FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mog, A AF Mog, Ashley TI Understanding Autism: Parents, Doctors, and the History of a Disorder SO ORAL HISTORY REVIEW LA English DT Book Review C1 [Mog, Ashley] Univ Kansas, Lawrence, KS 66045 USA. RP Mog, A (reprint author), Univ Kansas, Lawrence, KS 66045 USA. CR Silverman C, 2012, UNDERSTANDING AUTISM: PARENTS, DOCTORS, AND THE HISTORY OF A DISORDER, P1 NR 1 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0094-0798 EI 1533-8592 J9 ORAL HIST REV JI Oral Hist. Rev. PD WIN-SPR PY 2015 VL 42 IS 1 BP 170 EP 172 PG 4 WC History SC History GA CI9MG UT WOS:000355093600017 ER PT J AU Abdulla, AM Hegde, AM AF Abdulla, A. M. Hegde, A. M. TI Salivary Cortisol Levels and its Implication on Behavior In Children with Autism during Dental Treatment SO JOURNAL OF CLINICAL PEDIATRIC DENTISTRY LA English DT Article DE Autism; Cortisol; Stress; Diurnal Variation; children ID STRESS AB The aim of the study was to estimate the diurnal variations of salivary cortisol in children with autism and healthy children and it's implication on behavior during non-invasive dental procedures. Study design: 50 children with autism and 50 healthy children in the age group between 6 to 12 years of both genders with the need for dental treatment were included in the study Whole unstimulated saliva was collected from them during early hours of the day and during evenings for 2 consecutive days. The collected saliva was then subjected to electrochemiluminescence assay. Minimum invasive dental procedures like hand scaling, pit and fissure sealants and glass ionomer cement restorations were performed for the participants each time after the saliva sample collection and their behavior during the procedures was rated using Frankl's Behavior Rating Scale. Results:Significant correlation was seen between cortisol levels and behavior in children with autism. As cortisol levels increased in children with autism, behavior worsened and as the cortisol levels decreased they showed positive behaviour Conclusion: Cortisol acts as a stress marker and studying the diurnal variations of salivary cortisol can help us in attaining better knowledge about the behavior pattern and thereby assist us in modiffing the behavior modification procedures and treatment planning in this group of special children. C1 [Abdulla, A. M.; Hegde, A. M.] Nitte Univ, Dept Pedodont & Prevent Dent, AB Shetty Mem Inst Dent Sci, Mangalore 575018, Karnataka, India. 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PD WIN PY 2015 VL 39 IS 2 BP 128 EP 132 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CG6SW UT WOS:000353433700009 PM 25823482 ER PT J AU Simplican, SC AF Simplican, Stacy Clifford TI Care, Disability, and Violence: Theorizing Complex Dependency in Eva Kittay and Judith Butler SO HYPATIA-A JOURNAL OF FEMINIST PHILOSOPHY LA English DT Article ID BEHAVIOR PROBLEMS; CHILDREN; STRESS AB How do we theorize the experiences of caregivers abused by their children with autism without intensifying stigma toward disability? Eva Kittay emphasizes examples of extreme vulnerability to overturn myths of independence, but she ignores the possibility that dependents with disabilities may be vulnerable and aggressive. Instead, her work over-emphasizes care-givers' capabilities and the constancy of disabled dependents' vulnerability. I turn to Judith Butler's ethics and her conception of the self as opaque to rethink care amid conflict. Person-centered planning approaches, pioneered by disability rights activists, merge Butler's analysis of opacity with Kittay's work on embodied care, while also inviting a broader network of people to both interpret needs and change communities. By expanding our conceptions of dependency, feminist disability studies can continue the aim of both Kittay and Butler: to humanize unintelligible lives. C1 [Simplican, Stacy Clifford] Michigan State Univ, E Lansing, MI 48824 USA. [Simplican, Stacy Clifford] DOCTRID Res Inst, Dublin, Ireland. RP Simplican, SC (reprint author), Michigan State Univ, E Lansing, MI 48824 USA. 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TI Looking Backward, Thinking Forward: Occupational Therapy and Autism Spectrum Disorders SO OTJR-OCCUPATION PARTICIPATION AND HEALTH LA English DT Article DE autism spectrum disorders; literature review; occupational therapy ID SENSORY INTEGRATION; YOUNG-CHILDREN; BEHAVIORS; MOTOR; PARTICIPATION; INTERVENTIONS; DESIGN; ADOLESCENTS; FAMILIES; SERVICE AB As autism spectrum disorders become more prevalent and comprise a growing percentage of occupational therapists' caseloads, it is important to examine trends in the literature. The purpose of this scoping review is to provide a historical analysis to illuminate changes and gaps in the occupational therapy literature related to autism spectrum disorders to inform the direction of research and practice. A total of 115 articles published in five occupational therapy journals in the United States from 1980 to 2013 were reviewed. Publications were coded by article type, with intervention studies coded in detail. Results indicated a consistent increase in number of publications as years progressed. Analysis by decade highlighted a shift from a biomedical focus to an occupation focus. Suggestions for future research include building a stronger evidence base, developing occupation-based assessments and interventions, and addressing needs of individuals with autism spectrum disorders and their families across the life span. C1 [Bagatell, Nancy; Mason, Ashley E.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Bagatell, N (reprint author), Univ N Carolina, Div Occupat Sci & Occupat Therapy, Bondurant Hall,CB 7122, Chapel Hill, NC 27599 USA. 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TI "Don't Go Changing to Try and Please Me": Combating Essentialism through Ethnography in the Ethnomusicology of Autism SO ETHNOMUSICOLOGY LA English DT Article ID MUSIC-THERAPY; SPECTRUM DISORDER; CHILDREN; COMMUNICATION; CULTURE; NOTIONS; ABILITY AB Ethnomusicology is the study of how people make and experience music, and of why it matters to them that they do. Building from the epistemological foundations of the autistic self-advocacy and neurodiversity movements, as well as from the musical, ethnographic, and relativistic priorities of ethnomusicology itself, this article advances the position that our field, thus defined, is inherently well suited to the task of creating and sustaining vital, neurodiverse musical communities. The focus is on one such community; the Artism Ensemble, which serves as the basis of a case study featuring transcripts of dialogue with a child member of the group diagnosed with Asperger's syndrome. 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Couperus, Jane TI The Mating Life of Geeks: Love, Neuroscience, and the New Autistic Subject SO SIGNS LA English DT Article ID SPECTRUM DISORDERS; MIND; OXYTOCIN; INTERSEX; DEFICITS; GENDER; BRAIN; SEX AB In this article, we track the emergence of a new autistic subject, one that is socially inept yet brilliant, earnest yet charming, obsessive yet humorous, arrogant yet vulnerable, and unquestionably worthy of our attention. In contrast to the historic definition of the autist as one lacking the capacity for love, the new autistic subject is enabled and inflected by the gendered construction of autism spectrum disorder (ASD) and holds the promise of being potentially productive and even (desirably) reproductive. Through an analysis of current trends in autism science (extreme male brains and assortative mating) and shifting narratives about autism and love, we trace how processes of heterosexualization inform the shift from loveless to loving and lovable, and we further explore how such processes produce new forms of exclusions in the name of neurodiversity. We locate ASD as a site for the reinscription and biologization of historical ideas about gender as well as the naturalization of normative heterosexuality. Finally, we argue that it is through this process of normalization via heterosexualization that this new subject emerges, leaving many lost to the queer, to the feminine, or to the irredeemably abject. C1 [Willey, Angela; Subramaniam, Banu] Univ Massachusetts, Amherst, MA 01003 USA. [Hamilton, Jennifer A.] Hampshire Coll, Sch Crit Social Inquiry, Amherst, MA 01002 USA. [Couperus, Jane] Hampshire Coll, Sch Cognit Sci, Amherst, MA 01002 USA. 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Mass media are the primary channel through which people learn about autism. This article examines how leading newspapers in China covered autism in the 10-year period of 2003 through 2012 through a framing analysis. It finds that while autism has received increased media attention, it is increasingly framed as a family problem-family members are cited or quoted more than any other sources and the responsibility of dealing with autism is ultimately assigned to families. Autistic people are largely silenced unless they are autistic savants with special talents. The use of the scientific discourse and the human-interest discourse both decrease over time in percentage, while the use of other discourses such as the public relations discourse becomes more dominant. C1 [Bie, Bijie] Univ Alabama, Coll Commun & Informat Sci, Tuscaloosa, AL 35487 USA. [Tang, Lu] Univ Alabama, Coll Commun & Informat Sci, Dept Commun Studies, Tuscaloosa, AL 35487 USA. 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PD SEP 2 PY 2015 VL 30 IS 9 BP 884 EP 893 DI 10.1080/10410236.2014.889063 PG 10 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA CH4ZM UT WOS:000354043300004 PM 25074820 ER PT J AU Burket, JA Benson, AD Green, TL Rook, JM Lindsley, CW Conn, PJ Deutsch, SI AF Burket, Jessica A. Benson, Andrew D. Green, Torrian L. Rook, Jerri M. Lindsley, Craig W. Conn, P. Jeffrey Deutsch, Stephen I. TI Effects of VU0410120, a novel GlyT1 inhibitor, on measures of sociability, cognition and stereotypic behaviors in a mouse model of autism SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism Spectrum Disorders; Balb/c; GlyT1 inhibition; NMDA receptor ID CYCLOSERINE IMPROVES SOCIABILITY; NMDA RECEPTORS; BALB/C MOUSE; SPECTRUM DISORDERS; STRAINS DIFFER; MICE; SCHIZOPHRENIA; RELEVANT; MK-801; EXCITABILITY AB The NMDA receptor is a highly regulated glutamate-gated cationic channel receptor that has an important role in the regulation of sociability and cognition. The genetically-inbred Balb/c mouse has altered endogenous tone of NMDA receptor-mediated neurotransmission and is a model of impaired sociability, relevant to Autism Spectrum Disorders (ASDs). Because glycine is an obligatory co-agonist that works cooperatively with glutamate to promote opening of the ion channel, one prominent strategy to promote NMDA receptor-mediated neurotransmission involves inhibition of the glycine type 1 transporter (GlyT1). The current study evaluated the dose-dependent effects of VU0410120, a selective, high-affinity competitive GlyT1 inhibitor, on measures of sociability, cognition and stereotypic behaviors in Balb/c and Swiss Webster mice. The data show that doses of VU0410120 (i.e., 18 and 30 mg/kg) that improve measures of sociability and spatial working memory in the Balb/c mouse strain elicit intense stereotypic behaviors in the Swiss Webster comparator strain (i.e., burrowing and jumping). Furthermore, the data suggest that selective GlyT1 inhibition improves sociability and spatial working memory at doses that do not worsen or elicit stereotypic behaviors in a social situation in the Balb/c strain. However, the elicitation of stereotypic behaviors in the Swiss Webster comparator strain at therapeutically relevant doses of VU0410120 suggest that genetic factors (i.e., mouse strain differences) influence sensitivity to GlyT1-elicited stereotypic behaviors, and emergence of intense stereotypic behaviors may be dose-limiting side effects of this interventional strategy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Burket, Jessica A.; Benson, Andrew D.; Green, Torrian L.; Deutsch, Stephen I.] Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, Norfolk, VA 23501 USA. [Rook, Jerri M.; Lindsley, Craig W.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37235 USA. RP Deutsch, SI (reprint author), Dept Psychiat & Behav Sci, 825 Fairfax Ave,Suite 710, Norfolk, VA 23507 USA. EM deutscsi@evms.edu FU Bristol Myers Squibb; Astrazeneca FX PJ Conn and CW Lindsley receive research support from Bristol Myers Squibb and Astrazeneca and are inventors on multiple patents protecting GlyT1 inhibitors. JA Burket, AD Benson, TL Green, JM Rook, and SI Deutsch have nothing to disclose. 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TI Rising-falling mercury pollution causing the rising-falling IQ of the Lynn-Flynn effect, as predicted by the antiinnatia theory of autism and IQ SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Autism; Air pollution; Mercury; Flynn effect; IQ ID SEYCHELLES CHILD-DEVELOPMENT; METHYLMERCURY EXPOSURE; FISH CONSUMPTION; TEST-SCORES; INTELLIGENCE; DEPOSITION; DNA AB A fundamental principle of the antiinnatia theory of autism and IQ is that the same factors (genetic and environmental) which in extreme high levels cause autism, in more modal levels cause increased IQ. And the factors which generally cause raised IQ, in extreme levels cause autism. The antiinnatia theory further proposed that molecules randomly part-time binding to DNA and thereby reducing gene-expression would cause autism (and in less high levels cause raised IQ). 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Individ. Differ. PD AUG PY 2015 VL 82 BP 46 EP 51 DI 10.1016/j.paid.2015.02.039 PG 6 WC Psychology, Social SC Psychology GA CH6OZ UT WOS:000354157200008 ER PT J AU Byrd-Craven, J Massey, AR Calvi, JL Geary, DC AF Byrd-Craven, Jennifer Massey, Amber R. Calvi, Jessica L. Geary, David C. TI Is systemizing a feature of the extreme,male brain from an evolutionary perspective? SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Sex differences; Extreme male brain; Empathizing; Systemizing ID DIGIT RATIO 2D/4D; SEX-DIFFERENCES; ASPERGER-SYNDROME; AUTISM; EMPATHY; METAANALYSIS; ABILITIES; BEHAVIOR; ADULTS AB Sex differences in empathizing with others and systemizing the abstract rules that govern the operation of things and the natural world have been proposed as the core, essential differences between men and women. We evaluate this assertion in the context of Darwin's (1871) sexual selection and specifically test the hypothesis that the systemizing measure captures interest in evolutionarily novel occupational niches associated with interests in science, technology, engineering, and mathematics (STEM). Young adults (n = 233, 149 male) completed the Empathizing Quotient (EQ), the Systemizing Quotient (SQ) and the RIASEC Personality Type Inventory to assess six career interest groups. Sex differences were found on the EQ, SQ Investigative interests and interest in things, a subset of items from the Realistic scale. Mediation analyses revealed that occupational interests partially mediated the relation between sex and SQ scores, whereas controlling for Investigative interests increased the sex difference in EQ scores. These results provide partial support for the hypothesis and suggest SQ captures, in part, occupational interests in evolutionarily recent STEM fields. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Byrd-Craven, Jennifer; Massey, Amber R.; Calvi, Jessica L.] Oklahoma State Univ, Stillwater, OK 74078 USA. [Geary, David C.] Univ Missouri, Columbia, MO 65211 USA. RP Byrd-Craven, J (reprint author), Oklahoma State Univ, 116 North Murray Hall, Stillwater, OK 74078 USA. EM jennifer.byrd.craven@okstate.edu; mas-seya@okstate.edu; calvi@okstate.edu; GearyD@Missouri.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Andersson MB, 1994, SEXUAL SELECTION Armstrong PI, 2008, J VOCAT BEHAV, V73, P287, DOI 10.1016/j.jvb.2008.06.003 Auyeung B, 2012, J AUTISM DEV DISORD, V42, P2225, DOI 10.1007/s10803-012-1454-7 Auyeung B, 2009, J AUTISM DEV DISORD, V39, P1509, DOI 10.1007/s10803-009-0772-x Baron-Cohen S, 2005, SCIENCE, V310, P819, DOI 10.1126/science.1115455 Baron-Cohen S., 2003, ESSENTIAL DIFFERENCE Baron-Cohen S, 1999, NEUROCASE, V5, P475, DOI 10.1080/13554799908402743 BARONCOHEN S, 1994, BRIT J PSYCHIAT, V165, P640, DOI 10.1192/bjp.165.5.640 Baron-Cohen S, 2004, J AUTISM DEV DISORD, V34, P163, DOI 10.1023/B:JADD.0000022607.19833.00 Baron-Cohen Simon, 1995, MINDBLINDNESS ESSAY Betzig L, 2012, EVOL HUM BEHAV, V33, P309, DOI 10.1016/j.evolhumbehav.2011.10.008 Betzig L., 1993, SOCIAL STRATIFICATIO, V1, P37 Centers for Disease Control and Prevention, 2012, AUT DEV DIS MON NETW Costa M, 2001, J NONVERBAL BEHAV, V25, P225, DOI 10.1023/A:1012544204986 Darwin C., 1871, DESCENT MAN SELECTIO Davis M. 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PD AUG PY 2015 VL 82 BP 237 EP 241 DI 10.1016/j.paid.2015.03.026 PG 5 WC Psychology, Social SC Psychology GA CH6OZ UT WOS:000354157200041 ER PT J AU Wright, C AF Wright, C. TI Research in partnership: principles for good practice for involving young people with autism in research SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Meeting Abstract DE Children and families; Participation; Research C1 [Wright, C.] Bradford Dist Care Trust, Child & Adolescent Mental Hlth Serv, Bradford, W Yorkshire, England. EM catherine.wright@bdct.nhs.uk CR Baron-Cohen S, 2009, PREVALENCE OF AUTISM Clavering EK, 2010, CHILD CARE HLTH DEV, V36, P603, DOI 10.1111/j.1365-2214.2010.01094.x Holloway I, 2010, QUALITATIVE RESEARCH NR 3 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0308-0226 EI 1477-6006 J9 BRIT J OCCUP THER JI Br. J. Occup. Ther. PD AUG PY 2015 VL 77 SU 1 MA 48.2 BP 40 EP 41 PG 2 WC Rehabilitation SC Rehabilitation GA CF1KB UT WOS:000352302900085 ER PT J AU McCanney, J Kelly, G Casey, J Cross, S McCaffrey, F AF McCanney, J. Kelly, G. Casey, J. Cross, S. McCaffrey, F. TI Sensory processing patterns and activity choices of children with and without autism SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Meeting Abstract DE Children and families; Participation; Occupational science C1 [McCanney, J.; Cross, S.; McCaffrey, F.] Middletown Ctr Autism, Armagh, North Ireland. [Kelly, G.; Casey, J.] Univ Ulster, Coleraine BT52 1SA, Londonderry, North Ireland. EM jill.mccanney@middletownautism.com CR American Psychiatric Association, 2013, DIAGNOSTIC AND STATI Ayres A. J., 2005, SENSORY INTEGRATION, V25th Bundy A., 2002, SENSORY INTEGRATION Mattard-Labrecque Carolanne, 2013, J Can Acad Child Adolesc Psychiatry, V22, P139 Tseng MH, 2011, RES AUTISM SPECT DIS, V5, P1441, DOI 10.1016/j.rasd.2011.02.004 NR 5 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0308-0226 EI 1477-6006 J9 BRIT J OCCUP THER JI Br. J. Occup. Ther. PD AUG PY 2015 VL 77 SU 1 MA P35 BP 90 EP 90 PG 1 WC Rehabilitation SC Rehabilitation GA CF1KB UT WOS:000352302900186 ER PT J AU Barbu, E Martin-Valdivia, MT Martinez-Camara, E Urena-Lopez, LA AF Barbu, Eduard Teresa Martin-Valdivia, M. Martinez-Camara, Eugenio Alfonso Urena-Lopez, L. TI Language technologies applied to document simplification for helping autistic people SO EXPERT SYSTEMS WITH APPLICATIONS LA English DT Article DE Natural Language Processing; Text simplification; ASD; Image retrieval; Text summarization; Topic Models; Idiom detection ID SPECTRUM DISORDERS; READING-COMPREHENSION; CHILDREN; STUDENTS; DISABILITIES AB People affected by Autism Spectrum Disorders (ASD) have impairments in social interaction because they lack an adequate theory of mind. A significant percentile has inadequate reading comprehension skills. We present a multilingual tool called Open Book (OB) that applies Human Language Technologies (HLT) in order to identify reading comprehension obstacles in text documents and propose more simple alternatives with the aim of assisting the reading comprehension of users. OB involves several text transformations at lexical, syntactic and semantic level. In this paper we focus on three challenging components of the OB tool: the image retrieval component, the idiom detection component and the summarization module. There are very few studies that involve simplification by showing images associated to difficult concepts. In addition, the treatment of figurative language such as idioms or metaphors is one of the most challenging areas in Natural Language Processing (NLP). Finally, although text summarization is a more widely studied field in NLP, its application to text simplification remains as an open research issue. Thus, we focus on the integration of these three modules in our OB tool. We present the motivation for building these components and we describe how they are integrated in the whole system. Moreover, the usability and the usefulness of OB have been evaluated and analysed showing that the tool helps to produce texts easier to understand for autistic people. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Barbu, Eduard; Teresa Martin-Valdivia, M.; Martinez-Camara, Eugenio; Alfonso Urena-Lopez, L.] Univ Jaen, SINAI Res Grp, E-23071 Jaen, Spain. RP Martinez-Camara, E (reprint author), Univ Jaen, SINAI Res Grp, Campus Las Lagunillas, E-23071 Jaen, Spain. EM eduard_barbu@yahoo.com; maite@ujaen.es; emcamara@ujaen.es; laurena@ujaen.es FU Fondo Europeo de Desarrollo Regional (FEDER); ATTOS project from the Spanish Government [TIN2012-38536-C03-0]; project AORESCU from the regional government of Junta de Andalucia [P11-TIC-7684 MO]; University of Jaen [CEATIC-2013-001]; European Commission under the Seventh (FP7) Framework Program for Research and Technological Development through the FIRST project [FP7-287607] FX This work has been partially supported by a Grant from the Fondo Europeo de Desarrollo Regional (FEDER), ATTOS project (TIN2012-38536-C03-0) from the Spanish Government. The project AORESCU (P11-TIC-7684 MO) from the regional government of Junta de Andalucia and the project CEATIC-2013-001 from the University of Jaen partially supports this manuscript. The work in this paper is partially funded by the European Commission under the Seventh (FP7-2007-2013) Framework Program for Research and Technological Development through the FIRST project (FP7-287607). This publication reflects only the views of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein. 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TI Interpersonal distance and social anxiety in autistic spectrum disorders: A behavioral and ERP study SO SOCIAL NEUROSCIENCE LA English DT Article DE N1 ERP; Autism; Personal space; Interpersonal distance ID HIGH-FUNCTIONING CHILDREN; EVENT-RELATED POTENTIALS; PSYCHOMETRIC PROPERTIES; ASPERGER-SYNDROME; BRAIN POTENTIALS; SCALE; ATTENTION; ADULTS; RESPONSIVENESS; ADOLESCENTS AB An inherent feature of social interactions is the use of social space or interpersonal distance-the space between one individual and another. Because social deficits are core symptoms of Autistic Spectrum Disorder (ASD), we hypothesized that individuals on this spectrum will exhibit abnormal interpersonal distance preferences. The literature on interpersonal distance in ASD is not conclusive. While some studies show preferences for closer distances among this group, others show preferences for farther distances than controls. 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TI NMDA receptor activation regulates sociability by its effect on mTOR signaling activity SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE D-Cycloserine; mTOR; NMDA receptor; Sociability; Tuberous sclerosis ID AUTISM SPECTRUM DISORDERS; CYCLOSERINE IMPROVES SOCIABILITY; POSTTRAUMATIC-STRESS-DISORDER; TYROSINE-PHOSPHATASE STEP; MOUSE STRAINS DIFFER; FRAGILE-X-SYNDROME; BTBR-T+TF/J MICE; TUBEROUS SCLEROSIS; SOCIAL-BEHAVIOR; BALB/C MOUSE AB Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORC1 in neurons (e.g., cerebellar Purkinje cells). mTORC1 is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the transduction of neurotransmitters (e.g., glutamate and acetylcholine) and nerve growth factors (e.g., Brain-Derived Neurotrophic Factor). Interestingly, the severity of the intellectual disability in Tuberous Sclerosis Complex may relate more to this metabolic disturbance (i.e., overactivity of mTOR signaling) than the density of cortical tubers. Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. NMDA receptor activation may also dampen mTORC1 activity by at least two possible mechanisms: regulating intraneuronal accumulation of arginine and the phosphorylation status of a specific extracellular signal regulating kinase (i.e., ERK1/2), both of which are "drivers" of mTORC1 activity. Conceivably, the prosocial effects of targeting the NMDA receptor with agonists in mouse models of autism spectrum disorders result from their ability to dampen mTORC1 activity in neurons. Strategies for dampening mTORC1 overactivity by NMDA receptor activation may be preferred to its direct inhibition in chronic neurodevelopmental disorders, such as autism spectrum disorders. (C) 2015 Elsevier Inc. All rights reserved. C1 [Burket, Jessica A.; Benson, Andrew D.; Deutsch, Stephen I.] Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, Norfolk, VA 23501 USA. [Tang, Amy H.] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. RP Deutsch, SI (reprint author), Dept Psychiat & Behav Sci, 825 Fairfax Ave,Suite 710, Norfolk, VA 23507 USA. EM deutscsi@evms.edu FU Virginia's Commonwealth Health Research Board; Office of the Dean of Eastern Virginia Medical School FX The authors acknowledge the support they received from grant funding from Virginia's Commonwealth Health Research Board. The authors also acknowledge the support they received from the Office of the Dean of Eastern Virginia Medical School. 