy Small Grant [SG100507]; Nuffield Foundation Small Grant [SGS38957] FX This study was supported by a British Academy Small Grant (SG100507) and a Nuffield Foundation Small Grant (SGS38957) to E. L. H. The authors have declared that they have no competing or potential conflicts of interest. CR Alcock KJ, 2010, DEVELOPMENTAL SCI, V13, P677, DOI 10.1111/j.1467-7687.2009.00924.x American Psychiatric Association, 2000, DSM 4 TR DIAGN STAT, VFourth Archibald LMD, 2008, INT J LANG COMM DIS, V43, P165, DOI 10.1080/13682820701422809 Bagwell CL, 1998, CHILD DEV, V69, P140, DOI 10.1111/j.1467-8624.1998.tb06139.x Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Bar-Haim Y, 2006, SOC DEV, V15, P296, DOI 10.1111/j.1467-9507.2006.00342.x Barnhart RC, 2003, PHYS THER, V83, P722 Bart O, 2007, INFANT CHILD DEV, V16, P597, DOI 10.1002/icd.514 Bayley N, 1993, BAYLEY SCALES INFANT Berk L. E., 2006, CHILD DEV, V7th Bhat A. 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Ment. Health PD SEP PY 2014 VL 19 IS 3 BP 163 EP 170 DI 10.1111/camh.12055 PG 8 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AN3RU UT WOS:000340507000002 ER PT J AU Timimi, S AF Timimi, Sami TI Back to Normal: Why Ordinary Behaviour is Mistaken for ADHD, Bipolar Disorder, and Autism Spectrum Disorder SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Book Review C1 [Timimi, Sami] Lincolnshire Partnership NHS Fdn Trust, Lincoln, England. [Timimi, Sami] Lincoln Univ, Lincoln, England. RP Timimi, S (reprint author), Lincolnshire Partnership NHS Fdn Trust, Lincoln, England. CR GNAULTI E, 2013, BACK NORMAL WHY ORDI NR 1 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1475-357X EI 1475-3588 J9 CHILD ADOL MENT H-UK JI Child Adolesc. Ment. Health PD SEP PY 2014 VL 19 IS 3 BP 224 EP 224 DI 10.1111/camh.12073_6 PG 1 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AN3RU UT WOS:000340507000016 ER PT J AU Horan, W Pineda, J Wynn, J Iacoboni, M Green, M AF Horan, William P. Pineda, Jaime A. Wynn, Jonathan K. Iacoboni, Marco Green, Michael F. TI Some markers of mirroring appear intact in schizophrenia: evidence from mu suppression SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE mu suppression; Schizophrenia; Mirror neuron system; Empathy ID AUTISM SPECTRUM DISORDERS; PSYCHIATRIC RATING-SCALE; BORDERLINE PERSONALITY-DISORDER; SOCIAL COGNITION; NEURON DYSFUNCTION; EMPATHIC ACCURACY; IMITATION; NEUROSCIENCE; MECHANISMS; PSYCHOSIS AB Although schizophrenia is associated with impairments in social cognition, the scope and neural correlates of these disturbances are largely unknown. In this study, we investigated whether schizophrenia patients show impaired functioning of the mirror neuron system (MNS), as indexed by electroencephalographic (EEG) mu (8-13 Hz) suppression, a hypothesized biomarker of MNS activity that is sensitive to the degree of social interaction depicted in visual stimuli. A total of 32 outpatients and 26 healthy controls completed an EEG paradigm that included six action observation or execution conditions that differed in their degrees of social interaction. Participants also completed a validated empathy questionnaire. Across both groups, we found a significant linear increase in mu suppression across the conditions involving greater levels of social engagement and interaction, but no significant group or interaction effects. Patients self-reported diminished empathic concern and perspective taking, which showed some moderate relations to mu suppression levels. Thus, the schizophrenia group showed generally intact modulation of MNS functioning at the electrophysiological level, despite self-reporting empathic disturbances. The disturbances commonly seen on self-report, performance, and neuroimaging measures of mentalizing in schizophrenia may largely reflect difficulties with higher-level inferential processes about others' emotions, rather than a basic incapacity to share in these experiences. C1 [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Pineda, Jaime A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Iacoboni, Marco] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horan, W (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu FU Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion; VA Career Development Award; NIMH [MH065707, MH43292] FX M.F.G. reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. The rest of the authors report no biomedical financial interests or potential conflicts of interest. Support for this study came from a VA Career Development Award (to W. P. H.) and from NIMH Grant Nos. MH065707 and MH43292 (M. F. G.). The authors thank Amanda Bender, Michelle Dolinsky, Crystal Gibson, Cory Tripp, and Katherine Weiner for assistance in the data collection. 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Affect. Behav. Neurosci. PD SEP PY 2014 VL 14 IS 3 BP 1049 EP 1060 DI 10.3758/s13415-013-0245-8 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN3FT UT WOS:000340471500013 PM 24415272 ER PT J AU Radell, M Mercado, E AF Radell, Milen L. Mercado, Eduardo, III TI Modeling possible effects of atypical cerebellar processing on eyeblink conditioning in autism SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Classical conditioning; Cerebellum; Computational model; Autistic; Interneuron; Timing ID PARALLEL FIBER SYNAPSES; PURKINJE-CELL ACTIVITY; LONG-TERM DEPRESSION; FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC DISORDERS; FUNCTIONAL SPECIALIZATION; ASCENDING AXON; NETWORK MODEL AB Autism is unique among other disorders in that acquisition of conditioned eyeblink responses is enhanced in children, occurring in a fraction of the trials required for control participants. The timing of learned responses is, however, atypical. Two animal models of autism display a similar phenotype. Researchers have hypothesized that these differences in conditioning reflect cerebellar abnormalities. The present study used computer simulations of the cerebellar cortex, including inhibition by the molecular layer interneurons, to more closely examine whether atypical cerebellar processing can account for faster conditioning in individuals with autism. In particular, the effects of inhibitory levels on delay eyeblink conditioning were simulated, as were the effects of learning-related synaptic changes at either parallel fibers or ascending branch synapses from granule cells to Purkinje cells. Results from these simulations predict that whether molecular layer inhibition results in an enhancement or an impairment of acquisition, or changes in timing, may depend on (1) the sources of inhibition, (2) the levels of inhibition, and (3) the locations of learning-related changes (parallel vs. ascending branch synapses). Overall, the simulations predict that a disruption in the balance or an overall increase of inhibition within the cerebellar cortex may contribute to atypical eyeblink conditioning in children with autism and in animal models of autism. C1 [Radell, Milen L.; Mercado, Eduardo, III] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Radell, M (reprint author), SUNY Buffalo, Dept Psychol, Pk Hall, Buffalo, NY 14260 USA. EM mlradell@buffalo.edu FU NSF [SMA-1041755] FX This work was supported in part by a grant to E. Mercado, from NSF grant #SMA-1041755 to the Temporal Dynamics of Learning Center, an NSF Science of Learning Center. 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PD SEP PY 2014 VL 23 IS 3 BP 231 EP 233 DI 10.1017/S2045796014000286 PG 3 WC Psychiatry SC Psychiatry GA AN2FR UT WOS:000340400000005 PM 24786563 ER PT J AU Calderoni, S Bellani, M Hardan, AY Muratori, F Brambilla, P AF Calderoni, S. Bellani, M. Hardan, A. Y. Muratori, F. Brambilla, P. TI Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives SO EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES LA English DT Article DE Autism spectrum disorders (ASD); basal ganglia; structural magnetic resonance imaging (sMRI); volumes ID CAUDATE-NUCLEUS; BRAIN ANATOMY; VOLUME; PERFORMANCE; STRIATUM; FOCUS AB This editorial offers a concise overview of the recent structural magnetic resonance imaging studies that evaluate the basal ganglia (BG) volumes in autism spectrum disorders (ASD). 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C. was partly supported by the Italian Ministry of Health and by Tuscany Region with the grant 'GR-2010-2317873'. F. M. and S. C. were partly supported by the European Union (The MICHELANGELO Project). The other authors received no specific grant from any funding agency, commercial or not-for-profit sectors for this publication. 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Lin, C. Enjey Fujii, Cori Renno, Patricia Piacentini, John Laugeson, Elizabeth Wood, Jeffrey J. TI An Open Trial of Cognitive-Behavioral Therapy for Anxiety Disorders in Adolescents With Autism Spectrum Disorders SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorders; anxiety; comorbid conditions; evidence-based practices ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; ASPERGER-SYNDROME; PSYCHOSOCIAL TREATMENTS; INTERVIEW SCHEDULE; DSM-IV; CHILDHOOD ANXIETY; PARENT VERSION; CHILDREN AB The frequent co-occurrence of anxiety disorders and autism spectrum disorders (ASD) in youth has spurred study of intervention practices for this population. As anxiety disorders in the absence of ASD are effectively treated using cognitive-behavioral therapy (CBT) protocols, an initial step in evaluating treatments for comorbid youth has necessarily centered on adaptation of CBT. One primary limitation of this research, to date, is that interventions for adolescents with anxiety disorders and ASD have not been systematically tested. In this study, 20 adolescents (90% male) with ASD and a comorbid anxiety disorder, between ages 11 and 14 years (M = 12.2 years, SD = 1.11 years), participated in an open trial of modified CBT targeting anxiety with ASD. Findings demonstrated significant reductions in anxiety severity, as assessed by clinician and parent ratings, from baseline to post-treatment. In addition, reductions in parent-rated externalizing symptoms were observed. Gains were maintained at a 1-month follow-up. C1 Univ Miami, Coral Gables, FL 33146 USA. [Ehrenreich-May, Jill; Queen, Alexander H.; Ghilain, Christine S.; Alessandri, Michael] Univ S Florida, Tampa, FL USA. [Storch, Eric A.; Lewin, Adam B.; Arnold, Elysse B.; Murphy, Tanya K.] Univ Arkansas, Fayetteville, AR 72701 USA. [Rodriguez, Juventino Hernandez; Lin, C. 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PD SEP PY 2014 VL 29 IS 3 BP 145 EP 155 DI 10.1177/1088357614533381 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AN4HA UT WOS:000340547100002 ER PT J AU Bouck, EC Savage, M Meyer, NK Taber-Doughty, T Hunley, M AF Bouck, Emily C. Savage, Melissa Meyer, Nancy K. Taber-Doughty, Teresa Hunley, Megan TI High-Tech or Low-Tech? Comparing Self-Monitoring Systems to Increase Task Independence for Students With Autism SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE high school; age; functional skills; independence; autism spectrum disorders; daily living; skills; intellectual disability ID GENERAL-EDUCATION CLASSROOM; HIGH-SCHOOL; DISABILITIES; PERFORMANCE; CHILDREN; ADULTS; SKILLS AB Independence is the ultimate goal for students with disabilities, including secondary students with autism. One avenue targeted for increasing independence and decreasing prompt-dependency is through self-monitoring. In this study, investigators sought to determine whether a difference exists in levels of task independence when three students with autism complete food preparation tasks while self-monitoring using a low-tech treatment (paper/pencil) and high-tech treatment (iPad). Although both interventions decreased the need for prompting thereby increasing independence, students needed less assistance when using the iPad. Students also maintained their levels of independence in food preparation following summer vacation. Social validity interviews indicated students preferred self-monitoring with the iPad over the paper/pencil. C1 [Bouck, Emily C.; Savage, Melissa; Meyer, Nancy K.; Taber-Doughty, Teresa; Hunley, Megan] Purdue Univ, W Lafayette, IN 47907 USA. RP Bouck, EC (reprint author), Purdue Univ, 100 N Univ St, W Lafayette, IN 47907 USA. 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L., 1996, SELF DETERMINATION L, P15 Wehmeyer ML, 2003, EDUC TRAIN MENT RET, V38, P131 White O. R., 1980, EXCEPTIONAL TEACHING NR 28 TC 1 Z9 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 EI 1538-4829 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD SEP PY 2014 VL 29 IS 3 BP 156 EP 167 DI 10.1177/1088357614528797 PG 12 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AN4HA UT WOS:000340547100003 ER PT J AU Rieth, SR Stahmer, AC Suhrheinrich, J Schreibman, L Kennedy, J Ross, B AF Rieth, Sarah R. Stahmer, Aubyn C. Suhrheinrich, Jessica Schreibman, Laura Kennedy, Joanna Ross, Benjamin TI Identifying Critical Elements of Treatment: Examining the Use of Turn Taking in Autism Intervention SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE evidence-based intervention; naturalistic behavioral intervention; turn taking; critical elements AB Evidence-based treatments for autism spectrum disorders (ASD) are comprised of components that identify therapist behavior necessary to implement the treatment with integrity. Some components are shared across approaches from diverse theoretical backgrounds. One component included in several interventions that has not been researched in isolation is turn taking, or the manner in which the therapist facilitates back-and-forth interaction with the child. The current study used an alternating treatments design to examine the efficacy of four types of turn taking. Six children, ages 30 to 39 months, received behavioral treatment while therapists systematically varied the nature of the turn taking component. Children's responses were behaviorally scored to examine differences based on turn condition. Consistent patterns of behavior were found across children. Results suggest that the optimal type of turn is dependent on developmental level and target skill. Implications for treatment of ASD and future research directions are discussed. C1 [Rieth, Sarah R.; Stahmer, Aubyn C.; Suhrheinrich, Jessica] Rady Childrens Hosp, San Diego, CA 92123 USA. [Rieth, Sarah R.; Stahmer, Aubyn C.; Suhrheinrich, Jessica; Schreibman, Laura; Kennedy, Joanna; Ross, Benjamin] Univ Calif San Diego, San Diego, CA 92103 USA. RP Rieth, SR (reprint author), Rady Childrens Hosp, 3020 Childrens Way,MC 5033, San Diego, CA 92123 USA. 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Shanun TI Promoting Behavioral Variability in Individuals With Autism Spectrum Disorders: A Literature Review SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; repetitive; response diversity; response variation; variability ID RESPONSE VARIABILITY; CHILDREN; OPERANT; REINFORCEMENT; EXTINCTION; SCHEDULES; STUDENTS AB Repetitive behavior is a hallmark feature of autism spectrum disorders (ASD), and can have adverse consequences related to social stigma and low rates of skill acquisition. Basic research suggests that variability, or the extent to which one response differs from previous responses, is amenable to antecedent and consequence manipulations. This article describes the concept of variability, synthesizes the findings of 14 recent studies on interventions to increase the variability of behavior in individuals with ASD, and proposes preliminary guidelines for practitioners that focus on building response repertoires, implementing contingencies to produce and maintain variability, and incorporating prompts to vary responding. C1 [Wolfe, Katie] Univ S Carolina, Columbia, SC 29208 USA. [Slocum, Timothy A.; Kunnavatana, S. Shanun] Utah State Univ, Logan, UT 84322 USA. RP Wolfe, K (reprint author), Univ S Carolina, Dept Educ Studies, 820 Main St,235-B Wardlaw, Columbia, SC 29208 USA. 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PD SEP PY 2014 VL 29 IS 3 BP 180 EP 190 DI 10.1177/1088357614525661 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA AN4HA UT WOS:000340547100005 ER PT J AU Song, C Zhang, HP AF Song, Chi Zhang, Heping TI TARV: Tree-based Analysis of Rare Variants Identifying Risk Modifying Variants in CTNNA2 and CNTNAP2 for Alcohol Addiction SO GENETIC EPIDEMIOLOGY LA English DT Article DE mutation; classification tree; association analysis; alcoholism ID GENOME-WIDE ASSOCIATION; FUNCTIONAL LINEAR-MODELS; CLASSIFICATION TREES; COMMON DISEASES; AUTISM; DISORDERS; LINKAGE; TRAITS; GENES AB Since the development of next generation sequencing (NGS) technology, researchers have been extending their efforts on genome-wide association studies (GWAS) from common variants to rare variants to find the missing inheritance. Although various statistical methods have been proposed to analyze rare variants data, they generally face difficulties for complex disease models involving multiple genes. In this paper, we propose a tree-based analysis of rare variants (TARV) that adopts a nonparametric disease model and is capable of exploring gene-gene interactions. We found that TARV outperforms the sequence kernel association test (SKAT) in most of our simulation scenarios, and by notable margins in some cases. By applying TARV to the study of addiction: genetics and environment (SAGE) data, we successfully detected gene CTNNA2 and its 43 specific variants that increase the risk of alcoholism in women, with an odds ratio (OR) of 1.94. This gene has not been detected in the SAGE data. Post hoc literature search also supports the role of CTNNA2 as a likely risk gene for alcohol addiction. In addition, we also detected a plausible protective gene CNTNAP2, whose 97 rare variants can reduce the risk of alcoholism in women, with an OR of 0.55. These findings suggest that TARV can be effective in dissecting genetic variants for complex diseases using rare variants data. (C) 2014 Wiley Periodicals, Inc. C1 [Song, Chi; Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06511 USA. RP Zhang, HP (reprint author), Yale Univ, Sch Publ Hlth, Dept Biostat, 300 George St,Suite 523, New Haven, CT 06511 USA. EM heping.zhang@yale.edu FU National Institute on Drug Abuse [R01 DA016750] FX This research is supported in part by grants R01 DA016750 from the National Institute on Drug Abuse. The dataset used for the analyses described in this manuscript was obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. 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Epidemiol. PD SEP PY 2014 VL 38 IS 6 BP 552 EP 559 DI 10.1002/gepi.21843 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA AN4KP UT WOS:000340556900008 PM 25041903 ER PT J AU Fitzpatrick, EM Lambert, L Whittingham, J Leblanc, E AF Fitzpatrick, Elizabeth M. Lambert, Linda Whittingham, JoAnne Leblanc, Emma TI Examination of characteristics and management of children with hearing loss and autism spectrum disorders SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Hearing loss; autism spectrum disorder; hearing aids; cochlear implants ID COCHLEAR IMPLANTS; IMPAIRMENT; DIAGNOSIS; AGE; DEAFNESS; DISABILITIES; TODDLERS; OUTCOMES; REGIONS; CANADA AB Objective: Up to 40% of children with hearing loss present with other developmental disabilities. The purpose of this study was to document the prevalence of autism spectrum disorders (ASD) in children with permanent hearing loss, to describe the audiologic characteristics, and to examine clinical management. Design: Prospective data related to clinical characteristics of children identified with hearing loss and ASD were examined. A retrospective chart review was also conducted to explore clinical management and uptake of amplification. Study sample: The study included all children in one Canadian region identified with permanent hearing loss and followed from 2002-2010. Results: Of a total of 785 children with permanent hearing loss, 2.2% (n = 17) also received a diagnosis of ASD. The 13 boys and 4 girls presented with a range of audiologic profiles from unilateral to profound bilateral hearing loss. Four of five children with unilateral hearing loss experienced progression to bilateral loss. Amplification was recommended for all but one child and 9 of 16 children continued to use their hearing devices. Conclusions: The higher prevalence rate of ASD in this clinical population is consistent with previous reports. Our findings suggest that some children with autism can derive benefits from the use of amplification. C1 [Fitzpatrick, Elizabeth M.] Univ Ottawa, Fac Hlth Sci, Ottawa, ON K1H 8M5, Canada. [Fitzpatrick, Elizabeth M.; Whittingham, JoAnne] Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON K1H 8L1, Canada. [Lambert, Linda] Ctr Sante & Serv Sociaux Alphonse Desjardins, Levis, PQ, Canada. [Leblanc, Emma] Northwestern Univ, Dept Audiol, Chicago, IL 60611 USA. RP Fitzpatrick, EM (reprint author), Univ Ottawa, Fac Hlth Sci, Ottawa, ON K1H 8M5, Canada. EM elizabeth.fitzpatrick@uottawa.ca FU Canadian Institutes of Health New Investigator Award; Canadian Child Health Clinician Scientist Program Award FX This research was funded by a Canadian Institutes of Health New Investigator Award and a Canadian Child Health Clinician Scientist Program Award to the first author. We are grateful to the clinicians at the Children's Hospital of Eastern Ontario for their contributions of clinical data and for their collaboration throughout this study. We thank Viviane Grandpierre for assistance with updating the literature. 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J. Audiol. PD SEP PY 2014 VL 53 IS 9 BP 577 EP 586 DI 10.3109/14992027.2014.903338 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AN3AM UT WOS:000340457200001 PM 24832530 ER PT J AU Fredo, ARJ Kavitha, G Ramakrishnan, S AF Fredo, A. R. Jac Kavitha, G. Ramakrishnan, S. TI Segmentation and Analysis of Brain Subcortical Regions Using Regularized Multiphase Level Set in Autistic MRImages SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article DE autism; subcortical regions; multiphase level set; fuzzy c-means cluster; intelligent quotient values ID IMAGE SEGMENTATION; ACTIVE CONTOURS; CHILDREN; MRI; VOLUMES; MODEL AB In this work, subcortical regions of autistic magnetic resonance brain images are analyzed using multiphase level set method. The images considered in this work are obtained from autism brain image data exchange database. The subcortical regions such as corpus callosum, cerebellum, and brain stem are segmented from the cortical region using Fuzzy c-means (FCM)-based multiphase level set method. FCM with three cluster center is used as the intensity discriminator and the evolution of the level set curve is regularized by a distance function. The results show that the multiphase level set method is able to segment the desired subcortical regions. The results are validated with the ground truth images. The average similarity values are found to be 0.85. The segmented subcortical regions of autistic have reduced tissue area and are distinct from the controls (p<0.0001). Further, it is observed that the subcortical area gives comparable results with clinical intelligent quotient values and is able to discriminate the controls and autistic subjects. As the feature area extracted from brain subcortical regions are significant, this study seems to be clinically helpful in mass screening of autistic subjects. (C) 2014 Wiley Periodicals, Inc. C1 [Fredo, A. R. Jac; Kavitha, G.] Anna Univ, Dept Elect Engn, Madras 600025, Tamil Nadu, India. [Ramakrishnan, S.] Indian Inst Technol Madras, Dept Appl Mech, Biomed Engn Grp, Noninvas Imaging & Diagnost Lab, Madras, Tamil Nadu, India. RP Fredo, ARJ (reprint author), Anna Univ, Dept Elect Engn, MIT Campus, Madras 600025, Tamil Nadu, India. EM jack247029@gmail.com FU University Grant Commission under the scheme Maulana Azad National Fellowship for Minority students [F1-17.1/2011/MANF-CHRTAM-1826] FX Grant sponsors: The first author Jac Fredo A. R. is receiving fellowship from University Grant Commission under the scheme Maulana Azad National Fellowship for Minority students (F1-17.1/2011/MANF-CHRTAM-1826) for his research work. 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PD SEP PY 2014 VL 24 IS 3 BP 256 EP 262 DI 10.1002/ima.22101 PG 7 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA AN3NI UT WOS:000340494700007 ER PT J AU Goddard, L Dritschel, B Howlin, P AF Goddard, Lorna Dritschel, Barbara Howlin, Patricia TI A Preliminary Study of Gender Differences in Autobiographical Memory in Children with an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autobiographical memory; Gender; Autism spectrum disorder ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; EPISODIC MEMORY; SEX-DIFFERENCES; ADULTS; SELF; DEPRESSION; RETRIEVAL; CONSTRUCTION; INDIVIDUALS AB Autobiographical memory was assessed in 24 children (12 male, 12 female, aged between 8 and 16 years) with autism spectrum disorder (ASD) and a comparison group of 24 typically developing (TD) children matched for age, IQ, gender and receptive language. 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Behaviorally-based social skills interventions have been shown to be effective in attenuating such difficulties in these environments. In light of the increasing number of children with ASD being educated in inclusive settings and requirements for the use of research-based interventions in schools, this paper (1) analyzes the quality of single-case research using behaviorally-based interventions to improve social interaction skills of children with ASD in inclusive settings and (2) evaluates whether such interventions can be considered an evidence-based practice. Characteristics and components of the interventions are summarized, and their implications for practice and future research are discussed. C1 [Hoeher Camargo, Siglia Pimentel; Rispoli, Mandy; Ganz, Jennifer; Hong, Ee Rea; Davis, Heather; Mason, Rose] Texas A&M Univ, Dept Educ Psychol, College Stn, TX 77843 USA. RP Camargo, SPH (reprint author), Univ Fed Pelotas, Fac Educ, Rua Alberto Rosa 154, BR-96010770 Pelotas, RS, Brazil. 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McDermott, Katie Epstien, Cecily Walker, Rosemary Caron, Ashley Feinberg, Leah Biederman, Joseph TI Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Psychiatric comorbidity; Youth ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ASPERGER-SYNDROME; PSYCHIATRIC COMORBIDITY; REFERRED POPULATION; GLOBAL ASSESSMENT; BIPOLAR DISORDER; ANXIETY SYMPTOMS; YOUNG-ADULTS AB To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (pervasive developmental disorder not otherwise specified). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction. C1 [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Joshi, Gagan; Wozniak, Janet; Fried, Ronna; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2117 EP 2126 DI 10.1007/s10803-014-2063-4 PG 10 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400003 PM 24566937 ER PT J AU Sun, X Allison, C Auyeung, B Matthews, FE Sharp, SJ Baron-Cohen, S Brayne, C AF Sun, Xiang Allison, Carrie Auyeung, Bonnie Matthews, Fiona E. Sharp, Stephen J. Baron-Cohen, Simon Brayne, Carol TI The Mandarin Childhood Autism Spectrum Test (CAST): Sex Differences SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Social behaviours; Communication; Sex differences; China ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGER-SYNDROME; CHILDREN; QUOTIENT; PREVALENCE; ADULTS; POPULATION; UK; PSYCHOPATHOLOGY AB Sex differences in social and communication behaviours related to autism spectrum conditions (ASC) have been investigated mainly in Western populations. Little research has been done in Chinese populations. This study explored sex differences related to ASC characteristics by examining differences in item responses and score distributions in relation to a screening instrument, the Childhood Autism Spectrum Test (CAST), used with Chinese children. A Mandarin Chinese version of the CAST (M-CAST) was distributed to 737 children aged 6-11 years in mainstream schools in Beijing. Questionnaires from 682 (93 %) children were available for analysis. The median score for boys was higher than for girls [boys, median = 8 (IQR 6, 11); girls, median = 7 (IQR 4, 9); p < 0.001]. There were differences in the proportions of boys and girls across all three score groups (a parts per thousand currency sign11, 12-14, a parts per thousand yen15) with more boys being found in the higher score groups (p = 0.035). This finding provides evidence that boys and girls have different social and communication development profiles, consistent with previous findings in Western cultures. These results suggest that sex differences related to ASC are consistent across cultures. C1 [Sun, Xiang; Brayne, Carol] Univ Cambridge, Sch Clin Med, Cambridge Inst Publ Hlth, Cambridge CB2 0SR, England. [Sun, Xiang; Allison, Carrie; Auyeung, Bonnie; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Sun, Xiang] Chinese Univ Hong Kong, Jockey Club Sch Publ Hlth & Primary Care, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. [Auyeung, Bonnie] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Matthews, Fiona E.] Univ Cambridge, MRC Biostat Unit, Cambridge Inst Publ Hlth, Cambridge CB2 0SR, England. [Sharp, Stephen J.] Univ Cambridge, MRC Epidemiol Unit, Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England. RP Sun, X (reprint author), Univ Cambridge, Sch Clin Med, Cambridge Inst Publ Hlth, Forvie Site,Cambridge Biomed Campus, Cambridge CB2 0SR, England. 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PD SEP PY 2014 VL 44 IS 9 BP 2147 EP 2161 DI 10.1007/s10803-014-2089-7 PG 15 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400006 ER PT J AU Bottema-Beutel, K Yoder, PJ Hochman, JM Watson, LR AF Bottema-Beutel, Kristen Yoder, Paul J. Hochman, Julia M. Watson, Linda R. TI The Role of Supported Joint Engagement and Parent Utterances in Language and Social Communication Development in Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Parent-child interaction; Social communication; Language ID YOUNG-CHILDREN; 2ND YEAR; ATTENTION; PREDICTORS; PLAY; RESPONSIVENESS; BEHAVIORS; IMITATION; LIFE AB This study examined associations between three parent-child engagement states and social communication, expressive language, and receptive language at 8 month follow-up, in 63 preschool-age children with autism spectrum disorder. We extend the literature on supported joint engagement by dividing this state into higher order (HSJE) and lower order types, with HSJE involving greater reciprocity in toy play. We also examined parents' follow-in utterances that co-occurred with each state. We found that only HSJE predicts later social communication and expressive language, while object engagement predicts receptive language. HSJE combined with follow-in utterances (HSJE+FI) predicts all three outcomes when controlling for HSJE+FI in other engagement states. When controlling for total HSJE, HSJE+FI is predictive of receptive language. C1 [Bottema-Beutel, Kristen] Boston Coll, Lynch Sch Educ, Chestnut Hill, MA 02467 USA. [Yoder, Paul J.; Hochman, Julia M.] Vanderbilt Univ, Dept Special Educ, Peabody Coll, Nashville, TN 37203 USA. [Watson, Linda R.] Univ N Carolina, Div Speech & Hearing Sci, Chapel Hill, NC 27599 USA. 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PD SEP PY 2014 VL 44 IS 9 BP 2162 EP 2174 DI 10.1007/s10803-014-2092-z PG 13 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400007 PM 24658867 ER PT J AU Johnson, CR Turner, K Stewart, PA Schmidt, B Shui, A Macklin, E Reynolds, A James, J Johnson, SL Courtney, PM Hyman, SL AF Johnson, Cynthia R. Turner, Kylan Stewart, Patricia A. Schmidt, Brianne Shui, Amy Macklin, Eric Reynolds, Anne James, Jill Johnson, Susan L. Courtney, Patty Manning Hyman, Susan L. TI Relationships Between Feeding Problems, Behavioral Characteristics and Nutritional Quality in Children with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Feeding problems; Mealtime behaviors; Nutrition ID AUTISM SPECTRUM DISORDERS; TYPICALLY DEVELOPING-CHILDREN; PERVASIVE DEVELOPMENTAL DISORDERS; FOOD SELECTIVITY; YOUNG-CHILDREN; MEALTIME BEHAVIORS; REPETITIVE BEHAVIORS; SENSORY SENSITIVITY; ASPERGERS-DISORDER; TREATMENT OUTCOMES AB Many children with autism spectrum disorders (ASD) have co-occurring feeding problems. However, there is limited knowledge about how these feeding habits are related to other behavioral characteristics ubiqitious in ASD. In a relatively large sample of 256 children with ASD, ages 2-11, we examined the relationships between feeding and mealtime behaviors and social, communication, and cognitive levels as well repetitive and ritualistic behaviors, sensory behaviors, and externalizing and internalizing behaviors. 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TI Sexual Knowledge and Victimization in Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Sexual knowledge; Sexual victimization; Asperger syndrome; Education ID HIGH-FUNCTIONING AUTISM; WEAK CENTRAL COHERENCE; EXPERIENCES SURVEY; YOUNG-ADULTS; CONDOM USE; PARENTAL PERSPECTIVE; COGNITIVE PHENOTYPE; HEALTH KNOWLEDGE; COLLEGE-STUDENTS; BEHAVIOR AB There is a significant gap in understanding the risk of sexual victimization in individuals with autism spectrum disorders (ASD) and the variables that contribute to risk. Age appropriate sexual interest, limited sexual knowledge and experiences, and social deficits, may place adults with ASD at increased risk. Ninety-five adults with ASD and 117 adults without ASD completed questionnaires regarding sexual knowledge sources, actual knowledge, perceived knowledge, and sexual victimization. Individuals with ASD obtained less of their sexual knowledge from social sources, more sexual knowledge from non-social sources, had less perceived and actual knowledge, and experienced more sexual victimization than controls. The increased risk of victimization by individuals with ASD was partially mediated by their actual knowledge. The link between knowledge and victimization has important clinical implications for interventions. C1 [Brown-Lavoie, S. M.; Viecili, M. A.; Weiss, J. A.] York Univ, Dept Psychol, 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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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2185 EP 2196 DI 10.1007/s10803-014-2093-y PG 12 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400009 PM 24664634 ER PT J AU Koegel, RL Kim, S Koegel, LK AF Koegel, Robert L. Kim, Sunny Koegel, Lynn Kern TI Training Paraprofessionals to Improve Socialization in Students with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Paraprofessional; Training; Autism; Socialization; School ID INCLUSIVE SETTINGS; SPECIAL-EDUCATION; SCHOOL SETTINGS; AUTISM; CHILDREN; DISABILITIES; PEERS; PARAEDUCATORS; CLASSROOMS; INTERESTS AB An important line of research relates to whether school personnel, such as paraprofessionals, who are present during unstructured social periods, such as lunch-recess, could successfully implement interventions to improve socialization between students with ASD and their typical peers in a group setting. 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PD SEP PY 2014 VL 44 IS 9 BP 2197 EP 2208 DI 10.1007/s10803-014-2094-x PG 12 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400010 PM 24671749 ER PT J AU Hanaie, R Mohri, I Kagitani-Shimono, K Tachibana, M Matsuzaki, J Watanabe, Y Fujita, N Taniike, M AF Hanaie, Ryuzo Mohri, Ikuko Kagitani-Shimono, Kuriko Tachibana, Masaya Matsuzaki, Junko Watanabe, Yoshiyuki Fujita, Norihiko Taniike, Masako TI Abnormal Corpus Callosum Connectivity, Socio-communicative Deficits, and Motor Deficits in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Diffusion tensor imaging; Tractography; Corpus callosum; Autism spectrum disorder; Motor function ID HIGH-FUNCTIONING AUTISM; LANGUAGE-ASSOCIATION CORTEX; WHITE-MATTER INTEGRITY; DTI TRACTOGRAPHY; BRAIN VOLUME; OPTIC-NERVE; SPINAL-CORD; MRI; PARCELLATION; IMPAIRMENT AB In addition to social and communicative deficits, many studies have reported motor deficits in autism spectrum disorder (ASD). This study investigated the macro and microstructural properties of the corpus callosum (CC) of 18 children with ASD and 12 typically developing controls using diffusion tensor imaging tractography. We aimed to explore whether abnormalities of the CC were related to motor deficits, as well as social and communication deficits in children with ASD. The ASD group displayed abnormal macro and microstructure of the total CC and its subdivisions and its structural properties were related to socio-communicative deficits, but not to motor deficits in ASD. These findings advance our understanding of the contributions of the CC to ASD symptoms. C1 [Hanaie, Ryuzo; Mohri, Ikuko; Kagitani-Shimono, Kuriko; Tachibana, Masaya; Taniike, Masako] Osaka Univ, Div Dev Neurosci, United Grad Sch Child Dev, Suita, Osaka 5650871, Japan. [Mohri, Ikuko; Matsuzaki, Junko; Taniike, Masako] Osaka Univ, Mol Res Ctr Childrens Mental Dev, United Grad Sch Child Dev, Suita, Osaka 5650871, Japan. 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DOI 10.1016/J.NEUROIMAGE.2013.11.027 ZWARTS MJ, 1995, MUSCLE NERVE, V18, P1244, DOI 10.1002/mus.880181105 NR 83 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 SEP PY 2014 VL 44 IS 9 BP 2209 EP 2220 DI 10.1007/s10803-014-2096-8 PG 12 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400011 PM 24710811 ER PT J AU Ben-Itzchak, E Watson, LR Zachor, DA AF Ben-Itzchak, Esther Watson, Linda R. Zachor, Ditza A. TI Cognitive Ability is Associated with Different Outcome Trajectories in Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Early intensive behavioral intervention; Autism severity; Adaptive skills; Cognitive ability ID INTENSIVE BEHAVIORAL INTERVENTION; YOUNG-CHILDREN; PREDICTORS; SCHOOL; SEVERITY AB Variability in clinical expression and in intervention outcome has been described in autism spectrum disorder (ASD). The study examined progress after 1 and 2 years of intervention and compared the impact of baseline cognitive ability on outcome trajectories in 46 children (m = 25.5 months) with ASD. The entire group showed a gradual decrease in autism severity and increase in verbal cognitive scores. Only the low cognitive scores (DQ < 70) group significantly improved in fine motor and receptive language scores. Significant gains in adaptive skills were found only for the high cognitive scores (DQ a parts per thousand yen70) group after 2 years of intervention. The entire group progressed with intervention, but only children with higher cognitive levels at baseline transferred their acquired socio-communication skills into daily functioning. C1 [Ben-Itzchak, Esther] Ariel Univ, Dept Commun Disorders, IL-40700 Ariel, Israel. [Ben-Itzchak, Esther] Assaf Harofeh Med Ctr, Autism Ctr, IL-70300 Zerifin, Israel. [Watson, Linda R.] Univ N Carolina, Sch Med, Dept Allied Hlth Sci, Chapel Hill, NC USA. [Zachor, Ditza A.] Assaf Harofeh Med Ctr, Dept Pediat, Autism Ctr, IL-70300 Zerifin, Israel. [Zachor, Ditza A.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Zachor, DA (reprint author), Assaf Harofeh Med Ctr, Dept Pediat, Autism Ctr, IL-70300 Zerifin, Israel. 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PD SEP PY 2014 VL 44 IS 9 BP 2221 EP 2229 DI 10.1007/s10803-014-2091-0 PG 9 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400012 PM 24710810 ER PT J AU Chabani, E Hommel, B AF Chabani, Ellahe Hommel, Bernhard TI Visuospatial Processing in Children with Autism: No Evidence for (Training-Resistant) Abnormalities SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Visual spatial; Visualization; School based intervention; Response to intervention; Computer based instruction ID COMPUTER-ASSISTED-INSTRUCTION; HIGH-FUNCTIONING AUTISM; EARLY BEHAVIORAL INTERVENTION; SUPERIOR VISUAL-SEARCH; WEAK CENTRAL COHERENCE; SPECTRUM DISORDERS; ENHANCED DISCRIMINATION; ASPERGERS-DISORDER; LITERACY SKILLS; FORM SIMILARITY AB Individuals with autism spectrum disorders (ASDs) have been assumed to show evidence of abnormal visuospatial processing, which has been attributed to a failure to integrate local features into coherent global Gestalts and/or to a bias towards local processing. As the available data are based on baseline performance only, which does not provide insight into cognitive/neural plasticity and actual cognitive potential, we investigated how training-resistant possible visuospatial processing differences between children with and without ASD are. In particular, we studied the effect of computerized versus face-to-face visuospatial training in a group of normally intelligent children with ASD and typically developing children as control. Findings show that (a) children with and without ASD do not differ much in visuospatial processing (as assessed by a tangram-like task) and the few differences we observed were all eliminated by training; (b) training can improve visuospatial processing (equally) in both children with ASD and normally developing children; and (c) computer-based and face-to-face training was equally effective. C1 [Chabani, Ellahe; Hommel, Bernhard] Leiden Univ, Inst Psychol, Leiden, Netherlands. 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PD SEP PY 2014 VL 44 IS 9 BP 2230 EP 2243 DI 10.1007/s10803-014-2107-9 PG 14 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400013 PM 24696376 ER PT J AU Laugeson, EA Ellingsen, R Sanderson, J Tucci, L Bates, S AF Laugeson, Elizabeth A. Ellingsen, Ruth Sanderson, Jennifer Tucci, Lara Bates, Shannon TI The ABC's of Teaching Social Skills to Adolescents with Autism Spectrum Disorder in the Classroom: The UCLA PEERS (R) Program SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social skills; Autism spectrum disorder; PEERS; Friendship; Adolescents; School ID RANDOMIZED CONTROLLED-TRIAL; HIGH-FUNCTIONING AUTISM; INTERVENTION RESEARCH; SPECIAL-EDUCATION; CHILDREN; SCHOOL; STUDENTS; METAANALYSIS; FRIENDSHIPS; 1ST-GRADE AB Social skills training is a common treatment method for adolescents with autism spectrum disorder (ASD), yet very few evidence-based interventions exist to improve social skills for high-functioning adolescents on the spectrum, and even fewer studies have examined the effectiveness of teaching social skills in the classroom. This study examines change in social functioning for adolescents with high-functioning ASD following the implementation of a school-based, teacher-facilitated social skills intervention known as Program for the Education and Enrichment of Relational Skills (PEERS (A (R)) ). Seventy-three middle school students with ASD along with their parents and teachers participated in the study. Participants were assigned to the PEERS (A (R)) treatment condition or an alternative social skills curriculum. Instruction was provided daily by classroom teachers and teacher aides for 14-weeks. Results reveal that in comparison to an active treatment control group, participants in the PEERS (A (R)) treatment group significantly improved in social functioning in the areas of teacher-reported social responsiveness, social communication, social motivation, social awareness, and decreased autistic mannerisms, with a trend toward improved social cognition on the Social Responsiveness Scale. Adolescent self-reports indicate significant improvement in social skills knowledge and frequency of hosted and invited get-togethers with friends, and parent-reports suggest a decrease in teen social anxiety on the Social Anxiety Scale at a trend level. This research represents one of the few teacher-facilitated treatment intervention studies demonstrating effectiveness in improving the social skills of adolescents with ASD in the classroom: arguably the most natural social setting of all. C1 [Laugeson, Elizabeth A.; Ellingsen, Ruth; Tucci, Lara; Bates, Shannon] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Laugeson, Elizabeth A.; Tucci, Lara] UCLA Autism Res Alliance, Help Grp, Sherman Oaks, CA 91401 USA. [Ellingsen, Ruth] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Sanderson, Jennifer] Florida Atlantic Univ, Ctr Autism & Related Disabil, Boca Raton, FL 33431 USA. 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PD SEP PY 2014 VL 44 IS 9 BP 2244 EP 2256 DI 10.1007/s10803-014-2108-8 PG 13 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400014 PM 24715256 ER PT J AU Wood, JJ Fujii, C Renno, P Van Dyke, M AF Wood, Jeffrey J. Fujii, Cori Renno, Patricia Van Dyke, Marilyn TI Impact of Cognitive Behavioral Therapy on Observed Autism Symptom Severity During School Recess: A Preliminary Randomized, Controlled Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Cognitive behavioral therapy; Autism spectrum disorders; School-aged children; School observations ID HIGH-FUNCTIONING AUTISM; TREATING ANXIETY DISORDERS; LONG-TERM-MEMORY; SPECTRUM DISORDERS; ASPERGER-SYNDROME; SOCIAL-SKILLS; CLINICAL-TRIAL; CHILDREN; INTERVENTION; SERVICES AB This study compared cognitive behavioral therapy (CBT) and treatment-as-usual (TAU) in terms of effects on observed social communication-related autism symptom severity during unstructured play time at school for children with autism spectrum disorders (ASD). Thirteen children with ASD (7-11 years old) were randomly assigned to 32 sessions of CBT or community-based psychosocial treatment (TAU) for 16 weeks. The CBT program is based on the memory retrieval competition model and emphasizes the development of perspective-taking through guided behavioral experimentation supplemented with reflective Socratic discussion and supported by parent training and school consultation to promote generalization of social communication and emotion regulation skills. Trained observers blind to treatment condition observed each child during recess on two separate days at baseline and again at posttreatment, using a structured behavioral observation system that generates frequency scores for observed social communication-related autism symptoms. CBT outperformed TAU at posttreatment on the frequency of self-isolation, the proportion of time spent with peers, the frequency of positive or appropriate interaction with peers, and the frequency of positive or appropriate peer responses to the target child (d effect size range 1.34-1.62). On average, children in CBT were engaged in positive or appropriate social interaction with peers in 68.6 % of observed intervals at posttreatment, compared to 25 % of intervals for children in TAU. Further investigation of this intervention modality with larger samples and follow-up assessments is warranted. C1 [Wood, Jeffrey J.; Fujii, Cori; Renno, Patricia; Van Dyke, Marilyn] Univ Calif Los Angeles, Dept Educ, Los Angeles, CA 90095 USA. [Wood, Jeffrey J.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. RP Wood, JJ (reprint author), Univ Calif Los Angeles, Dept Educ, Moore Hall,Box 951521, Los Angeles, CA 90095 USA. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2277 EP 2289 DI 10.1007/s10803-014-2098-6 PG 13 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400017 PM 24658868 ER PT J AU Morgan, L Leatzow, A Clark, S Siller, M AF Morgan, Lindee Leatzow, Allison Clark, Sarah Siller, Michael TI Interview Skills for Adults with Autism Spectrum Disorder: A Pilot Randomized Controlled Trial SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Autism; Adults; Randomized controlled trial; Social skills; Intervention ID ADAPTIVE-BEHAVIOR SCALES; HIGH-FUNCTIONING AUTISM; QUALITY-OF-LIFE; SOCIAL-SKILLS; YOUNG-ADULTS; ASPERGERS SYNDROME; EMPLOYMENT; VINELAND; INDIVIDUALS; ADOLESCENTS AB The purpose of this pilot study was to evaluate the efficacy of the interview skills curriculum (ISC), a manualized 12-week group-delivered intervention for young adults with autism spectrum disorder (ASD). 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Brewer, Neil TI Using the Autism Detection in Early Childhood (ADEC) and Childhood Autism Rating Scales (CARS) to Predict Long Term Outcomes in Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Predictive validity; ADEC; CARS; Long term outcomes ID DIAGNOSTIC OBSERVATION SCHEDULE; BEHAVIOR CHECKLIST; VALIDITY; STAT; AGE AB This study evaluated the predictive validity of the Autism Detection in Early Childhood (ADEC; Young, Autism detection in early childhood: ADEC. Australian Council of Educational Research, Camberwell, VIC 2007) and a well-established screening tool, the Childhood Autism Rating Scale (CARS; Schopler et al. The childhood autism rating scale (CARS). Western Psychological Services, Los Angeles 1988), for long term outcomes of children with ASD engaged in an early intervention program. Participants were 55 children (44 male, 11 female) aged 19-42 months (M = 33.5, SD = 5.6) at initial assessment who were followed up 2 and 6 years after their initial assessment. The ADEC and the CARS performed similarly when predicting long term outcomes such as clinical diagnostic outcome and overall adaptive functioning level. However, only the ADEC score was significantly correlated with ASD symptom severity at the 6-year follow up. Although these findings need to be replicated with additional and larger samples, this study extends our understanding of the psychometric properties of both the ADEC and the CARS. C1 [Nah, Yong-Hwee; Young, Robyn L.; Brewer, Neil] Flinders Univ S Australia, Sch Psychol, Adelaide, SA 5001, Australia. RP Nah, YH (reprint author), Flinders Univ S Australia, Sch Psychol, POB 2100, Adelaide, SA 5001, Australia. 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L., 2009, STRUCTURED PROGRAM E NR 41 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 SEP PY 2014 VL 44 IS 9 BP 2301 EP 2310 DI 10.1007/s10803-014-2102-1 PG 10 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400019 PM 24658894 ER PT J AU Crais, ER McComish, CS Humphreys, BP Watson, LR Baranek, GT Reznick, JS Christian, RB Earls, M AF Crais, Elizabeth R. McComish, Cara S. Humphreys, Betsy P. Watson, Linda R. Baranek, Grace T. Reznick, J. Steven Christian, Rob B. Earls, Marian TI Pediatric Healthcare Professionals' Views on Autism Spectrum Disorder Screening at 12-18 Months SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorder (ASD); Screening; Infants; Pediatric healthcare professionals ID FOLLOW-UP; MODIFIED CHECKLIST; EARLY-DIAGNOSIS; YOUNG-CHILDREN; AGE; IDENTIFICATION; TODDLERS; INTERVENTIONS; SURVEILLANCE; INFANTS AB This study explored North Carolina pediatric healthcare professional's (PHP) perceptions of screening 12-18 month old infants for Autism Spectrum Disorder (ASD). Eight focus groups (66 PHPs) were conducted across practice settings. The purpose was to explore PHP's perspectives to: inform development of ASD screening tools and ultimately impact their use in PHP settings. PHPs reported concerns, barriers, and the need for research to support early ASD screening. Additionally, they expressed the need for: (a) clear "red flags" of ASD for 12-18 month olds; (b) socioculturally sensitive and effective screening tools; (c) effective early interventions; (d) systems to handle potential increases in referrals; and (e) continuing education. PHPs also demonstrated preferences about screening tool characteristics and processes for enhancing screening efforts. C1 [Crais, Elizabeth R.; McComish, Cara S.; Watson, Linda R.] Univ N Carolina, Div Speech & Hearing Sci, Chapel Hill, NC 27599 USA. [Humphreys, Betsy P.] Univ New Hampshires Inst Disabil, Durham, NH USA. [Baranek, Grace T.] Univ N Carolina, Div Occupat Sci & Occupat Therapy, Chapel Hill, NC 27599 USA. [Reznick, J. Steven] Univ N Carolina, Chapel Hill, NC 27599 USA. [Christian, Rob B.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Earls, Marian] Triad Adult & Pediat Med, Highpoint, NC USA. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2311 EP 2328 DI 10.1007/s10803-014-2101-2 PG 18 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400020 PM 24700359 ER PT J AU Kassardjian, A Leaf, JB Ravid, D Leaf, JA Alcalay, A Dale, S Tsuji, K Taubman, M Leaf, R McEachin, J Oppenheim-Leaf, ML AF Kassardjian, Alyne Leaf, Justin B. Ravid, Daniel Leaf, Jeremy A. Alcalay, Aditt Dale, Stephanie Tsuji, Kathleen Taubman, Mitchell Leaf, Ronald McEachin, John Oppenheim-Leaf, Misty L. TI Comparing the Teaching Interaction Procedure to Social Stories: A Replication Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Behavioral skills training; Social skills; Social skills groups; Social stories; Teaching interaction procedure ID ASPERGER-SYNDROME; AUTISM; CHILDREN; SKILLS; COMMUNICATION; DISORDER; INCREASE; BEHAVIOR AB This study compared the teaching interaction procedure to social stories implemented in a group setting to teach social skills to three children diagnosed with autism spectrum disorder. The researchers taught each participant one social skill with the teaching interaction procedure, one social skill with the social story procedure, and one social skill was assigned to a no intervention condition. The teaching interaction procedure consisted of didactic questions, teacher demonstration, and role-play; the social story procedure consisted of reading a book and answering comprehension questions. The researchers measured participants' performances during probes, responses to comprehension questions, and responding during role-plays. The results indicated that the teaching interaction procedure was more efficacious than the social story procedure across all three participants. C1 [Kassardjian, Alyne; Leaf, Justin B.; Ravid, Daniel; Leaf, Jeremy A.; Alcalay, Aditt; Dale, Stephanie; Tsuji, Kathleen; Taubman, Mitchell; Leaf, Ronald; McEachin, John; Oppenheim-Leaf, Misty L.] Autism Partnership Fdn, Seal Beach, CA 90740 USA. RP Leaf, JB (reprint author), Autism Partnership Fdn, 200 Marina Dr, Seal Beach, CA 90740 USA. EM jblautpar@aol.com CR Adams L., 2004, FOCUS AUTISM OTHER D, V19, P87, DOI DOI 10.1177/10883576040190020301 [Anonymous], 2009, NAT STAND PROJ ADDR Ayllon T., 1968, TOKEN EC MOTIVATIONA BAER DM, 1968, J APPL BEHAV ANAL, V1, P91, DOI 10.1901/jaba.1968.1-91 Barry L. 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PD SEP PY 2014 VL 44 IS 9 BP 2329 EP 2340 DI 10.1007/s10803-014-2103-0 PG 12 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400021 PM 24682708 ER PT J AU Kimhi, Y Shoam-Kugelmas, D Ben-Artzi, GA Ben-Moshe, I Bauminger-Zviely, N AF Kimhi, Yael Shoam-Kugelmas, Dana Ben-Artzi, Galit Agam Ben-Moshe, Inbal Bauminger-Zviely, Nirit TI Theory of Mind and Executive Function in Preschoolers with Typical Development Versus Intellectually Able Preschoolers with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Theory of mind; Executive functions; Preschool ID FALSE BELIEF; INHIBITORY CONTROL; INDIVIDUAL-DIFFERENCES; FUNCTION DEFICITS; YOUNG-CHILDREN; DYSFUNCTION; LANGUAGE; ABILITY; DESIRES; IMPAIRMENTS AB Children with autism spectrum disorder (ASD) have difficulties in theory of mind (ToM) and executive function (EF), which may be linked because one domain (EF) affects the other (ToM). Group differences (ASD vs. typical development) were examined in both cognitive domains, as well as EF's associations and regressions with ToM. Participants included 29 intellectually able preschoolers with ASD and 30 typical preschoolers, aged 3-6 years. EF tasks included planning and cognitive shifting measures. ToM tasks included predicting and explaining affective and location false-belief tasks. The novelty of this study lies in its in-depth examination of ToM explanation abilities in ASD alongside the role of verbal abilities (VIQ). Significant group differences emerged on most EF and ToM measures, in favor of typically developing children. Overall in the study group, EF-planning skills, EF-cognitive shifting and VIQ significantly contributed to the explained variance of ToM measures. Implications are discussed regarding the social-cognitive deficit in ASD. C1 [Kimhi, Yael; Shoam-Kugelmas, Dana; Ben-Artzi, Galit Agam; Ben-Moshe, Inbal; Bauminger-Zviely, Nirit] Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. [Kimhi, Yael] Levinsky Coll Educ, Tel Aviv, Israel. RP Bauminger-Zviely, N (reprint author), Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2341 EP 2354 DI 10.1007/s10803-014-2104-z PG 14 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400022 PM 24696374 ER PT J AU Bowler, DM Gaigg, SB Gardiner, JM AF Bowler, Dermot M. Gaigg, Sebastian B. Gardiner, John M. TI Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Memory; Relational binding ID EPISODIC FUTURE THINKING; ASPERGERS-SYNDROME; RECALL; RECOGNITION; DEFICITS; CHILDREN; CONTEXT; BRAIN AB Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D'Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD. C1 [Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.] City Univ London, Dept Psychol, Autism Res Grp, London EC1V 0HB, England. 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Disord. PD SEP PY 2014 VL 44 IS 9 BP 2355 EP 2362 DI 10.1007/s10803-014-2105-y PG 8 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400023 PM 24696375 ER PT J AU Fink, E de Rosnay, M Wierda, M Koot, HM Begeer, S AF Fink, Elian de Rosnay, Marc Wierda, Marlies Koot, Hans M. Begeer, Sander TI Brief Report: Accuracy and Response Time for the Recognition of Facial Emotions in a Large Sample of Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Emotion recognition; Emotion processing; Social communication ID INDIVIDUALS; ADOLESCENTS; DEFICITS AB The empirical literature has presented inconsistent evidence for deficits in the recognition of basic emotion expressions in children with autism spectrum disorders (ASD), which may be due to the focus on research with relatively small sample sizes. Additionally, it is proposed that although children with ASD may correctly identify emotion expression they rely on more deliberate, more time-consuming strategies in order to accurately recognize emotion expressions when compared to typically developing children. In the current study, we examine both emotion recognition accuracy and response time in a large sample of children, and explore the moderating influence of verbal ability on these findings. The sample consisted of 86 children with ASD (M (age) = 10.65) and 114 typically developing children (M (age) = 10.32) between 7 and 13 years of age. All children completed a pre-test (emotion word-word matching), and test phase consisting of basic emotion recognition, whereby they were required to match a target emotion expression to the correct emotion word; accuracy and response time were recorded. Verbal IQ was controlled for in the analyses. We found no evidence of a systematic deficit in emotion recognition accuracy or response time for children with ASD, controlling for verbal ability. However, when controlling for children's accuracy in word-word matching, children with ASD had significantly lower emotion recognition accuracy when compared to typically developing children. The findings suggest that the social impairments observed in children with ASD are not the result of marked deficits in basic emotion recognition accuracy or longer response times. However, children with ASD may be relying on other perceptual skills (such as advanced word-word matching) to complete emotion recognition tasks at a similar level as typically developing children. C1 [Fink, Elian; de Rosnay, Marc; Begeer, Sander] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. [Wierda, Marlies; Koot, Hans M.; Begeer, Sander] Vrije Univ Amsterdam, Amsterdam, Netherlands. RP Begeer, S (reprint author), Vrije Univ Amsterdam, Amsterdam, Netherlands. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2363 EP 2368 DI 10.1007/s10803-014-2084-z PG 6 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400024 PM 24634064 ER PT J AU Albrecht, MA Stuart, GW Falkmer, M Ordqvist, A Leung, D Foster, JK Falkmer, T AF Albrecht, Matthew A. Stuart, Geoffrey W. Falkmer, Marita Ordqvist, Anna Leung, Denise Foster, Jonathan K. Falkmer, Torbjorn TI Brief Report: Visual Acuity in Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger syndrome; Case control study; ETDRS; High functioning autism; Perception; Vision ID COGNITIVE-STYLE; PERCEPTION; VISION AB Recently, there has been heightened interest in suggestions of enhanced visual acuity in autism spectrum disorders (ASD) which was sparked by evidence that was later accepted to be methodologically flawed. However, a recent study that claimed children with ASD have enhanced visual acuity (Brosnan et al. in J Autism Dev Disord 42:2491-2497, 2012) repeated a critical methodological flaw by using an inappropriate viewing distance for a computerised acuity test, placing the findings in doubt. We examined visual acuity in 31 children with ASD and 33 controls using the 2 m 2000 Series Revised Early Treatment Diabetic Retinopathy Study chart placed at twice the conventional distance to better evaluate possible enhanced acuity. Children with ASD did not demonstrate superior acuity. The current findings strengthen the argument that reports of enhanced acuity in ASD are due to methodological flaws and challenges the reported association between visual acuity and systemising type behaviours. C1 [Albrecht, Matthew A.; Foster, Jonathan K.] Curtin Univ, Sch Psychol & Speech Pathol, Curtin Hlth Innovat Res Inst, Perth, WA 6845, Australia. [Stuart, Geoffrey W.] La Trobe Univ, Sch Psychol Sci, Olga Tennison Autism Res Ctr, Melbourne, Vic, Australia. [Falkmer, Marita; Leung, Denise; Falkmer, Torbjorn] Curtin Univ, Fac Hlth Sci, Sch Occupat Therapy & Social Work, Curtin Hlth Innovat Res Inst, Perth, WA 6845, Australia. [Falkmer, Marita] Jonkoping Univ, Inst Disabil Res, Sch Educ & Commun, CHILD Programme, Jonkoping, Sweden. [Ordqvist, Anna; Falkmer, Torbjorn] Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci IMH, Linkoping, Sweden. [Ordqvist, Anna; Falkmer, Torbjorn] Cty Council, UHL, Pain & Rehabil Ctr, Linkoping, Sweden. [Foster, Jonathan K.] Hlth Dept WA, Neurosci Unit, Perth, WA, Australia. [Falkmer, Torbjorn] La Trobe Univ, Sch Occupat Therapy, Melbourne, Vic, Australia. RP Falkmer, T (reprint author), Curtin Univ, Fac Hlth Sci, Sch Occupat Therapy & Social Work, Curtin Hlth Innovat Res Inst, GPO Box U1987, Perth, WA 6845, Australia. 