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Neuro-Psychopharmacol. Biol. Psychiatry PD JUL 3 PY 2015 VL 60 BP 60 EP 65 DI 10.1016/j.pnpbp.2015.02.009 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CH4ST UT WOS:000354023900007 ER PT J AU Shafritz, KM Bregman, JD Ikuta, T Szeszko, PR AF Shafritz, Keith M. Bregman, Joel D. Ikuta, Toshikazu Szeszko, Philip R. TI Neural systems mediating decision-making and response inhibition for social and nonsocial stimuli in autism SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Cognition; Emotion; Executive function; fMRI ID FUNCTIONAL MAGNETIC-RESONANCE; SPECTRUM DISORDERS; ASPERGER-SYNDROME; BEHAVIORAL-RESPONSE; SPATIAL ATTENTION; BIPOLAR DISORDER; FUSIFORM GYRUS; COGNITIVE SET; FACIAL AFFECT; GO/NO-GO AB Autism is marked by impairments in social reciprocity and communication, along with restricted, repetitive and stereotyped behaviors. Prior studies have separately investigated social processing and executive function in autism, but little is known about the brain mechanisms of cognitive control for both emotional and nonemotional stimuli. We used functional magnetic resonance imaging to identify differences in neurocircuitry between individuals with high functioning autism (HFA) and neurotypical controls during two versions of a go/no-go task: emotional (fear and happy faces) and nonemotional (English letters). During the letter task, HFA participants showed hypoactivation in the ventral prefrontal cortex. During the emotion task, happy faces elicited activation in the ventral striatum, nucleus accumbens and anterior amygdala in neurotypical, but not HFA, participants. Response inhibition for fear faces compared with happy faces recruited occipitotemporal regions in HFA, but not neurotypical, participants. In a direct contrast of emotional no-go and letter no-go blocks, HFA participants showed hyperactivation in extrastriate cortex and fusiform gyrus. Accuracy for emotional no-go trials was negatively correlated with activation in fusiform gyrus in the HFA group. These results indicate that autism is associated with abnormal processing in socioemotional brain networks, and support the theory that autism is marked by a social motivational deficit. (C) 2015 Elsevier Inc. All rights reserved. C1 [Shafritz, Keith M.] Dept Psychol, Hempstead, NY 11549 USA. [Shafritz, Keith M.; Bregman, Joel D.; Szeszko, Philip R.] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Ikuta, Toshikazu] Univ Mississippi, Dept Commun Sci & Disorders, University, MS 38677 USA. [Szeszko, Philip R.] Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY 11004 USA. [Szeszko, Philip R.] Hofstra North Shore LIJ Sch Med, Hempstead, NY 11549 USA. [Bregman, Joel D.] Ctr Autism, Philadelphia, PA 19131 USA. RP Shafritz, KM (reprint author), Dept Psychol, 135 Hofstra Univ, Hempstead, NY 11549 USA. EM keith.shafritz@hofstra.edu FU National Institutes of Health [M01RR018535]; Hofstra University FX We thank Linda Spritzer, Melissa Buchman, Rachel Ginsberg, and Elizabeth Mansdorf for help with subject recruitment, cognitive test administration, and data analysis; Dr. Peter Kingsley and John Ferrannini for technical assistance with MRI data collection; Blair Shevlin and Cori Fisher for help with paradigm development and fMRI data analysis. This study was funded by National Institutes of Health Grant M01RR018535 and grants from Hofstra University. The authors declare no competing financial interests. 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Neuro-Psychopharmacol. Biol. Psychiatry PD JUL 3 PY 2015 VL 60 BP 112 EP 120 DI 10.1016/j.pnpbp.2015.03.001 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CH4ST UT WOS:000354023900012 PM 25765593 ER PT J AU Engineer, CT Rahebi, KC Buell, EP Fink, MK Kilgard, MP AF Engineer, Crystal T. Rahebi, Kimiya C. Buell, Elizabeth P. Fink, Melyssa K. Kilgard, Michael P. TI Speech training alters consonant and vowel responses in multiple auditory cortex fields SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Speech therapy; Auditory processing; Receptive field plasticity; Map reorganization ID DISCRIMINATION ABILITY; CORTICAL PLASTICITY; NEURAL RESPONSES; MAP PLASTICITY; NOISE; REPRESENTATION; AUTISM; RAT; SOUNDS; PATTERNS AB Speech sounds evoke unique neural activity patterns in primary auditory cortex (A1). Extensive speech sound discrimination training alters A1 responses. While the neighboring auditory cortical fields each contain information about speech sound identity, each field processes speech sounds differently. We hypothesized that while all fields would exhibit training-induced plasticity following speech training, there would be unique differences in how each field changes. In this study, rats were trained to discriminate speech sounds by consonant or vowel in quiet and in varying levels of background speech-shaped noise. Local field potential and multiunit responses were recorded from four auditory cortex fields in rats that had received 10 weeks of speech discrimination training. Our results reveal that training alters speech evoked responses in each of the auditory fields tested. The neural response to consonants was significantly stronger in anterior auditory field (AAF) and A1 following speech training. The neural response to vowels following speech training was significantly weaker in ventral auditory field (VAF) and posterior auditory field (PAF). This differential plasticity of consonant and vowel sound responses may result from the greater paired pulse depression, expanded low frequency tuning, reduced frequency selectivity, and lower tone thresholds, which occurred across the four auditory fields. These findings suggest that alterations in the distributed processing of behaviorally relevant sounds may contribute to robust speech discrimination. (C) 2015 Elsevier B.V. All rights reserved. C1 [Engineer, Crystal T.; Rahebi, Kimiya C.; Buell, Elizabeth P.; Fink, Melyssa K.; Kilgard, Michael P.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA. RP Engineer, CT (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, 800 West Campbell Rd,GR41, Richardson, TX 75080 USA. EM novitski@utdallas.edu FU National Institutes of Health [R01DC010433] FX We would like to thank Michael Borland and Linda Wilson for assistance with auditory cortex recordings, and Bogdan Bordieanu for assistance with speech training sessions. This research was supported by a grant from the National Institutes of Health to MPK (Grant # R01DC010433). 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Brain Res. PD JUL 1 PY 2015 VL 287 BP 256 EP 264 DI 10.1016/j.bbr.2015.03.044 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CI8QV UT WOS:000355037700033 PM 25827927 ER PT J AU Kratz, HE Locke, J Piotrowski, Z Ouellette, RR Xie, M Stahmer, AC Mandell, DS AF Kratz, Hilary E. Locke, Jill Piotrowski, Zinnia Ouellette, Rachel R. Xie, Ming Stahmer, Aubyn C. Mandell, David S. TI All Together Now: Measuring Staff Cohesion in Special Education Classrooms SO JOURNAL OF PSYCHOEDUCATIONAL ASSESSMENT LA English DT Article DE autism; classroom cohesion; teacher-staff relationship; classroom team ID EMPIRICAL-EXAMINATION; AUTISM INTERVENTION; INNOVATION; TEAMS; SPORT AB This study sought to validate a new measure, the Classroom Cohesion Survey (CCS), designed to examine the relationship between teachers and classroom assistants in autism support classrooms. Teachers, classroom assistants, and external observers showed good inter-rater agreement on the CCS and good internal consistency for all scales. Simple factor structures were found for both teacher- and classroom assistant-rated scales, with one-factor solutions for both scales. Paired t tests revealed that on average, classroom assistants rated classroom cohesion stronger than teachers. The CCS may be an effective tool for measuring cohesion between classroom staff and may have an important impact on various clinical and implementation outcomes in school settings. C1 [Kratz, Hilary E.; Locke, Jill; Piotrowski, Zinnia; Ouellette, Rachel R.; Xie, Ming; Mandell, David S.] Univ Penn, Philadelphia, PA 19104 USA. [Stahmer, Aubyn C.] Rady Childrens Hosp, San Diego, CA USA. [Stahmer, Aubyn C.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Kratz, HE (reprint author), Univ Penn, 3535 Market St,Suite 600, Philadelphia, PA 19104 USA. EM dingfeld@mail.med.upenn.edu FU NIMH [1R01MH083717-01A1, F31-MH088172]; IES [R324A08195]; FARFund; Autism Science Foundation Early Career Award FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was drawn from the Philadelphia Autism Instructional Methods Study, which was supported by NIMH Grant 1R01MH083717-01A1 and IES Grant R324A08195. This study was also funded by the NIMH F31-MH088172 grant awarded to the first author and the FARFund and the Autism Science Foundation Early Career Award granted to the second author. 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TI The Acquisition of Problem Behavior in Individuals With Developmental Disabilities as a Behavioral Cusp SO BEHAVIOR MODIFICATION LA English DT Article DE behavioral cusp; problem behavior; developmental disabilities ID SELF-INJURIOUS-BEHAVIOR; AUTISM SPECTRUM DISORDERS; CHALLENGING BEHAVIORS; INTELLECTUAL DISABILITY; DESCRIPTIVE ANALYSIS; STAFF BEHAVIOR; YOUNG-CHILDREN; PEOPLE; REINFORCEMENT; CLASSROOMS AB A behavioral cusp has been defined as a behavior change that produces contact with new contingencies with important and far-reaching consequences. The concept of behavioral cusps has most frequently been used to select target skills taught to learners and to evaluate the importance of those skills; however, the concept is equally applicable to behavior changes that bring about important and far-reaching negative consequences. Although it has been acknowledged that socially undesirable behavior change can also qualify as a behavioral cusp, this area of the cusp concept has been under-examined. In this article, an undesirable behavior change, the acquisition of problem behavior in individuals with developmental disabilities, is compared with criteria for behavioral cusps previously identified in the literature. The advantages of viewing problem behavior as a behavioral cusp are outlined, and implications for practice and research from a behavioral cusp approach to problem behavior are provided. C1 [Robertson, Rachel E.] Univ Pittsburgh, Special Educ, Pittsburgh, PA 15260 USA. RP Robertson, RE (reprint author), Univ Pittsburgh, Dept Instruct & Learning, 5146 WWPH,230 S Bouquet St, Pittsburgh, PA 15260 USA. EM rachelr@pitt.edu FU Office of Special Education Programs Leadership Training Grants [H325D020022, H325D070083] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Preparation of this manuscript was funded in part by the Office of Special Education Programs Leadership Training Grants (H325D020022; H325D070083). The opinions expressed in this article are those of the author and do not necessarily reflect those of the funding agency. 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Modificat. PD JUL PY 2015 VL 39 IS 4 BP 475 EP 495 DI 10.1177/0145445515572185 PG 21 WC Psychology, Clinical SC Psychology GA CI8BQ UT WOS:000354992900001 PM 25733661 ER PT J AU Scalzo, R Henry, K Davis, TN Amos, K Zoch, T Turchan, S Wagner, T AF Scalzo, Rachel Henry, Kelsey Davis, Tonya N. Amos, Kally Zoch, Tamara Turchan, Sarah Wagner, Tara TI Evaluation of Interventions to Reduce Multiply Controlled Vocal Stereotypy SO BEHAVIOR MODIFICATION LA English DT Article DE vocal stereotypy; autism; functional communication training ID DEVELOPMENTAL-DISABILITIES; INAPPROPRIATE VOCALIZATIONS; AUTOMATIC REINFORCEMENT; MATCHED STIMULATION; ABERRANT BEHAVIOR; AUTISM; CHILDREN; INDIVIDUALS; IMMEDIATE AB This study examined four interventions targeted at decreasing multiply controlled vocal stereotypy for a 12-year-old boy diagnosed with autism spectrum disorder and a severe intellectual disability. These interventions included Noncontingent Music, Differential Reinforcement of Other Behaviors, Self-Recording, and Functional Communication Training (FCT). In addition to measuring vocal stereotypy during each condition, task engagement and challenging behavior were also monitored. Across conditions, vocal stereotypy did not vary significantly from baseline except in FCT, when it decreased significantly. Task engagement was higher in this condition as well. It is hypothesized that FCT provided an enriched environment by increasing social interaction and access to desired items as well as removal of less preferred activities. For these reasons, there was a decrease in the need for the participant to engage in vocal stereotypy and challenging behavior and increase in his ability to engage in a task. C1 [Scalzo, Rachel] Baylor Univ, Educ Psychol Specializing Appl Behav Anal, Waco, TX 76798 USA. [Henry, Kelsey] Baylor Univ, Sch Psychol, Waco, TX 76798 USA. 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F., 1957, VERBAL BEHAV Taylor BA, 2005, BEHAV INTERVENT, V20, P239, DOI 10.1002/bin.200 NR 24 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2015 VL 39 IS 4 BP 496 EP 509 DI 10.1177/0145445515573986 PG 14 WC Psychology, Clinical SC Psychology GA CI8BQ UT WOS:000354992900002 PM 25733663 ER PT J AU Allen, KD Vatland, C Bowen, SL Burke, RV AF Allen, Keith D. Vatland, Christopher Bowen, Scott L. Burke, Raymond V. TI An Evaluation of Parent-Produced Video Self-Modeling to Improve Independence in an Adolescent With Intellectual Developmental Disorder and an Autism Spectrum Disorder: A Controlled Case Study SO BEHAVIOR MODIFICATION LA English DT Article DE video modeling; community living; transition; parents; autism; intellectual disability ID INTERVENTIONS; DISABILITY; CHILDREN AB We evaluated a parent-created video self-modeling (VSM) intervention to improve independence in an adolescent diagnosed with Intellectual Developmental Disorder (IDD) and Autism Spectrum Disorder (ASD). In a multiple baseline design across routines, a parent and her 17-year-old daughter created self-modeling videos of three targeted routines needed for independence in the community. The parent used a tablet device with a mobile app called VideoTote to produce videos of the daughter performing the targeted routines. The mobile app includes a 30-s tutorial about making modeling videos. The parent and daughter produced and watched a VSM scene prior to performing each of the three routines in an analogue community setting. The adolescent showed marked, immediate, and sustained improvements in performing each routine following the production and implementation of the VSM. Performance was found to generalize to the natural community setting. Results suggest that parents can use available technology to promote community independence for transition age individuals. C1 [Allen, Keith D.] Munroe Meyer Inst Genet & Rehabil, Omaha, NE USA. [Vatland, Christopher] Univ S Florida, Dept Child & Family Studies, Tampa, FL USA. [Bowen, Scott L.; Burke, Raymond V.] Prevent Grp, Omaha, NE USA. RP Allen, KD (reprint author), Munroe Meyer Inst, 985450 Nebraska Med Ctr, Omaha, NE 68198 USA. EM kdallen@unmc.edu FU Autism Action Partnership, Omaha, Nebraska; Maternal and Child Bureau, Health Resources and Services Administration [T73MC00023]; Administration on Intellectual and Developmental Disabilities, Department of Health and Human Services [90DD0701] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was made possible in large part by the generous support of the Autism Action Partnership, Omaha, Nebraska. Support was also provided by Grant T73MC00023 from the Maternal and Child Bureau, Health Resources and Services Administration, and by Grant 90DD0701 from the Administration on Intellectual and Developmental Disabilities, Department of Health and Human Services. CR [Anonymous], 2009, NAT STAND PROJ ADDR Barlow D., 2009, SINGLE CASE EXPT DES Bellini S., 2010, PREVENTING SCH FAILU, V54, P220, DOI DOI 10.1080/10459881003742275 Burke R. 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Howard, Monica R. Fienup, Daniel M. TI The Effects of Work-Reinforcer Schedules on Skill Acquisition for Children With Autism SO BEHAVIOR MODIFICATION LA English DT Article DE work-reinforcer schedules; preference; skill acquisition; autism; reinforcement ID PREFERENCE AB This study evaluated the effects of continuous and discontinuous work-reinforcer schedule arrangements on skill acquisition for three students with autism. Participants were initially exposed to both schedules in an alternating schedules condition where they were taught different but equivalent skills for each schedule. In the discontinuous schedule condition, participants completed work in small increments to gain access to a reinforcer for short periods of time. In the continuous schedule condition, participants completed larger increments of work to gain longer access to a reinforcer. Results showed that two participants mastered the target responses with both schedules and the third participant only met mastery criterion with the continuous schedule. Preference for schedules varied across participants. Session duration was consistently shorter during the continuous work-reinforcer schedule, suggesting that continuous work-reinforcer schedules are more efficient. Participants engaged with the reinforcer less when provided longer access, suggesting that reinforcer access might be reduced with continuous schedules for further efficiency gains. C1 [Kocher, Colleen P.; Howard, Monica R.] ELIJA Sch, Levittown, NY USA. [Kocher, Colleen P.; Fienup, Daniel M.] CUNY Queens Coll, Flushing, NY 11367 USA. RP Fienup, DM (reprint author), CUNY Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. 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PD JUL PY 2015 VL 39 IS 4 BP 600 EP 621 DI 10.1177/0145445515583246 PG 22 WC Psychology, Clinical SC Psychology GA CI8BQ UT WOS:000354992900007 PM 25896361 ER PT J AU Chen, N Koopmans, F Gordon, A Paliukhovich, I Klaassen, RV van der Schors, RC Peles, E Verhage, M Smit, AB Li, KW AF Chen, Ning Koopmans, Frank Gordon, Aaron Paliukhovich, Iryna Klaassen, Remco V. van der Schors, Roe C. Peles, Elior Verhage, Matthijs Smit, August B. Li, Ka Wan TI Interaction proteomics of canonical Caspr2 (CNTNAP2) reveals the presence of two Caspr2 isoforms with overlapping interactomes SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE Autism; Caspr2; Interaction proteomics; Mouse model; Brain ID AUTISM SPECTRUM DISORDERS; MYELINATED AXONS; PROTEIN; CHANNELS; REGIONS; TWIN AB Autism is a human developmental brain disorder characterized by impaired social interaction and communication. Contactin-associated protein-like 2 (Caspr2, CNTNAP2) is a known genetic risk factor of autism. However, how this protein might contribute to pathology is unclear. In this study, we demonstrate that Caspr2 is abundantly present in lipid raft and in the synaptic membrane but is highly depleted in the postsynaptic density. The Caspr2 protein level in hippocampus is present at a constant level during synapse formation and myelination from PO to P84. Interaction proteomics revealed the interactors of Caspr2, including CNTN2, KCNAs, members of the ADAM family (ADAM22, ADAM23 and ADAM11), members of LGI family and MAGUKs (DLGs and MPPs). Interestingly, a short form of Caspr2 was detected, which lacks most of the extracellular domains, however, is still associated with ADAM22 and to a lesser extent LGI1 and Kv1 channels. The comprehensive Caspr2 interactome revealed here might aid in understanding the molecular mechanisms underlying autism. This article is part of a Special Issue titled Neuroproteomics: Applications in Neuroscience and Neurology. (C) 2015 Elsevier B.V. All rights reserved. C1 [Chen, Ning; Paliukhovich, Iryna; Klaassen, Remco V.; van der Schors, Roe C.; Smit, August B.; Li, Ka Wan] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, NL-1081 HV Amsterdam, Netherlands. [Chen, Ning; Koopmans, Frank; Verhage, Matthijs] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. [Gordon, Aaron; Peles, Elior] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Li, KW (reprint author), Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, Neurosci Campus Amsterdam,Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM k.w.li@vu.nl FU Netherlands Institute for Systems Biology (NISB (NWO-ALW)); NIH [NS50220]; Israel Science Foundation; Netherlands Organization for Scientific Research (NWO) Complexity project [645.000.003]; EU-FP7 'SynSys' [HEALTH-2009-2.1.2-1, 242167] FX Ning Chen was funded by a grant from the Netherlands Institute for Systems Biology (NISB (NWO-ALW)). Aaron Gordon and Elior Peles received support from the NIH (NS50220 to EP) and the Israel Science Foundation. Ka Wan Li, Roel C. van der Schors and August B. Smit received support from HEALTH-2009-2.1.2-1 EU-FP7 'SynSys' (#242167). Frank Koopmans was funded from the Netherlands Organization for Scientific Research (NWO) Complexity project 645.000.003. 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Amarasiriwardena, Dulasiri TI Photocatalytic degradation of thimerosal in human vaccine's residues and mercury speciation of degradation by-products SO MICROCHEMICAL JOURNAL LA English DT Article DE Thimerosal degradation; Vaccines; Mercury; Heterogeneous photocatalysis; TiO2; Mercury speciation; Mercury vapor ID ADVANCED OXIDATION PROCESSES; WASTE-WATER TREATMENT; NEURODEVELOPMENTAL DISORDERS; AUTISM; EXPOSURE; PHARMACEUTICALS; IDENTIFICATION; METHYLMERCURY; ETHYLMERCURY AB Thimerosal (sodium ethylmercury thiosalicylate) has been intensively used as a stabilizer of pharmaceuticals, mainly in human and veterinary vaccines. Yearly loss of thousands of vaccines occurs due to expiration, loss of cold chain and overstock; therefore safe disposal of expired vaccines containing thimerosal has become high priority. In this work, UVA light assisted TiO2 heterogeneous photocatalysis has been applied for the first time in order to degrade thimerosal contained in hepatitis B vaccine residues (HibTITER). The photocatalytic process was optimized using the Response Surface Methodology (RSM). Most favorable experimental conditions to achieve the maximum degradation of thimerosal were pH 2 and 0.2 g L-1 TiO2 under nitrogen bubbling. Under these conditions thimerosal contained in vaccine residues was completely degraded within 20 min by UV-A assisted photocatalysis. The mercury in thimerosal was reduced to elemental mercury and removed from the solution in vapor form. The organic groups of thimerosal were oxidized to thiosalicylic acid, salicylic acid and dithiosalicylic acid, identified as by-products. The degradation pathway of thimerosal by photocatalysis and photolysis is proposed. This photocatalytic procedure is environmentally friendly and it could be considered as promising treatment approach for hazardous organomercurial compounds. (C) 2015 Elsevier B.V. All rights reserved. C1 [Yepsen, Orlando; Contreras, David; Santander, Paola; Yanez, Jorge] Univ Concepcion, Fac Chem Sci, Dept Analyt & Inorgan Chem, Concepcion, Chile. [Mansilla, Hector D.] Univ Concepcion, Fac Chem Sci, Dept Organ Chem, Concepcion, Chile. [Amarasiriwardena, Dulasiri] Hampshire Coll, Sch Nat Sci, Amherst, MA 01002 USA. RP Yanez, J (reprint author), Univ Concepcion, Fac Chem Sci, Edmundo Larenas 129, Concepcion, Chile. EM jyanez@udec.cl; hmansill@udec.cl FU National Commission for Scientific and Technological Research (Conicyt) project Fondecyt [1121128, 1130502]; National Commission for Scientific and Technological Research (Conicyt) project Conicyt/FONDAP [15110019]; Red Doctoral REDOC.CTA; MINEDUC [UCO1202]; international collaboration program of project Fondecyt [1121128] FX The authors thank the support of the National Commission for Scientific and Technological Research (Conicyt) projects Fondecyt nos. 1121128 and 1130502, and Conicyt/FONDAP 15110019. Furthermore, the authors appreciate the support of Red Doctoral REDOC.CTA, MINEDUC project UCO1202 at the University of Concepcion and the international collaboration program of project Fondecyt no. 1121128 for the financial support of Professor Dulasiri Amarasiriwardena visit to the University of Concepcion. 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PD JUL PY 2015 VL 121 BP 41 EP 47 DI 10.1016/j.microc.2015.02.001 PG 7 WC Chemistry, Analytical SC Chemistry GA CI2PO UT WOS:000354589700007 ER PT J AU Khosrowabadi, R Quek, C Ang, KK Wahab, A Chen, SHA AF Khosrowabadi, Reza Quek, Chai Ang, Kai Keng Wahab, Abdul Chen, Shen-Hsing Annabel TI Dynamic screening of autistic children in various mental states using pattern of connectivity between brain regions SO APPLIED SOFT COMPUTING LA English DT Article DE Autism screening; EEG; Connectivity feature; Affective face perception; Pattern recognition ID EEG PHASE RESET; SPECTRUM DISORDER; FUNCTIONAL CONNECTIVITY; TYPICAL DEVELOPMENT; CORPUS-CALLOSUM; FACE; RECOGNITION; EMOTION; NETWORK; UNDERCONNECTIVITY AB In this study, a dynamic screening strategy is proposed to discriminate subjects with autistic spectrum disorder (ASD) from healthy controls. The ASD is defined as a neurodevelopmental disorder that disrupts normal patterns of connectivity between the brain regions. Therefore, the potential use of such abnormality for autism screening is investigated. The connectivity patterns are estimated from electroencephalogram (EEG) data collected from 8 brain regions under various mental states. The EEG data of 12 healthy controls and 6 autistic children (age matched in 7-10) were collected during eyes-open and eyes-close resting states as well as when subjects were exposed to affective faces (happy, sad and calm). Subsequently, the subjects were classified as autistic or healthy groups based on their brain connectivity patterns using pattern recognition techniques. Performance of the proposed system in each mental state is separately evaluated. The results present higher recognition rates using functional connectivity features when compared against other existing feature extraction methods. (C) 2015 Published by Elsevier B.V. C1 [Khosrowabadi, Reza; Quek, Chai] Nanyang Technol Univ, Sch Comp Engn, Singapore 639798, Singapore. [Khosrowabadi, Reza] Shahid Beheshti Univ, Inst Cognit & Brain Sci, Tehran 1983963113, Iran. [Ang, Kai Keng] Agcy Sci Technol & Res, Inst Infocomm Res, Singapore 138632, Singapore. [Wahab, Abdul] Int Islamic Univ, Sch Informat & Commun Technol, Kuala Lumpur 50728, Malaysia. [Chen, Shen-Hsing Annabel] Nanyang Technol Univ, Sch Humanities & Social Sci, Singapore 637332, Singapore. [Chen, Shen-Hsing Annabel] Nanyang Technol Univ, Ctr Res & Dev Learning CRADLE, Singapore 637459, Singapore. RP Khosrowabadi, R (reprint author), Nanyang Technol Univ, Sch Comp Engn, Block N4 2A-32,Nanyang Ave, Singapore 639798, Singapore. EM reza0004@e.ntu.edu.sg; ashcqueck@ntu.edu.sg; kkang@i2r.a-star.edu.sg; abdulwahab@iium.edu.my; annabelchen@ntu.edu.sg RI ahmed, Jamila/E-8653-2015 FU International Islamic University of Malaysia (IIUM) [EDW A-10554] FX This project is supported by the International Islamic University of Malaysia (IIUM) endowment fund (EDW A-10554). The authors would like to thank Drs. Bjorn Cri its from Biometrisch centrum for sponsoring the EEG machine, the National Autism Society of Malaysia (NASOM) for conducting the intelligence and screening tests and coordination of EEG sessions with ASD children, Ms. Marini Othman and Ms. Najwani Razali from IIUM department of computer science for their support in the data collection of the experiment and Dr. Elsbeth Huberta Peters-Gruetzmacher from university of Malaya Centre Of Addiction Sciences (UMCAS) for her advice on the design phase of this experiment. 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Soft. Comput. PD JUL PY 2015 VL 32 BP 335 EP 346 DI 10.1016/j.asoc.2015.03.030 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA CH7AD UT WOS:000354187000029 ER PT J AU Aradhye, C Vonk, J Arida, D AF Aradhye, Chinmay Vonk, Jennifer Arida, Danielle TI Adults' responsiveness to children's facial expressions SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE Young children's expressions; Emotion; Responsiveness; Cuteness; Nurture; Parenting ID EARLY INFANT COMMUNICATION; HIGH-FUNCTIONING AUTISM; SEX-DIFFERENCES; PHYSICAL ATTRACTIVENESS; BABY SCHEMA; PARENTAL SENSITIVITY; MATERNAL SENSITIVITY; PERSPECTIVE-TAKING; MOTHER ATTACHMENT; PREMATURE-INFANTS AB We investigated the effect of young children's (hereafter children's) facial expressions on adult responsiveness. In Study 1, 131 undergraduate students from a midsized university in the midwestern United States rated children's images and videos with smiling, crying, or neutral expressions on cuteness, likelihood to adopt, and participants' experienced distress. Looking times at images and videos along with perception of cuteness, likelihood to adopt, and experienced distress using 10-point Likert scales were measured. Videos of smiling children were rated as cuter and more likely to be adopted and were viewed for longer times compared with videos of crying children, which evoked more distress. In Study 2, we recorded responses from 101 of the same participants in an online survey measuring gender role identity, empathy, and perspective taking. Higher levels of femininity (as measured by Bem's Sex Role Inventory) predicted higher "likely to adopt" ratings for crying images. 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These networks are built upon a structural scaffolding with intrinsic neuroplasticity that changes with development, aging, disease, and personal experience. In this article, we begin from the perspective that successful interregional communication relies upon the transient synchronization between distinct low-frequency (<80 Hz) oscillations, allowing for brief windows of communication via phase-coordinated local neuronal spiking. From this, we construct a theoretical framework for dynamic network communication, arguing that these networks reflect a balance between oscillatory coupling and local population spiking activity and that these two levels of activity interact. We theorize that when oscillatory coupling is too strong, spike timing within the local neuronal population becomes too synchronous; when oscillatory coupling is too weak, spike timing is too disorganized. Each results in specific disruptions to neural communication. These alterations in communication dynamics may underlie cognitive changes associated with healthy development and aging, in addition to neurological and psychiatric disorders. A number of neurological and psychiatric disorders-including Parkinson's disease, autism, depression, schizophrenia, and anxiety-are associated with abnormalities in oscillatory activity. Although aging, psychiatric and neurological disease, and experience differ in the biological changes to structural gray or white matter, neurotransmission, and gene expression, our framework suggests that any resultant cognitive and behavioral changes in normal or disordered states or their treatment are a product of how these physical processes affect dynamic network communication. C1 [Voytek, Bradley] Univ Calif San Diego, Dept Cognit Sci, Neurosci Grad Program, La Jolla, CA 92093 USA. [Voytek, Bradley] Univ Calif San Diego, Inst Neural Computat, La Jolla, CA 92093 USA. [Knight, Robert T.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Knight, Robert T.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Voytek, B (reprint author), Univ Calif San Diego, Dept Cognit Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM bradley.voytek@gmail.com FU University of California, San Diego; Sloan Research Fellowship; National Institute of Neurological Disorders and Stroke Grant [R37 NS21135-27]; Defense Advanced Research Projects Agency Systems-Based Neurotechnology for Emerging Therapies; Qualcomm Institute; California Institute for Telecommunications and Information Technology, Strategic Research Opportunities program FX This work was supported by the University of California, San Diego, Qualcomm Institute, California Institute for Telecommunications and Information Technology, Strategic Research Opportunities program (BV) and a Sloan Research Fellowship (BV), as well as National Institute of Neurological Disorders and Stroke Grant R37 NS21135-27 (RTK) and Defense Advanced Research Projects Agency Systems-Based Neurotechnology for Emerging Therapies (RTK). 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Psychiatry PD JUN 15 PY 2015 VL 77 IS 12 BP 1089 EP 1097 DI 10.1016/j.biopsych.2015.04.016 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ0BX UT WOS:000355138500011 ER PT J AU Park, M Baek, IJ Kim, H Woo, DK Park, YJ Shim, S AF Park, Minsoo Baek, In-Jeoung Kim, Hyunduk Woo, Dong Kyun Park, Young-Jun Shim, Sungbo TI CCN3 overexpression inhibits growth of callosal projections via upregulation of RAB25 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CCN3; RAB25; Neurite outgrowth; Callosal projection; Cortex ID DEVELOPING CEREBRAL-CORTEX; NEURON IDENTITY; EXPRESSION; BRAIN; TRANSCRIPTOME; PROTEINS; SYSTEM; FAMILY; AUTISM; SIZE AB The cysteine-rich 61/connective tissue growth factor 3 (CCN3) is a member of the CCN family of secreted multifunctional proteins involved in a variety of cellular processes including migration, adhesion, and differentiation. Previous studies have shown that CCN3 is expressed in the developing rat central nervous system, and enhanced CCN3 expression is highly correlated with tumorigenesis. However, the expression pattern and influence of abnormal CCN3 expression during mouse cortical development remains to be elucidated. Here, we show that CCN3 expression in mice is first detectable at embryonic day 15 and increases until postnatal day 21. We overexpressed CCN3 in mouse cortical neurons using uni- and bilateral electroporation. Our in vivo overexpression experiments showed that elevated CCN3 expression inhibited the axonal outgrowth of callosal projection neurons. Moreover, we identified the small GTPase RAB25 as a downstream effector molecule of CCN3 using transcriptomic analysis with CCN3 overexpressed in cortical tissue. In vivo ectopic expression of RAB25 or the dominant-negative RAB25-T26N also revealed that the GTPase activity of RAB25 is involved in the CCN3-mediated regulation of neuronal outgrowth. Taken together, our results suggest that tight regulation of CCN3 expression is necessary for normal cortical neuronal connectivity during development, and RAB25 negatively regulates neuronal differentiation as a downstream effector of CCN3. (C) 2015 Elsevier Inc. All rights reserved. C1 [Park, Minsoo; Kim, Hyunduk; Shim, Sungbo] Univ Ulsan Coll Med, Dept Biomed Sci, Seoul 138736, South Korea. [Park, Young-Jun] Korea Res Inst Biosci & Biotechnol, Immunotherapy Res Ctr, Daejeon, South Korea. [Park, Minsoo; Baek, In-Jeoung; Kim, Hyunduk; Shim, Sungbo] Neuromarker Resource Bank NRB, Seoul 138736, South Korea. [Woo, Dong Kyun] Gyeongsang Natl Univ, Coll Pharm, Gyeongnam, South Korea. [Woo, Dong Kyun] Gyeongsang Natl Univ, Pharmaceut Sci Res Inst, Gyeongnam, South Korea. [Baek, In-Jeoung] Asan Inst Life Sci, Seoul 138736, South Korea. RP Shim, S (reprint author), Univ Ulsan Coll Med, Dept Biomed Sci, Seoul 138736, South Korea. EM pyj71@kribb.re.kr; sungbo@ulsan.ac.kr FU Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIP) [NRF-2014M3A9B8023198, NRF-2013M3A9B6046567, NRF-2014R1A1A1003690]; Ministry of Education, Science Technology; KRIBB Research Initiative Program, Republic of Korea; Korean Health Technology R&D Project, Ministry of Health Welfare [A121338] FX This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (NRF-2014M3A9B8023198, NRF-2013M3A9B6046567 and NRF-2014R1A1A1003690). This study was also supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (A121338), and the Ministry of Education, Science & Technology, and the KRIBB Research Initiative Program, Republic of Korea. 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PD JUN 5 PY 2015 VL 461 IS 3 BP 456 EP 462 DI 10.1016/j.bbrc.2015.04.016 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CJ0HU UT WOS:000355157200004 PM 25871796 ER PT J AU Quintela, I Barros, F Lago-Leston, R Castro-Gago, M Carracedo, A Eiris, J AF Quintela, Ines Barros, Francisco Lago-Leston, Ramon Castro-Gago, Manuel Carracedo, Angel Eiris, Jesus TI A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 16p13; 11-p12; 3 duplication; 12p12; 1 deletion; SOX5; intellectual disability; global developmental delay; disruptive behavior; obsessive behavior; dysmorphism ID TRANSCRIPTION FACTORS; LONG FORM; L-SOX5; HAPLOINSUFFICIENCY; DISORDERS; VARIANTS; ACTIVATE; AUTISM; GENE; CNVS AB We detail here the clinical description and the family genetic study of a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features and a combination of two rare genetic variants: a maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion affecting SOX5. The 16p13.11 microduplication has been implicated in several neurodevelopmental and behavioral disorders and is characterized by variable expressivity and incomplete penetrance. The causes of this variation in phenotypic expression are not fully clear, representing a challenge in genetic diagnosis and counseling. However, several authors have proposed the two-hit model as one of the underlying mechanisms for this phenotypic heterogeneity. Our data could also support this two-hit model in which the 16p13.11-p12.3 duplication might contribute to the phenotype, not only as a single event but also in association with the SOX5 deletion. The SOX5 gene plays important roles in various developmental processes and has been associated with several neurodevelopmental disorders, mainly intellectual disability, developmental delay and language and/or speech delay as well as with behavior problems and dysmorphic features. However, many of the physical features and behavioral manifestations as well as language deficiencies present in our patient are consistent with those previously reported for SOX5 deletions. Patients carrying multiple genomic variants, as the one presented here, illustrate the difficulty in analyzing genotypes when the contribution of each variant results in overlapping phenotypes and/or, alternatively, in the modification of the clinical manifestations defined by the coexisting variant. (c) 2015 Wiley Periodicals, Inc. C1 [Quintela, Ines; Carracedo, Angel] Univ Santiago de Compostela, Ctr Nacl Genotipado, Inst Salud Carlos III, Grp Med Xenom, Santiago De Compostela, Spain. [Barros, Francisco; Carracedo, Angel] Fdn Publ Galega Med Xenom, SERGAS, CIBERER, Grp Med Xenom,USC, Santiago De Compostela 15707, Spain. [Lago-Leston, Ramon] Fdn Publ Galega Med Xenom, SERGAS, Grp Med Xenom, USC, Santiago De Compostela 15707, Spain. [Castro-Gago, Manuel; Eiris, Jesus] Hosp Clin Univ Santiago de Compostela, Dept Pediat, Unidad Neurol Pediat, Santiago De Compostela, Spain. [Carracedo, Angel] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21413, Saudi Arabia. RP Barros, F (reprint author), Fdn Publ Galega Med Xenom, Hosp Clin Univ, Edif Consultas Planta 2, Santiago De Compostela 15707, Spain. 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Gai, Zhongtao TI De novo exon 1 deletion of AUTS2 gene in a patient with autism spectrum disorder and developmental delay: A case report and a brief literature review SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autism susceptibility candidate 2; neurodevelopmental disorders; autism spectrum disorder; developmental delay ID COPY-NUMBER VARIATION; AUTISM-SUSCEPTIBILITY-CANDIDATE-2 AUTS2; TRANSLOCATION BREAKPOINT; IDENTIFICATION; RISK; MUTATIONS; GENOME; BRAIN AB Exonic deletions disrupting the autism susceptibility candidate 2 (AUTS2) gene have been demonstrated as causal variants leading to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and developmental delay (DD). Here, we report on 830kb de novo deletion at chromosome 7q11.22 in a 4-year-old male patient with ASD and DD. This deletion disrupts the promoter region and exon 1 of AUTS2, potentially leading to complete haploinsuffiency of the gene. In addition, we discuss the clinical presentation of the de novo deletion in the light of the previous studies describing deletions of AUTS2 in NDDs. (c) 2015 Wiley Periodicals, Inc. C1 [Liu, Yi; Dong, Rui; Yang, Xiaomeng; Gai, Zhongtao] Shandong Univ, Qilu Childrens Hosp, Pediat Res Inst, Jinan 250022, Peoples R China. [Zhao, Dongmei; Zhang, Yanqing; Gai, Zhongtao] Shandong Univ, Qilu Childrens Hosp, Pediat Hlth Inst, Jinan 250022, Peoples R China. [Tammimies, Kristiina; Uddin, Mohammed; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Scherer, SW (reprint author), Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. EM stephen.scherer@sickkids.ca; gaizhongtao@sina.com FU GSK-CIHR Endowed Chair in Genome Sciences FX The authors are grateful to the patient and his family for their contribution to the project. We would like to thank Shanghai Biotechnology Co., Shanghai Biochip National Engineering Research Center for technical support, as well as The Centre for Applied Genomics at the Hospital for Sick Children and the University of Toronto McLaughlin Centre. S.W.S. is supported by the GSK-CIHR Endowed Chair in Genome Sciences. 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[Heath, Anna; Fullerton, Janice M.] Neurosci Res Australia, Sydney, NSW, Australia. [Fullerton, Janice M.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. RP Kamien, B (reprint author), Hunter Genet, POB 84 Waratah, Newcastle, NSW 2298, Australia. EM benkamien@yahoo.com.au CR Kamien B, 2014, AM J MED GENET A, V164, P782, DOI 10.1002/ajmg.a.36345 NR 1 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2015 VL 167A IS 6 BP 1424 EP 1424 DI 10.1002/ajmg.a.36846 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA CJ1WV UT WOS:000355276700043 PM 25846131 ER PT J AU Le Couteur, AS Singh, MK Sharma, AN AF Le Couteur, A. S. Singh, M. K. Sharma, A. N. TI Understanding adolescent bipolar disorder (BD-A): when is a dual diagnosis of autism spectrum disorder (ASD) appropriate? Experiences from the USA and UK SO BIPOLAR DISORDERS LA English DT Meeting Abstract C1 [Le Couteur, A. S.; Sharma, A. N.] Newcastle Univ, Acad Child & Adolescent Mental Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Singh, M. K.] Stanford Univ, Pediat Bipolar Disorders Program, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2015 VL 17 SU 1 SI SI BP 117 EP 117 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2TS UT WOS:000355338100328 ER PT J AU Lambert-Brown, BL McDonald, NM Mattson, WI Martin, KB Ibanez, LV Stone, WL Messinger, DS AF Lambert-Brown, Brittany L. McDonald, Nicole M. Mattson, Whitney I. Martin, Katherine B. Ibanez, Lisa V. Stone, Wendy L. Messinger, Daniel S. TI Positive Emotional Engagement and Autism Risk SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE smiling; affective communication; autism risk; infancy ID SIBLINGS RESEARCH CONSORTIUM; UNAFFECTED SIBLINGS; SPECTRUM DISORDERS; INFANT INTERACTION; STILL-FACE; CHILDREN; MOTHER; RESPONSIVENESS; COMMUNICATION; ATTENTION AB Positive emotional engagement develops in the context of face-to-face interactions during the first 6 months of life. Deficits in emotional engagement are characteristic of autism spectrum disorder (ASD) and may characterize the younger siblings of children with ASD (high-risk siblings). High-risk siblings are likely to exhibit a broad range of positive emotional engagement that may or may not be associated with ASD outcomes. We examined positive emotional engagement (i.e., smiling rate and contingent responsiveness to the partner's smile) during the infant-parent interaction episodes of the face-to-face/still face protocol at 6 months of age. The sample included 43 high-risk infant siblings, 11 of whom went on to an ASD diagnosis, and 25 low-risk siblings with no family history of ASD. Low-risk siblings and high-risk siblings without ASD showed the typical still-face effect (i.e., decreases in smiling rate after period of parental nonresponsiveness), but high-risk siblings with later ASD outcomes did not show this decrease. Although high-risk siblings without an ASD diagnosis were less likely to respond to their parents' smiles than were low-risk siblings, the children with eventual ASD did not differ from the other groups in contingent responsiveness. Findings suggest that subtle differences in positive emotional engagement are present in the early development of high-risk siblings but are not consistently associated with ASD outcomes. C1 [Lambert-Brown, Brittany L.; McDonald, Nicole M.; Mattson, Whitney I.; Martin, Katherine B.; Messinger, Daniel S.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Ibanez, Lisa V.; Stone, Wendy L.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Messinger, Daniel S.] Univ Miami, Dept Pediat, Coral Gables, FL 33146 USA. [Messinger, Daniel S.] Univ Miami, Dept Elect & Comp Engn, Coral Gables, FL 33146 USA. [Messinger, Daniel S.] Univ Miami, Dept Mus Engn, Coral Gables, FL 33146 USA. RP Messinger, DS (reprint author), Univ Miami, Dept Psychol, 5665 Ponce Leon, Coral Gables, FL 33146 USA. EM dmessinger@miami.edu FU National Institute of Child Health and Development [R01HD057284, R01HD047417]; National Institute of General Medical Sciences [R01GM105004]; National Science Foundation [1052736] FX The research reported in this article was supported by the National Institute of Child Health and Development (Grants R01HD057284 and R01HD047417), the National Institute of General Medical Sciences (Grant R01GM105004), and the National Science Foundation (Grant 1052736). We thank the families who participated in this research. 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Psychol. PD JUN PY 2015 VL 51 IS 6 BP 848 EP 855 DI 10.1037/a0039182 PG 8 WC Psychology, Developmental SC Psychology GA CJ0MA UT WOS:000355169100011 PM 25938555 ER PT J AU Fejzo, MS Magtira, A Schoenberg, FP Macgibbon, K Mullin, PM AF Fejzo, Marlena S. Magtira, Aromalyn Schoenberg, Frederic Paik Macgibbon, Kimber Mullin, Patrick M. TI Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Hyperemesis gravidarum; Outcome; Nausea; Pregnancy; Attention, learning, sensory, speech; Neurodevelopmental delay ID PREGNANCY OUTCOMES; PRENATAL EXPOSURE; INCREASED RISK; DEFICIENCY; DISEASE; HEALTH; NAUSEA; WOMEN; CONSEQUENCES; SENSITIVITY AB Objective: The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Study design: Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Results: Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (P < 0.0005). Among characteristics of HG pregnancies, only early onset of symptoms (prior to 5 weeks gestation) was significantly linked to neurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Conclusion: Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Fejzo, Marlena S.] Univ Calif Los Angeles, Dept Obstet Gynecol & Med, Los Angeles, CA USA. [Magtira, Aromalyn; Schoenberg, Frederic Paik] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. [Macgibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA. [Fejzo, Marlena S.; Mullin, Patrick M.] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90033 USA. RP Fejzo, MS (reprint author), 675 Charles E Young Dr S, Los Angeles, CA USA. EM mfejzo@mednet.ucla.edu FU Hyperemesis Education and Research Foundation FX We are grateful to our students, Arteen Pirverdian and Erina Szeto for their work on this project. This research was funded, in part, by the Hyperemesis Education and Research Foundation (helpher.org). 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1499 EP 1512 DI 10.1007/s10803-014-2293-5 PG 14 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700001 PM 25518823 ER PT J AU Whalon, KJ Conroy, MA Martinez, JR Werch, BL AF Whalon, Kelly J. Conroy, Maureen A. Martinez, Jose R. Werch, Brittany L. TI School-Based Peer-Related Social Competence Interventions for Children with Autism Spectrum Disorder: A Meta-Analysis and Descriptive Review of Single Case Research Design Studies SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social competence; Social communication; Autism spectrum disorder; Literature review; Meta-analysis ID YOUNG-CHILDREN; COMMUNICATION-SKILLS; PRESCHOOL-CHILDREN; ASPERGER-SYNDROME; STORIES; BEHAVIOR; INITIATIONS; INCREASE; SETTINGS; DISABILITIES AB The purpose of this review was to critically examine and summarize the impact of school-based interventions designed to facilitate the peer-related social competence of children with autism spectrum disorder (ASD). Reviewed studies employed a single-case experimental design, targeted peer-related social competence, included children 3-12 years old with an ASD, and took place in school settings. Articles were analyzed descriptively and using the evaluative method to determine study quality. Additionally, effect size estimates were calculated using nonoverlap of all pairs method and Tau-U. A total of 37 studies including 105 children were reviewed. Overall, ES estimates ranged from weak to strong, but on average, the reviewed interventions produced a moderate to strong effect, and quality ratings were generally in the acceptable to high range. Findings suggest that children with ASD can benefit from social skill interventions implemented with peers in school settings. C1 [Whalon, Kelly J.] Florida State Univ, Coll Educ, Tallahassee, FL 32306 USA. [Conroy, Maureen A.; Martinez, Jose R.; Werch, Brittany L.] Univ Florida, Coll Educ, Tallahassee, FL USA. RP Whalon, KJ (reprint author), Florida State Univ, Coll Educ, 1114 W Call St,POB 3064450, Tallahassee, FL 32306 USA. 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PD JUN PY 2015 VL 45 IS 6 BP 1513 EP 1531 DI 10.1007/s10803-015-2373-1 PG 19 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700002 PM 25641004 ER PT J AU Dekker, LP van der Vegt, EJM Visser, K Tick, N Boudesteijn, F Verhulst, FC Maras, A Greaves-Lord, K AF Dekker, Linda P. van der Vegt, Esther J. M. Visser, Kirsten Tick, Nouchka Boudesteijn, Frieda Verhulst, Frank C. Maras, Athanasios Greaves-Lord, Kirstin TI Improving Psychosexual Knowledge in Adolescents with Autism Spectrum Disorder: Pilot of the Tackling Teenage Training Program SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Psychosexual functioning; Autism spectrum disorder; Psychosexual knowledge; Training program ID DIAGNOSTIC OBSERVATION SCHEDULE; SEXUAL-BEHAVIOR; CONDOM USE; ADULTS; COMMUNICATION; PERCEPTIONS; ATTITUDES AB Previous studies have shown that psychosexual functioning in adolescents with autism spectrum disorder (ASD) is hampered and emphasize the need for a specialized training program tailored to their needs. Therefore, an individual training program was developed; the Tackling Teenage Training (TTT) program. The current pilot study systematically evaluated whether psychosexual knowledge increased after taking part in the TTT program, using a pre- and post-training design in 30 adolescents with ASD (77 % male, mean age = 14.80 years, mean intelligence = 96.96). Psychosexual knowledge increased significantly (pre-training total score: M = 25.74, SD = 6.20; post-training total score: M = 33.52 (SD = 2.78); F(1,29) = 65.20, p < .001). The TTT program may be useful to improve psychosexual knowledge and functioning in adolescents with ASD, yet these findings are preliminary, and a more elaborate controlled trial is needed. C1 [Dekker, Linda P.; van der Vegt, Esther J. M.; Visser, Kirsten; Tick, Nouchka; Verhulst, Frank C.; Greaves-Lord, Kirstin] Erasmus MC Sophia, Dept Child & Adolescent Psychiat Psychol, NL-3015 CN Rotterdam, Netherlands. [Dekker, Linda P.; van der Vegt, Esther J. M.; Visser, Kirsten; Tick, Nouchka; Boudesteijn, Frieda; Maras, Athanasios; Greaves-Lord, Kirstin] Mental Hlth Org, Yulius, Yulius Acad & Yulius Autism, NL-3013 HH Rotterdam, Netherlands. RP Dekker, LP (reprint author), Erasmus MC Sophia, Dept Child & Adolescent Psychiat Psychol, Wytemaweg 8,Room KP 2881, NL-3015 CN Rotterdam, Netherlands. EM l.p.dekker@erasmusmc.nl FU Sophia Children's Hospital Fund [617]; Anthonia Wilhelimina Fund of the Psychological Health fund (Fonds Psychische Gezondheid) FX This project was financially supported by the Sophia Children's Hospital Fund (Grant Number 617, titled Tackling Teenage: a multicenter study on psychosexual development and intimacy in adolescents with Autism Spectrum Disorder). The professionalization of the Tackling Teenage Training was financially supported by the Anthonia Wilhelimina Fund which is a part of the Psychological Health fund (i.e. Fonds Psychische Gezondheid). 