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Autism Dev. Disord. PD SEP PY 2014 VL 44 IS 9 BP 2369 EP 2374 DI 10.1007/s10803-014-2086-x PG 6 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400025 PM 24639028 ER PT J AU Taylor, CM Vehorn, A Noble, H Weitlauf, AS Warren, ZE AF Taylor, Cora M. Vehorn, Alison Noble, Hylan Weitlauf, Amy S. Warren, Zachary E. TI Brief Report: Can Metrics of Reporting Bias Enhance Early Autism Screening Measures? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Screening; Early identification; Internal metrics ID SPECTRUM DISORDERS; MODIFIED CHECKLIST; TODDLERS; CHILDREN; SCALE AB The goal of the current study was to develop and pilot the utility of two simple internal response bias metrics, over-reporting and under-reporting, in terms of additive clinical value within common screening practices for early detection of autism spectrum disorder risk. Participants were caregivers and children under 36 months of age (n = 145) participating in first-time diagnostic appointments across our clinical research center due to developmental concerns. Caregivers were asked to complete the Modified Checklist for Autism in Toddlers (MCHAT) as well as a questionnaire embedding six response bias indicator questions. These questions were items that in previous clinical studies had been endorsed by an overwhelming majority of parents within clinically identified populations. Results indicated that removal of self-reports indicative of potential response bias dramatically reduced both false positives and false negatives on the MCHAT within this sample. This suggests that future work developing internal metrics of response bias may be promising in addressing limits of current screening measures and practices. C1 [Taylor, Cora M.; Vehorn, Alison; Noble, Hylan; Weitlauf, Amy S.; Warren, Zachary E.] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37235 USA. [Weitlauf, Amy S.; Warren, Zachary E.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. [Warren, Zachary E.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37235 USA. RP Taylor, CM (reprint author), Geisinger Hlth Syst, Autism & Dev Med Inst, 120 Hamm Dr,Suite 2A, Lewisburg, PA 17837 USA. EM cmtaylor1@geisinger.edu CR Barton ML, 2012, J AUTISM DEV DISORD, V42, P1165, DOI 10.1007/s10803-011-1343-5 Butcher J. N., 2001, MINNESOTA MULTIPHASI Chlebowski C, 2013, PEDIATRICS, V131, pE1121, DOI 10.1542/peds.2012-1525 Corsello CM, 2013, J CHILD PSYCHOL PSYC, V54, P178, DOI 10.1111/j.1469-7610.2012.02607.x Dawson G, 2010, PEDIATRICS, V125, pE17, DOI 10.1542/peds.2009-0958 Hus V, 2013, J CHILD PSYCHOL PSYC, V54, P216, DOI 10.1111/j.1469-7610.2012.02589.x Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 Lord C., 2001, AUTISM DIAGNOSTIC OB Miller JS, 2011, PEDIATRICS, V127, P866, DOI 10.1542/peds.2010-0136 Pandey J, 2008, AUTISM, V12, P513, DOI 10.1177/1362361308094503 Reynolds C. R., 2006, BEHAV ASSESSMENT SYS Robins D., 1999, MODIFIED CHECKLIST A Swanson AR, 2014, AUTISM, V18, P555, DOI 10.1177/1362361313481507 Young Margaret B., 2012, Morbidity and Mortality Weekly Report, V61, P1 Warren Z, 2011, PEDIATRICS, V127, pE1303, DOI 10.1542/peds.2011-0426 Wetherby A. M., 2002, INFANT TODDLER CHECK Wetherby AM, 2008, AUTISM, V12, P487, DOI 10.1177/1362361308094501 Zwiagenbaum L., 2011, AUTISM SPECTRUM DISO, P75 NR 18 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 SEP PY 2014 VL 44 IS 9 BP 2375 EP 2380 DI 10.1007/s10803-014-2099-5 PG 6 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400026 PM 24682706 ER PT J AU Oien, R AF Oien, Roald TI Lois Jean Brady: Apps for Autism: An Essential Guide to Over 200 Effective Apps for Improving Communication, Behavior, Social Skills, and More! SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Book Review C1 [Oien, Roald] Yale Child Study Ctr, New Haven, CT 06405 USA. RP Oien, R (reprint author), Yale Child Study Ctr, 230 South Frontage Rd, New Haven, CT 06405 USA. EM roald.oien@yale.edu CR OIEN R, 2008, LJ BRADY APPS AUTISM NR 1 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 SEP PY 2014 VL 44 IS 9 BP 2381 EP 2382 DI 10.1007/s10803-014-2134-6 PG 2 WC Psychology, Developmental SC Psychology GA AN4HW UT WOS:000340549400027 ER PT J AU Williamson, KE Jakobson, LS AF Williamson, Kathryn E. Jakobson, Lorna S. TI Social perception in children born at very low birthweight and its relationship with social/behavioral outcomes SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Prematurity; low birthweight; autism spectrum disorder; social perception; social cognition ID AUTISM SPECTRUM DISORDER; EX-PRETERM INFANTS; BIOLOGICAL MOTION; BEHAVIORAL OUTCOMES; ADOLESCENTS BORN; METAANALYSIS; POPULATION; PREVALENCE; COGNITION; SKILLS AB Background: Research has shown that children born very prematurely are at substantially elevated risk for social and behavioral difficulties similar to those seen in full-term children with autism spectrum disorders (ASDs). Methods: To gain insight into core deficits that may underlie these difficulties, in this study, we assessed the social perceptual skills of 8-to 11-year-old children born at very low birthweight (VLBW) (< 1,500 g) and age-matched, full-term controls, using the Child and Adolescent Social Perception Measure. We also assessed social and behavioral outcomes with two parent-report measures used in ASD screening. Results: Children in the preterm group had normal range estimated verbal IQ. However, we found that they were impaired in their ability to use nonverbal cues from moving faces and bodies, and situational cues, to correctly identify the emotions of characters depicted in videotaped social interactions. Their performance on this task was related to the number of 'autistic-like' traits they displayed. Conclusions: This research highlights links between social perceptual deficits and poor social and behavioral outcomes in children born very prematurely. The results also suggest that even those who have escaped major intellectual/language problems are at risk for social and behavioral problems that can be of clinical concern. C1 [Williamson, Kathryn E.; Jakobson, Lorna S.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. RP Jakobson, LS (reprint author), Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. EM jakobson@cc.umanitoba.ca FU University of Manitoba Graduate Fellowship; Manitoba Institute for Child Health/Manitoba Health Research Council Studentship; Natural Sciences and Engineering Research Council of Canada FX This research was supported by a University of Manitoba Graduate Fellowship and a Manitoba Institute for Child Health/Manitoba Health Research Council Studentship to K. E. W., and by a grant from the Natural Sciences and Engineering Research Council of Canada to L. S J. The authors have declared that they have no competing or potential conflicts of interest. The authors thank Joyce Magill-Evans and Cyndie De Koning for advice regarding the scoring of the Child and Adolescent Social Perception measure, Sarah Rigby and Lauren Galbraith for their help with scoring; the staff of the High-Risk Newborn Follow-up Program, and the children and parents who took part in this research. 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Psychiatry PD SEP PY 2014 VL 55 IS 9 BP 990 EP 998 DI 10.1111/jcpp.12210 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AN2JD UT WOS:000340410000004 PM 24552579 ER PT J AU Kaluzna-Czaplinska, J Zurawicz, E Struck, W Markuszewski, M AF Kaluzna-Czaplinska, Joanna Zurawicz, Ewa Struck, Wiktoria Markuszewski, Michal TI Identification of organic acids as potential biomarkers in the urine of autistic children using gas chromatography/mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Organic acids; Gas chromatography-mass spectrometry; Biomarkers; Autism; Principal component analysis ID BLOOD-BRAIN-BARRIER; PROPIONIC-ACID; SPECTRUM DISORDERS; 2-HYDROXYBUTYRIC ACID; CEREBROSPINAL-FLUID; DICARBOXYLIC-ACIDS; MASS-SPECTROMETRY; SOCIAL-BEHAVIOR; ASCORBIC-ACID; SAUDI-ARABIA AB There is a need to identify metabolic phenotypes in autism as they might each require unique approaches to prevention. Biological markers can help define autism subtypes and reveal potential therapeutic targets. The aim of the study was to identify alterations of small molecular weight compounds and to find potential biomarkers. Gas chromatography/mass spectrometry was employed to evaluate major metabolic changes in low molecular weight urine metabolites of 14 children with autism spectrum disorders vs. 10 non-autistic subjects. The results prove the usefulness of an identified set of 21 endogenous compounds (including 14 organic acids), whose levels are changed in diseased children. Gas chromatography/mass spectrometry method combined with multivariate statistical analysis techniques provide an efficient way of depicting metabolic perturbations of diseases, and may potentially be applicable as a novel strategy for the noninvasive diagnosis and treatment of autism. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kaluzna-Czaplinska, Joanna; Zurawicz, Ewa] Lodz Univ Technol, Dept Chem, Inst Gen & Ecol Chem, PL-90924 Lodz, Poland. [Struck, Wiktoria; Markuszewski, Michal] Med Univ Gdansk, Dept Biopharm & Pharmacodynam, PL-80416 Gdansk, Poland. RP Kaluzna-Czaplinska, J (reprint author), Lodz Univ Technol, Dept Chem, Inst Gen & Ecol Chem, Zeromskiego 116, PL-90924 Lodz, Poland. 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Chromatogr. B PD SEP 1 PY 2014 VL 966 SI SI BP 70 EP 76 DI 10.1016/j.jchromb.2014.01.041 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AN1DP UT WOS:000340323200008 PM 24565890 ER PT J AU Grondhuis, SN Aman, MG AF Grondhuis, S. N. Aman, M. G. TI Overweight and obesity in youth with developmental disabilities: a call to action SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Review DE autism; carers; intellectual disability; learning disability; parents ID PRADER-WILLI-SYNDROME; AUTISM SPECTRUM DISORDERS; BODY-MASS INDEX; OBSESSIVE-COMPULSIVE DISORDER; DISEASE RISK-FACTORS; CHILDHOOD OBESITY; INTELLECTUAL DISABILITIES; WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTICS; PHYSICAL-FITNESS AB Elevated weight status has become a leading problem for adults and children around the world, regardless of the presence or lack of disability. Youth with intellectual and developmental disabilities are more vulnerable than the typical population to overweight in recent decades, and these individuals often experience overweight and obesity at higher rates than their typically developing peers. Young people with disabilities have many circumstances, beyond those of typically developing children, which increase their risk for greater body mass. These include greater medication use, having syndromes with obesity as an associated symptom, and possessing altered eating habits related to their disability. We discuss obesity-related health risks, possible weight management options, recommendations for weight maintenance or loss, and future research. 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Intell. Disabil. Res. PD SEP PY 2014 VL 58 IS 9 BP 787 EP 799 DI 10.1111/jir.12090 PG 13 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AN2OQ UT WOS:000340425600001 PM 24020517 ER PT J AU Bostrom, PK Broberg, M AF Bostrom, P. K. Broberg, M. TI Openness and avoidance - a longitudinal study of fathers of children with intellectual disability SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; Down syndrome; father; intellectual disability; learning disability; parents ID DOWN-SYNDROME; PRESCHOOL-CHILDREN; DEVELOPMENTAL-DISABILITIES; EMOTIONAL AVAILABILITY; DISABLED-CHILDREN; PARENTING STRESS; MOTHERS; AUTISM; FAMILIES; INVOLVEMENT AB Background Fathers' interactions with children who have intellectual disabilities (ID) or developmental delays (DD) have increased over the past few decades and may be expected to continue to increase as maternal and paternal roles, along with other gender roles, become more equal. The aim of the present study was to explore fathers' experiences of parenthood in relation to a child with ID/DD from the initial discovery of the disability to 5 years later. Methods Fathers' experiences of parenting children with ID/DD were explored in a longitudinal framework. Seven Swedish fathers of young children with ID/DD participated in a series of semi-structured interviews from 2005 to 2010, and their accounts were subjected to interpretative phenomenological analysis. Results The analysis revealed three themes: (1) An interrupted path - no longer taking things for granted, which describes the fathers' reactions to their children's diagnosis; (2) Being a good father, which describes the fathers' overall perceptions of their parenting of a child with ID/DD; and (3) Dealing with the unexpected, which describes fathers' individual ways of integrating, managing, and living with the knowledge of their child's disability over the 5 years during which fathers were interviewed. Conclusions Fathers' individual paths need to be taken into consideration when offering psychological support to families of children with ID/DD. C1 [Bostrom, P. K.; Broberg, M.] Univ Gothenburg, Dept Psychol, S-40530 Gothenburg, Sweden. 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PD SEP PY 2014 VL 58 IS 9 BP 810 EP 821 DI 10.1111/jir.12093 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA AN2OQ UT WOS:000340425600003 PM 24020633 ER PT J AU Kovacs, T Bansagi, B Kelemen, O Keri, S AF Kovacs, Tamas Bansagi, Boglarka Kelemen, Oguz Keri, Szabolcs TI Neuregulin 1-Induced AKT and ERK Phosphorylation in Patients with Fragile X Syndrome (FXS) and Intellectual Disability Associated with Obstetric Complications SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Fragile X syndrome; Neuregulin 1; AKT; ERK ID MENTAL-RETARDATION PROTEIN; SIGNALING PATHWAY; MESSENGER-RNA; SCHIZOPHRENIA; DISORDERS; EXPRESSION; FMRP; AUTISM; DYSFUNCTION; MECHANISMS AB Animal models of fragile X syndrome (FXS) suggest the impairment of the intracellular AKT messenger system, which is activated by neuregulin 1 (NRG1), a key regulator of neurodevelopment. We investigated NRG1-induced activation of the AKT and extracellular signal-regulated kinase (ERK) systems by the measurement of the phosphorylated AKT/ERK to total AKT/ERK ratio in peripheral B lymphoblasts of patients with FXS, IQ-matched controls with intellectual disability (obstetric complications, preterm birth, perinatal hypoxia, and low birth weight), and typically developed healthy participants. Results revealed that patients with FXS displayed decreased AKT but normal ERK activation after the administration of NRG1. IQ-matched controls with intellectual disability displayed intact AKT/ERK activation. In conclusion, FXS, but not intellectual disability associated with obstetric complications, is associated with decreased NRG1-induced AKT phosphorylation. C1 [Kovacs, Tamas; Keri, Szabolcs] Nyiro Gyula Hosp, Natl Inst Psychiat & Addict, Budapest, Hungary. [Bansagi, Boglarka] Semmelweis Univ, Dept Pediat 2, H-1085 Budapest, Hungary. [Kelemen, Oguz] Bacs Kiskun Cty Hosp, Ctr Psychiat, Kecskemet, Hungary. [Keri, Szabolcs] Univ Szeged, Fac Med, Dept Physiol, H-6720 Szeged, Hungary. [Keri, Szabolcs] Budapest Univ Technol & Econ, Dept Cognit Sci, Budapest, Hungary. RP Keri, S (reprint author), Univ Szeged, Fac Med, Dept Physiol, Dom Sq 10, H-6720 Szeged, Hungary. EM szkeri2000@yahoo.com FU [TAMOP-4.2.2.A-11/1/KONV-2012-0052] FX This study was supported by TAMOP-4.2.2.A-11/1/KONV-2012-0052. 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Mol. Neurosci. PD SEP PY 2014 VL 54 IS 1 BP 119 EP 124 DI 10.1007/s12031-014-0257-z PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AN3GP UT WOS:000340474200013 PM 24563264 ER PT J AU Cortez, MD de Rose, JC Miguel, CF AF Cortez, Mariele Diniz de Rose, Julio C. Miguel, Caio F. TI The Role of Correspondence Training on Children's Self-Report Accuracy across Tasks SO PSYCHOLOGICAL RECORD LA English DT Article DE Correspondence training; Do-say correspondence; Generalization; Lying; Self-report ID VERBAL NONVERBAL CORRESPONDENCE; ACTIVITY SCHEDULES; INCREASING PLAY; VERBALIZATION; BEHAVIOR; REINFORCEMENT; MAINTENANCE; THOUGHTS; AUTISM; SAMPLE AB This study investigated children's self-report accuracy as a function of task type and also verified generalization of do-say correspondence across tasks. Six children between 6 and 11 years of age participated in the study. "Doing" consisted of reading words, playing a computer game, solving a math problem, and labeling music-related stimuli. "Saying" consisted of reporting on the accuracy of performance following the automated computer feedback. Baseline assessed correspondence for the different tasks. Correspondence training was conducted for the task in which levels of accuracy were the lowest. Generalized do-say correspondence was then assessed in untrained tasks. For four children, correspondence was lowest for the academic tasks. Four of six children exhibited generalized correspondence after the first training, and the remaining two children did so following a second training with a different task. Distinct tasks seemed to control different patterns of self-report accuracy. Results on generalization indicated do-say correspondence as a generalized operant behavior. C1 [Cortez, Mariele Diniz; de Rose, Julio C.] Univ Fed Sao Carlos, BR-13560 Sao Carlos, SP, Brazil. 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PD SEP PY 2014 VL 64 IS 3 BP 393 EP 402 DI 10.1007/s40732-014-0061-8 PG 10 WC Psychology, Multidisciplinary SC Psychology GA AN1VS UT WOS:000340372700005 ER PT J AU Perez-Gonzalez, LA Belloso-Diaz, C Carames-Mendez, M Alonso-Alvarez, B AF Antonio Perez-Gonzalez, Luis Belloso-Diaz, Carlota Carames-Mendez, Maria Alonso-Alvarez, Benigno TI Emergence of Complex Intraverbals Determined by Simpler Intraverbals SO PSYCHOLOGICAL RECORD LA English DT Article DE Intraverbals; Verbal behavior; Stimulus equivalence; Stimulus relations; Reasoning; Answering questions; Adults ID STIMULUS-CONTROL PROCEDURES; DEVELOPMENTAL-DISABILITIES; EMERGING SPEECH; CHILDREN; BEHAVIOR; RESPONSES; AUTISM AB This research explored some factors involved in the emergence of intraverbals as demonstrated by P,rez-Gonzalez, Herszlikowicz, and Williams (2008) in three experiments. Eleven adults learned to say the chemical elements corresponding to two chemical groups (the A-B relations) and to say the atomic numbers of two elements (the B-C relations). Thereafter, we probed the relations that result from combining these stimuli. For example, we asked the groups corresponding to the atomic numbers (the C-A relations). In Experiment 1, we taught A-B and B-C and probed the remaining relations without additional teaching. In Experiment 2, with Categories, participants learned to say the categories of the exemplars (i.e., "What is polonium?" -the correct answer was "an element"). In Experiment 3, with Exemplars, participants learned to say the exemplars of the categories (i.e., "Name a chemical element"; the correct answers were the two chemical elements). The Categories facilitated emergence in some but not all participants. The Exemplars was shown to be effective in promoting the emergence of the emergent relations. 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F., 1957, VERBAL BEHAV Sundberg C T, 1990, Anal Verbal Behav, V8, P31 Sundberg M L, 1990, Anal Verbal Behav, V8, P83 Vedora Joseph, 2009, Anal Verbal Behav, V25, P79 Vignes Tore, 2007, Anal Verbal Behav, V23, P113 Watkins C L, 1989, Anal Verbal Behav, V7, P69 NR 37 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-2933 EI 2163-3452 J9 PSYCHOL REC JI Psychol. Rec. PD SEP PY 2014 VL 64 IS 3 BP 509 EP 526 DI 10.1007/s40732-014-0047-6 PG 18 WC Psychology, Multidisciplinary SC Psychology GA AN1VS UT WOS:000340372700017 ER PT J AU Gliga, T Jones, EJH Bedford, R Charman, T Johnson, MH AF Gliga, T. Jones, E. J. H. Bedford, R. Charman, T. Johnson, M. H. TI From early markers to neuro-developmental mechanisms of autism SO DEVELOPMENTAL REVIEW LA English DT Article DE Infants; Autism; The "social brain"; Sensory processing ID SPECTRUM DISORDERS; EXECUTIVE FUNCTION; SOCIAL-PERCEPTION; JOINT ATTENTION; YOUNG-CHILDREN; EYE-GAZE; COMMUNICATION DIFFICULTIES; FUNCTIONAL CONNECTIVITY; ORBITOFRONTAL CORTEX; BIOLOGICAL MOTION AB A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the "social brain". Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions. (c) 2014 The Authors. Published by Elsevier Inc. C1 [Gliga, T.; Jones, E. J. H.; Johnson, M. H.] Univ London Birkbeck Coll, Ctr Brain & Cognit Dev, London WC1E 7HX, England. [Bedford, R.] Kings Coll London, Inst Psychiat, Dept Biostat, London WC2R 2LS, England. [Charman, T.] Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England. RP Gliga, T (reprint author), Univ London Birkbeck Coll, Ctr Brain & Cognit Dev, Malet St, London WC1E 7HX, England. 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Twenty-eight (N = 28) studies published from 2000-2012 that met the criteria for inclusion were located, reviewed, and synthesized. Findings revealed the vast majority of research has been conducted at the elementary and mixed grade-levels, while only a few studies were found focusing on students in the secondary grade levels. In addition, we found most of the existing research to focus primarily on reading, writing, mathematics, and/or a combination of these areas; however, studies in social studies and science instruction were scant, with only three studies identified. Effective interventions that emerged from this review included such strategies as: (a) visual supports; (b) technology-based instruction; (c) concrete representation; (d) direct instruction; and (e) behavioral interventions. Implications for both general and special educators working with students with ASD, limitations, and directions for future research are discussed. 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D., 2005, HDB AUTISM PERVASIVE, P772 U. S. Department of Education, 2011, CHILDR YOUTH DIS Waters HE, 2011, EDUC TRAIN AUTISM DE, V46, P544 Whalon K, 2007, YOUNG EXCEPTIONAL CH, V11, P16, DOI 10.1177/109625060701100102 Whalon K, 2008, EDUC TRAIN DEV DISAB, V43, P367 Whalon KJ, 2009, FOCUS AUTISM DEV DIS, V24, P3, DOI 10.1177/1088357608328515 WILKINS A, 1994, OPHTHAL PHYSL OPT, V14, P97, DOI 10.1111/j.1475-1313.1994.tb00567.x Wilkins AJ, 1996, OPHTHAL PHYSL OPT, V16, P491, DOI 10.1016/0275-5408(96)00028-2 NR 70 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 SEP PY 2014 VL 49 IS 3 BP 331 EP 353 PG 23 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AN0XH UT WOS:000340306800001 ER PT J AU Lo, YY Burk, B Anderson, AL AF Lo, Ya-yu Burk, Bradley Anderson, Adrienne L. TI Using Progressive Video Prompting to Teach Students with Moderate Intellectual Disability to Shoot a Basketball SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID DAILY LIVING SKILLS; AUTISM SPECTRUM DISORDERS; OF-THE-LITERATURE; DEVELOPMENTAL-DISABILITIES; COOKING SKILLS; INTERVENTION; INDIVIDUALS; ADOLESCENTS; INSTRUCTION; CHILDREN AB The current study examined the effects of a modified video prompting procedure, namely progressive video prompting, to increase technique accuracy of shooting a basketball in the school gymnasium of three 11th-grade students with moderate intellectual disability. The intervention involved participants viewing video clips of an adult model who showed progressively chucked steps for making a free throw. We used a single-case, multiple probe across participants design to evaluate the intervention effects. The results of this study showed that all three participants increased the number of steps performed correctly and maintained the skill at the 1-week and 2-week maintenance check without the video viewing. Implications for practice and future research related to video prompting variations are discussed. C1 [Lo, Ya-yu] Univ N Carolina, Charlotte, NC 28223 USA. [Anderson, Adrienne L.] Western Carolina Univ, Cullowhee, NC USA. RP Lo, YY (reprint author), Univ N Carolina, Dept Special Educ & Child Dev, 9201 Univ City Blvd, Charlotte, NC 28223 USA. 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A., 1999, CAREER DEV EXCEPTION, V22, P233, DOI 10.1177/088572889902200206 Woodward J, 1997, REV EDUC RES, V67, P503, DOI 10.3102/00346543067004503 Zisimopoulos D, 2011, EDUC TRAIN AUTISM DE, V46, P238 NR 46 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 SEP PY 2014 VL 49 IS 3 BP 354 EP 367 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AN0XH UT WOS:000340306800002 ER PT J AU Pennington, RC Collins, BC Stenhoff, DM Turner, K Gunselman, K AF Pennington, Robert C. Collins, Belva C. Stenhoff, Donald M. Turner, Kennedy Gunselman, Karen TI Using Simultaneous Prompting and Computer-Assisted Instruction to Teach Narrative Writing Skills to Students with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID LEARNING-DISABLED STUDENTS; OF-THE-LITERATURE; NO CHILD LEFT; DEVELOPMENTAL-DISABILITIES; ASPERGER-SYNDROME; PLANNING INSTRUCTION; SPECTRUM DISORDERS; WRITTEN; ADOLESCENTS; PERFORMANCE AB Despite the importance of written expression to the lives of individuals with autism spectrum disorders (ASD), there is limited research on teaching writing skills to this population. In the current study, we used a multiple probe across behaviors design to evaluate the effects of simultaneous prompting (SP) and computer-assisted instruction (CAI) on the story writing responses of five males with autism, 6 to 10 years of age. The data indicated that SP and CAI were effective in improving the story writing skills of all five participants. In addition, all participants increased non-targeted reading skills, the use of novel response forms, and demonstrated at least partial maintenance and generalization of story writing skills. C1 [Pennington, Robert C.] Univ Louisville, Louisville, KY 40292 USA. [Collins, Belva C.] Univ Kentucky, Lexington, KY 40506 USA. [Stenhoff, Donald M.] Bista Autism Ctr, Phoenix, AZ USA. [Turner, Kennedy; Gunselman, Karen] Jefferson Cty Publ Sch, Lakewood, CO USA. RP Pennington, RC (reprint author), Univ Louisville, Coll Educ & Human Dev, Dept Special Educ, Louisville, KY 40292 USA. 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PD SEP PY 2014 VL 49 IS 3 BP 396 EP 414 PG 19 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AN0XH UT WOS:000340306800005 ER PT J AU Odluyurt, S Tekin-Iftar, E Ersoy, G AF Odluyurt, Serhat Tekin-Iftar, Elif Ersoy, Gulhan TI Effects of School Counselor Supervised Peer Tutoring in Inclusive Settings on Meeting IEP Outcomes of Students with Developmental Disabilities SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SIGHT WORDS; AUTISM; INSTRUCTION; CHILDREN; SKILLS; INDIVIDUALS; BEHAVIORS; ADULTS; TEACH AB The purpose of this study was to investigate the effects of school counselor supervised peer tutoring intervention on meeting IEP outcomes of six inclusion students with developmental disabilities in a public elementary and secondary school. The effectiveness of this intervention was evaluated by using multiple probe design across students. Elementary school students (3rd graders) were taught purchasing skill at school canteen and the secondary level students (7th and 8th graders) were taught first-aid skill. Three typical peers served as tutors for each student. The results showed that the school counselor successfully supervised peer tutoring intervention, the tutor reliably delivered intervention to their peers with developmental disabilities, and tutees acquired, maintained and generalized the skills on their IEPs. In addition, tutees reported positive opinions regarding the social validity of the study. Results, future research, and implications for practice are discussed. C1 [Odluyurt, Serhat; Tekin-Iftar, Elif] Anadolu Univ, TR-26470 Eskisehir, Turkey. [Ersoy, Gulhan] Barbaros Primary Sch, Kutahya, Turkey. RP Tekin-Iftar, E (reprint author), Anadolu Univ, Engelliler Arastirma Enstitusu, TR-26470 Eskisehir, Turkey. 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TI Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; GENES; ADNP C1 [Pescosolido, Matthew F.; Schwede, Matthew; Schmidt, Michael; Gamsiz, Ece D.; Morrow, Eric M.] Dept Mol Biol Cell Biol & Biochem, Providence, RI USA. [Pescosolido, Matthew F.] Brown Univ, Mol Med Lab, Inst Brain Sci, Providence, RI 02912 USA. [Pescosolido, Matthew F.; Harrison, Ashley Johnson; Gamsiz, Ece D.; Jerskey, Beth A.; Morrow, Eric M.] Brown Univ, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, East Providence, RI USA. [Pescosolido, Matthew F.; Harrison, Ashley Johnson; Gamsiz, Ece D.; Jerskey, Beth A.; Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, East Providence, RI USA. [Pescosolido, Matthew F.; Harrison, Ashley Johnson; Schmidt, Michael; Gamsiz, Ece D.; Jerskey, Beth A.; Morrow, Eric M.] Rhode Isl Consortium Autism Res & Treatment RI CA, Providence, RI USA. [Chen, Wendy S.; Donahue, John P.] Brown Univ, Dept Surg, Alpert Med Sch, Div Ophthalmol, Providence, RI 02912 USA. [Shur, Natasha] Albany Med Ctr, Childrens Hosp, Div Genet, Dept Pediat, Albany, NY USA. [Phornphutkul, Chanika] Rhode Isl Hosp, Div Human Genet, Dept Pediat, Providence, RI USA. [Phornphutkul, Chanika] Brown Univ, Providence, RI 02912 USA. RP Morrow, EM (reprint author), Brown Univ, Mol Med Lab, 70 Ship St, Providence, RI 02912 USA. EM eric_morrow@brown.edu FU Burroughs Wellcome Fund; NIH NIGMS [P20GM103645]; Simons Foundation (SFARI) [239834, 286756]; Nancy Lurie Marks Foundation; Brown Institute for Brain Science (BIBS); Norman Prince Neuroscience Institute (NPNI) FX EMM has received a Career Award in Medical Science from the Burroughs Wellcome Fund and support from NIH NIGMS P20GM103645. This work was supported by grants from the Simons Foundation (SFARI #239834 & #286756 to EMM) and also generous support to EMM from the Nancy Lurie Marks Foundation. Brown Institute for Brain Science (BIBS) and Norman Prince Neuroscience Institute (NPNI). 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Tommerup, Niels TI Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID 3Q13.31 MICRODELETION; DEVELOPMENTAL DELAY; PREPULSE INHIBITION; NEURON DEVELOPMENT; AUTISM RESEARCH; DATABASE; RESOURCE; TRANSCRIPTION; HIPPOCAMPUS; PHENOTYPE AB Background Recently, a number of patients have been described with structural rearrangements at 3q13.31, delineating a novel microdeletion syndrome with common clinical features including developmental delay and other neurodevelopmental disorders (NDD). A smallest region of overlapping deletions (SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome. Methods and results We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural rearrangements involving ZBTB20 in two patients with NDD. In a patient with developmental delay, attention-deficit hyperactivity disorder, psychosis, Tourette's syndrome and autistic traits, a de novo balanced t(3; 18) translocation truncated ZBTB20. The other breakpoint did not disrupt any gene. In a second patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20 candidate target genes, we found 68 associated with NDD. Using chromatin immunoprecipitation and quantitative PCR, we validated the in vivo binding of Zbtb20 in evolutionary conserved regions in six of these genes (Cntn4, Gad1, Nrxn1, Nrxn3, Scn2a, Snap25). Conclusions Our study links dosage imbalance of ZBTB20 to a range of neurodevelopmental, cognitive and psychiatric disorders, likely mediated by dysregulation of multiple ZBTB20 target genes, and provides new knowledge on the genetic background of the NDD seen in the 3q13.31 microdeletion syndrome. C1 [Rasmussen, Malene B.; Halgren, Christina; Bak, Mads; Hansen, Claus; Henriksen, Karen F.; Lind-Thomsen, Allan; Tommerup, Niels] Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genome Res, Dept Cellular & Mol Med, Fac Hlth Sci, DK-2200 Copenhagen N, Denmark. [Nielsen, Jakob V.; Jensen, Niels A.] Univ Southern Denmark, Inst Mol Med, Dept Neurobiol Res, Odense C, Denmark. [Loureno, Charles M.; Marques, Wilson, Jr.; Rodrigues, Guilherme R.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Neurogenet Unit, BR-14049 Ribeirao Preto, Brazil. [Melo, Joana B.; Carreira, Isabel M.] Univ Coimbra, Lab Citogenet & Genom, Coimbra, Portugal. [Melo, Joana B.; Carreira, Isabel M.] Univ Coimbra, CIMAGO, Fac Med, Coimbra, Portugal. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. [Ferreira, Susana I.] Univ Coimbra, Fac Med, Lab Clin & Genet, Coimbra, Portugal. [Venancio, Margarida] Ctr Hosp & Univ Coimbra, Serv Genet Med, Coimbra, Portugal. [Venancio, Margarida] Univ Coimbra, Fac Med, Coimbra, Portugal. RP Tommerup, N (reprint author), Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genome Res, Dept Cellular & Mol Med, Fac Hlth Sci, Blegdamsvej 3,24-4-30, DK-2200 Copenhagen N, Denmark. EM ntommerup@sund.ku.dk RI Melo, Joana/K-8347-2014; Marques, Wilson/G-4240-2012 OI Melo, Joana/0000-0001-5049-2670; Marques, Wilson/0000-0002-4589-2749 FU Lundbeck Foundation; Augustinus Foundation; Aase & Ejnar Danielsen's Foundation; Faculty of Health Sciences, University of Copenhagen FX This study was supported by grants from the Lundbeck Foundation, the Augustinus Foundation and Aase & Ejnar Danielsen's Foundation and from the Faculty of Health Sciences, University of Copenhagen. 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Med. Genet. PD SEP PY 2014 VL 51 IS 9 BP 605 EP U6613 DI 10.1136/jmedgenet-2014-102535 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AN0AE UT WOS:000340242400007 PM 25062845 ER PT J AU Furlong, MA Engel, SM Barr, DB Wolff, MS AF Furlong, Melissa A. Engel, Stephanie M. Barr, Dana Boyd Wolff, Mary S. TI Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood SO ENVIRONMENT INTERNATIONAL LA English DT Article DE Social Responsiveness Scale; Organophosphate pesticides; Environmental exposures; Neurodevelopment ID NEONATAL CHLORPYRIFOS EXPOSURE; MEXICAN-AMERICAN CHILDREN; AUTISM SPECTRUM DISORDER; IN-UTERO; SEROTONERGIC MECHANISMS; BRAIN-DEVELOPMENT; YOUNG-CHILDREN; FETAL-GROWTH; NEURODEVELOPMENT; POPULATION AB Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in New York City recruited between 1998 and 2002 (n = 404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (Sigma DAP) OP metabolites and SRS scores among 136 children who returned for the 7-9 year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (Sigma DEP) was associated with poorer social responsiveness (beta = 5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ZDAP or total dimethylphosphate (Sigma DMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for Sigma DEPs (beta = 3.5 points, 95% CI 02, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Furlong, Melissa A.; Engel, Stephanie M.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Wolff, Mary S.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. RP Furlong, MA (reprint author), Univ N Carolina, Box 7435, Chapel Hill, NC 27599 USA. 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This difficulty underlines the need for reliable methods to capture sample characteristics of heterogeneity using a single continuous measure, incorporating the multitude of score used to describe different aspects of functioning. This study addresses this challenge by proposing a gener method of identifying and quantifying the heterogeneity of any clinical population using a severity meastn, called the PUNCH (Population Characterization of Heterogeneity). PUNCH is a decision level fusion techniquc to incorporate decisions of various phenotypic scores, while providing interpretable weights for scores. We provide applications of our framework to simulated datasets and to a large sample of youth with Autism Spectrun Disorder (ASD). Next we stratify PUNCH scores in our ASD sample and show how severity moderates findings o group differences in diffusion weighted brain imaging data; more severely affected subgroups of ASD sho) expanded differences compared to age and gender matched healthy controls. Results demonstrate the abilit of our measure in quantifying the underlying heterogeneity of the clinical samples, and suggest its utility in providing researchers with reliable severity assessments incorporating population heterogeneity. (C) 2014 Elsevier Inc. All rights reserved C1 [Tunc, Birkan; Ghanbari, Yasser; Smith, Alex R.; Verma, Ragini] Univ Penn, Perelman Sch Med, Dept Radiol, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA. [Pandey, Juhi; Browne, Aaron; Schultz, Robert T.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Schultz, Robert T.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. 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Pang, Elizabeth W. Vara, Anjili S. Batty, Magali TI Neural Substrates of Numerosity Estimation in Autism SO HUMAN BRAIN MAPPING LA English DT Article DE numerosity estimation; local and global perception; autism; MEG ID MENTAL NUMBER LINE; POSTERIOR PARIETAL CORTEX; PRIMATE PREFRONTAL CORTEX; HIGH-FUNCTIONING AUTISM; VOXEL-BASED MORPHOMETRY; VISUAL WORKING-MEMORY; MEDIAL TEMPORAL-LOBE; INTRAPARIETAL SULCUS; ELECTROPHYSIOLOGICAL EVIDENCE; PERCEIVED NUMEROSITY AB Visual skills, including numerosity estimation are reported to be superior in autism spectrum disorders (ASD). This phenomenon is attributed to individuals with ASD processing local features, rather than the Gestalt. We examined the neural correlates of numerosity estimation in adults with and without ASD, to disentangle perceptual atypicalities from numerosity processing. Fourteen adults with ASD and matched typically developed (TD) controls estimated the number of dots (80-150) arranged either randomly (local information) or in meaningful patterns (global information) while brain activity was recorded with magnetoencephalography (MEG). Behavioral results showed no significant group difference in the errors of estimation. However, numerical estimation in ASD was more variable across numerosities than TD and was not affected by the global arrangement of the dots. At 80-120 ms, MEG analyses revealed early significant differences (TD>ASD) in source amplitudes in visual areas, followed from 120 to 400 ms by group differences in temporal, and then parietal regions. After 400 ms, a source was found in the superior frontal gyrus in TD only. Activation in temporal areas was differently sensitive to the global arrangement of dots in TD and ASD. MEG data show that individuals with autism exhibit widespread functional abnormalities. Differences in temporal regions could be linked to atypical global perception. Occipital followed by parietal and frontal differences might be driven by abnormalities in the processing and conversion of visual input into a number-selective neural code and complex cognitive decisional stages. These results suggest overlapping atypicalities in sensory, perceptual and number-related processing during numerosity estimation in ASD. Hum Brain Mapp 35:4362-4385, 2014. (C) 2014 Wiley Periodicals, Inc. C1 [Meaux, Emilie] Univ Med Ctr, Dept Neurosci & Clin Neurol, Lab Neurol & Imaging Cognit, Geneva, Switzerland. [Taylor, Margot J.; Vara, Anjili S.] Univ Toronto, Hosp Sick Children, Dept Diagnost Imaging, Toronto, ON M5S 1A1, Canada. [Taylor, Margot J.; Vara, Anjili S.] Univ Toronto, Dept Psychol & Med Imaging, Toronto, ON M5S 1A1, Canada. [Pang, Elizabeth W.] Univ Toronto, Hosp Sick Children, Div Neurol, Toronto, ON M5S 1A1, Canada. 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Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4362 EP 4385 DI 10.1002/hbm.22480 PG 24 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000008 PM 24639374 ER PT J AU Romano, D Nicolau, M Quintin, EM Mazaika, PK Lightbody, AA Hazlett, HC Piven, J Carlsson, G Reiss, AL AF Romano, David Nicolau, Monica Quintin, Eve-Marie Mazaika, Paul K. Lightbody, Amy A. Hazlett, Heather Cody Piven, Joseph Carlsson, Gunnar Reiss, Allan L. TI Topological Methods Reveal High and Low Functioning Neuro-Phenotypes Within Fragile X Syndrome SO HUMAN BRAIN MAPPING LA English DT Article DE autism spectrum behavior; MRI; topological data analysis; multivariate pattern analysis; voxel-based morphometry ID IMAGE-ANALYSIS; AUTISM; BOYS; DISORDERS; THRESHOLD; SPECTRUM AB Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single-gene risk factor for autism. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism-related behaviors. To this end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57-4.15 years) diagnosed with FXS. Application of topological methods to structural MRI data revealed two large subgroups within the study population. Comparison of these subgroups showed significant between-subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e. g., enlarged caudate). In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders. (C) 2014 Wiley Periodicals, Inc. C1 [Romano, David; Quintin, Eve-Marie; Mazaika, Paul K.; Lightbody, Amy A.; Reiss, Allan L.] Stanford Univ, Sch Med, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. [Nicolau, Monica; Carlsson, Gunnar] Stanford Univ, Dept Math, Stanford, CA 94305 USA. [Hazlett, Heather Cody; Piven, Joseph] UNC, Carolina Inst Dev Disabil, Chapel Hill, NC USA. RP Romano, D (reprint author), Stanford Univ, 401 Quarry Rd,Rm 1356,MC 5795, Stanford, CA 94305 USA. EM dromano@stanford.edu FU National Institute of Mental Health [R01MH050047, R01MH064708, R01MH064580, MH061696, 5T32MH019908]; National Institute of Child Health and Human Development [P30HD003110]; Canel Family Fund FX Contract grant sponsor: National Institute of Mental Health; Contract grant numbers: R01MH050047, R01MH064708, R01MH064580; MH061696, 5T32MH019908; Contract grant sponsor: National Institute of Child Health and Human Development; Contract grant number: P30HD003110; Contract grant sponsor: the Canel Family Fund. 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Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4904 EP 4915 DI 10.1002/hbm.22521 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000048 PM 24737721 ER PT J AU de Rosnay, M Fink, E Begeer, S Slaughter, V Peterson, C AF de Rosnay, Marc Fink, Elian Begeer, Sander Slaughter, Virginia Peterson, Candida TI Talking theory of mind talk: young school-aged children's everyday conversation and understanding of mind and emotion SO JOURNAL OF CHILD LANGUAGE LA English DT Article ID FALSE-BELIEF; INDIVIDUAL-DIFFERENCES; AUTISM-SPECTRUM; LANGUAGE; BEHAVIOR; DEAFNESS; METAANALYSIS; TEMPERAMENT; SKILLS AB Links between young children's everyday use of mindful conversational skills and their success on laboratory tests of theory of mind understanding (ToM) were evaluated. Using published scales, teachers rated the conversational behavior and shyness of 129 children aged 60 to 101 months (M=78.8 months) who were in their first years of primary school. The children also took batteries of first-and second-order false-belief tests along with tests of emotion understanding and general language ability. Correlational and regression analyses showed that performance on false-belief tests of ToM significantly predicted children's competence at reading others' minds in their everyday conversational interactions. Furthermore, these links transcended individual differences in language ability, shy personality, emotion understanding, and age. These findings augment and extend a growing body of evidence linking performance on laboratory ToM tests to socially competent real-world behavior. C1 [de Rosnay, Marc; Fink, Elian; Begeer, Sander] Univ Sydney, Sydney, NSW 2006, Australia. [Begeer, Sander] Vrije Univ Amsterdam, Amsterdam, Netherlands. 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Child Lang. PD SEP PY 2014 VL 41 IS 5 BP 1179 EP 1193 DI 10.1017/S0305000913000433 PG 15 WC Psychology, Developmental; Linguistics; Psychology, Experimental SC Psychology; Linguistics GA AM0PR UT WOS:000339548200009 PM 24229511 ER PT J AU Hensley, MK El-Baz, AS Sokhadze, EM Sears, LL Casanova, MF AF Hensley, Marie K. El-Baz, Ayman S. Sokhadze, Estate (Tato) M. Sears, Lonnie L. Casanova, Manuel F. TI EFFECTS OF 18 SESSION TMS THERAPY ON GAMMA COHERENCE IN AUTISM SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE autism; transcranial magnetic stimulation; gamma coherence C1 [Hensley, Marie K.; El-Baz, Ayman S.; Sokhadze, Estate (Tato) M.; Sears, Lonnie L.; Casanova, Manuel F.] Univ Louisville, Louisville, KY 40292 USA. NR 0 TC 2 Z9 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 1-16 BP S16 EP S16 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500088 ER PT J AU Sokhadze, EM Sears, LL Sokhadze, GE Edelson, SM Tasman, A Casanova, MF AF Sokhadze, Estate (Tato) M. Sears, Lonnie L. Sokhadze, Guela E. Edelson, Stephen M. Tasman, Allan Casanova, Manuel F. TI MOTOR RESPONSE PREPARATION DEFICITS IN A CUED SPATIAL ATTENTION TASK IN AUTISM SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE LRP; spatial attention task; autism C1 [Sokhadze, Estate (Tato) M.; Sears, Lonnie L.; Sokhadze, Guela E.; Tasman, Allan; Casanova, Manuel F.] Univ Louisville, Louisville, KY 40292 USA. [Edelson, Stephen M.] Autism Res Inst, San Diego, CA USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 1-15 BP S16 EP S16 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500087 ER PT J AU Pedersen, L Parlar, S Kvist, K Whiteley, P Shattock, P AF Pedersen, Lennart Parlar, Sarah Kvist, Kajsa Whiteley, Paul Shattock, Paul TI Data mining the ScanBrit study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders: Behavioural and psychometric measures of dietary response SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE Autism spectrum disorder; Dietary intervention; Gluten; Casein ID URINARY INDOLYL-3-ACRYLOYLGLYCINE; RISK; MUTATIONS AB We previously reported results based on the examination of a gluten- and casein-free diet as an intervention for children diagnosed with an autism spectrum disorder as part of the ScanBrit collaboration. Analysis based on grouped results indicated several significant differences between dietary and non-dietary participants across various core and peripheral areas of functioning. Results also indicated some disparity in individual responses to dietary modification potentially indicative of responder and non-responder differences. Further examination of the behavioural and psychometric data garnered from participants was undertaken, with a view to determining potential factors pertinent to response to dietary intervention. Participants with clinically significant scores indicative of inattention and hyperactivity behaviours and who had a significant positive changes to said scores were defined as responders to the dietary intervention. Analyses indicated several factors to be potentially pertinent to a positive response to dietary intervention in terms of symptom presentation. Chronological age was found to be the strongest predictor of response, where those participants aged between 7 and 9 years seemed to derive most benefit from dietary intervention. Further analysis based on the criteria for original study inclusion on the presence of the urine compound, trans-indolyl-3-acryloylglycine may also merit further investigation. These preliminary observations on potential best responder characteristics to a gluten-and casein-free diet for children with autism require independent replication. C1 [Pedersen, Lennart; Parlar, Sarah] Ctr Autisme, DK-2730 Herlev, Denmark. [Kvist, Kajsa] PFA Pens, DK-2100 Copenhagen, Denmark. [Whiteley, Paul; Shattock, Paul] ESPA Res, BIC, Unit 133i, Sunderland SR5 2TA, England. RP Pedersen, L (reprint author), Ctr Autisme, Herlev Hovedgade 199, DK-2730 Herlev, Denmark. EM lpe@centerforautisme.dk FU Center for Autisme; Nils O. Seim Family Fund for Medical Research; Eric Birger Christensen Fond; Norwegian Protein Intolerance Association; Robert Luff Foundation; Glashofs Legat FX The authors thank all the parents who gave their time and permission for their children to take part in this difficult study. We owe a huge debt of thanks to Maureen Pilvang and Jonna Deibjerg who provided nutritional advice and support to parents and Charlotte Mathiesen who provided administrative support. The study was supported by grants from the Center for Autisme, the Nils O. Seim Family Fund for Medical Research, the Eric Birger Christensen Fond, the Norwegian Protein Intolerance Association, The Robert Luff Foundation and Glashofs Legat. 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Neurosci. PD SEP PY 2014 VL 17 IS 5 BP 207 EP 213 DI 10.1179/1476830513Y.0000000082 PG 7 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA AL1DI UT WOS:000338865600002 PM 24075141 ER PT J AU Bernard, PB Castano, AM Bayer, KU Benke, TA AF Bernard, Paul B. Castano, Anna M. Bayer, K. Ulrich Benke, Tim A. TI Necessary, but not sufficient: Insights into the mechanisms of mGluR mediated long-term depression from a rat model of early life seizures SO NEUROPHARMACOLOGY LA English DT Article DE Early life seizure; Long-term depression; Metabotropic glutamate receptor; CaMKII; Voltage-gated calcium channels; Autism ID FRAGILE-X-SYNDROME; METABOTROPIC GLUTAMATE RECEPTORS; MENTAL-RETARDATION PROTEIN; SIGNALING PATHWAY; MOUSE MODEL; SYNAPTIC PLASTICITY; CAMKII AUTONOMY; KINASE; PHOSPHORYLATION; POTENTIATION AB Using the rat model of early life seizures (ELS), which has exaggerated mGluR mediated long-term depression of synaptic strength (mGluR-LTD) in adulthood, we probed the signaling cascades underlying mGluR-LTD induction. Several inhibitors completely blocked mGluR-LTD in control but not in ELS rats: the proteasome, the mammalian target of rapamycin (mTOR), S6 kinase (S6K), or L-type voltage-gated calcium channels (L-type VGCC). Inhibition of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) resulted in a near complete block of mGluR-LTD in control rats and a slight reduction of mGluR-LTD in ELS rats. "Autonomous" CaMKII was found to be upregulated in ELS rats, while elevated S6K activity, which is stimulated by mTOR, was described previously. Thus, modulation of each of these factors was necessary for mGluR-LTD induction in control rats, but even their combined, permanent activation in the ELS rats was not sufficient to individually support mGluR-LTD induction following ELS. This implies that while these factors may act sequentially in controls to mediate mGluR-LTD, this is no longer the case after ELS. In contrast, activated ERK was found to be significantly down-regulated in ELS rats. Inhibition of MEK/ERK activation in control rats elevated mGluR-LTD to the exaggerated levels seen in ELS rats. Together, these results elucidate both the mechanisms that persistently enhance mGluR-LTD after ELS and the mechanisms underlying normal mGluR-LTD by providing evidence for multiple, convergent pathways that mediate mGluR-LTD induction. With our prior work, this ties these signaling cascades to the ELS behavioral phenotype that includes abnormal working memory, fear conditioning and socialization. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bernard, Paul B.; Castano, Anna M.; Benke, Tim A.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80045 USA. [Bayer, K. Ulrich; Benke, Tim A.] Univ Colorado, Sch Med, Neurosci Grad Program, Denver, CO 80045 USA. [Benke, Tim A.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80045 USA. [Bayer, K. Ulrich; Benke, Tim A.] Univ Colorado, Sch Med, Dept Pharmacol, Denver, CO 80045 USA. [Benke, Tim A.] Univ Colorado, Sch Med, Dept Otolaiyngol, Denver, CO 80045 USA. RP Benke, TA (reprint author), Univ Colorado, Sch Med, Dept Pediat, 12800 E 19th,MS8102, Denver, CO 80045 USA. EM tim.benke@ucdenver.edu FU Children's Hospital Colorado Research Institute; Epilepsy Foundation; National Institutes of Health [R01 NS076577, R01 NS081248] FX Special thanks to Drs. Heather O'Leary, Mark Dell'Acqua, Steve Coultrap and other members of the Benke, Bayer and Dell'Acqua labs and the Neuroscience Program Machine Shop Core. Funding provided by the Children's Hospital Colorado Research Institute, Epilepsy Foundation, and National Institutes of Health grants R01 NS076577 (to T.B.) and R01 NS081248 (to K.U.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of NINDS or NIH. 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Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600001 PM 24780380 ER PT J AU Lin, CY Chang, YM AF Lin, Chien-Yu Chang, Yu-Ming TI Increase in physical activities in kindergarten children with cerebral palsy by employing MaKey-MaKey-based task systems SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Interaction; Cerebral palsy; MaKey MaKey; Conductive materials; Single-case design ID DESIGNATED OCCUPATIONAL ACTIVITIES; ENVIRONMENTAL STIMULATION; ASSISTING PEOPLE; DISABILITIES; REHABILITATION; EXERCISE; LIFE; AUTISM; ADULTS AB In this study, we employed Flash- and Scratch-based multimedia by using a MaKey-MaKey-based task system to increase the motivation level of children with cerebral palsy to perform physical activities. 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PD SEP PY 2014 VL 35 IS 9 BP 2003 EP 2007 DI 10.1016/j.ridd.2014.04.020 PG 5 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK1MM UT WOS:000338179200010 PM 24864053 ER PT J AU Visser, EM Berger, HJC Prins, JB Lantman-De Valk, HMJV Teunisse, JP AF Visser, E. M. Berger, H. J. C. Prins, J. B. Lantman-De Valk, H. M. J. Van Schrojenstein Teunisse, J. P. TI Shifting impairment and aggression in intellectual disability and Autism Spectrum Disorder SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Cognitive shifting; Aggression; Autism; Intellectual disability ID BEHAVIOR RATING INVENTORY; CARD SORTING TEST; CHALLENGING BEHAVIOR; EXECUTIVE FUNCTION; PHYSICAL AGGRESSION; NEUROPSYCHOLOGICAL TESTS; TOTAL POPULATION; RISK MARKERS; YOUNG-ADULTS; CHILDREN AB Aggressive behaviour is a major problem in individuals with an intellectual disability (ID)as well as in individuals with an Autism Spectrum Disorder (ASD). There are indications that suggest a link between cognitive shifting and aggression. In this study, reports of aggressive incidents of adolescents and young adults with different clinical diagnoses (ID, ID + ASD, ASD) were collected during 1 year, using the Staff Observation Aggression Scale-Revised. Whether they were diagnosed with ID, ASD or both; individuals who displayed aggression were found to face more cognitive shifting difficulties than non-aggressive individuals, while no significant differences were found on severity of ASD symptoms. Study results support the assumption that a cognition-based model for aggression may be more adequate than a diagnose-based model. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Visser, E. M.; Berger, H. J. C.; Prins, J. B.; Teunisse, J. P.] Radboud Univ Nijmegen, Med Ctr, Dept Med Psychol, NL-6500 HB Nijmegen, Netherlands. [Lantman-De Valk, H. M. J. 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Sigafoos, Jeff Alberti, Gloria Perilli, Viviana Oliva, Doretta Buono, Serafino TI Microswitch-aided programs to support physical exercise or adequate ambulation in persons with multiple disabilities SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Microswitch-aided programs; Head movements; Arms movements; Ambulation; Toe walking; Multiple disabilities ID PROFOUND INTELLECTUAL DISABILITIES; AUTISM SPECTRUM DISORDERS; IDIOPATHIC TOE WALKING; DEVELOPMENTAL-DISABILITIES; SELF-DETERMINATION; SOCIAL VALIDATION; ENVIRONMENTAL STIMULATION; ASSISTING PEOPLE; CHILDREN; ADULTS AB Three microswitch-aided programs were assessed in three single-case studies to enhance physical exercise or ambulation in participants with multiple disabilities. Study I was aimed at helping a woman who tended to have the head bending forward and the arms down to exercise a combination of appropriate head and arms movements. Study II was aimed at promoting ambulation continuity with a man who tended to have ambulation breaks. Study III was aimed at promoting ambulation with appropriate foot position in a girl who usually showed toe walking. The experimental designs of the studies consisted of a multiple probe across responses (Study I), an ABAB sequence (Study II), and an ABABB(1) sequence (Study III). The last phase of each study was followed by a post-intervention check. The microswitches monitored the target responses selected for the participants and triggered a computer system to provide preferred stimuli contingent on those responses during the intervention phases of the studies. Data showed that the programs were effective with each of the participants who learned to exercise head and arms movements, increased ambulation continuity, and acquired high levels of appropriate foot position during ambulation, respectively. The positive performance levels were retained during the post-intervention checks. The discussion focused on (a) the potential of technology-aided programs for persons with multiple disabilities and (b) the need of replication studies to extend the evidence available in the area. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lancioni, Giulio E.] Univ Bari, I-70100 Bari, Italy. [Singh, Nirbhay N.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [O'Reilly, Mark F.] Univ Texas Austin, Austin, TX 78712 USA. [Sigafoos, Jeff] Victoria Univ Wellington, Wellington, New Zealand. [Alberti, Gloria; Perilli, Viviana; Oliva, Doretta] Lega F DOro Res Ctr, Osimo, Italy. [Alberti, Gloria; Perilli, Viviana; Oliva, Doretta] Lega F DOro Res Ctr, Lesmo, Italy. [Buono, Serafino] IRCCS Oasi Troina, Troina Enna, Italy. RP Lancioni, GE (reprint author), Univ Bari, Dept Neurosci & Sense Organs, Via Quintino Sella 268, I-70100 Bari, Italy. 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Gallagher, Stephen TI Social support and mastery influence the association between stress and poor physical health in parents caring for children with developmental disabilities SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Parents; Developmental disability; Physical health; Mastery; Social support; Stress ID AUTISM SPECTRUM DISORDER; BEHAVIOR PROBLEMS; INTELLECTUAL DISABILITIES; YOUNG-ADULTS; DIFFICULTIES QUESTIONNAIRE; SYNDROME SPECIFICITY; EXPRESSED EMOTION; ANTIBODY-RESPONSE; PERCEIVED STRESS; RECEIVED SUPPORT AB To date, much of the research linking the stress of caring for children with developmental disabilities (e.g. Autism & Down syndrome) with parental health outcomes have tended to concentrate on mental health with less attention paid to the physical health consequences. Thus, this study sought to explore the psychosocial predictors of poor physical health in these caring parents. One hundred and sixty-seven parents (109 caregivers and 58 control parents) completed measures of stress, child problem behaviours, social support, mastery and physical health. Parents of children with developmental disabilities had poorer physical health compared to control parents. Stress and mastery, but not social support and problem behaviours, were significant predictors of poor physical health within caring parents for children with developmental disabilities. However, the association between mastery and physical health was mediated by perceived stress such that those parents who were higher on mastery reported less stress and better physical health; furthermore, the association between stress and physical health was moderated by social support; those parents high on social support and low in stress had better physical health. 