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R., 2013, RECENT ADV AUTISM SP, VI Wechsler D., 2004, WECHSLER INTELLIGENC Wolters CA, 2003, EDUC PSYCHOL, V38, P189, DOI 10.1207/S15326985EP3804_1 ZIMET GD, 1992, J ADOLESCENT HEALTH, V13, P493, DOI 10.1016/1054-139X(92)90013-2 NR 34 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 JUN PY 2015 VL 45 IS 6 BP 1532 EP 1540 DI 10.1007/s10803-014-2301-9 PG 9 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700003 PM 25399394 ER PT J AU Minshawi, NF Hurwitz, S Morriss, D McDougle, CJ AF Minshawi, Noha F. Hurwitz, Sarah Morriss, Danielle McDougle, Christopher J. TI Multidisciplinary Assessment and Treatment of Self-Injurious Behavior in Autism Spectrum Disorder and Intellectual Disability: Integration of Psychological and Biological Theory and Approach SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Intellectual disability; Self-injurious behavior; Behavior therapy; Pharmacotherapy ID PRADER-WILLI-SYNDROME; LESCH-NYHAN-SYNDROME; PERVASIVE DEVELOPMENTAL DISORDERS; MENTALLY RETARDED CHILDREN; PATHOLOGICAL SKIN-PICKING; DU-CHAT-SYNDROME; DOUBLE-BLIND; CHALLENGING BEHAVIOR; NONCONTINGENT REINFORCEMENT; ATYPICAL ANTIPSYCHOTICS AB The objective of this review is to consider the psychological (largely behavioral) and biological [neurochemical, medical (including genetic), and pharmacological] theories and approaches that contribute to current thinking about the etiology and treatment of self-injurious behavior (SIB) in individuals with autism spectrum disorder and/or intellectual disability. Algorithms for the assessment and treatment of SIB in this context, respectively, from a multidisciplinary, integrative perspective are proposed and challenges and opportunities that exist in clinical and research settings are discussed. C1 [Minshawi, Noha F.] Indiana Univ Sch Med, Dept Psychiat, James Whitcomb Riley Hosp Children, Christian Sarkine Autism Treatment Ctr, Indianapolis, IN 46202 USA. [Hurwitz, Sarah] Indiana Univ, Sch Educ, Bloomington, IN 47405 USA. [Morriss, Danielle] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Psychiat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Pediat, Lexington, MA 02421 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, MassGen Hosp Children, Lexington, MA 02421 USA. 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We examine individuals with Prader-Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to that routine. Play based challenges exposed 16 participants to routines, which were either adhered to or changed. Temper outburst behaviors, heart rate and movement were measured. As participants were exposed to routines for longer before a change (between 10 and 80 min; within participants), more temper outburst behaviors were elicited by changes. Increased emotional arousal was also elicited, which was indexed by heart rate increases not driven by movement. Further study will be important to understand whether current intervention approaches that limit exposure to changes, may benefit from the structured integration of flexibility to ensure that the opportunity for routine establishment is also limited. C1 [Bull, Leah E.; Oliver, Chris; Callaghan, Eleanor; Woodcock, Kate A.] Univ Birmingham, Cerebra Ctr Neurodev Disorders, Birmingham B15 2TT, W Midlands, England. RP Woodcock, KA (reprint author), Queens Univ Belfast, Sch Psychol, Univ Rd, Belfast BT7 1NN, Antrim, North Ireland. EM k.woodcock@qub.ac.uk FU Jerome Lejeune Foundation; Cerebra FX This work was supported by a project grant from the Jerome Lejeune Foundation to KAW and CO, and Cerebra who provide core funding to the Cerebra Centre for Neurodevelopmental Disorders (to director CO). Special thanks to the Prader-Will Syndrome Association, UK and Gretton Homes for their assistance in recruitment; Emma Cross, Laura Heath-Jones Campbell, Victoria Johnson, Jessica Penhallow, Amy Perry and Helena Todd, for assistance with data collection and processing; and Prof. Tony Holland for advice on project design and assistance with recruitment. Finally, we are extremely grateful for the support of the participants, their families and caregivers, without whom the work would not have been possible. 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Kenworthy, Lauren TI Increasing Adaptive Behavior Skill Deficits From Childhood to Adolescence in Autism Spectrum Disorder: Role of Executive Function SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Adaptive behavior; Executive function; Cognitive ability ID DEVELOPMENTAL DISORDERS; COMMUNICATION DEFICITS; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; REAL-WORLD; INDIVIDUALS; CHILDREN; VINELAND; MIND; ABILITIES AB Almost half of all children with autism spectrum disorder have average cognitive abilities, yet outcome remains poor. Because outcome in HFASD is more related to adaptive behavior skills than cognitive level it is important to identify predictors of adaptive behavior. This study examines cognitive and demographic factors related to adaptive behavior, with specific attention to the role of executive function (EF) in youth with HFASD aged 4-23. There was a negative relationship between age and adaptive behavior and the discrepancy between IQ and adaptive behavior increased with age. EF problems contributed to lower adaptive behavior scores across domains. As such, it is important to target adaptive skills, and the EF problems that may contribute to them, in youth with HFASD. C1 [Pugliese, Cara E.; Anthony, Laura; Strang, John F.; Dudley, Katerina; Kenworthy, Lauren] Childrens Natl Hlth Syst, Ctr Autism Spectrum Disorders, Div Neuropsychol, Rockville, MD USA. [Pugliese, Cara E.] Childrens Res Inst, Ctr Autism Spectrum Disorders, Div Neuropsychol, Rockville, MD 20850 USA. [Wallace, Gregory L.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA. RP Pugliese, CE (reprint author), Childrens Res Inst, Ctr Autism Spectrum Disorders, Div Neuropsychol, 15245 Shady Grove Rd 350, Rockville, MD 20850 USA. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1579 EP 1587 DI 10.1007/s10803-014-2309-1 PG 9 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700006 PM 25398602 ER PT J AU Mehling, MH Tasse, MJ AF Mehling, Margaret H. Tasse, Marc J. TI Impact of Choice on Social Outcomes of Adults with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Social relationships; Social participation; Access to services; Personal control; National core indicators ID QUALITY-OF-LIFE; RECEPTIVE LANGUAGE DISORDER; HIGH-FUNCTIONING ADULTS; FOLLOW-UP; ASPERGER-SYNDROME; AUTISM; DISABILITIES; ADOLESCENTS; PREDICTORS; CHILDHOOD AB This study explores social outcomes for adults with autism spectrum disorder (ASD) in comparison to adults with developmental disabilities other than ASD by investigating the relationships between the constructs Social Participation and Relationships, Social Determination, and Personal Control. Structural equation modeling (SEM) was used to test a model of the relationships among constructs of interest and structured means analysis was used to test for mean group differences on these constructs. Results indicated that individuals with ASD had lower levels of Social Determination and Friendships than individuals with other developmental disabilities. SEM analyses yielded significant relationships between constructs. Results provide insight with regards to novel statistical, theoretical, and practical approaches to the study of social outcomes for individuals with ASD. C1 [Mehling, Margaret H.; Tasse, Marc J.] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. RP Mehling, MH (reprint author), Ohio State Univ, Nisonger Ctr, 279 McCambbell Hall,1581 Dodd Dr, Columbus, OH 43210 USA. EM mehling.19@osu.edu; Marc.tasse@osumc.edu FU U.S. Administration on Intellectual and Developmental Disabilities Grant [99-DD-0621] FX The authors would like to acknowledge Robert Cudeck, Ph.D. and Rebecca Andridge Ph.D. for their consultation regarding the statistical analyses carried out in this study. Authors would also like to acknowledge Human Services Research Institute (HSRI) and the National Association of State Directors of Developmental Disabilities Services (NASDDDS) and thank these organizations for their contribution of the National Core Indicators (NCI) dataset to this study. This study was supported in part with funding from the U.S. Administration on Intellectual and Developmental Disabilities Grant #99-DD-0621. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Ashbaugh J., 2001, NATL CORE INDICATORS Billstedt E, 2005, J AUTISM DEV DISORD, V35, P351, DOI 10.1007/s10803-005-3302-5 Billstedt E, 2011, AUTISM, V15, P7, DOI 10.1177/1362361309346066 Browne M. 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TI Decision-Making in a Changing World: A Study in Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Social; Instability; Decision-making ID HIGH-FUNCTIONING AUTISM; CINGULATE CORTEX; SOCIAL-STIMULI; NORMAL ADULTS; CHILDREN; ATTENTION; INFERENCE; BEHAVIOR; ORIENT AB To learn to deal with the unexpected is essential to adaptation to a social, therefore often unpredictable environment. Fourteen adults with autism spectrum disorders (ASD) and 15 controls underwent a decision-making task aimed at investigating the influence of either a social or a non-social environment, and its interaction with either a stable (with constant probabilities) or an unstable (with changing probabilities) context on their performance. Participants with ASD presented with difficulties in accessing underlying statistical rules in an unstable context, a deficit especially enhanced in the social environment. These results point out that the difficulties people with ASD encounter in their social life might be caused by impaired social cues processing and by the unpredictability associated with the social world. C1 [Robic, S.; Sonie, S.; Fonlupt, P.; Henaff, M. -A.; Mattout, J.; Schmitz, C.] CNRS, INSERM, Lyon Neurosci Res Ctr, Brain Dynam & Cognit Team,UMR 5292,U1028, Lyon, France. [Robic, S.; Sonie, S.; Fonlupt, P.; Henaff, M. -A.; Mattout, J.; Schmitz, C.] Univ Lyon, Lyon, France. [Sonie, S.] Le Vinatier Hosp, CEDA, Bron, France. [Touil, N.] CHU Lyon, EPICIME CIC, Bron, France. [Coricelli, G.] Ecole Normale Super, INSERM, U960, Lab Neurosci Cognit, F-75231 Paris, France. RP Schmitz, C (reprint author), CNRS, INSERM, Lyon Neurosci Res Ctr, Brain Dynam & Cognit Team,UMR 5292,U1028, Lyon, France. EM christina.schmitz@inserm.fr FU Scientific Research Council from Vinatier Hospital Center; LABEX CORTEX of Universite de Lyon within program "Investissements d'Avenir'' [ANR-11-LABX-0042, ANR-11-IDEX-0007] FX We would like to thank all of the participants for making this research possible. This study was supported by a Scientific Research Council grant from the Vinatier Hospital Center; the work was performed within the framework of the LABEX CORTEX (ANR-11-LABX-0042) of Universite de Lyon, within the program "Investissements d'Avenir'' (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). 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Keen, Deb TI Knowledge and Use of Intervention Practices by Community-Based Early Intervention Service Providers SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Evidence-based practice; Implementation; Knowledge transfer; Early intervention; Research-practice gap ID AUTISM SPECTRUM DISORDERS; CHILDREN; PROGRAMS; THERAPY; PARENTS; SCHOOLS AB This study investigated staff attitudes, knowledge and use of evidence-based practices (EBP) and links to organisational culture in a community-based autism early intervention service. An EBP questionnaire was completed by 99 metropolitan and regionally-based professional and paraprofessional staff. Participants reported greater knowledge and use of EBPs compared to emerging and unsupported practices. Knowledge and use of EBPs were linked to each other independent of significant correlations with organisational culture and attitudes. 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PD JUN PY 2015 VL 45 IS 6 BP 1614 EP 1623 DI 10.1007/s10803-014-2316-2 PG 10 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700009 PM 25398604 ER PT J AU Ledford, JR Wehby, JH AF Ledford, Jennifer R. Wehby, Joseph H. TI Teaching Children with Autism in Small Groups with Students Who are At-Risk for Academic Problems: Effects on Academic and Social Behaviors SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Small group instruction; Social skills; Progressive time delay ID GROUP DIRECT INSTRUCTION; SPECTRUM DISORDER; PEER INTERACTIONS AB Students with ASD are often taught in individual instructional arrangements, even when they receive educational services in inclusive settings. Providing intervention in small group arrangements may increase opportunities for social interactions, particularly when these opportunities are systematically planned. 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TI Support Needs of Fathers and Mothers of Children and Adolescents with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Support; Services; Parent; Father ID FRAGILE-X-SYNDROME; DOWN-SYNDROME; BEHAVIOR PROBLEMS; SOCIAL SUPPORT; YOUNG-CHILDREN; PARENTS; DISABILITIES; STRESS; HEALTH; FAMILIES AB Little research has examined the support needs of mothers versus fathers of children and adolescents with autism spectrum disorder (ASD). We identified and compared the important and unmet support needs of mothers and fathers, and evaluated their association with family and child factors, within 73 married couples who had a child or adolescent with ASD. Mothers had a higher number of important support needs and higher proportion of important support needs that are unmet than fathers. Multilevel modeling indicated that child age, co-occurring behavior problems, presence of intellectual disability, parent education, and household income were related to support needs. Findings offer insight into the overlapping and unique support needs of mothers and fathers of children and adolescents with ASD. C1 [Hartley, Sigan L.] Univ Wisconsin, Waisman Ctr, Dept Human Dev & Family Studies, Madison, WI 53705 USA. [Schultz, Haley M.] Univ Wisconsin, Waisman Ctr, Dept Rehabil Psychol, Madison, WI 53705 USA. RP Hartley, SL (reprint author), Univ Wisconsin, Waisman Ctr, Dept Human Dev & Family Studies, 1500 Highland Ave, Madison, WI 53705 USA. EM hartley@waisman.wisc.edu FU University of Wisconsin Graduate School; National Institute on Mental Health [R01MH099190]; National Institute on Child Health and Human Development [P30 HD03352] FX This research was supported by Grants from the University of Wisconsin Graduate School (to S. Hartley), National Institute on Mental Health (R01MH099190 to S. Hartley), and the National Institute on Child Health and Human Development (P30 HD03352 to M. Seltzer). We would like to thank the families who participated in this study for their ongoing support. CR Abbeduto L, 2004, AM J MENT RETARD, V109, P237, DOI 10.1352/0895-8017(2004)109<237:PWACIM>2.0.CO;2 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Arango P, 1999, J DEV BEHAV PEDIATR, V20, P123 BAILEY DB, 1992, AM J MENT RETARD, V97, P1 Brobst JB, 2009, FOCUS AUTISM DEV DIS, V24, P38, DOI 10.1177/1088357608323699 Bromley J, 2004, AUTISM, V8, P409, DOI 10.1177/1362361304047224 Bruininks R., 1996, SCALES INDEPENDENT B Bryk A. 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PD JUN PY 2015 VL 45 IS 6 BP 1636 EP 1648 DI 10.1007/s10803-014-2318-0 PG 13 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700011 PM 25433405 ER PT J AU Garg, S Plasschaert, E Descheemaeker, MJ Huson, S Borghgraef, M Vogels, A Evans, DG Legius, E Green, J AF Garg, Shruti Plasschaert, Ellen Descheemaeker, Mie-Jef Huson, Susan Borghgraef, Martine Vogels, Annick Evans, D. Gareth Legius, Eric Green, Jonathan TI Autism Spectrum Disorder Profile in Neurofibromatosis Type I SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE NF1; ASD; Neurofibromatosis Type 1; Autism spectrum disorder; SRS; ADOS ID CONTROLLED-TRIAL; MOUSE MODEL; CHILDREN; POPULATION; PREVALENCE; DEFICITS; SIMVASTATIN; GENETICS; TRAITS; NF1 AB Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40 %. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4-16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2. Compared to IQ-matched reference groups of children with autism and ASD, the NF1 profile shows overall similarity but improved eye contact, less repetitive behaviors and better language skills. C1 [Garg, Shruti; Green, Jonathan] Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester M13 9PL, Lancs, England. [Plasschaert, Ellen; Descheemaeker, Mie-Jef; Borghgraef, Martine; Vogels, Annick; Legius, Eric] Univ Hosp Leuven, Ctr Human Genet, Leuven, Belgium. [Plasschaert, Ellen; Vogels, Annick; Legius, Eric] Univ Hosp Leuven, Dept Human Genet, B-3000 Leuven, Belgium. [Plasschaert, Ellen; Descheemaeker, Mie-Jef] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [Huson, Susan; Evans, D. Gareth] Univ Manchester, Cent Manchester Univ Hosp NHS Trust, St Marys Hosp, Manchester Acad Hlth Sci Ctr,Inst Human Dev,Genom, Manchester M13 9WL, Lancs, England. RP Green, J (reprint author), Univ Manchester, Inst Brain Behav & Mental Hlth, Oxford Rd, Manchester M13 9PL, Lancs, England. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1649 EP 1657 DI 10.1007/s10803-014-2321-5 PG 9 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700012 PM 25475362 ER PT J AU Duvekot, J van der Ende, J Verhulst, FC Greaves-Lord, K AF Duvekot, Jorieke van der Ende, Jan Verhulst, Frank C. Greaves-Lord, Kirstin TI The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social Responsiveness Scale (SRS); Autism spectrum disorder (ASD); Screening; Multi-informant ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC-OBSERVATION-SCHEDULE; IV-TR CLASSIFICATION; ADI-R; COMBINING INFORMATION; MENTAL-RETARDATION; REVISED ALGORITHMS; SYMPTOM SEVERITY; MULTIPLE SOURCES AB The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3Di and ADOS, in 186 children referred to six mental health centers. The parent report showed excellent correspondence to an ASD classification according to the 3Di and both the 3Di and ADOS. The teacher report added significantly to the screening accuracy over and above the parent report when compared with the ADOS classification. Findings support the screening utility of the parent-reported SRS among clinically referred children and indicate that different informants may provide unique information relevant for ASD assessment. C1 [Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C.; Greaves-Lord, Kirstin] Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, NL-3015 CN Rotterdam, Netherlands. [Duvekot, Jorieke; Greaves-Lord, Kirstin] Yulius Mental Hlth, Yulius Acad, NL-3300 AT Dordrecht, Netherlands. RP Greaves-Lord, K (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Wytemaweg 8, NL-3015 CN Rotterdam, Netherlands. EM k.greaves-lord@erasmusmc.nl FU Sophia Foundation for Scientific Research (SSWO) [958] FX We gratefully acknowledge the contribution of all graduate students, PhD-students, and research assistants involved in the study, as well as the clinical professionals, management and administrative staff of the participating mental health care centers: Emergis, Erasmus MC-Sophia Children's Hospital, GGZ WNB, Lucertis, Riagg Rijnmond, Yulius. We thank all children and parents who participated in the study. This research was supported by a Grant from the Sophia Foundation for Scientific Research (SSWO; project number 958). 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PD JUN PY 2015 VL 45 IS 6 BP 1658 EP 1672 DI 10.1007/s10803-014-2323-3 PG 15 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700013 PM 25428292 ER PT J AU Van Hees, V Moyson, T Roeyers, H AF Van Hees, Valerie Moyson, Tinneke Roeyers, Herbert TI Higher Education Experiences of Students with Autism Spectrum Disorder: Challenges, Benefits and Support Needs SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Higher education; Qualitative research; Students' challenges; Benefits; Support needs and recommendations ID ASPERGER SYNDROME; COLLEGE-STUDENTS; INDIVIDUALS; ADOLESCENTS; TRANSITION; ADULTHOOD; MIND; DISABILITIES; PERSPECTIVE; LONELINESS AB The transition into higher education constitutes a precarious life stage for students with autism spectrum disorder (ASD). Research on how students with ASD navigate college life is needed for the development of adequate support. This study investigated the challenges and support needs of 23 students with ASD in higher education through semi-structured interviews. Data were analyzed following the principles of Grounded Theory. Students faced difficulties with new situations and unexpected changes, social relationships, problems with information processing and time management and had doubts about disclosure. Facing these challenges simultaneously in the domains of education, student life and daily (independent) living, had a major impact on students' well being. Besides these challenges, students also reported benefits that contributed to success in the three domains. They pointed out to a set of recommendations for support. These findings are linked with previous research and implications for higher education institutions are extrapolated on the basis of these findings. C1 [Van Hees, Valerie] Artevelde Univ Coll Ghent, Off Study & Career Guidance, B-9000 Ghent, Belgium. 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Lee, Brian K. Lee, Nora L. Yang, Yunwen Burstyn, Igor TI Maternal Smoking and Autism Spectrum Disorder: A Meta-analysis SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Tobacco smoke; Epidemiology; Systematic review; In-utero exposure; Environmental risk; Exposure misclassification ID PERINATAL RISK-FACTORS; COMPREHENSIVE METAANALYSIS; DEVELOPMENTAL-DISABILITIES; SOCIOECONOMIC-STATUS; INFANTILE-AUTISM; NEONATAL FACTORS; PREGNANCY; POPULATION; BIRTH; PREVALENCE AB We conducted a meta-analysis of 15 studies on maternal prenatal smoking and ASD risk in offspring. Using a random-effects model, we found no evidence of an association (summary OR 1.02, 95 % CI 0.93-1.12). Stratifying by study design, birth year, type of healthcare system, and adjustment for socioeconomic status or psychiatric history did not alter the findings. There was evidence that ascertaining exposure at the time of birth produced a lower summary OR than when this information was gathered after birth. There was no evidence of publication bias. Non-differential exposure misclassification was shown to have the potential for negligible influence on the results. We found no evidence to support a measurable association between maternal prenatal smoking and ASD in offspring. C1 [Rosen, Brittany N.; Burstyn, Igor] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [Lee, Brian K.; Lee, Nora L.; Yang, Yunwen; Burstyn, Igor] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Burstyn, I (reprint author), Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Nesbitt Hall,Room 614,3215 Market St, Philadelphia, PA 19104 USA. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1689 EP 1698 DI 10.1007/s10803-014-2327-z PG 10 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700015 PM 25432101 ER PT J AU Klusek, J Hunt, AW Mirrett, PL Hatton, DD Hooper, SR Roberts, JE Bailey, DB AF Klusek, Jessica Hunt, Anna W. Mirrett, Penny L. Hatton, Deborah D. Hooper, Stephen R. Roberts, Jane E. Bailey, Donald B. TI Reading and Phonological Skills in Boys with Fragile X Syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Fragile X syndrome; Autism spectrum disorder; Literacy; Reading; Phonological skills; Phonological awareness ID AUTISM SPECTRUM DISORDERS; DOWN-SYNDROME; WORKING-MEMORY; YOUNG MALES; LEITER-R; DEVELOPMENTAL TRAJECTORIES; BEHAVIORAL-PHENOTYPE; LANGUAGE IMPAIRMENT; CONCURRENT VALIDITY; PANELS METAANALYSIS AB Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in standardized assessments of reading and phonological skills. Phonological skills were impaired in FXS, while reading was on-par with that of controls. Phonological awareness predicted reading ability and ASD severity predicted poorer phonological abilities in FXS. Boys with FXS are capable of attaining reading skills that are commensurate with developmental level and phonological awareness skills may play a critical role in reading achievement in FXS. C1 [Klusek, Jessica] Univ S Carolina, Barnwell Coll, Dept Psychol, Columbia, SC 29208 USA. [Hunt, Anna W.] Clarity, Greenville, SC USA. [Mirrett, Penny L.] Univ S Carolina, Frank Porter Graham Child Dev Inst, Columbia, SC 29208 USA. [Hatton, Deborah D.] Vanderbilt Univ, Kennedy Ctr, Nashville, TN 37235 USA. [Hooper, Stephen R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Hooper, Stephen R.] Univ N Carolina, Dept Allied Hlth Sci, Chapel Hill, NC USA. [Roberts, Jane E.] Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. [Bailey, Donald B.] RTI Int, Res Triangle Pk, NC USA. RP Klusek, J (reprint author), Univ S Carolina, Barnwell Coll, Dept Psychol, 1512 Pendleton St, Columbia, SC 29208 USA. EM klusek@mailbox.sc.edu FU Office of Special Education and Rehabilitative Services of the U.S. Department of Education [H324C010007]; National Institutes of Health [F32DC013934, R01MH090194, R01HD40602, R01HD024356] FX This research supported by the Office of Special Education and Rehabilitative Services of the U.S. Department of Education Grant (H324C010007), the National Institutes of Health (F32DC013934; R01MH090194; R01HD40602; R01HD024356). Components of this paper were completed as part of the dissertation of Anna L. Hunt (Williams) at the School of Education, University of North Carolina at Chapel Hill. We would like to acknowledge John Sideris for his assistance with the statistical models for earlier drafts of this manuscript. We also thank the children and families who participated in this research. 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Goods, Kelly Shih, Wendy Distefano, Charlotte Kaiser, Ann Wright, Courtney Mathy, Pamela Landa, Rebecca Kasari, Connie TI Parents' Adoption of Social Communication Intervention Strategies: Families Including Children with Autism Spectrum Disorder Who are Minimally Verbal SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Parent training; Autism; Minimally verbal; Intervention; Coaching ID JOINT ATTENTION; PSYCHOSOCIAL INTERVENTIONS; LANGUAGE; DISABILITIES; GROWTH; TRIAL AB Notably absent from the intervention literature are parent training programs targeting school-aged children with autism who have limited communication skills (Tager-Flusberg and Kasari in Autism Res 6:468-478, 2013). Sixty-one children with autism age 5-8 with minimal spontaneous communication received a 6-month social communication intervention including parent training. Parent-child play interactions were coded for parents' strategy implementation and children's time jointly engaged (Adamson et al. in J Autism Dev Disord 39:84-96, 2009). Parents mastered an average of 70 % of the strategies. Further analyses indicated some gains in implementation occurred from mere observation of sessions, while the greatest gains occurred in the first month of active coaching and workshops. Children's joint engagement was associated with parents' implementation success across time demonstrating parents' implementation was relevant to children's social engagement. C1 [Shire, Stephanie Y.] Univ Calif Los Angeles, Dept Psychiat, Neuropsychiat Inst NPI 67 448, Los Angeles, CA 90024 USA. [Shire, Stephanie Y.; Goods, Kelly; Shih, Wendy; Distefano, Charlotte; Kasari, Connie] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90024 USA. [Goods, Kelly] First Five Calif, Los Angeles, CA 90012 USA. [Shih, Wendy] Univ Calif Los Angeles, Dept Biostat, Neuropsychiat Inst NPI 67 448, Los Angeles, CA 90024 USA. [Kaiser, Ann; Wright, Courtney] Vanderbilt Univ, Educ & Human Dev, Nashville, TN 37203 USA. [Wright, Courtney] Vanderbilt Univ, Dept Special Educ, Nashville, TN 37203 USA. [Mathy, Pamela; Landa, Rebecca] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD 21211 USA. RP Shire, SY (reprint author), Univ Calif Los Angeles, Dept Psychiat, Neuropsychiat Inst NPI 67 448, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM sypatterson@ucla.edu; wshih@mednet.ucla.edu; cmucchetti@mednet.ucla.edu; ann.kaiser@vanderbilt.edu; courtney.a.wright@vanderbilt.edu; Pamela.Mathy@hsc.utah.edu; Landa@kennedykrieger.org; ckasari@mednet.ucla.edu FU Autism Speaks [5666, 7036]; Canadian Institutes for Health Research FX We would like to acknowledge funding for the study provided by Autism Speaks (PI Kasari: #5666), Characterizing Cognition in Nonverbal Individuals with Autism. In addition, the first author received a Dennis Weatherstone Pre-Doctoral Fellowship from Autism Speaks (#7036) as well a Doctoral Foreign Study Award from the Canadian Institutes for Health Research. Thank you to the children and families who participated in this study as well as interventionists who provided the services across the three sites. A version of this paper was presented at the 2013 Biennial Meeting of the Society for Research in Child Development in Seattle Washington and was developed from a master's thesis. CR Adamson L. B., 2011, J SPEECH LANG HEAR R, V53, P1769 Adamson LB, 2001, J APPL DEV PSYCHOL, V22, P439, DOI 10.1016/S0193-3973(01)00089-2 Adamson LB, 2009, J AUTISM DEV DISORD, V39, P84, DOI 10.1007/s10803-008-0601-7 Anderson DK, 2007, J CONSULT CLIN PSYCH, V75, P594, DOI 10.1037/0022-006X.75.4.594 Brady N. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1712 EP 1724 DI 10.1007/s10803-014-2329-x PG 13 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700017 PM 25475363 ER PT J AU Joseph, JE Zhu, X Gundran, A Davies, F Clark, JD Ruble, L Glaser, P Bhatt, RS AF Joseph, Jane E. Zhu, Xun Gundran, Andrew Davies, Faraday Clark, Jonathan D. Ruble, Lisa Glaser, Paul Bhatt, Ramesh S. TI Typical and Atypical Neurodevelopment for Face Specialization: An fMRI Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Face processing; Typical development; Autism spectrum disorder; Undiagnosed siblings; fMRI ID AUTISM SPECTRUM DISORDERS; PLACE-RELATED CORTEX; OBJECT RECOGNITION; FUNCTIONAL CONNECTIVITY; BRAIN ACTIVATION; IMAGING ENDOPHENOTYPE; FACIAL EXPRESSION; AMYGDALA RESPONSE; ASPERGER-SYNDROME; NEURAL CIRCUITRY AB Individuals with autism spectrum disorder (ASD) and their relatives process faces differently from typically developed (TD) individuals. In an fMRI face-viewing task, TD and undiagnosed sibling (SIB) children (5-18 years) showed face specialization in the right amygdala and ventromedial prefrontal cortex, with left fusiform and right amygdala face specialization increasing with age in TD subjects. SIBs showed extensive antero-medial temporal lobe activation for faces that was not present in any other group, suggesting a potential compensatory mechanism. In ASD, face specialization was minimal but increased with age in the right fusiform and decreased with age in the left amygdala, suggesting atypical development of a frontal-amygdala-fusiform system which is strongly linked to detecting salience and processing facial information. C1 [Joseph, Jane E.; Zhu, Xun; Gundran, Andrew; Davies, Faraday] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Clark, Jonathan D.; Glaser, Paul] Univ Kentucky, Albert B Chandler Med Ctr, Dept Anat & Neurobiol, Lexington, KY 40536 USA. [Ruble, Lisa] Univ Kentucky, Dept Educ Sch & Counseling Psychol, Lexington, KY USA. [Glaser, Paul] Univ Kentucky, Dept Psychiat, Lexington, KY USA. [Bhatt, Ramesh S.] Univ Kentucky, Dept Psychol, Lexington, KY 40506 USA. RP Joseph, JE (reprint author), Med Univ S Carolina, Dept Neurosci, Clin Sci Bldg,Room 325E,MSC 616, Charleston, SC 29425 USA. EM josep@musc.edu; zhuxun@musc.edu; andrewgundran0@gmail.com; faradaydavies@gmail.com; jdclar3@uky.edu; lisa.ruble@uky.edu; pglas0@email.uky.edu; rbhatt@uky.edu FU Autism Speaks; National Institutes of Health [R01 HD052724, R01 HD042452] FX This research was sponsored by Autism Speaks and the National Institutes of Health (R01 HD052724, R01 HD042452). We thank Christine Corbly, Myra Huffman and Melissa Wheatley for assistance with data collection and Michelle DiBartolo for help with manuscript preparation. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1725 EP 1741 DI 10.1007/s10803-014-2330-4 PG 17 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700018 PM 25479816 ER PT J AU VanderLaan, DP Leef, JH Wood, H Hughes, SK Zucker, KJ AF VanderLaan, Doug P. Leef, Jonathan H. Wood, Hayley Hughes, S. Kathleen Zucker, Kenneth J. TI Autism Spectrum Disorder Risk Factors and Autistic Traits in Gender Dysphoric Children SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Gender dysphoria; Autism spectrum disorder; Birth weight; Parental age; Sibling sex ratio ID SIBLING SEX-RATIO; PREHOMOSEXUAL FEMININE BOYS; IDENTITY DISORDER; BIRTH-WEIGHT; ADOLESCENTS; PREGNANCY; ORDER; RECALL; INDIVIDUALS; GROWTH AB Gender dysphoria (GD) and autism spectrum disorder (ASD) are associated. In 49 GD children (40 natal males), we examined ASD risk factors (i.e., birth weight, parental age, sibling sex ratio) in relation to autistic traits. Data were gathered on autistic traits, birth weight, parents' ages at birth, sibling sex ratio, gender nonconformity, age, maternal depression, general behavioral and emotional problems, and IQ. High birth weight was associated with both high gender nonconformity and autistic traits among GD children. Developmental processes associated with high birth weight are, therefore, likely to underlie the GD-ASD link either directly or indirectly. The present study is the first to provide quantitative data bearing on possible mechanisms that lead GD and ASD to co-occur. C1 [VanderLaan, Doug P.; Leef, Jonathan H.; Wood, Hayley; Hughes, S. Kathleen; Zucker, Kenneth J.] Ctr Addict & Mental Hlth, Gender Ident Serv, Beamish Family Wing, Child Serv, Toronto, ON M6J 1H4, Canada. [VanderLaan, Doug P.; Leef, Jonathan H.; Wood, Hayley; Hughes, S. Kathleen; Zucker, Kenneth J.] Ctr Addict & Mental Hlth, Gender Ident Serv, Beamish Family Wing, Youth Serv, Toronto, ON M6J 1H4, Canada. [VanderLaan, Doug P.; Leef, Jonathan H.; Wood, Hayley; Hughes, S. Kathleen; Zucker, Kenneth J.] Ctr Addict & Mental Hlth, Gender Ident Serv, Beamish Family Wing, Family Serv, Toronto, ON M6J 1H4, Canada. [Zucker, Kenneth J.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP VanderLaan, DP (reprint author), Ctr Addict & Mental Hlth, Gender Ident Serv, Beamish Family Wing, Child Serv, 80 Workman Way,5th Floor, Toronto, ON M6J 1H4, Canada. EM doug.vanderlaan@camh.ca FU Canadian Institutes of Health Research FX D.P.V. was supported by a Canadian Institutes of Health Research Postdoctoral Fellowship. We thank two anonymous reviewers for comments on an earlier version of this article. 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TI Sketching to Remember: Episodic Free Recall Task Support for Child Witnesses and Victims with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Cognitive interview; Drawing; Free recall; Eyewitness ID FRONTLINE POLICE INVESTIGATORS; SCHOOL-AGE-CHILDREN; COGNITIVE INTERVIEW; MENTAL REINSTATEMENT; ASPERGERS-SYNDROME; CONTEXT REINSTATEMENT; EYEWITNESS MEMORY; ADULTS; EVENTS; ABILITY AB Deficits in episodic free-recall memory performance have been reported in children with autism spectrum disorder (ASD), yet best practice dictates that child witness/victim interviews commence with a free-recall account. No 'tools' exist to support children with ASD to freely recall episodic information. Here, the efficacy of a novel retrieval technique, Sketch reinstatement of context (Sketch-RC), is compared with mental reinstatement of context and a no support control. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1751 EP 1765 DI 10.1007/s10803-014-2335-z PG 15 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700020 PM 25503484 ER PT J AU Idring, S Lundberg, M Sturm, H Dalman, C Gumpert, C Rai, D Lee, BK Magnusson, C AF Idring, Selma Lundberg, Michael Sturm, Harald Dalman, Christina Gumpert, Clara Rai, Dheeraj Lee, Brian K. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1766 EP 1773 DI 10.1007/s10803-014-2336-y PG 8 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700021 PM 25475364 ER PT J AU Evers, K Steyaert, J Noens, I Wagemans, J AF Evers, Kris Steyaert, Jean Noens, Ilse Wagemans, Johan TI Reduced Recognition of Dynamic Facial Emotional Expressions and Emotion-Specific Response Bias in Children with an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder (ASD); Dynamic facial expressions; Emotion recognition; Face perception; Response bias; Theory of mind ID 1ST-DEGREE RELATIVES; PERCEPTION; INDIVIDUALS; PHENOTYPE; INTENSITIES; CHILDHOOD; DISPLAYS; DEFICITS; PARENTS; ADULTS AB Emotion labelling was evaluated in two matched samples of 6-14-year old children with and without an autism spectrum disorder (ASD; N = 45 and N = 50, resp.), using six dynamic facial expressions. The Emotion Recognition Task proved to be valuable demonstrating subtle emotion recognition difficulties in ASD, as we showed a general poorer emotion recognition performance, in addition to some emotion-specific impairments in the ASD group. Participants' preference for selecting a certain emotion label, irrespective of the stimulus presented, played an important role in our results: response bias-corrected data still showed an overall decreased emotion recognition performance in ASD, but no emotion-specific impairments anymore. Moreover, ASD traits and empathy were correlated with emotion recognition performance. C1 [Evers, Kris; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Evers, Kris; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Leuven, Belgium. [Evers, Kris; Steyaert, Jean; Noens, Ilse; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Leuven, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Evers, K (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, Tiensestr 102,Box 3711, B-3000 Leuven, Belgium. EM kris.evers@ppw.kuleuven.be FU Methusalem program by Flemish Government [METH 08/02]; Research Council of the KU Leuven [IDO/080/013]; Marguerite Marie Delacroix Support Fund [GV/B-141] FX We want to thank all participating children and their parents. Special thanks go to the participating schools, Ten Bunderen (Moorslede), De Puzzel (Kleine-Brogel) and De Schommel (Lommel). Thanks to Dr. Ervin Poljac for sharing his expertise with the Emotion Recognition Task. We thank Birgitt Haesen and the following master students for their assistance with data collection: Nele Berghmans, Stephanie Deckmyn, Sanne Drees, Tine Herreman, Ellen Janssen, Loes Steegmans, Lotte van Esch, Alysee Van Laeken, and Leen Vercammen. This research was funded by the Methusalem program by the Flemish Government (METH 08/02) awarded to J.W., by a grant from the Research Council of the KU Leuven (IDO/080/013) awarded to J.S., J.W. and I.N., and by a grant from the Marguerite Marie Delacroix Support Fund (GV/B-141) awarded to K.E. 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PD JUN PY 2015 VL 45 IS 6 BP 1774 EP 1784 DI 10.1007/s10803-014-2337-x PG 11 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700022 PM 25563453 ER PT J AU Brosnan, M Johnson, H Grawmeyer, B Chapman, E Benton, L AF Brosnan, Mark Johnson, Hilary Grawmeyer, Beate Chapman, Emma Benton, Laura TI Emotion Recognition in Animated Compared to Human Stimuli in Adolescents with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Emotion recognition; Multimodal; Animated cartoon stimuli ID HIGH-FUNCTIONING AUTISM; FACIAL EXPRESSIONS; ASPERGERS-SYNDROME; INDIVIDUALS; ADULTS; PERCEPTION; FACES; INTENSITIES; EXTRACTION; SYMPTOMS AB There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon face). Participants were 37 adolescents (age 11-16) with a diagnosis of ASD (33 male, 4 female). 42 males and 39 females served as typically developing, age-matched controls. Overall there was significant advantage for control groups over the ASD group for emotion recognition in human stimuli but not animated stimuli, across modalities. For static animated images specifically, those with ASD significantly outperformed controls. The findings are consistent with the ASD group using atypical explicit strategies. C1 [Brosnan, Mark; Johnson, Hilary; Chapman, Emma] Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. [Grawmeyer, Beate] Univ London, Birkbeck Coll, London Knowledge Lab, London WC1N 3QS, England. [Benton, Laura] Univ London, Inst Educ, London Knowledge Lab, London WC1N 3QS, England. RP Brosnan, M (reprint author), Univ Bath, Dept Psychol, Bath BA2 7AY, Avon, England. EM M.J.Brosnan@Bath.ac.uk FU EPSRC [EP/G031975/1] FX Grant sponsor EPSRC; Grant Number EP/G031975/1. 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A., 2013, J AUTISM DEV DISORDE Wechsler D, 1999, WECHSLER ABBREVIATED Widen SC, 2003, DEV PSYCHOL, V39, P114, DOI 10.1037//0012-1649.39.1.114 World Health Organisation, 1992, ICD 10 CLASS MENT BE NR 55 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 JUN PY 2015 VL 45 IS 6 BP 1785 EP 1796 DI 10.1007/s10803-014-2338-9 PG 12 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700023 PM 25567528 ER PT J AU Khowaja, MK Hazzard, AP Robins, DL AF Khowaja, Meena K. Hazzard, Ann P. Robins, Diana L. TI Sociodemographic Barriers to Early Detection of Autism: Screening and Evaluation Using the M-CHAT, M-CHAT-R, and Follow-Up SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Screening; Disparities; Socioeconomic status; Maternal education; Race; Autism ID PERVASIVE DEVELOPMENTAL DISORDERS; FUNCTIONAL HEALTH LITERACY; SPECTRUM DISORDERS; MODIFIED CHECKLIST; CHRONIC DISEASE; UNITED-STATES; CHILDREN; KNOWLEDGE; DIAGNOSIS; DISPARITIES AB Parents (n = 11,845) completed the Modified Checklist for Autism in Toddlers (or its latest revision) at pediatric visits. Using sociodemographic predictors of maternal education and race, binary logistic regressions were utilized to examine differences in autism screening, diagnostic evaluation participation rates and outcomes, and reasons for non-participation. Families of lower maternal education and racial minorities exhibited inflated initial screen positive rates and lower participation at Follow-Up, although not at the evaluation. Economic challenges, such as invalid phone numbers, were identified as barriers to reaching these families. Families of higher education and White race were more likely to decline participation in evaluation. Results suggest the need for increased public education about childhood development to enhance awareness, reduce stigma, and streamline screening. C1 [Khowaja, Meena K.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Hazzard, Ann P.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30303 USA. [Robins, Diana L.] Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. RP Khowaja, MK (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. EM mkhowaja1@student.gsu.edu FU Centers for Disease Control Prevention; Georgia State University; Eunice Kennedy Shriver National Institute for Child Health and Human Development [R01HD039961] FX We would like to thank our financial support sources, a joint Centers for Disease Control & Prevention and Georgia State University seed grant, as well as a research grant from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, R01HD039961. Statistical consultation was provided by Lucy Robinson, Ph.D. (Drexel University) and Wing Yi Chan, Ph.D. (Georgia State University). We would also like to acknowledge the families who participated in the study, as well as the pediatricians who assisted by offering the M-CHAT(-R) questionnaire to their patients. Additionally, we are grateful for the time and effort put forth by the Developmental Neuropsychology Lab research staff involved in data collection for the project at Georgia State University. Data presented in the manuscript are a subset of a larger ongoing research study. Preliminary findings from the research presented in the enclosed manuscript were presented at a regional and international meeting, and have not been published elsewhere. 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PD JUN PY 2015 VL 45 IS 6 BP 1797 EP 1808 DI 10.1007/s10803-014-2339-8 PG 12 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700024 PM 25488122 ER PT J AU Kamps, D Thiemann-Bourque, K Heitzman-Powell, L Schwartz, I Rosenberg, N Mason, R Cox, S AF Kamps, Debra Thiemann-Bourque, Kathy Heitzman-Powell, Linda Schwartz, Ilene Rosenberg, Nancy Mason, Rose Cox, Suzanne TI A Comprehensive Peer Network Intervention to Improve Social Communication of Children with Autism Spectrum Disorders: A Randomized Trial in Kindergarten and First Grade SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Peer networks; Social-communication skills; Text cues ID HIGH-FUNCTIONING CHILDREN; SKILLS INTERVENTIONS; YOUNG-CHILDREN; STUDENTS; RECOMMENDATIONS; ADOLESCENTS; INITIATIONS; SETTINGS; SCRIPTS; CUES AB The purpose of this randomized control group study was to examine the effects of a peer network intervention that included peer mediation and direct instruction for Kindergarten and First-grade children with autism spectrum disorders. Trained school staff members provided direct instruction for 56 children in the intervention group, and 39 children participated in a comparison group. Results showed children in the intervention group displayed significantly more initiations to peers than did the comparison group during non-treatment social probes and generalization probes. Treatment session data showed significant growth for total communications over baseline levels. Children in treatment also showed more growth in language and adaptive communication. Finally, teachers' ratings of prosocial skills revealed significantly greater improvements for the intervention group. C1 [Kamps, Debra; Thiemann-Bourque, Kathy; Cox, Suzanne] Univ Kansas, Juniper Gardens Childrens Project, Life Span Inst, Kansas City, KS 66101 USA. [Heitzman-Powell, Linda] Univ Kansas, Med Ctr, Kansas City, KS 66101 USA. [Schwartz, Ilene; Rosenberg, Nancy] Univ Washington, Dept Special Educ, Seattle, WA 98195 USA. [Mason, Rose] Univ Kansas, Kansas City, KS 66101 USA. RP Kamps, D (reprint author), Univ Kansas, Juniper Gardens Childrens Project, Life Span Inst, 444 Minnesota Ave,3rd Floor, Kansas City, KS 66101 USA. EM dkamps@ku.edu; thiemann@ku.edu; lhpowell@ku.edu; ilene@u.washington.edu; nancy@u.washington.edu; rmason519@ku.edu; scox@ku.edu FU Institute of Education Sciences, Department of Education [R324A090091] FX The research was funded by the Institute of Education Sciences, Department of Education (R324A090091). Opinions expressed herein are those of the authors and do not necessarily reflect the position of the funding agency. We gratefully acknowledge our graduate research assistants: Marissa Congdon, Sarah Feldmiller, Shane Herriot, Emily Kroman, Alison Marti, Brandon McFadden, Todd Miller, Lindsay Myatich, and Veronica Pamparo, and research assistants: Tonya Evans and Amy Turcotte, for their assistance in consultation with school staff and data collection; and the participating teachers, students, and families for their time and ongoing support. CR Agresti A., 2002, CATEGORICAL DATA ANA American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bauminger N, 2008, J AUTISM DEV DISORD, V38, P1211, DOI 10.1007/s10803-007-0501-2 Bellini S, 2007, REM SPEC EDUC, V28, P153, DOI 10.1177/07419325070280030401 Cappadocia MC, 2011, RES AUTISM SPECT DIS, V5, P70, DOI 10.1016/j.rasd.2010.04.001 Cheng J., 2005, MIXED MODELS Cohen J., 1988, STAT POWER ANAL BEHA, V2nd Constantino JN, 2005, SOCIAL RESPONSIVENES Dunn L. 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TI Variation in the Profile of Anxiety Disorders in Boys with an ASD According to Method and Source of Assessment SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ASD; Anxiety; Assessment; Parent ID AUTISM SPECTRUM DISORDERS; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; SYMPTOMS; YOUTH; COMORBIDITY; AGREEMENT AB To determine any variation that might occur due to the type of assessment and source used to assess them, the prevalence of 7 anxiety disorders were investigated in a sample of 140 boys with an Autism spectrum disorder (ASD) and 50 non-ASD (NASD) boys via the Child and Adolescent Symptom Inventory and the KIDSCID Clinical Interview. Boys with an ASD were significantly more anxious than their NASD peers. Data collected from the boys with an ASD themselves showed differences in the severity and diagnostic criterion of anxiety disorders to data collected from the boys' parents. There were age-related variations to the pattern of anxiety disorder differences across reports from the boys with an ASD and reports from their parents. C1 [Bitsika, Vicki; Sharpley, Christopher F.] Bond Univ, Ctr Autism Spectrum Disorders, Robina, Qld 4229, Australia. [Sharpley, Christopher F.] Univ New England, Brain Behav Res Grp, Sch Sci & Technol, Armidale, NSW 2351, Australia. RP Sharpley, CF (reprint author), Univ New England, Brain Behav Res Grp, Sch Sci & Technol, Armidale, NSW 2351, Australia. EM csharpley@onthenet.com.au CR ACHENBACH TM, 1987, PSYCHOL BULL, V101, P213, DOI 10.1037/0033-2909.101.2.213 American Psychiatric Association APA, 2013, DIAGN STAT MAN MENT, V5th An JY, 2014, TRANSL PSYCHIAT, V4, DOI 10.1038/tp.2014.38 Bitsika V, 2014, PHYSIOL BEHAV, V127, P1, DOI 10.1016/j.physbeh.2013.12.011 Blakeley-Smith A, 2012, RES AUTISM SPECT DIS, V6, P707, DOI 10.1016/j.rasd.2011.07.020 Bryson S. 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PD JUN PY 2015 VL 45 IS 6 BP 1825 EP 1835 DI 10.1007/s10803-014-2343-z PG 11 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700026 PM 25503485 ER PT J AU Boets, B Verhoeven, J Wouters, J Steyaert, J AF Boets, Bart Verhoeven, Judith Wouters, Jan Steyaert, Jean TI Fragile Spectral and Temporal Auditory Processing in Adolescents with Autism Spectrum Disorder and Early Language Delay SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Auditory processing; Hemispheric lateralization; Spectral; Temporal; Pitch ID EVENT-RELATED POTENTIALS; SPEECH-PERCEPTION; ASPERGER-SYNDROME; PITCH DISCRIMINATION; ABSOLUTE PITCH; HEMISPHERIC-SPECIALIZATION; MISMATCH NEGATIVITY; PRESCHOOL-CHILDREN; EVOKED POTENTIALS; CENTRAL COHERENCE AB We investigated low-level auditory spectral and temporal processing in adolescents with autism spectrum disorder (ASD) and early language delay compared to matched typically developing controls. Auditory measures were designed to target right versus left auditory cortex processing (i.e. frequency discrimination and slow amplitude modulation (AM) detection versus gap-in-noise detection and faster AM detection), and to pinpoint the task and stimulus characteristics underlying putative superior spectral processing in ASD. We observed impaired frequency discrimination in the ASD group and suggestive evidence of poorer temporal resolution as indexed by gap-in-noise detection thresholds. These findings question the evidence of enhanced spectral sensitivity in ASD and do not support the hypothesis of superior right and inferior left hemispheric auditory processing in ASD. C1 [Boets, Bart; Steyaert, Jean] Univ Leuven KU Leuven, Dept Neurosci, Child & Adolescent Psychiat, B-3000 Leuven, Belgium. [Boets, Bart] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Boets, Bart; Verhoeven, Judith; Steyaert, Jean] Univ Leuven KU Leuven, Leuven Autism Res LAuRes, B-3000 Leuven, Belgium. [Verhoeven, Judith] Kempenhaeghe, Dept Epilepsy, NL-5590 AB Heeze, Netherlands. [Wouters, Jan] Univ Leuven KU Leuven, Dept Neurosci, ExpORL, B-3000 Leuven, Belgium. RP Boets, B (reprint author), Univ Leuven KU Leuven, Dept Neurosci, Child & Adolescent Psychiat, Herestr 49,Box 7003, B-3000 Leuven, Belgium. EM bart.boets@med.kuleuven.be FU Research Council of KU Leuven [IDO/08/013] FX Bart Boets is a post-doctoral research fellow of the Research Foundation Flanders and a Fulbright Visiting Scholar. The research was financed by a grant from the Research Council of KU Leuven (IDO/08/013). We thank Heleen Luts, Thea Van Werde and Loes Verber for assistance with testing, and all participating children and their families for their time and effort. 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Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were gathered prior to and following the 1-year intervention. Analyses were conducted for three groups based on baseline IQ: Higher IQ (a parts per thousand yen70; n = 36), Moderately Low IQ (40-69; n = 40), and Very Low IQ (< 40, n = 42). Observed gains in key language and cognitive outcomes were significant for all groups. Baseline cognitive scores significantly predicted 1-year outcomes. Results are encouraging for this relatively low-intensity community-based intervention program. C1 [Smith, Isabel M.; Bryson, Susan E.] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. [Smith, Isabel M.; Bryson, Susan E.] Dalhousie Univ, Dept Psychol & Neurosci, Halifax, NS, Canada. [Smith, Isabel M.; Flanagan, Helen E.; Bryson, Susan E.] IWK Hlth Ctr, Autism Res Ctr, Halifax, NS, Canada. [Flanagan, Helen E.] IWK Hlth Ctr, EIBI Program, Halifax, NS, Canada. [Garon, Nancy] Mt Allison Univ, Dept Psychol, Sackville, NB E0A 3C0, Canada. RP Smith, IM (reprint author), IWK Hlth Ctr, Autism Res Ctr, POB 9700, Halifax, NS, Canada. EM isabel.smith@iwk.nshealth.ca FU Canadian Institutes of Health Research; Nova Scotia Health Research Foundation; Dalhousie University Faculty of Medicine; Autism Research at Dalhousie University/IWK Health Centre FX This research was supported by grants from the Canadian Institutes of Health Research, and the Nova Scotia Health Research Foundation. Dr. Smith was supported by a Clinical Research Scholar Award from the Dalhousie University Faculty of Medicine, and now holds the Craig Chair in Autism Research at Dalhousie University/IWK Health Centre. At the time the study took place, Dr. Bryson held the Craig Chair in Autism Research. We are grateful to the families who participated in this study, to the clinical teams responsible for the intervention, especially Dr. Dorothy Chitty, and to Ms. Patricia Murray of the Nova Scotia Department of Health and Wellness, who has championed this research program. We also thank the staff and students of the IWK Autism Research Centre for their roles in data collection. Portions of this study were presented at the International Meeting for Autism Research in May, 2012. 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PD JUN PY 2015 VL 45 IS 6 BP 1858 EP 1872 DI 10.1007/s10803-014-2345-x PG 15 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700029 PM 25563454 ER PT J AU Bottema-Beutel, K Li, ZS AF Bottema-Beutel, Kristen Li, Zhushan TI Adolescent Judgments and Reasoning About the Failure to Include Peers with Social Disabilities SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Inclusion; Moral reasoning; Domain theory; Adolescents ID EDUCATIONAL INTERVENTION; AMERICAN CHILDRENS; MAINSTREAM SCHOOL; AUTISM; EXCLUSION; INCLUSION; STUDENTS; CONTACT; ASD AB Adolescents with autism spectrum disorder often do not have access to crucial peer social activities. This study examines how typically developing adolescents evaluate decisions not to include a peer based on disability status, and the justifications they apply to these decisions. A clinical interview methodology was used to elicit judgments and justifications across four contexts. We found adolescents are more likely to judge the failure to include as acceptable in personal as compared to public contexts. Using logistic regression, we found that adolescents are more likely to provide moral justifications as to why failure to include is acceptable in a classroom as compared to home, lab group, and soccer practice contexts. Implications for intervention are also discussed. C1 [Bottema-Beutel, Kristen] Boston Coll, Lynch Sch Educ, Dept Teacher Educ Special Educ & Curriculum & Ins, Chestnut Hill, MA 02467 USA. [Li, Zhushan] Boston Coll, Lynch Sch Educ, Dept Educ Res Measurement & Evaluat, Chestnut Hill, MA 02467 USA. RP Bottema-Beutel, K (reprint author), Boston Coll, Lynch Sch Educ, Dept Teacher Educ Special Educ & Curriculum & Ins, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM kristen.bottema-beutel@bc.edu FU IES [R324B080005]; OSEP [H325D060036] FX The first author received partial support in writing this manuscript from IES Grant No. R324B080005 and OSEP Grant No. H325D060036. We would like to thank the adolescents that participated in this research, Rose Cartwright and Christina Jones for their diligent work on this project, Jennifer Gilbert for statistical consultation, and Elliot Turiel for comments on an earlier draft of this manuscript. We would also like to thank the anonymous reviewers for their helpful feedback. 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PD JUN PY 2015 VL 45 IS 6 BP 1873 EP 1886 DI 10.1007/s10803-014-2348-7 PG 14 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700030 PM 25575622 ER PT J AU Fitch, A Fein, DA Eigsti, IM AF Fitch, Allison Fein, Deborah A. Eigsti, Inge-Marie TI Detail and Gestalt Focus in Individuals with Optimal Outcomes from Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Pragmatic language; Global/local bias; Weak central coherence; Optimal outcomes; Executive function ID HIGH-FUNCTIONING CHILDREN; DISCOURSE COHERENCE; LANGUAGE DEFICITS; WEAK COHERENCE; 2 THINGS; HISTORY; ADOLESCENTS; INTERFERENCE; PERCEPTION; CONTEXT AB Individuals with high-functioning autism (HFA) have a cognitive style that privileges local over global or gestalt details. While not a core symptom of autism, individuals with HFA seem to reliably show this bias. 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1887 EP 1896 DI 10.1007/s10803-014-2347-8 PG 10 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700031 PM 25563455 ER PT J AU Falck-Ytter, T Thorup, E Bolte, S AF Falck-Ytter, Terje Thorup, Emilia Bolte, Sven TI Brief Report: Lack of Processing Bias for the Objects Other People Attend to in 3-Year-Olds with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Communication; Development; Cognition; Neurodevelopmental disorders; Vision ID JOINT VISUAL-ATTENTION; SPECTRUM DISORDER; EYE-MOVEMENTS; GAZE; CHILDREN; INFANTS; RISK; MICROSTRUCTURE; DEFICITS; TRACKING AB Whether gaze following-a key component of joint attention-is impaired in children with autism spectrum disorder (ASD) is currently debated. Functional gaze following involves saccading towards the attended rather than unattended targets (accuracy) as well as a subsequent processing bias for attended objects. Using non-invasive eye tracking technology, we show that gaze following accuracy is intact in intellectually low-functioning 3-year-olds with ASD. However, analyses of the duration of first fixations at the objects in the scene revealed markedly weaker initial processing bias for attended objects in children with ASD compared to children with typical development and non-autistic children with developmental delays. Limited processing bias for the objects other people attend to may negatively affect learning opportunities in ASD. C1 [Falck-Ytter, Terje; Bolte, Sven] Karolinska Inst, Child & Adolescent Psychiat Res Ctr, Karolinska Inst KIND,Dept Womens & Childrens Hlth, Pediat Neuropsychiat Unit,Ctr Neurodev Disorders, S-11330 Stockholm, Sweden. [Falck-Ytter, Terje; Thorup, Emilia] Uppsala Univ, Dept Psychol, Uppsala Child & Babylab, S-75142 Uppsala, Sweden. [Bolte, Sven] Stockholm Cty Council, Div Child & Adolescent Psychiat, Stockholm, Sweden. RP Thorup, E (reprint author), Uppsala Univ, Dept Psychol, Uppsala Child & Babylab, S-75142 Uppsala, Sweden. EM emilia.thorup@psyk.uu.se FU Swedish Research Council; FAS; FORMAS; VINNOVA [259-2012-24]; ESF COST Action [BM1004]; Bank of Sweden Tercentenary Foundation [P12-0270:1, P10-078]; Swedish Research Council [523-2009-7054] FX We are thankful to Erik Rehnberg for invaluable help during data collection. This research was supported by a grant to SB and TFY from the Swedish Research Council in partnership with FAS, FORMAS, and VINNOVA (Crossdisciplinary research programme concerning children's and young people's mental health; grant number 259-2012-24). The work of all authors was supported by the ESF COST Action BM1004 'Enhancing the Scientific Study of Early Autism' (ESSEA). TFY and SB were supported by The Bank of Sweden Tercentenary Foundation [P12-0270:1 and P10-078, respectively]. SB was supported by the Swedish Research Council [Nr. 523-2009-7054]. 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PD JUN PY 2015 VL 45 IS 6 BP 1897 EP 1904 DI 10.1007/s10803-014-2278-4 PG 8 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700032 PM 25331324 ER PT J AU Karten, A Hirsch, J AF Karten, Ariel Hirsch, Joy TI Brief Report: Anomalous Neural Deactivations and Functional Connectivity During Receptive Language in Autism Spectrum Disorder: A Functional MRI Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Functional magnetic resonance imaging (fMRI); Functional connectivity; Psychophysiological interactions (PPI); Negative BOLD response (NBR); Neural inhibition; Autism; Receptive language processing ID NEGATIVE BOLD; HUMAN BRAIN; DEFAULT NETWORK; FMRI; CORTEX; DYSFUNCTION; SPEECH; EXCITATION/INHIBITION; STIMULATION; INHIBITION AB Neural mechanisms that underlie language disability in autism spectrum disorder (ASD) have been associated with reduced excitatory processes observed as positive blood oxygen level dependent (BOLD) responses. However, negative BOLD responses (NBR) associated with language and inhibitory processes have been less studied in ASD. In this study, functional magnetic resonance imaging showed that the NBR in ASD participants was reduced during passive listening to spoken narratives compared to control participants. Further, functional connectivity between the superior temporal gyrus and regions that exhibited a NBR during receptive language in control participants was increased in ASD participants. These findings extend models for receptive language disability in ASD to include anomalous neural deactivations and connectivity consistent with reduced or poorly modulated inhibitory processes. C1 [Karten, Ariel; Hirsch, Joy] Yale Univ, Sch Med, Dept Psychiat, Brain Funct Lab, New Haven, CT 06511 USA. [Karten, Ariel; Hirsch, Joy] Yale Univ, Sch Med, Dept Neurobiol, Brain Funct Lab, New Haven, CT 06511 USA. [Karten, Ariel] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. [Hirsch, Joy] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Hirsch, Joy] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06511 USA. RP Hirsch, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 902, New Haven, CT 06511 USA. EM joy.hirsch@yale.edu FU Gatsby Initiative in Brain Circuitry [GAT 2742]; US Army RDECOM-TARDEC [W56H2 V-04-P-L]; NIH [RO1NS0 56274] FX Authors are grateful for significant contributions by students and subjects who have participated in the development of this project, including Grace Lai (Columbia University Graduate Program in Neuroscience) and Spiro Pantazatos (Columbia University Graduate Program in Physiology and Cellular Biophysics), and for mentoring guidance, Jay Edelman (The City College of College [A.K]). Funding for this project includes a Grant from the Gatsby Initiative in Brain Circuitry, GAT 2742 (GL); US Army RDECOM-TARDEC W56H2 V-04-P-L (J.H); and NIH RO1NS0 56274 (sub-contract to J.H, PI Nicholas Schiff). 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Autism Dev. Disord. PD JUN PY 2015 VL 45 IS 6 BP 1915 EP 1924 DI 10.1007/s10803-014-2346-9 PG 10 WC Psychology, Developmental SC Psychology GA CI7XC UT WOS:000354977700034 PM 25526953 ER PT J AU van Steensel, FJA Bogels, SM AF van Steensel, F. J. A. Bogels, S. M. TI CBT for Anxiety Disorders in Children With and Without Autism Spectrum Disorders SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE CBT; anxiety; ASD; children ID COGNITIVE-BEHAVIORAL THERAPY; HIGH-FUNCTIONING AUTISM; RANDOMIZED CONTROLLED-TRIAL; DIAGNOSTIC INTERVIEW; ADOLESCENTS; INTERVENTION; METAANALYSIS; SCHEDULE; EFFICACY; EUROQOL AB Objective: The effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders in children with autism spectrum disorders (ASD) was examined, and compared with children without ASD. Method: Children with ASD and comorbid anxiety disorders (n = 79, 58 boys; M-age = 11.76) and children with anxiety disorders (n = 95, 46 boys; M-age = 12.85), and their parents, participated. All families were referred to 1 of 7 mental health care centers and received the same CBT. Anxiety, quality of life, ASD-like behaviors, and emotional-behavioral problems were measured at waitlist (ASD-group only, n = 17), pretest, posttest, and 3 months, 1 year, and 2 years after CBT. Results: CBT was more effective than waitlist for treating anxiety disorders (d = -1.45) and anxiety symptoms (d = -0.48) in children with ASD. At 2 years follow-up, 61% of the children with and 64% without ASD were free of their primary anxiety disorder (percentages not significantly different). The decrease in severity of anxiety disorders after CBT (d values ranging between -1.05 and -1.46) was not different for children with and without ASD. Improvements were less in children with ASD for (only) 2 out of 7 continuous outcomes measures: anxiety symptoms (d values ranging between -0.68 and -0.94 vs. d values ranging between -0.98 and -1.25) and quality of life (d values ranging between 0.39 and 0.56 vs. d values ranging between 0.77 and 0.98). Conclusions: CBT for anxiety disorders is effective for children with ASD, also in the long-term. Treatment gains may be somewhat less compared with children without ASD. C1 [van Steensel, F. J. A.; Bogels, S. M.] Univ Amsterdam, Child Dev & Educ, NL-1018 WS Amsterdam, Netherlands. RP van Steensel, FJA (reprint author), Univ Amsterdam, Child Dev & Educ, Res Prior Area Yield, Nieuwe Achtergracht 127, NL-1018 WS Amsterdam, Netherlands. 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Consult. Clin. Psychol. PD JUN PY 2015 VL 83 IS 3 BP 512 EP 523 DI 10.1037/a0039108 PG 12 WC Psychology, Clinical SC Psychology GA CJ0LK UT WOS:000355167300008 PM 25894668 ER PT J AU Kasari, C Gulsrud, A Paparella, T Hellemann, G Berry, K AF Kasari, Connie Gulsrud, Amanda Paparella, Tanya Hellemann, Gerhard Berry, Kathleen TI Randomized Comparative Efficacy Study of Parent-Mediated Interventions for Toddlers With Autism SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE autism toddlers; early intervention; parent training; JASPER; parenting stress ID JOINT ATTENTION INTERVENTION; CONTROLLED-TRIAL; YOUNG-CHILDREN; SPECTRUM DISORDERS; PRESCHOOL-CHILDREN; CLINICAL-TRIAL; MENTAL-HEALTH; COUNT DATA; FOLLOW-UP; PLAY AB Objective: This study compared effects of two parent-mediated interventions on joint engagement outcomes as augmentations of an early intervention program for toddlers with autism spectrum disorder (ASD). Method: Participants included 86 toddlers (range 22-36 months) with ASD and their primary caregiver. Caregiver-child dyads were randomized to receive 10 weeks of hands-on parent training in a naturalistic, developmental behavioral intervention (joint attention, symbolic play, engagement and regulation-JASPER) or a parent-only psychoeducational intervention (PEI). Dose was controlled in terms of researcher-parent contact and early intervention services received by the child. Results: Results yielded significant effects of the JASPER intervention on the primary outcome of joint engagement. The treatment effect was large (Cohen's f(2) = .69) and maintained over the 6-month follow-up. JASPER effects were also found on secondary outcomes of play diversity, highest play level achieved, and generalization to the child's classroom for child-initiated joint engagement. The PEI intervention was found to be effective in reducing parenting stress associated with child characteristics. All secondary effects were generally small to moderate. Conclusions: These data highlight the benefit of a brief, targeted, parent-mediated intervention on child outcomes. Future studies may consider the combination of JASPER and PEI treatments for optimal parent and child outcomes. Trial registry no. NCT00999778. C1 [Kasari, Connie; Berry, Kathleen] Univ Calif Los Angeles, Dept Human Dev & Psychol, Los Angeles, CA 90024 USA. [Gulsrud, Amanda; Paparella, Tanya] Univ Calif Los Angeles, Dept Child Psychiat, Los Angeles, CA 90024 USA. [Hellemann, Gerhard] Univ Calif Los Angeles, Semel Inst Biostat Core, Los Angeles, CA 90024 USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, Semel Inst 68 268, Los Angeles, CA 90024 USA. EM Kasari@gseis.ucla.edu FU NICHD, Autism Center of Excellence [P50-HD-055784]; Determinants of Social, Communicative; [4] FX This study was supported by NICHD, Autism Center of Excellence P50-HD-055784, Determinants of Social, Communicative, and Other Core Deficits in Autism (Bookheimer, PI) project 4, Optimizing Communication in Toddlers with Autism (Connie Kasari, PI), Clinical trials. gov no. NCT00999778. We appreciate the contributions of our therapists and coders: Janet Bang, Marina Farberov, Amy Fuller, Kelly Goods, Dalia Kabab, Kathy Lawton, Sara Levitt, Cordelia Ross, and our families and children. CR Adamson LB, 2004, CHILD DEV, V75, P1171, DOI 10.1111/j.1467-8624.2004.00732.x [Anonymous], 2005, JOINT ATT SYMB UNPUB Carter AS, 2011, J CHILD PSYCHOL PSYC, V52, P741, DOI 10.1111/j.1469-7610.2011.02395.x Cidav Z, 2012, PEDIATRICS, V129, P617, DOI 10.1542/peds.2011-2700 Cohen J., 1988, STAT POWER ANAL BEHA, V2nd Curwen M. 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Consult. Clin. Psychol. PD JUN PY 2015 VL 83 IS 3 BP 554 EP 563 DI 10.1037/a0039080 PG 10 WC Psychology, Clinical SC Psychology GA CJ0LK UT WOS:000355167300012 PM 25822242 ER PT J AU Dolen, G AF Doelen, Guel TI Oxytocin: Parallel Processing in the Social Brain? SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE 5-HT; oxytocin; vasopressin; autism; schizophrenia; synaptic plasticity ID FRAGILE-X-SYNDROME; AUTISM SPECTRUM DISORDERS; RANDOMIZED-CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; DE-NOVO MUTATIONS; HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; CEREBROSPINAL-FLUID OXYTOCIN; POTENTIATED STARTLE PARADIGM; NUCLEUS-ACCUMBENS OXYTOCIN; REDUCES BACKGROUND ANXIETY AB Early studies attempting to disentangle the network complexity of the brain exploited the accessibility of sensory receptive fields to reveal circuits made up of synapses connected both in series and in parallel. More recently, extension of this organisational principle beyond the sensory systems has been made possible by the advent of modern molecular, viral and optogenetic approaches. Here, evidence supporting parallel processing of social behaviours mediated by oxytocin is reviewed. Understanding oxytocinergic signalling from this perspective has significant implications for the design of oxytocin-based therapeutic interventions aimed at disorders such as autism, where disrupted social function is a core clinical feature. Moreover, identification of opportunities for novel technology development will require a better appreciation of the complexity of the circuit-level organisation of the social brain. C1 Johns Hopkins Univ, Sch Med, Wendy Klag Inst Dev Disabil & Autism, Dept Neurosci,Brain Sci Inst, Baltimore, MD 21205 USA. RP Dolen, G (reprint author), Johns Hopkins Univ, Sch Med, Wendy Klag Inst Dev Disabil & Autism, Dept Neurosci,Brain Sci Inst, Baltimore, MD 21205 USA. 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Neuroendocrinol. PD JUN PY 2015 VL 27 IS 6 SI SI BP 516 EP 535 DI 10.1111/jne.12284 PG 20 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA CJ1HA UT WOS:000355233400016 PM 25912257 ER PT J AU Frederikse, PH Kasinathan, C AF Frederikse, Peter H. Kasinathan, Chinnaswamy TI Lens GABA receptors are a target of GABA-related agonists that mitigate experimental myopia SO MEDICAL HYPOTHESES LA English DT Article ID FRAGILE-X-SYNDROME; DEVELOPING MOUSE LENS; RAT LENS; MESSENGER-RNAS; FIBER CELLS; EXPRESSION; BRAIN; MELATONIN; CHICK; EYE AB Coordinated growth of eye tissues is required to achieve visual acuity. However, visual experience also guides this process. Experimental myopia can be produced by altering light entering the eye, but also by changing light/dark regimens. Drug discovery studies demonstrated that gamma-aminobutyric acid (GABA)-related agonists (e.g., baclofen) will mitigate experimental myopia, and are also drugs studied for their capacity to affect neurodevelopmental disorders that include Fragile X Syndrome and related autism spectrum disorders. GABA receptors thought to mediate these responses in the eye have been studied in the neural retina as well as the cornea and sclera which are both innervated tissues. In addition to neurons, lenses express GAD25/65/67 GABA metabolic enzymes and at least 13 GABA receptor sub-units with developmental expression profiles that match neural development. Evidence that lens GABA receptors are expressed in a cell environment comparable to neurons is seen in the lens expression of AMPA and NMDA glutamate receptors together with an unexpectedly comprehensive array of associated signaling proteins that include post-synaptic-density 95 (PSD95), calcium calmodulin kinase Il alpha (CaMKII alpha), Fragile X Syndrome mental retardation protein (FMRP), ephrin receptors, Ca(V)1.2, 1.3 channels, cyclin-dependent kinase 5 (Cdk5), and neuronal C-src among others. Moreover, lens cells share fundamental molecular regulatory mechanisms that integrate the regulation and function of these genes at the DNA, RNA, and protein levels in neurons. GABA has trophic, growth promoting effects early in neuron development and later assumes its classic inhibitory role in the adult neural system. We hypothesize that the extensive parallels between GABA and glutamate receptor biology in lens and brain identifies the lens as a site of GABA agonist drug action affecting experimental myopia, acting through lens GABA receptors to similarly affect growth in both elongated cell types. (c) 2015 Elsevier Ltd. All rights reserved. C1 [Frederikse, Peter H.; Kasinathan, Chinnaswamy] Rutgers SDM & BHS, Dept Oral Biol, Newark, NJ 07103 USA. [Frederikse, Peter H.] Rutgers SDM & BHS, Dept Physiol & Pharmacol, Newark, NJ 07103 USA. RP Frederikse, PH (reprint author), Rutgers SDM, 185 S Orange Ave C866, Newark, NJ 07103 USA. 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TI Excess of rare, inherited truncating mutations in autism SO NATURE GENETICS LA English DT Article ID DE-NOVO MUTATIONS; EXOME SEQUENCE DATA; SPECTRUM DISORDERS; TRANSMISSION DISEQUILIBRIUM; DEVELOPMENTAL DELAY; GROWTH-FACTOR; GENES; MODEL; DELETIONS; SUPPORTS AB To assess the relative impact of inherited and de novo variants on autism risk, we generated a comprehensive set of exonic single-nucleotide variants (SNVs) and copy number variants (CNVs) from 2,377 families with autism. We find that private, inherited truncating SNVs in conserved genes are enriched in probands (odds ratio = 1.14, P = 0.0002) in comparison to unaffected siblings, an effect involving significant maternal transmission bias to sons. We also observe a bias for inherited CNVs, specifically for small (<100 kb), maternally inherited events (P = 0.01) that are enriched in CHD8 target genes (P = 7.4 x 10(-3)). Using a logistic regression model, we show that private truncating SNVs and rare, inherited CNVs are statistically independent risk factors for autism, with odds ratios of 1.11 (P = 0.0002) and 1.23 (P = 0.01), respectively. This analysis identifies a second class of candidate genes (for example, RIMS 1, CUL7 and LZTR1) where transmitted mutations may create a sensitized background but are unlikely to be completely penetrant. C1 [Krumm, Niklas; Turner, Tychele N.; Baker, Carl; Vives, Laura; Mohajeri, Kiana; Witherspoon, Kali; Raja, Archana; Coe, Bradley P.; Stessman, Holly A.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98104 USA. [Raja, Archana; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [He, Zong-Xiao; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA. [Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98104 USA. EM eee@gs.washington.edu FU US National Institutes of Health [1U01MH100233]; National Institute for Mental Health [R01MH101221, R01MH100047]; Simons Foundation [SFARI 89368, SFARI 137578] FX We thank D. Obenshain, D. Hall, B. Koser and S. Novikova for providing support for usage of the Amazon Cloud and for assistance in the deposition of SNV and CNV call sets into the National Database for Autism Research (NDAR). We are grateful to the laboratories of M. Wigler and M. State for providing early access to exome sequencing data as well as access to SNP microarray data. We also thank T. Brown for assistance in editing this manuscript. Funding for this study was provided, in part, by the US National Institutes of Health (1U01MH100233 to E.E.E.), by the National Institute for Mental Health (R01MH101221 to E.E.E. and R01MH100047 to R.B.) and by the Simons Foundation (SFARI 89368 to R.B. and SFARI 137578 to E.E.E.). E.E.E. is an investigator of the Howard Hughes Medical Institute. We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren and E. Wijsman). We appreciate obtaining access to phenotypic data on Simons Foundation Autism Research Initiative (SFARI) Base. Approved researchers can obtain the SSC population data set described in this study by applying at https://base.sfari.org/. 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PD JUN PY 2015 VL 47 IS 6 BP 582 EP 588 DI 10.1038/ng.3303 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CJ3LW UT WOS:000355386500008 PM 25961944 ER PT J AU Angriman, M Caravale, B Novelli, L Ferri, R Bruni, O AF Angriman, Marco Caravale, Barbara Novelli, Luana Ferri, Raffaele Bruni, Oliviero TI Sleep in Children with Neurodevelopmental Disabilities SO NEUROPEDIATRICS LA English DT Review DE sleep disorders; neurodevelopmental disabilities; Down syndrome; Fragile X syndrome; Prader-Willi syndrome; Angelman syndrome; Rett syndrome; Smith-Magenis syndrome; cerebral palsy; autism spectrum disorders ID PRADER-WILLI-SYNDROME; SMITH-MAGENIS-SYNDROME; AUTISM SPECTRUM DISORDERS; FRAGILE-X-SYNDROME; EXCESSIVE DAYTIME SLEEPINESS; PLACEBO-CONTROLLED TRIAL; GROWTH-HORMONE THERAPY; PERIODIC LIMB MOVEMENT; ANGELMAN-SYNDROME; RETT-SYNDROME AB This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families. C1 [Angriman, Marco] Cent Hosp Bolzano, Dept Pediat, Child Neurol & Neurorehabil Unit, Bolzano, Italy. [Caravale, Barbara; Novelli, Luana; Bruni, Oliviero] Univ Roma La Sapienza, Dept Dev & Social Psychol, I-00185 Rome, Italy. 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Furlow, Christopher M. Collins, Tai A. Brewer, Elizabeth Gresham, Frank M. Chenier, Katherine H. TI Peer-Mediated Check-In/Check-Out for Students At-Risk for Internalizing Disorders SO SCHOOL PSYCHOLOGY QUARTERLY LA English DT Article DE check-in/check-out; internalizing behavior; multi-tiered service delivery; peer-mediated; school-based mental health ID DISRUPTIVE CLASSROOM-BEHAVIOR; HIGH-SCHOOL-STUDENTS; SOCIAL-INTERACTION; INTERVENTION; ADOLESCENT; EDUCATION; CHILDREN; AUTISM AB The present study investigated the effectiveness of peer-mediated check-in/check-out (CICO) on the internalizing behaviors of elementary school students. A nonconcurrent multiple-baseline design across participants was utilized to evaluate the intervention's effectiveness for 3 students in 1st and 2nd grade. Two 5th grade students were trained to implement CICO under the supervision of an adult intervention specialist. The peer-mediated CICO procedure was effective for 2 of the 3 participants as evidenced by moderate to large effect sizes; however, all 3 participants were identified as "at-risk" on a universal screener for internalizing problems. The results suggest peer-mediated CICO may be a resource-efficient Tier II strategy to meet the needs of students engaging in internalizing behavior within a multitiered framework of service delivery. C1 [Dart, Evan H.; Furlow, Christopher M.; Brewer, Elizabeth] Univ So Mississippi, Dept Psychol, Hattiesburg, MS 39406 USA. [Collins, Tai A.] Univ Cincinnati, Sch Human Serv, Cincinnati, OH 45221 USA. [Gresham, Frank M.; Chenier, Katherine H.] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. RP Dart, EH (reprint author), Univ So Mississippi, Dept Psychol, 118 Coll Dr 5025, Hattiesburg, MS 39406 USA. EM evan.dart@usm.edu CR Bradshaw CP, 2008, SCHOOL PSYCHOL QUART, V23, P169, DOI 10.1037/1045-3830.23.2.169 Chafouleas S. 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C., 1985, ADV SCH PSYCHOL, V4, P251 Zeller R., 2000, ASSESSMENT EFFECTIVE, V26, P29, DOI 10.1177/073724770002600105 NR 41 TC 1 Z9 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1045-3830 EI 1939-1560 J9 SCHOOL PSYCHOL QUART JI Sch. Psychol. Q. PD JUN PY 2015 VL 30 IS 2 BP 229 EP 243 DI 10.1037/spq0000092 PG 15 WC Psychology, Educational SC Psychology GA CJ2GZ UT WOS:000355303500007 PM 25286311 ER PT J AU Segal, NL AF Segal, Nancy L. TI Centenary Celebration for Scottish Missionary Mary Slessor: A Lasting Legacy for Twins/Twin Research: Twins With Kleinfelter's Syndrome; Twin Research on Atopic Diseases; Twin Study of Autism; Psychotherapy with Twins / General Interest: Female Twin Pole-Vaulters; Longest Twin Birth Interval; Pair of Franco-Cuban Vocalists; Croatian Twin Models SO TWIN RESEARCH AND HUMAN GENETICS LA English DT News Item AB The centenary celebration for Scottish missionary, Mary Slessor, took place on February 14, 2015 in Melle, Belgium. Slessor saved many newborn twins and their mothers from death and disownment by members of their community, including their families, who believed twins harbored evil spirits. The events of this unusual and significant gathering are described. Next, twin research and reports concerning Kleinfelter's disease, atopic diseases, autism and psychotherapy are presented. General interest subjects include identical female twin pole-vaulters, the longest twin birth interval, Franco-Cuban twin vocalists, and Croatian twin models. C1 Calif State Univ Fullerton, Dept Psychol, Fullerton, CA 92834 USA. RP Segal, NL (reprint author), Calif State Univ Fullerton, Dept Psychol, Fullerton, CA 92834 USA. EM nsegal@fullerton.edu CR [Anonymous], 2015, MOTHER INFORMED BOTH Asteroid, 2015, WIKIPEDIA Benaiges D., 2014, ANDROLOGIA, V47, P116 Bennett-Smith M, 2013, HUFFINGTON POST Binder D, 2015, LEXI TORI WEEKS RAIS Bueltmann A. J., 2011, WHITE QUEEN CANNIBAL Croatian model arrested faces attempted murder charge after stabbing twin sister in jealous rage over boyfriend, 2015, NEW YORK DAILY NEWS Finding a balance between two worlds, 2015, NY TIMES, pAR2 Frazier TW, 2014, J AUTISM DEV DISORD, V44, P2013, DOI 10.1007/s10803-014-2081-2 Hester J, 1996, NY TIMES Inquisitur, 2015, MOTH INF BOTH COULD Kahr N., 2014, CLIN RESPIR J, V9, P79 Longman J., 2015, NY TIMES Mary Slessor Foundation, 2015, HER AD FAM Planetary Society, 2015, AST NAM GUID Segal NL, 2014, TWIN RES HUM GENET, V17, P134, DOI 10.1017/thg.2014.7 Stevenson J., 2015, LEXI WEEKS SETS POLE Wikipedia, 2015, PROV DES ASTR Wright E., 2010, NEW DIR PSYCH, V4, P268 NR 19 TC 0 Z9 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 EI 1839-2628 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD JUN PY 2015 VL 18 IS 3 BP 328 EP 333 DI 10.1017/thg.2015.24 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA CJ2BC UT WOS:000355288200013 PM 25906830 ER PT J AU Eriksson, MA Lieden, A Westerlund, J Bremer, A Wincent, J Sahlin, E Gillberg, C Fernell, E Anderlid, BM AF Eriksson, Mats Anders Lieden, Agne Westerlund, Joakim Bremer, Anna Wincent, Josephine Sahlin, Ellika Gillberg, Christopher Fernell, Elisabeth Anderlid, Britt-Marie TI Rare copy number variants are common in young children with autism spectrum disorder SO ACTA PAEDIATRICA LA English DT Article DE Autism; Autism spectrum disorder; Chromosomal microarray; Copy number variants ID PARENTAL PSYCHIATRIC-DISORDERS; DE-NOVO MUTATIONS; RISK; CNVS; GENETICS AB AimSeveral studies have suggested that rare copy number variants (CNVs) are an important genetic contributor to autism spectrum disorders. The aims of the study were to use chromosomal microarray to investigate the presence of rare copy number variants in a population-based cohort of well-characterised young children with autism spectrum disorders and to relate the genetic results to neurodevelopmental profiles and medical conditions. MethodsWe performed chromosomal microarray on samples from 162 children who had been referred to the Stockholm Autism Centre for Young Children in Sweden after being diagnosed with autism spectrum disorder between 20 and 54months of age. ResultsPathogenic aberrations were detected in 8.6% of the children and variants of uncertain significance were present in another 8.6%. CNVs were more frequent in children with congenital malformations or dysmorphic features as well as in the subgroup with intellectual disability. ConclusionOur results support the use of chromosomal microarray methods for the first tier genetic analysis of autism spectrum disorder. However, it is likely in the near future that chromosomal microarray methods will probably be replaced by whole-exome and whole-genome sequencing technologies in clinical genetic testing. C1 [Eriksson, Mats Anders] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Eriksson, Mats Anders] Karolinska Univ Hosp, Astrid Lindgrens Childrens Hosp, Dept Neuropediat, Stockholm, Sweden. [Eriksson, Mats Anders; Gillberg, Christopher; Fernell, Elisabeth] Gothenburg Univ, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Lieden, Agne; Wincent, Josephine; Sahlin, Ellika; Anderlid, Britt-Marie] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Lieden, Agne; Wincent, Josephine; Sahlin, Ellika; Anderlid, Britt-Marie] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Lieden, Agne; Sahlin, Ellika; Anderlid, Britt-Marie] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Westerlund, Joakim] Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. [Bremer, Anna] Univ Hosp, Div Clin Genet, Linkoping, Sweden. RP Eriksson, MA (reprint author), Karolinska Univ Hosp, Neuropaediat Dept, S-17176 Stockholm, Sweden. EM mats.a.eriksson@ki.se FU Swedish Research Council; Stockholm City Council; Frimurare Barnhuset Foundation; Linnea and Josef Carlsson Foundation; Kronprinsessan Lovisas Foundation; Sunnerdahls Foundation; Samariten Foundation; Karolinska Institutet Center of Neurodevelopmental Disorders; Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg FX Financial support was given from the Swedish Research Council, Stockholm City Council, Frimurare Barnhuset Foundation, Linnea and Josef Carlsson Foundation, Kronprinsessan Lovisas Foundation, Sunnerdahls Foundation, Samariten Foundation, Karolinska Institutet Center of Neurodevelopmental Disorders and Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg. 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PD JUN PY 2015 VL 104 IS 6 BP 610 EP 618 DI 10.1111/apa.12969 PG 9 WC Pediatrics SC Pediatrics GA CI1TR UT WOS:000354528100021 PM 25661985 ER PT J AU Bystrom, KM Persson, CAL AF Bystrom, Kristina M. Persson, Cristina A. Lundqvist TI The Meaning of Companion Animals for Children and Adolescents with Autism: The Parents' Perspective SO ANTHROZOOS LA English DT Article DE autism spectrum disorders; child development; human-companion animal interaction ID SPECTRUM DISORDERS; THERAPY; IMPACT AB The aim of this study was to understand parents' perspectives on how children and adolescents with autism spectrum disorders (ASD) benefit from a relationship with companion animals. Parents were invited to participate in focus-group discussions. One open-ended question with follow-up questions was asked and the parents' responses were subsequently categorized. Three main themes emerged: the quality of the relationship with the companion animal; increased interaction with people; and optimization of the child's function and development. The results show that companion animals can contribute to social and behavioral development support, and improved mental health and quality of life. The children's and adolescents' interests and activities with companion animals were more social than non-social and of different quality than the restricted and repetitive activities in which children with ASD are normally engaged. Our findings describe a complementary developmental support for this vulnerable group of children and adolescents, which give them possibilities for expanded social contacts, diminished anxiety and depression, and facilitated learning. C1 [Bystrom, Kristina M.] Swedish Univ Agr Sci, Dept Work Sci Business Econ & Environm Psychol, Alnarp, Sweden. [Persson, Cristina A. Lundqvist] Lund Univ, Dept Psychol, S-22100 Lund, Sweden. 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O., 1984, BLOPHILIA NR 45 TC 0 Z9 0 PU BLOOMSBURY PUBLISHING PLC PI LONDON PA 50 BEDFORD SQ, LONDON, WC1B 3DP, ENGLAND SN 0892-7936 EI 1753-0377 J9 ANTHROZOOS JI Anthrozoos PD JUN PY 2015 VL 28 IS 2 BP 263 EP 275 DI 10.2752/089279315X14219211661813 PG 13 WC Anthropology; Environmental Studies; Sociology; Veterinary Sciences SC Anthropology; Environmental Sciences & Ecology; Sociology; Veterinary Sciences GA CI8SD UT WOS:000355041100006 ER PT J AU Light, J Mcnaughton, D AF Light, Janice Mcnaughton, David TI Designing AAC Research and Intervention to Improve Outcomes for Individuals with Complex Communication Needs SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Editorial Material DE AAC; Autism; Cerebral palsy; Aphasia; Amyotrophic lateral sclerosis; Intellectual disability; ICF; Intervention; Outcomes; Research ID LONG-TERM OUTCOMES; ALTERNATIVE COMMUNICATION; DEVELOPMENTAL-DISABILITIES; REQUIRE AAC; AIDED AAC; ADULTS; PEOPLE; INCLUSION; CHILDREN; AUTISM AB There is a rapidly growing body of research that demonstrates the positive effects of augmentative and alternative communication (AAC) intervention on the communication of children and adults with complex communication needs. Despite the positive impact of many AAC interventions, however, many individuals with complex communication needs continue to experience serious challenges participating in educational, vocational, healthcare, and community environments. In this paper, we apply the framework proposed by the International Classification of Functioning, Disability and Health (ICF) to illustrate the need to re-think AAC intervention to improve outcomes for individuals with complex communication needs, and to foster a new generation of intervention research that will provide a solid foundation for improved services. Specifically, the paper emphasizes the need to take a more holistic view of communication intervention and highlights the following key principles to guide AAC intervention and research: (a) build on the individual's strengths and focus on the integration of skills to maximize communication, (b) focus on the individual's participation in real-world contexts, (c) address psychosocial factors as well as skills, and (d) attend to extrinsic environmental factors as well as intrinsic factors related to the individual who requires AAC. C1 [Light, Janice] Penn State Univ, Dept Commun Sci & Disorders, University Pk, PA 16802 USA. [Mcnaughton, David] Penn State Univ, Dept Educ Psychol Counseling & Special Educ, University Pk, PA 16802 USA. RP Light, J (reprint author), Penn State Univ, Dept Commun Sci & Disorders, 308 Ford Bldg, University Pk, PA 16802 USA. EM JCL4@psu.edu FU U.S. Department of Health and Human Services, National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [H133E140026] FX The contents of this paper were developed, in part, under a grant (The RERC on AAC) from the U.S. Department of Health and Human Services, National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [grant number H133E140026]. 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Altern. Commun. PD JUN PY 2015 VL 31 IS 2 BP 85 EP 96 DI 10.3109/07434618.2015.1036458 PG 12 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA CI5KL UT WOS:000354794600001 PM 25904008 ER PT J AU Ferm, UM Claesson, BK Ottesjo, C Ericsson, S AF Ferm, Ulrika M. Claesson, Britt K. Ottesjo, Cajsa Ericsson, Stina TI Participation and Enjoyment in Play with a Robot between Children with Cerebral Palsy who use AAC and their Peers SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Augmentative and alternative communication; Cerebral palsy; Children; Complex communication needs; Peers; Robotics; Play; Participation; Enjoyment ID COMPLEX COMMUNICATION NEEDS; ALTERNATIVE COMMUNICATION; YOUNG-CHILDREN; AGED CHILDREN; CONVERSATION; AUTISM; TECHNOLOGIES; ORGANIZATION; EXPERIENCES; PARENTS AB This study explores children with complex communication needs, their peers and adult support persons in play with the talking and moving robot LekBot. Two triads were filmed playing with LekBot at pre-school. LekBot was developed to facilitate independent and enjoyable play on equal terms for children with significant communication disabilities and their peers. Using Conversation Analysis, participatory symmetry and enjoyment were investigated in relation to spoken and gestural communication, embodied stance, gaze, and affective display. Data originated from three video-recorded sessions that were approximately 2 hours long. Four different interaction situations were identified and explored: Participatory Asymmetry, Adult Facilitation, Greater Participatory Symmetry and Creativity, and Turn-taking and Enjoyable Play with LekBot. Neither participatory symmetry nor enjoyment were easily achieved in the play sessions and may require considerable effort, including adult involvement, but creative, spontaneous and highly enjoyable play, correlating with participatory symmetry to various degrees, was observed in a few instances. The findings are discussed with regard to play, AAC and the future development of robots to facilitate play. C1 [Ferm, Ulrika M.; Claesson, Britt K.] Sahlgrens Univ Hosp, Queen Silvia Childrens Hosp, DART Ctr AAC&AT, S-41104 Gothenburg, Sweden. [Ottesjo, Cajsa] Univ Gothenburg, Dept Philosophy Theory Sci & Linguist, Gothenburg, Sweden. [Ericsson, Stina] Linnaeus Univ, Dept Swedish, Vaxjo, Sweden. RP Ferm, UM (reprint author), Sahlgrens Univ Hosp, Queen Silvia Childrens Hosp, DART Ctr AAC&AT, Kruthusgatan 17, S-41104 Gothenburg, Sweden. EM ulrika.ferm@vgregion.se FU Swedish Governmental Agency for Innovation Systems VINNOVA; Promobilia Foundation; Petter Silfverskiold Foundation; Research Council of the Swedish National Association for Disabled Children and Young People FX LekBot has received financial support from the Swedish Governmental Agency for Innovation Systems VINNOVA, The Promobilia Foundation, The Petter Silfverskiold Foundation, and The Research Council of the Swedish National Association for Disabled Children and Young People. 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Altern. Commun. PD JUN PY 2015 VL 31 IS 2 BP 108 EP 123 DI 10.3109/07434618.2015.1029141 PG 16 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA CI5KL UT WOS:000354794600003 PM 25921358 ER PT J AU Evans, DW Lazar, SM Boomer, KB Mitchel, AD Michael, AM Moore, GJ AF Evans, David W. Lazar, Steven M. Boomer, K. B. Mitchel, Aaron D. Michael, Andrew M. Moore, Gregory J. TI Social Cognition and Brain Morphology: Implications for Developmental Brain Dysfunction SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE MRI; Brain morphology; Autism spectrum disorder; Social cognition; Quantitative traits ID AUTISM SPECTRUM DISORDER; HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; ASPERGER-SYNDROME; GENERAL-POPULATION; SYSTEMATIZING QUOTIENT; HIPPOCAMPAL VOLUMES; HEAD CIRCUMFERENCE; CEREBRAL ASYMMETRY; EMPATHY QUOTIENT AB The social-cognitive deficits associated with several neurodevelopmental and neuropsychiatric disorders have been linked to structural and functional brain anomalies. Given the recent appreciation for quantitative approaches to behavior, in this study we examined the brain-behavior links in social cognition in healthy young adults from a quantitative approach. Twenty-two participants were administered quantitative measures of social cognition, including the social responsiveness scale (SRS), the empathizing questionnaire (EQ) and the systemizing questionnaire (SQ). Participants underwent a structural, 3-T magnetic resonance imaging (MRI) procedure that yielded both volumetric (voxel count) and asymmetry indices. Model fitting with backward elimination revealed that a combination of cortical, limbic and striatal regions accounted for significant variance in social behavior and cognitive styles that are typically associated with neurodevelopmental and neuropsychiatric disorders. Specifically, as caudate and amygdala volumes deviate from the typical R > L asymmetry, and cortical gray matter becomes more R > L asymmetrical, overall SRS and Emotion Recognition scores increase. Social Avoidance was explained by a combination of cortical gray matter, pallidum (rightward asymmetry) and caudate (deviation from rightward asymmetry). Rightward asymmetry of the pallidum was the sole predictor of Interpersonal Relationships and Repetitive Mannerisms. Increased D-scores on the EQ-SQ, an indication of greater systemizing relative to empathizing, was also explained by deviation from the typical R > L asymmetry of the caudate. These findings extend the brain-behavior links observed in neurodevelopmental disorders to the normal distribution of traits in a healthy sample. C1 [Evans, David W.; Lazar, Steven M.; Michael, Andrew M.; Moore, Gregory J.] Geisinger Bucknell Autism & Dev Med Ctr, Lewisburg, PA 17837 USA. [Evans, David W.; Lazar, Steven M.; Mitchel, Aaron D.] Bucknell Univ, Program Neurosci, Lewisburg, PA 17837 USA. [Boomer, K. B.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. [Moore, Gregory J.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. RP Evans, DW (reprint author), Geisinger Bucknell Autism & Dev Med Ctr, 120 Hamm Dr,Suite 2, Lewisburg, PA 17837 USA. 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PD JUN PY 2015 VL 9 IS 2 BP 264 EP 274 DI 10.1007/s11682-014-9304-1 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CI7TB UT WOS:000354966600012 PM 24788335 ER PT J AU Coles, B AF Coles, Barbara TI A "Suitable Person': an "insider' perspective SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE Autism; challenging behaviour; Health & social care policy and practice; independent living; intellectual disability; Parenting AB Accessible Summary The purpose of this article is to demonstrate how insider' research can make an effective contribution to policy debates. It draws on a study which looked at the experiences of twelve parents in England who manage a Direct Payment for an adult child who has a learning disability and complex support needs. This article matters to people with learning disabilities because it reveals some of the challenges faced by some parents who are managing Direct Payments on their behalf. SummaryThis article draws on a doctoral study carried out across seven counties in England which focused on twelve parents' experiences of carrying out the role of a suitable person' (SP') by managing a direct payment for an adult child (living in her/his own home) who has severe learning disabilities, autism and very complex support needs. Evidence came from naturally occurring qualitative data using (auto) ethnography. The research exposed how vital these parents' expertise and skills are to their adult children, but also how they themselves are being used within the care system. This article considers whether research has greater impact if a researcher who has direct experience of the research problem has conducted it. It argues that insider' research can uncover a unique perspective of some of the issues that directly affect the lives of SP'. 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PD JUN PY 2015 VL 43 IS 2 SI SI BP 135 EP 141 DI 10.1111/bld.12125 PG 7 WC Education, Special SC Education & Educational Research GA CI3IF UT WOS:000354640600009 ER PT J AU Murtaza, M Jolly, LA Gecz, J Wood, SA AF Murtaza, Mariyam Jolly, Lachlan A. Gecz, Jozef Wood, Stephen A. TI La FAM fatale: USP9X in development and disease SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Ubiquitin; Fat facets; Embryo; Stem cells ID FACETS DEUBIQUITINATING ENZYME; UBIQUITIN LIGASE ITCH; ALPHA-SYNUCLEIN FATE; EMBRYONIC STEM-CELLS; DEUBIQUITYLATING ENZYME; BETA-CATENIN; PROLYL HYDROXYLATION; PROTEIN TRAFFICKING; EXPRESSION ANALYSIS; NEURONAL MIGRATION AB Deubiquitylating enzymes (DUBs), act downstream of ubiquitylation. As such, these post-posttranslational modifiers function as the final arbitrators of a protein substrate's ubiquitylation status, thus regulating its fate. In most instances, DUBs moderate the absolute level of a substrate, its locality or activity, rather than being an "all-or-none'' phenomenon. Yet, disruption of this quantitative regulation can produce dramatic qualitative differences. The ubiquitin-specific protease 9X (USP9X/FAM) is a substrate-specific DUB, which displays an extraordinarily high level of sequence conservation from Drosophila to mammals. It is primarily the recent revelations of USP9X's pivotal role in human cancers, both as oncogene or tumour suppressor, in developmental disorders including intellectual disability, epilepsy, autism and developmental delay that has led to a subsequent re-examination of its molecular and cellular functions. Results from experimental animal models have implicated USP9X in neurodegeneration, including Parkinson's and Alzheimer's disease, as well as autoimmune diseases. 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Mol. Life Sci. PD JUN PY 2015 VL 72 IS 11 BP 2075 EP 2089 DI 10.1007/s00018-015-1851-0 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CI6PV UT WOS:000354883800003 PM 25672900 ER PT J AU Bearss, K Burrell, TL Stewart, L Scahill, L AF Bearss, Karen Burrell, T. Lindsey Stewart, Lindsay Scahill, Lawrence TI Parent Training in Autism Spectrum Disorder: What's in a Name? SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Review DE Autism spectrum disorder; Parent training; Parent-mediated intervention; Psychoeducation; Care coordination ID PERVASIVE DEVELOPMENTAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; OF-THE-LITERATURE; YOUNG-CHILDREN; EARLY INTERVENTION; MENTAL-HEALTH; MEDICAL HOME; MEDIATED INTERVENTION; DISRUPTIVE BEHAVIOR; PRESCHOOL-CHILDREN AB Parent training (PT) is well understood as an evidence-based treatment for typically developing children with disruptive behavior. Within the field of autism spectrum disorder (ASD), the term parent training has been used to describe a wide range of interventions including care coordination, psychoeducation, treatments for language or social development, as well as programs designed to address maladaptive behaviors. As a result, the meaning of "parent training" in ASD is profoundly uncertain. This paper describes the need to delineate the variants of PT in ASD and offers a coherent taxonomy. Uniform characterization of PT programs can facilitate communication with families, professionals, administrators, and third-party payers. Moreover, it may also serve as a framework for comparing and contrasting PT programs. In support of the taxonomy, a purposive sampling of the literature is presented to illustrate the range of parent training interventions in ASD. C1 [Bearss, Karen; Burrell, T. Lindsey; Scahill, Lawrence] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Marcus Autism Ctr, Atlanta, GA 30329 USA. [Stewart, Lindsay] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA. RP Bearss, K (reprint author), Emory Univ, Sch Med, Childrens Healthcare Atlanta, Marcus Autism Ctr, 1920 Briarcliff Rd,NE, Atlanta, GA 30329 USA. EM karen.bearss@emory.edu FU National Institute of Mental Health NIMH [R01 MH081148]; Healthcare Innovation Program/Atlanta Clinical & Translational Research Seed Grant Program; National Center for Research Resources (NCRR) of the National Institutes of Health (NIH) [UL1 RR024139, 5KL2RR024138]; NIH roadmap for Medical Research FX This publication was made possible by the following grants: the National Institute of Mental Health NIMH R01 MH081148 (principal investigator: L. Scahill); Healthcare Innovation Program/Atlanta Clinical & Translational Research Seed Grant Program. This publication was also made possible by a Clinical and Translational Scholar Award (CTSA) Grant Number UL1 RR024139 and 5KL2RR024138 (principal investigator: K Bearss) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. 