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Disabil. PD SEP PY 2014 VL 35 IS 9 BP 2215 EP 2223 DI 10.1016/j.ridd.2014.05.012 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK1MM UT WOS:000338179200031 PM 24927515 ER PT J AU Kim, MS Blair, KSC Lim, KW AF Kim, Mi-seon Blair, Kwang-Sun Cho Lim, Kyoung-won TI Using tablet assisted Social Stories (TM) to improve classroom behavior for adolescents with intellectual disabilities SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Tablet; Multimedia; Social Stories (TM); Intellectual disabilities; Problem behavior; Academic engagement ID AUTISM SPECTRUM DISORDERS; SPEECH-GENERATING DEVICE; 2 STUDENTS; CHILDREN; SKILLS; IPOD; IPAD; INDIVIDUALS; INSTRUCTION; ENGAGEMENT AB The present study examined the use of tablet assisted Social Stories (TM) intervention for three high school students with severe intellectual disabilities whose problem behavior interfered with their learning and caused classroom disruptions. A multiple probe design across participants was employed to test the impact of the tablet assisted SS on the participants' target behaviors. During intervention, the participants read the Social Stories that were created on Prezi and accessed via Quick Response (QR) codes using a Galaxy Tap smart tablet before participating in an academic period. Data indicated that the SS intervention decreased disruptive behavior and increased academic engagement in all three participants. All three demonstrated generalization of behaviors to a nontargeted academic period and maintenance of improved behaviors at the 2-week follow-up. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kim, Mi-seon; Lim, Kyoung-won] Kongju Natl Univ, Gongju, South Korea. [Blair, Kwang-Sun Cho] Univ S Florida, Tampa, FL 33612 USA. RP Blair, KSC (reprint author), Univ S Florida, 13301 Bruce B Downs Blvd,MHC 2336, Tampa, FL 33612 USA. 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M., 1991, SYSTEMATIC SCREENING Zaranis N., 2013, CREATIVE ED, V4, P1 NR 75 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-4222 J9 RES DEV DISABIL JI Res. Dev. Disabil. PD SEP PY 2014 VL 35 IS 9 BP 2241 EP 2251 DI 10.1016/j.ridd.2014.05.011 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK1MM UT WOS:000338179200034 PM 24927518 ER PT J AU Konst, MJ Matson, JL Goldin, R Rieske, R AF Konst, Matthew J. Matson, Johnny L. Goldin, Rachel Rieske, Robert TI How does ASD symptomology correlate with ADHD presentations? SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorders; Tantrum behavior; Autism Spectrum Disorders - Comorbidity for Children (ASD-CC); Comorbidity ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT HYPERACTIVITY DISORDER; DSM-IV-TR; SEVERE RETARDATION MESSIER; SOCIAL-SKILLS; DIAGNOSTIC-CRITERIA; PSYCHIATRIC-DISORDERS; MENTAL-RETARDATION AB Elevated rates of attention deficit/hyperactivity disorder (ADHD) symptoms have been documented in the autism spectrum disorder (ASD) population. However, the recent restructuring of the ASD diagnostic category and its respective symptom structure has elicited concern about how these changes may impact prevalence rates, the deliverance of services, and the rates of comorbid psychopathology. At present, few researchers have investigated the prevalence rates of specific ADHD presentations within ASD populations. As we seek to increase our understanding of ADHD symptom manifestation in ASD populations it is important to establish base rates of attention and hyperactive symptoms. The current manuscript sought to investigate the prevalence of inattention and impulsive symptoms in 1722 infants and toddlers. Individuals were separated into three diagnostic groups for analyses, a DSM-5 ASD group, an atypically developing group, and a DSM-IV-TR ASD group. Initial analysis extended previous research by demonstrating significantly elevated rates of inattention/impulsive symptoms in toddlers meeting DSM-5 criteria for ASD when compared to the DSM-IV-TR ASD and atypically developing groups. Additional analysis demonstrated that ASD symptom severity was positively correlated with inattention/impulsive symptoms regardless of primary diagnosis. Lastly, analyses examined the exhibition of inattention and impulsive symptoms separately within diagnostic groups. 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Dev. Disabil. PD SEP PY 2014 VL 35 IS 9 BP 2252 EP 2259 DI 10.1016/j.ridd.2014.05.017 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AK1MM UT WOS:000338179200035 PM 24929307 ER PT J AU El-Ansary, A Al-Ayadhi, L AF El-Ansary, Afaf Al-Ayadhi, Laila TI Relative abundance of short chain and polyunsaturated fatty acids in propionic acid-induced autistic features in rat pups as potential markers in autism SO LIPIDS IN HEALTH AND DISEASE LA English DT Article DE Propionic acid; Rodent model; Autism; Short chain fatty acids; Polyunsaturated fatty acids; Relative values ID NF-KAPPA-B; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; SPECTRUM DISORDERS; OXIDATIVE STRESS; SODIUM-BUTYRATE; NA+ CHANNELS; GLIOMA-CELLS; BRAIN; METABOLISM AB Background: Fatty acids are essential dietary nutrients, and one of their important roles is providing polyunsaturated fatty acids (PUFAs) for the growth and function of nervous tissue. Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome that were recently linked to effects on the gut, the brain, and behavior. They are therefore linked to neurodevelopmental disorders such as autism. Reduced levels of PUFAs are associated with impairments in cognitive and behavioral performance, which are particularly important during brain development. Recent studies suggest that omega -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are involved in neurogenesis, neurotransmission, and protection from oxidative stress. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, AA)-induced proinflammatory prostaglandin E-2 (PGE(2)) formation. Methods: In this work, the absolute and relative concentrations of propionic (PPA), butyric and acetic acids, as well as PUFAs and their precursors (alpha-Linolenic and linoleic), were measured in the brain tissue of PPA-neurointoxicated rat pups (receiving 250 mg PPA/Kg body weight for 3 consecutive days) as a rodent model with persistent autistic features compared with healthy controls. Results: The data revealed remarkably lower levels of omega6/omega3, alpha-Linolenic/Linoleic, alpha-Linolenic/EPA, alpha-Linolenic/DHA, EPA/DHA, and AA/Linoleic acid ratios in PPA-intoxicated rats. The role of these impaired ratios is discussed in relation to the activity of desaturases and elongases, which are the two enzymatic groups involved in the synthesis of PUFAs from their precursors. The relationship between the abnormal relative concentrations of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation is also discussed in detail. Conclusions: This study demonstrates that fatty acid ratios are useful for understanding the mechanism of PPA neurotoxicity in a rodent model of autism. Therefore, it is possible to use these ratios for predictions in patients with this disorder. C1 [El-Ansary, Afaf] King Saud Univ, Coll Sci, Dept Biochem, 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. RP El-Ansary, A (reprint author), King Saud Univ, Coll Sci, Dept Biochem, POB 22452, Riyadh 11495, Saudi Arabia. EM elansary@ksu.edu.sa FU Research Center of the Center for Female Scientific and Medical Colleges in King Saud University FX This research project was supported by a grant from the Research Center of the Center for Female Scientific and Medical Colleges in King Saud University. 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PD AUG 31 PY 2014 VL 13 AR 140 DI 10.1186/1476-511X-13-140 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA AP2HH UT WOS:000341892800001 PM 25175350 ER PT J AU Gerlai, R AF Gerlai, Robert TI Social behavior of zebrafish: From synthetic images to biological mechanisms of shoaling SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Ontogenesis and mechanisms of shoaling; Social behavior; Zebrafish; Alcoholism; Fetal alcohol spectrum disorder ID AUTISM SPECTRUM DISORDERS; DANIO-RERIO; SEROTONINERGIC SYSTEMS; FISH; EXPOSURE; EXPRESSION; BRAIN; MODEL; NEUROCHEMISTRY; QUANTIFICATION AB The zebrafish strikes a good balance between system complexity and practical simplicity and as a result it is becoming increasingly frequently utilized in biomedical research as a translational tool. Numerous human brain disorders are associated with abnormal social behavior and the zebrafish has been suggested for modeling such disorders. To start this line of research, however, one may need to first thoroughly examine the laboratory organism, zebrafish, and its features, social behavior in this case. Proper methods need be developed to induce and quantify social behavior. These paradigms maybe able to open a window to the brain and facilitate the understanding of the biological mechanisms of social behavior and its abnormalities. This review is based on an oral paper presented at the last Measuring Behavior Conference, and as such it is mainly focused on research conducted in my own laboratory. Tracing the temporal progression of our own work, it discusses questions including what shoaling is, how it can be induced and measured and how it can be utilized in the modeling of certain human brain disorders, for example, alcohol induced abnormalities. (C) 2014 Elsevier B.V. All rights reserved. C1 Univ Toronto, Dept Psychol, Mississauga, ON L5L 1C6, Canada. RP Gerlai, R (reprint author), Univ Toronto, Dept Psychol, 3359 Mississauga Rd North,Rm DV4023C, Mississauga, ON L5L 1C6, Canada. 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Neurosci. Methods PD AUG 30 PY 2014 VL 234 SI SI BP 59 EP 65 DI 10.1016/j.jneumeth.2014.04.028 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AO0GE UT WOS:000340986300007 PM 24793400 ER PT J AU Seffer, D Schwarting, RKW Wohr, M AF Seffer, Dominik Schwarting, Rainer K. W. Woehr, Markus TI Pro-social ultrasonic communication in rats: Insights from playback studies SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Ultrasonic communication; Ultrasonic vocalizations; Social behavior; Animal model; Autism; Schizophrenia ID ANXIETY-RELATED BEHAVIOR; RATTUS-NORVEGICUS; SEXUAL-BEHAVIOR; FEMALE RATS; STIMULUS CONFIGURATION; CATEGORICAL PERCEPTION; 50-KHZ VOCALIZATIONS; JUVENILE RATS; MOUSE MODELS; ALARM CRIES AB Rodent ultrasonic vocalizations (USV) serve as situation-dependent affective signals and convey important communicative functions. In the rat, three major USV types exist: (I) 40-kHz USV, which are emitted by pups during social isolation: (II) 22-kHz USV, which are produced by juvenile and adult rats in aversive situations, including social defeat: and (III) 50-kHz USV, which are uttered by juvenile and adult rats in appetitive situations, including rough-and-tumble play. Here, evidence for a communicative function of 50-kHz USV is reviewed, focusing on findings obtained in the recently developed 50-kHz USV radial maze playback paradigm. Up to now, the following five acoustic stimuli were tested in this paradigm: (A) natural 50-kHz USV, (B) natural 22-kHz USV, (C) artificial 50-kHz sine wave tones, (D) artificial time- and amplitude-matched white noise, and (E) background noise. All studies using the 50-kHz USV radial maze playback paradigm indicate that 50-kHz USV serve a pro-social affiliative function as social contact calls. While playback of the different kinds of acoustic stimuli used so far elicited distinct behavioral response patterns, 50-kHz USV consistently led to social approach behavior in the recipient, indicating that pro-social ultrasonic communication can be studied in a reliable and highly standardized manner by means of the 50-kHz USV radial maze playback paradigm. This appears to be particularly relevant for rodent models of neurodevelopmental disorders, as there is a tremendous need for reliable behavioral assays with face validity to social communication deficits seen in autism and schizophrenia in order to study underlying genetic and neurobiological alterations. (C) 2014 Elsevier B.V. All rights reserved. C1 [Seffer, Dominik; Schwarting, Rainer K. W.; Woehr, Markus] Univ Marburg, D-35032 Marburg, Germany. RP Wohr, M (reprint author), Univ Marburg, Gutenbergstr 18, D-35032 Marburg, Germany. 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Neurosci. Methods PD AUG 30 PY 2014 VL 234 SI SI BP 73 EP 81 DI 10.1016/j.jneumeth.2014.01.023 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AO0GE UT WOS:000340986300009 PM 24508146 ER PT J AU Sungur, AO Vorckel, KJ Schwarting, RKW Wohr, M AF Sungur, A. Oezge Voerckel, Karl J. Schwarting, Rainer K. W. Woehr, Markus TI Repetitive behaviors in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Animal model; Neurodevelopmental disorders; Postsynaptic density; Repetitive behavior; Marble burying; Self-grooming ID SCAFFOLDING PROTEIN SHANK3; FEMALE HOUSE MICE; ULTRASONIC VOCALIZATIONS; PSYCHIATRIC-DISORDERS; SYNAPTIC-TRANSMISSION; SCENT-MARKING; SEX-PHEROMONE; MUS-MUSCULUS; MUTANT MICE; MUTATIONS AB Background: Autism spectrum disorder (ASD) is characterized by persistent deficits in social behavior and communication, together with restricted and repetitive patterns of behavior. Several ASD candidate genes have been identified, including the SHANK gene family with its three family members SHANK1, SHANK2, and SHANK3. Methods: Typically, repetitive behavior in mouse models for ASD is assessed by measuring self-grooming behavior. The first aim of the current study was to assess repetitive behaviors in Shank1(-/-) null mutant, Shank1(+/-) heterozygous, and Shank1(+/+) wildtype littermate control mice by means of a comprehensive approach, including the assessment of self-grooming, digging behavior, and marble burying. The second aim was to establish a test paradigm that allows for assessing the effects of social context on the occurrence of repetitive behaviors in a genotype-dependent manner. To this aim, repetitive behaviors were repeatedly tested on three consecutive days in distinct social contexts, namely in presence or absence of social odors. Results: Shank1(+/-) heterozygous and to a lesser extent Shank1(-/-) null mutant mice displayed slightly elevated levels of self-grooming behavior as adults, but not as juveniles, with genotype differences being most prominent in the social context. In contrast to elevated self-grooming behavior, marble burying was strongly reduced in adult Shank1(+/-) heterozygous and Shank1(-/-) null mutant mice across social contexts, as compared to adult Shank1(+/+) wildtype littermate controls. Conclusion: The opposite effects of the Shank1 deletion on the two types of repetitive behaviors are in line with a number of studies on repetitive behaviors in other genetic Shank models. (C) 2014 Elsevier B.V. All rights reserved. C1 [Sungur, A. Oezge; Voerckel, Karl J.; Schwarting, Rainer K. W.; Woehr, Markus] Philipps Univ Marburg, D-35032 Marburg, Germany. RP Wohr, M (reprint author), Philipps Univ Marburg, Gutenbergstr 18, D-35032 Marburg, Germany. EM markus.woehr@staff.uni-marburg.de FU German Research Foundation (Deutsche Forschungsgemeinschaft) [DFG WO 1732/1-1] FX This work was supported by a grant by the German Research Foundation (Deutsche Forschungsgemeinschaft) to M.W. (DFG WO 1732/1-1). The authors wish to thank Jacqueline Crawley, University of California Davis School of Medicine, and the Howard Hughes Medical Institute investigators Albert Hung and Morgan Sheng for providing the Shank1 mouse line. The authors also wish to thank Clara Krzikalla and Max Rollwage for their help in data acquisition. 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Methods PD AUG 30 PY 2014 VL 234 SI SI BP 92 EP 100 DI 10.1016/j.jneumeth.2014.05.003 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AO0GE UT WOS:000340986300011 PM 24820912 ER PT J AU Riedel, A Maier, S Ulbrich, M Biscaldi, M Ebert, D Fangmeier, T Perlov, E van Elst, LT AF Riedel, Andreas Maier, Simon Ulbrich, Melanie Biscaldi, Monica Ebert, Dieter Fangmeier, Thomas Perlov, Evgeniy van Elst, Ludger Tebartz TI No significant brain volume decreases or increases in adults with high-functioning autism spectrum disorder and above average intelligence: A voxel-based morphometric study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Autism spectrum disorder (ASD); Asperger's syndrome; Voxel-based morphometry (VBM); High IQ ID ROSTRAL PREFRONTAL CORTEX; LIKELIHOOD ESTIMATION; DIAGNOSTIC INTERVIEW; SEX-DIFFERENCES; METAANALYSIS; VERSION; MATTER; SCALE; MRI; ABNORMALITIES AB Autism spectrum disorder (ASD) is increasingly being recognized as an important issue in adult psychiatry and psychotherapy. High intelligence indicates overall good brain functioning and might thus present a particularly good opportunity to study possible cerebral correlates of core autistic features in terms of impaired social cognition, communication skills, the need for routines, and circumscribed interests. Anatomical MRI data sets for 30 highly intelligent patients with high-functioning autism and 30 pairwise-matched control subjects were acquired and analyzed with voxel-based morphometry. The gray matter volume of the pairwise-matched patients and the controls did not differ significantly. When correcting for total brain volume influences, the patients with ASD exhibited smaller left superior frontal volumes on a trend level. Heterogeneous volumetric findings in earlier studies might partly be explained by study samples biased by a high inclusion rate of secondary forms of ASD, which often go along with neuronal abnormalities. Including only patients with high IQ scores might have decreased the influence of secondary forms of ASD and might explain the absence of significant volumetric differences between the patients and the controls in this study. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Riedel, Andreas; Ulbrich, Melanie; Ebert, Dieter; Fangmeier, Thomas; Perlov, Evgeniy; van Elst, Ludger Tebartz] Univ Freiburg, Clin Psychiat & Psychotherapy, Sect Expt Neuropsychiat, D-79104 Freiburg, Germany. [Riedel, Andreas; Ebert, Dieter; Fangmeier, Thomas; van Elst, Ludger Tebartz] Univ Freiburg, Clin Psychiat & Psychotherapy, Univ Zentrum Autismus Spektrum, D-79104 Freiburg, Germany. [Maier, Simon; van Elst, Ludger Tebartz] Univ Med Ctr Freiburg, Freiburg Brain Imaging, D-79106 Freiburg, Germany. [Maier, Simon] Univ Freiburg, Inst Biol 3, Fac Biol, D-79104 Freiburg, Germany. [Biscaldi, Monica] Univ Freiburg, Dept Child & Adolescent Psychiat & Psychotherapy, D-79104 Freiburg, Germany. RP Maier, S (reprint author), Univ Med Ctr Freiburg, Freiburg Brain Imaging, Breisacher Str 64, D-79106 Freiburg, Germany. EM simon.maier@uniklinik-freiburg.de FU Federal Ministry of Education and Research [BMBF 01GV0606] FX We thank Christoph Kaller for providing help and codes for the pair-wise matching procedure. Part of the study was supported by a grant from the Federal Ministry of Education and Research to LTVE (BMBF 01GV0606 to LTvE). 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Rubia, Katya CA MRC Aims Consortium TI Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ADHD; Autism; ASD; fMRI; Temporal discounting ID DEFICIT/HYPERACTIVITY DISORDER; DECISION-MAKING; SPECTRUM DISORDERS; BRAIN ACTIVATION; FMRI; CHILDREN; METAANALYSIS; POPULATION; BEHAVIOR; CORTEX AB Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have, additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. C1 [Chantiluke, Kaylita; Murphy, Clodagh M.] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London WC2R 2LS, England. [Murphy, Clodagh M.; Daly, Eileen M.; Ecker, Christina; Murphy, Declan G.; Rubia, Katya] Kings Coll London, Inst Psychiat, Sackler Inst Translat Neurodev, London WC2R 2LS, England. [Murphy, Clodagh M.; Daly, Eileen M.; Ecker, Christina; Murphy, Declan G.; Rubia, Katya] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London WC2R 2LS, England. [Giampietro, Vincent; Brammer, Michael] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Christakou, Anastasia] Univ Reading, Ctr Integrat Neurosci & Neurodynam, Reading, Berks, England. [Christakou, Anastasia] Univ Reading, Sch Psychol & Clin Language Sci, Reading, Berks, England. RP Rubia, K (reprint author), MRC Ctr Social Genet & Dev Psychiat SGDP, Dept Child Psychiat, Inst Psychiat, PO46,16 De Crespigny Pk, London SE5 8AF, England. EM katya.rubia@kcl.ac.uk RI Williams, Steve/D-6979-2011; Ecker, Christine/E-5194-2010; Bailey, Anthony/J-2860-2014 OI Bailey, Anthony/0000-0003-4257-972X FU Medical Research Council [MRC GO300155]; MRC UK Autism Imaging Multicentre Study [G0400061]; MRC [G0300155]; Institute of Psychiatry, King's College London FX This study was supported by Grants from the Medical Research Council (MRC GO300155) to Prof. Katya Rubia and the MRC UK Autism Imaging Multicentre Study (G0400061) to Prof. Declan Murphy. Dr. Anastasia Christakou was supported by a post-doctoral fellowship from MRC G0300155. Kaylita Chantiluke was supported by a Ph.D. studentship from the Institute of Psychiatry, King's College London. 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Neuroimaging PD AUG 30 PY 2014 VL 223 IS 2 BP 113 EP 120 DI 10.1016/j.pscychresns.2014.04.006 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AM6ZK UT WOS:000340014300008 PM 24929553 ER PT J AU Papadopoulos, N McGinley, JL Bradshaw, JL Rinehart, NJ AF Papadopoulos, Nicole McGinley, Jennifer L. Bradshaw, John L. Rinehart, Nicole J. TI An investigation of gait in children with Attention Deficit Hyperactivity Disorder: A case controlled study SO PSYCHIATRY RESEARCH LA English DT Article DE ADHD; Autism; Gait; Social-communication disturbance; Inattention ID HIGH-FUNCTIONING AUTISM; ASPERGERS-DISORDER; DEFICIT/HYPERACTIVITY DISORDER; MOTOR; ADHD; PERFORMANCE; TASK; DISTURBANCE; CEREBELLUM; BOYS AB This study aimed to compare the gait of children with ADHD - Combined Type (ADHD-CT) to typically developing (TD) children. Children with ADHD-CT (n=14; mean age 10 years 4 months) and a TD group (n=13; mean age 10 years 9 months) walked at self-selected slow, preferred and fast speed on an electronic walkway system. Participants completed a total of 15 walking trials; 5 trials per walking condition. Groups were matched on age, intellectual functioning, height and weight. In the preferred walking condition, there was no difference in spatio-temporal gait variables between the ADHD-CT and TD control groups. At self-selected fast speed, children with ADHD-CT were faster and walked with a higher cadence. The subtle alterations in gait pattern that may reflect a timing deficit is consistent with previous ADHD motor studies. In addition, this study extends previous studies in characterising the unique gait profile of non-medicated children with ADHD-CT where a diagnosis of autism spectrum disorder has been ruled out. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Papadopoulos, Nicole; Bradshaw, John L.; Rinehart, Nicole J.] Monash Univ, Ctr Dev Psychiat & Psychol, Sch Psychol & Psychiat, Clayton, Vic 3800, Australia. [McGinley, Jennifer L.] Univ Melbourne, Melbourne, Vic 3010, Australia. [McGinley, Jennifer L.] Southern Hlth, Clin Res Ctr Movement & Gait Disorders, Clayton, Vic, Australia. [Papadopoulos, Nicole; Rinehart, Nicole J.] Deakin Univ, Sch Psychol, Deakin Child Study Ctr, Burwood, Vic 3125, Australia. RP Papadopoulos, N (reprint author), Deakin Univ, Sch Psychol, Burwood Campus,Melbourne Burwood Campus, Burwood, Vic 3125, Australia. 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PD AUG 30 PY 2014 VL 218 IS 3 BP 319 EP 323 DI 10.1016/j.psychres.2014.04.037 PG 5 WC Psychiatry SC Psychiatry GA AK7GZ UT WOS:000338598000009 PM 24837426 ER PT J AU Corbett, BA Newsom, C Key, AP Qualls, LR Edmiston, EK AF Corbett, Blythe A. Newsom, Cassandra Key, Alexandra P. Qualls, Lydia R. Edmiston, E. Kale TI Examining the relationship between face processing and social interaction behavior in children with and without autism spectrum disorder SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Play; Ecological validity; Neuropsychology; Face memory ID ECOLOGICAL VALIDITY; FACIAL EXPRESSIONS; RECOGNITION; EMOTIONS; BRAIN; ADOLESCENTS; MOTIVATION; COGNITION; CORTISOL; IDENTITY AB Background: Children with autism spectrum disorder (ASD) show impairment in reciprocal social communication, which includes deficits in social cognition and behavior. Since social cognition and social behavior are considered to be interdependent, it is valuable to examine social processes on multiple levels of analysis. Neuropsychological measures of face processing often reveal deficits in social cognition in ASD including the ability to identify and remember facial information. However, the extent to which neuropsychological measures are associated with or predictive of real-world social behavior is unclear. Methods: The study investigated 66 children (ASD 34, typically developing (TD) 32) using neuropsychological measures of face processing (identity, affect, and memory). Children also participated in a peer interaction paradigm, which allowed observation and coding of natural social interaction behaviors during play with peers (e. g., Self-Play, Cooperative Play, Verbal Bout). ANCOVA, regression, and correlation models analyzed between-group differences, the ability of neuropsychological measures to predict social behavior, and the strength of the associations. Results: Between-group differences were shown on Memory for Faces Delayed and the peer interaction variables Self-Play and Verbal Bout. Regression models indicated that Memory for Faces Delayed predicted the amount of Self-Play, Equipment use alone, and Cooperative Play with peers on the playground. Autism symptomology only predicted verbal exchange with peers. Conclusions: Face memory strongly predicts relevant social engagement patterns in both children with and without ASD. Impairment in facial memory is associated with reduced 'real-world' social interaction and more self-play, whereas higher performance in face memory predicts more cooperative play. Results highlight the strong connection between face memory and reciprocal social interaction, suggesting that improvement in one may benefit the other. C1 [Corbett, Blythe A.; Newsom, Cassandra; Qualls, Lydia R.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37203 USA. [Corbett, Blythe A.; Newsom, Cassandra; Key, Alexandra P.; Qualls, Lydia R.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37203 USA. [Corbett, Blythe A.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37203 USA. [Newsom, Cassandra] Vanderbilt Univ, Dept Pediat, Nashville, TN 37203 USA. [Key, Alexandra P.] Vanderbilt Univ, Dept Hearing & Speech Sci, Nashville, TN 37203 USA. [Edmiston, E. Kale] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37203 USA. RP Corbett, BA (reprint author), Vanderbilt Univ, Dept Psychiat, PMB 40,230 Appleton Pl, Nashville, TN 37203 USA. EM blythe.corbett@vanderbilt.edu FU National Institute of Mental Health (NIMH) [MH085717]; National Institute of Child Development (NICHD) [P30 HD15052]; CTSA award, National Center for Advancing Translational Sciences [UL1TR000445] FX The study was funded by a grant from the National Institute of Mental Health (NIMH) MH085717 awarded to Blythe Corbett, a grant from the National Institute of Child Development (NICHD) P30 HD15052 awarded to the Vanderbilt Kennedy Center and a CTSA award No. UL1TR000445 from the National Center for Advancing Translational Sciences. The NIMH and NICHD did not have any involvement in the design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. 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Agarwal, Raj MacFabe, Derrick F. La Gamma, Edmund F. TI Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells - Possible Relevance to Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID CHAIN FATTY-ACIDS; TYROSINE-HYDROXYLASE GENE; GLUTATHIONE REDOX IMBALANCE; RAT DISTAL COLON; VALPROIC ACID; RODENT MODEL; NEURODEVELOPMENTAL DISORDERS; HISTONE-DEACETYLASE; GUT MICROBIOTA; MESSENGER-RNA AB Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA) like propionic (PPA), and butyric acid (BA), which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD). Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal) or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH) mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s) was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals such as increased levels of SCFA's can epigenetically modulate cell function further supporting their role as environmental contributors to ASD. C1 [Nankova, Bistra B.; Agarwal, Raj; La Gamma, Edmund F.] Maria Fareri Childrens Hosp, Dept Pediat, New York Med Coll, Valhalla, NY 10595 USA. [MacFabe, Derrick F.] Univ Western Ontario, Kilee Patchell Evans Autism Res Grp, Dept Psychol Neurosci, London, ON, Canada. [MacFabe, Derrick F.] Univ Western Ontario, Dept Psychiat, Div Dev Disabil, London, ON N6A 3K7, Canada. RP Nankova, BB (reprint author), Maria Fareri Childrens Hosp, Dept Pediat, New York Med Coll, Valhalla, NY 10595 USA. EM bistra_nankova@nymc.edu FU Children's Research Foundation; Children's and Women's Physicians of Westchester (CWPW); GoodLife's Children's Foundation; Autism Research Institute FX Children's Research Foundation and Children's and Women's Physicians of Westchester (CWPW) to BN and ELG; GoodLife's Children's Foundation and Autism Research Institute to DM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Other Topics GA AN8RE UT WOS:000340870900029 ER PT J AU Yu, QW Peng, Y Mishra, V Ouyang, A Li, H Zhang, H Chen, M Liu, SW Huang, H AF Yu, Qiaowen Peng, Yun Mishra, Virendra Ouyang, Austin Li, Hang Zhang, Hong Chen, Min Liu, Shuwei Huang, Hao TI Microstructure, length, and connection of limbic tracts in normal human brain development SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE limbic tract; development; trajectory; length; microstructure; DTI; connectivity; free water elimination ID RESTING-STATE NETWORKS; OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR CINGULATE CORTEX; WHITE-MATTER MATURATION; CENTRAL-NERVOUS-SYSTEM; DEFAULT MODE NETWORK; DIFFUSION-TENSOR; STRUCTURAL CONNECTIVITY; FUNCTIONAL CONNECTIVITY; ALZHEIMERS-DISEASE AB The cingulum and fornix play an important role in memory, attention, spatial orientation, and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer's disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length, and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc), hippocampal part of the cingulum (cgh) and fornix (fx) were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial, and radial diffusivity were measured for traced limbic tracts. Free water elimination (EWE) algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for EWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2 years old followed by a slow increase to 25 years old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of the right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network was confirmed as early as birth. Systematic characterization of length and DTI metrics after EWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with mental disorders. C1 [Yu, Qiaowen; Liu, Shuwei] Shandong Univ, Sch Med, Res Ctr Sect & Imaging Anat, Shandong Prov Key Lab Mental Disorders, Jinan 250012, Shandong, Peoples R China. [Yu, Qiaowen; Mishra, Virendra; Ouyang, Austin; Huang, Hao] Univ Texas SW Med Ctr Dallas, Adv Imag Res Ctr, Dallas, TX 75390 USA. [Peng, Yun; Li, Hang; Zhang, Hong] Capital Med Univ, Beijing Childrens Hosp, Dept Radiol, Beijing, Peoples R China. [Chen, Min] Univ Texas Dallas, Dept Math Sci, Richardson, TX 75083 USA. [Huang, Hao] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Liu, SW (reprint author), Shandong Univ, Sch Med, Res Ctr Sect & Imaging Anat, Shandong Prov Key Lab Mental Disorders, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China. EM liusw@sdu.edu.cn; hao.huang@utsouthwestern.edu FU NIH [MH092535, MH092535-S1]; Natural Science Foundation of China [31271161, 31071050]; Specialized Research Fund for the Doctoral Program of Higher Education of China [20120131130008] FX This study is sponsored by NIH (MH092535 and MH092535-S1), Natural Science Foundation of China (Grant Nos. 31271161 and 31071050), and Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20120131130008). 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I., 1967, REGIONAL DEV BRAIN E, P3 NR 62 TC 0 Z9 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD AUG 28 PY 2014 VL 6 AR 228 DI 10.3389/fnagi.2014.00228 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AN9NT UT WOS:000340934400001 PM 25221509 ER PT J AU Weinstein, TAR Bales, KL Maninger, N Hostetler, CM Capitanio, JP AF Weinstein, Tamara A. R. Bales, Karen L. Maninger, Nicole Hostetler, Caroline M. Capitanio, John P. TI Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta) SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE affiliation; friendship; oxytocin; rhesus macaque; social behavior; vasopressin ID MALE PRAIRIE VOLES; AUTISM SPECTRUM DISORDERS; CORTICOTROPIN-RELEASING-FACTOR; WILD FEMALE BABOONS; SEX-DIFFERENCES; ARGININE-VASOPRESSIN; INTRANASAL OXYTOCIN; SOCIAL SUPPORT; MICROTUS-OCHROGASTER; DEVELOPMENTAL EXPOSURE AB The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques' (Macaca mulatta) friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center (CNPRC). Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay (EIA). Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject), multiplex friendships (friendships displayed in more than one behavioral domain), and total number of friendships. Females' number of reciprocal and play friendships at age one significantly predicted later OT, additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males' plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual's psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in which it is administered. C1 [Weinstein, Tamara A. R.; Bales, Karen L.; Maninger, Nicole; Hostetler, Caroline M.; Capitanio, John P.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Hostetler, Caroline M.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Weinstein, TAR (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, 1 Shields Ave, Davis, CA 95616 USA. EM tarweinstein@ucdavis.edu FU NIH [RR00169, RR019970, MH20006, HD053555, HD071998]; NSF; Good Nature Institute FX We are very grateful to Laura Del Rosso, Erna Tarara., Isabel Shelton-Mottsmith, Christine Brennan, Katie Hinde, and Susie Kang for assisting with data collection, and to the CNPRC animal care staff for their help with Mood sampling, animal identification, and accommodating our research schedule. This work was supported by NIH grant RR00169 to the CNPRC and NIH grant RR019970 to John P. Capitanio. While conducting this research, Tamara A. R. Weinstein was supported by the NSF Graduate Research Fellowship and by the NIH training grant MH20006. During the writing of this paper, Karen L. Bales was funded by NIH grants HD053555 and HD071998, and the Good Nature Institute. 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Neurosci. PD AUG 28 PY 2014 VL 8 AR 295 DI 10.3389/fnbeh.2014.00295 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN9DY UT WOS:000340907400001 PM 25221489 ER PT J AU Wilkins, RW Hodges, DA Laurienti, PJ Steen, M Burdette, JH AF Wilkins, R. W. Hodges, D. A. Laurienti, P. J. Steen, M. Burdette, J. H. TI Network Science and the Effects of Music Preference on Functional Brain Connectivity: From Beethoven to Eminem SO SCIENTIFIC REPORTS LA English DT Article ID DEFAULT MODE NETWORK; SMALL-WORLD; EMOTIONAL RESPONSES; MEMORY; AUTISM; CONSCIOUSNESS; PERSONALITY; CORRELATE; PLEASANT; DISEASE AB Most people choose to listen to music that they prefer or 'like' such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music-regardless of the type-people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, we evaluated differences in functional brain connectivity when individuals listened to complete songs. We show that a circuit important for internally-focused thoughts, known as the default mode network, was most connected when listening to preferred music. We also show that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of our results was unexpected. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed. C1 [Wilkins, R. W.; Laurienti, P. J.; Steen, M.; Burdette, J. H.] Wake Forest Sch Med, Lab Complex Brain Networks, Winston Salem, NC 27157 USA. [Wilkins, R. W.] Univ N Carolina, Gateway MRI Ctr, Joint Sch Nanosci & Nanoengn, Neuroimaging Lab Complex Syst, Greensboro, NC 27401 USA. [Wilkins, R. W.; Hodges, D. A.] Univ N Carolina, Mus Res Inst, Greensboro, NC 27403 USA. RP Wilkins, RW (reprint author), Wake Forest Sch Med, Lab Complex Brain Networks, Winston Salem, NC 27157 USA. 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W., 2012, LEONARDO, V45 Zatorre RJ, 2003, ANN NY ACAD SCI, V999, P4, DOI 10.1196/annals.1284.001 NR 63 TC 2 Z9 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD AUG 28 PY 2014 VL 4 AR 6130 DI 10.1038/srep06130 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9NZ UT WOS:000340935000001 PM 25167363 ER PT J AU Ciranna, L Catania, MV AF Ciranna, Lucia Catania, Maria Vincenza TI 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE serotonin; 5-HT7 receptor; synaptic function; autism spectrum disorders; Fragile X Syndrome ID CA1 PYRAMIDAL NEURONS; RAT PREFRONTAL CORTEX; FRAGILE-X-SYNDROME; HYPERPOLARIZATION-ACTIVATED CURRENT; EXTRACELLULAR-REGULATED KINASE; MOUSE SUPRACHIASMATIC NUCLEUS; SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT-LIKE BEHAVIOR; NOVELTY-SEEKING BEHAVIOR; TEMPORAL-LOBE EPILEPSY AB Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD. C1 [Ciranna, Lucia] Univ Catania, Dept Biomed Sci, I-95125 Catania, Italy. [Catania, Maria Vincenza] Natl Res Council Italy CNR, Catania, Italy. [Catania, Maria Vincenza] IRCCS Oasi Maria SS, Neurobiol Lab, Troina, Italy. RP Ciranna, L (reprint author), Univ Catania, Dept Biomed Sci, 6 Viale Andrea Doria, I-95125 Catania, Italy. EM ciranna@unict.it FU FRAXA Research Foundation; Telethon Foundation [GGP13145] FX We wish to thank or Derek Bowie (McGill University, Montreal, QC, Canada) for critical reading of the manuscript. The present work was financed by FRAXA Research Foundation (call 2013) and Telethon Foundation (grant GGP13145). Part of images from Motifolio drawing toolkit1 were utilized in the figure preparation. 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Cell. Neurosci. PD AUG 27 PY 2014 VL 8 DI 10.3389/fncel.2014.00250 PG 17 WC Neurosciences SC Neurosciences & Neurology GA AP2ZT UT WOS:000341945400001 PM 25221471 ER PT J AU Kashihara, K AF Kashihara, Koji TI A brain-computer interface for potential non-verbal facial communication based on EEG signals related to specific emotions SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE neutral faces; source localization; aversive conditioning; face recognition; electroencephalogram; brain computer interfaces ID AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN NEURAL SYSTEM; FACE PERCEPTION; RECOGNITION; AMYGDALA; CORTEX; PROSOPAGNOSIA; EXPRESSIONS; PERFORMANCE; SYNCHRONY AB Unlike assistive technology for verbal communication, the brain-machine or brain-computer interface (BMI/BCI) has not been established as a non-verbal communication tool for amyotrophic lateral sclerosis (ALS) patients. Face-to-face communication enables access to rich emotional information, but individuals suffering from neurological disorders, such as ALS and autism, may not express their emotions or communicate their negative feelings. Although emotions may be inferred by looking at facial expressions, emotional prediction for neutral faces necessitates advanced judgment. The process that underlies brain neuronal responses to neutral faces and causes emotional changes remains unknown. To address this problem, therefore, this study attempted to decode conditioned emotional reactions to neutral face stimuli. This direction was motivated by the assumption that if electroencephalogram (EEG) signals can be used to detect patients' emotional responses to specific inexpressive faces, the results could be incorporated into the design and development of BMI/BCI-based non-verbal communication tools. To these ends, this study investigated how a neutral face associated with a negative emotion modulates rapid central responses in face processing and then identified cortical activities. The conditioned neutral face-triggered event-related potentials that originated from the posterior temporal lobe statistically significantly changed during late face processing (600-700 ms) after stimulus, rather than in early face processing activities, such as P1 and N170 responses. Source localization revealed that the conditioned neutral faces increased activity in the right fusiform gyrus (FG). This study also developed an efficient method for detecting implicit negative emotional responses to specific faces by using EEG signals. A classification method based on a support vector machine enables the easy classification of neutral faces that trigger specific individual emotions. In accordance with this classification, a face on a computer morphs into a sad or displeased countenance. The proposed method could be incorporated as a part of non-verbal communication tools to enable emotional expression. C1 Univ Tokushima, Inst Technol & Sci, Tokushima 7708506, Japan. RP Kashihara, K (reprint author), Univ Tokushima, Inst Technol & Sci, 2-1 Minamijyousanjima, Tokushima 7708506, Japan. EM kashihara.koji@tokushima-u.ac.jp FU Japan Society for the Promotion of Science (KAKENHI) [25330171] FX This study was partially funded by a Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (KAKENHI, 25330171). The author would like to thank Nagoya University and JST for providing assistance during the EEG experiment. 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Neurosci. PD AUG 26 PY 2014 VL 8 AR 244 DI 10.3389/fnins.2014.00244 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW8LA UT WOS:000346512100001 PM 25206321 ER PT J AU Soiza-Reilly, M Commons, KG AF Soiza-Reilly, Mariano Commons, Kathryn G. TI Unraveling the architecture of the dorsal raphe synaptic neuropil using high-resolution neuroanatomy SO FRONTIERS IN NEURAL CIRCUITS LA English DT Review DE vesicular glutamate transporter; glutamate decarboxylase 65; synapses; uttrathin serial-sections; axo-axonic ID VESICULAR GLUTAMATE TRANSPORTERS; MESSENGER-RNA EXPRESSION; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; SEROTONERGIC NEURONS; ARRAY TOMOGRAPHY; PERIAQUEDUCTAL GRAY; EXCITATORY SYNAPSE; MAJOR DEPRESSION; LATERAL HABENULA AB The dorsal raphe nucleus (DRN), representing the main source of brains serotonin, is implicated in the pathophysiology and therapeutics of several mental disorders that can be debilitating and life-long including depression, anxiety and autism. The activity of DRN neurons is precisely regulated, both phasically and tonically, by excitatory glutamate and inhibitory GABAergic axons arising from extra-raphe areas as well as from local sources within the nucleus. Changes in serotonin neurotransmission associated with pathophysiology may be encoded by alterations within this network of regulatory afferents. However, the complex organization of the DRN circuitry remains still poorly understood. Using a recently developed high-resolution immunofluorescence technique called array tomography (AT) we quantitatively analyzed the relative contribution of different populations of glutamate axons originating from different brain regions to the excitatory drive of the DRN. Additionally, we examined the presence of GABA axons within the DRN and their possible association with glutamate axons. In this review, we summarize our findings on the architecture of the rodent DRN synaptic neuropil using high-resolution neuroanatomy, and discuss possible functional implications for the nucleus. Understanding of the synaptic architecture of neural circuits at high resolution will pave the way to understand how neural structure and function may be perturbed in pathological states. C1 [Soiza-Reilly, Mariano] INSERM, Inst Fer Moulin, UMR S 839, F-75005 Paris, France. [Soiza-Reilly, Mariano] Univ Paris 06, Paris, France. [Commons, Kathryn G.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Commons, Kathryn G.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Soiza-Reilly, M (reprint author), INSERM, Inst Fer Moulin, UMR S 839, 17 Rue Fer Moulin, F-75005 Paris, France. EM mariano.soiza-reilly@inserm.fr; kathryn.commons@childrens.harvard.edu FU Sara Page Mayo Foundation for Pediatric Pain Research FX This work was supported by the Sara Page Mayo Foundation for Pediatric Pain Research. 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Neural Circuits PD AUG 26 PY 2014 VL 8 AR 105 DI 10.3389/fncir.2014.00105 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AP3BB UT WOS:000341948800001 PM 25206323 ER PT J AU Cea-Del Rio, CA Huntsman, MM AF Cea-Del Rio, Christian A. Huntsman, Molly M. TI The contribution of inhibitory interneurons to circuit dysfunction in Fragile X Syndrome SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE GABA; synchronization; inhibitory neurotransmission; synaptic transmission; interneurons ID AUTISM SPECTRUM DISORDER; PARVALBUMIN-POSITIVE INTERNEURONS; CRITICAL PERIOD PLASTICITY; KNOCKOUT MOUSE MODEL; FMR1 KO MICE; MENTAL-RETARDATION; GABA(A) RECEPTOR; NEURODEVELOPMENTAL DISORDERS; POSTSYNAPTIC POTENTIALS; GABAERGIC INTERNEURONS AB Many neurological disorders, including neurodevelopmental disorders, report hypersynchrony of neuronal networks. These alterations in neuronal synchronization suggest a link to the function of inhibitory interneurons. In Fragile X Syndrome (FXS), it has been reported that altered synchronization may underlie hyperexcitability, cognitive dysfunction and provide a link to the increased incidence of epileptic seizures. Therefore, understanding the roles of inhibitory intemeurons and how they control neuronal networks is of great importance in studying neurodevelopmental disorders such as FXS. Here, we present a review of how interneuron populations and inhibition are important contributors to the loss of excitatory/inhibitory balance seen in hypersynchronous and hyperexcitable networks from neurodevelopmental disorders, and specifically in FXS. C1 [Cea-Del Rio, Christian A.; Huntsman, Molly M.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA. [Huntsman, Molly M.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. 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PD AUG 25 PY 2014 VL 8 AR 245 DI 10.3389/fncel.2014.00245 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AP2ZN UT WOS:000341944800001 PM 25202236 ER PT J AU Rossignol, R Ranchon-Cole, I Paris, A Herzine, A Perche, A Laurenceau, D Bertrand, P Cercy, C Pichon, J Mortaud, S Briault, S Menuet, A Perche, O AF Rossignol, Rafaelle Ranchon-Cole, Isabelle Paris, Arnaud Herzine, Ameziane Perche, Astrid Laurenceau, David Bertrand, Pauline Cercy, Christine Pichon, Jacques Mortaud, Stephane Briault, Sylvain Menuet, Arnaud Perche, Olivier TI Visual Sensorial Impairments in Neurodevelopmental Disorders: Evidence for a Retinal Phenotype in Fragile X Syndrome SO PLOS ONE LA English DT Article ID FMR1 KNOCKOUT MICE; MENTAL-RETARDATION PROTEIN; SYNDROME MOUSE MODEL; RECEPTOR-DEPENDENT TRANSLATION; SYNAPTIC DEVELOPMENT; SOCIAL-INTERACTION; RHODOPSIN CONTENT; DENDRITIC SPINES; AUTISM; PSD-95 AB Visual sensory impairments are common in Mental Deficiency (MD) and Autism Spectrum Disorder (ASD). These defects are linked to cerebral dysfunction in the visual cortical area characterized by the deregulation of axon growth/guidance and dendrite spine immaturity of neurons. However, visual perception had not been addressed, although the retina is part of the central nervous system with a common embryonic origin. Therefore, we investigated retinal perception, the first event of vision, in a murine model of MD with autistic features. We document that retinal function is altered in Fmr1 KO mice, a model of human Fragile X Syndrome. Indeed, In Fmr1 KO mice had a lower retinal function characterized by a decreased photoreceptors neuron response, due to a 40% decrease in Rhodopsin content and to Rod Outer Segment destabilization. In addition, we observed an alteration of the visual signal transmission between photoreceptors and the inner retina which could be attributed to deregulations of pre- and post-synaptic proteins resulting in retinal neurons synaptic destabilization and to retinal neurons immaturity. Thus, for the first time, we demonstrated that retinal perception is altered in a murine model of MD with autistic features and that there are strong similarities between cerebral and retinal cellular and molecular defects. Our results suggest that both visual perception and integration must be taken into account in assessing visual sensory impairments in MD and ASD. C1 [Rossignol, Rafaelle; Paris, Arnaud; Herzine, Ameziane; Pichon, Jacques; Mortaud, Stephane; Briault, Sylvain; Menuet, Arnaud; Perche, Olivier] CNRS, UMR7355, F-45071 Orleans, France. [Rossignol, Rafaelle; Paris, Arnaud; Herzine, Ameziane; Pichon, Jacques; Mortaud, Stephane; Briault, Sylvain; Menuet, Arnaud; Perche, Olivier] Univ Orleans, Orleans, France. [Perche, Astrid; Laurenceau, David; Briault, Sylvain; Perche, Olivier] Reg Hosp, Dept Genet, Orleans, France. [Ranchon-Cole, Isabelle; Bertrand, Pauline; Cercy, Christine] Univ Clermont 1, Lab Sensorial Biophys, Clermont Ferrand, France. RP Perche, O (reprint author), CNRS, UMR7355, F-45071 Orleans, France. EM operche@cnrs-orleans.fr FU CNRS; Regional Hospital of Orleans; University of Orleans; FEDER [35106]; FRAXA Research Foundation FX Research was supported by CNRS, Regional Hospital of Orleans, University of Orleans, FEDER 35106, and FRAXA Research 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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Other Topics GA AN9TR UT WOS:000340952200103 PM 25153086 ER PT J AU Rahbar, MH Samms-Vaughan, M Dickerson, AS Loveland, KA Ardjomand-Hessabi, M Bressler, J Shakespeare-Pellington, S Grove, ML Pearson, DA Boerwinkle, E AF Rahbar, Mohammad H. Samms-Vaughan, Maureen Dickerson, Aisha S. Loveland, Katherine A. Ardjomand-Hessabi, Manouchehr Bressler, Jan Shakespeare-Pellington, Sydonnie Grove, Megan L. Pearson, Deborah A. Boerwinkle, Eric TI Blood manganese concentrations in Jamaican children with and without autism spectrum disorders SO ENVIRONMENTAL HEALTH LA English DT Article DE Manganese; Autism Spectrum Disorder; Neurodevelopment; Seafood; Vegetables; Jamaica ID HEAVY-METAL CONTAMINATION; DRINKING-WATER; SEAFOOD CONSUMPTION; GENERAL-POPULATION; CHILDHOOD AUTISM; RISK-ASSESSMENT; EXPOSURE; AGE; BIOMARKERS; HAIR AB Background: Manganese is an essential element for human health and development. Previous studies have shown neurotoxic effects in children exposed to higher levels of manganese. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that impairs social interaction and communication. Several studies have hypothesized that ASD is caused through environmental exposures during crucial stages in brain development. We investigated the possible association between blood manganese concentrations (BMC) and ASD. We also identified factors associated with BMC in typically developing (TD) Jamaican children. Methods: We used data from 109 ASD cases with their 1:1 age- and sex-matched TD controls to compare mean BMC in Jamaican children (2-8 years of age) with and without ASD. We administered a pre-tested questionnaire to assess demographic and socioeconomic information, medical history, and potential exposure to manganese. Finally, we collected 2 mL of whole blood from each child for analysis of manganese levels. Using General Linear Models (GLM), we assessed the association between BMC and ASD status. Furthermore, we used two independent sample t-tests to identify factors associated with BMC in TD children. Results: In univariable GLM analysis, we found no significant association between BMC and ASD, (10.9 mu g/L for cases vs. 10.5 mu g/L for controls; P = 0.29). In a multivariable GLM adjusting for paternal age, parental education, place of child's birth (Kingston parish), consumption of root vegetables, cabbage, saltwater fish, and cakes/buns, there was still no significant association between BMC and ASD status, (11.5 mu g/L for cases vs. 11.9 mu g/L for controls; P = 0.48). Our findings also indicated TD children who ate fresh water fish had a higher BMC than children who did not (11.0 mu g/L vs. 9.9 mu g/L; P = 0.03) as younger TD children (i.e., 2 <= age <= 4), (12.0 mu g/L vs. 10.2 mu g/L; P = 0.01). Conclusions: While these results cannot be used to assess early exposure at potentially more susceptible time period, our findings suggest that there is no significant association between manganese exposures and ASD case status in Jamaica. Our findings also indicate that BMC in Jamaican children resemble those of children in the developed world and are much lower than those in the developing countries. C1 [Rahbar, Mohammad H.; Boerwinkle, Eric] Univ Texas Sch Publ Hlth Houston, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX 77030 USA. [Rahbar, Mohammad H.] Univ Texas Med Sch Houston, Dept Internal Med, Div Clin & Translat Sci, Houston, TX 77030 USA. [Rahbar, Mohammad H.; Dickerson, Aisha S.; Ardjomand-Hessabi, Manouchehr] Univ Texas Hlth Sci Ctr Houston, CCTS, Houston, TX 77030 USA. [Samms-Vaughan, Maureen; Shakespeare-Pellington, Sydonnie] Univ W Indies, Dept Child & Adolescent Hlth, Kingston, Jamaica. [Loveland, Katherine A.; Pearson, Deborah A.] Univ Texas Med Sch Houston, Dept Psychiat & Behav Sci, Houston, TX 77054 USA. [Bressler, Jan; Grove, Megan L.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA. RP Rahbar, MH (reprint author), Univ Texas Sch Publ Hlth Houston, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX 77030 USA. EM Mohammad.H.Rahbar@uth.tmc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health Fogarty International Center (NIH-FIC) [R21HD057808]; National Institute of Environmental Health Sciences (NIEHS) [R01ES022165]; NIH Centers for Translational Science Award (NIH CTSA) [UL1 RR024148]; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS) [UL1 TR000371]; Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS) FX This research is co-funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health Fogarty International Center (NIH-FIC) by a grant [R21HD057808] as well as National Institute of Environmental Health Sciences (NIEHS) by a grant [R01ES022165] awarded to University of Texas Health Science Center at Houston. We also acknowledge the support provided by the Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the NIH Centers for Translational Science Award (NIH CTSA) grant (UL1 RR024148), awarded to University of Texas Health Science Center at Houston in 2006 by the National Center for Research Resources (NCRR) and its renewal (UL1 TR000371) by the National Center for Advancing Translational Sciences (NCATS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the NIH-FIC or NIEHS or the NCRR or the NCATS. 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Health PD AUG 23 PY 2014 VL 13 AR 69 DI 10.1186/1476-069X-13-69 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AP4KA UT WOS:000342044400001 PM 25149876 ER PT J AU Gazzellone, MJ Zhou, X Lionel, AC Uddin, M Thiruvahindrapuram, B Liang, S Sun, CH Wang, J Zou, MY Tammimies, K Walker, S Selvanayagam, T Wei, J Wang, ZZ Wu, LJ Scherer, SW AF Gazzellone, Matthew J. Zhou, Xue Lionel, Anath C. Uddin, Mohammed Thiruvahindrapuram, Bhooma Liang, Shuang Sun, Caihong Wang, Jia Zou, Mingyang Tammimies, Kristiina Walker, Susan Selvanayagam, Thanuja Wei, John Wang, Zhuozhi Wu, Lijie Scherer, Stephen W. TI Copy number variation in Han Chinese individuals with autism spectrum disorder SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Copy number variations (CNVs); Microarray diagnostic testing; Han Chinese ID MILLER-DIEKER-SYNDROME; STRUCTURAL VARIATION; VARIANTS; GENES; IDENTIFICATION; MICRODELETIONS; PHENOTYPES; MUTATIONS; DISCOVERY; FAMILIES AB Background: Autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background. Methods: DNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity. Results: Of the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism. Conclusions: Our findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations. C1 [Gazzellone, Matthew J.; Zhou, Xue; Lionel, Anath C.; Uddin, Mohammed; Thiruvahindrapuram, Bhooma; Tammimies, Kristiina; Walker, Susan; Selvanayagam, Thanuja; Wei, John; Wang, Zhuozhi; Scherer, Stephen W.] Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Ctr Appl Genom, Toronto, ON M5G 0A4, Canada. [Gazzellone, Matthew J.; Zhou, Xue; Lionel, Anath C.; Uddin, Mohammed; Thiruvahindrapuram, Bhooma; Tammimies, Kristiina; Walker, Susan; Selvanayagam, Thanuja; Wei, John; Wang, Zhuozhi; Scherer, Stephen W.] Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Program Genet & Genome Biol, Toronto, ON M5G 0A4, Canada. [Gazzellone, Matthew J.; Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Gazzellone, Matthew J.; Lionel, Anath C.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Zhou, Xue; Liang, Shuang; Sun, Caihong; Wang, Jia; Zou, Mingyang; Wu, Lijie] Harbin Med Univ, Dept Childrens & Adolescent Hlth, Coll Publ Hlth, Harbin 150086, Heilongjiang, Peoples R China. [Zhou, Xue] Heilongjiang Prov Ctr Dis Control & Prevent, Harbin 150030, Heilongjiang, Peoples R China. [Tammimies, Kristiina] Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders, S-11330 Stockholm, Sweden. RP Scherer, SW (reprint author), Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Ctr Appl Genom, 686 Bay St,Room 139800, Toronto, ON M5G 0A4, Canada. EM stephen.scherer@sickkids.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU Centre for Applied Genomics; University of Toronto McLaughlin Centre; NeuroDevNet; Genome Canada; Ontario Genomics Institute [4445]; Canadian Institutes for Health Research (CIHR) [FRN 74527, FRNXGG818]; Canadian Institute for Advanced Research; Canada Foundation for Innovation; Government of Ontario [GL2-01-013]; Ontario Brain Institute; Autism Speaks; Ontario Graduate Scholarship; Frederick Banting and Charles Best Canada Graduate Scholarship (CIHR-Masters) FX The authors would like to thank Dr. Berivan Baskin and Dr. Peter Ray for scientific advice, Hong Yang Chen for technical assistance, and The Centre for Applied Genomics for support. This project was supported by grants from the University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada and the Ontario Genomics Institute (Project 4445), the Canadian Institutes for Health Research (CIHR) (FRN 74527 and FRNXGG818), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the Government of Ontario (GL2-01-013), the Ontario Brain Institute, and Autism Speaks. MJG was supported by the Ontario Graduate Scholarship and a Frederick Banting and Charles Best Canada Graduate Scholarship (CIHR-Masters). SWS holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children. 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Losh, Molly TI Eye-voice span during rapid automatized naming: evidence of reduced automaticity in individuals with autism spectrum disorder and their siblings SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Siblings; Language; Rapid automatized naming; Eye tracking; Endophenotype ID DYSLEXIA; CHILDREN; DEFICITS; DISABILITIES; FLUENCY; FAMILY; RISK; RAN AB Background: Individuals with autism spectrum disorder (ASD) and their parents demonstrate impaired performance in rapid automatized naming (RAN), a task that recruits a variety of linguistic and executive processes. Though the basic processes that contribute to RAN differences remain unclear, eye-voice relationships, as measured through eye tracking, can provide insight into cognitive and perceptual processes contributing to RAN performance. For example, in RAN, eye-voice span (EVS), the distance ahead the eyes are when articulation of a target item's label begins, is an indirect measure of automaticity of the processes underlying RAN. The primary objective of this study was to investigate automaticity in naming processes, as indexed by EVS during RAN. The secondary objective was to characterize RAN difficulties in individuals with ASD and their siblings. Methods: Participants (aged 15-33 years) included 21 individuals with ASD, 23 siblings of individuals with ASD, and 24 control subjects, group-matched on chronological age. Naming time, frequency of errors, and EVS were measured during a RAN task and compared across groups. Results: A stepwise pattern of RAN performance was observed, with individuals with ASD demonstrating the slowest naming across all RAN conditions, controls demonstrating the fastest naming, and siblings demonstrating intermediate performance. Individuals with ASD exhibited smaller EVSs than controls on all RAN conditions, and siblings exhibited smaller EVSs during number naming (the most highly automatized type of naming). EVSs were correlated with naming times in controls only, and only in the more automatized conditions. Conclusions: These results suggest that reduced automaticity in the component processes of RAN may underpin differences in individuals with ASD and their siblings. These findings also provide further support that RAN abilities are impacted by genetic liability to ASD. This study has important implications for understanding the underlying skills contributing to language-related deficits in ASD. C1 [Hogan-Brown, Abigail L.; Losh, Molly] Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL 60208 USA. [Hoedemaker, Renske S.; Gordon, Peter C.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. RP Losh, M (reprint author), Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL 60208 USA. EM m-losh@northwestern.edu RI Hogan-Brown, Abigail/I-8091-2012 OI Hogan-Brown, Abigail/0000-0002-2913-7356 FU National Institute of Deafness and Other Communication Disorders [R01DC010191, T32DC009399] FX This study was supported by grants R01DC010191 and T32DC009399 from the National Institute of Deafness and Other Communication Disorders. The study sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We also acknowledge the support of the Research Participant Registry Core of the Carolina Institute for Developmental Disabilities (P30HD03110) for their role in participant recruitment. The authors would like to thank Sejal Shah and Bret Kravis for their assistance with data processing. The authors are also grateful to the individuals and families who participated in this study. 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TI Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Autism spectrum disorders; Gastrointestinal abnormalities; Immune activation; Crohn's disease; Neuropeptides; Brain-derived neurotrophic factor; Mycobacterium paratuberculosis ID GENE-RELATED PEPTIDE; AVIUM SUBSPECIES PARATUBERCULOSIS; TRIGEMINAL GANGLION NEURONS; CROHNS-DISEASE; INTESTINAL PERMEABILITY; NEUROTROPHIC FACTOR; DEVELOPMENTAL DELAY; RECEPTOR ANTAGONIST; MENTAL-RETARDATION; MOOD DISORDERS AB Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. 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Theor. Biol. PD AUG 21 PY 2014 VL 355 BP 33 EP 39 DI 10.1016/j.jtbi.2014.03.036 PG 7 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA AJ7GL UT WOS:000337865100004 PM 24703983 ER PT J AU Righi, G Tierney, AL Tager-Flusberg, H Nelson, CA AF Righi, Giulia Tierney, Adrienne L. Tager-Flusberg, Helen Nelson, Charles A. TI Functional Connectivity in the First Year of Life in Infants at Risk for Autism Spectrum Disorder: An EEG Study SO PLOS ONE LA English DT Article ID BRAIN; LANGUAGE; ACTIVATION; COHERENCE; CHILDREN; SPEECH; UNDERCONNECTIVITY; REPRESENTATIONS; SYNCHRONIZATION; TODDLERS AB In the field of autism research, recent work has been devoted to studying both behavioral and neural markers that may aide in early identification of autism spectrum disorder (ASD). These studies have often tested infants who have a significant family history of autism spectrum disorder, given the increased prevalence observed among such infants. In the present study we tested infants at high-and low-risk for ASD (based on having an older sibling diagnosed with the disorder or not) at 6-and 12-months-of-age. We computed intrahemispheric linear coherence between anterior and posterior sites as a measure of neural functional connectivity derived from electroencephalography while the infants were listening to speech sounds. We found that by 12-months-of-age infants at risk for ASD showed reduced functional connectivity compared to low risk infants. Moreover, by 12-months-of-age infants later diagnosed with ASD showed reduced functional connectivity, compared to both infants at low risk for the disorder and infants at high risk who were not later diagnosed with ASD. Significant differences in functional connectivity were also found between low-risk infants and high-risk infants who did not go onto develop ASD. These results demonstrate that reduced functional connectivity appears to be related to genetic vulnerability for ASD. Moreover, they provide further evidence that ASD is broadly characterized by differences in neural integration that emerge during the first year of life. C1 [Righi, Giulia] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Tierney, Adrienne L.] Harvard Univ, Harvard Coll Writing Program, Cambridge, MA 02138 USA. [Tager-Flusberg, Helen] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Nelson, Charles A.] Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. [Nelson, Charles A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Nelson, Charles A.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Nelson, CA (reprint author), Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. EM charles_nelson@harvard.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD) [R21 DC 08637]; Autism Speaks; NIDCD [RO1 DC 10290]; Simon's Foundation FX Funding was provided by grant from National Institute on Deafness and Other Communication Disorders (NIDCD) R21 DC 08637 and Autism Speaks to HTF. Funding was provided by grant NIDCD RO1 DC 10290 and the Simon's Foundation to CAN and HTF. The agencies/funders had NO role in design data analysis or publication. 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Mueller, Sophia Snyder, Abraham Z. Mukherjee, Pratik Berman, Jeffrey I. Roberts, Timothy P. L. Nagarajan, Srikantan S. Spiro, John E. Chung, Wendy K. Sherr, Elliott H. Buckner, Randy L. CA Simons VIP Consortium TI Opposing Brain Differences in 16p11.2 Deletion and Duplication Carriers SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 16p11.2; ASD; CNV; copy number variation; morphometry; structural MRI ID AUTISM SPECTRUM DISORDER; SURFACE-BASED ANALYSIS; WHITE-MATTER; CORTICAL THICKNESS; HEAD CIRCUMFERENCE; NORMAL INDIVIDUALS; COSTELLO SYNDROME; HUMAN NEOCORTEX; CHILDREN; VOLUME AB Deletions and duplications of the recurrent similar to 600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. C1 [Qureshi, Abid Y.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Qureshi, Abid Y.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Qureshi, Abid Y.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller, Sophia; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany. [Snyder, Abraham Z.] Washington Univ, Sch Med St Louis, Dept Neurol, St Louis, MO 63110 USA. [Snyder, Abraham Z.] Washington Univ, Sch Med St Louis, Dept Radiol, St Louis, MO 63110 USA. [Mukherjee, Pratik; Nagarajan, Srikantan S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94158 USA. [Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Berman, Jeffrey I.; Roberts, Timothy P. L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Spiro, John E.] Simons Fdn, New York, NY 10010 USA. [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat & Med, New York, NY 10032 USA. RP Buckner, RL (reprint author), Harvard Univ, Northwest Bldg,Room 280-06,52 Oxford St, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu FU Simons Foundation (SFARI) [219193]; NIH/NINDS [5R25NS065743] FX This work was supported by a Grant from the Simons Foundation (SFARI no. 219193 to R.B.). We thank all of the families at the participating Simons Variation in Individuals Project (VIP) sites, as well as the Simons VIP Consortium. We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the Simons VIP population dataset described in this study by contacting the Simons Foundation Autism Research Initiative. A.Q. was supported by NIH/NINDS 5R25NS065743. We thank Avram Holmes for helpful advice on data analysis and Dr Nicholas Katsanis for insightful discussion. 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Neurosci. PD AUG 20 PY 2014 VL 34 IS 34 BP 11199 EP 11211 DI 10.1523/JNEUROSCI.1366-14.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AO4MI UT WOS:000341312600005 PM 25143601 ER PT J AU Diehl, MM Romanski, LM AF Diehl, Maria M. Romanski, Lizabeth M. TI Responses of Prefrontal Multisensory Neurons to Mismatching Faces and Vocalizations SO JOURNAL OF NEUROSCIENCE LA English DT Article DE communication; faces; multisensory integration; prefrontal cortex; primate; vocalizations ID AUTISM SPECTRUM DISORDERS; SUPERIOR TEMPORAL SULCUS; CROSS-MODAL INTEGRATION; AUDITORY-CORTEX; RHESUS-MONKEY; AUDIOVISUAL SPEECH; FRONTAL-CORTEX; FACIAL EXPRESSIONS; VISUAL INFORMATION; MACAQUE MONKEYS AB Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. C1 [Diehl, Maria M.] Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. [Romanski, Lizabeth M.] Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Rochester, NY 14642 USA. RP Romanski, LM (reprint author), Univ Rochester, Sch Med, Dept Neurobiol & Anat, Rochester, NY 14642 USA. EM Liz_romanski@urmc.rochester.edu FU National Institutes of Health [DC004845]; Center for Navigation and Communication Sciences [(P30) DC 005409]; Center for Visual Sciences [(P30) EY001319] FX This work was supported by the National Institutes of Health DC004845 (L.M.R.), Center for Navigation and Communication Sciences (P30) DC 005409, and Center for Visual Sciences (P30) EY001319. We thank Mark Diltz, Jaewon Hwang, John Housel, and Christopher Louie for technical assistance and Bethany Plakke for critical comments. 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TI Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cell adhesion; cortical pyramidal neurons; NrCAM; semaphorin; spine morphogenesis; visual cortex ID PRIMARY VISUAL-CORTEX; AUTISM SPECTRUM DISORDERS; NR-CAM; HOMOPHILIC INTERACTION; THALAMOCORTICAL AXONS; FUNCTIONAL PLASTICITY; ASSOCIATION ANALYSIS; MOUSE; EXPERIENCE; BRAIN AB Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression ofNrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Igl domain. A trans heterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interacted in vivo to regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits. C1 [Demyanenko, Galina P.; Mohan, Vishwa; Zhang, Xuying; Brennaman, Leann H.; Dharbal, Katherine E. S.; Maness, Patricia F.] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Manis, Paul B.] Univ N Carolina, Sch Med, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC 27599 USA. [Manis, Paul B.] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. [Tran, Tracy S.] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. RP Maness, PF (reprint author), Univ N Carolina, Sch Med, Dept Biochem & Biophys, Campus Box 7260, Chapel Hill, NC 27599 USA. EM srclab@med.unc.edu FU National Institutes of Health (NIH) [R21MH098138, R01MH101605]; Charles and Johanna Busch Biomedical Award; University of North Carolina (UNC) [NIH P30NS045892] FX This work was supported by National Institutes of Health (NIH) grants R21MH098138 and R01MH101605 (P.F.M.) and R01DC009809 (P.B.M.), Charles and Johanna Busch Biomedical Award (T.S.T.), and NIH P30NS045892 for University of North Carolina (UNC) Neuroscience Research Center core support. We gratefully acknowledge Dirk Montag (Leibniz Institute for Neurobiology, Magdeburg, Germany) for the NrCAM plasmid, Takeshi Sakurai and Carol Mason (Columbia University) for probes, Alex Kolodkin and David Ginty for Sema3F mice and probes, and Ben Philpot and Thorfinn Riday (UNC Chapel Hill) for advice on monocular deprivation. We are also grateful to Sam George, Eli Darnell, Jasbir Dalal, Sneha Venkatramen, and Erin Moore for experimental assistance. 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PD AUG 20 PY 2014 VL 34 IS 34 BP 11274 EP 11287 DI 10.1523/JNEUROSCI.1774-14.2014 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AO4MI UT WOS:000341312600012 PM 25143608 ER PT J AU Matthes, M Preusse, M Zhang, JZ Schechter, J Mayer, D Lentes, B Theis, F Prakash, N Wurst, W Trumbach, D AF Matthes, Michaela Preusse, Martin Zhang, Jingzhong Schechter, Julia Mayer, Daniela Lentes, Bernd Theis, Fabian Prakash, Nilima Wurst, Wolfgang Truembach, Dietrich TI Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID DOPAMINE NEURON DEVELOPMENT; SEGMENT POLARITY NETWORK; BETA-CATENIN; EXPRESSION PATTERNS; HINDBRAIN MALFORMATIONS; SIGNALING PATHWAY; ISTHMIC ORGANIZER; WNT/BETA-CATENIN; SPINAL-CORD; CYCLIN D1 AB The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial-lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/beta-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. C1 [Matthes, Michaela; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Prakash, Nilima; Wurst, Wolfgang; Truembach, Dietrich] German Res Ctr Environm Hlth, Inst Dev Genet, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Matthes, Michaela] Tech Univ Munchen Weihenstephan, Lehrstuhl Genet, D-85354 Freising Weihenstephan, Germany. [Preusse, Martin] German Res Ctr Environm Hlth, Inst Diabet & Regenerat Res, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Preusse, Martin; Theis, Fabian] German Res Ctr Environm Hlth, Inst Computat Biol, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Theis, Fabian] Tech Univ Munich, Zentrum Math, D-85747 Garching, Germany. [Wurst, Wolfgang; Truembach, Dietrich] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Wurst, Wolfgang] Deutsch Zentrum Neurodegenerat Erkrankungen eV DZ, Standort Munchen, D-80336 Munich, Germany. [Wurst, Wolfgang] Tech Univ Munchen Weihenstephan, Helmholtz Zentrum Munchen, Lehrstuhl Entwicklungsgenet, D-85764 Neuherberg, Germany. [Wurst, Wolfgang] Univ Munich, Adolf Butenandt Inst, Munich Cluster Syst Neurol SyNergy, D-80336 Munich, Germany. RP Trumbach, D (reprint author), German Res Ctr Environm Hlth, Inst Dev Genet, Helmholtz Zentrum Munchen, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM nilima.prakash@helmholtz-muenchen.de; wurst@helmholtz-muenchen.de; dietrich.truembach@helmholtz-muenchen.de FU EU [FP7-Health-F4-2010-242129]; 'Bundesministerium fur Bildung und Forschung' in the consortium 'From Disease Genes to Protein Pathways' [FKZ01GS0858]; Helmholtz Zentrum Munchen - Deutsches Forschungszentrum fur Gesundheit und Umwelt (HMGU); 'Deutsche Forschungsgemeinschaft' ('German Research Foundation') [EXC 1010] FX The 'Deutsche Forschungsgemeinschaft' ('German Research Foundation') within the framework of the Munich Cluster for Systems Neurology EXC 1010 SyNergy]; the EU grant 'Systems Biology of Stem Cells and Reprogramming' [FP7-Health-F4-2010-242129]; the 'Bundesministerium fur Bildung und Forschung' in the consortium 'From Disease Genes to Protein Pathways' [FKZ01GS0858]. Funding for open access charge: Helmholtz Zentrum Munchen - Deutsches Forschungszentrum fur Gesundheit und Umwelt (HMGU). 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Kandalaft, Michelle R. Didehbani, Nyaz Allen, Tandra T. McClelland, M. Michelle Tamminga, Carol A. Chapman, Sandra B. TI An investigation of reasoning by analogy in schizophrenia and autism spectrum disorder SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE analogy; reasoning; schizophrenia; autism spectrum disorder; distraction ID HIGH-FUNCTIONING AUTISM; WORKING-MEMORY; PREFRONTAL CORTEX; RELATIONAL INTEGRATION; ASPERGERS SYNDROME; SOCIAL COGNITION; MORAL JUDGMENT; SIMILARITY; MIND; CHILDREN AB Relational reasoning ability relies upon by both cognitive and social factors. We compared analogical reasoning performance in healthy controls (HC) to performance in individuals with Autism Spectrum Disorder (ASD), and individuals with schizophrenia (SZ). The experimental task required participants to find correspondences between drawings of scenes. Participants were asked to infer which item within one scene best matched a relational item within the second scene. We varied relational complexity, presence of distraction, and type of objects in the analogies (living or non-living items). We hypothesized that the cognitive differences present in SZ would reduce relational inferences relative to ASD and HC. We also hypothesized that both SZ and ASD would show lower performance on living item problems relative to HC due to lower social function scores. Overall accuracy was higher for HC relative to SZ, consistent with prior research. Across groups, higher relational complexity reduced analogical responding, as did the presence of non-living items. Separate group analyses revealed that the ASD group was less accurate at making relational inferences in problems that involved mainly non-living items and when distractors were present. The SZ group showed differences in problem type similar to the ASD group. Additionally, we found significant correlations between social cognitive ability and analogical reasoning, particularly for the SZ group. These results indicate that differences in cognitive and social abilities impact the ability to infer analogical correspondences along with numbers of relational elements and types of objects present in the problems. C1 [Krawczyk, Daniel C.; Kandalaft, Michelle R.; Didehbani, Nyaz; Allen, Tandra T.; McClelland, M. Michelle; Chapman, Sandra B.] Univ Texas Dallas, Sch Behav & Brain Sci, Ctr BrainHlth, Dallas, TX 75235 USA. [Krawczyk, Daniel C.; Kandalaft, Michelle R.; Tamminga, Carol A.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Krawczyk, DC (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, Ctr BrainHlth, 2200 Mockingbird Lane, Dallas, TX 75235 USA. EM daniel.krawczyk@utdallas.edu FU Lattner Foundation; Crystal Charity Ball; Wacker Foundation FX We thank Lindsey Richland for contributions to the development of the task. 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Hum. Neurosci. PD AUG 20 PY 2014 VL 8 AR 517 DI 10.3389/fnhum.2014.00517 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AN6YY UT WOS:000340746100001 PM 25191240 ER PT J AU Germain, ND Chen, PF Plocik, AM Glatt-Deeley, H Brown, J Fink, JJ Bolduc, KA Robinson, TM Levine, ES Reiter, LT Graveley, BR Lalande, M Chamberlain, SJ AF Germain, Noelle D. Chen, Pin-Fang Plocik, Alex M. Glatt-Deeley, Heather Brown, Judith Fink, James J. Bolduc, Kaitlyn A. Robinson, Tiwanna M. Levine, Eric S. Reiter, Lawrence T. Graveley, Brenton R. Lalande, Marc Chamberlain, Stormy J. TI Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1 SO MOLECULAR AUTISM LA English DT Article DE UBE3A; autism; induced pluripotent stem cells; 15q duplication; Angelman syndrome ID METHYLATION-SPECIFIC PCR; ANGELMAN SYNDROME; PRADER-WILLI; 15Q DUPLICATION; HUMAN GENOME; AUTISM; PROTEIN; MITHRAMYCIN; BRAIN; TRANSCRIPTION AB Background: Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehavioral phenotypes associated with chromosome 15q11-q13.1 duplication (Dup15q) syndrome. Methods: We have generated induced pluripotent stem cell (iPSC) lines from five different individuals containing CNVs of 15q11-q13.1. The iPSC lines were differentiated into mature, functional neurons. Gene expression across the 15q11-q13.1 locus was compared among the five iPSC lines and corresponding iPSC-derived neurons using quantitative reverse transcription PCR (qRT-PCR). Genome-wide gene expression was compared between neurons derived from three iPSC lines using mRNA-Seq. Results: Analysis of 15q11-q13.1 gene expression in neurons derived from Dup15q iPSCs reveals that gene copy number does not consistently predict expression levels in cells with interstitial duplications of 15q11-q13.1. mRNA-Seq experiments show that there is substantial overlap in the genes differentially expressed between 15q11-q13.1 deletion and duplication neurons, Finally, we demonstrate that UBE3A transcripts can be pharmacologically rescued to normal levels in iPSC-derived neurons with a 15q11-q13.1 duplication. Conclusions: Chromatin structure may influence gene expression across the 15q11-q13.1 region in neurons. Genome-wide analyses suggest that common neuronal pathways may be disrupted in both the Angelman and Dup15q syndromes. These data demonstrate that our disease-specific stem cell models provide a new tool to decipher the underlying cellular and genetic disease mechanisms of ASD and may also offer a pathway to novel therapeutic intervention in Dup15q syndrome. C1 [Germain, Noelle D.; Chen, Pin-Fang; Plocik, Alex M.; Glatt-Deeley, Heather; Graveley, Brenton R.; Lalande, Marc; Chamberlain, Stormy J.] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06032 USA. [Brown, Judith] Univ Connecticut, Dept Mol & Cell Biol, Chromosome Core, Storrs, CT 06269 USA. [Brown, Judith] Univ Connecticut, Dept Allied Hlth Sci, Storrs, CT 06269 USA. [Fink, James J.; Bolduc, Kaitlyn A.; Robinson, Tiwanna M.; Levine, Eric S.] Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. [Reiter, Lawrence T.] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN 38163 USA. [Graveley, Brenton R.] Univ Connecticut, Inst Syst Genom, Farmington, CT 06030 USA. RP Chamberlain, SJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, 400 Farmington Ave, Farmington, CT 06032 USA. EM chamberlain@uchc.edu FU NIH/NICHD [5R01HD068730-02]; Raymond and Beverly Sackler Foundation; Prutting fund; Autism Speaks FX The authors would like to thank the members of the Chamberlain, Lalande, Graveley, and Levine labs for helpful discussions. This work was funded by NIH/NICHD grant 5R01HD068730-02 (S.J.C), the Raymond and Beverly Sackler Foundation (S.J.C), the Prutting fund (M.L.), and Autism Speaks (E.S.L.). 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Chiu, Carina G. Diaz, Ruth L. Goghari, Vina M. TI Intact anger recognition in depression despite aberrant visual facial information usage SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Anxiety; Anger; Emotion recognition; Bubbles task ID MAJOR DEPRESSION; EMOTION PERCEPTION; AMYGDALA DAMAGE; EXPRESSION; DISORDER; SCHIZOPHRENIA; BUBBLES; MEMORY; DEFICITS; ANXIETY AB Background: Previous literature has indicated abnormalities in facial emotion recognition abilities, as well as deficits in basic visual processes in major depression. However, the literature is unclear on a number of important factors including whether or not these abnormalities represent deficient or enhanced emotion recognition abilities compared to control populations, and the degree to which basic visual deficits might impact this process. Methods: The present study investigated emotion recognition abilities for angry versus neutral facial expressions in a sample of undergraduate students with Beck Depression Inventory-II (BDI-II) scores indicative of moderate depression (i.e. >= 20), compared to matched low-BDI-II score (i.e. <= 2) controls via the Bubbles Facial Emotion Perception Task. Results: Results indicated unimpaired behavioural performance in discriminating angry from neutral expressions in the high depressive symptoms group relative to the minimal depressive symptoms group, despite evidence of an abnormal pattern of visual facial information usage. Limitations: The generalizability of the current findings is limited by the highly structured nature of the facial emotion recognition task used, as well as the use of an analog sample undergraduates scoring high in self-rated symptoms of depression rather than a clinical sample. Conclusions: Our findings suggest that basic visual processes are involved in emotion recognition abnormalities in depression, demonstrating consistency with the emotion recognition literature in other psychopathologies (e.g. schizophrenia, autism, social anxiety). Future research should seek to replicate these findings in clinical populations with major depression, and assess the association between aberrant face gaze behaviours and symptom severity and social functioning. (C) 2014 Elsevier B.V. All rights reserved. C1 [Clark, Cameron M.; Chiu, Carina G.; Diaz, Ruth L.; Goghari, Vina M.] Univ Calgary, Dept Psychol, Calgary, AB T2N 1N4, Canada. RP Goghari, VM (reprint author), Univ Calgary, Dept Psychol, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada. EM vmgoghar@ucalgary.ca FU Canadian Institutes of Health Research; University of Calgary; University Research Grant Committee; Canada Vanier Graduate Scholarship; Alberta Innovates Health Solutions studentship; Canadian Institutes of Health Research New Investigator Award FX We thank Frederic Gosselin for sharing his Bubbles task with our research group. Data collection was supported by a Canadian Institutes of Health Research operating grant, a University of Calgary Seed Grant, and a University Research Grant Committee Starter Grant. Cameron M. Clark was supported by a Canada Vanier Graduate Scholarship, as well as an Alberta Innovates Health Solutions studentship. Vina Goghari was supported by a Canadian Institutes of Health Research New Investigator Award. 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The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and 2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed. C1 [Sundquist, Jan; Sundquist, Kristina; Ji, Jianguang] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. [Sundquist, Jan; Sundquist, Kristina] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA USA. RP Sundquist, J (reprint author), Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. EM sundquist@med.lu.se; jianguang.ji@med.lu.se RI Ji, Jianguang/E-9579-2011 OI Ji, Jianguang/0000-0003-0324-9496 FU Vetenskapsradet [2012-2378]; National Institute of Drug Abuse [R01 DA030005] FX Vetenskapsradet 2012-2378 Jan SundquistNational Institute of Drug Abuse R01 DA030005 Jan SundquistThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. 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Iizuka, Kunio Yokoyama, Ryoichi Shinada, Takamitsu Yamamoto, Yuki Hanawa, Sugiko Araki, Tsuyoshi Hashizume, Hiroshi Sassa, Yuko Kawashima, Ryuta TI Creativity measured by divergent thinking is associated with two axes of autistic characteristics SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE creativity; divergent thinking; empathizing; systemizing; D score; autistic characteristics ID FALSE DISCOVERY RATE; VOXEL-BASED MORPHOMETRY; HIGH-FUNCTIONING AUTISM; WHITE-MATTER STRUCTURES; NORMAL SEX-DIFFERENCES; EMPATHY QUOTIENT EQ; SYSTEMATIZING QUOTIENT; ASPERGER-SYNDROME; EMOTIONAL INTELLIGENCE; EXECUTIVE FUNCTION AB Creativity generally involves the conception of original and valuable ideas, and it plays a key role in scientific achievement. Moreover, individuals with autistic spectrum conditions (ASCs) tend to achieve in scientific fields. Recently, it has been proposed that low empathizing and high systemizing characterize individuals with ASCs. Empathizing is the drive to identify the mental status of other individuals and respond to it with an appropriate emotion; systemizing is the drive to analyze a system. It has been proposed that this higher systemizing underlies the scientific achievement of individuals with ASCs, suggesting the possible positive association between creativity and systemizing. However, previous findings on the association between ASCs and creativity were conflicting. Conversely, previous studies have suggested an association between prosocial traits and creativity, indicating the possible association between empathizing and creativity. Here we investigated the association between creativity measured by divergent thinking (CDT) and empathizing, systemizing, and the discrepancy between systemizing and empathizing, which is called D score. CDT was measured using the S-A creativity test. The individual degree of empathizing (empathizing quotient, EQ) and that of systemizing (systemizing quotient, SQ), and D score was measured via a validated questionnaire (SQ and EQ questionnaires). The results showed that higher CDT was significantly and positively correlated with both the score of EQ and the score of SQ but not with D score. These results suggest that CDT is positively associated with one of the characteristics of ASCs (analytical aspects), while exhibiting a negative association with another (lower social aspects). Therefore, the discrepancy between systemizing and empathizing, which is strongly associated with autistic tendency, was not associated with CDT. C1 [Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta] Tohoku Univ, Inst Dev Aging & Canc, Div Dev Cognit Neurosci, Sendai, Miyagi 9808575, Japan. 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PD AUG 19 PY 2014 VL 5 AR 921 DI 10.3389/fpsyg.2014.00921 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AO5JJ UT WOS:000341380200001 PM 25191299 ER PT J AU Barua, S Kuizon, S Junaid, MA AF Barua, Subit Kuizon, Salomon Junaid, Mohammed A. TI Folic acid supplementation in pregnancy and implications in health and disease SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE Folic acid; DNA methylation; Epigenetic; Imprinting; Prenatal nutrition; Neural tube defects; Autism ID NEURAL-TUBE DEFECTS; PERICONCEPTIONAL VITAMIN SUPPLEMENTATION; CHILDHOOD RESPIRATORY HEALTH; AUTISM SPECTRUM DISORDERS; NATIONAL BIRTH COHORT; DOWN-SYNDROME PROJECT; DNA METHYLATION; S-ADENOSYLHOMOCYSTEINE; FOLATE-DEFICIENCY; FETAL-GROWTH AB Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies. C1 [Barua, Subit; Kuizon, Salomon; Junaid, Mohammed A.] New York State Inst Basic Res Dev Disabil, Dept Dev Biochem, Staten Isl, NY 10314 USA. RP Barua, S (reprint author), New York State Inst Basic Res Dev Disabil, Dept Dev Biochem, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. 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Biomed. Sci. PD AUG 19 PY 2014 VL 21 AR 77 DI 10.1186/s12929-014-0077-z PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AO1CW UT WOS:000341050500002 PM 25135350 ER PT J AU Parker, KJ Garner, JP Libove, RA Hyde, SA Hornbeak, KB Carson, DS Liao, CP Phillips, JM Hallmayer, JF Hardan, AY AF Parker, Karen J. Garner, Joseph P. Libove, Robin A. Hyde, Shellie A. Hornbeak, Kirsten B. Carson, Dean S. Liao, Chun-Ping Phillips, Jennifer M. Hallmayer, Joachim F. Hardan, Antonio Y. TI Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR GENE OXTR; PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; GENOME-WIDE; BEHAVIOR; ASSOCIATION; BRAIN; HUMANS; NEUROPEPTIDES; VASOPRESSIN AB The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD. C1 [Parker, Karen J.; Garner, Joseph P.; Libove, Robin A.; Hyde, Shellie A.; Hornbeak, Kirsten B.; Carson, Dean S.; Liao, Chun-Ping; Phillips, Jennifer M.; Hallmayer, Joachim F.; Hardan, Antonio Y.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Garner, Joseph P.] Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. RP Parker, KJ (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. EM kjparker@stanford.edu FU National Institutes of Health [RR000167]; Simons Foundation Autism Research Initiative; Mosbacher Family Fund for Autism Research; Escher Fund at the Silicon Valley Community Foundation; Stanford University's Child Health Research Institute FX We thank Wendy Kalkus, Serena Tanaka, Kaeli Yuen, and Katy Brewster for help with blood sample collection and processing as well as data entry. We also thank Dr. Carl Feinstein (Director of the Stanford Autism Center) for his unwavering support of this research program. Additionally, we thank Dr. Toni Zeigler and Dan Wittwer (University of Wisconsin National Primate Research Center Assay Services) for conducting the OXT assays which were made possible by National Institutes of Health Grant RR000167. This research program was supported by grants from the Simons Foundation Autism Research Initiative (to K.J.P.), the Mosbacher Family Fund for Autism Research (to K.J.P.), the Escher Fund at the Silicon Valley Community Foundation (to A.Y.H.), and Stanford University's Child Health Research Institute (to K.J.P. and A.Y.H.). 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Natl. Acad. Sci. U. S. A. PD AUG 19 PY 2014 VL 111 IS 33 BP 12258 EP 12263 DI 10.1073/pnas.1402236111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN2TS UT WOS:000340438800080 PM 25092315 ER PT J AU Dal Monte, O Noble, PL Turchi, J Cummins, A Averbeck, BB AF Dal Monte, Olga Noble, Pamela L. Turchi, Janita Cummins, Alex Averbeck, Bruno B. TI CSF and Blood Oxytocin Concentration Changes following Intranasal Delivery in Macaque SO PLOS ONE LA English DT Article ID CEREBROSPINAL-FLUID; PLASMA OXYTOCIN; RHESUS-MONKEYS; MACACA-MULATTA; DRUG-DELIVERY; BRAIN-BARRIER; SPINAL-CORD; VASOPRESSIN; RATS; HUMANS AB Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels. C1 [Dal Monte, Olga; Noble, Pamela L.; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B.] NIH, NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy. RP Averbeck, BB (reprint author), NIH, NIMH, Neuropsychol Lab, Bldg 10, Bethesda, MD 20892 USA. EM averbeckbb@mail.nih.gov FU Intramural Research Program of the NIMH/NIH/DHHS FX This research was supported by the Intramural Research Program of the NIMH/NIH/DHHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance. C1 [Kim, Ji-Woon; Seung, Hana; Ko, Mee Jung; Lee, Eun Joo; Oh, Hyun Ah; Choi, Chang Soon; Kim, Ki Chan; Gonzales, Edson Luck; You, Jueng Soo; Choi, Dong-Hee; Lee, Jongmin; Han, Seol-Heui; Yang, Sung Min; Shin, Chan Young] Konkuk Univ, Sch Med, Dept Neurosci, Seoul, South Korea. [Kwon, Kyung Ja] Konkuk Univ, Ctr Res Neurosci, Inst Biomed Sci & Technol, Seoul, South Korea. [Cheong, Jae Hoon] Sahmyook Univ, Coll Pharm, Dept Pharmacol, Seoul, South Korea. [Bahn, Geon Ho] Kyung Hee Univ, Sch Med, Dept Neuropsychiat, Seoul, South Korea. RP Shin, CY (reprint author), Konkuk Univ, Sch Med, Dept Neurosci, Seoul, South Korea. EM chanyshin@kku.ac.k; mompeian@khu.ac.kr FU Korean Health Technology R&D Project, Ministry of health & welfare, Republic of Korea [A120029] FX This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of health & welfare, Republic of Korea (No. A120029). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Bowler, Dermot M. Gardiner, John M. TI Episodic but not semantic order memory difficulties in autism spectrum disorder: Evidence from the Historical Figures Task SO MEMORY LA English DT Article DE Memory development; Episodic memory; Semantic memory; Order memory; Autism spectrum disorder ID ASPERGERS-SYNDROME; AUTOBIOGRAPHICAL MEMORY; FREE-RECALL; AUTONOETIC CONSCIOUSNESS; AMNESIC SYNDROME; FUTURE THINKING; EARLY-CHILDHOOD; ADULTS; CHILDREN; RECOGNITION AB Considerable evidence suggests that the episodic memory system operates abnormally in autism spectrum disorder (ASD) whereas the functions of the semantic memory system are relatively preserved. Here we show that the same dissociation also applies to the domain of order memory. We asked adult participants to order the names of famous historical figures either according to their chronological order in history (probing semantic memory) or according to a random sequence shown once on a screen (probing episodic memory). As predicted, adults with ASD performed less well than age- and IQ-matched comparison individuals only on the episodic task. This observation is of considerable importance in the context of developmental theory because semantic and episodic order memory abilities can be dissociated in typically developing infants before they reach the age at which the behavioural markers associated with ASD are first apparent. This raises the possibility that early emerging memory abnormalities play a role in shaping the developmental trajectory of the disorder. We discuss the broader implications of this possibility and highlight the urgent need for greater scrutiny of memory competences in ASD early in development. C1 [Gaigg, Sebastian B.; Bowler, Dermot M.; Gardiner, John M.] City Univ London, Dept Psychol, Northampton EC1V 0HB, England. RP Gaigg, SB (reprint author), City Univ London, Dept Psychol, Northampton Sq, Northampton EC1V 0HB, England. 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Cortactin-binding protein 2 (CTTNBP2), a neuron-specific F-actin regulator, has been shown to play a role in the regulation of dendritic spine formation and their maintenance. Here, we show that, in addition to F-actin, CTTNBP2 also associates with microtubules before mature dendritic spines form. This association of CTTNBP2 and microtubules induced the formation of microtubule bundles. Although the middle (Mid) region of CTTNBP2 was sufficient for its association with microtubules, for microtubule bundling, the N-terminal region containing the coiled-coil motifs (NCC), which mediates the dimerization or oligomerization of CTTNBP2, was also required. Our study indicates that CTTNBP2 proteins form a dimer or oligomer and brings multiple microtubule filaments together to form bundles. In cultured hippocampal neurons, knockdown of CTTNBP2 or expression of the Mid or NCC domain alone reduced the acetylation levels of microtubules and impaired dendritic arborization. This study suggests that CTTNBP2 influences both the F-actin and microtubule cytoskeletons and regulates dendritic spine formation and dendritic arborization. C1 [Shih, Pu-Yun; Hsueh, Yi-Ping] Natl Yang Ming Univ, Fac Life Sci, Inst Genome Sci, Taipei 112, Taiwan. [Shih, Pu-Yun; Lee, Sue-Ping; Chen, Yi-Kai; Hsueh, Yi-Ping] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. RP Hsueh, YP (reprint author), Natl Yang Ming Univ, Fac Life Sci, Inst Genome Sci, Taipei 112, Taiwan. EM yph@gate.sinica.edu.tw FU Academia Sinica [AS-100TP- B09, AS-103-TP-B05]; National Science Council of Taiwan [NSC 102-2321-B-001-054, NSC 102-2321-B-001-029] FX This work is supported by grants from Academia Sinica [grant numbers AS-100TP-B09, AS-103-TP-B05]; and the National Science Council of Taiwan [grant numbers NSC 102-2321-B-001-054, NSC 102-2321-B-001-029] to Y.P.H. 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Cell Sci. PD AUG 15 PY 2014 VL 127 IS 16 BP 3521 EP 3534 DI 10.1242/jcs.149476 PG 14 WC Cell Biology SC Cell Biology GA AO2TX UT WOS:000341180000011 PM 24928895 ER PT J AU Martin, BS Corbin, JG Huntsman, MM AF Martin, Brandon S. Corbin, Joshua G. Huntsman, Molly M. TI Deficient tonic GABAergic conductance and synaptic balance in the fragile X syndrome amygdala SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE tonic inhibition; GABA; amygdala; fragile X syndrome ID CONTAINING GABA(A) RECEPTORS; ADULT-RAT BRAIN; MOUSE MODEL; PHARMACOLOGICAL CHARACTERIZATION; CONTAINING INTERNEURONS; FEEDFORWARD INHIBITION; BASOLATERAL AMYGDALA; MENTAL-RETARDATION; PYRAMIDAL NEURONS; CGG REPEAT AB Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability. Comorbidities of FXS such as autism are increasingly linked to imbalances in excitation and inhibition (E/I) as well as dysfunction in GABAergic transmission in a number of brain regions including the amygdala. However, the link between E/I imbalance and GABAergic transmission deficits in the FXS amygdala is poorly understood. Here we reveal that normal tonic GABA(A) receptor-mediated neurotransmission in principal neurons (PNs) of the basolateral amygdala (BLA) is comprised of both delta- and alpha 5-subunit-containing GABA(A) receptors. Furthermore, tonic GABAergic capacity is reduced in these neurons in the Fmr1 knockout (KO) mouse model of FXS (1.5-fold total, 3-fold delta-subunit, and 2-fold alpha 5-subunit mediated) as indicated by application of gabazine (50 mu M), 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 1 mu M), and alpha 5ia (1.5 mu M) in whole cell patch-clamp recordings. Moreover, alpha 5-containing tonic GABA(A) receptors appear to preferentially modulate nonsomatic compartments of BLA PNs. Examination of evoked feedforward synaptic transmission in these cells surprisingly revealed no differences in overall synaptic conductance or E/I balance between wild-type (WT) and Fmr1 KO mice. Instead, we observed altered feedforward kinetics in Fmr1 KO PNs that supports a subtle yet significant decrease in E/I balance at the peak of excitatory conductance. Blockade of alpha 5-subunit-containing GABA(A) receptors replicated this condition in WT PNs. Therefore, our data suggest that tonic GABA(A) receptor-mediated neurotransmission can modulate synaptic E/I balance and timing established by feedforward inhibition and thus may represent a therapeutic target to enhance amygdala function in FXS. C1 [Martin, Brandon S.; Corbin, Joshua G.] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. [Martin, Brandon S.] Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20007 USA. [Huntsman, Molly M.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA. [Huntsman, Molly M.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. RP Huntsman, MM (reprint author), Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Anschutz Med Campus, Aurora, CO 80045 USA. EM molly.huntsman@ucdenver.edu FU National Institute of Neurological Disorders and Stroke [NS-053719]; Epilepsy Foundation; Autism Speaks; FRAXA Foundation FX This work was supported by grants from National Institute of Neurological Disorders and Stroke (M. M. Huntsman; Grant NS-053719), the Epilepsy Foundation (B. S. Martin), Autism Speaks (M. M. Huntsman and J. G. Corbin), and the FRAXA Foundation (M. M. Huntsman and J. G. Corbin). 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Neurophysiol. PD AUG 15 PY 2014 VL 112 IS 4 BP 890 EP 902 DI 10.1152/jn.00597.2013 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AN8FR UT WOS:000340839300013 PM 24848467 ER PT J AU Pragnya, B Kameshwari, JSL Veeresh, B AF Pragnya, B. Kameshwari, J. S. L. Veeresh, B. TI Ameliorating effect of piperine on behavioral abnormalities and oxidative markers in sodium valproate induced autism in BALB/C mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism; Valproate; Mice; Piperine; Behavior ID CULTURED HIPPOCAMPAL-NEURONS; PRENATAL EXPOSURE; ANIMAL-MODEL; INDUCED APOPTOSIS; ACID; RATS; SYSTEM; BRAIN; NOREPINEPHRINE; DISORDERS AB Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism. Piperine has been reported to have protective effect on brain. The present study aimed at evaluating effect of piperine on VPA induced neurobehavioral and biochemical alterations in BALB/c mice. Young BALB/c mice 13 days old were procured from five different litters and segregated into five groups (n = 6; 3 male, 3 female) i.e., Group I served as control group, received physiological saline on PND (Post natal day) 14 & Tween 80 p.o. from PND13-40. Group II served as normal treated group and received piperine (20 mg/kg p.o.) from PND 13-40 and saline s.c. on PND 14. Group III served as valproate treated group received VPA (400 mg/kg s.c.) on PND 14 and Tween 80 p.o. from PND 13-40. Group IV & V served as disease treated group received VPA (400 mg/kg s.c.) on PND 14 & piperine (5 & 20 mg/kg p.o.) from PND 13-40 respectively. BALB/c mice pups were subjected to behavioral testing to assess motor skill development, nociceptive response, locomotion, anxiety, and cognition on various postnatal days up to PND 40. At the end of behavioral evaluation, mice were sacrificed; brain was isolated for biochemical estimations (serotonin, glutathione, MDA and nitric oxide) and histopathological examination. Our study revealed that treatment with piperine significantly improved behavioral alterations, lowered oxidative stress markers, and restored histoarchitecture of cerebellum. This ameliorating effect of piperine is attributed to its anti-oxidant activity, cognition enhancing and neuroprotective activity. (C) 2014 Elsevier B.V. All rights reserved. C1 [Pragnya, B.; Kameshwari, J. S. L.; Veeresh, B.] Osmania Univ, Dept Pharmacol, G Pulla Reddy Coll Pharm, Hyderabad 500027, Andhra Pradesh, India. RP Pragnya, B (reprint author), Osmania Univ, Dept Pharmacol, G Pulla Reddy Coll Pharm, Hyderabad 500027, Andhra Pradesh, India. 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Adult NIgn4 null mutant (N1g174-1-) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile NIgn4-/- mice have not been reported yet. The present study has been designed to systematically investigate in male and female NIgn4-/- pups versus wildtype littermates NIgn4+1+) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between NIgn4-/- and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in NIgn4-/- mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in NIgn4-/- mice that appear more pronounced in immature females with their overall stronger USV as compared to males. (C) 2014 Elsevier B.V. All rights reserved. C1 Max Planck Inst Expt Med, Clin Neuroscience, Gottingen, Germany. [Hammerschmidt, Kurt] DFG Ctr Nanoscale Microscopy & Mol Physiol, Gottingen, Germany. [Krueger, Dilja; Brose, Nils] Max Planck Inst Expt Med, Dept Mol Neurobiol, Gottingen, Germany. RP Ehrenreich, H (reprint author), Max Planck Inst Expt Med, Clin Neuroscience, Gottingen, Germany. EM ehrenreich@em.mpg.de FU Max Planck Society; Max Planck Forderstiftung; DFG (CNMPB); EU-AIMS; Innovative Medicines Initiative Joint Undertaking [115300]; European Union; EFPIA companies; Autism Speaks FX This work was supported by the Max Planck Society, the Max Planck Forderstiftung, the DFG (CNMPB) as well as by EU-AIMS. The research of EU-AIMS receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013), from the EFPIA companies, and from Autism Speaks. 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However, application to the embryonic mouse central nervous system has been limited by the insufficient anatomical detail. Here we present a method that combines staining of live embryos with a contrast agent together with MR microscopy after fixation, to provide unprecedented anatomical detail at relevant embryonic stages. By using this method we have phenotyped the embryonic forebrain of Robo1/2(-/-) double mutant mice enabling us to identify most of the well-known anatomical defects in these mutants, as well as novel more subtle alterations. We thus demonstrate the potential of this methodology for a fast and reliable screening of subtle structural abnormalities in the developing mouse brain, as those associated to defects in disease-susceptibility genes of neurologic and psychiatric relevance. (C) 2014 Elsevier Inc. All rights reserved. C1 [Martinez-Martinez, M. A.; Borrell, V.] CSIC, Inst Neurociencias, Dev Neurobiol Unit, Sant Joan dAlacant 03550, Spain. [Martinez-Martinez, M. A.; Pacheco-Torres, J.; Borrell, V.] Univ Miguel Hernandez, Sant Joan dAlacant 03550, Spain. [Pacheco-Torres, J.; Canals, S.] CSIC, Inst Neurociencias, Cellular & Syst Neurobiol Unit, Sant Joan dAlacant 03550, Spain. RP Borrell, V (reprint author), CSIC, Inst Neurociencias, Dev Neurobiol Unit, Sant Joan dAlacant 03550, Spain. EM vborrell@umh.es; scanals@umh.es RI Canals, Santiago/N-5838-2014 OI Canals, Santiago/0000-0003-2175-8139 FU Spanish Ministry of Science and Innovation MICINN, Era-Net NEURON TRANSALC [CSD2007-00023, BFU2009-09938, BFU2012-39958, PIM2010ERN-00679]; [SAF2009-07367]; [BFU2012-33473] FX We are grateful to M. Tessier-Lavigne for the Robo1/2 mouse colony and thankful to C. Vegar, M.A. Fernandez and B. Fernandez for excellent technical assistance. Supported by grants from the Spanish Ministry of Science and Innovation MICINN to S.C. (CSD2007-00023, BFU2009-09938, BFU2012-39958 and PIM2010ERN-00679 as part of the Era-Net NEURON TRANSALC project) and to V.B. 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Brown, Warren S. Spezio, Michael L. Leonard, Matthew K. Adolphs, Ralph Paul, Lynn K. TI Facial emotion recognition in agenesis of the corpus callosum SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Corpus callosum agenesis; Corpus callosum; Facial emotion ID HIGH-FUNCTIONING AUTISM; SENTENCE COMPREHENSION; PSYCHOPHYSICS TOOLBOX; SPECTRUM DISORDERS; CHILDREN; DEFICITS; LANGUAGE; CONNECTIVITY; PERCEPTION; ADULTS AB Background: Impaired social functioning is a common symptom of individuals with developmental disruptions in callosal connectivity. Among these developmental conditions, agenesis of the corpus callosum provides the most extreme and clearly identifiable example of callosal disconnection. To date, deficits in nonliteral language comprehension, humor, theory of mind, and social reasoning have been documented in agenesis of the corpus callosum. Here, we examined a basic social ability as yet not investigated in this population: recognition of facial emotion and its association with social gaze. Methods: Nine individuals with callosal agenesis and nine matched controls completed four tasks involving emotional faces: emotion recognition from upright and inverted faces, gender recognition, and passive viewing. Eye-tracking data were collected concurrently on all four tasks and analyzed according to designated facial regions of interest. Results: Individuals with callosal agenesis exhibited impairments in recognizing emotions from upright faces, in particular lower accuracy for fear and anger, and these impairments were directly associated with diminished attention to the eye region. The callosal agenesis group exhibited greater consistency in emotion recognition across conditions (upright vs. inverted), with poorest performance for fear identification in both conditions. The callosal agenesis group also had atypical facial scanning (lower fractional dwell time in the eye region) during gender naming and passive viewing of faces, but they did not differ from controls on gender naming performance. The pattern of results did not differ when taking into account full-scale intelligence quotient or presence of autism spectrum symptoms. Conclusions: Agenesis of the corpus callosum results in a pattern of atypical facial scanning characterized by diminished attention to the eyes. This pattern suggests that reduced callosal connectivity may contribute to the development and maintenance of emotion processing deficits involving reduced attention to others' eyes. C1 [Bridgman, Matthew W.] DuBois Reg Med Ctr, Du Bois, PA 15801 USA. [Brown, Warren S.] Fuller Theol Seminary, Travis Res Inst, Pasadena, CA 91101 USA. [Spezio, Michael L.; Adolphs, Ralph; Paul, Lynn K.] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. [Spezio, Michael L.] Scripps Coll, Claremont, CA 91711 USA. [Leonard, Matthew K.] Univ Calif San Francisco, San Francisco, CA 94117 USA. [Adolphs, Ralph] CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Paul, LK (reprint author), CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. EM lkpaul@hss.caltech.edu FU Pfeiffer Foundation; Simons Foundation; Travis Research Institute FX This research was supported in part by the Pfeiffer Foundation, the Simons Foundation, and the Travis Research Institute. The authors would like to thank Candace Markley for her contributions in data management. 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Neurodev. Disord. PD AUG 14 PY 2014 VL 6 AR 32 DI 10.1186/1866-1955-6-32 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW1DO UT WOS:000346031000001 PM 25705318 ER PT J AU Oberman, LM Pascual-Leone, A Rotenberg, A AF Oberman, Lindsay M. Pascual-Leone, Alvaro Rotenberg, Alexander TI Modulation of corticospinal excitabilty by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism spectrum disorders; transcranial magnetic stimulation; development; plasticity; GABA; theta burst stimulation ID THETA-BURST STIMULATION; HUMAN MOTOR CORTEX; CORTICAL INHIBITION; FUTURE-DIRECTIONS; ASPERGER-SYNDROME; POSTURAL CONTROL; IN-VIVO; GABA; BRAIN; MODEL AB The developmental pathophysiology of autism spectrum disorders (ASD) is currently not fully understood. However, multiple lines of evidence suggest that the behavioral phenotype may result from dysfunctional inhibitory control over excitatory synaptic plasticity. Consistent with this claim, previous studies indicate that adults with Asperger's Syndrome show an abnormally extended modulation of corticospinal excitability following a train of repetitive transcranial magnetic stimulation (rTMS). As ASD is a developmental disorder, the current study aimed to explore the effect of development on the duration of modulation of corticospinal excitability in children and adolescents with ASD. Additionally, as the application of rTMS to the understanding and treatment of pediatric neurological and psychiatric disorders is an emerging field, this study further sought to provide evidence for the safety and tolerability of rTMS in children and adolescents with ASD. Corticospinal excitability was measured by applying single pulses of TMS to the primary motor cortex both before and following a 40 s train of continuous theta burst stimulation. 19 high-functioning males ages 9-18 with ASD participated in this study. Results from this study reveal a positive linear relationship between age and duration of modulation of rTMS aftereffects. Specifically we found that the older participants had a longer lasting response. Furthermore, though the specific protocol employed typically suppresses corticospinal excitability in adults, more than one third of our sample had a paradoxical facilitatory response to the stimulation. Results support the safety and tolerability of rTMS in pediatric clinical populations. Data also support published theories implicating aberrant plasticity and GABAergic dysfunction in this population. C1 [Oberman, Lindsay M.; Pascual-Leone, Alvaro; Rotenberg, Alexander] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Sch Med,Dept Neurol, Boston, MA 02215 USA. [Oberman, Lindsay M.; Rotenberg, Alexander] Harvard Univ, Sch Med, Dept Neurol, Neuromodulat Program,Boston Childrens Hosp, Boston, MA 02115 USA. [Oberman, Lindsay M.; Rotenberg, Alexander] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Epilepsy & Clin Neurophysiol,Dept Neurol, Boston, MA 02115 USA. [Oberman, Lindsay M.] EP Bradley Hosp, Neuroplast & Autism Spectrum Disorder Program, East Providence, RI 02915 USA. [Oberman, Lindsay M.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, East Providence, RI USA. RP Oberman, LM (reprint author), EP Bradley Hosp, Neuroplast & Autism Spectrum Disorder Program, 1011 Vet Mem Pkwy, East Providence, RI 02915 USA. EM loberman@lifespan.org; alexander.rotenberg@childrens.harvard.edu FU Boston Children's Hospital Translational Research Program; National Institutes of Health and National Institute of Mental Health [1R01MH100186]; Harvard Catalyst; Harvard Clinical and Translational Science Center; NCRR; WAITS NIH [8KL2TR000168-05]; Harvard Clinical and Translational Science Center [8UL1TR000170-05]; Epilepsy Research Foundation; Simons Foundation; Nancy Lurie Marks Family Foundation; National Institutes of Health [R01 HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758]; Michael J. Fox Foundation; Sidney R. Baer Foundation; Center for Integration of Medicine and Innovative Technology (CIMIT); Department of Defense [PR121509]; Autism Speaks [48702]; Eisai Inc.; epilepsy therapy project FX Work on the project is supported grants the Boston Children's Hospital Translational Research Program (Alexander Rotenberg), National Institutes of Health and National Institute of Mental Health (1R01MH100186), and Harvard Catalyst, The Harvard Clinical and Translational Science Center (NCRR and the WAITS NIH 8KL2TR000168-05). Lindsay M. Oberman is further supported by grants from the Harvard Clinical and Translational Science Center (8UL1TR000170-05), the Epilepsy Research Foundation, the Simons Foundation and the Nancy Lurie Marks Family Foundation, Alvaro Pascual-Leone is further supported by grants from the National Institutes of Health (R01 HD069776, R01NS073601, R21 MH099196, R21 NS082870, R21 NS085491, R21 HD07616, UL1 RR025758), Michael J. Fox Foundation and Sidney R. Baer Foundation. Alexander Roten berg is further supported by the Center for Integration of Medicine and Innovative Technology (CIMIT), Department of Defense PR121509, Autism Speaks Grant 48702, and grants from Eisai Inc. and the Epilepsy Research Foundation and epilepsy therapy project. 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Hum. Neurosci. PD AUG 13 PY 2014 VL 8 AR 627 DI 10.3389/fnhum.2014.00627 PG 8 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AN6YF UT WOS:000340744000001 PM 25165441 ER PT J AU Adamsen, D Ramaekers, V Ho, HTB Britschgi, C Rufenacht, V Meili, D Bobrowski, E Philippe, P Nava, C Van Maldergem, L Bruggmann, R Walitza, S Wang, J Grunblatt, E Thony, B AF Adamsen, Dea Ramaekers, Vincent Ho, Horace T. B. Britschgi, Corinne Ruefenacht, Veronique Meili, David Bobrowski, Elise Philippe, Paule Nava, Caroline Van Maldergem, Lionel Bruggmann, Remy Walitza, Susanne Wang, Joanne Gruenblatt, Edna Thoeny, Beat TI Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Serotonin end-metabolite 5-hydroxyindolacetic acid; SERT; PMAT ID 1ST-DEGREE RELATIVES; BRAIN-DEVELOPMENT; NEURONS; DISRUPTION; BEHAVIORS; CHILDREN AB Background: Patients with autism spectrum disorder (ASD) may have low brain serotonin concentrations as reflected by the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in cerebrospinal fluid (CSF). Methods: We sequenced the candidate genes SLC6A4 (SERT), SLC29A4 (PMAT), and GCHFR (GFRP), followed by whole exome analysis. Results: The known heterozygous p.Gly56Ala mutation in the SLC6A4 gene was equally found in the ASD and control populations. Using a genetic candidate gene approach, we identified, in 8 patients of a cohort of 248 with ASD, a high prevalence (3.2%) of three novel heterozygous non-synonymous mutations within the SLC29A4 plasma membrane monoamine transporter (PMAT) gene, c.86A > G (p.Asp29Gly) in two patients, c.412G > A (p.Ala138Thr) in five patients, and c.978 T > G (p.Asp326Glu) in one patient. Genome analysis of unaffected parents confirmed that these PMAT mutations were not de novo but inherited mutations. Upon analyzing over 15,000 normal control chromosomes, only SLC29A4 c.86A > G was found in 23 alleles (0.14%), while neither c.412G > A (<0.007%) nor c.978 T > G (<0.007%) were observed in all chromosomes analyzed, emphasizing the rareness of the three alterations. Expression of mutations PMAT-p.Ala138Thr and p.Asp326Glu in cellulae revealed significant reduced transport uptake activity towards a variety of substrates including serotonin, dopamine, and 1-methyl-4-phenylpyridinium (MPP+), while mutation p.Asp29Gly had reduced transport activity only towards MPP+. At least two ASD subjects with either the PMAT-Ala138Thr or the PMAT-Asp326Glu mutation with altered serotonin transport activity had, besides low 5HIAA in CSF, elevated serotonin levels in blood and platelets. Moreover, whole exome sequencing revealed additional alterations in these two ASD patients in mainly serotonin-homeostasis genes compared to their non-affected family members. Conclusions: Our findings link mutations in SLC29A4 to the ASD population although not invariably to low brain serotonin. PMAT dysfunction is speculated to raise serotonin prenatally, exerting a negative feedback inhibition through serotonin receptors on development of serotonin networks and local serotonin synthesis. Exome sequencing of serotonin homeostasis genes in two families illustrated more insight in aberrant serotonin signaling in ASD. C1 [Adamsen, Dea; Ruefenacht, Veronique; Thoeny, Beat] Univ Zurich, Dept Pediat, Div Metab, CH-8032 Zurich, Switzerland. [Adamsen, Dea; Walitza, Susanne; Gruenblatt, Edna; Thoeny, Beat] Univ Zurich, Neurosci Ctr Zurich, CH-8000 Zurich, Switzerland. [Adamsen, Dea; Walitza, Susanne; Gruenblatt, Edna; Thoeny, Beat] ETH Zurich ZNZ, CH-8000 Zurich, Switzerland. [Adamsen, Dea; Thoeny, Beat] Childrens Res Ctr CRC, CH-8032 Zurich, Switzerland. [Ramaekers, Vincent; Philippe, Paule] Univ Hosp Liege, Ctr Autism Liege, B-4000 Liege, Belgium. [Ramaekers, Vincent; Philippe, Paule] Univ Hosp Liege, Div Pediat Neurol, B-4000 Liege, Belgium. [Ho, Horace T. B.; Wang, Joanne] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Britschgi, Corinne; Meili, David; Thoeny, Beat] Univ Zurich, Dept Pediat, Div Clin Chem & Biochem, CH-8032 Zurich, Switzerland. [Bobrowski, Elise; Walitza, Susanne; Gruenblatt, Edna] Univ Zurich, Univ Clin Child & Adolescent Psychiat, CH-8050 Zurich, Switzerland. [Nava, Caroline] Hop La Pitie Salpetriere, Dept Genet Cytogenet & Human Genet, F-75651 Paris, France. [Van Maldergem, Lionel] Univ Franche Comte, Ctr Human Genet, F-25030 Besancon, France. [Bruggmann, Remy] Univ Zurich, ETH Zurich, Funct Genom Ctr Zurich, CH-8057 Zurich, Switzerland. [Walitza, Susanne; Thoeny, Beat] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, CH-8000 Zurich, Switzerland. RP Thony, B (reprint author), Univ Zurich, Dept Pediat, Div Metab, CH-8032 Zurich, Switzerland. EM beat.thony@kispi.uzh.ch FU "Fonds National de Recherches Scientifiques", Belgium (FNRS) [3.4.540.09.F]; Centre for Neuroscience Zurich; Swiss National Science Foundation; Novartis "Stiftung fur medizinisch-biologische Forschung"; National Institutes of Health [GM066233]; University Children's Hospital Zurich FX We thank Anahita Rassi for technical assistance, Nenad Blau for valuable discussions, and the University Children's Hospital Zurich for their general support. This project was supported by grants from the "Fonds National de Recherches Scientifiques", Belgium (FNRS No: 3.4.540.09.F to VR), the Centre for Neuroscience Zurich (to BT), the Swiss National Science Foundation (to BT), Novartis "Stiftung fur medizinisch-biologische Forschung" (to BT), and the National Institutes of Health (GM066233 to JW). 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Autism PD AUG 13 PY 2014 VL 5 AR 43 DI 10.1186/2040-2392-5-43 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA AO2NA UT WOS:000341159100001 PM 25802735 ER PT J AU Gimelli, S Capra, V Di Rocco, M Leoni, M Mirabelli-Badenier, M Schiaffino, MC Fiorio, P Cuoco, C Gimelli, G Tassano, E AF Gimelli, Stefania Capra, Valeria Di Rocco, Maja Leoni, Massimiliano Mirabelli-Badenier, Marisol Schiaffino, Maria Cristina Fiorio, Patrizia Cuoco, Cristina Gimelli, Giorgio Tassano, Elisa TI Interstitial 7q31.1 copy number variations disrupting IMMP2L gene are associated with a wide spectrum of neurodevelopmental disorders SO MOLECULAR CYTOGENETICS LA English DT Article DE IMMP2L; Neurodevelopmental disorders; Copy number variation; Array-CGH ID TOURETTE-SYNDROME; MITOCHONDRIAL DYSFUNCTION; AUTISM; ACTIVATION; BREAKPOINT; MUTATION AB Background: Since the introduction of the array-CGH technique in the diagnostic workup of mental retardation, new recurrent copy number variations and novel microdeletion/microduplication syndromes were identified. These findings suggest that some genomic disorders have high penetrance but a wide range of phenotypic severity. Results: We present the clinical and molecular description of four unrelated patients affected by neurodevelopmental disorders and overlapping 7q31.1 microdeletion/microduplication, identified by array-CGH and involving only part of the IMMP2L gene. Conclusion: IMMP2L encodes an inner mitochondrial membrane protease-like protein, which is required for processing of cytochromes inside mitochondria. Numerous studies reported that this gene is implicated in behavioural disorders such as autistic spectrum disorders, attention-deficit hyperactivity disorders, and Gilles de la Tourette syndrome. We discuss the functions of the gene suggesting that IMMP2L may act as risk factor for neurological disease. C1 [Gimelli, Stefania] Univ Hosp Geneva, Serv Genet Med, Geneva, Switzerland. [Capra, Valeria] Ist Giannina Gaslini, UO Neurochirurg, I-16147 Genoa, Italy. [Di Rocco, Maja] Ist Giannina Gaslini, USD Malattie Rare, I-16147 Genoa, Italy. [Leoni, Massimiliano] Ist Giannina Gaslini, I-16147 Genoa, Italy. [Mirabelli-Badenier, Marisol] Univ Genoa, DINOMGI Dipartimento, Genoa, Italy. [Schiaffino, Maria Cristina] Ist Giannina Gaslini, Dipartimento Pediat, Genoa, Italy. [Fiorio, Patrizia; Cuoco, Cristina; Gimelli, Giorgio; Tassano, Elisa] Ist Giannina Gaslini, Lab Citogenet, I-16147 Genoa, Italy. RP Tassano, E (reprint author), Ist Giannina Gaslini, Lab Citogenet, I-16147 Genoa, Italy. EM eli.tassano@gmail.com FU Cinque per mille dell'IRPEF-Finanziamento della ricerca sanitaria; Finanziamento Ricerca Corrente, Ministero Salute (contributo per la ricerca intramurale) FX We thank the patient's parents for their kind participation and support. We are grateful to Marco Bertorello and Corrado Torello for their technical assistance. This work was supported by "Cinque per mille dell'IRPEF-Finanziamento della ricerca sanitaria" and "Finanziamento Ricerca Corrente, Ministero Salute" (contributo per la ricerca intramurale). 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Cytogenet. PD AUG 13 PY 2014 VL 7 AR 54 DI 10.1186/s13039-014-0054-y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AN7TM UT WOS:000340803500001 PM 25478008 ER PT J AU Meilleur, AAS Berthiaume, C Bertone, A Mottron, L AF Meilleur, Andree-Anne S. Berthiaume, Claude Bertone, Armando Mottron, Laurent TI Autism-Specific Covariation in Perceptual Performances: "g'' or "p'' Factor? SO PLOS ONE LA English DT Article ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; GENERAL INTELLIGENCE; PITCH DISCRIMINATION; GABA CONCENTRATION; ASPERGER SYNDROME; AUDITORY-CORTEX; INSPECTION TIME; VISUAL-CORTEX; SENSITIVITY AB Background: Autistic perception is characterized by atypical and sometimes exceptional performance in several low- (e.g., discrimination) and mid-level (e. g., pattern matching) tasks in both visual and auditory domains. A factor that specifically affects perceptive abilities in autistic individuals should manifest as an autism-specific association between perceptual tasks. The first purpose of this study was to explore how perceptual performances are associated within or across processing levels and/or modalities. The second purpose was to determine if general intelligence, the major factor that accounts for covariation in task performances in non-autistic individuals, equally controls perceptual abilities in autistic individuals. Methods: We asked 46 autistic individuals and 46 typically developing controls to perform four tasks measuring low-or mid-level visual or auditory processing. Intelligence was measured with the Wechsler's Intelligence Scale (FSIQ) and Raven Progressive Matrices (RPM). We conducted linear regression models to compare task performances between groups and patterns of covariation between tasks. The addition of either Wechsler's FSIQ or RPM in the regression models controlled for the effects of intelligence. Results: In typically developing individuals, most perceptual tasks were associated with intelligence measured either by RPM or Wechsler FSIQ. The residual covariation between unimodal tasks, i.e. covariation not explained by intelligence, could be explained by a modality-specific factor. In the autistic group, residual covariation revealed the presence of a plurimodal factor specific to autism. Conclusions: Autistic individuals show exceptional performance in some perceptual tasks. Here, we demonstrate the existence of specific, plurimodal covariation that does not dependent on general intelligence (or "g'' factor). Instead, this residual covariation is accounted for by a common perceptual process (or "p'' factor), which may drive perceptual abilities differently in autistic and non-autistic individuals. C1 [Meilleur, Andree-Anne S.; Berthiaume, Claude; Bertone, Armando; Mottron, Laurent] Univ Montreal, Hop Riviere Des Prairies, Ctr Excellence Pervas Dev Disorders CETEDUM, Montreal, PQ, Canada. [Bertone, Armando] McGill Univ, Sch Appl Child Psychol, Dept Educ & Counselling Psychol, Montreal, PQ, Canada. RP Mottron, L (reprint author), Univ Montreal, Hop Riviere Des Prairies, Ctr Excellence Pervas Dev Disorders CETEDUM, Montreal, PQ, Canada. EM laurent.mottron@gmail.com FU CIHR [171795]; Autism Speaks Foundation [2706]; Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS-D) FX This work was supported by grants from CIHR (171795); Autism Speaks Foundation (2706) and the Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS-D) (AASM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Park, Su-Bin D'Angiulli, Amedeo TI Air pollution and detrimental effects on children's brain. The need for a multidisciplinary approach to the issue complexity and challenges SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE urban children; air pollution; cognition; brain volumetric changes; white matter hyperintensities; cytokines; Alzheimer; Parkinson ID PARTICULATE MATTER; SYSTEMIC INFLAMMATION; SUPERIOR OLIVE; MEXICO-CITY; EXPOSURE; AUTISM; HEALTH; NANOPARTICLES; COGNITION; RISK AB Millions of children in polluted cities are showing brain detrimental effects. Urban children exhibit brain structural and volumetric abnormalities, systemic inflammation, olfactory, auditory, vestibular and cognitive deficits v low-pollution controls. Neuroinflammation and blood-brain-barrier (BBB) breakdown target the olfactory bulb, prefrontal cortex and brainstem, but are diffusely present throughout the brain. Urban adolescent Apolipoprotein E4 carriers significantly accelerate Alzheimer pathology. Neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation and neurodegeneration forces to employ a weight of evidence approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiological research. Pediatric air pollution research requires extensive multidisciplinary collaborations to accomplish a critical goal: to protect exposed children through multidimensional interventions having both broad impact and reach. Protecting children and teens from neural effects of air pollution should be of pressing importance for public health. C1 [Calderon-Garciduenas, Lilian] Univ Montana, Ctr Struct & Funct Neurosci, Dept Biomed Sci, Missoula, MT 59812 USA. [Torres-Jardon, Ricardo] Univ Nacl Autonoma Mexico, Ctr Ciencias Atmosfera, Mexico City 04510, DF, Mexico. [Kulesza, Randy J.] Lake Erie Coll Osteopath Med, Auditory Res Ctr, Erie, PA USA. [Park, Su-Bin; D'Angiulli, Amedeo] Carleton Univ, NICER Lab, Neurosci Imagery Cognit & Emot Res Lab, Ottawa, ON K1S 5B6, Canada. RP D'Angiulli, A (reprint author), Carleton Univ, NICER Lab, Neurosci Imagery Cognit & Emot Res Lab, IIS, 1125 Colonel Dr,Dunton Tower,Room 2202A, Ottawa, ON K1S 5B6, Canada. 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Hum. Neurosci. PD AUG 12 PY 2014 VL 8 AR 613 DI 10.3389/fnhum.2014.00613 PG 7 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AN6NB UT WOS:000340710100001 PM 25161617 ER PT J AU Abney, DH Warlaumont, AS Haussman, A Ross, JM Wallot, S AF Abney, Drew H. Warlaumont, Anne S. Haussman, Anna Ross, Jessica M. Wallot, Sebastian TI Using nonlinear methods to quantify changes in infant limb movements and vocalizations SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE motor development; infant vocalization; nonlinear methods; recurrence; Allan factor ID MOTOR DEVELOPMENT; LANGUAGE-DEVELOPMENT; SPONTANEOUS KICKING; UPRIGHT LOCOMOTION; SPEECH DEVELOPMENT; COORDINATION; AUTISM; COGNITION; CHILDREN; DYNAMICS AB The pairing of dynamical systems theory and complexity science brings novel concepts and methods to the study of infant motor development. Accordingly, this longitudinal case study presents a new approach to characterizing the dynamics of infant limb and vocalization behaviors. A single infant's vocalizations and limb movements were recorded from 51-days to 305-days of age. On each recording day, accelerometers were placed on all four of the infant's limbs and an audio recorder was worn on the child's chest. Using nonlinear time series analysis methods, such as recurrence quantification analysis and Allan factor, we quantified changes in the stability and multiscale properties of the infant's behaviors across age as well as how these dynamics relate across modalities and effectors. We observed that particular changes in these dynamics preceded or coincided with the onset of various developmental milestones. For example, the largest changes in vocalization dynamics preceded the onset of canonical babbling. 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PD AUG 12 PY 2014 VL 5 AR 771 DI 10.3389/fpsyg.2014.00771 PG 15 WC Psychology, Multidisciplinary SC Psychology GA AO5EP UT WOS:000341366500001 PM 25161629 ER PT J AU Kasirer, A Mashal, N AF Kasirer, Anat Mashal, Nira TI Verbal creativity in autism: comprehension and generation of metaphoric language in high-functioning autism spectrum disorder and typical development SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; novel metaphors; executive functioning; metaphor generation ID VEGETATIVE STATE; AUTOBIOGRAPHICAL MEMORY; CONSCIOUSNESS; HABITUATION; COGNITION; STIMULI; BRAIN; ATTENTION; AWARENESS; EMOTION AB Studies on creativity in participants with autism generally show impoverished performance as well as deficient comprehension of metaphoric language. However, very little is known about the ability to generate metaphors in this population. The present study examines verbal creativity in adults with autism-spectrum disorder (ASD) through tasks that rely on novel metaphoric language. Seventeen adults with ASD (mean age = 21.06) and 17 typically developing peers (mean age = 22.71) participated in the study. A multiple-choice questionnaire consisting of conventional and novel metaphors was used to test comprehension, and a sentence completion questionnaire was used to test generation of creative language. Results show similar performance in comprehension of conventional and novel metaphors in both groups, whereas adults with ASD generated more creative metaphors relative to the control group. Scores on tests of vocabulary and naming contributed to the prediction of conventional metaphor comprehension, while scores on tests of mental flexibility contributed to the prediction of novel metaphor comprehension. In addition, scores on a test of non-verbal intelligence contributed to the prediction of metaphor generation. 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PD AUG 11 PY 2014 VL 8 AR 615 DI 10.3389/fnhum.2014.00615 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AN6MR UT WOS:000340709100001 PM 25157225 ER PT J AU Xuan, ICY Hampson, DR AF Xuan, Ingrid C. Y. Hampson, David R. TI Gender-Dependent Effects of Maternal Immune Activation on the Behavior of Mouse Offspring SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; SEX-DIFFERENCES; ANIMAL-MODELS; INFECTION; SCHIZOPHRENIA; CHILDREN; RECEPTOR; BRAIN; MICE; AGE AB Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation'' model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic: polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior. C1 [Xuan, Ingrid C. Y.; Hampson, David R.] Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON, Canada. [Hampson, David R.] Univ Toronto, Dept Pharmacol & Toxicol, Fac Med, Toronto, ON, Canada. RP Hampson, DR (reprint author), Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON, Canada. EM d.hampson@utoronto.ca FU Canadian Institutes for Health Research (CIHR); CIHR Strategic Training Program in Biological Therapeutics FX This work was supported by the Canadian Institutes for Health Research (CIHR) and the CIHR Strategic Training Program in Biological Therapeutics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Retrospective cohort study; Psychological development disability; Synthetic oxytocin; Battelle Inventory ID LOGISTIC-REGRESSION ANALYSIS; AUTISM SPECTRUM DISORDERS; PITUITARY-ADRENAL AXIS; SOCIAL BEHAVIORS; VASOPRESSIN; LABOR; RECEPTOR; BRAIN; RISK; INDUCTION AB Objective: The objective was to evaluate the potential influence of oxytocin administered during delivery on children's development at the age of 5. Method: This study was designed as a retrospective cohort study where children from patients given synthetic oxytocin during delivery were considered as the exposed cohort and children from patients not given oxytocin as the nonexposed cohort. From a total of 7465 births attended at our maternity ward in 2006, an initial sample of 400 was randomly selected. A total of 148 children were evaluated using the Battelle Developmental Inventory. Potential confounding and adjustment factors were analyzed using stratified analysis and multivariate analysis (logistic regression). Results: Oxytocin use did not significantly affect the overall risk of developmental delay in the study sample (relative risk, RR, 1.46; 95% confidence interval, CI [0.79-2.71]). The best fit regression model included twin delivery, type of delivery, and maternal age. In the group of vaginal noninstrumental deliveries, oxytocin administration increased the risk of poor Battelle Developmental Inventory outcome, particularly when maternal age was under 28 or over 35 years of age (odds ratio, OR, 67.14; 95% CI [5.46-824.86]). When delivery was instrumental or through cesarean section in mothers aged 28-35 years, oxytocin administration decreased the risk of developmental disorders (OR 0.16; 95% CI [0.04-0.66]). Conclusion: Although oxytocin administration during delivery did not affect the overall risk of low Battelle Developmental Inventory scores in the study sample, some effects were seen according to maternal age and type of birth. C1 [Jose Gonzalez-Valenzuela, Maria; Delgado-Rios, Myriam; Cazorla-Granados, Olga] Univ Malaga, Fac Psychol, Dept Dev & Educ Psychol, Malaga 29011, Spain. [Garcia-Fortea, Pedro; Blasco-alonso, Marta; Gonzalez-Mesa, Ernesto] Univ Malaga, Malaga Obstet & Gynecol Res Grp, IBIMA, Malaga 29011, Spain. RP Gonzalez-Mesa, E (reprint author), Univ Malaga, Obstet & Gynecol Res Grp, IBIMA, Arroyo Angeles S-N, Malaga 29011, Spain. 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Despite its popularity, some serious issues arise with this approach to cooperation. First, one may challenge the assumption that high-level mental processes are necessary for engaging in acting cooperatively. If they are, then how do agents that do not possess such ability (preverbal children, or children with autism who are often claimed to be mind-blind) engage in cooperative exchanges, as the evidence suggests? Secondly, to define cooperation as the result of two de-contextualized minds reading each other's intentions may fail to fully acknowledge the complexity of situated, interactional dynamics and the interplay of variables such as the participants' relational and personal history and experience. In this paper we challenge such accounts of cooperation, calling for an embodied approach that sees cooperation not only as an individual attitude toward the other, but also as a property of interaction processes. 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PD AUG 8 PY 2014 VL 5 AR 874 DI 10.3389/fpsyg.2014.00874 PG 11 WC Psychology, Multidisciplinary SC Psychology GA AN8XM UT WOS:000340889200001 PM 25152745 ER PT J AU Pakarinen, S Sokka, L Leinikka, M Henelius, A Korpela, J Huotilainen, M AF Pakarinen, Satu Sokka, Laura Leinikka, Marianne Henelius, Andreas Korpela, Jussi Huotilainen, Minna TI Fast determination of MMN and P3a responses to linguistically and emotionally relevant changes in pseudoword stimuli SO NEUROSCIENCE LETTERS LA English DT Article DE Mismatch negativity (MMN); Event-related potential (ERP); Multi-feature paradigm; Central auditory processing; Emotion; Language ID MISMATCH NEGATIVITY MMN; INVOLUNTARY ATTENTION; BRAIN POTENTIALS; AUDITORY-STIMULI; SENSORY MEMORY; COMPLEX SOUND; DURATION; NOVELTY; P300; DISCRIMINATION AB We developed a new multi-feature mismatch negativity (MMN) paradigm with two improvements: Firstly, the standard tone, a pseudoword /ta-ta/ was presented with equal probability to the nine linguistically relevant deviants, reducing the recording time by 45%. Secondly, three rare, emotionally valenced stimuli: happy, angry, and sad utterances of the standard pseudoword were included in the sequence. MMN signals reflecting the perceptual properties of the sounds were observed for all stimuli. In addition, P3a signals were observed for the rare emotionally uttered pseudowords. This 28-min paradigm allows a multi-dimensional evaluation of central speech-sound representations (MMN), and attention allocation (P3a) to emotional information content of speech. We recommend this paradigm for studies on subject groups with impairments in language or emotional information processing, such as autism spectrum disorders, attention disorders, and alexithymia. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Pakarinen, Satu; Sokka, Laura; Leinikka, Marianne; Henelius, Andreas; Korpela, Jussi; Huotilainen, Minna] Finnish Inst Occupat Hlth, FI-00250 Helsinki, Finland. RP Pakarinen, S (reprint author), Finnish Inst Occupat Hlth, Brain & Technol Team, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland. EM satu.pakarinen@ttl.fi FU SalWe Research Programme for Mind and Body [1104/10] FX The authors thank RN Nina Lapvetelainen and Riitta Velin for their assistance in data collection. The present study was supported by the SalWe Research Programme for Mind and Body (Tekes - Grant 1104/10). 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Lett. PD AUG 8 PY 2014 VL 577 BP 28 EP 33 DI 10.1016/j.neulet.2014.06.004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AN0XY UT WOS:000340308500006 PM 24928223 ER PT J AU Manzini, MC Xiong, L Shaheen, R Tambunan, DE Di Costanzo, S Mitisalis, V Tischfield, DJ Cinquino, A Ghaziuddin, M Christian, M Jiang, Q Laurent, S Nanjiani, ZA Rasheed, S Hill, RS Lizarraga, SB Gleason, D Sabbagh, D Salih, MA Alkuraya, FS Walsh, CA AF Manzini, M. Chiara Xiong, Lan Shaheen, Ranad Tambunan, Dimira E. Di Costanzo, Stefania Mitisalis, Vanessa Tischfield, David J. Cinquino, Antonella Ghaziuddin, Mohammed Christian, Mehtab Jiang, Qin Laurent, Sandra Nanjiani, Zohair A. Rasheed, Saima Hill, R. Sean Lizarraga, Sofia B. Gleason, Danielle Sabbagh, Diya Salih, Mustafa A. Alkuraya, Fowzan S. Walsh, Christopher A. TI CC2D1A Regulates Human Intellectual and Social Function as well as NF-kappa B Signaling Homeostasis SO CELL REPORTS LA English DT Article ID NONSYNDROMIC MENTAL-RETARDATION; C2 DOMAIN PROTEIN; NOTCH; GENE; IDENTIFICATION; TRAFFICKING; PLASTICITY; DROSOPHILA; DISORDERS; RECEPTORS AB Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor kappa B (NF-kappa B). Cc2d1a gain and loss of function both increase activation of NF-kappa B, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons reduces dendritic complexity and increases NF-kappa B activity, and the effects of Cc2d1a depletion can be rescued by inhibiting NF-kappa B activity. Homeostatic regulation of neuronal signaling pathways provides a mechanism whereby common founder mutations could manifest diverse symptoms in different patients. C1 [Manzini, M. Chiara; Tambunan, Dimira E.; Di Costanzo, Stefania; Mitisalis, Vanessa; Tischfield, David J.; Cinquino, Antonella; Hill, R. Sean; Lizarraga, Sofia B.; Gleason, Danielle; Sabbagh, Diya; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. [Manzini, M. Chiara; Tambunan, Dimira E.; Di Costanzo, Stefania; Mitisalis, Vanessa; Tischfield, David J.; Cinquino, Antonella; Hill, R. Sean; Lizarraga, Sofia B.; Gleason, Danielle; Sabbagh, Diya; Walsh, Christopher A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Manzini, M. Chiara; Tambunan, Dimira E.; Di Costanzo, Stefania; Mitisalis, Vanessa; Tischfield, David J.; Cinquino, Antonella; Hill, R. Sean; Lizarraga, Sofia B.; Gleason, Danielle; Sabbagh, Diya; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Manzini, M. Chiara; Tambunan, Dimira E.; Di Costanzo, Stefania; Mitisalis, Vanessa; Tischfield, David J.; Cinquino, Antonella; Hill, R. Sean; Lizarraga, Sofia B.; Gleason, Danielle; Sabbagh, Diya; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Xiong, Lan; Jiang, Qin] Univ Montreal, Montreal Mental Hlth Univ Inst, Res Ctr, Dept Psychiat, Montreal, PQ H1N 3V2, Canada. [Xiong, Lan; Christian, Mehtab; Laurent, Sandra] Univ Montreal Hosp, Res Ctr, Montreal, PQ H2L 2W5, Canada. [Shaheen, Ranad; Sabbagh, Diya; Alkuraya, Fowzan S.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Ghaziuddin, Mohammed] Univ Michigan Hlth Syst, Dept Child & Adolescent Psychiat, Ann Arbor, MI 48109 USA. [Nanjiani, Zohair A.] Univ Karachi, Ma Ayesha Mem Ctr, Karachi 75350, Pakistan. [Rasheed, Saima] Autism Inst, Karachi 74000, Pakistan. [Salih, Mustafa A.] King Saud Univ, Coll Med, Dept Pediat, Div Pediat Neurol, Riyadh 11461, Saudi Arabia. [Walsh, Christopher A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Salih, MA (reprint author), King Saud Univ, Coll Med, Dept Pediat, Div Pediat Neurol, Riyadh 11461, Saudi Arabia. EM mustafa_salih05@yahoo.com; falkuraya@kfshrc.edu.sa; christopher.walsh@childrens.harvard.edu FU NIH [R01MH083565, R01NS032457, R00HD067379]; Simons Foundation; KACST [13-BIO1113-20]; Centro per la Comunicazione e Ricerca del Collegio Ghislieri; Hearst Fund; Manton Center for Orphan Disease Research; Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia [RGP-VPP-301]; Italian National Research Council; Giovanni Armenise-Harvard Foundation FX The authors would like to thank the families for their constant availability and collaboration, Dilenny Gonzalez and Daniel Rakiec for technical help, Adria Bodell for help with patient recruitment, Tom Maynard at the George Washington University for help with qPCR, and the Genotyping and Sequencing Core Facility at KFSHRC for help with analysis of families 1 and 2. They are also grateful to Jenny Yang, Tim Yu, and Adam Oaks for helpful discussion. Research was supported by grants from the NIH (R01MH083565 and R01NS032457 to C.A.W. and R00HD067379 to M.C.M.) the Simons Foundation (to C.A.W.), and KACST (Grant 13-BIO1113-20 to F.S.A.). M.C.M. was also supported by grants from the Centro per la Comunicazione e Ricerca del Collegio Ghislieri, the Hearst Fund, and the Manton Center for Orphan Disease Research. M.A.S. was supported by the Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia through the research group project number RGP-VPP-301. A.C. was supported by a fellowship from the Italian National Research Council and the Giovanni Armenise-Harvard Foundation. C.A.W. is an Investigator of the Howard Hughes Medical Institute. 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We report a study in which a crossed-hands illusion was investigated in autistic children. Neurotypical individuals often experience a subjective reversal of temporal order judgments when their hands are stimulated while crossed, and the illusion is known to be acquired in early childhood. However, under those conditions where the somatotopic representation is given priority over the actual spatial location of the hands, such reversals may not occur. Here, we showed that a significantly smaller illusory reversal was demonstrated in autistic children than in neurotypical children. Furthermore, in an additional experiment, the young boys who had higher Autism Spectrum Quotient (AQ) scores generally showed a smaller crossed hands deficit. These results suggest that rudimentary spatio-temporal processing of tactile stimuli exists in autistic children, and the altered processing may interfere with the development of an external frame of reference in real-life situations. C1 [Wada, Makoto; Kansaku, Kenji] Natl Rehabil Ctr Persons Disabil, Inst Res, Dept Rehabil Brain Funct, Syst Neurosci Sect, Tokorozawa, Saitama 3598555, Japan. [Wada, Makoto] Natl Rehabil Ctr Persons Disabil, Inst Res, Dept Rehabil Brain Funct, Dev Disorders Sect, Tokorozawa, Saitama 3598555, Japan. [Miyao, Masutomo] Natl Ctr Child Hlth & Dev, Dept Med Psychol, Div Dev Neuropsychol, Tokyo, Tokyo 1578535, Japan. [Spence, Charles] Univ Oxford, Dept Expt Psychol, Crossmodal Res Lab, Oxford OX1 3UD, England. [Kansaku, Kenji] Univ Electrocommun, Brain Sci Inspired Life Support Res, Tokyo 1828585, Japan. RP Kansaku, K (reprint author), Natl Rehabil Ctr Persons Disabil, Inst Res, Dept Rehabil Brain Funct, Syst Neurosci Sect, Tokorozawa, Saitama 3598555, Japan. EM kansaku-kenji@rehab.go.ip FU MEXT [23300151] FX This study was partly supported by a MEXT grant (#23300151) to K. Kansaku. We would like to thank S. Iwama for technical assistance; H. Hirose, H. Agarie, S. Kim and S. Kitazawa for their valuable comments; and Y. Nakajima and S. Kato for their continuous encouragement. 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It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication. C1 [Yasuda, Yuka; Hashimoto, Ryota; Yamamori, Hidenaga; Fujimoto, Michiko; Ohi, Kazutaka; Takeda, Masatoshi] Osaka Univ, Grad Sch Med, Dept Psychiat, Suita, Osaka 5650871, Japan. [Hashimoto, Ryota; Taniike, Masako; Mohri, Ikuko] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Suita, Osaka 5650871, Japan. [Fukai, Ryoko] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. [Fukai, Ryoko; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Matsumoto, Naomichi; Miyake, Noriko] Yokohama City Univ, Grad Sch Med, Dept Neurol & Stroke Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. [Okamoto, Nobuhiko] Osaka Med Ctr, Div Med Genet, Izumi 5941101, Japan. [Okamoto, Nobuhiko] Res Inst Maternal & Child Hlth, Izumi 5941101, Japan. [Hiraki, Yoko] Hiroshima Municipal Ctr Child Hlth & Dev, Hiroshima 7320052, Japan. [Yamamori, Hidenaga] Osaka Univ, Grad Sch Med, Dept Mol Neuropsychiat, Suita, Osaka 5650871, Japan. RP Hashimoto, R (reprint author), Osaka Univ, Grad Sch Med, Dept Psychiat, D3,2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM hashimor@psy.med.osaka-u.ac.jp RI Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 FU Japanese Ministry of Health, Labor, and Welfare [H22-seishin-ippan-001, H23-jitsuyouka (nanbyo)-ippan-005, H25-shinkei kin-ippan-001]; Japan Society for the Promotion of Science (JSPS) [24249019, 22390225, 25293250, 25293085, 25293235, 24591680]; Challenging Exploratory Research grant [23659565]; Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [25129704, 12024421, 18023045]; Strategic Research Program for Brain Sciences [11105137]; Fund for the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems; Japan Foundation for Neuroscience and Mental Health; Takeda Science Foundation FX We thank the patients and their families for participating in this study. Additionally, we thank Ms. Y. Yamashita, Ms. E. Koike, Ms. S. Sugimoto, Ms. N. Watanabe, and Ms. K. Takabe for their technical assistance. This work was supported by research grants from the Japanese Ministry of Health, Labor, and Welfare (H22-seishin-ippan-001, H23-jitsuyouka (nanbyo)-ippan-005, H25-shinkei kin-ippan-001), the Japan Society for the Promotion of Science (JSPS) through a Grant-in-Aid for Scientific Research [(A) (24249019), (B) (22390225, 25293250, 25293085, and 25293235), and (C) (24591680)] and a Challenging Exploratory Research grant (23659565), the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT) through a Grant-in-Aid for Scientific Research in Innovative Areas (Comprehensive Brain Science Network, 25129704) (Transcription Cycle, 12024421), Priority Areas-Research on the Pathomechanisms of Brain Disorders (18023045), the Strategic Research Program for Brain Sciences (11105137), the Fund for the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems, the Japan Foundation for Neuroscience and Mental Health, and the Takeda Science Foundation. 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Gen. Psychiatr. PD AUG 6 PY 2014 VL 13 AR 22 DI 10.1186/s12991-014-0022-2 PG 5 WC Psychiatry SC Psychiatry GA AN9EO UT WOS:000340909000001 PM 25126106 ER PT J AU Kulesskaya, N Karpova, NN Ma, L Tian, L Voikar, V AF Kulesskaya, Natalia Karpova, Nina N. Ma, Li Tian, Li Voikar, Vootele TI Mixed housing with DBA/2 mice induces stress in C57BL/6 mice: implications for interventions based on social enrichment SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE animal model; stress; mixed housing; stress-related genes; behavioral interventions; social enrichment; social learning ID INBRED MOUSE STRAINS; BEHAVIORAL TASKS RELEVANT; BTBR-T+TF/J MICE; DEFEAT STRESS; GLUCOCORTICOID-RECEPTOR; EPIGENETIC REGULATION; ALZHEIMERS-DISEASE; ADRENAL AXIS; DEPRESSION; AUTISM AB Several behavioral interventions, based on social enrichment and observational learning are applied in treatment of neuropsychiatric disorders. However, the mechanism of such modulatory effect and the safety of applied methods on individuals involved in social support need further investigation. We took advantage of known differences between inbred mouse strains to reveal the effect of social enrichment on behavior and neurobiology of animals with different behavioral phenotypes. C57BL/6 and DBA/2 female mice displaying multiple differences in cognitive, social, and emotional behavior were group-housed either in same-strain or in mixed-strain conditions. Comprehensive behavioral phenotyping and analysis of expression of several plasticity- and stress-related genes were done to measure the reciprocal effects of social interaction between the strains. Contrary to our expectation, mixed housing did not change the behavior of DBA/2 mice. Nevertheless, the level of serum corticosterone and the expression of glucocorticoid receptor Nr3c1 in the brain were increased in mixed housed DBA/2 as compared with those of separately housed DBA/2 mice. In contrast, socially active C57BL/6 animals were more sensitive to the mixed housing, displaying several signs of stress: alterations in learning, social, and anxiety-like behavior and anhedonia. These behavioral impairments were accompanied by the elevated serum corticosterone and the reduced expression of Nr3c1, as well as the elevated Bdnf levels in the cortex and hippocampus. Our results demonstrate the importance of social factors in modulation of both behavior and the underlying neurobiological mechanisms in stress response, and draw attention to the potential negative impact of social interventions for individuals involved in social support. C1 [Kulesskaya, Natalia; Karpova, Nina N.; Ma, Li; Tian, Li; Voikar, Vootele] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. RP Kulesskaya, N (reprint author), Univ Helsinki, Ctr Neurosci, POB 56,Viikinkaari 4, FIN-00014 Helsinki, Finland. EM natalia.kulesskaya@helsinki.fi; nina.karpova@helsinki.fi FU Biocenter Finland; Helsinki graduate program in biotechnology and molecular biology; Ida Montinin saasto; Academy of Finland FX This work was supported by Biocenter Finland, Helsinki graduate program in biotechnology and molecular biology, Ida Montinin saasto and Academy of Finland. We would like to thank Prof. Heikki Rauvala for critical reading and discussion, and Sissi Pastell for animal care. 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Behav. Neurosci. PD AUG 6 PY 2014 VL 8 AR 257 DI 10.3389/fnbeh.2014.00257 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN9BZ UT WOS:000340902200001 PM 25147512 ER PT J AU Wang, SSH Kloth, AD Badura, A AF Wang, Samuel S. -H. Kloth, Alexander D. Badura, Aleksandra TI The Cerebellum, Sensitive Periods, and Autism SO NEURON LA English DT Review ID FRAGILE-X-SYNDROME; INTRINSIC FUNCTIONAL CONNECTIVITY; COGNITIVE-AFFECTIVE SYNDROME; VENTRAL TEGMENTAL AREA; MONKEYS MACACA-MULATTA; ORBITAL FRONTAL-CORTEX; SPECTRUM DISORDERS; PREFRONTAL CORTEX; MATERNAL INFECTION; SOCIAL-BEHAVIOR AB Cerebellar research has focused principally on adult motor function. However, the cerebellum also maintains abundant connections with nonmotor brain regions throughout postnatal life. 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EM sswang@princeton.edu FU NIH [R01 NS045193, F31 MH098651]; Nancy Lurie Marks Family Foundation; Sutherland Cook Fund FX We thank Benjamin Campbell, Sara Connolly, Cristina Domnisoru, Jeff Erlich, Daniel Geschwind, Elizabeth Gould, David Heeger, Mala Murthy, Bence Olveczky, Jordan Taylor, Huda Zoghbi, and members of the S.S.-H.W. lab for discussion and comments. We thank Randy Buckner and Partha Mitra for the use of images. This work was supported by NIH R01 NS045193 (S.S.-H.W.), NIH F31 MH098651 (A. D. K.), the Nancy Lurie Marks Family Foundation (S.S.-H.W), and the Sutherland Cook Fund (S.S.-H.W). 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Adolphs, Ralph TI Violations of Personal Space by Individuals with Autism Spectrum Disorder SO PLOS ONE LA English DT Article ID SOCIAL-BEHAVIOR; DIAGNOSTIC INTERVIEW; ETHOLOGICAL APPROACH; AMYGDALA; CHILDREN; ADOLESCENTS; TRAITS; BRAIN AB The ability to maintain an appropriate physical distance (i.e., interpersonal distance) from others is a critical aspect of social interaction and contributes importantly to real-life social functioning. In Study 1, using parent-report data that had been acquired on a large number of individuals (ages 4-18 years) for the Autism Genetic Resource Exchange and the Simons Simplex Collection, we found that those with Autism Spectrum Disorder (ASD; n = 766) more often violated the space of others compared to their unaffected siblings (n = 766). This abnormality held equally across ASD diagnostic categories, and correlated with clinical measures of communication and social functioning. In Study 2, laboratory experiments in a sample of high-functioning adults with ASD demonstrated an altered relationship between interpersonal distance and personal space, and documented a complete absence of personal space in 3 individuals with ASD. Furthermore, anecdotal self-report from several participants confirmed that violations of social distancing conventions continue to occur in real-world interactions through adulthood. We suggest that atypical social distancing behavior offers a practical and sensitive measure of social dysfunction in ASD, and one whose psychological and neurological substrates should be further investigated. C1 [Kennedy, Daniel P.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Kennedy, Daniel P.; Adolphs, Ralph] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. [Adolphs, Ralph] CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Kennedy, DP (reprint author), Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. EM dpk@indiana.edu; radolphs@hss.caltech.edu FU Simons Foundation [SFARI-07-01]; National Institute of Mental Health [R01 MH080721]; Tamagawa University global Centers of Excellence program of the Japanese Ministry of Education, Culture, Sports and Technology FX This work was supported by the Simons Foundation (SFARI-07-01 to R.A.), the National Institute of Mental Health (R01 MH080721 to R.A.), and the Tamagawa University global Centers of Excellence program of the Japanese Ministry of Education, Culture, Sports and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI Transient Overexposure of Neuregulin 3 during Early Postnatal Development Impacts Selective Behaviors in Adulthood SO PLOS ONE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; DEVELOPING NEOCORTEX; RECOGNITION MEMORY; PREFRONTAL CORTEX; ANIMAL-MODEL; SCHIZOPHRENIA; MICE; RECEPTOR; SUSCEPTIBILITY; INTERNEURONS AB Neuregulin 3 (NRG3), a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB). In this study we synthesized the bioactive epidermal growth factor (EGF) domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2-10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to be distinct from its paralog NRG1. Furthermore we demonstrate how perturbations in NRG3 expression at distinct developmental stages may contribute to the neurological deficits observed in brain disorders such as schizophrenia and autism. C1 [Paterson, Clare; Law, Amanda J.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. [Law, Amanda J.] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO USA. RP Law, AJ (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. EM amanda.law@ucdenver.edu FU National Institute of Mental Health; Brain Behavior Research Foundations, Sidney R. Baer Jr. Award for Schizophrenia Research FX This work was supported by funds from the Intramural Research Program, National Institute of Mental Health, and from the Brain Behavior Research Foundations, Sidney R. Baer Jr. Award for Schizophrenia Research, awarded to Amanda J. Law at the University of Colorado, Denver, School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Affordances are the possibilities for action offered by the environment. In contrast to ToM approaches, the concept of affordances implies the complementarity of person and environment and rejects the dualism of mind and behavior. In line with the Gibsonian idea that a child must eventually perceive the affordances of the environment for others as well for herself in order to become socialized, I will hypothesize that individuals with ASD often do not perceive the same affordances in the environment as other people do and have difficulties perceiving others' affordances. This can lead to a disruption of interpersonal behaviors. I will further argue that the methods for studying social engagement should be adapted if we want to take interaction into account. C1 Univ Utrecht, Ctr Cognit & Motor Disabil, Dept Special Educ, NL-3508 TC Utrecht, Netherlands. RP Hellendoorn, A (reprint author), Univ Utrecht, Ctr Cognit & Motor Disabil, Dept Special Educ, Heidelberglaan 1,POB 80-140, NL-3508 TC Utrecht, Netherlands. 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Each classroom was responsible for conducting communication assessments and developing interventions focused on increasing functional communication. One intervention, the Picture Exchange Communication System (PECS (TM)), was taught to three pre-service teachers and staff who implemented PECS (TM) with four students who lacked functional communication skills. The teachers were mentored as they implemented the appropriate level of PECS (TM) and developed communication books for the students to use in school, home, and other settings. C1 [Hill, Doris Adams] Auburn Univ, Dept Special Educ Rehabil & Counseling, Educ & Community Supports, Auburn, AL 36849 USA. [Flores, Margaret M.] Auburn Univ, Dept Special Educ Rehabil & Counseling, Special Educ, Auburn, AL 36849 USA. [Kearley, Regina F.] Auburn Univ, Special Edcuat, Auburn, AL 36849 USA. RP Hill, DA (reprint author), Auburn Univ, Dept Special Educ Rehabil & Counseling, 215 South Donahue Dr, Auburn, AL 36849 USA. 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Spanagel, Rainer TI Enhanced Extinction of Contextual Fear Conditioning in Clock Delta 19 Mutant Mice SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE circadian; clock; Clock Delta 19 mutant mice; contextual fear conditioning; dopamine; extinction; modafinil ID PLACE PREFERENCE; CIRCADIAN CLOCK; DOPAMINE; COCAINE; RECEPTOR; GENE; ACQUISITION; BEHAVIORS; MODAFINIL; MUTATION AB Clock genes have been implicated in several disorders, such as schizophrenia, bipolar disorder, autism spectrum disorders, and drug dependence. However, few studies to date have examined the role of clock genes in fear-related behaviors. The authors used mice with the Clock Delta 19 mutation to assess the involvement of this gene in contextual fear conditioning. Male wild-type (WT) and Clock Delta 19 mutant mice underwent a single session of contextual fear conditioning (12 min, 4 unsignaled shocks), followed by daily 12-min retention trials. There were no differences between mutant and WT mice in the acquisition of contextual fear, and WT and mutant mice demonstrated similar freezing during the first retention session. However, extinction of contextual fear was accelerated in mutant mice across the remaining retention sessions, as compared to WT mice, suggesting a role for Clock in extinction following aversive learning. Because the Clock Delta 19 mutation has previously been demonstrated to result in an increase in dopamine signaling, the authors confirmed the role of dopamine in extinction learning using preretention session administration of a low dose of the dopamine transport reuptake inhibitor modafinil (0.75 mg/kg), which resulted in decreased freezing across retention sessions. These findings are consistent with an emerging portrayal of the importance of Clock genes in noncircadian functions, as well as the important role of dopamine in extinction learning. C1 [Bernardi, Rick E.; Spanagel, Rainer] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany. RP Bernardi, RE (reprint author), Cent Inst Mental Hlth, Inst Psychopharmacol, J5, D-68159 Mannheim, Germany. EM rick.bernardi@zi-mannheim.de FU Deutsche Forschungsgemeinschaft (DFG) [SPP1226, SP 383/4-1] FX Rick E. Bernardi was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, SPP1226, SP 383/4-1). We report no conflicts of interest. 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Neurosci. PD AUG PY 2014 VL 128 IS 4 BP 468 EP 473 DI 10.1037/a0037020 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CA8KQ UT WOS:000349169300006 PM 24865659 ER PT J AU Bone, D Lee, CC Black, MP Williams, ME Lee, S Levitt, P Narayanan, S AF Bone, Daniel Lee, Chi-Chun Black, Matthew P. Williams, Marian E. Lee, Sungbok Levitt, Pat Narayanan, Shrikanth TI The Psychologist as an Interlocutor in Autism Spectrum Disorder Assessment: Insights From a Study of Spontaneous Prosody SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism spectrum disorder; children; prosody; social communication; assessment; dyadic interaction ID HIGH-FUNCTIONING AUTISM; CLASSIFICATION-SYSTEM SDCS; BREATHY VOCAL QUALITY; CHILDREN; SPEECH; COMMUNICATION; LANGUAGE; EMOTION; EXTENSIONS; ENGAGEMENT AB Purpose: The purpose of this study was to examine relationships between prosodic speech cues and autism spectrum disorder (ASD) severity, hypothesizing a mutually interactive relationship between the speech characteristics of the psychologist and the child. The authors objectively quantified acoustic-prosodic cues of the psychologist and of the child with ASD during spontaneous interaction, establishing a methodology for future large-sample analysis. Method: Speech acoustic-prosodic features were semiautomatically derived from segments of semistructured interviews (Autism Diagnostic Observation Schedule, ADOS; Lord, Rutter, DiLavore, & Risi, 1999; Lord et al., 2012) with 28 children who had previously been diagnosed with ASD. Prosody was quantified in terms of intonation, volume, rate, and voice quality. Research hypotheses were tested via correlation as well as hierarchical and predictive regression between ADOS severity and prosodic cues. Results: Automatically extracted speech features demonstrated prosodic characteristics of dyadic interactions. As rated ASD severity increased, both the psychologist and the child demonstrated effects for turn-end pitch slope, and both spoke with atypical voice quality. The psychologist's acoustic cues predicted the child's symptom severity better than did the child's acoustic cues. Conclusion: The psychologist, acting as evaluator and interlocutor, was shown to adjust his or her behavior in predictable ways based on the child's social-communicative impairments. The results support future study of speech prosody of both interaction partners during spontaneous conversation, while using automatic computational methods that allow for scalable analysis on much larger corpora. C1 [Bone, Daniel; Lee, Chi-Chun; Black, Matthew P.; Lee, Sungbok; Narayanan, Shrikanth] Univ So Calif, SAIL, Los Angeles, CA 90095 USA. [Williams, Marian E.] Univ So Calif, Keck Sch Med, Univ Ctr Excellence Dev Disabil, Los Angeles, CA 90033 USA. [Williams, Marian E.; Levitt, Pat] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Bone, D (reprint author), Univ So Calif, SAIL, Los Angeles, CA 90095 USA. 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Shelton, W. M. R. Ing, Caleb Newnham, John P. TI Prenatal, Perinatal, and Neonatal Risk Factors for Specific Language Impairment: A Prospective Pregnancy Cohort Study SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE specific language impairment; prenatal; obstetric ID OBSTETRIC COMPLICATIONS; FOLLOW-UP; AUTISM; CHILDREN; DISORDERS; OUTCOMES; ATTRITION AB Purpose: Although genetic factors are known to play a causal role in specific language impairment (SLI), environmental factors may also be important. This study examined whether there are prenatal, perinatal, and neonatal factors that are associated with childhood SLI. Method: Participants were members of the Raine Study, a prospective cohort investigation of pregnant women and their offspring. Parent report indicated that 26 children had received a clinical diagnosis of SLI. Data from antenatal and birth medical records were compared between the children with SLI and typically developing comparison children (N = 1,799). Results: There were no statistically significant differences between the SLI and comparison groups in the individual prenatal, perinatal, and neonatal factors examined. Aggregate risk scores were calculated for each period on the basis of factors known to be associated with neurodevelopmental disorder. There were no group differences in aggregate risk scores in the prenatal and perinatal periods. However, significantly more children in the SLI group (50%) compared with the comparison group (27.6%) experienced 2 or more risk factors during the neonatal period. Conclusion: The vast majority of prenatal, perinatal, and neonatal complications do not play a clear causal role in childhood SLI. However, poor neonatal health may signify increased risk for SLI. C1 [Whitehouse, Andrew J. O.; Shelton, W. M. R.] Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia. [Ing, Caleb] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Newnham, John P.] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia. RP Whitehouse, AJO (reprint author), Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia. EM awhitehouse@ichr.uwa.edu.au FU 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 and Infants Research Foundation; NHMRC [1004065, 1003424] FX The authors would like to acknowledge the National Health and Medical Research Council (NHMRC) for its long-term contribution to 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 and Infants Research Foundation. Andrew J. O. Whitehouse is funded by a Career Development Fellowship from the NHMRC (No. 1004065). This study was partly funded by NHMRC Project Grant No. 1003424. These funders had no further role in study design, analysis, data interpretation, or manuscript writing and submission. 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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Speech Lang. Hear. Res. PD AUG PY 2014 VL 57 IS 4 BP 1418 EP 1427 DI 10.1044/2014_JSLHR-L-13-0186 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4NF UT WOS:000348198000023 PM 24686440 ER PT J AU Kover, ST Weismer, SE AF Kover, Sara T. Weismer, Susan Ellis TI Lexical Characteristics of Expressive Vocabulary in Toddlers With Autism Spectrum Disorder SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism; statistical learning; vocabulary; language development; production ID LATE-TALKING TODDLERS; COMMUNICATIVE DEVELOPMENT; SIMILARITY NEIGHBORHOODS; PHONOTACTIC PROBABILITY; LANGUAGE-ACQUISITION; COGNITIVE SKILLS; WORKING-MEMORY; YOUNG-CHILDREN; INFANTS; PRESCHOOLERS AB Purpose: Vocabulary is a domain of particular challenge for many children with autism spectrum disorder (ASD). Recent research has drawn attention to ways in which lexical characteristics relate to vocabulary acquisition. The current study tested the hypothesis that lexical characteristics account for variability in vocabulary size of young children with ASD, applying the extended statistical learning theory of vocabulary delay in late talkers (Stokes, Kern, & Dos Santos, 2012) to toddlers with ASD. Method: Parents reported the words produced by toddlers with ASD (n = 57; age 21-37 months) or toddlers without ASD (n = 41; age 22-26 months) on the MacArthur-Bates Communicative Development Inventories. The average phonological neighborhood density, word frequency, and word length of each toddler's lexicon were calculated. These lexical characteristics served as predictors of vocabulary size. Results: Findings differed for toddlers with and without ASD and according to subsamples. Word length was the most consistent predictor of vocabulary size for toddlers with ASD. Conclusions: Distinct relationships between lexical characteristics and vocabulary size were observed for toddlers with and without ASD. Experimental studies on distributional cues to vocabulary acquisition are needed to inform what is known about mechanisms of learning in neurodevelopmental disorders. C1 [Kover, Sara T.; Weismer, Susan Ellis] Waisman Ctr Mental Retardat & Human Dev, Madison, WI 53705 USA. [Kover, Sara T.; 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, R01 DC03731, T32 DC05359, P30 HD03352] FX This research was supported by National Institutes of Health Grants R01 DC07223, R01 DC03731, T32 DC05359 (Susan Ellis Weismer, principal investigator [PI]), and P30 HD03352 (Marsha Mailick, PI). We offer sincere appreciation to the families who participated in this study. A portion of these data was presented at the 2013 biennial meeting of the Society for Research in Child Development in Seattle, Washington. 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PD AUG PY 2014 VL 57 IS 4 BP 1428 EP 1441 DI 10.1044/2014_JSLHR-L-13-0006 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AZ4NF UT WOS:000348198000024 PM 24687027 ER PT J AU Langone, SR Luiselli, JK Galvin, D Hamill, J AF Langone, Serra R. Luiselli, James K. Galvin, Denise Hamill, Jessica TI Effects of Fixed-Time Release Fading on Frequency and Duration of Aggression-Contingent Physical Restraint (Protective Holding) in a Child With Autism SO CLINICAL CASE STUDIES LA English DT Article DE physical restraint; autism; aggression; restraint reduction; fixed-time release fading ID BEHAVIOR; INJURY; STAFF; IMPLEMENTATION; INTERVENTION; DISABILITIES; ADOLESCENTS; PEOPLE; SAFETY AB We report the case of an 11-year-old boy with autism who displayed aggressive behavior and required aggression-contingent physical restraint (protective holding) to protect peers and teachers from injury. During a baseline phase, teachers implemented the boy's behavior support plan and applied protective holding according to a behavior-contingent release (BCR) criterion in which they maintained physical contact with him until he was "calm" for a minimum of 30 consecutive seconds. In the intervention phase, baseline procedures remained in effect, but the teachers terminated protective holding with the boy according to a fixed-time release (FTR) criterion that was independent of his behavior during protective holding and faded (decreased) systematically over time. In contrast to BCR, FTR fading was associated with less exposure to and fewer applications of protective holding. Post-intervention and follow-up results revealed that protective holding was no longer required. We discuss the clinical implications of these findings. C1 [Langone, Serra R.; Luiselli, James K.; Galvin, Denise; Hamill, Jessica] May Inst, Randolph, MA 02368 USA. 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Abbeduto, Leonard TI Sentence Comprehension in Boys With Autism Spectrum Disorder SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE autism; grammar; syntax; receptive language; intellectual disability ID FRAGILE-X-SYNDROME; DEVELOPMENTAL TRAJECTORIES; INTELLECTUAL DISABILITIES; METHODOLOGICAL ISSUES; LANGUAGE-ACQUISITION; PRESCHOOL-CHILDREN; ADOLESCENTS; SKILLS; IMPAIRMENT; DELAY AB Purpose: Previous research has suggested that language comprehension might be particularly impaired in children with autism spectrum disorder (ASD), but this profile has been only broadly characterized. In the current study, the authors examined sentence comprehension in school-age boys with ASD, including a subgroup with intellectual disability (ID), with particular attention paid to errors that might differentiate between lexically and syntactically based difficulties. Method: Participants were boys with ASD (n = 45, ages 4-11 years) and younger typically developing boys (n = 45, ages 2-6 years). Comprehension was assessed with the Test for Reception of Grammar-Version 2 (TROG-2; Bishop, 2003). Error types were analyzed for a subset of items. Results: Boys with ASD did not differ from younger typically developing boys matched on receptive vocabulary in overall sentence comprehension on the TROG-2 or the number of lexical errors committed. In contrast, the subgroup of boys with ASD and ID (n = 16) had poorer overall performance and committed more lexical errors than younger typically developing boys matched on nonverbal cognition. Conclusions: On average, comprehension was delayed in school-age boys with ASD but not beyond receptive vocabulary expectations. Boys with ASD and ID, however, had a weakness in sentence comprehension beyond nonverbal cognitive expectations. 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J. Speech-Lang. Pathol. PD AUG PY 2014 VL 23 IS 3 BP 385 EP 394 DI 10.1044/2014_AJSLP-13-0073 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AU5ZQ UT WOS:000345682300002 PM 24687049 ER PT J AU Murza, KA Nye, C Schwartz, JB Ehren, BJ Hahs-Vaughn, DL AF Murza, Kimberly A. Nye, Chad Schwartz, Jamie B. Ehren, Barbara J. Hahs-Vaughn, Debbie L. TI A Randomized Controlled Trial of an Inference Generation Strategy Intervention for Adults With High-Functioning Autism Spectrum Disorder SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE autism; intervention; language; reading; pragmatics; adults ID ASPERGER-SYNDROME; READING-COMPREHENSION; SOCIAL-PERCEPTION; YOUNG-ADULTS; CHILDREN; STUDENTS; DISABILITIES; ADOLESCENTS; SKILLS; MIND AB Purpose: The present intervention study investigated the efficacy of the ACT & Check Strategy intervention to improve inference generation when reading, metacognitive ability, general reading comprehension, and social inference ability in adults with high-functioning autism spectrum disorder (HF-ASD). Method: Twenty-five adults with HF-ASD were randomly assigned to either a treatment or a control group. Treatment sessions were conducted in 1-hr sessions, twice a week, for a total of 6 weeks. Treatment focused on explicit instruction of components of inference generation, categories of inferences, and increasingly independent strategy use. Results: The treatment group demonstrated significantly superior performance on 1 of 2 measures of inference generation in reading and 1 measure of metacognitive ability compared with the control group. Significant differences between groups were not found on measures of reading comprehension or social inference ability. Conclusion: These findings suggest that the ACT & Check Strategy was effective in improving participants' ability to generate inferences in reading and certain metacognitive abilities, but the skills do not appear to generalize to other social communication contexts, such as social inference generation. This research provides a measure of support for explicitly teaching inference generation to address a reading inference deficit in adults with HF-ASD. C1 [Murza, Kimberly A.] Univ No Colorado, Greeley, CO 80639 USA. 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T., 2001, GRADE GROUP READING Woodbury-Smith MR, 2009, EUR CHILD ADOLES PSY, V18, P2, DOI 10.1007/s00787-008-0701-0 NR 82 TC 0 Z9 0 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1058-0360 EI 1558-9110 J9 AM J SPEECH-LANG PAT JI Am. J. Speech-Lang. Pathol. PD AUG PY 2014 VL 23 IS 3 BP 461 EP 473 DI 10.1044/2014_AJSLP-13-0012 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AU5ZQ UT WOS:000345682300008 PM 24687182 ER PT J AU Thiemann-Bourque, KS Warren, SF Brady, N Gilkerson, J Richards, JA AF Thiemann-Bourque, Kathy S. Warren, Steven F. Brady, Nancy Gilkerson, Jill Richards, Jeffrey A. TI Vocal Interaction Between Children With Down Syndrome and Their Parents SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE Down syndrome; speech development; parent-child communication; vocalizations; automated vocal analysis ID YOUNG-CHILDREN; INTELLECTUAL DISABILITIES; INFANT VOCALIZATIONS; COMMUNICATION; INTERVENTION; AUTISM; WORDS; PAIRS AB Purpose: The purpose of this study was to describe differences in parent input and child vocal behaviors of children with Down syndrome (DS) compared with typically developing (TD) children. The goals were to describe the language learning environments at distinctly different ages in early childhood. Method: Nine children with DS and 9 age-matched TD children participated; 4 children in each group were ages 9-11 months, and 5 were between 25 and 54 months. Measures were derived from automated vocal analysis. A digital language processor measured the richness of the child's language environment, including number of adult words, conversational turns, and child vocalizations. Results: Analyses indicated no significant differences in words spoken by parents of younger versus older children with DS and significantly more words spoken by parents of TD children than parents of children with DS. Differences between the DS and TD groups were observed in rates of all vocal behaviors, with no differences noted between the younger versus older children with DS, and the younger TD children did not vocalize significantly more than the younger DS children. Conclusions: Parents of children with DS continue to provide consistent levels of input across the early language learning years; however, child vocal behaviors remain low after the age of 24 months, suggesting the need for additional and alternative intervention approaches. 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PD AUG PY 2014 VL 23 IS 3 BP 474 EP 485 DI 10.1044/2014_AJSLP-12-0010 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA AU5ZQ UT WOS:000345682300009 PM 24686777 ER PT J AU Wink, LK O'Melia, AM Shaffer, RC Pedapati, E Friedmann, K Schaefer, T Erickson, CA AF Wink, Logan K. O'Melia, Anne M. Shaffer, Rebecca C. Pedapati, Ernest Friedmann, Katherine Schaefer, Tori Erickson, Craig A. TI Intranasal Ketamine Treatment in an Adult With Autism Spectrum Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article C1 [Wink, Logan K.; Shaffer, Rebecca C.; Pedapati, Ernest; Friedmann, Katherine; Schaefer, Tori; Erickson, Craig A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [O'Melia, Anne M.] Univ Cincinnati, Cincinnati, OH USA. RP Wink, LK (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave MLC 4002, Cincinnati, OH 45229 USA. EM logan.wink@cchmc.org FU Simons Foundation; John Merck Fund; US Department of Defense; Autism Speaks; SynapDx; Cures Within Reach; Angelman Syndrome Foundation FX Dr Wink has been a consultant for Otsuka and has received grant/research support from Simons Foundation, John Merck Fund, US Department of Defense, Autism Speaks, SynapDx, and Cures Within Reach. Dr Shaffer has received grant/research support from Autism Speaks. Dr Erickson has been a consultant for Alcobra, Roche Group, and Confluence Pharmaceuticals; has received grant/research support from Simons Foundation, Angelman Syndrome Foundation, John Merck Fund, US Department of Defense, and Autism Speaks; and is a stock shareholder in Confluence Pharmaceuticals. Drs O'Melia, Pedapati, and Schaefer and Ms Friedmann report no potential conflict of interest. CR Papolos DF, 2013, J AFFECT DISORDERS, V147, P431, DOI 10.1016/j.jad.2012.08.040 Tottenham N, 2002, 9 ANN M COGN NEUR SO Zarate CA, 2006, ARCH GEN PSYCHIAT, V63, P856, DOI 10.1001/archpsyc.63.8.856 NR 3 TC 0 Z9 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2014 VL 75 IS 8 BP 835 EP 836 DI 10.4088/JCP.13cr08917 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU3RC UT WOS:000345530300010 PM 25191906 ER PT J AU Du Bois, JW Hobson, RP Hobson, JA AF Du Bois, John W. Hobson, R. Peter Hobson, Jessica A. TI Dialogic resonance and intersubjective engagement in autism SO COGNITIVE LINGUISTICS LA English DT Article DE autism; resonance; dialogic syntax; structural priming; intersubjectivity; identification; stance; attitude; linkage; engagement ID LANGUAGE PRODUCTION; JOINT ATTENTION; CHILDREN; COMMUNICATION; IDENTIFICATION; CONVERSATION; IMPAIRMENTS; PSYCHOLOGY; IMITATION; DISORDER AB How can we investigate the relation between language and the human capacity for intersubjective engagement? Here we combine insights from linguistics and psychology to study the language of children with autism. We begin by reviewing why it might be worthwhile to study autism from the perspective of dialogic resonance, defined as the catalytic activation of affinities across utterances. Then we report on a controlled study of conversations involving individual children with autism and an interested adult interviewer. According to reliable ratings of the transcribed conversations, each considered as a whole, the speech of participants with autism was characterized by atypical forms of dialogic resonance. On the other hand, the children with autism were similar to control participants insofar as their conversations manifested "typically developed frame grabs" in which dialogic resonance was accompanied by a coherent expansion. These findings were compatible with those that emerged from utterance-by-utterance analyses of the same conversations reported elsewhere (Hobson et al. 2012). To complement the quantitative findings, we present illustrative excerpts of language use. We consider how dialogic resonance relates to structural priming, and consider implications for understanding the relations among intersubjectivity, language, and autism. C1 [Du Bois, John W.] Univ Calif Santa Barbara, Dept Linguist, Santa Barbara, CA 93106 USA. [Hobson, R. Peter] UCL, Tavistock Clin, London WC1E 6BT, England. 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TI Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice SO DISEASE MODELS & MECHANISMS LA English DT Article DE AVPR1A; Humanized mouse; Social behavior; Species-specific; Microsatellite; Autism ID ANXIETY-RELATED BEHAVIOR; VASOPRESSIN RECEPTOR; KNOCKOUT MICE; PREPULSE INHIBITION; PROMOTER REGION; PSYCHIATRIC-DISORDERS; MONOGAMOUS VOLE; BINDING-SITES; MESSENGER-RNA; V-1A RECEPTOR AB Central arginine vasopressin receptor 1A(AVPR1A) modulates a wide range of behaviors, including stress management and territorial aggression, as well as social bonding and recognition. Inter- and intra-species variations in the expression pattern of AVPR1A in the brain and downstream differential behavioral phenotypes have been attributed to differences in the non-coding regions of the AVPR1A gene, including polymorphic elements within upstream regulatory areas. Gene association studies have suggested a link between AVPR1A polymorphisms and autism, and AVPR1A has emerged as a potential pharmacological target for treatment of social cognitive impairments and mood and anxiety disorders. To further investigate the genetic mechanism giving rise to species differences in AVPR1A expression patterns and associated social behaviors, and to create a preclinical mouse model useful for screening drugs targeting AVPR1A, we engineered and extensively characterized bacterial artificial chromosome(BAC) transgenic mice harboring the entire human AVPR1A locus with the surrounding regulatory elements. Compared with wild-type animals, the humanized mice displayed a more widely distributed ligand-AVPR1A binding pattern, which overlapped with that of primates. Furthermore, humanized AVPR1A mice displayed increased reciprocal social interactions compared with wild-type animals, but no differences in social approach and preference for social novelty were observed. Aspects of learning and memory, specifically novel object recognition and spatial relocation recognition, were unaffected. The biological alterations in humanized AVPR1A mice resulted in the rescue of the prepulse inhibition impairments that were observed in knockout mice, indicating conserved functionality. Although further behavioral paradigms and additional cohorts need to be examined in humanized AVPR1A mice, the results demonstrate that species-specific variations in the genomic content of regulatory regions surrounding the AVPR1A locus are responsible for differential receptor protein expression patterns across species and that they are likely to contribute to species-specific behavioral variation. The humanized AVPR1A mouse is a potential preclinical model for further understanding the regulation of receptor gene expression and the impact of variation in receptor expression on behaviors, and should be useful for screening drugs targeting human AVPR1A, taking advantage of the expression of human AVPR1A in human-relevant brain regions. C1 [Charles, Rhonda; Sakurai, Takeshi; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Charles, Rhonda; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Sakurai, Takeshi; Takahashi, Nagahide; Elder, Gregory A.; Sosa, Miguel A. Gama; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Sosa, Miguel A. Gama] James J Peters VA Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Young, Larry J.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Translat Social Neurosci, Atlanta, GA 30329 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.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu FU Seaver Foundation; Autism Science Foundation; National Institutes of Health [MH056897, MH064692, P51OD11132] FX This work was supported by the Seaver Foundation and a predoctoral fellowship from the Autism Science Foundation to R. C. Additional support was provided by National Institutes of Health grants [MH056897 and MH064692 to L.J.Y. and P51OD11132 to Yerkes National Primate Research Center]. 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Model. Mech. PD AUG PY 2014 VL 7 IS 8 BP 1013 EP 1022 DI 10.1242/dmm.017053 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AT5TF UT WOS:000345004200009 PM 24924430 ER PT J AU Duda, M Kosmicki, JA Wall, DP AF Duda, M. Kosmicki, J. A. Wall, D. P. TI Testing the accuracy of an observation-based classifier for rapid detection of autism risk SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC-OBSERVATION-SCHEDULE; SPECTRUM DISORDERS; REVISED ALGORITHMS; ADOS SCORES; SEVERITY; CHILDREN AB Current approaches for diagnosing autism have high diagnostic validity but are time consuming and can contribute to delays in arriving at an official diagnosis. In a pilot study, we used machine learning to derive a classifier that represented a 72% reduction in length from the gold-standard Autism Diagnostic Observation Schedule-Generic (ADOS-G), while retaining >97% statistical accuracy. The pilot study focused on a relatively small sample of children with and without autism. The present study sought to further test the accuracy of the classifier (termed the observation-based classifier (OBC)) on an independent sample of 2616 children scored using ADOS from five data repositories and including both spectrum (n = 2333) and non-spectrum (n = 283) individuals. We tested OBC outcomes against the outcomes provided by the original and current ADOS algorithms, the best estimate clinical diagnosis, and the comparison score severity metric associated with ADOS-2. The OBC was significantly correlated with the ADOS-G (r = -0.814) and ADOS-2 (r = -0.779) and exhibited >97% sensitivity and >77% specificity in comparison to both ADOS algorithm scores. The correspondence to the best estimate clinical diagnosis was also high (accuracy = 96.8%), with sensitivity of 97.1% and specificity of 83.3%. The correlation between the OBC score and the comparison score was significant (r = -0.628), suggesting that the OBC provides both a classification as well as a measure of severity of the phenotype. These results further demonstrate the accuracy of the OBC and suggest that reductions in the process of detecting and monitoring autism are possible. C1 [Duda, M.; Wall, D. P.] Stanford Univ, Div Syst Med, Dept Pediat, Stanford, CA 94305 USA. [Kosmicki, J. A.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kosmicki, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Kosmicki, J. A.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Wall, DP (reprint author), Stanford Univ, Div Syst Med, Dept Pediat, 1265 Welch Rd, Stanford, CA 94305 USA. EM dpwall@stanford.edu FU Simons Foundation; Nancy Lurie Marks Family Foundation; Harvard Catalyst Program; National Institutes of Health [1R01MH090611-01A1] FX Work was supported in part by funds to DPW from the Simons Foundation, Nancy Lurie Marks Family Foundation, the Harvard Catalyst Program, and grant 1R01MH090611-01A1 from the National Institutes of Health. We thank the reviewers whose comments substantially improved the quality of the manuscript. We also thank the families who contributed the data that made this study possible. 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Psychiatr. PD AUG PY 2014 VL 4 AR e424 DI 10.1038/tp.2014.65 PG 6 WC Psychiatry SC Psychiatry GA AT3HR UT WOS:000344826900005 PM 25116834 ER PT J AU Pathania, M Davenport, EC Muir, J Sheehan, DF Lopez-Domenech, G Kittler, JT AF Pathania, M. Davenport, E. C. Muir, J. Sheehan, D. F. Lopez-Domenech, G. Kittler, J. T. TI The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (vol 4, pg e374, 2014) SO TRANSLATIONAL PSYCHIATRY LA English DT Correction CR DERUBEIS, 2014, TRANSL PSYCHIAT, V4, pE374, DOI DOI 10.1038/TP.2014.16 NR 1 TC 1 Z9 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD AUG PY 2014 VL 4 AR e423 DI 10.1038/tp.2014.36 PG 1 WC Psychiatry SC Psychiatry GA AT3HR UT WOS:000344826900004 ER PT J AU Squillace, M Dodero, L Federici, M Migliarini, S Errico, F Napolitano, F Krashia, P Di Maio, A Galbusera, A Bifone, A Scattoni, ML Pasqualetti, M Mercuri, NB Usiello, A Gozzi, A AF Squillace, M. Dodero, L. Federici, M. Migliarini, S. Errico, F. Napolitano, F. Krashia, P. Di Maio, A. Galbusera, A. Bifone, A. Scattoni, M. L. Pasqualetti, M. Mercuri, N. B. Usiello, A. Gozzi, A. TI Dysfunctional dopaminergic neurotransmission in asocial BTBR mice SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDER; T PLUS TF/J; SOCIAL ANXIETY DISORDER; GLUR1 AMPA RECEPTOR; MOUSE MODEL; NUCLEUS-ACCUMBENS; D2 RECEPTORS; T+TF/J MICE; UNUSUAL REPERTOIRE; IN-VIVO AB Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T+ Itpr3(tf)/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre-and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations. C1 [Squillace, M.; Errico, F.; Napolitano, F.; Di Maio, A.; Usiello, A.] Ceinge Biotecnol Avanzate, Naples, Italy. [Dodero, L.; Galbusera, A.; Bifone, A.; Gozzi, A.] Ist Italiano Tecnol, Ctr Neurosci & Cognit Syst, Rovereto, Italy. [Dodero, L.] Ist Italiano Tecnol, Genoa, Italy. [Federici, M.; Krashia, P.; Mercuri, N. B.] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy. [Federici, M.; Mercuri, N. B.] IRCCS Fdn Santa Lucia, Lab Neurol Sperimentale, Rome, Italy. [Migliarini, S.; Pasqualetti, M.] Univ Pisa, Dept Biol, Unit Cell & Dev Biol, Pisa, Italy. [Errico, F.; Napolitano, F.] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Scattoni, M. L.] Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Usiello, A.] Univ Naples 2, Dept Environm Biol & Pharmaceut Sci & Technol, Caserta, Italy. RP Usiello, A (reprint author), Ceinge Biotecnol Avanzate, Naples, Italy. EM Alessandro.usiello@ceinge.it; alessandro.gozzi@iit.it FU Istituto Italiano di Tecnologia; NARSAD, Italian Ministry of Health 'Young investigators' [GR3-2008]; Simons Foundation [SFARI 314688] FX The study was funded by the Istituto Italiano di Tecnologia, and supported by a NARSAD Independent Investigator 2013 award (AU), Italian Ministry of Health 'Young investigators' GR3-2008 (MLS) and by a grant from the Simons Foundation (SFARI 314688, AG). 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Psychiatr. PD AUG PY 2014 VL 4 AR e427 DI 10.1038/tp.2014.69 PG 11 WC Psychiatry SC Psychiatry GA AT3HR UT WOS:000344826900008 PM 25136890 ER PT J AU Grainger, C Williams, DM Lind, SE AF Grainger, Catherine Williams, David M. Lind, Sophie E. TI Metacognition, Metamemory, and Mindreading in High-Functioning Adults With Autism Spectrum Disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism; metacognition; metamemory; feeling-of-knowing; theory of mind; mindreading ID ASPERGER SYNDROME; AMNESIC PATIENTS; MEMORY; SELF; CHILDREN; MIND; INDIVIDUALS; EXPERIENCE; JUDGMENTS; KNOWLEDGE AB Metacognition refers to cognition about cognition and encompasses both knowledge of cognitive processes and the ability to monitor and control one's own cognitions. The current study aimed to establish whether metacognition is impaired in autism spectrum disorder (ASD). According to some theories, the ability to represent one's own mental states (an aspect of metacognition) relies on the same mechanism as the ability to represent others' mental states ("mindreading"). Given numerous studies have shown mindreading is impaired in ASD, there is good reason to predict concurrent impairments in metacognition. Metacognition is most commonly explored in the context of memory, often by assessing people's ability to monitor their memory processes. The current study addressed the question of whether people with ASD have difficulty monitoring the contents of their memory (alongside impaired mindreading). Eighteen intellectually high-functioning adults with ASD and 18 IQ-and age-matched neurotypical adults participated. Metamemory monitoring ability and mindreading ability were assessed by using a feeling-of-knowing task and the "animations" task, respectively. Participants also completed a self-report measure of metacognitive ability. In addition to showing impaired mindreading, participants with ASD made significantly less accurate feeling-of-knowing judgments than neurotypical adults, suggesting that metamemory monitoring (an aspect of metacognition) was impaired. Conversely, participants with ASD self-reported superior metacognitive abilities compared with those reported by neurotypical participants. This study provides evidence that individuals with ASD have metamemory monitoring impairments. The theoretical and practical implications of these findings for our current understanding of metacognition in ASD and typical development are discussed. C1 [Grainger, Catherine; Williams, David M.] Univ Kent, Sch Psychol, Keynes Coll, Canterbury CT2 7NP, Kent, England. [Lind, Sophie E.] City Univ London, Autism Res Grp, Dept Psychol, London, England. RP Grainger, C (reprint author), Univ Kent, Sch Psychol, Keynes Coll, Canterbury CT2 7NP, Kent, England. 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Abnorm. Psychol. PD AUG PY 2014 VL 123 IS 3 BP 650 EP 659 DI 10.1037/a0036531 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA AS1AH UT WOS:000344008000016 PM 24955572 ER PT J AU Meaux, E Roux, S Batty, M AF Meaux, Emilie Roux, Sylvie Batty, Magali TI Early visual ERPs are influenced by individual emotional skills SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE facial expression of emotion; visual ERPs; emotional skills; healthy adults ID EVENT-RELATED POTENTIALS; AUTISM SPECTRUM DISORDER; FACIAL EXPRESSIONS; BIPOLAR DISORDER; SEX-DIFFERENCES; FEARFUL FACES; CATEGORICAL PERCEPTION; BRAIN POTENTIALS; TIME-COURSE; SOCIAL-INTERACTION AB Processing information from faces is crucial to understanding others and to adapting to social life. Many studies have investigated responses to facial emotions to provide a better understanding of the processes and the neural networks involved. Moreover, several studies have revealed abnormalities of emotional face processing and their neural correlates in affective disorders. The aim of this study was to investigate whether early visual event-related potentials (ERPs) are affected by the emotional skills of healthy adults. Unfamiliar faces expressing the six basic emotions were presented to 28 young adults while recording visual ERPs. No specific task was required during the recording. Participants also completed the Social Skills Inventory (SSI) which measures social and emotional skills. The results confirmed that early visual ERPs (P1, N170) are affected by the emotions expressed by a face and also demonstrated that N170 and P2 are correlated to the emotional skills of healthy subjects. While N170 is sensitive to the subject's emotional sensitivity and expressivity, P2 is modulated by the ability of the subjects to control their emotions. We therefore suggest that N170 and P2 could be used as individual markers to assess strengths and weaknesses in emotional areas and could provide information for further investigations of affective disorders. C1 [Meaux, Emilie; Roux, Sylvie; Batty, Magali] Univ Tours, CHRU Tours, Ctr Univ Pedopsychiat, UMR Inserm U930, F-37044 Tours 9, France. RP Meaux, E (reprint author), Univ Med Ctr, Lab Behav Neurol & Imaging Cognit LabNIC, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM Emilie.Meaux@unige.ch FU Foundation ORANGE FX The authors thank all the subjects for their time and effort spent participating in this study. Special thanks are due to Sylvie Roux for her valuable help with the experimental design and analyses. This work was supported by grants from Foundation ORANGE. 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Cogn. Affect. Neurosci. PD AUG PY 2014 VL 9 IS 8 BP 1089 EP 1098 DI 10.1093/scan/nst084 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IA UT WOS:000342984900007 PM 23720573 ER PT J AU Schulte-Ruther, M Greimel, E Piefke, M Kamp-Becker, I Remschmidt, H Fink, GR Herpertz-Dahlmann, B Konrad, K AF Schulte-Ruether, Martin Greimel, Ellen Piefke, Martina Kamp-Becker, Inge Remschmidt, Helmut Fink, Gereon R. Herpertz-Dahlmann, Beate Konrad, Kerstin TI Age-dependent changes in the neural substrates of empathy in autism spectrum disorder SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE social cognition; theory of mind; medial prefrontal cortex; facial emotion; developmental trajectories ID NETWORKS SUPPORTING EMPATHY; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; RESPONSE-INHIBITION; COGNITIVE CONTROL; MIRROR NEURON; MIND; BRAIN; CHILDREN; SELF AB In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12-31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face's emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the 'fine-tuning' of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms. C1 [Schulte-Ruether, Martin; Greimel, Ellen; Konrad, Kerstin] Univ Hosp RWTH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Child Neuropsychol Sect, D-52074 Aachen, Germany. [Schulte-Ruether, Martin; Greimel, Ellen; Piefke, Martina; Fink, Gereon R.; Konrad, Kerstin] Forschungszentrum Julich, Inst Neurosci & Med INM 3, D-52425 Julich, Germany. [Schulte-Ruether, Martin; Herpertz-Dahlmann, Beate; Konrad, Kerstin] Univ Hosp Munich, JARA Translat Brain Med, Munich, Germany. [Greimel, Ellen] Univ Hosp Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. [Piefke, Martina] Univ Witten Herdecke, Dept Psychol & Psychotherapy, Witten, Germany. [Kamp-Becker, Inge; Remschmidt, Helmut] Univ Marburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, Marburg, Germany. [Fink, Gereon R.] Univ Hosp Cologne, Dept Neurol, Cologne, Germany. [Herpertz-Dahlmann, Beate] Univ Hosp RWTH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany. RP Schulte-Ruther, M (reprint author), Univ Hosp RWTH Aachen, Dept Child & Adolescent Psychiat, Child Neuropsychol Sect, Neuenhofer Weg 21, D-52074 Aachen, Germany. EM mschulte@ukaachen.de RI Konrad, Kerstin/H-7747-2013; Fink, Gereon/E-1616-2012 OI Konrad, Kerstin/0000-0001-9039-2615; Fink, Gereon/0000-0002-8230-1856 FU Bundeministerium fur Bildung und Forschung [01GW0751]; Hans-Lungwitz-Foundation FX The authors are grateful to all volunteers who took part in this study. They thank their colleagues in the Brain Imaging Physics (INM-4) and Cognitive Neuroscience groups (INM-3) at the Research Center Julich (Institute of Neuroscience and Medicine) and the Child Neuropsychology section at the University Hospital RWTH Aachen for their support and helpful advice. K.K. and B.H.-D. were supported by the Bundeministerium fur Bildung und Forschung grant 01GW0751. M. P. was supported by a grant from the Hans-Lungwitz-Foundation. 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Cogn. Affect. Neurosci. PD AUG PY 2014 VL 9 IS 8 BP 1118 EP 1126 DI 10.1093/scan/nst088 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IA UT WOS:000342984900010 PM 23784073 ER PT J AU Fan, YT Chen, CY Chen, SC Decety, J Cheng, YW AF Fan, Yang-Teng Chen, Chenyi Chen, Shih-Chuan Decety, Jean Cheng, Yawei TI Empathic arousal and social understanding in individuals with autism: evidence from fMRI and ERP measurements SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE autism spectrum disorder (ASD); empathy; pressure pain thresholds (PPT); functional MRI (fMRI); electroencephalography/event-related potentials (EEG/ERP) ID EVENT-RELATED POTENTIALS; MIRROR NEURON SYSTEM; SPECTRUM DISORDERS; ASPERGER-SYNDROME; FUNCTIONING AUTISM; EMOTIONAL EMPATHY; CINGULATE CORTEX; INSULAR CORTEX; PAIN; BRAIN AB Lack of empathy is a hallmark of social impairments in individuals with autism spectrum disorder (ASD). However, the concept empathy encompasses several socio-emotional and behavioral components underpinned by interacting brain circuits. This study examined empathic arousal and social understanding in individuals with ASD and matched controls by combining pressure pain thresholds (PPT) with functional magnetic resonance imaging (study 1) and electroencephalography/event-related potentials and eye-tracking responses (study 2) to empathy-eliciting stimuli depicting physical bodily injuries. Results indicate that participants with ASD had lower PPT than controls. When viewing body parts being accidentally injured, increased hemodynamic responses in the somatosensory cortex (SI/SII) but decreased responses in the anterior mid-cingulate and anterior insula as well as heightened N2 but preserved late-positive potentials (LPP) were detected in ASD participants. When viewing a person intentionally hurting another, decreased hemodynamic responses in the medial prefrontal cortex and reduced LPP were observed in the ASD group. PPT was a mediator for the SI/SII response in predicting subjective unpleasantness ratings to others' pain. Both ASD and control groups had comparable mu suppression, indicative of typical sensorimotor resonance. The findings demonstrate that, in addition to reduced pain thresholds, individuals with ASD exhibit heightened empathic arousal but impaired social understanding when perceiving others' distress. C1 [Fan, Yang-Teng; Chen, Chenyi; Chen, Shih-Chuan; Cheng, Yawei] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. [Fan, Yang-Teng; Chen, Chenyi; Chen, Shih-Chuan; Cheng, Yawei] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan. [Decety, Jean] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. [Decety, Jean] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Cheng, Yawei] Natl Yang Ming Univ Hosp, Dept Rehabil, Yilan, Taiwan. RP Cheng, YW (reprint author), Natl Yang Ming Univ, Inst Neurosci, 155,Sec 2,St Linong, Taipei 112, Taiwan. EM ywcheng2@ym.edu.tw FU National Science Council [NSC 99-2314-B-010-037-MY3, NSC 100-2628-H-010-001-MY3]; National Yang-Ming University Hospital [RD 2011-005]; Health Department of Taipei City Government [10201-62-064]; Ministry of Education (Aim for the Top University Plan); NSF [BCS-0718480] FX The authors thank Dr. Yu-Yu Wu for helpful support on clinical assessments. The study was funded by National Science Council (NSC 99-2314-B-010-037-MY3; NSC 100-2628-H-010-001-MY3), National Yang-Ming University Hospital (RD 2011-005), the Health Department of Taipei City Government (10201-62-064) and a grant from the Ministry of Education (Aim for the Top University Plan). Dr. Jean Decety was supported by an NSF grant (BCS-0718480). 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Cogn. Affect. Neurosci. PD AUG PY 2014 VL 9 IS 8 BP 1203 EP 1213 DI 10.1093/scan/nst101 PG 11 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IA UT WOS:000342984900020 PM 23929944 ER PT J AU Kroger, A Bletsch, A Krick, C Siniatchkin, M Jarczok, TA Freitag, CM Bender, S AF Kroeger, Anne Bletsch, Anke Krick, Christoph Siniatchkin, Michael Jarczok, Tomasz A. Freitag, Christine M. Bender, Stephan TI Visual event-related potentials to biological motion stimuli in autism spectrum disorders SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE event-related-potentials; motion perception; P100; N200; hemisphere-asymmetry ID SUPERIOR TEMPORAL SULCUS; EVOKED-POTENTIALS; DEVELOPMENTAL-CHANGES; COHERENT MOTION; YOUNG-CHILDREN; ATYPICAL FACE; ERP EVIDENCE; TIME-COURSE; PERCEPTION; LANGUAGE AB Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD. C1 [Kroeger, Anne; Bletsch, Anke; Siniatchkin, Michael; Jarczok, Tomasz A.; Freitag, Christine M.; Bender, Stephan] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany. [Krick, Christoph] Saarland Univ Hosp, Dept Neuroradiol, D-66424 Homburg, Germany. [Bender, Stephan] Tech Univ Dresden, Dept Child & Adolescent Psychiat & Psychotherapy, D-01307 Dresden, Germany. RP Kroger, A (reprint author), Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Deutschordenstr 50, D-60528 Frankfurt, Germany. EM Anne.Kroeger@kgu.de FU foundation of Marie Christine Held and Erika Hecker; German Research foundation 'Deutsche Forschungsgemeinschaft' [FR2069/2-1]; LOEWE-Program 'Neuronal Coordination Research Focus Frankfurt' (NeFF) FX First, we thank all families, who supported our work by participating in our study. We also thank Jennifer Bohm and Katharina Hof for assistance with the data collection, Benjamin Teufert for data calculations and our clinical colleagues for helping us with recruiting participants. This work was supported by the foundation of Marie Christine Held and Erika Hecker to A.K., the German Research foundation 'Deutsche Forschungsgemeinschaft' to C.M.F. (FR2069/2-1), and by the LOEWE-Program 'Neuronal Coordination Research Focus Frankfurt' (NeFF) to C.M.F. and S.B. 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Cogn. Affect. Neurosci. PD AUG PY 2014 VL 9 IS 8 BP 1214 EP 1222 DI 10.1093/scan/nst103 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AQ7IA UT WOS:000342984900021 PM 23887808 ER PT J AU Hebron, J Humphrey, N AF Hebron, Judith Humphrey, Neil TI Exposure to bullying among students with autism spectrum conditions: A multi-informant analysis of risk and protective factors SO AUTISM LA English DT Article DE bullying; protection; risk; school; victimisation ID HIGH-FUNCTIONING AUTISM; SCHOOL-AGED CHILDREN; PARENTAL INVOLVEMENT; ACADEMIC-ACHIEVEMENT; PEER RELATIONSHIPS; ASPERGER-SYNDROME; ADOLESCENT BOYS; VICTIMIZATION; DISORDERS; PREVALENCE AB Research has consistently shown that children and young people with autism spectrum conditions are more likely to be bullied than those with other or no special educational needs. The aim of this study was to examine risk and protective factors that could help to explain variation in exposure to bullying within this group. A sample of 722 teachers and 119 parents reported on their child's experience of being bullied. This response variable was regressed onto a range of explanatory variables representing individual and contextual factors. The teacher-and parent-rated regression models were statistically significant, explaining large proportions of variance in exposure to bullying. Behaviour difficulties and increased age were associated with bullying in both models. Positive relationships and attending a special school were associated with a decrease in bullying in the teacher model, with use of public/school transport predicting an increase. In the parent model, special educational needs provision at School Action Plus (as opposed to having a Statement of Special Educational Needs) was a significant risk factor, and higher levels of parental engagement and confidence were associated with reductions in bullying. These findings are discussed in relation to the autism spectrum conditions literature, and opportunities for intervention are considered. C1 [Hebron, Judith; Humphrey, Neil] Univ Manchester, Manchester M13 9PL, Lancs, England. RP Hebron, J (reprint author), Univ Manchester, Sch Educ, Oxford Rd, Manchester M13 9PL, Lancs, England. 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Camacho, Fabian Leslie, Douglas TI Psychotropic medication trends among children and adolescents with autism spectrum disorder in the Medicaid program SO AUTISM LA English DT Article DE autism spectrum disorder; children and adolescents; Medicaid; psychotropic medications ID PREVALENCE; PATTERNS; MANAGEMENT; DRUGS AB This study characterized psychotropic medication use among Medicaid-enrolled children and adolescents with autism spectrum disorders by examining trends over time, including length of treatment and polypharmacy using 4 years of administrative claims data from 41 state Medicaid programs (2000-2003). The data set included nearly 3 million children and adolescents who were 17 years or younger. Approximately, 65% of children with autism spectrum disorder received a psychotropic medication. The results indicate an increasing overall trend in the use of psychotropic drugs among children and adolescents with autism spectrum disorders. 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Elia, Maurizio TI Effects of repetitive transcranial magnetic stimulation in performing eye-hand integration tasks: Four preliminary studies with children showing low-functioning autism SO AUTISM LA English DT Article DE autism spectrum disorders; premotor cortex; rehabilitation; transcranial magnetic stimulation ID SPECTRUM DISORDERS; TOOL USE; MOTOR; ATTENTION; CORTEX; BRAIN; INTERFERENCE; PREVALENCE; DEFICITS AB This report, based on four studies with children with low-functioning autism, aimed at evaluating the effects of repetitive transcranial magnetic stimulation delivered on the left and right premotor cortices on eye-hand integration tasks; defining the long-lasting effects of high-frequency repetitive transcranial magnetic stimulation; and investigating the real efficacy of high-frequency repetitive transcranial magnetic stimulation by comparing three kinds of treatments (high-frequency repetitive transcranial magnetic stimulation, a traditional eye-hand integration training, and both treatments combined). Results showed a significant increase in eye-hand performances only when high-frequency repetitive transcranial magnetic stimulation was delivered on the left premotor cortex; a persistent improvement up to 1 h after the end of the stimulation; better outcomes in the treatment combining high-frequency repetitive transcranial magnetic stimulation and eye-hand integration training. Based on these preliminary findings, further evaluations on the usefulness of high-frequency repetitive transcranial magnetic stimulation in rehabilitation of children with autism are strongly recommended. C1 [Panerai, Simonetta; Tasca, Domenica; Lanuzza, Bartolo; Trubia, Grazia; Ferri, Raffaele; Musso, Sabrina; Di Guardo, Giuseppe; Barone, Concetta; Gaglione, Maria P.; Elia, Maurizio] IRCCS Assoc Oasi Maria SS, Troina, EN, Italy. [Alagona, Giovanna] Azienda Osped Emergenza Cannizzaro, Catania, Italy. RP Panerai, S (reprint author), Oasi Inst Res Mental Retardat & Brain Aging, Via Conte Ruggero 73, I-94018 Troina, EN, Italy. 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Muncer, Steven J. TI Parents' views of the National Autistic Society's EarlyBird Plus Programme SO AUTISM LA English DT Article DE autism; EarlyBird Plus; parent training programme; post-diagnostic support; psychoeducation ID PRESCHOOL-CHILDREN; SPECTRUM DISORDER; DOWN-SYNDROME; INTERVENTION; DIAGNOSIS; MOTHERS AB Parent training interventions are recommended for parents soon after their child's autism spectrum condition diagnosis with the aim of improving parents' psychological well-being and coping, as well as the child's behaviour. This report explores parents' views of the EarlyBird Plus Programme through data collected routinely in the post-programme questionnaire. Participants' reported increased understanding of autism and improvements in their communication with their child and their ability to manage their child's behaviour. Parents appeared to value the opportunity to meet with other parents, and the programme seemed acceptable to the majority of parents who attended. 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In this study, we examined the possibility of promoting imitation and joint attention by means of a training programme specifically designed for low-intensity, non-residential treatment. Two matched groups of 18 children each participated in the study. The experimental group, receiving the training programme, improved significantly more on joint attention than the group receiving only treatment as usual. Only the experimental group obtained a significantly higher imitation score during the post-test compared to the pre-test. This study shows that it is possible to promote joint attention with a low-intensity treatment programme. The results concerning imitation are more modest. Future replications should involve measures of stability and generalization. C1 [Warreyn, Petra; Roeyers, Herbert] Univ Ghent, B-9000 Ghent, Belgium. RP Warreyn, P (reprint author), Univ Ghent, Dept Expt Clin & Hlth Psychol, Res Grp Dev Disorders, Henri Dunantlaan 2, B-9000 Ghent, Belgium. 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This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions' similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout. C1 [Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Bejerot, Susanne] St Goran Hosp, VUB KOGNUS, Northern Stockholm Psychiat, SE-11281 Stockholm, Sweden. RP Hesselmark, E (reprint author), St Goran Hosp, VUB KOGNUS, Northern Stockholm Psychiat, SE-11281 Stockholm, Sweden. 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This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents with autism spectrum disorder and 19 carefully matched typically developing controls completed the Dewey Story Test. 'Explicit' (multiple-choice answering format) and 'implicit' (free interview) measures of social cognition were obtained. Autism spectrum disorder participants did not differ from controls regarding explicit social cognition performance. However, the autism spectrum disorder group performed more poorly than controls on implicit social cognition performance in terms of spontaneous perspective taking and social awareness. Findings suggest that social cognition alterations in autism spectrum disorder are primarily implicit in nature and that an apparent absence of social cognition difficulties on certain tests using rather explicit testing formats does not necessarily mean social cognition typicality in autism spectrum disorder. C1 [Callenmark, Bjorn] Stockholm Cty Council, Stockholm, Sweden. [Callenmark, Bjorn; Kjellin, Lars] Orebro Cty Council, Orebro, Sweden. [Kjellin, Lars] Univ Orebro, Orebro, Sweden. [Ronnqvist, Louise] Umea Univ, S-90187 Umea, Sweden. [Bolte, Sven] Karolinska Inst, S-10401 Stockholm, Sweden. RP Bolte, S (reprint author), Karolinska Inst KIND, CAP Res Ctr, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, Gavlegatan 22 B, S-11330 Stockholm, Sweden. EM sven.bolte@ki.se CR Baird J. 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Campbell, Susan B. Butler, Derrecka Iverson, Jana M. TI Maternal verbal responses to communication of infants at low and heightened risk of autism SO AUTISM LA English DT Article DE autism spectrum disorder; communication development; gesture; parent verbal responsiveness ID YOUNG-CHILDREN; SIBLINGS; LANGUAGE; MOTHERS; SPECTRUM; GESTURES AB This study investigates mothers' responses to infant communication among infants at heightened genetic risk (high risk) of autism spectrum disorder compared to infants with no such risk (low risk). A total of 26 infants, 12 of whom had an older sibling with autism spectrum disorder, were observed during naturalistic in-home interaction and semistructured play with their mothers at 13 and 18 months of age. Results indicate that overall, mothers of low-risk and high-risk infants were highly and similarly responsive to their infants' communicative behaviors. However, examination of infant vocal and gestural communication development together with maternal verbal responses and translations (i.e. verbally labeling a gesture referent) suggests that delays in early communication development observed among high-risk infants may alter the input that these infants receive; this in turn may have cascading effects on the subsequent development of communication and language. C1 [Leezenbaum, Nina B.; Campbell, Susan B.; Iverson, Jana M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Butler, Derrecka] No Illinois Univ, De Kalb, IL 60115 USA. RP Leezenbaum, NB (reprint author), Univ Pittsburgh, Dept Psychol, 3309 Sennott Sq,210 S Bouquet St, Pittsburgh, PA 15260 USA. 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How typically developing children respond initially to children with autism SO AUTISM LA English DT Article DE autism spectrum disorder; facial expressivity; first impressions; friendship formation ID PHYSICAL ATTRACTIVENESS; IMPRESSION-FORMATION; ASPERGERS-SYNDROME; 1ST IMPRESSIONS; EMOTION; INTERVENTION; CONSEQUENCES; PERCEPTIONS; ADOLESCENTS; LONELINESS AB Research investigating expressivity in children with autism spectrum disorder has reported flat affect or bizarre facial expressivity within this population; however, the impact expressivity may have on first impression formation has received little research input. We examined how videos of children with autism spectrum disorder were rated for expressivity by adults blind to the condition. We further investigated the friendship ratings given by 44 typically developing children to the same videos. These ratings were compared to friendship ratings given to video clips of typically developing children. Results demonstrated that adult raters, blind to the diagnosis of the children in the videos, rated children with autism spectrum disorder as being less expressive than typically developing children. These autism spectrum disorder children were also rated lower than typically developing children on all aspects of our friendship measures by the 44 child raters. Results suggest that impression formation is less positive towards children with autism spectrum disorder than towards typically developing children even when exposure time is brief. C1 [Stagg, Steven D.] Anglia Ruskin Univ, Cambridge CB1 1PT, England. [Slavny, Rachel; Hand, Charlotte; Cardoso, Alice; Smith, Pamela] Univ London, London WC1E 7HU, England. RP Stagg, SD (reprint author), Anglia Ruskin Univ, East Rd, Cambridge CB1 1PT, England. 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Burrell, T. Lindsey Jaquess, David L. TI The Autism MEAL Plan: A parent-training curriculum to manage eating aversions and low intake among children with autism SO AUTISM LA English DT Article DE autism; food selectivity; intervention; mealtime problems; parent training; pediatric feeding disorders ID SPECTRUM DISORDERS; FEEDING PROBLEMS; FOOD SELECTIVITY; DISRUPTIVE BEHAVIOR; TREATMENT PROGRAM; YOUNG-CHILDREN; OUTCOMES; INTERVENTION; FAMILIES; STRESS AB Feeding problems represent a frequent concern reported by caregivers of children with autism spectrum disorders, and growing evidence suggests atypical patterns of intake may place this population at risk of nutritional and/or related medical issues, including chronic vitamin and mineral deficiencies, poor bone growth, and obesity. This combination of factors emphasizes a clear need to identify and disseminate evidence-based treatment of feeding problems associated with autism spectrum disorders. Behavioral intervention represents an effective treatment for chronic feeding concerns in this population; however, evidence has largely been established with trained therapists working in highly structured settings. This pilot study seeks to fill this gap in the literature by describing and evaluating the Autism MEAL Plan, a behaviorally based parent-training curriculum to address feeding problems associated with autism spectrum disorders. We assessed the feasibility of the intervention in terms of program content and study protocol (e. g. recruitment and retention of participants, assessment procedures), as well as efficacy in terms of changes in feeding behaviors. A total of 10 families participated in the treatment condition, and the program was evaluated using a waitlist control design (n = 9), representing the first randomized-control study of a feeding intervention in autism spectrum disorders. Results provide provisional support regarding the utility of the program, including high social validity, parent perception of effectiveness, and reduced levels of caregiver stress following intervention. Implications, limitations, and future directions for this line of research are discussed. C1 [Sharp, William G.; Burrell, T. Lindsey; Jaquess, David L.] Marcus Autism Ctr, Atlanta, GA 30329 USA. [Sharp, William G.; Jaquess, David L.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Burrell, T. Lindsey] Texas Tech Univ, Lubbock, TX 79409 USA. RP Sharp, WG (reprint author), Marcus Autism Ctr, Pediat Psychol & Feeding Disorders Program, 1920 Briarcliff Rd, Atlanta, GA 30329 USA. 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Method: A total of 32 children aged 9-13 years were randomised to immediate or delayed therapy using the 'Exploring Feelings' manual (Attwood, 2004). Child and parent groups were run in parallel, for seven weekly sessions, under the supervision of experienced psychologists. The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months. Results: Children met diagnostic criteria for 1-6 anxiety disorders (median 3). At end point, both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms. Fidelity of delivery of the group therapy was high, and attendance was 91%. Conclusions: This pilot trial established that children and families were willing to be recruited and randomised, the outcome measures were acceptable, the format and content of the groups were feasible within UK child and adolescent mental health services, the intervention was appreciated by families and attrition was very small. C1 [McConachie, Helen; Rodgers, Jacqui; Freeston, Mark; Hemm, Cahley; Steen, Nick; Le Couteur, Ann] Newcastle Univ, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [McLaughlin, Eleanor; Grahame, Victoria; Taylor, Helen; Honey, Emma; Tavernor, Laura] Northumberland Tyne & Wear NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England. RP McConachie, H (reprint author), Newcastle Univ, Royal Victoria Infirm, Inst Hlth & Soc, Sir James Spence Inst, 3rd Floor, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. 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We examined three groups of children (18-60 months) comparable in age (18-24 month, 24-36 month, 36-60 preschool subgroups) and gender distribution: n = 86 with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) autism spectrum disorders; n = 76 with developmental delay without autism spectrum disorders; and n = 97 with typical development. The Three-Item Direct Observation Screen test included the following (a) Joint Attention, (b) Eye Contact, and (c) Responsiveness to Name. The parent Social Communication Questionnaire ratings had a sensitivity of .73 and specificity of .70 for diagnosis of autism spectrum disorders. The Three-Item Direct Observation Screen test item Joint Attention had a sensitivity of .82 and specificity of .90, Eye Contact had a sensitivity of .89 and specificity of .91, and Responsiveness to Name had a sensitivity of .67 and specificity of .87. In the Three-Item Direct Observation Screen test, having at least one of the three items positive had a sensitivity of .95 and specificity of .85. Age, diagnosis of autism spectrum disorder, and developmental level were important factors affecting sensitivity and specificity. The results indicate that augmentation of autism spectrum disorder screening by observational items completed by trained pediatric-oriented professionals can be a highly effective tool in improving screening performance. If supported by future population studies, the results suggest that primary care practitioners will be able to be trained to use this direct procedure to augment screening for autism spectrum disorders in the community. C1 [Oner, Pinar; Oner, Ozgur] Dr Sami Ulus Childrens Hosp, Child & Adolescent Psychiat Dept, Autism Ctr Excellence, TR-06100 Ankara, Turkey. [Munir, Kerim] Childrens Hosp Boston, Boston, MA USA. [Munir, Kerim] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Oner, O (reprint author), Dr Sami Ulus Childrens Hosp, Dept Child & Adolescent Psychiat, TR-06100 Ankara, Turkey. 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TI The presence of migraines and its association with sensory hyperreactivity and anxiety symptomatology in children with autism spectrum disorder SO AUTISM LA English DT Article DE anxiety; autism; hyperreactivity; migraines; sensory processing ID OVER-RESPONSIVITY; SYMPTOMS AB Migraine headaches are associated with sensory hyperreactivity and anxiety in the general population, but it is unknown whether this is also the case in autism spectrum disorders. This pilot study asked parents of 81 children (aged 7-17 years) with autism spectrum disorders to report their child's migraine occurrence, sensory hyperreactivity (Sensory Over-Responsivity Inventory), and anxiety symptoms (Spence Child Anxiety Scale). Children with autism spectrum disorders who experienced migraine headaches showed greater sensory hyperreactivity and anxiety symptomatology (p < 0.01; medium effect size for both) than those without migraines. Sensory hyperreactivity and anxiety symptomatology were additionally correlated (rho = 0.31, p = 0.005). This study provides preliminary evidence for a link between migraine headaches, sensory hyperreactivity, and anxiety symptomatology in autism spectrum disorders, which may suggest strategies for subtyping and exploring a common pathogenesis. C1 [Sullivan, Jillian C.; Miller, Lucy J.; Nielsen, Darcy M.; Schoen, Sarah A.] Sensory Proc Disorder Fdn, Greenwood Village, CO 80111 USA. [Miller, Lucy J.; Schoen, Sarah A.] Rocky Mt Univ Hlth Profess, Provo, UT USA. [Miller, Lucy J.] Univ Colorado Denver, Denver, CO USA. RP Sullivan, JC (reprint author), Sensory Proc Disorder Fdn, 5420 S Quebec St,Suite 135, Greenwood Village, CO 80111 USA. 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Mandell, David S. TI Home- and Community-Based Waivers for Children With Autism: Effects on Service Use and Costs SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Medicaid; outpatient care; inpatient/long-term care; home- and community-based waivers ID HEALTH-CARE EXPENDITURES; LONG-TERM CARE; MEDICAID HOME; SPECTRUM DISORDERS; PROGRAM; DIAGNOSIS; CLAIMS; STATES AB We examined (a) the associations between Medicaid home and community-based waiver participation and service use and expenditures among children with ASD; and (b) how states' waiver spending moderates these effects. We used 2005 Medicaid claims to identify a sample of children with autism spectrum disorder (ASD). We selected two comparison groups who had no waiver participation: (a) children who were eligible for Medicaid through disability (disability group), and (b) children who had at least one inpatient/long-term care (IP/LT) episode (IP/LT group). Waiver participants were less likely to use IP/LT services and had lower associated expenditures than the disability group. As states' waiver spending increased, waiver participants became increasingly less likely to use IP/LT services. Waiver participants had more outpatient visits and associated expenditures; this difference increased as state waiver spending increased. Compared with the IP/LT group, waiver participants had lower IP/LT expenditures, more outpatient visits, and associated expenditures. Higher state waiver generosity increased this effect on outpatient visits and expenditures. C1 [Cidav, Zuleyha; Marcus, Steven C.; Mandell, David S.] Univ Penn, Philadelphia, PA 19104 USA. RP Cidav, Z (reprint author), Univ Penn, 3535 Market St, Philadelphia, PA 19104 USA. 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Dev. Disabil. PD AUG PY 2014 VL 52 IS 4 BP 239 EP 248 DI 10.1352/1934-9556-52.4.239 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AQ3VW UT WOS:000342722600001 PM 25061768 ER PT J AU Mehling, MH Tasse, MJ AF Mehling, Margaret H. Tasse, Marc J. TI Empirically Derived Model of Social Outcomes and Predictors for Adults With ASD SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism Spectrum Disorder; social outcomes; community inclusion; social relationships; friendships; choice; access to services; social determination; National Core Indicators ID RECEPTIVE LANGUAGE DISORDER; AUTISM SPECTRUM DISORDERS; QUALITY-OF-LIFE; FOLLOW-UP; DISABILITIES; ADOLESCENCE; CHILDHOOD; CHILDREN AB This study used data from the National Core Indicators (NCI) Survey to derive an empirically validated measurement model for social outcomes and associated constructs for both individuals with Autism Spectrum Disorder (ASD) and individuals with other disabilities. Items consistent with the survey structure of the NCI were selected as initial indicators of the latent constructs Social Relationships, Community Inclusion, and Opportunity for Choice in factor analyses. Results yielded a novel factor structure that is different from the original NCI survey structure. Three factors emerged as a result of these analyses: Personal Control, Social Determination, and Social Participation and Relationships. The factor structure of each of these constructs was consistent although not identical across individuals with ASD and individuals with developmental disabilities other than ASD. C1 [Mehling, Margaret H.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Tasse, Marc J.] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. RP Mehling, MH (reprint author), Ohio State Univ, Dept Psychol, Nisonger Ctr, McCampbell Hall,1581 Dodd Dr, Columbus, OH 43210 USA. 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A., 1996, FOCUS AUTISM OTHER D, V11, P3 Seltzer MM, 2003, J AUTISM DEV DISORD, V33, P565, DOI 10.1023/B:JADD.0000005995.02453.0b Seltzer MM, 2004, MENT RETARD DEV D R, V10, P234, DOI 10.1002/mrdd.20038 Smith KRM, 2010, RES DEV DISABIL, V31, P1366, DOI 10.1016/j.ridd.2010.07.002 Venter A., 1992, HIGH FUNCTIONING IND, P187 Whitehouse AJO, 2009, INT J LANG COMM DIS, V44, P511, DOI 10.1080/13682820802708098 NR 31 TC 1 Z9 1 PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES PI WASHINGTON PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA SN 1934-9491 EI 1934-9556 J9 INTELLECT DEV DISAB JI Intellect. Dev. Disabil. PD AUG PY 2014 VL 52 IS 4 BP 282 EP 295 DI 10.1352/1934-9556-52.4.282 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AQ3VW UT WOS:000342722600005 PM 25061772 ER PT J AU Wehman, P Chan, F Ditchman, N Kang, HJ AF Wehman, Paul Chan, Fong Ditchman, Nicole Kang, Hyun-Ju TI Effect of Supported Employment on Vocational Rehabilitation Outcomes of Transition-Age Youth With Intellectual and Developmental Disabilities: A Case Control Study SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE supported employment; intellectual disability; developmental disability; vocational rehabilitation; propensity score matching ID AUTISM SPECTRUM DISORDER; YOUNG-ADULTS; EXPERIENCES; SERVICES; SCHOOL; WORK AB The purpose of this study was to examine the effect of supported employment intervention on the employment outcomes of transition-age youth with intellectual and developmental disabilities served by the public vocational rehabilitation system using a case-control study design. Data for this study were extracted from the Rehabilitation Services Administration Case Service Report (RSA911) database for fiscal year 2009. The sample included 23,298 youth with intellectual and developmental disabilities aged between 16 and 25 years old at the time of application. The classification and regression tree (CART) method was used to estimate propensity scores and to adjust for selection bias on the basis of all prominent covariates relevant to the dependent variable (i.e., competitive employment). Results yielded six homogeneous subgroups, and receipt of supported employment was found to increase the employment rates across all of the groups. The effect of supported employment was especially strong for youth who were Social Security beneficiaries, special education students, and individuals with intellectual disabilities or autism who were high school graduates. These findings suggest that supported employment is an effective service for enhancing the vocational rehabilitation outcomes of young adults and provides valuable information for policy makers, health care providers, rehabilitation counselors, and educators. C1 [Wehman, Paul] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA 23284 USA. [Chan, Fong] Univ Wisconsin Madison, Rehabil Res & Training Ctr Evidence Based Vocat R, Madison, WI USA. [Ditchman, Nicole] IIT, Dept Psychol, Chicago, IL 60616 USA. [Kang, Hyun-Ju] Univ Wisconsin Madison, Dept Rehabil Psychol & Special Educ, Madison, WI USA. RP Wehman, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, 1314 W Main St, Richmond, VA 23284 USA. 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Government Accountability Office, 2005, GAO05865 Wehman P, 2005, J HEAD TRAUMA REHAB, V20, P115, DOI 10.1097/00001199-200503000-00001 Wehman P, 2014, J DISABIL POLICY STU, V25, P30, DOI 10.1177/1044207313518071 Wehman P., 2014, PREDICTORS SUC UNPUB Wehman P., 2012, RES PRACT PERS SEV D, V37, P1 Wehman P, 1981, COMPETITIVE EMPLOYME Wehman P., 2007, REAL WORK REAL PAY I Wehman P., 1997, SUPPORTED EMPLOYMENT WEHMAN PH, 1991, ARCH PHYS MED REHAB, V72, P101 Zhang H, 1999, RECURSIVE PARTITIONI NR 46 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 1934-9491 EI 1934-9556 J9 INTELLECT DEV DISAB JI Intellect. Dev. Disabil. PD AUG PY 2014 VL 52 IS 4 BP 296 EP 310 DI 10.1352/1934-9556-52.4.296 PG 15 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AQ3VW UT WOS:000342722600006 PM 25061773 ER PT J AU Shaddel, F Ghazirad, M Bryant, M AF Shaddel, Farshad Ghazirad, Marjan Bryant, Mark TI What Is the Best Available Evidence for Using Homeopathy in Patients with Intellectual Disabilities? SO IRANIAN JOURNAL OF PEDIATRICS LA English DT Review DE Homeopathy; Intellectual Disability; Mental Retardation; Learning Disability; Systematic Review ID RANDOMIZED CONTROLLED-TRIALS; DISORDER; CHILDREN AB Objective: The debate about the effectiveness of homeopathy hits the headlines from time to time. Reported evidences for the role of homeopathy in psychiatric illness relevant to people with intellectual disabilities are patchy and inconsistent In this review we summarize the best available evidence for the use of homeopathy to treat the psychiatric disorders common in this population. Methods: Systematic literature review was conducted through February 2012 to July 2012 in AMED, CINHAL, BNI, EMBASE, MEDLINE, PSYCHINFO and GOOGLE SCHOLAR In the next steps thirty eight homeopathic associations were contacted and a top-up literature search was done on Scopus and World of Science databases till March 2014. Twelve relevant clinical trials were identified and included in this study. The quality of each trial was assessed by the Oxford quality scoring system (Known as Jadad score) as well as subjective review by two reviewers independently (good versus poor). Findings: The largest body of evidence pertained to the use of homeopathy in the treatment of attention deficit hyperactivity disorder (ADHD). There is heterogeneity in the quality of trials and also the outcome of studies but overall our findings suggest some potential for using homeopathy in ADHD. Current evidences do not support the use of homeopathy for treatment of speech and language difficulties. There was only one trial concerning the use of homeopathy in Autistic Spectrum Disorder. This was of a poor quality and unable to provide any recommendation. Conclusion: Whilst acknowledging the risk of publication and language bias in our study, the currently available evidences are neither conclusive nor comprehensive enough to give us a clear picture for the use of homeopathy in patients with intellectual disabilities. There are large gaps in the body of evidence concerning the role of homeopathy in the treatment of common disorders in intellectual disability, such as autism, challenging behavior or developmental arrest in childhood. C1 [Shaddel, Farshad; Ghazirad, Marjan] Univ Oxford, Oxford Learning Disabil, Oxford OX1 2JD, England. Dermot Rowe Lib, Oxford Learning Disabil, Oxford, England. RP Shaddel, F (reprint author), Univ Oxford, Royal Coll Psychiat Oxford Deanery, Oxford OX1 2JD, England. EM f_shaddel@yahoo.com RI ezeluomba, ndubuisi/O-2495-2014 OI ezeluomba, ndubuisi/0000-0002-6547-9011 CR Adler RH, EUR J PEDIAT Aust N., 2013, FOCUS ALTERNATIVE CO, V18, P171 Bull Leona, 2007, Complement Ther Clin Pract, V13, P15, DOI 10.1016/j.ctcp.2006.07.003 Davidson JRT, 2011, J CLIN PSYCHIAT, V72, P795, DOI 10.4088/JCP.10r06580 Dhawale KM, 2011, EXPLORING ROLE HOMEO Ernst E, 2010, MED J AUSTRALIA, V192, P458 Frei H, 2007, HOMEOPATHY, V96, P35 Frei H, 2005, EUR J PEDIATR, V164, P758, DOI 10.1007/s00431-005-1735-7 Frei H, 2001, Br Homeopath J, V90, P183, DOI 10.1054/homp.1999.0506 Haynes RB, 2005, CLIN EPIDEMIOLOGY, P31 Heirs M, 2007, COCHRANE DATABASA SY, V17 Jacobs J, 2005, J ALTERN COMPLEM MED, V11, P799, DOI 10.1089/acm.2005.11.799 Jadad Alejandro R., 2007, RANDOMIZED CONTROLLE Lamont J., 1998, BIOMEDICAL THERAPY, V16, P219 Laures JS, 2004, DISABIL REHABIL, V26, P315, DOI 10.1080/0963828032000174106 Lottering JB, 2006, RELATIVE EFFICACY AD Nuhn T, 2010, HOMEOPATHY, V99, P76, DOI 10.1016/j.homp.2009.11.002 Oberai SP, 2013, INDIAN J RES HOMOEOP, V7, P4 Olivo SA, 2008, PHYS THER, V88, P156, DOI 10.2522/ptj.20070147 Patel NC, 2002, PHARMACOTHERAPY, V22, P905, DOI 10.1592/phco.22.11.905.33622 Robinson T W, 2001, Br Homeopath J, V90, P86, DOI 10.1054/homp.1999.0468 Sajedi F, 2007, IRAN J PEDIATR, V17, P41 Spence DS, 2005, J ALTERN COMPLEM MED, V11, P793, DOI 10.1089/acm.2005.11.793 Strauss LC, 2000, BIOMED THER, V18, P197 Thompson Trevor D B, 2004, BMC Med Res Methodol, V4, P4, DOI 10.1186/1471-2288-4-4 von Ammon K, 2007, FOCUS ALTERN COMPLEM, V12, P5 NR 26 TC 0 Z9 0 PU IRANIAN SCIENTIFIC SOCIETY MEDICAL ENTOMOLOGY PI TEHRAN PA SCHOOL PUBLIC HEALTH & INST HEALTH RESEARCH, TEHRAN UNIV MEDICAL SCIENCES, P O BOX 6446-14155, TEHRAN, 00000, IRAN SN 2008-2142 EI 2008-2150 J9 IRAN J PEDIATR JI Iran. J. Pediatr. PD AUG PY 2014 VL 24 IS 4 BP 339 EP 344 PG 6 WC Pediatrics SC Pediatrics GA AQ0YF UT WOS:000342507900002 PM 25755852 ER PT J AU Seltzer, LE Ma, MD Ahmed, S Bertrand, M Dobyns, WB Wheless, J Paciorkowski, AR AF Seltzer, Laurie E. Ma, Mandy Ahmed, Sohnee Bertrand, Mary Dobyns, William B. Wheless, James Paciorkowski, Alex R. TI Epilepsy and outcome in FOXG1-related disorders SO EPILEPSIA LA English DT Article DE FOXG1; 14q12; Infantile spasms; Epilepsy; Developmental outcome ID RETT-SYNDROME; INFANTILE SPASMS; MENTAL-RETARDATION; CONGENITAL VARIANT; FOXG1; PHENOTYPE; ENCEPHALOPATHIES; GENOTYPE; 14Q12; TELENCEPHALON AB Objective: FOXG1-related disorders are associated with severe intellectual disability, absent speech with autistic features, and epilepsy. Children with deletions or intragenic mutations of FOXG1 also have postnatal microcephaly, morphologic abnormalities of the corpus callosum, and choreiform movements. Duplications of 14q12 often present with infantile spasms, and have subsequent intellectual disability with autistic features. Long-term epilepsy outcome and response to treatment have not been studied systematically in a well-described cohort of subjects with FOXG1-related disorders. We report on the epilepsy features and developmental outcome of 23 new subjects with deletions or intragenic mutations of FOXG1, and 7 subjects with duplications. Methods: Subjects had either chromosomal microarray or FOXG1 gene sequencing performed as part of routine clinical care. Development and epilepsy follow-up data were collected from medical records from treating neurologists and through telephone parental interviews using standardized questionnaires. Results: Epilepsy was diagnosed in 87% of the subjects with FOXG1-related disorders. The mean age of epilepsy diagnosis in FOXG1 duplications was significantly younger than those with deletions/intragenic mutations (p = 0.0002). All of the duplication FOXG1 children with infantile spasms responded to hormonal therapy, and only one required long-term antiepileptic therapy. In contrast, more children with deletions/intragenic mutations required antiepileptic drugs on follow-up (p < 0.0005). All subjects with FOXG1-related disorders had neurodevelopmental disabilities after 3 years of age, regardless of the epilepsy type or intractability of seizures. All had impaired verbal language and social contact, and three duplication subjects were formally diagnosed with autism. Subjects with deletion/intragenic mutations, however, had significantly worse ambulation (p = 0.04) and functional hand use (p < 0.0005). Significance: Epilepsy and developmental outcome characteristics allow clinicians to distinguish among the FOXG1-related disorders. Further genotype-phenotype studies of FOXG1 may help to elucidate why children develop different forms of developmental epilepsy. C1 [Seltzer, Laurie E.; Ahmed, Sohnee; Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Ma, Mandy; Bertrand, Mary] Washington Univ, Pediat Epilepsy Ctr, Dept Neurol, St Louis, MO USA. [Bertrand, Mary] Washington Univ, Dept Pediat, Pediat Epilepsy Ctr, St Louis, MO 63130 USA. [Dobyns, William B.] Univ Washington, Ctr Integrat Brain Res, Seattle Res Inst, Dept Neurol, Seattle, WA 98195 USA. [Dobyns, William B.] Univ Washington, Ctr Integrat Brain Res, Seattle Res Inst, Div Genet Med,Dept Pediat, Seattle, WA 98195 USA. [Wheless, James] LeBonheur Childrens Hosp, Memphis, TN USA. [Wheless, James] Univ Tennessee, Memphis, TN USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Ctr Neural Dev & Dis, Dept Pediat, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Ctr Neural Dev & Dis, Dept Biomed Genet, Rochester, NY 14642 USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Alex_Paciorkowski@urmc.rochester.edu FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) [K12NS066098, R01NS058721]; Child Neurology Foundation; [K08NS078054] FX We wish to acknowledge the FOXG1 Foundation for referring subjects to this study. Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under award numbers K12NS066098 (to L. E. S.) R01NS058721 (to W. B. D.), the Child Neurology Foundation Logan Infantile Spasms Award (to A. R. P), and K08NS078054 (to A.R.P.). 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Puzia, Megan E. Weissman, Alexandra B. Kim, Kerri L. Laird, Angela R. Dickstein, Daniel P. TI Developmental Meta-analyses of the Functional Neural Correlates of Bipolar Disorder SO JAMA PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; VOXEL-BASED MORPHOMETRY; FALSE DISCOVERY RATE; RESPONSE-INHIBITION; FACIAL EXPRESSIONS; MOTOR INHIBITION; ALE METAANALYSIS; NATIONAL TRENDS; FOLLOW-UP; BRAIN AB IMPORTANCE Bipolar disorder (BD) is a debilitating mental illness associated with high costs to diagnosed individuals and society. Within the past 2 decades, increasing numbers of children and adolescents have been diagnosed as having BD. While functional magnetic resonance imaging (fMRI) studies have begun to investigate the neural mechanisms underlying BD, few have directly compared differences in youths with BD and adults with BD (hereafter BD-youths and BD-adults, respectively). OBJECTIVE To test the hypothesis that BD-youths (<18 years old) would show greater convergence of amygdala hyperactivation and prefrontal cortical hypoactivation vs BD-adults. DATA SOURCES PubMed and PsycINFO databases were searched on July 17, 2013, for original, task-related coordinate-based fMRI articles. STUDY SELECTION In total, 21 pediatric studies, 73 adult studies, and 2 studies containing distinct pediatric and adult groups within the same study met inclusion criteria for our ALE analyses. DATA EXTRACTION AND SYNTHESIS Coordinates of significant between-group differences were extracted from each published study. Recent improvements in GingerALE software were used to perform direct comparisons of pediatric and adult fMRI findings. We conducted activation likelihood estimation (ALE) meta-analyses directly comparing the voxelwise convergence of fMRI findings in BD-youths vs BD-adults, both relative to healthy control (HC) participants. RESULTS Analyses of emotional face recognition fMRI studies showed significantly greater convergence of amygdala hyperactivation among BD-youths than BD-adults. More broadly, analyses of fMRI studies using emotional stimuli showed significantly greater convergence of hyperactivation among BD-youths than BD-adults in the inferior frontal gyrus and precuneus. In contrast, analyses of fMRI studies using nonemotional cognitive tasks and analyses aggregating emotional and nonemotional tasks showed significantly greater convergence of hypoactivation among BD-youths than BD-adults in the anterior cingulate cortex. CONCLUSIONS AND RELEVANCE Our data suggest that amygdala, prefrontal, and visual system hyperactivation is important in the emotional dysfunction present in BD-youths, as well as that anterior cingulate cortex hypoactivation is relevant to the cognitive deficits in BD-youths. Future studies are required to determine if the developmental fMRI differences between BD-youths and BD-adults identified by our ALE meta-analyses are useful as brain-based diagnostic or treatment markers of BD, including either longitudinal neuroimaging studies of BD-youths as they become adults or cross-sectional imaging studies directly comparing BD-youths with BD-adults. C1 [Wegbreit, Ezra; Cushman, Grace K.; Puzia, Megan E.; Weissman, Alexandra B.; Kim, Kerri L.; Dickstein, Daniel P.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Pediat Mood Imaging & Neurodev Program, East Providence, RI 02915 USA. [Wegbreit, Ezra; Cushman, Grace K.; Puzia, Megan E.; Weissman, Alexandra B.; Kim, Kerri L.; Dickstein, Daniel P.] Bradley Hosp, East Providence, RI USA. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. RP Wegbreit, E (reprint author), Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Pediat Mood Imaging & Neurodev Program, 1011 Vet Mem Pkwy, East Providence, RI 02915 USA. EM ezra_wegbreit@brown.edu FU National Institutes of Health [5T32-MH019927-20, R01-MH074457, R01-MH084812, 5R01-MH087513, 1R21-MH096850, 1R01-MH099703, 5R01-MH092450] FX Dr Wegbreit is supported by grant 5T32-MH019927-20 from the National Institutes of Health. Dr Laird is supported by grants R01-MH074457 and R01-MH084812 from the National Institutes of Health. Mss Cushman, Puzia, and Weissman and Drs Kim and Dickstein are supported by grants 5R01-MH087513, 1R21-MH096850, 1R01-MH099703, and 5R01-MH092450 from the National Institutes of Health, although the present study was not part of any of these grants. 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Weisskopf, Marc G. Roberts, Andrea L. Ascherio, Alberto Santangelo, Susan L. TI Parental Social Responsiveness and Risk of Autism Spectrum Disorder in Offspring SO JAMA PSYCHIATRY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; GENERAL-POPULATION; SCALE SRS; DIAGNOSTIC INTERVIEW; TRAITS; SIBLINGS; TWIN; IMPAIRMENT; VALIDATION; RECURRENCE AB IMPORTANCE Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood. OBJECTIVE To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD. DESIGN, SETTING, AND PARTICIPANTS We performed a nested case-control study (pilot study: July 1, 2007, through June 30,2009; full-scale study: September 15, 20 08, through September 14, 2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116 430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses. EXPOSURE The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status. MAIN OUTCOMES AND MEASURES Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised. RESULTS A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR] 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (P < .001). CONCLUSIONS AND RELEVANCE These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits. C1 [Lyall, Kristen; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lyall, Kristen] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Constantino, John N.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Weisskopf, Marc G.; Ascherio, Alberto; Santangelo, Susan L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Roberts, Andrea L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. 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Windham, Gayle C. Anderson, Meredith Croen, Lisa A. Grether, Judith K. Risch, Neil TI Evidence of Reproductive Stoppage in Families With Autism Spectrum Disorder A Large, Population-Based Cohort Study SO JAMA PSYCHIATRY LA English DT Article ID EPIDEMIOLOGIC SURVEY; RISK; RECURRENCE; TWIN; SIBLINGS AB IMPORTANCE Few studies have examined the curtailment of reproduction (ie, stoppage) after the diagnosis of a child with autism spectrum disorder (ASD). OBJECTIVE To examine stoppage in a large, population-based cohort of families in which a child has received a diagnosis of ASD. DESIGN, SETTING, AND PARTICIPANTS Individuals with ASD born from January 1,1990, through December 31, 2003, were identified in the California Department of Developmental Services records, which were then linked to state birth certificates to identify full sibs and half-sibs and to obtain information on birth order and demographics. A total of 19 710 case families in which the first birth occurred within the study period was identified. These families included 39 361 individuals (sibs and half-sibs). Control individuals were randomly sampled from birth certificates and matched 2:1 to cases by sex, birth year, and maternal age, self-reported race/ethnicity, and county of birth after removal of children receiving services from the California Department of Developmental Services. Using similar linkage methods as for case families, 36 215 pure control families (including 75 724 total individuals) were identified that had no individuals with an ASD diagnosis. EXPOSURES History of affected children. MAIN OUTCOMES AND MEASURES Stoppage was investigated by comparing the reproductive behaviors of parents after the birth of a child with ASD vs an unaffected child using a survival analysis framework for time to next birth and adjusting for demographic variables. RESULTS For the first few years after the birth of a child with ASD, the parents' reproductive behavior was similar to that of control parents. However, birth rates differed in subsequent years; overall, families whose first child had ASD had a second child at a rate of 0.668 (95% CI, 0.635-0.701) that of control families, adjusted for birth year, birth weight, maternal age, and self-reported maternal race/ethnicity. Results were similar when a later-born child was the first affected child in the family. Reproductive curtailment was slightly stronger among women who changed partners (relative rate for second-born children, 0.553 [95% CI, 0.498-0.614]). CONCLUSIONS AND RELEVANCE These results provide the first quantitative assessment and convincing statistical evidence of reproductive stoppage related to ASD. These findings have implications for recurrence risk estimation and genetic counseling. C1 [Hoffmann, Thomas J.; Risch, Neil] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Hoffmann, Thomas J.; Risch, Neil] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Windham, Gayle C.; Anderson, Meredith; Grether, Judith K.] Calif Dept Publ Hlth, Environm Hlth Invest Branch, Richmond, CA USA. [Croen, Lisa A.; Risch, Neil] Kaiser Permanente, Div Res, Oakland, CA USA. RP Risch, N (reprint author), Univ Calif San Francisco, Inst Human Genet, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM rischn@humgen.ucsf.edu FU Institute for Human Genetics, University of California, San Francisco; National Cancer Institute [R25 CA112355] FX This work was supported by funds from the Institute for Human Genetics, University of California, San Francisco, and by grant R25 CA112355 from the National Cancer Institute. 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Tan, Li-Tao Zhou, Li Liu, Jian-Jun Wang, Wen-Yue Xiao, Zhi-Cheng Zhou, Xin-Fu TI Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE affective behavior; CUMS; fluoxetine; locomotor activity; TRIM32 ID ADULT HIPPOCAMPAL NEUROGENESIS; ELEVATED ZERO-MAZE; DYSTROPHY TYPE 2H; SOCIAL-ISOLATION; MOUSE MODEL; RAT MODEL; APOPTOSIS; CELLS; DOPAMINE; DIFFERENTIATION AB Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors. Using a chronic unpredictable mild stress mouse depression model, we studied expression of TRIM32 in brain tissue samples and observed behavioral changes in Trim32 knockout mice. The results showed that TRIM32 protein but not its mRNA was significantly reduced in hippocampus in a time-dependent manner within 8 weeks of chronic stress. These stress-induced affective behaviors and reduction of TRIM32 protein expression were significantly reversed by antidepressant fluoxetine treatment. In addition, Trim32 knockout mice showed reduced anxiety and depressive behaviors and hyperactivities compared with Trim32 wild-type mice under normal and mild stress conditions. We conclude that TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. C1 [Ruan, Chun-Sheng; Wang, Shu-Fen; Shen, Yan-Jun; Guo, Yi; Yang, Chun-Rui; Tan, Li-Tao; Zhou, Li; Liu, Jian-Jun; Wang, Wen-Yue; Xiao, Zhi-Cheng; Zhou, Xin-Fu] Kunming Med Univ, Inst Mol & Clin Med, Key Lab Stem Cell & Regenerat Med, Kunming, Peoples R China. [Ruan, Chun-Sheng; Zhou, Fiona H.; Zhou, Xin-Fu] Univ S Australia, Sch Pharm & Med Sci, Div Hlth Sci, Adelaide, SA 5000, Australia. [Shen, Yan-Jun; Guo, Yi; Yang, Chun-Rui] Kunming Med Univ, Sch Med Sci, Kunming, Peoples R China. [Xiao, Zhi-Cheng] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia. RP Ruan, CS (reprint author), Univ S Australia, Sch Pharm & Med Sci, Div Hlth Sci, Adelaide, SA 5000, Australia. EM ruacy004@mymail.unisa.edu.au FU Chinese MST [2011CB944200]; NHMRC [APP1021408, APP1021409]; Talent Program of Yunnan Province, China; Monash University, Australia; KMU-UIEP [CX201111, CX201244, CX201241] FX We thank Dr H. Ding for kindly providing TRIM32 knockout mice and Dr J. C. Schwamborn for kindly providing antibody against TRIM32. We thank Dr B. T. Baune for valuable comments. This work was supported by grants from the Chinese MST 2011CB944200 and NHMRC grants (APP1021408 and APP1021409), the Talent Program of Yunnan Province, China, and The Professorial Fellowship of Monash University, Australia, to Z.C.X., and KMU-UIEP grants (CX201111, CX201244 and CX201241) to C. S. R. X.F.Z. is a visiting Professor of KMU. 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PD AUG PY 2014 VL 10 IS 8 BP 431 EP + DI 10.1038/nrneurol.2014.126 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AP0YE UT WOS:000341791700002 PM 25023342 ER PT J AU Hebert, B Pietropaolo, S Meme, S Laudier, B Laugeray, A Doisne, N Quartier, A Lefeuvre, S Got, L Cahard, D Laumonnier, F Crusio, WE Pichon, J Menuet, A Perche, O Briault, S AF Hebert, Betty Pietropaolo, Susanna Meme, Sandra Laudier, Beatrice Laugeray, Anthony Doisne, Nicolas Quartier, Angelique Lefeuvre, Sandrine Got, Laurence Cahard, Dominique Laumonnier, Frederic Crusio, Wim E. Pichon, Jacques Menuet, Arnaud Perche, Olivier Briault, Sylvain TI Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Article DE Fragile X Syndrome; BMS-204352; BKCa channel; Sociability; Cognition; Anxiety ID ELEVATED PLUS-MAZE; MENTAL-RETARDATION SYNDROME; SYNDROME MOUSE MODEL; 2-TRIAL MEMORY TASK; KNOCKOUT MICE; POTASSIUM CHANNELS; BEHAVIOR; AUTISM; MORPHOLOGY; ANXIETY AB Background: Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is also associated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesis of FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXS neurobehavioral phenotypes. Methods and results: We used a selective BKCa channel opener molecule (BMS-204352) to address this issue in Fmr1 KO mice, modeling the FXS pathophysiology. In vitro, acute BMS-204352 treatment (10 mu M) restored the abnormal dendritic spine phenotype. In vivo, a single injection of BMS-204352 (2 mg/kg) rescued the hippocampal glutamate homeostasis and the behavioral phenotype. Indeed, disturbances in social recognition and interaction, non-social anxiety, and spatial memory were corrected by BMS-204352 in Fmr1 KO mice. Conclusion: These results demonstrate that the BKCa channel is a new therapeutic target for FXS. We show that BMS-204352 rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of FXS. This pharmacological molecule might open new ways for FXS therapy. C1 [Hebert, Betty; Laudier, Beatrice; Laugeray, Anthony; Doisne, Nicolas; Quartier, Angelique; Pichon, Jacques; Menuet, Arnaud; Perche, Olivier; Briault, Sylvain] CNRS, UMR7355, F-45071 Orleans, France. [Hebert, Betty; Laudier, Beatrice; Laugeray, Anthony; Doisne, Nicolas; Quartier, Angelique; Pichon, Jacques; Menuet, Arnaud; Perche, Olivier; Briault, Sylvain] Univ Orleans, F-45071 Orleans 2, France. [Pietropaolo, Susanna; Crusio, Wim E.] CNRS, Aquitaine Inst Cognit & Integrat Neurosci, UMR 5287, Talence, France. [Pietropaolo, Susanna; Crusio, Wim E.] Univ Bordeaux, Aquitaine Inst Cognit & Integrat Neurosci, F-33405 Talence, France. [Meme, Sandra] Univ Orleans, CNRS, Ctr Biophys Mol, UPR4301, F-45071 Orleans, France. [Laudier, Beatrice; Lefeuvre, Sandrine; Got, Laurence; Perche, Olivier; Briault, Sylvain] Reg Hosp, Dept Genet, F-45100 Orleans, France. [Cahard, Dominique] INSA Rouen, UMR CNRS CBRA 6014, F-76821 Mont St Aignan, France. [Laumonnier, Frederic] INSERM, U930, F-37032 Tours, France. [Laumonnier, Frederic] Univ Tours, UMR Imagerie & Cerveau, F-37000 Tours, France. RP Briault, S (reprint author), CNRS, UMR7355, F-45071 Orleans, France. EM sbriault@cnrs-orleans.fr RI Crusio, Wim/A-7070-2008 OI Crusio, Wim/0000-0001-6638-202X FU Fondation de France [015448]; FRAXA Research Foundation (USA); FEDER Autism [35106]; Fondation Lejeune; CNRS (Soutien au transfert) [04388-02]; Region Centre; Regional Hospital of Orleans; University of Orleans; Project FP7 GENCODYS [241995]; March of Dimes [12-FY05-1198]; Conseil Regional d'Aquitaine; CNRS; University of Bordeaux 1 FX We would like to thank Melanie Marcos for her excellent technical support and Alexandre Herpin, Jerome Larrigaldie and Ludovic Mercier for animal breeding. We also thank Jean-Claude Beloeil and Valerie Quesniaux for their continued support of the project. Research was supported in part by grants from Fondation de France 015448, The FRAXA Research Foundation (USA), FEDER Autism 35106, Fondation Lejeune, CNRS (Soutien au transfert 04388-02), Region Centre, Regional Hospital of Orleans, the University of Orleans and Project FP7 GENCODYS (no241995, to FL). W.C. and S.P. were supported by grants from the March of Dimes (12-FY05-1198), Conseil Regional d'Aquitaine, CNRS, and the University of Bordeaux 1 to W.C. 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Rare Dis. PD AUG 1 PY 2014 VL 9 AR 124 DI 10.1186/s13023-014-0124-6 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA AP0FC UT WOS:000341735700001 PM 25079250 ER PT J AU Lancioni, GE Singh, NN O'Reilly, MF Sigafoos, J Boccasini, A La Martire, ML Lang, R AF Lancioni, Giulio E. Singh, Nirbhay N. O'Reilly, Mark F. Sigafoos, Jeff Boccasini, Adele La Martire, Maria L. Lang, Russell TI CASE STUDIES OF TECHNOLOGY FOR ADULTS WITH MULTIPLE DISABILITIES TO MAKE TELEPHONE CALLS INDEPENDENTLY SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID AUTISM SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; ASSISTIVE TECHNOLOGY; SOCIAL VALIDATION; BRAIN-INJURY; YOUNG-ADULTS; COMMUNICATION; INDIVIDUALS; COMPUTER; SYSTEM AB Recent literature has shown the possibility of enabling individuals with multiple disabilities to make telephone calls independently via computer-aided telephone technology. These two case studies assessed a modified version of such technology and a commercial alternative to it for a woman and a man with multiple disabilities, respectively. The modified version used in Study 1 (a) presented the names of the persons available for a call and (b) reminded the participant of the response she needed to perform (i.e., pressing a microswitch) if she wanted to call any of those names/persons. The commercial device used in Study 2 was a Galaxy S3 (Samsung) equipped with the S-voice module, which allowed the participant to activate phone calls by uttering the word "Call" followed by the name of the persons he wanted to call. The results of the studies showed that the participants learned to make phone calls independently using the technology/device available. Implications of the results are discussed. C1 [Lancioni, Giulio E.] Univ Bari, I-70100 Bari, Italy. [Singh, Nirbhay N.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. 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Mot. Skills PD AUG PY 2014 VL 119 IS 1 BP 320 EP 331 DI 10.2466/15.PMS.119c14z4 PG 12 WC Psychology, Experimental SC Psychology GA AO7GV UT WOS:000341521400028 PM 25153758 ER PT J AU Honti, F Meader, S Webber, C AF Honti, Frantisek Meader, Stephen Webber, Caleb TI Unbiased Functional Clustering of Gene Variants with a Phenotypic-Linkage Network SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DE-NOVO MUTATIONS; SEMANTIC SIMILARITY; INTELLECTUAL DISABILITY; COMPREHENSIVE RESOURCE; EXPRESSION PATTERNS; DISEASE GENES; DATABASE; AUTISM; MOUSE; ONTOLOGY AB Groupwise functional analysis of gene variants is becoming standard in next-generation sequencing studies. As the function of many genes is unknown and their classification to pathways is scant, functional associations between genes are often inferred from large-scale omics data. Such data types-including protein-protein interactions and gene co-expression networks-are used to examine the interrelations of the implicated genes. Statistical significance is assessed by comparing the interconnectedness of the mutated genes with that of random gene sets. However, interconnectedness can be affected by confounding bias, potentially resulting in false positive findings. We show that genes implicated through de novo sequence variants are biased in their coding-sequence length and longer genes tend to cluster together, which leads to exaggerated p-values in functional studies; we present here an integrative method that addresses these bias. To discern molecular pathways relevant to complex disease, we have inferred functional associations between human genes from diverse data types and assessed them with a novel phenotype-based method. Examining the functional association between de novo gene variants, we control for the heretofore unexplored confounding bias in coding-sequence length. We test different data types and networks and find that the disease-associated genes cluster more significantly in an integrated phenotypic-linkage network than in other gene networks. We present a tool of superior power to identify functional associations among genes mutated in the same disease even after accounting for significant sequencing study bias and demonstrate the suitability of this method to functionally cluster variant genes underlying polygenic disorders. C1 [Honti, Frantisek; Meader, Stephen; Webber, Caleb] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford, England. RP Honti, F (reprint author), Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford, England. EM caleb.webber@dpag.ox.ac.uk FU Medical Research Council, UK under the EU [241995] FX This work was funded by the Medical Research Council, UK, under the EU 7th Framework Programme, project GENCODYS (grant no. 241995). 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 AUG PY 2014 VL 10 IS 8 AR e1003815 DI 10.1371/journal.pcbi.1003815 PG 7 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AO8AE UT WOS:000341573600050 PM 25166029 ER PT J AU Sondenaa, E Helverschou, SB Steindal, K Rasmussen, K Nilson, B Nottestad, JA AF Sondenaa, Erik Helverschou, Sissel Berge Steindal, Kari Rasmussen, Kirsten Nilson, Britta Nottestad, Jim Aage TI VIOLENCE AND SEXUAL OFFENDING BEHAVIOR IN PEOPLE WITH AUTISM SPECTRUM DISORDER WHO HAVE UNDERGONE A PSYCHIATRIC FORENSIC EXAMINATION SO PSYCHOLOGICAL REPORTS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGERS-SYNDROME; CRIMINAL BEHAVIOR; PREVALENCE; PERSONALITY; JUVENILE; DEFICITS; SAMPLE; CRIME; RISK AB The increased awareness of Autism Spectrum Disorders (ASD) over the last few decades as well as the potential association between ASD and off ending behaviors has spurred a need for increased research in this area. In order to explore any possible relationship between ASD and violent or sexual crime the present study examines all forensic examination reports over a 10-yr. period in Norway where the charged persons were diagnosed with ASD and charged with either a violent (N = 21) or a sexual (N = 12) offense. Differences between these two groups regarding previous contact with child welfare and confessions to the offense were found. There was also a tendency toward more severe mental health problems and less intellectual problems among the violent off enders than the sexual off enders. C1 [Sondenaa, Erik] St Olavs Hosp, N-7440 Trondheim, Norway. [Sondenaa, Erik] Univ Coll Sor Trondelag, Trondheim, Norway. [Helverschou, Sissel Berge; Steindal, Kari; Nilson, Britta] Oslo Univ Hosp, Natl Autism Unit, Oslo, Norway. [Rasmussen, Kirsten] St Olavs Hosp, Trondheim, Norway. [Rasmussen, Kirsten; Nottestad, Jim Aage] NTNU Inst Psychol, Trondheim, Norway. [Sondenaa, Erik; Nottestad, Jim Aage] St Olavs Hosp, Dep Broset, N-7440 Trondheim, Norway. RP Sondenaa, E (reprint author), St Olavs Hosp, Dep Broset, Postbox 1803, N-7440 Trondheim, Norway. 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PD AUG PY 2014 VL 115 IS 1 BP 32 EP 43 DI 10.2466/16.15.PR0.115c16z5 PG 12 WC Psychology, Multidisciplinary SC Psychology GA AO7HB UT WOS:000341522100005 PM 25073065 ER PT J AU Cafferkey, M Ahn, JW Flinter, F Ogilvie, C AF Cafferkey, Michiala Ahn, Joo Wook Flinter, Frances Ogilvie, Caroline TI Phenotypic Features in Patients With 15q11.2(BP1-BP2) Deletion: Further Delineation of an Emerging Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 15q11.2(BP1-BP2) deletion; array CGH; CNV; NIPA1 ID PRADER-WILLI-SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION; GLOBUS-PALLIDUS DYSFUNCTION; COPY NUMBER VARIATION; TEST IN-PLACE; DEVELOPMENTAL DELAY; RECURRENT MICRODELETIONS; ANGELMAN-SYNDROME; CRITICAL REGION; ARRAY CGH AB 15q11.2 deletions flanked by BP1 and BP2 of the Prader-Willi/Angelman syndrome region have recently been linked to a range of neurodevelopment disorders including intellectual disability, speech and language delay, motor delay, autism spectrum disorders, epilepsy, and schizophrenia. Array CGH analysis of 14,605 patients referred for diagnostic cytogenetic testing found that 83 patients (0.57%) carried the 15q11.2(BP1-BP2) deletion. Phenotypic frequencies in the deleted cohort (n = 83) were compared with frequencies in the non-deleted cohort (n = 14,522); developmental delay, motor delay, and speech and language delay were all more prevalent in the deleted cohort. Notably, motor delay was significantly more common (OR = 6.37). These data indicate that developmental delay, motor delay, and speech and language delay are common clinical features associated with this deletion, providing substantial evidence to support this CNV as a susceptibility locus for a spectrum of neurodevelopmental disorders. (C) 2014 Wiley Periodicals, Inc. C1 [Cafferkey, Michiala; Flinter, Frances; Ogilvie, Caroline] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Ahn, Joo Wook; Flinter, Frances; Ogilvie, Caroline] Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England. RP Ogilvie, C (reprint author), Guys & St Thomas NHS Fdn Trust, Dept Cytogenet, 5th Floor,Tower Wing,St Thomas St, London SE1 9RT, England. 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A PD AUG PY 2014 VL 164A IS 8 BP 1916 EP 1922 DI 10.1002/ajmg.a.36554 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AN5YD UT WOS:000340667900052 PM 24715682 ER PT J AU Mignon-Ravix, C Cacciagli, P Choucair, N Popovici, C Missirian, C Milh, M Megarbane, A Busa, T Julia, S Girard, N Badens, C Sigaudy, S Philip, N Villard, L AF Mignon-Ravix, Cecile Cacciagli, Pierre Choucair, Nancy Popovici, Cornel Missirian, Chantal Milh, Mathieu Megarbane, Andre Busa, Tiffany Julia, Sophie Girard, Nadine Badens, Catherine Sigaudy, Sabine Philip, Nicole Villard, Laurent TI Intragenic Rearrangements in X-Linked Intellectual Deficiency: Results of a-CGH in a Series of 54 Patients and Identification of TRPC5 and KLHL15 As Potential XLID Genes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE X-linked intellectual disability; array CGH; TRPC5; KLHL15 ID NONSPECIFIC MENTAL-RETARDATION; CEREBELLAR HYPOPLASIA; XLMR GENES; DISABILITY; DELETION; CHANNEL; FAMILY; OPHN1; MUTATION; GROWTH AB High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the identification of new disease genes. We report on the analysis of 54 male patients presenting with intellectual deficiency (ID) and a family history suggesting X-linked (XL) inheritance or maternal skewed X-chromosome inactivation(XCI), using a home-made X-chromosome-specific microarray covering the whole human X-chromosome at high resolution. The majority of patients had whole genome array-CGH prior to the selection and we did not include large rearrangements such as MECP2 and FMR1 duplications. We identified four rearrangements considered as causative or potentially pathogenic, corresponding to a detection rate of 8%. Two CNVs affected known XLID genes and were therefore considered as causative (IL1RAPL1 and OPHN1 intragenic deletions). Two new CNVs were considered as potentially pathogenic as they affected interesting candidates for ID. The first CNV is a deletion of the first exon of the TRPC5 gene, encoding a cation channel implicated in dendrite growth and patterning, in a child presenting with ID and an autism spectrum disorder (ASD). The second CNV is a partial deletion of KLHL15, in a patient with severe ID, epilepsy, and anomalies of cortical development. In both cases, in spite of strong arguments for clinical relevance, we were not able at this stage to confirm pathogenicity of the mutations, and the causality of the variants identified in XLID remains to be confirmed. (C) 2014 Wiley Periodicals, Inc. C1 [Mignon-Ravix, Cecile; Cacciagli, Pierre; Choucair, Nancy; Milh, Mathieu; Megarbane, Andre; Badens, Catherine; Philip, Nicole; Villard, Laurent] INSERM, UMR S 910, F-13258 Marseille, France. [Mignon-Ravix, Cecile; Cacciagli, Pierre; Choucair, Nancy; Milh, Mathieu; Megarbane, Andre; Girard, Nadine; Badens, Catherine; Philip, Nicole; Villard, Laurent] Aix Marseille Univ, GMGF, Marseille, France. [Cacciagli, Pierre; Popovici, Cornel; Missirian, Chantal; Busa, Tiffany; Badens, Catherine; Sigaudy, Sabine; Philip, Nicole] Hop Enfants La Timone, Dept Genet Med & Biol Cellulaire, Marseille, France. [Choucair, Nancy; Megarbane, Andre] Univ St Joseph, Unite Genet Med, Beirut, Lebanon. [Choucair, Nancy; Megarbane, Andre] Univ St Joseph, Lab Associe INSERM, Unite UMR S 910, Pole Technol Sante, Beirut, Lebanon. [Milh, Mathieu] Hop Enfants La Timone, Serv Neurol Pediat, Marseille, France. [Julia, Sophie] Hop Purpan, Serv Genet Med, Toulouse, France. [Girard, Nadine] Hop Enfants La Timone, Serv Neuroradiol, Marseille, France. RP Villard, L (reprint author), Fac Med La Timone, Inserm UMR S 910, 27 Bd Jean Moulin, F-13385 Marseille 5, France. EM laurent.villard@univ-amu.fr RI POPOVICI, Cornel/A-2027-2009 OI POPOVICI, Cornel/0000-0001-8226-3127 FU INSERM; Aix Marseille University FX Grant sponsor: INSERM; Grant sponsor: Aix Marseille University. 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J. Med. Genet. A PD AUG PY 2014 VL 164A IS 8 BP 1991 EP 1997 DI 10.1002/ajmg.a.36602 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AN5YD UT WOS:000340667900061 PM 24817631 ER PT J AU Filges, I Sparagana, S Sargent, M Selby, K Schlade-Bartusiak, K Lueder, GT Robichaux-Viehoever, A Schlaggar, BL Shimony, JS Shinawi, M AF Filges, Isabel Sparagana, Steven Sargent, Michael Selby, Kathryn Schlade-Bartusiak, Kamilla Lueder, Gregg T. Robichaux-Viehoever, Amy Schlaggar, Bradley L. Shimony, Joshua S. Shinawi, Marwan TI Brain MRI Abnormalities and Spectrum of Neurological and Clinical Findings in Three Patients With Proximal 16p11.2 Microduplication SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 16p11.2; microduplication; T2-hyperintensity; MRI; neurological ID CHROMOSOME 16P11.2; AUTISM; PHENOTYPES; DISORDERS; REARRANGEMENTS; MICRODELETION; EXPRESSION; DELETIONS; DOSAGE AB The phenotype of recurrent similar to 600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuro-radiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications. (C) 2014 Wiley Periodicals, Inc. C1 [Filges, Isabel] Univ British Columbia, Dept Med Genet, BC Childrens & Womens Hosp, Child & Family Res Inst, Vancouver, BC, Canada. [Filges, Isabel] Univ Basel Hosp, Dept Biomed, Div Med Genet, CH-4031 Basel, Switzerland. [Sparagana, Steven] Texas Scottish Rite Hosp Children, Dept Pediat Neurol, Dallas, TX 75219 USA. [Sargent, Michael] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada. [Selby, Kathryn] Univ British Columbia, Dept Pediat, Div Pediat Neurol, Vancouver, BC V6T 1W5, Canada. [Schlade-Bartusiak, Kamilla] Univ British Columbia, Dept Pathol & Lab Med, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. [Lueder, Gregg T.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Lueder, Gregg T.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Robichaux-Viehoever, Amy; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Shimony, Joshua S.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Shinawi, Marwan] Washington Univ, Sch Med, Dept Pediat, Div Genet & Genom Med, St Louis, MO 63110 USA. RP Filges, I (reprint author), BC Childrens & Womens Hosp, Dept Med Genet, Box 153,4480 Oak St, Vancouver, BC V6H 3V4, Canada. EM Isabel.Filges@unibas.ch FU Swiss Foundation for Grants in Biology; Medicine/Swiss National Science Foundation (SFGBM/SNSF); Freie Akademische Gesellschaft (FAG) Basel FX Grant sponsor: Swiss Foundation for Grants in Biology; Grant sponsor: Medicine/Swiss National Science Foundation (SFGBM/SNSF); Grant sponsor: Freie Akademische Gesellschaft (FAG) Basel. 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J. Med. Genet. A PD AUG PY 2014 VL 164A IS 8 BP 2003 EP 2012 DI 10.1002/ajmg.a.36605 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AN5YD UT WOS:000340667900063 PM 24891046 ER PT J AU Joosten, AV Safe, AP AF Joosten, Annette V. Safe, Anneleise P. TI Management strategies of mothers of school-age children with autism: Implications for practice SO AUSTRALIAN OCCUPATIONAL THERAPY JOURNAL LA English DT Article DE autism spectrum disorder; family-centred practice; mothers; research related; self management; wellbeing ID SELF-MANAGEMENT; CHRONIC ILLNESS; SOCIAL SUPPORT; MENTAL-HEALTH; PARENTS; CARE; STRESS; IMPACT; PROFESSIONALS; PERSPECTIVES AB Background/aim: Mothering children with autism results in mothers spending more time on daily tasks as well as managing the disorder. The need for mothers to self-manage often increases when the child is school aged. Mothers develop strategies, and occupational therapists and other health professional rely on or expect mothers to be involved in meeting the extra needs of their children with autism and other family members. Little is known about the strategies adopted by the mothers. The aim of this study was to explore the strategies mothers used to manage their roles and emotions, and their child's behaviours. Method: In-depth individual interviews were conducted with seven mothers and data were analysed in this qualitative study using phenomenological analysis. Results: Findings revealed that the mothers had adopted strategies to manage their roles, their emotions and their child's behaviour. However, the strategies were often shaped by the expectations of others or circumstances beyond their control and at times added further to their stress. Conclusions: Mothers of children with autism developed strategies to self-manage their lives and their child's disorder. However, even when these strategies were effective, they sometimes placed further stress on the mothers. The mothers provided insights to how they coped but need help to consider the support they require and therapists need to consider the pressures of expecting mothers to self-manage their child's disorder, their own lives and their family. Family-centred practice emphasising collaboration with mothers needs to be maintained with school-aged children. C1 [Joosten, Annette V.] Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Occupat Therapy & Social Work, Perth, WA 6102, Australia. [Safe, Anneleise P.] Ctr Cerebral Palsy, Therapy Serv, Perth, WA, Australia. RP Joosten, AV (reprint author), Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Occupat Therapy & Social Work, Perth, WA 6102, Australia. 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PD AUG PY 2014 VL 61 IS 4 BP 249 EP 258 DI 10.1111/1440-1630.12116 PG 10 WC Rehabilitation SC Rehabilitation GA AO1UF UT WOS:000341099700006 PM 24499184 ER PT J AU Geurts, HM van den Bergh, SFWM Ruzzano, L AF Geurts, Hilde M. van den Bergh, Sanne F. W. M. Ruzzano, Laura TI Prepotent Response Inhibition and Interference Control in Autism Spectrum Disorders: Two Meta-Analyses SO AUTISM RESEARCH LA English DT Article DE ASD; autism; inhibition; interference; cognitive control; meta-analysis ID HIGH-FUNCTIONING AUTISM; DEFICIT HYPERACTIVITY DISORDER; LATENT-VARIABLE ANALYSIS; CHOICE REACTION-TIME; COGNITIVE CONTROL; EXECUTIVE FUNCTION; NEURODEVELOPMENTAL DISORDERS; IMPAIRED COGNITION; WORKING-MEMORY; STOP-SIGNAL AB There is a substantial amount of data providing evidence for, but also against the hypothesis that individuals with autism spectrum disorders (ASD) encounter inhibitory control deficits. ASD is often associated with interference control deficits rather than prepotent response inhibition. Moreover, the developmental trajectory for these inhibitory control processes is hypothesized to differ in ASD as compared to typical development. In efforts to gain a more comprehensive perspective of inhibition in ASD, separate quantitative analysis for prepotent response inhibition studies and interference control studies were conducted. Together, these two meta-analyses included 41 studies with a combined sample size of 1,091 people with ASD (M age 14.8 years), and 1,306 typically developing (TD) controls (M age 13.8 years). The meta-analyses indicated that individuals with ASD show increased difficulties in prepotent response inhibition (effect size 0.55) and in interference control (effect size 0.31). In addition, age was a relevant moderator for prepotent response inhibition but not for interference control. Exploratory analyses revealed that when IQ was taken into account, heterogeneity considerably decreased among interference control studies but not among prepotent response inhibition. In contrast to the general belief, both prepotent response inhibition and interference control problems were observed in individuals with ASD. However, a large variation between studies was also found. Therefore, there remain factors beyond inhibition type, age, or IQ that significantly influence inhibitory control performance among individuals with ASD. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Geurts, Hilde M.] Univ Amsterdam, Dept Psychol Brain & Cognit, NL-1018 XA Amsterdam, Netherlands. [Geurts, Hilde M.; van den Bergh, Sanne F. W. M.; Ruzzano, Laura] Dr Leo Kannerhuis, Res & Dev, Ctr Autism, Amsterdam, Netherlands. [Geurts, Hilde M.; van den Bergh, Sanne F. W. M.; Ruzzano, Laura] Dutch Autism & ADHD Res Ctr Arc, Amsterdam, Netherlands. [Geurts, Hilde M.] Univ Amsterdam, Cognit Sci Ctr Amsterdam, NL-1018 XA Amsterdam, Netherlands. RP Geurts, HM (reprint author), Univ Amsterdam, Dept Psychol, Dutch Autism & ADHD Res Ctr ARC, Weesperpl 4, NL-1018 XA Amsterdam, Netherlands. EM H.M.Geurts@uva.nl FU VIDI grant, Netherlands Organization for Scientific Research (NWO) [452-10-003] FX This work is part of the research program "Autism and Aging: A Double Jeopardy, which is financed (VIDI grant number 452-10-003) by the Netherlands Organization for Scientific Research (NWO). Dr. Geurts, M.Sc. van den Bergh, and M.Sc. Ruzzano reported no biomedical financial interests or potential conflicts of interest. 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PD AUG PY 2014 VL 7 IS 4 BP 407 EP 420 DI 10.1002/aur.1369 PG 14 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300001 PM 24596300 ER PT J AU Sparaci, L Stefanini, S D'Elia, L Vicari, S Rizzolatti, G AF Sparaci, Laura Stefanini, Silvia D'Elia, Lidia Vicari, Stefano Rizzolatti, Giacomo TI What and Why Understanding in Autism Spectrum Disorders and Williams Syndrome: Similarities and Differences SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorders; Williams syndrome; social cognition; motor skills ID YOUNG-CHILDREN; NEURAL BASIS; MOTOR; INFANTS; HYPERSOCIABILITY; INTENTIONS; DEFICIT; BRAIN; PERCEPTION; MECHANISMS AB Children with autism spectrum disorders (ASD) and children with Williams syndrome (WS) show divergent social phenotypes, but also several similarities in their socio-cognitive deficits. Cross-syndrome direct comparisons could lead to a better understanding of mechanisms that determine deficits in social cognition in the two syndromes. A fundamental factor for social cognition is the ability to understand and predict others' actions (e. g. what action is being done and why it is being done when observing a goal-related act). Here we compared the understanding of others' actions in children with ASD, WS and in children with typical development. Comprehension of what motor act was being done and of why it was being done was assessed with or without contextual cueing using a computer-based task. The results showed that what understanding was impaired in the WS group, but not in the ASD group, which showed mental-age appropriate performance. Why understanding was impaired in both experimental groups. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Sparaci, Laura; Stefanini, Silvia; Rizzolatti, Giacomo] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. [Sparaci, Laura] Natl Res Council CNR Italy, Inst Cognit Sci & Technol ISTC, I-00161 Rome, Italy. [Sparaci, Laura; D'Elia, Lidia; Vicari, Stefano] Bambino Gesu Childrens Hosp IRCCS, Rome, Italy. [Stefanini, Silvia] Local Hlth Unit AUSL, Dept Mental Hlth, Parma, Italy. [Rizzolatti, Giacomo] Italian Inst Technol, Parma Unit, Brain Ctr Social & Motor Cognit, Parma, Italy. RP Sparaci, L (reprint author), Natl Res Council CNR Italy, Inst Cognit Sci & Technol ISTC, Via Nomentana 56, I-00161 Rome, Italy. EM laura.sparaci@istc.cnr.it FU Fondazione Monte Parma; ERC Advanced Grant "Cogsystems" [250013]; Fondazione Handicap Dopodinoi, Onlus; MIUR-FIRB TOUM project [RBFR086HEW] FX The work reported in this paper was supported by: Fondazione Monte Parma and ERC Advanced Grant "Cogsystems" (no. 250013) to G. R.; Fondazione Handicap Dopodinoi, Onlus to S. V.; MIUR-FIRB TOUM project (no. RBFR086HEW) to L. S. We are very grateful to the Italian Williams Syndrome Association (AISW) as well as to the Primary and Secondary Schools San Vitale-Fra' Salimbene Parma and San Francesco D'Assisi Rome for helping us in this study. We wish to thank Dr Patrizio Pasqualetti and Dr Pasquale Rinaldi for their help with statistical analyses. In particular, we wish to thank all the children and families who have participated in this research. 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PD AUG PY 2014 VL 7 IS 4 BP 421 EP 432 DI 10.1002/aur.1370 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300002 PM 24604708 ER PT J AU Warner, G Moss, J Smith, P Howlin, P AF Warner, Georgina Moss, Joanna Smith, Patrick Howlin, Patricia TI Autism Characteristics and Behavioural Disturbances in similar to 500 Children with Down's Syndrome in England and Wales SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorder; Down's syndrome; social communication questionnaire; strengths and difficulties questionnaire ID FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; DIFFICULTIES QUESTIONNAIRE; PREVALENCE; DIAGNOSIS; STRENGTHS; CHECKLIST; VALIDITY; PROJECT AB Recent research shows that a significant minority of children with Down's syndrome (DS) also meet diagnostic criteria for an autism spectrum disorder (ASD). The present study investigated what proportion of children aged 6-15 years with a confirmed diagnosis of DS in England and Wales display autistic-type behaviours, and explored the characteristics of this group of children. The Social Communication Questionnaire (SCQ) was used to screen for autism characteristics and the Strengths and Difficulties Questionnaire (SDQ) to explore behavioural difficulties. The proportion of children who met the cut-off score for ASD on the SCQ (total score >= 15) was 37.7% (95% CI: 33.4-42.0%); for autism (total score >= 22) the proportion was 16.5% (95% CI: 13.2-19.8%). Children who met the cut-off for ASD were significantly more likely to be reported as having emotional symptoms, conduct problems and hyperactivity on the SDQ than children who scored well below cut-off (total score < 10). However, the profile of their autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD. The pervasiveness of ASD in children with DS in England and Wales is substantially higher than in the general population. These children also experience significantly greater behavioural problems than children with DS only. Early detection of autism characteristics is important for appropriate intervention. However, the unusual profile of autism characteristics in this group may affect the recognition of the disorder and hinder the implementation of appropriate interventions. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Warner, Georgina; Smith, Patrick; Howlin, Patricia] Kings Coll London, Inst Psychiat, Dept Psychol, London SE5 8AF, England. [Moss, Joanna] Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Birmingham B15 2TT, W Midlands, England. [Moss, Joanna] UCL, Inst Cognit Neurosci, London, England. [Howlin, Patricia] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia. 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Molholm, Sophie TI Susceptibility to Distraction in Autism Spectrum Disorder: Probing the Integrity of Oscillatory Alpha-Band Suppression Mechanisms SO AUTISM RESEARCH LA English DT Article DE autism; EEG; oscillations; attention ID SELECTIVE VISUAL-ATTENTION; EVENT-RELATED POTENTIALS; SPATIAL ATTENTION; VISUOSPATIAL ATTENTION; INNER SPEECH; FUNCTIONAL CONNECTIVITY; CORTICAL CONNECTIVITY; OCCIPITAL CORTEX; CHILDREN; EEG AB When attention is directed to one information stream over another, the brain can be configured in advance to selectively process the relevant stream and suppress potentially distracting inputs. One key mechanism of suppression is through the deployment of anticipatory alpha-band (similar to 10 Hz) oscillatory activity, with greater alpha-band power observed in cortical regions that will ultimately process the distracting stream. Atypical attention has been implicated in autism spectrum disorder (ASD), including greater interference by distracting task-irrelevant inputs. Here we tested the integrity of these alpha-band mechanisms in ASD using an intersensory attention task. Electroencephalography (EEG) was recorded while participants were cued on a trial-by-trial basis to selectively deploy attention to the visual or auditory modality in anticipation of a target within the cued modality. Whereas typically developing (TD) children showed the predicted alpha-band modulation, with increased alpha-band power over parieto-occipital scalp when attention was deployed to the auditory compared with the visual modality, this differential pattern was entirely absent at the group level in the ASD cohort. Further, only the ASD group showed impaired performance due to the presence of task-irrelevant sensory information. These data suggest that impaired modulation of alpha-band activity plays a role in increased distraction from extraneous sensory inputs in ASD. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Murphy, Jeremy W.; Foxe, John J.; Peters, Joanna B.; Molholm, Sophie] Albert Einstein Coll Med, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, Childrens Evaluat & Rehabil Ctr, Dept Pediat, Bronx, NY 10461 USA. [Murphy, Jeremy W.; Foxe, John J.; Peters, Joanna B.; Molholm, Sophie] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. [Murphy, Jeremy W.; Foxe, John J.; Molholm, Sophie] CUNY City Coll, Dept Psychol, Program Cognit Neurosci, New York, NY 10031 USA. [Murphy, Jeremy W.; Foxe, John J.; Molholm, Sophie] CUNY City Coll, Dept Biol, Program Cognit Neurosci, New York, NY 10031 USA. [Peters, Joanna B.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Program Clin Psychol, Bronx, NY USA. RP Molholm, S (reprint author), Albert Einstein Coll Med, Sheryl & Daniel R Tishman Cognit Neurophysiol Lab, Childrens Evaluat & Rehabil Ctr, Dept Pediat, Van Etten Bldg,Wing 1C,1225 Morris Pk Ave, Bronx, NY 10461 USA. EM sophie.molholm@einstein.yu.edu FU U.S. National Institute of Mental Health [MH085322]; Eunice Kennedy Shriver National Institute of Child Health & Human Development [NICHD P30 HD071593] FX Primary funding for this work was provided by a grant from the U.S. National Institute of Mental Health (MH085322 to S. M and J.J.F). The Human Clinical Phenotyping Core, where the children enrolled in this study were clinically evaluated, is a facility of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) which is funded through a center grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD P30 HD071593). 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TI Family-Based Clinical Associations and Functional Characterization of the Serotonin 2A Receptor Gene (HTR2A) in Autism Spectrum Disorder SO AUTISM RESEARCH LA English DT Article DE autism; serotonin; gene expression; HTR2A; rs6311; monoamine ID DIAGNOSTIC OBSERVATION SCHEDULE; GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; DE-NOVO MUTATIONS; 5-HT2A RECEPTOR; SYNAPTIC PATHOPHYSIOLOGY; MESSENGER-RNA; COMMON; CHILDREN; POLYMORPHISMS AB The serotonin 2A receptor gene (HTR2A) harbors two functional single nucleotide polymorphisms (SNPs) that are frequent in populations of African and European descent; rs6311, which affects mRNA expression, and rs6314, which changes the amino acid sequence of the encoded protein and affects the signaling properties of the receptor. Multiple clinical associations support a role for these SNPs in cognitive and neuropsychiatric phenotypes, although studies in autism spectrum disorder (ASD) remain equivocal. Here, we tested transmission disequilibrium of rs6311 and rs6314 in a cohort of 158 ASD trios (simplex and multiplex), observing significant under-transmission of the minor "A" allele of rs6311 to offspring with ASD (permuted P = 0.0004). Consistent with our previous findings in the dorsolateral prefrontal cortex of unaffected individuals, rs6311/A decreases expression of HTR2A mRNA with an extended 5' untranslated region (UTR) in the frontopolar cortex in brain samples from 54 ASD patients and controls. Interpreting the clinical results in the context of our mRNA expression analysis, we speculate that any risk associated with rs6311 is conferred by greater expression of the long 5' UTR mRNA isoform. The current study corroborates earlier associations between rs6311 and ASD in a family study, supporting the hypothesis that rs6311 plays a modulatory role in ASD risk. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Smith, Ryan M.; Sadee, Wolfgang] Ohio State Univ, Dept Pharmacol, Coll Med, Ctr Pharmacogen, Columbus, OH 43210 USA. [Banks, Wesley; Hansen, Emily; Herman, Gail E.] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet, Columbus, OH 43210 USA. [Banks, Wesley; Hansen, Emily; Herman, Gail E.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Sadee, Wolfgang] Ohio State Univ, Dept Pharm, Columbus, OH 43210 USA. [Sadee, Wolfgang] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [Sadee, Wolfgang] Ohio State Univ, Dept Human Genet Internal Med, Columbus, OH 43210 USA. [Sadee, Wolfgang] Ohio State Univ, Dept Environm Hlth Sci, Columbus, OH 43210 USA. RP Smith, RM (reprint author), Ohio State Univ, Dept Pharmacol, 5184A Graves Hall,333 W10th Ave, Columbus, OH 43210 USA. EM Ryan.Smith2@osumc.edu FU National Institute of General Medical Sciences [U01GM092655]; United States Air Force Department of Defense [FA7014-09-2-0004, FA8650-12-2-6359] FX The authors declare no competing interests. This work was supported by the National Institute of General Medical Sciences (U01GM092655 to W. S.) and the United States Air Force Department of Defense (FA7014-09-2-0004 and FA8650-12-2-6359 to Gail E. Herman). We are grateful to all the families participating in the CORA registry. We thankfully acknowledge Harvard Brain Tissue Resource Center and the NICHD Brain and Tissue Bank for providing brain tissues, granted to Ryan M. Smith and Wolfgang Sadee from the Autism Tissue Program, made possible by the donations of generous family members. 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PD AUG PY 2014 VL 7 IS 4 BP 459 EP 467 DI 10.1002/aur.1383 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300005 PM 24753316 ER PT J AU McCormick, C Hessl, D Macari, SL Ozonoff, S Green, C Rogers, SJ AF McCormick, Carolyn Hessl, David Macari, Suzanne L. Ozonoff, Sally Green, Cherie Rogers, Sally J. TI Electrodermal and Behavioral Responses of Children With Autism Spectrum Disorders to Sensory and Repetitive Stimuli SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorder; psychophysiology; sensory; repetitive behaviors ID DEVELOPMENTAL DELAYS; YOUNG-CHILDREN; MISSING DATA; INDIVIDUALS; INTEGRATION; PATTERNS; MOTOR; AGE AB Parents frequently report that their children with autism spectrum disorders (ASD) respond atypically to sensory stimuli. Repetitive behaviors are also part of the ASD behavioral profile. Abnormal physiological arousal may underlie both of these symptoms. Electrodermal activity (EDA) is an index of sympathetic nervous system arousal. The goals of this study were twofold: (1) to pilot methods for collecting EDA data in young children and (2) to examine hypothesized relationships among EDA, and sensory symptoms and repetitive behaviors in children with ASD as compared with children with typical development. EDA was recorded on 54 young children with ASD and on 33 children with typical development (TD) during a protocol that included baseline, exposure to sensory and repetitive stimuli, and play. Parents completed standardized questionnaires regarding their child's sensory symptoms and repetitive behaviors. Frequency and type of repetitive behavior during play was coded offline. Comparisons between EDA data for ASD and TD groups indicated no significant between-group differences in any measures. Parents of children with ASD reported more abnormal responses to sensory stimuli and more repetitive behaviors, but scores on these measures were not significantly correlated with EDA or with frequency of observed repetitive behaviors. Parent report of frequency and severity of sensory symptoms was significantly correlated with reports of repetitive behaviors in both groups. Although parents of children with ASD report high levels of sensory symptoms and repetitive behaviors, these differences are not related to measured EDA arousal or reactivity. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [McCormick, Carolyn; Hessl, David; Ozonoff, Sally; Rogers, Sally J.] Univ Calif Davis, MIND Inst, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Macari, Suzanne L.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Green, Cherie] La Trobe Univ, Olga Tennison Autism Res Ctr, Melbourne, Vic, Australia. RP McCormick, C (reprint author), Univ Calif Davis, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA. EM carolyn.mccormick@ucdmc.ucdavis.edu FU UC Davis MIND Institute FX This research was conducted as part of the Autism Phenome Project and supported by the UC Davis MIND Institute. We would like to acknowledge Cynthia Zierhut, Lisa Cochran, Susan Rumberg, and Lou Ann Barnett for their roles on the project, as well as Jennifer Bernstein and Olha Kalish for help with coding. We want to thank all of the families who made this research possible. 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PD AUG PY 2014 VL 7 IS 4 BP 468 EP 480 DI 10.1002/aur.1382 PG 13 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300006 PM 24788961 ER PT J AU Cook, R Brewer, R Shah, P Bird, G AF Cook, Richard Brewer, Rebecca Shah, Punit Bird, Geoffrey TI Intact Facial Adaptation in Autistic Adults SO AUTISM RESEARCH LA English DT Article DE autism; adaptation; aftereffects; facial identity; facial expressions ID FACE RECOGNITION; SPECTRUM DISORDERS; CHILDREN; IDENTITY; EMOTION; ALEXITHYMIA; EXPRESSIONS; PERCEPTION; FEATURES; 1ST AB Adaptation paradigms seek to bias subsequently viewed stimuli through prolonged exposure to an adapting stimulus, thereby giving rise to an aftereffect. Recent experiments have found that children with autism spectrum disorders (ASD) show reduced facial aftereffects, prompting some researchers to speculate that all individuals with ASD exhibit deficient facial adaptation. However, caution is required when generalizing findings from samples of children with ASD to the wider ASD population. The reduced facial aftereffects seen in child samples may instead reflect delayed or atypical developmental trajectories, whereby individuals with ASD are slower to develop adaptive mechanisms. In the present study, two experiments were conducted to determine whether high-functioning adults with ASD also show diminished aftereffects for facial identity and expression. In Experiment 1, using a procedure that minimized the contribution of low-level retinotopic adaptation, we observed substantial aftereffects comparable to those seen in matched controls, for both facial identity and expression. A similar pattern of results was seen in Experiment 2 using a revised procedure that increased the contribution of retinotopic adaptation to the facial aftereffects observed. That adults with autism can show robust facial aftereffects raises the possibility that group differences are seen only at particular points during development, and may not be a lifelong feature of the condition. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Cook, Richard] City Univ London, Dept Psychol, London EC1R OJD, England. [Brewer, Rebecca; Shah, Punit; Bird, Geoffrey] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Shah, Punit] Univ London, Birkbeck Coll, Dept Psychol Sci, London, England. [Bird, Geoffrey] UCL, Inst Cognit Neurosci, London, England. RP Cook, R (reprint author), City Univ London, Dept Psychol, Whiskin St, London EC1R OJD, England. 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PD AUG PY 2014 VL 7 IS 4 BP 481 EP 490 DI 10.1002/aur.1381 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300007 PM 24757172 ER PT J AU Hauth, I de Bruijn, YGE Staal, W Buitelaar, JK Rommelse, NN AF Hauth, Ingeborg de Bruijn, Yvette G. E. Staal, Wouter Buitelaar, Jan K. Rommelse, Nanda N. TI Testing the Extreme Male Brain Theory of Autism Spectrum Disorder in a Familial Design SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorder; extreme male brain theory; testosterone; 2D:4D; finger length; siblings; parents; empathizing; systemizing ID 4TH DIGIT LENGTH; FETAL TESTOSTERONE; SEX-DIFFERENCES; DIAGNOSTIC VALIDITY; RECEPTOR GENE; RATIO; CHILDREN; 2ND; TRAITS; HORMONE AB Autism Spectrum Disorder (ASD) may be an extreme manifestation of some male-typical traits in both neuroanatomy and cognition. Using the ratio of the second to fourth digit (2D:4D) and digit length as biomarkers of (pre- and postnatal) testosterone levels, examined was whether hypermasculinized digit ratios and/or lengths were familial traits in ASD and investigated their relation to sexually dimorphic cognitive abilities. 2D: 4D ratios and digit lengths of 216 children with ASD, 202 unaffected siblings, and 360 parents were compared with those of 174 control children and their 146 parents. Generalized Estimation Equations, Generalized Linear Models, and Linear Mixed Models were used to investigate parent-offspring relationships and group differences. In ASD probands and their relatives alike, digit length relative to overall height was significantly increased in comparison to controls. No significant group differences were found between affected and unaffected subjects, or between males and females. Additionally, 2D: 4D ratios increased with age. No (consistent) associations were found between 2D: 4D ratio or digit lengths and systemizing and empathizing skills. The findings emphasize the role of familially based elevated pre- and postnatal testosterone levels in the liability for ASD, but challenge the use of 2D: 4D ratio as a proxy of prenatal testosterone exposure solely. Given that many genes influence digit length, the exact mechanisms underlying a familial predisposition toward increased digit length in ASD are as yet unknown and needs to be explored in future studies. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Hauth, Ingeborg; Staal, Wouter; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Cognit & Behav Dept Cognit Neurosci, NL-6525 GC Nijmegen, Netherlands. [de Bruijn, Yvette G. E.; Staal, Wouter; Buitelaar, Jan K.; Rommelse, Nanda N.] Child & Adolescent Psychiat Univ Ctr, Karakter, Nijmegen, Netherlands. [Rommelse, Nanda N.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain, Cognit & Behav Dept Psychiat, NL-6525 GC Nijmegen, Netherlands. RP Rommelse, NN (reprint author), Radboud Univ Nijmegen, Med Ctr, Reinier Postlaan 12, NL-6525 GC Nijmegen, Netherlands. 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PD AUG PY 2014 VL 7 IS 4 BP 491 EP 500 DI 10.1002/aur.1384 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300008 PM 24777834 ER PT J AU Kang, V Wagner, GC Ming, X AF Kang, Victor Wagner, George C. Ming, Xue TI Gastrointestinal Dysfunction in Children With Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorders; gastrointestinal disorders; comorbid disorders; endoscopy; colonoscopy; inflammation ID SYMPTOMS; ABNORMALITIES; POPULATION; PREVALENCE; DISEASE; ASDS AB Gastrointestinal (GI) dysfunctions are frequently reported by parents of children with autism spectrum disorders (ASD) and have been recently recognized as a comorbid condition. However, the clinical significance of these GI dysfunctions remains to be delineated. This study describes the clinical characteristics, associated comorbid disorders, and endoscopic and colonoscopic evaluation of GI dysfunction in a cohort of 164 children with ASD evaluated at a pediatric neurology practice. Symptoms of GI dysfunction were prevalent: 49% of the children reported one or more chronic GI complaints, 22% exhibited diarrhea, 26% suffered from constipation. Furthermore 13% of the parents reported their children to suffer from bloating and/or being gassy and while 10% of the parents reported vomiting or gastroesophageal reflux problems. Similar rates of GI symptoms were reported among pre-school and school-aged children. Inflammation of the gut was found in 6 of the 12 subjects who underwent endoscopic and colonoscopic evaluations, however clinical symptoms did not predict the results of the evaluation. GI dysfunction was significantly associated with sleep disorders and food intolerance, but not with irritability or aggressiveness. In summary, GI dysfunction was prevalent in this cohort of children with ASD, observations consistent with the reports of parents and other clinicians. We conclude that the GI dysfunction in ASD requires proper evaluation and treatment. (C) 2014 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Kang, Victor] Johns Hopkin Univ, Sch Arts & Sci, Baltimore, MD USA. [Wagner, George C.] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Ming, Xue] Rutgers State Univ, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. [Ming, Xue] JFK Med Ctr, New Jersey Neurosci Inst, Sleep Med Ctr, Edison, NJ USA. RP Ming, X (reprint author), Rutgers State Univ, New Jersey Med Sch, 90 Bergen St,DOC 8100, Newark, NJ 07103 USA. EM mingxu@njms.rutgers.edu FU Knights of Columbus, East Hanover, NJ FX The authors wish to acknowledge the cooperation of all the parents and guardians of the participating subjects with ASD and the generous support from Knights of Columbus, East Hanover, NJ. All authors declare no conflict of interest in this study and approve this final version of the revised manuscript. 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PD AUG PY 2014 VL 7 IS 4 BP 501 EP 506 DI 10.1002/aur.1386 PG 6 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300009 PM 24753336 ER PT J AU Segers, M Rawana, J AF Segers, Magali Rawana, Jennine TI What Do We Know About Suicidality in Autism Spectrum Disorders? A Systematic Review SO AUTISM RESEARCH LA English DT Review DE autism spectrum disorders; suicide; suicidality; prevalence; risk factors; protective factors ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; DIAGNOSTIC INTERVIEW; SELF-HARM; ASPERGERS-DISORDER; ADOLESCENTS; CHILDREN; RISK; DEPRESSION; QUOTIENT AB Suicidality is a common and concerning issue across development, and there is a plethora of research on this topic among typically developing children and youth. Very little is known, however, about the nature of suicidality among individuals with autism spectrum disorders (ASDs). The purpose of the current study was to undertake a systematic literature review to assess the current state of the research literature to examine the prevalence of suicidality among individuals with ASD, related demographic and clinical profiles, and associated risk and protective factors. A literature search using key terms related to suicidality and ASD yielded 10 topical studies that were evaluated for the study objectives. Suicidality was present in 10.9-50% of the ASD samples identified in the systematic review. Further, several large-scale studies found that individuals with ASD comprised 7.3-15% of suicidal populations, a substantial subgroup. Risk factors were identified and included peer victimization, behavioral problems, being Black or Hispanic, being male, lower socioeconomic status, and lower level of education. Only one study reported on protective factors, and this is identified as a significant gap in the literature. 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PD AUG PY 2014 VL 7 IS 4 BP 507 EP 521 DI 10.1002/aur.1375 PG 15 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA AN5VJ UT WOS:000340659300010 PM 24798640 ER PT J AU Gentile, S AF Gentile, Salvatore TI Risks of neurobehavioral teratogenicity associated with prenatal exposure to valproate monotherapy: a systematic review with regulatory repercussions SO CNS SPECTRUMS LA English DT Review DE neurobehavioral teratogenicity; pregnancy; valproate ID ANTIEPILEPTIC DRUG EXPOSURE; AUTISM SPECTRUM DISORDERS; SCHOOL-AGED CHILDREN; IN-UTERO EXPOSURE; BIPOLAR DISORDER; MOOD STABILIZERS; PSYCHOLOGICAL-DEVELOPMENT; EPILEPTIC PARENTS; SODIUM VALPROATE; PREGNANCY AB Beyond its formal indications (epilepsy, bipolar disorder, and migraine), valproate sodium (VPA) is widely used in a number of other clinical conditions. Recently, however, the U. S. Food and Drug Administration (FDA) issued a warning regarding a decrease in IQ scores in children prenatally exposed to the drug. For patients with migraine, the pregnancy labeling of VPA will be changed from Category "D'' to "X.'' VPA products will remain in pregnancy category "D'' for treating epilepsy and manic episodes associated with bipolar disorder. Thus, this article aims to assess (through a computerized Medline/PubMed search) the neurobehavioral teratogenicity of valproate monotherapy, in order to evaluate alternative regulatory decisions. Reviewed information suggests a detrimental impact of antenatal valproate exposure on the global child neurodevelopment. Affected areas include not just reduced IQ scores, but also behavioral problems and a potential increase in the risk for a future diagnosis of attention-deficit/ hyperactivity disorder. An increased risk of developing autism-spectrum disorders has also been reported. Thus, in my opinion, VPA should be assigned definitively to the Category "X,'' independent of any considerations about its clinical indications, and should be strictly avoided during pregnancy, due to the demonstrated risk of both neurobehavioral and neurocognitive teratogenicity. C1 [Gentile, Salvatore] ASL Salerno, Mental Hlth Ctr, Dept Mental Hlth, Salerno, Italy. [Gentile, Salvatore] Univ Naples Federico II, Med Sch Federico II, Dept Neurosci, Naples, Italy. RP Gentile, S (reprint author), ASL Salerno, Mental Hlth Ctr, Dept Mental Hlth, 63 Cava Tirreni Vietri Mare,Piazza Galdi, Salerno, Italy. 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PD AUG PY 2014 VL 19 IS 4 BP 305 EP 315 DI 10.1017/S1092852913000990 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AN9RD UT WOS:000340944500004 PM 24571806 ER PT J AU Blockus, H Chedotal, A AF Blockus, Heike Chedotal, Alain TI The multifaceted roles of Slits and Robos in cortical circuits: from proliferation to axon guidance and neurological diseases SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID F-BAR DOMAIN; NEURONAL MIGRATION; INTERNEURON MIGRATION; THALAMIC PROJECTIONS; MAMMALIAN FOREBRAIN; CORPUS-CALLOSUM; CEREBRAL-CORTEX; MIDLINE; EXPRESSION; RECEPTORS AB Slit repulsion, mediated by Robe receptors, is known to play a major role in axon guidance in the nervous system. However, recent studies have revealed that in the mammalian cortex these molecules are highly versatile and that their function extends far beyond axon guidance. They act at all phases of development to control neurogenesis, neuronal migration, axon patterning, dendritic outgrowth and spinogenesis. The expression of Robe receptors in cortical and thalamocortical axons (TCAs) is tightly regulated by a combination of transcription factors (TFs), proteases and activity. These findings also suggest that Slit and Robes have influenced the evolution of cortical circuits. Last, novel genetic evidence associates various neurological disorders, such as autism, to abnormal Slit/Robo signaling. C1 [Blockus, Heike; Chedotal, Alain] INSERM, UMR S968, Inst Vis, F-75012 Paris, France. [Blockus, Heike; Chedotal, Alain] Univ Paris 06, Sorbonne Univ, UMR S968, Inst Vis, F-75012 Paris, France. [Blockus, Heike; Chedotal, Alain] CNRS, UMR7210, F-75012 Paris, France. RP Chedotal, A (reprint author), INSERM, UMR S968, Inst Vis, F-75012 Paris, France. EM alain.chedotal@inserm.fr FU Fondation pour la recherche Medicale (Programme equipe FRM); Labex Lifesciences; Ecole des Neurosciences de Paris Ile-de-France (ENP); DIM Cerveau Pensee FX A.C. is supported by grants from the Fondation pour la recherche Medicale (Programme equipe FRM) and the Labex Lifesciences. H.B. is a recipient of the ENP Graduate Program fellowship from Ecole des Neurosciences de Paris Ile-de-France (ENP) and DIM Cerveau & Pensee. 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Opin. Neurobiol. PD AUG PY 2014 VL 27 BP 82 EP 88 DI 10.1016/j.conb.2014.03.003 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AO3HN UT WOS:000341220400013 PM 24698714 ER PT J AU Ackerman, S Wenegrat, J Rettew, D Althoff, R Bernier, R AF Ackerman, Sean Wenegrat, Julia Rettew, David Althoff, Robert Bernier, Raphael TI No increase in autism-associated genetic events in children conceived by assisted reproduction SO FERTILITY AND STERILITY LA English DT Article DE Assisted reproduction; assisted reproductive technology; autism; copy number variation ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; LOW-BIRTH-WEIGHT; SPECTRUM DISORDERS; INCREASED RISK; HEALTH OUTCOMES; PRETERM BIRTH; FOLLOW-UP; TECHNOLOGY; BORN AB Objective: To understand the rate of genetic events in patients with autism spectrum disorder (ASD) who were exposed to assisted reproduction. Design: Case control study using genetics data. Setting: Twelve collaborating data collection sites across North America as part of the Simons Simplex Collection. Patient(s): 2,760 children with ASD, for whom 1,994 had published copy number variation data and 424 had published gene mutation status available. Intervention(s): None. Main Outcome Measure(s): Rates of autism-associated genetic events in children with ASD conceived with assisted reproduction versus those conceived naturally. Result(s): No statistically significant differences in copy number variations or autism-associated gene-disrupting events were found when comparing ASD patients exposed to assisted reproduction with those not exposed to assisted reproduction. Conclusion(s): This is the first large genetic association to concurrently examine the genotype of individuals with ASD in relation to their exposure to ART versus natural conception, and it adds reassuring evidence to the argument that ART does not increase the risk of ASD. ((C)2014 by American Society for Reproductive Medicine.) C1 [Ackerman, Sean; Rettew, David; Althoff, Robert] Univ Vermont, Sch Med, Dept Psychiat, Burlington, VT 05401 USA. [Wenegrat, Julia; Bernier, Raphael] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Ackerman, S (reprint author), Univ Vermont, Fletcher Allen Hlth Care, 111 Colchester Ave,MS 341BA1, Burlington, VT 05401 USA. EM sean.ackerman@vtmednet.org FU Simons Foundation Autism Research Initiative FX Funded by the Simons Foundation Autism Research Initiative. 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Steril. PD AUG PY 2014 VL 102 IS 2 BP 388 EP 393 DI 10.1016/j.fertnstert.2014.04.020 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AO4HX UT WOS:000341299000015 PM 24842673 ER PT J AU Batey, CA Missiuna, CA Timmons, BW Hay, JA Faught, BE Cairney, J AF Batey, C. A. Missiuna, C. A. Timmons, B. W. Hay, J. A. Faught, B. E. Cairney, J. TI Self-efficacy toward physical activity and the physical activity behavior of children with and without Developmental Coordination Disorder SO HUMAN MOVEMENT SCIENCE LA English DT Article DE Developmental Coordination Disorder; Self-efficacy; Physical activity; Developmental disorders and autism ID DEFICIT HYPERACTIVITY DISORDER; ACTIVITY ENERGY-EXPENDITURE; MOVEMENT ASSESSMENT BATTERY; ADOLESCENTS; MOTOR; RISK; PERCEPTIONS; HYPOTHESIS; CLUMSINESS; FITNESS AB Purpose: Affecting 5-6% of children, Developmental Coordination Disorder (DCD) is a prevalent chronic condition. The nature of the disorder - impaired motor coordination - makes avoidance of physical activity (PA) common. The purpose of this study was to examine the effect of barrier and task self-efficacy on PA behavior in children with DCD and a group of typically developing (TD) children. Methods: Children were compared on their perceived ability to complete different intensities and duration of PA (task efficacy) and their confidence in completing PA when faced with everyday barriers (barrier efficacy). An accelerometer was used to record their activity over the subsequent week. Results: Children with DCD were found to have significantly lower task efficacy and barrier efficacy. They also spent significantly less time in moderate to vigorous physical activity (MVPA). Multivariate analyses revealed that gender modified the relationship for both groups. Separate multivariate regressions, were therefore conducted by gender. A direct effect of DCD on PA was observed for boys, but not for girls. Further analyses showed that neither task efficacy nor barrier efficacy influenced the relationship between DCD and PA. Conclusion: Results from this study confirm that children with DCD have lower task and barrier self-efficacy than TD children and that males have lower PA levels than their TD peers; however neither task or barrier self-efficacy mediated the relationship between DCD and PA. (C) 2013 Published by Elsevier B.V. C1 [Batey, C. A.; Missiuna, C. A.; Timmons, B. W.; Cairney, J.] McMaster Univ, Fac Hlth Sci, Hamilton, ON L8S 4K1, Canada. [Hay, J. A.; Faught, B. E.] Brock Univ, Fac Appl Hlth Sci, St Catharines, ON L2S 3A1, Canada. RP Cairney, J (reprint author), Dept Family Med, 175 Longwood Rd South, Hamilton, ON L8P 0A1, Canada. EM cairnej@mcmaster.ca FU Canadian Institutes of Health Research [66959]; Department of Family Medicine at McMaster University FX This study was supported by the Canadian Institutes of Health Research (Grant #: 66959). Dr. Cairney is supported through an endowed professorship in the Department of Family Medicine at McMaster University. The Physical Health Activity Study Team (PHAST) appreciates the commitment by children, parents and teachers from the District School Board of Niagara. Laboratory and home-based assessment would not have been successful without the diligent efforts of the PHAST research coordinator, Nadilein Mahlberg. Finally, thanks to Joyce Obeid for all of her hard work and help with analyzing the accelerometer data. 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PD AUG PY 2014 VL 36 BP 258 EP 271 DI 10.1016/j.humov.2013.10.003 PG 14 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA AO4XW UT WOS:000341345700021 PM 24345354 ER PT J AU Aresti-Bartolome, N Garcia-Zapirain, B AF Aresti-Bartolome, Nuria Garcia-Zapirain, Begonya TI Technologies as Support Tools for Persons with Autistic Spectrum Disorder: A Systematic Review SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Review DE ASD; tools for therapy; robots; telehealth systems; dedicated applications; virtual reality applications ID HIGH-FUNCTIONING AUTISM; VIRTUAL-REALITY; SOCIAL-SKILLS; YOUNG-CHILDREN; TELEHEALTH SYSTEM; ASPERGER-SYNDROME; PROBLEM BEHAVIOR; MIXED REALITY; ADOLESCENTS; ADULTS AB This study analyzes the technologies most widely used to work on areas affected by the Autistic Spectrum Disorder (ASD). Technologies can focus on the strengths and weaknesses of this disorder as they make it possible to create controlled environments, reducing the anxiety produced by real social situations. Extensive research has proven the efficiency of technologies as support tools for therapy and their acceptation by ASD sufferers and the people who are with them on a daily basis. This article is organized by the types of systems developed: virtual reality applications, telehealth systems, social robots and dedicated applications, all of which are classified by the areas they center on: communication, social learning and imitation skills and other ASD-associated conditions. 40.5% of the research conducted is found to be focused on communication as opposed to 37.8% focused on learning and social imitation skills and 21.6% which underlines problems associated with this disorder. Although most of the studies reveal how useful these tools are in therapy, they are generic tools for ASD sufferers in general, which means there is a lack of personalised tools to meet each person's needs. C1 [Aresti-Bartolome, Nuria; Garcia-Zapirain, Begonya] Univ Deusto, DeustoTech LIFE Unit, DeustoTech Inst Technol, Bilbao 48007, Spain. RP Aresti-Bartolome, N (reprint author), Univ Deusto, DeustoTech LIFE Unit, DeustoTech Inst Technol, Avda Univ 24, Bilbao 48007, Spain. EM nuria.aresti@deusto.es; mbgarciazapi@deusto.es RI Garcia-Zapirain, Begona/L-5619-2014 OI Garcia-Zapirain, Begona/0000-0002-9356-1186 FU Regional Council of Bizkaia, the Basque Country Department of Education, Universities and Research FX This work was partially supported by the Regional Council of Bizkaia, the Basque Country Department of Education, Universities and Research. 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Public Health PD AUG PY 2014 VL 11 IS 8 BP 7767 EP 7802 DI 10.3390/ijerph110807767 PG 36 WC Environmental Sciences SC Environmental Sciences & Ecology GA AO1UX UT WOS:000341101700015 PM 25093654 ER PT J AU Rahbar, MH Samms-Vaughan, M Ma, JZ Bressler, J Loveland, KA Ardjomand-Hessabi, M Dickerson, AS Grove, ML Shakespeare-Pellington, S Beecher, C McLaughlin, W Boerwinkle, E AF Rahbar, Mohammad H. Samms-Vaughan, Maureen Ma, Jianzhong Bressler, Jan Loveland, Katherine A. Ardjomand-Hessabi, Manouchehr Dickerson, Aisha S. Grove, Megan L. Shakespeare-Pellington, Sydonnie Beecher, Compton McLaughlin, Wayne Boerwinkle, Eric TI Role of Metabolic Genes in Blood Arsenic Concentrations of Jamaican Children with and without Autism Spectrum Disorder SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE arsenic; autism spectrum disorder (ASD); glutathione S-transferase (GST) genes; detoxification; interactions ID GLUTATHIONE S-TRANSFERASES; OXIDATIVE STRESS; DRINKING-WATER; CHILDHOOD AUTISM; DNA METHYLATION; MERCURY LEVELS; SKIN-LESIONS; EXPOSURE; POLYMORPHISMS; RISK AB Arsenic is a toxic metalloid with known adverse effects on human health. Glutathione-S-transferase (GST) genes, including GSTT1, GSTP1, and GSTM1, play a major role in detoxification and metabolism of xenobiotics. We investigated the association between GST genotypes and whole blood arsenic concentrations (BASC) in Jamaican children with and without autism spectrum disorder (ASD). We used data from 100 ASD cases and their 1: 1 age- and sex-matched typically developing (TD) controls (age 2-8 years) from Jamaica. Using log-transformed BASC as the dependent variable in a General Linear Model, we observed a significant interaction between GSTP1 and ASD case status while controlling for several confounding variables. However, for GSTT1 and GSTM1 we did not observe any significant associations with BASC. Our findings indicate that TD children who had the Ile/Ile or Ile/Val genotype for GSTP1 had a significantly higher geometric mean BASC than those with genotype Val/Val (3.67 mu g/L vs. 2.69 mu g/L, p < 0.01). Although, among the ASD cases, this difference was not statistically significant, the direction of the observed difference was consistent with that of the TD control children. These findings suggest a possible role of GSTP1 in the detoxification of arsenic. C1 [Rahbar, Mohammad H.; Boerwinkle, Eric] Univ Texas Sch Publ Hlth Houston, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX 77030 USA. [Rahbar, Mohammad H.; Ma, Jianzhong] Univ Texas Hlth Sci Ctr Houston, Div Clin & Translat Sci, Dept Internal Med, Sch Med, Houston, TX 77030 USA. [Rahbar, Mohammad H.; Ardjomand-Hessabi, Manouchehr; Dickerson, Aisha S.] Univ Texas Hlth Sci Ctr Houston, CCTS, Houston, TX 77030 USA. [Samms-Vaughan, Maureen; Shakespeare-Pellington, Sydonnie] Univ W Indies, Dept Child & Adolescent Hlth, Kingston 7, Jamaica. [Bressler, Jan; Grove, Megan L.; Boerwinkle, Eric] Univ Texas Sch Publ Hlth Houston, Ctr Human Genet, Houston, TX 77030 USA. [Loveland, Katherine A.] Univ Texas Med Sch Houston, Dept Psychiat & Behav Sci, Houston, TX 77054 USA. [Beecher, Compton; McLaughlin, Wayne] Univ W Indies, Dept Basic Med Sci, Kingston 7, Jamaica. [McLaughlin, Wayne] Univ W Indies, Caribbean Genet CARIGEN, Kingston 7, Jamaica. RP Rahbar, MH (reprint author), Univ Texas Sch Publ Hlth Houston, Div Epidemiol Human Genet & Environm Sci EHGES, Houston, TX 77030 USA. EM Mohammad.H.Rahbar@uth.tmc.edu; msammsvaughan@gmail.com; Jianzhong.Ma@uth.tmc.edu; Jan.Bressler@uth.tmc.edu; Katherine.A.Loveland@uth.tmc.edu; Manouchehr.A.Hessabi@uth.tmc.edu; Aisha.S.Dickerson@uth.tmc.edu; Megan.L.Grove@uth.tmc.edu; sydonniesp@gmail.com; compton.beecher@uwimona.edu.jm; wayne.mclaughlin@uwimona.edu.jm; Eric.Boerwinkle@uth.tmc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health Fogarty International Center (NIH-FIC) [R21HD057808]; National Institute of Environmental Health Sciences (NIEHS) [R01ES022165]; Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS); NIH Centers for Translational Science Award (NIH CTSA) [UL1 RR024148]; National Center for Research Resources (NCRR) [UL1 TR000371]; National Center for Advancing Translational Sciences (NCATS) FX This research is co-funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health Fogarty International Center (NIH-FIC) by a grant (R21HD057808) as well as National Institute of Environmental Health Sciences (NIEHS) by a grant (R01ES022165) awarded to University of Texas Health Science Center at Houston. We also acknowledge the support provided by the Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the NIH Centers for Translational Science Award (NIH CTSA) grant (UL1 RR024148), awarded to University of Texas Health Science Center at Houston in 2006 by the National Center for Research Resources (NCRR) and its renewal (UL1 TR000371) by the National Center for Advancing Translational Sciences (NCATS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the NIH-FIC or NIEHS or the NCRR or the NCATS. 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Here, we apply such findings to a minimalist robot face design, which was run through a series of experiments with human subjects (n = 75) exploring the effect of various factors, including added neck motion and degree of expression. Facial expression identification rates were similar to more complex robots. In addition, added neck motion significantly improved facial expression identification rates to 100 % for all expressions (except Fear). The Negative Attitudes towards Robots (NARS) and Godspeed scales were also collected to examine user perceptions, e.g. perceived animacy and intelligence. The project aims to answer a number of fundamental questions about robotic face design, as well as to develop inexpensive and replicable robotic faces for experimental purposes. C1 [Bennett, Casey C.; Sabanovic, Selma] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47408 USA. [Bennett, Casey C.] Centerstone Res Inst, Dept Informat, Bloomington, IN 47401 USA. RP Bennett, CC (reprint author), Centerstone Res Inst, Dept Informat, 365 South Pk Ridge Rd, Bloomington, IN 47401 USA. EM cabennet@indiana.edu FU Indiana University's School of Informatics and Computing FX The authors would like to thank Amyra Asamoah, Kay Jessee, and Matthew R. Francisco for their assistance in performing this research. Funding was provided by Indiana University's School of Informatics and Computing. 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J. Soc. Robot. PD AUG PY 2014 VL 6 IS 3 SI SI BP 367 EP 381 DI 10.1007/s12369-014-0237-z PG 15 WC Robotics SC Robotics GA AN3NW UT WOS:000340496200006 ER PT J AU Robins, B Dautenhahn, K AF Robins, Ben Dautenhahn, Kerstin TI Tactile Interactions with a Humanoid Robot: Novel Play Scenario Implementations with Children with Autism SO INTERNATIONAL JOURNAL OF SOCIAL ROBOTICS LA English DT Article DE Robot-assisted play; Assistive technology; Human-robot interaction; Autism therapy ID ASSISTED PLAY AB The work presented in this paper was part of our investigation in the ROBOSKIN project. The project has developed new robot capabilities based on the tactile feedback provided by novel robotic skin, with the aim to provide cognitive mechanisms to improve human-robot interaction capabilities. This article presents two novel tactile play scenarios developed for robot-assisted play for children with autism. The play scenarios were developed against specific educational and therapeutic objectives that were discussed with teachers and therapists. These objectives were classified with reference to the ICF-CY, the International Classification of Functioning-version for Children and Youth. The article presents a detailed description of the play scenarios, and case study examples of their implementation in HRI studies with children with autism and the humanoid robot KASPAR. C1 [Robins, Ben; Dautenhahn, Kerstin] Univ Hertfordshire, Sch Comp Sci, Adapt Syst Res Grp, Hatfield AL10 9AB, Herts, England. RP Robins, B (reprint author), Univ Hertfordshire, Sch Comp Sci, Adapt Syst Res Grp, Hatfield AL10 9AB, Herts, England. EM b.robins@herts.ac.uk; K.Dautenhahn@herts.ac.uk FU European Commission [FP7-231500-ROBOSKIN] FX This work has been partially supported by the European Commission under contract number FP7-231500-ROBOSKIN CR Amirabdollahian F, 2009, TACTILE SENSING WORK Bannerman-Haig S, 1999, PROCESS ARTS THERAPI Baron-Cohen Simon, 1995, MINDBLINDNESS ESSAY Bernstein P, 1986, THEORETICAL APPROACH Boccanfuso L, 2011, INT J SOC ROBOT, V3, P337, DOI 10.1007/s12369-011-0110-2 Bruner J. S., 1990, ACTS MEANING Cabibihan JJ, 2013, INT J SOC ROBOT, V5, P593, DOI 10.1007/s12369-013-0202-2 Caldwell P, 1996, GETTING TOUCH WAYS W Carroll J. 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S., 1978, MIND SOC Wing L., 1996, AUTISTIC SPECTRUM Winnicott D. W., 1971, PLAYING REALITY World Health Organisation, 2001, INT CLASS FUNCT DIS NR 51 TC 1 Z9 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1875-4791 EI 1875-4805 J9 INT J SOC ROBOT JI Int. J. Soc. Robot. PD AUG PY 2014 VL 6 IS 3 SI SI BP 397 EP 415 DI 10.1007/s12369-014-0228-0 PG 19 WC Robotics SC Robotics GA AN3NW UT WOS:000340496200008 ER PT J AU Wolbring, G Yumakulov, S AF Wolbring, Gregor Yumakulov, Sophya TI Social Robots: Views of Staff of a Disability Service Organization SO INTERNATIONAL JOURNAL OF SOCIAL ROBOTICS LA English DT Article DE Disabled people; People with disabilities; Disability service organization; Perception of social robots ID AUTISM SPECTRUM DISORDERS; CHILDREN; THERAPY; DESIGN; CARE; MACHINES; BEHAVIOR AB Social robotics is an emerging field, with many applications envisioned for people with disabilities. This project examined the so far invisible views of disability service organization workers towards social robotics. Because community service workers' views shape community-based rehabilitation (an area of health interventions that focuses on social determinants), it is important to examine their views towards social robotics applications which are largely developed under a clinical/medical view of disability. We administered a survey to employees of a Saskatchewan disability service organization. Out of 44 respondents, 80 % were female, most aged 21-65 years. Robotics applications perceived to be important included domestic robots, and rehabilitation robots. Least important applications included eldercare robots, companion robots, and pet robots. Most participants felt that robots cannot replace human touch, human interaction, or emotional companionship, and that they cannot/should not replace human workers in the disability setting. Many expressed concerns about safety, normality for disabled people, and artificial interactions. Respondents also had views on whether a social robot can be a bully or could be bullied. We submit that the perspectives our respondents exhibited might be useful to consider in the development of social robots for applications around disability in order to ensure acceptable and relevant products. C1 [Wolbring, Gregor; Yumakulov, Sophya] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. RP Wolbring, G (reprint author), Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. EM gwolbrin@ucalgary.ca; syumakul@ucalgary.ca FU Faculty of Medicine, University of Calgary FX This work was in part supported by a Bridge funding grant of GW from the Faculty of Medicine, University of Calgary; we would like to thank the University of Calgary for paying for the Springer open access option through their open access fund. 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PD AUG PY 2014 VL 168 IS 8 BP 698 EP 699 DI 10.1001/jamapediatrics.2014.585 PG 2 WC Pediatrics SC Pediatrics GA AN0TZ UT WOS:000340298200004 PM 24911611 ER PT J AU Buescher, AVS Cidav, Z Knapp, M Mandell, DS AF Buescher, Ariane V. S. Cidav, Zuleyha Knapp, Martin Mandell, David S. TI Costs of Autism Spectrum Disorders in the United Kingdom and the United States SO JAMA PEDIATRICS LA English DT Article ID HEALTH-CARE UTILIZATION; PSYCHIATRIC-HOSPITALIZATION; CHILDREN; EXPENDITURES; EMPLOYMENT; SERVICE; UK; EXPERIENCES; ADULTS; HOME AB IMPORTANCE The economic effect of autism spectrum disorders (ASDs) on individuals with the disorder, their families, and society as a whole is poorly understood and has not been updated in light of recent findings. OBJECTIVE To update estimates of age-specific, direct, indirect, and lifetime societal economic costs, including new findings on indirect costs, such as individual and parental productivity costs, associated with ASDs. DESIGN, SETTING, AND PARTICIPANTS A literature review was conducted of US and UK studies on individuals with ASDs and their families in October 2013 using the following keywords: age, autism spectrum disorder, prevalence, accommodation, special education, productivity loss, employment, costs, and economics. Current data on prevalence, level of functioning, and place of residence were combined with mean annual costs of services and support, opportunity costs, and productivity losses of individuals with ASDs with or without intellectual disability. EXPOSURE Presence of ASDs. MAIN OUTCOMES AND MEASURES Mean annual medical, nonmedical, and indirect economic costs and lifetime costs were measured for individuals with ASDs separately for individuals with and without intellectual disability in the United States and the United Kingdom. RESULTS The cost of supporting an individual with an ASD and intellectual disability during his or her lifespan was $2.4 million in the United States and 1.5 pound million (US $2.2 million) in the United Kingdom. The cost of supporting an individual with an ASD without intellectual disability was $1.4 million in the United States and 0.92 pound million (US $1.4 million) in the United Kingdom. The largest cost components for children were special education services and parental productivity loss. During adulthood, residential care or supportive living accommodation and individual productivity loss contributed the highest costs. Medical costs were much higher for adults than for children. CONCLUSIONS AND RELEVANCE The substantial direct and indirect economic effect of ASDs emphasizes the need to continue to search for effective interventions that make best use of scarce societal resources. The distribution of economic effect across many different service systems raises questions about coordination of services and sectors. The enormous effect on families also warrants policy attention. C1 [Buescher, Ariane V. S.; Knapp, Martin] Univ London London Sch Econ & Polit Sci, Personal Social Serv Res Unit, London WC2A 2AE, England. [Cidav, Zuleyha; Mandell, David S.] Univ Penn, Ctr Mental Hlth Policy & Serv Res, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cidav, Zuleyha; Mandell, David S.] Childrens Hosp Philadelphia, Ctr ASD Res, Philadelphia, PA 19104 USA. RP Mandell, DS (reprint author), Univ Penn, Ctr Mental Hlth Policy & Serv Res, 3535 Market St, Philadelphia, PA 19104 USA. EM mandelld@upenn.edu RI Mandell, David/H-2730-2012 OI Mandell, David/0000-0001-8240-820X FU Autism Speaks; Steve Shirley Foundation FX This study was funded by Autism Speaks. Estimates for the United Kingdom were built on previous research funded by the Steve Shirley Foundation. 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PD AUG PY 2014 VL 168 IS 8 BP 721 EP 728 DI 10.1001/jamapediatrics.2014.210 PG 8 WC Pediatrics SC Pediatrics GA AN0TZ UT WOS:000340298200011 PM 24911948 ER PT J AU Millard, H McLaren, JL Coffey, BJ AF Millard, Hun McLaren, Jennifer L. Coffey, Barbara J. TI Lurasidone Treatment in a Child with Autism Spectrum Disorder with Irritability and Aggression SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article C1 [Millard, Hun; McLaren, Jennifer L.] Geisel Sch Med Dartmouth, Dept Psychiat, Lebanon, NH USA. [Coffey, Barbara J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Coffey, BJ (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Barbara.coffey@mssm.edu FU Boehringer Ingelheim; Bristol-Myers; Eli Lilly Pharmaceutical; National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS); Otsuka; Pfizer; Shire; Tourette Syndrome Association FX Drs. Millard and McLaren have no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Boehringer Ingelheim, Bristol-Myers, Eli Lilly Pharmaceutical, National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), Otsuka, Pfizer, Shire, and Tourette Syndrome Association. CR Baribeau DA, 2014, CURR PSYCHIAT REP, V16, DOI 10.1007/s11920-014-0437-0 Doyle CA, 2012, EXPERT OPIN PHARMACO, V13, P1615, DOI 10.1517/14656566.2012.674110 Politte LC, 2014, PSYCHOPHARMACOLOGY, V231, P1023, DOI 10.1007/s00213-013-3068-y Stahl SM, 2013, STAHLS ESSENTIAL PSY NR 4 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 AUG PY 2014 VL 24 IS 6 BP 354 EP 356 DI 10.1089/cap.2014.2462 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AN7ZW UT WOS:000340820700009 ER PT J AU Maloney, A Mick, EO Frazier, J AF Maloney, Ann Mick, Eric O. Frazier, Jean TI Aripiprazole Decreases Irritability in 12 out of 14 Youth with Autism Spectrum Disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Letter ID PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIORAL SYMPTOMS; DOUBLE-BLIND; CHILDREN; HALOPERIDOL; RISPERIDONE; PLACEBO; DESIGN C1 [Maloney, Ann; Mick, Eric O.; Frazier, Jean] UMASS Med Sch, Dept Psychiat, Worcester, MA USA. RP Maloney, A (reprint author), Univ Massachusetts, Dept Psychiat, Sch Med, 55 Lake Ave North, Worcester, MA 01566 USA. 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Child Adolesc. Psychopharmacol. PD AUG PY 2014 VL 24 IS 6 BP 357 EP 359 DI 10.1089/cap.2013.0143 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA AN7ZW UT WOS:000340820700010 PM 24828130 ER PT J AU Otsuka, Y Mareschal, I Calder, AJ Clifford, CWG AF Otsuka, Yumiko Mareschal, Isabelle Calder, Andrew J. Clifford, Colin W. G. TI Dual-Route Model of the Effect of Head Orientation on Perceived Gaze Direction SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article DE gaze perception; cue combination; head orientation; Wollaston effect; dual-route model ID UNIQUE MORPHOLOGY; TEMPORAL CORTEX; EYE DIRECTION; PERCEPTION; LOOKING; AUTISM; JUDGMENT; FACE; ACCURACY; CHILDREN AB Previous studies on gaze perception have identified 2 opposing effects of head orientation on perceived gaze direction-1 repulsive and the other attractive. However, the relationship between these 2 effects has remained unclear. By using a gaze categorization task, the current study examined the effect of head orientation on the perceived direction of gaze in a whole-head condition and an eye-region condition. We found that the perceived direction of gaze was generally biased in the opposite direction to head orientation (a repulsive effect). Importantly, the magnitude of the repulsive effect was more pronounced in the eye-region condition than in the whole-head condition. Based on these findings, we developed a dual-route model, which proposes that the 2 opposing effects of head orientation occur through 2 distinct routes. In the framework of this dual-route model, we explain and reconcile the findings from previous studies, and provide a functional account of attractive and repulsive effects and their interaction. C1 [Otsuka, Yumiko; Clifford, Colin W. G.] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. [Mareschal, Isabelle] Univ Sydney, Sydney, NSW 2006, Australia. [Mareschal, Isabelle] Queen Mary Univ London, Dept Psychol, Sch Chem & Biol Sci, London, England. [Calder, Andrew J.] MRC Cognit & Brain Sci Unit, Cambridge, England. [Clifford, Colin W. G.] Univ Sydney, Australian Ctr Excellence Vis Sci, Sydney, NSW 2006, Australia. RP Otsuka, Y (reprint author), Univ New S Wales, Sch Psychol, Mathews Bldg, Sydney, NSW 2052, Australia. EM yumikoot@gmail.com RI Otsuka, Yumiko/J-5628-2014 FU Australian Research Council [DP120102589]; Medical Research Council, United Kingdom [MC_US_A060_5PQ50] FX This work is supported by Australian Research Council Discovery Project [DP120102589] to Colin Clifford and Andrew Calder; Colin Clifford is supported by an Australian Research Council Future Fellowship; Andrew Calder is supported by the Medical Research Council, United Kingdom [grant ref. MC_US_A060_5PQ50]. 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Neural Transm. PD AUG PY 2014 VL 121 IS 8 SI SI BP 891 EP 905 DI 10.1007/s00702-014-1216-0 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN6BU UT WOS:000340679500008 PM 24752754 ER PT J AU Rutkowski, EM Brimer, D AF Rutkowski, Elaine M. Brimer, Debbie TI Physical Education Issues for Students With Autism: School Nurse Challenges SO JOURNAL OF SCHOOL NURSING LA English DT Article DE autism spectrum disorder (ASD); Individualized Education Plan (IEP); physical education (PE) ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; ASPERGERS-DISORDER; MOTOR; CHILDREN; PREVALENCE AB Extant studies indicate persons with autism have difficulties in social interaction, verbal and nonverbal communication, repetitive behaviors, and poor ability to generalize learned skills. Obesity has also been identified as significantly affecting children with autism spectrum disorders (ASD). Negative experience in physical education (PE) may be the antecedent behavior to lack of activities that are mediators to sedentary lifestyles and contributors to the chronic illnesses associated with overweight and obesity. Students with ASD often cannot perform required activities to meet required PE standards. It is imperative school nurses be aware of the many challenges students with ASD bring into a PE class. School nurses provide education for the members of the school community, including the Individualized Education Plan team, regarding the need for attention to limitations, including physical activity, of students with ASD. C1 [Rutkowski, Elaine M.] Calif State Univ Fullerton, Fullerton, CA 92834 USA. [Brimer, Debbie] Antelope Valley Union High Sch Dist, Lancaster, CA USA. RP Rutkowski, EM (reprint author), Calif State Univ Fullerton, POB 6868, Fullerton, CA 92834 USA. 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PD AUG PY 2014 VL 30 IS 4 BP 256 EP 261 DI 10.1177/1059840513503686 PG 6 WC Nursing SC Nursing GA AN6QE UT WOS:000340719800004 PM 24014552 ER PT J AU Chiu, YN Chou, MC Lee, JC Wong, CC Chou, WJ Wu, YY Chien, YL Gau, SSF AF Chiu, Yen-Nan Chou, Miao-Chun Lee, Ju-Chin Wong, Ching-Ching Chou, Wen-Jiun Wu, Yu-Yu Chien, Yi-Ling Gau, Susan Shur-Fen TI Determinants of maternal satisfaction with diagnosis disclosure of autism SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE autism; disclosure; informed counseling; mothers; satisfaction ID SEVERE MENTAL HANDICAP; DOWNS-SYNDROME; SPECTRUM DISORDER; PARENTING STYLE; 1ST INFORMATION; CHILDREN; DISABILITY; FAMILIES; COMMUNICATION; PROFESSIONALS AB Background/Purpose: Diagnosis disclosure is an important clinical issue in developmental disabilities, which may influence parents' ability to cope with their child's conditions. This paper presents the content and patterns of diagnosis-informed counseling for mothers of children with autism and investigates the determinants for maternal satisfaction with this counseling, in order to improve clinical practice. Methods: Mothers of 151 children, aged 3-12 years, with DSM-IV autistic disorder, confirmed by the Chinese version of the Autism Diagnostic Interview-Revised, were assessed. We collected information about the mothers' experience with diagnosis-informed counseling, their personality characteristics, and the extent to which they were satisfied with the counseling. Results: Satisfaction with diagnosis-informed counseling was related more to the context of the counseling, including the attitude of the counselors and the timing and duration of counseling, than to its content. Parents' social desirability, educational level, and employment status were negatively associated with their satisfaction with counseling. However, immediate emotion, neuroticism, and extroversion did not have a significant effect on the satisfaction with counseling. Approximately 60% of the mothers preferred to be informed of having an autistic child after the diagnosis had been confirmed. Conclusion: Our findings suggest that more efforts are needed to improve the quality of diagnosis-informed counseling in autism, particularly in the context of breaking the news to mothers of children with autism. Future study could further examine the moderating effect of diagnostic subtype of autism spectrum disorders, treatment response, or social support on maternal satisfaction with diagnosis-informed counseling (ClinicalTrials.gov number, NCT00494754). Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved. C1 [Chiu, Yen-Nan; Chien, Yi-Ling; Gau, Susan Shur-Fen] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10002, Taiwan. [Chiu, Yen-Nan; Chien, Yi-Ling; Gau, Susan Shur-Fen] Coll Med, Taipei, Taiwan. [Chou, Miao-Chun; Chou, Wen-Jiun] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan. [Chou, Miao-Chun; Chou, Wen-Jiun] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Lee, Ju-Chin] Wan Fang Hosp, Dept Psychiat, Taipei, Taiwan. [Wong, Ching-Ching] Taipei City Hosp, Branch Women & Children, Taipei Child Assessment & Early Intervent Ctr, Taipei, Taiwan. [Wu, Yu-Yu] Chang Gung Mem Hosp, Dept Child Psychiat, Linkou Med Ctr, Taoyuan, Taiwan. RP Chien, YL (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan South Rd, Taipei 10002, Taiwan. EM ylchien@hotmail.com FU National Science Council (gs1), Taiwan [NSC96-3112-B-002-033, NSC97-3112-B-002-009, N5C98-3112-B-002-004] FX This work was supported by grants from the National Science Council (gs1) (NSC96-3112-B-002-033; NSC96-3112-B-002-033; NSC97-3112-B-002-009; N5C98-3112-B-002-004), Taiwan. 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In the discovery sample, 4 single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (OR range= 0.59 to 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (OR = 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors could potentially explain this association. C1 [Wolf, Erika J.; Mitchell, Karen S.; Reardon, Annemarie F.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.; Mitchell, Karen S.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Logue, Mark W.; Baldwin, Clinton T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Baldwin, Clinton T.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Aiello, Alison] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Galea, Sandro; Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Uddin, Monica; Wildman, Derek] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Uddin, Monica] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. RP Miller, MW (reprint author), 150 South Huntington Ave 116B-2, Boston, MA 02130 USA. 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Here we examine this possibility by using in vivo spine imaging in the early postnatal cortex of ASD mouse models. Spines are classified by the presence of either the excitatory postsynaptic marker PSD-95 or the inhibitory postsynaptic marker gephyrin. ASD mouse models show consistent upregulation in the dynamics of PSD-95-positive spines, which may subsequently contribute to stable synaptic connectivity. In contrast, spines receiving inputs from the thalamus, detected by the presence of gephyrin clusters, are larger, highly stable and unaffected in ASD mouse models. Importantly, two distinct mouse models, human 15q11-13 duplication and neuroligin-3 R451C point mutation, show highly similar phenotypes in spine dynamics. This selective impairment in dynamics of PSD-95-positive spines receiving intracortical projections may be a core component of early pathological changes and be a potential target of early intervention. C1 [Isshiki, Masaaki; Tanaka, Shinji; Okabe, Shigeo] Univ Tokyo, Grad Sch Med, Dept Cellular Neurobiol, Bunkyo Ku, Tokyo 1130033, Japan. [Kuriu, Toshihiko] Tokushima Bunri Univ, Kagawa Sch Pharmaceut Sci, Dept Neurophysiol, Tokushima, Kagawa 7692193, Japan. [Tabuchi, Katsuhiko] Shinshu Univ, Dept Mol & Cellular Physiol, Sch Med, Matsumoto, Nagano 3908621, Japan. [Tabuchi, Katsuhiko] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama 3320012, Japan. [Takumi, Toru] RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Takumi, Toru] Japan Sci & Technol Agcy JST, CREST, Kawaguchi, Saitama 3320012, Japan. RP Okabe, S (reprint author), Univ Tokyo, Grad Sch Med, Dept Cellular Neurobiol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM okabe@m.u-tokyo.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [21220008, 25117006, 26250014]; Global COE Program; Takeda Science Foundation [11J05614]; Naito Memorial Foundation FX We thank Taisuke Mizuguchi and Noriyuki Hayashi for data analysis, Satoe Ebihara for technical support, and Dr Shigeo Takamori for providing VGluT1 antibody. The BTBR T + tf mouse strain (RBRC 01206) was provided by RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. This work was supported by Grants-in-Aid for Scientific Research (21220008, 25117006 and 26250014 to S.O.), 'Development of biomarker candidates for social behavior' study conducted under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.O.), Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms to S.O.), Grant-in-Aid for JSPS Fellows (11J05614 to M.I.), Takeda Science Foundation (S.O.) and Naito Memorial Foundation (S.O.). 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Commun. PD AUG PY 2014 VL 5 AR 4742 DI 10.1038/ncomms5742 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO1OC UT WOS:000341081500001 PM 25144834 ER PT J AU Zhu, XQ Song, YW Bi, HY AF Zhu Xiao-Qian Song Yao-Wu Bi Hong-Yan TI Researches on Atypical Lateralization of Autisms' Language Development SO PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS LA Chinese DT Review DE autism; atypical lateralization; temporal lobe; frontal lobe; handness ID SPECTRUM DISORDER; FUNCTIONAL MRI; INFANTILE-AUTISM; COMPLEX SOUNDS; CHILDREN; BRAIN; ACTIVATION; HAND; PERCEPTION; HANDEDNESS AB Autism spectrum disorders (ASD) is a widely developmental disabilities, with the main clinical features including barriers to social interaction, verbal and non-verbal communication defects, narrow interests and stereotyped behaviors. The present article aims to introduce some information about language impairment of autism, including relative researches published from 1986 to the current time on the neural mechanisms underlying autism's language impairment. This issue was addressed from brain structural, brain functional asymmetry, and the influence of handness, and at last, a summary was given based on the literatures, which is that the autism has an atypical right language lateralization both of structural and functional, there also exist available evidence that atypical handness is associated with poorer neurocognition or anomalous cerebral asymmetries. This article will be helpful for diagnosis and therapy to the autism in the future and will facilitate the research of ASDs under Chinese culture. C1 [Zhu Xiao-Qian; Bi Hong-Yan] Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China. [Zhu Xiao-Qian] Univ Chinese Acad Sci, Beijing 100049, Peoples R China. [Song Yao-Wu] Hebei Univ, Coll Educ, Baoding 071002, Peoples R China. RP Bi, HY (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China. EM bihy@psych.ac.cn FU National Natural Science Foundation of China [31371044, 30970910] FX This work was supported by a grant from The National Natural Science Foundation of China (31371044, 30970910). 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Biochem. Biophys. PD AUG PY 2014 VL 41 IS 8 BP 749 EP 754 DI 10.3724/SP.J.1206.2013.00296 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AN6JN UT WOS:000340700900004 ER PT J AU Kallen, B AF Kallen, Bengt TI The risk of neurodisability and other long-term outcomes for infants born following ART SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Review DE Assisted reproductive technology; Asthma; Attention deficit/hyperactivity disorder; Autism; Childhood cancer; Epilepsy ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; AUTISM SPECTRUM DISORDERS; HOSPITAL-CARE UTILIZATION; DANISH NATIONAL COHORT; CHILDREN BORN; CEREBRAL-PALSY; TWINS BORN; NEUROLOGICAL SEQUELAE; IVF CHILDREN AB Children born after assisted reproductive technologies (ART) have an increased morbidity. The risk of developing cerebral palsy is nearly doubled and the risk of developing epilepsy is also higher. Behavioural problems including attention deficit/hyperactivity disorder may be more common in children born following ART than among naturally conceived children but the finding is uncertain. Data on autism are difficult to interpret. There may exist a small increase in the incidence of childhood cancer and there is greater evidence of an elevated risk of asthma. To some extent, these risks are mediated by neonatal complications including prematurity and low birth weight but some effects such as cerebral palsy are likely to be linked to the increased rate of multiple births after ART. Many of the neonatal complications after ART are most likely linked to parental subfertility and are less an effect of the ART technology. The possibility exists that imprinting errors, associated with subfertility and/or ART, may result in long-term morbidity. (C) 2014 Elsevier Ltd. All rights reserved. C1 Lund Univ, Tornblad Inst, SE-22362 Lund, Sweden. RP Kallen, B (reprint author), Lund Univ, Tornblad Inst, Biskospgatan 7, SE-22362 Lund, Sweden. 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Fetal Neonatal Med. PD AUG PY 2014 VL 19 IS 4 BP 239 EP 244 DI 10.1016/j.siny.2014.04.002 PG 6 WC Pediatrics SC Pediatrics GA AN6JB UT WOS:000340699700005 PM 24793634 ER PT J AU Abdel-Mannan, O Sutcliffe, A AF Abdel-Mannan, Omar Sutcliffe, Alastair TI I was born following ART: how will I get on at school? SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Review DE Assisted reproductive techniques; Children; Intracytoplasmic sperm injection; In-vitro fertilisation; Neurodevelopmental outcome ID INTRACYTOPLASMIC SPERM INJECTION; SPONTANEOUSLY CONCEIVED CHILDREN; AUTISM SPECTRUM DISORDERS; VITRO FERTILIZATION; ASSISTED CONCEPTION; CONGENITAL-MALFORMATIONS; CRYOPRESERVED EMBRYOS; SINGLETON CHILDREN; MOTOR DEVELOPMENT; CEREBRAL-PALSY AB With an ever-expanding population of children born after in-vitro fertilisation (IVF), the widespread use of assisted reproductive techniques (ART) has placed a great emphasis on the need to study their long-term outcomes. Indeed, there has been concern that mechanisms used in ART may have a detrimental effect on the neurocognitive development of these children. Reassuringly, most neurocognitive and motor development studies using various assessment scales have generally found no differences between intracytoplasmic sperm injection, IVF and naturally conceived children. Only a few studies have reported concerns. In terms of predictors of intelligence in children, ART appears to have a minimal effect in comparison to birth weight, gestational age, socio-economic status, and parental educational levels. Nevertheless, further research of higher methodological quality in children beyond pre-school age and on newer ART procedures is needed. (C) 2014 Published by Elsevier Ltd. C1 [Abdel-Mannan, Omar; Sutcliffe, Alastair] Inst Child Hlth, Gen & Adolescent Paediat Unit, London WC1N 3HZ, England. RP Abdel-Mannan, O (reprint author), Inst Child Hlth, Gen & Adolescent Paediat Unit, 43 Great Ormond St, London WC1N 3HZ, England. EM o.abdel-mannan@ucl.ac.uk FU Human Fertilisation and Embryology Authority FX Dr Sutcliffe would like to acknowledge the historical and present continuing support for his work from collaborating members of the British Fertility Society, the Human Fertilisation and Embryology Authority, and equivalent organisations in other countries such as Belgium, Germany, Italy and others. 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Methods. Res. PD AUG PY 2014 VL 43 IS 3 BP 406 EP 415 DI 10.1177/0049124114521149 PG 10 WC Social Sciences, Mathematical Methods; Sociology SC Mathematical Methods In Social Sciences; Sociology GA AN6SH UT WOS:000340726700005 ER PT J AU Muller, M Can, K AF Mueller, Michael Can, Karolina TI Aberrant redox homoeostasis and mitochondrial dysfunction in Rett syndrome SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE antioxidant; autism spectrum disorder; mitochondrial disease; oxidative stress; reactive oxygen species (ROS); redox imaging ID MOUSE MODEL; OXIDATIVE STRESS; CARBOHYDRATE-METABOLISM; MECP2; BRAIN; ABNORMALITIES; NEURONS; EXPRESSION; MUTATION; DISEASE AB RTT (Rett syndrome) is a severe progressive neurodevelopmental disorder with a monogenetic cause, but complex and multifaceted clinical appearance. Compelling evidence suggests that mitochondrial alterations and aberrant redox homoeostasis result in oxidative challenge. Yet, compared with other severe neuropathologies, RTT is not associated with marked neurodegeneration, but rather a chemical imbalance and miscommunication of neuronal elements. Different pharmacotherapies mediate partial improvement of conditions in RTT, and also antioxidants or compounds improving mitochondrial function may be of potential merit. In the present paper, we summarize findings from patients and transgenic mice that point towards the nature of RTT as a mitochondrial disease. Also, open questions are addressed that require clarification to fully understand and successfully target the associated cellular redox imbalance. C1 [Mueller, Michael; Can, Karolina] Univ Gottingen, Inst Neuro & Sinnesphysiol, Zentrum Physiol & Pathophysiol,Univ Med, Ctr Nanoscale Microscopy & Mol Physiol Brain CNMP, D-37073 Gottingen, Germany. RP Muller, M (reprint author), Univ Gottingen, Inst Neuro & Sinnesphysiol, Zentrum Physiol & Pathophysiol,Univ Med, Ctr Nanoscale Microscopy & Mol Physiol Brain CNMP, Humboldtallee 23, D-37073 Gottingen, Germany. EM mmuelle7@gwdg.de RI Muller, Michael/F-7222-2010 FU Deutsche Forschungsgemeinschaft (Center for Nanoscale Microscopy and Molecular Physiology of the Brain, CNMPB); International Rett Syndrome Foundation (IRSF) [2817] FX Our research was funded by the Deutsche Forschungsgemeinschaft (Center for Nanoscale Microscopy and Molecular Physiology of the Brain, CNMPB) and the International Rett Syndrome Foundation (IRSF) [grant number 2817]. 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Soc. Trans. PD AUG PY 2014 VL 42 BP 959 EP 964 DI 10.1042/BST20140071 PN 4 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN1FX UT WOS:000340329200039 PM 25109986 ER PT J AU El Marroun, H White, TJH van der Knaap, NJF Homberg, JR Fernandez, G Schoemaker, NK Jaddoe, VWV Hofman, A Verhulst, FC Hudziak, JJ Stricker, BHC Tiemeier, H AF El Marroun, Hanan White, Tonya J. H. van der Knaap, Noortje J. F. Homberg, Judith R. Fernandez, Guilen Schoemaker, Nikita K. Jaddoe, Vincent W. V. Hofman, Albert Verhulst, Frank C. Hudziak, James J. Stricker, Bruno H. C. Tiemeier, Henning TI Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT EXPOSURE; FETAL-GROWTH; IN-UTERO; MATERNAL DEPRESSION; SPECTRUM DISORDERS; BEHAVIOR CHECKLIST; NEONATAL OUTCOMES; STATISTICS NOTES; BIRTH OUTCOMES; PREGNANT-WOMEN AB Background Selective serotonin reuptake inhibitors (SSRIs) are considered safe and are frequently used during pregnancy. However, two case-control studies suggested an association between prenatal SSRI exposure with childhood autism. Aims To prospectively determine whether intra-uterine SSSRI exposure is associated with childhood autistic symptoms in a population-based study. Method A total of 376 children prenatally exposed to maternal depressive symptoms (no SSRI exposure), 69 children prenatally exposed to SSRIs and 5531 unexposed children were included. Child pervasive developmental and affective problems were assessed by parental report with the Child Behavior Checklist at ages 1.5, 3 and 6. At age 6, we assessed autistic traits using the Social Responsiveness Scale (n = 4264). Results Prenatal exposure to maternal depressive symptoms without SSRIs was related to both pervasive developmental (odds ratio (OR) = 1.44, 95% CI 1.07-1.93) and affective problems (OR = 1.44, 95% CI 1.15-1.81). Compared with unexposed children, those prenatally exposed to SSRIs also were at higher risk for developing pervasive developmental problems (OR = 1.91, 95% CI 1.13-3.47), but not for affective problems. Children prenatally exposed to SSRIs also had more autistic traits (B=0.15, 95% CI 0.08-0.22) compared with those exposed to depressive symptoms only. Conclusions Our results suggest an association between prenatal SSRI exposure and autistic traits in children. Prenatal depressive symptoms without SSRI use were also associated with autistic traits, albeit this was weaker and less specific. Longterm drug safety trials are needed before evidence-based recommendations are possible. C1 [El Marroun, Hanan; White, Tonya J. H.; Schoemaker, Nikita K.] Sophia Childrens Univ Hosp, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [El Marroun, Hanan; Schoemaker, Nikita K.] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands. [White, Tonya J. H.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [van der Knaap, Noortje J. F.; Homberg, Judith R.; Fernandez, Guilen] Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Jaddoe, Vincent W. V.] Erasmus MC, Dept Epidemiol, Generat R Study Grp, Rotterdam, Netherlands. [Jaddoe, Vincent W. V.] Erasmus MC, Dept Pediat, Rotterdam, Netherlands. [Hofman, Albert; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Verhulst, Frank C.; Hudziak, James J.; Tiemeier, Henning] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [Hudziak, James J.] Univ Vermont, Coll Med, Deptartment Psychiat, Burlington, VT USA. [Stricker, Bruno H. C.] Inspectorate Healthcare, The Hague, Netherlands. [Tiemeier, Henning] Sophia Childrens Univ Hosp, Dept Child & Adolescent Psychiat, Dept Epidemiol, NL-3000 CB Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands. RP Tiemeier, H (reprint author), Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. EM h.tiemeier@erasmusmc.nl RI Fernandez, Guillen/B-3771-2009; Homberg, Judith/D-2473-2010 OI Fernandez, Guillen/0000-0002-5522-0604; FU Sophia Children's Hospital Fund [SSWO-616]; Erasmus Medical Centre; Netherlands Organization for Health Research and Development (Zon MW Geestkracht Program) [10.000.1003]; Netherlands Organization for Health Research and Development (ZonMw TOP) [40-00812-98-11021]; Netherlands Organization for Health Research and Development (NWO Brain & Cognition Program) [433-09-311]; Netherlands Organization for Health Research and Development (VIDI) [017.106.370] FX The Sophia Children's Hospital Fund (SSWO-616) supported this work financially. 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