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(vol 18, pg 170, 2015) SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Correction C1 [Bearss, Karen; Burrell, T. Lindsey; Scahill, Lawrence] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Marcus Autism Ctr, Atlanta, GA 30329 USA. [Stewart, Lindsay] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA. RP Bearss, K (reprint author), Emory Univ, Sch Med, Childrens Healthcare Atlanta, Marcus Autism Ctr, 1920 Briarcliff Rd,NE, Atlanta, GA 30329 USA. EM karen.bearss@emory.edu CR Bearss K, 2015, CLIN CHILD FAM PSYCH, V18, P170, DOI 10.1007/s10567-015-0179-5 NR 1 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1096-4037 EI 1573-2827 J9 CLIN CHILD FAM PSYCH JI Clin. Child Fam. Psychol. Rev. PD JUN PY 2015 VL 18 IS 2 BP 183 EP 183 DI 10.1007/s10567-015-0183-9 PG 1 WC Psychology, Clinical SC Psychology GA CI0FC UT WOS:000354410900005 PM 25840684 ER PT J AU Silva, GFM Raposo, A Suplino, M AF Mireya Silva, Greis F. Raposo, Alberto Suplino, Maryse TI Exploring Collaboration Patterns in a Multitouch Game to Encourage Social Interaction and Collaboration Among Users with Autism Spectrum Disorder SO COMPUTER SUPPORTED COOPERATIVE WORK-THE JOURNAL OF COLLABORATIVE COMPUTING LA English DT Article DE Autism spectrum disorder; Collaborative games; Collaboration patterns; Multitouch tabletop; User study ID CHILDREN AB In this paper, we present a design and evaluation of four Collaboration Patterns on a multitouch collaborative game designed to encourage collaboration among people diagnosed with ASD (autism spectrum disorder). We define Collaboration Patterns as collaborative interaction strategies on elements in a multiuser interface. The patterns presented here were designed according to both recommendations from experts in ASD and requirements of a group of youths with high ASD-related impairment in their social interactions and were inspired by collaborative methods used in other studies. The proposed Collaboration Patterns were evaluated using research criteria relating to social interaction actions and collaborative tasks achieved by users during a multitouch game. The evaluation results suggest that each Collaboration Pattern motivates the need for collaboration and encourages creation of social interaction expressions among users. The applied sequence of patterns gradually encouraged collaborative activities and verbal and gestural interaction expressions among users. The significant characteristics of the proposed Collaboration Patterns allow us to suggest that they might be used in other collaborative applications aimed at fostering social interaction and collaboration among people with ASD. C1 [Mireya Silva, Greis F.; Raposo, Alberto] Pontifical Cathol Univ Rio de Janeiro PUC Rio, Dept Informat, BR-22451900 Rio De Janeiro, Brazil. [Suplino, Maryse] Ann Sullivan Inst, BR-20780170 Rio De Janeiro, Brazil. RP Silva, GFM (reprint author), Pontifical Cathol Univ Rio de Janeiro PUC Rio, Dept Informat, BR-22451900 Rio De Janeiro, Brazil. EM gcalpa@inf.puc-rio.br; abraposo@inf.puc-rio.br; instituto.ann.sullivan@gmail.com FU CAPES; CNPq [process 310607/2013-2]; FAPERJ [process 190.243/2013] FX Greis Silva thanks CAPES, CNPq and FAPERJ for supporting this research. Alberto Raposo thanks CNPq for the individual grant (process 310607/2013-2) and FAPERJ (Assistive Technology Program, process 190.243/2013). 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 207 EP 212 DI 10.1007/s11013-015-9450-y PG 6 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100001 PM 25930688 ER PT J AU Rios, C Andrada, BC AF Rios, Clarice Andrada, Barbara Costa TI The changing face of autism in Brazil SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Autism; Public policies; Disability; Mental health; Identity politics ID CHALLENGES; SEARCH AB At the end of 2012, after intensive lobbying by parent activist associations, a federal law recognized autism as a "disability for all legal purposes" in Brazil. Defining autism as a disability was more than a change of legal status to guarantee social benefits. It was also a political maneuver, orchestrated by parent associations, aimed to take the responsibility for treatment away from the public mental health network of services. This article examines the controversies that have set parent associations in direct antagonism with mental health professionals in the public health system. We draw from ethnographic data and theoretical discussions in the field of disability studies to situate these controversies within the context of a larger debate on the relationship between health, rights, and citizenship. We found similarities between the ethical and political goals of parent activists and mental health professionals in Brazil, but we argue that the main cause of dissent is the role that each of these social actors assigns to identity politics in their clinical and political projects. C1 [Rios, Clarice; Andrada, Barbara Costa] Univ Estado Rio De Janeiro, Inst Social Med, BR-20550900 Rio De Janeiro, Brazil. RP Rios, C (reprint author), Univ Estado Rio De Janeiro, Inst Social Med, Rua Sao Francisco Xavier 524, BR-20550900 Rio De Janeiro, Brazil. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 213 EP 234 DI 10.1007/s11013-015-9448-5 PG 22 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100002 PM 25842350 ER PT J AU Cascio, MA AF Cascio, M. Ariel TI Rigid Therapies, Rigid Minds: Italian Professionals' Perspectives on Autism Interventions SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Autism; Ethnography; Health and human services; Italy; Metaphor ID CHILDREN; NEURODIVERSITY; SPECTRUM; DISORDER; METAPHOR AB Many therapies, interventions, and programs seek to improve outcomes and quality of life for people diagnosed with autism spectrum conditions. This paper addresses Italian professionals' perspectives on a variety of such interventions, including TEACCH, ABA, Defeat Autism Now!, and Doman-Delacato. Drawing on participant-observation and interviews collected in 2012-2013 in a northern region of Italy, it highlights the theme of "rigidity" that appears in professionals' discourses about both the characteristics of people with autism and the potential risks of adhering too strictly to any particular treatment protocol. The co-occurrence of the theme of rigidity across different domains demonstrates a way in which diagnostic characteristics become metaphors for medical practice. This paper proposes that such discursive moves may help bridge the gap between people with autism and people who work with them because a key attribute of people with autism-thinking and/or acting rigidly-is also a potential pitfall for people without autism. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Cascio, MA (reprint author), Case Western Reserve Univ, Cleveland, OH 44106 USA. EM ariel.cascio@case.edu FU Institute of International Education Fulbright Grant; Dissertation Research Assistance Grant; Baker Nord Center for the Humanities Graduate Research Grant at Case Western Reserve University; Arts & Sciences Dissertation Fellowship at Case Western Reserve University FX This submission represents original work and has not been submitted or published elsewhere. Portions of this work were presented on March 19, 2014 at the Society for Applied Anthropology Annual Meeting in Albuquerque, NM, under the title " 'This Is the Italian Variant on TEACCH': Italian Adaptation of a North Carolina Autism Service Model." Research for this article was funded by an Institute of International Education Fulbright Grant, academic year 2012-2013; a Dissertation Research Assistance Grant under the supervision of Eileen-Anderson-Fye; a Baker Nord Center for the Humanities Graduate Research Grant at Case Western Reserve University; and an Arts & Sciences Dissertation Fellowship at Case Western Reserve University. Several Italian individuals and organizations made this research possible including Professor Roberto Malighetti and the Universita degli Studi di Milano-Bicocca; Cascina Rossago; Cooperativa Aurora 2000 and the Spazio Autismo; Cooperativa I Percorsi; Cooperativa Spazio Aperto Servizi; Fondazione Istitute Sacra Famiglia ONLUS; Gruppo Asperger ONLUS; and Progetto Filippide. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 235 EP 253 DI 10.1007/s11013-015-9439-6 PG 19 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100003 PM 25743186 ER PT J AU Sarrett, JC AF Sarrett, Jennifer C. TI Custodial Homes, Therapeutic Homes, and Parental Acceptance: Parental Experiences of Autism in Kerala, India and Atlanta, GA USA SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Autism Spectrum Disorders (ASD); Cross-cultural; India; Homes; Parental attitudes ID SPECTRUM DISORDER; YOUNG-CHILDREN; SOUTH-INDIA; DISABILITY; PERCEPTIONS; WORLDS; IMPACT; ASD AB The home is a critical place to learn about cultural values of childhood disability, including autism and intellectual disabilities. The current article describes how the introduction of autism into a home and the availability of intervention options change the structure and meaning of a home and reflect parental acceptance of a child's autistic traits. Using ethnographic data from Kerala, India and Atlanta, GA USA, a description of two types of homes are developed: the custodial home, which is primarily focused on caring for basic needs, and the therapeutic home, which is focused on changing a child's autistic traits. The type of home environment is respondent to cultural practices of child rearing in the home and influences daily activities, management, and care in the home. Further, these homes differ in parental acceptance of their autistic children's disabilities, which is critical to understand when engaging in international work related to autism and intellectual disability. It is proposed that parental acceptance can be fostered through the use of neurodiverse notions that encourage autism acceptance. C1 Emory Univ, Atlanta, GA 30322 USA. RP Sarrett, JC (reprint author), Emory Univ, Atlanta, GA 30322 USA. EM jsarret@emory.edu FU Organization for Autism Research; Emory University FX We thank the Organization for Autism Research and Emory University for supporting this research as well as Ariel Cascio for organizing this special issue. We also thank the families, professionals, and children who participated in this project. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 254 EP 276 DI 10.1007/s11013-015-9441-z PG 23 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100004 PM 25772598 ER PT J AU Brezis, RS Weisner, TS Daley, TC Singhal, N Barua, M Chollera, SP AF Brezis, Rachel S. Weisner, Thomas S. Daley, Tamara C. Singhal, Nidhi Barua, Merry Chollera, Shreya P. TI Parenting a Child with Autism in India: Narratives Before and After a Parent-Child Intervention Program SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Autism; India; Parents; Intervention; Five Minute Speech Sample; Socioeconomic status (SES) ID RELATIVES EXPRESSED EMOTION; SCHIZOPHRENIA; DISABILITY; FAMILIES; MOTHERS; PERCEPTIONS; CHANDIGARH; IMPACT AB In many low and middle income countries where autism-related resources are scarce, interventions must rely on family and parents. A 3-month Parent-Child Training Program (PCTP) at Action For Autism, New Delhi, India is aimed at empowering and educating parents, encouraging acceptance of their child, and decreasing parent stress. Forty couples were asked to describe their child with autism using the Five Minute Speech Sample (FMSS), an open-ended narrative method, before and after the program. Parents described a wide range of child behaviors, primarily social and cognitive skills. While all families were of a relatively affluent strata compared to the general Indian population, there were nonetheless significant differences in parents' narratives based on their income levels. Coming into the program, parents with relatively less income focused on their child's immediate and material needs, while higher income parents discussed their parental roles and vision for society. After the PCTP, parents were more likely to reflect on their child beyond comparisons to 'normality,' and beyond the here-and-now. Mothers were more likely than fathers to reflect on themselves and their relationships with their child. Understanding parents' experiences and narratives is essential for the evaluation of interventions such as the PCTP, as Indian parents are incorporated into a growing global network of 'parents of children with autism.'. C1 [Brezis, Rachel S.; Chollera, Shreya P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Ctr Culture & Hlth, Los Angeles, CA 90024 USA. [Brezis, Rachel S.] Interdisciplinary Ctr, Sch Psychol, Herzliyya, Israel. [Weisner, Thomas S.] Univ Calif Los Angeles, Dept Psychiat, Semel Inst, Ctr Culture & Hlth, Los Angeles, CA 90024 USA. [Weisner, Thomas S.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. [Daley, Tamara C.] Westat Corp, Durham, NC USA. [Singhal, Nidhi; Barua, Merry] Act Autism, New Delhi, India. RP Brezis, RS (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Ctr Culture & Hlth, Los Angeles, CA 90024 USA. EM brezisrs@gmail.com FU Center for Culture and Health (Semel Institute, Department of Psychiatry, UCLA); Foundation for Psychocultural Research FX The authors wish to thank the families who participated in the study. Assistance to the project was provided by Deepali Taneja, Sachita Suryanarayan, Simi Sunny, Rubina Pradhan, Tanvi Behl and Shaivalini Singh at AFA, and by Gail Fox Adams, Avani Bedagkar, Navjot Sandhu, and Fatima Burney at UCLA. The Center for Culture and Health (Semel Institute, Department of Psychiatry, UCLA) also provided support. The project is part of the Culture, Brain, Development, and Mental Health Program (CBDMH), [http://cbdmh.org] funded by the Foundation for Psychocultural Research, Robert Lemelson, President. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 277 EP 298 DI 10.1007/s11013-015-9434-y PG 22 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100005 PM 25739529 ER PT J AU Fein, E AF Fein, Elizabeth TI Making Meaningful Worlds: Role-Playing Subcultures and the Autism Spectrum SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Autism; Asperger's syndrome; LARP; Neurodiversity ID ASPERGER-SYNDROME; FUNCTIONING AUTISM; EXECUTIVE FUNCTION; COGNITIVE-STYLE; DISORDERS; CHILDREN; INDIVIDUALS; COHERENCE; QUOTIENT; DEFICITS AB Every summer, a group of role-playing gamers gathers in an American town. Dressed up as moon goddesses, mad scientists, and other fantastical characters, they act out elaborate, improvised narratives of transformation, destruction, and redemption. For several summers, this group, who I call the Journeyfolk, ran a camp for teenagers on the autism spectrum, engaging campers in therapeutic reconfigurations of self and social role. Through this folk healing practice, the meaning of autism was itself transformed; what had been a source of isolation became a source of commonality and community. This paper takes the camp as a case study for examining the co-productive relationship between culture and neurodiversity. Cognitive tendencies often found in autism are often thought to preclude socio-cultural participation. However, such tendencies can also facilitate the co-creation of innovative cultural spaces, through processes of affinity and affiliation. Drawing on ethnographic fieldwork at the camp, I identify three sites of congruity between the culture of the camp and the cognitive and phenomenological experiences associated with autism, at which this "work of culture" (Obeysekere in The Work of Culture: Symbolic Transformation in Psychoanalysis and Anthropology, University of Chicago Press, Chicago, 1990) took place: the structure of social interactions within roleplaying games, the narratives enacted within these games, and the interpersonal relationships within which the games were embedded. C1 Duquesne Univ, Dept Psychol, Pittsburgh, PA 15219 USA. RP Fein, E (reprint author), Duquesne Univ, Dept Psychol, Pittsburgh, PA 15219 USA. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 299 EP 321 DI 10.1007/s11013-015-9443-x PG 23 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100006 PM 25812848 ER PT J AU Fein, E AF Fein, Elizabeth TI Making Meaningful Worlds: Role-Playing Subcultures and the Autism Spectrum (vol 39, pg 299, 2015) SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Correction C1 Duquesne Univ, Dept Psychol, Pittsburgh, PA 15219 USA. RP Fein, E (reprint author), Duquesne Univ, Dept Psychol, Pittsburgh, PA 15219 USA. EM feine@duq.edu CR Fein E, 2015, CULT MED PSYCHIAT, V39, P299, DOI 10.1007/s11013-015-9443-x NR 1 TC 0 Z9 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X EI 1573-076X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 322 EP 322 DI 10.1007/s11013-015-9454-7 PG 1 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100007 PM 25894003 ER PT J AU Solomon, O AF Solomon, Olga TI "But-He'll Fall!": Children with Autism, Interspecies Intersubjectivity, and the Problem of 'Being Social' SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Animal-assisted activity; Autism Spectrum Disorder; Human-animal interaction; Intersubjectivity; Psychological testing; Sociality; Therapy animals ID SERVICE DOGS; THERAPY; EXPERIENCES; ENCOUNTERS; DISORDERS; FAMILIES; BEHAVIOR; PEOPLE; WORLD AB 'Being autistic' or 'having Autism Spectrum Disorder' implies a limited range of 'being social,' but the in situ organization of interaction, what Maynard and Marlaire (Qual Soc 15(2):177-202, 1992) call the 'interactional substrate,' within which this delimitation enfolds is usually hidden from sight. Analysis of processes constituting different 'interactional substrates' provides a view of how one comes to be known by and to self and others as a certain kind of being who is available (or not) for acting and feeling in certain ways. People diagnosed with Autism Spectrum Disorder (American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013) are often described as 'being' impaired in intersubjective understanding of others. But the story of ASD as an impairment of sociality and intersubjectivity becomes more complicated when animals enter into the picture. I consider two interactional substrates: a psychological interview in a mental health clinic, and an animal-assisted activity in a child's neighborhood. I aim to elucidate the practical problems of 'being social' encountered by two children with ASD, both nine-year-old girls, within these two very differently organized interactional substrates. I consider ways in which 'being with' therapy animals provides a way of 'being social' through "sensory modalities of knowing" (Haraway, When species meet, 2008:371). C1 Univ So Calif, USC Mrs TH Chan Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. RP Solomon, O (reprint author), Univ So Calif, USC Mrs TH Chan Div Occupat Sci & Occupat Therapy, 1540 East Alcazar St,CHP 133, Los Angeles, CA 90089 USA. EM olga.solomon@usc.edu FU National Institute of Mental Health [R01 MH089474]; Cure Autism Now foundation's Innovative Technology for Autism Bridge Grant; James H. Zumberge Faculty Research and Innovation award; USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy FX I am deeply grateful to the children and their families who participated in this research, and to Susan Kraft, the animal trainer extraordinaire who contributed her unique understanding of children with ASD. I would be remiss not to thank the animals, those who participated in this research and those who have taught me at different times about interspecies intersubjectivity. An earlier version of this paper was presented in June 2014 in a panel 'Interactional matrix of communication in autism' organized by Laura Sterponi and John Rae at the International Conference on Conversation Analysis at the University of California, Los Angeles. I thank two anonymous reviewers, and Ariel Casio and Douglas Maynard for their generous feedback on the final version. I also thank my colleagues at the University of Southern California, Mary Lawlor, Sharon Cermak, and Kate Crawley, and my academic 'family of origin' at UCLA, Elinor Ochs, Alessandro Duranti, Marjory Harness Goodwin, and Charles Goodwin for their encouragement of this research. The study 'Autism in Urban Context: Linking Heterogeneity with Health and Service Disparities' was supported by the National Institute of Mental Health (Grant # R01 MH089474, 2009-2012, O. Solomon, P.I.). The content of this article is solely the responsibility of the author and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The study 'Animal-Assisted Therapy as Socially Assistive Technology: Implications for Autism' was supported by the Cure Autism Now foundation's Innovative Technology for Autism Bridge Grant (2006-2007) and the James H. Zumberge Faculty Research and Innovation award (2008). I am also deeply grateful to the USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy that provided support for both studies. 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Med. Psychiatr. PD JUN PY 2015 VL 39 IS 2 SI SI BP 323 EP 344 DI 10.1007/s11013-015-9446-7 PG 22 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100008 PM 25926308 ER PT J AU Grinker, RR AF Grinker, Roy Richard TI Reframing the Science and Anthropology of Autism SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Editorial Material C1 George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. RP Grinker, RR (reprint author), George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. 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PD JUN PY 2015 VL 39 IS 2 SI SI BP 345 EP 350 DI 10.1007/s11013-015-9444-9 PG 6 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA CI7QC UT WOS:000354958100009 PM 25792459 ER PT J AU Leaf, JB Oppenheim-Leaf, ML Leaf, RB Taubman, M McEachin, J Parker, T Waks, AB Mountjoy, T AF Leaf, Justin B. Oppenheim-Leaf, Misty L. Leaf, Ronald B. Taubman, Mitchell McEachin, John Parker, Tracee Waks, Andrea B. Mountjoy, Toby TI What is the Proof? A Methodological Review of Studies That Have Utilized Social Stories SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Review ID AUTISM SPECTRUM DISORDERS; DECREASING DISRUPTIVE BEHAVIORS; ASPERGER-SYNDROME; CHILDREN; INTERVENTION; STUDENTS; IMPROVE; SKILLS; SOCIAL-STORIES(TM); COMMUNICATION AB Social stories are a commonly empirically evaluated and implemented procedure to increase pro-social behaviors and decrease aberrant behaviors for individuals diagnosed with an autism spectrum disorder. Despite their widespread use there have been questions raised to the soundness of the research methodology and the results which have been demonstrated within these research studies. This paper is a methodological review of 41 studies that evaluated social stories for individuals diagnosed with autism. We classified each study as one that utilized either a case study design, a reversal design, or a multiple baseline design. After classification we evaluated each study across multiple methodological dimensions and used this analysis to determine if a study showed either a clear demonstration, partial demonstration, or if there was no clear demonstration that the social story was responsible for behavior change. Results of this analysis indicated that the majority of studies either showed only a partial demonstration or no clear demonstration that the social story procedure was responsible for the behavior change. Based upon this analysis recommendations for clinicians and future researchers are discussed. C1 [Leaf, Justin B.; Oppenheim-Leaf, Misty L.; Leaf, Ronald B.; Taubman, Mitchell; McEachin, John; Parker, Tracee; Waks, Andrea B.; Mountjoy, Toby] Autism Partnership Fdn, Seal Beach, CA 90740 USA. RP Leaf, JB (reprint author), Autism Partnership Fdn, 200 Marina Dr, Seal Beach, CA 90740 USA. 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PD JUN PY 2015 VL 50 IS 2 BP 127 EP 141 PG 15 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700001 ER PT J AU Cihak, DF Wright, R Smith, CC McMahon, D Kraiss, K AF Cihak, David F. Wright, Rachel Smith, Cate C. McMahon, Don Kraiss, Kelly TI Incorporating Functional Digital Literacy Skills as Part of the Curriculum for High School Students with Intellectual Disability SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID AUTISM SPECTRUM DISORDERS; SEVERE DEVELOPMENTAL-DISABILITIES; GENERAL-EDUCATION CLASSROOM; HELD PROMPTING SYSTEM; MENTAL-RETARDATION; TECHNOLOGY USE; TIME-DELAY; COMPUTER; INDIVIDUALS; CHILDREN AB The purpose of this study was to examine the effects of teaching functional digital literacy skills to three high school students with intellectual disability. Functional digital literacy skills included sending and receiving email messages, organizing social bookmarking to save, share, and access career websites, and accessing cloud storage to download, revise, and upload documents. Results indicated that all students acquired and maintained these functional digital literacy skills. Findings are discussed in the context of teaching essential digital literacy skills to increase greater participation in a digital society. C1 [Cihak, David F.; Wright, Rachel; Kraiss, Kelly] Univ Tennessee, Knoxville, TN 37996 USA. [Smith, Cate C.] Appalachian State Univ, Boone, NC 28608 USA. [McMahon, Don] Washington State Univ, Pullman, WA 99164 USA. RP Cihak, DF (reprint author), Univ Tennessee, Coll Educ Hlth & Human Sci, A412 Bailey Educ Complex, Knoxville, TN 37996 USA. EM dcihak@utk.edu CR Alberto P. A., 2007, FOCUS AUTISM OTHER D, V22, P234, DOI DOI 10.1177/10883576070220040501 Ault M. 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J., 2002, MANAGING HUMAN SIDE Taber TA, 2003, RES PRACT PERS SEV D, V28, P105, DOI 10.2511/rpsd.28.3.105 Tanis ES, 2012, INTELLECT DEV DISAB, V50, P53, DOI 10.1352/1934-9556-50.1.53 U. S. Census Bureau, 2010, AM DIS 2010 Wehmeyer M. L., 2004, Journal of Special Education Technology, V19 NR 49 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2015 VL 50 IS 2 BP 155 EP 171 PG 17 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700003 ER PT J AU Barnett, JEH Cleary, S AF Barnett, Juliet E. Hart Cleary, Shannon TI Review of Evidence-based Mathematics Interventions for Students with Autism Spectrum Disorders SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Review ID HIGH-FUNCTIONING AUTISM; MODERATE INTELLECTUAL DISABILITIES; LOW-ACHIEVING STUDENTS; TEACH ADDITION FACTS; ASPERGER-SYNDROME; STRATEGY INSTRUCTION; SCHOOL-STUDENTS; WORD-PROBLEMS; CHILDREN; SKILLS AB Students with autism spectrum disorders (ASD) are being included more frequently in the general educational setting, and are therefore increasingly expected to access and master core curricular content, including mathematics. However, mathematics often presents challenges to students with ASD. Interventions to improve the mathematics skills of students with ASD have been recommended. This comprehensive literature review synthesized eleven studies of mathematics intervention strategies for students with ASD. Though studies related to instructional interventions in mathematics for students with ASD are limited, these students can benefit from mathematics interventions, which can help them strengthen their mathematics skills, increase independence when completing problems, and use acquired skills in community or other applied settings. Future implications include the need for additional, empirically-supported interventions in mathematics for students with ASD and the need to target more academically-oriented math interventions for this population, particularly in the context of problem solving, which will assist in determining the potential of students with ASD to achieve mathematic success. C1 [Barnett, Juliet E. Hart; Cleary, Shannon] Arizona State Univ, Phoenix, AZ 85069 USA. RP Barnett, JEH (reprint author), Arizona State Univ, Mary Lou Fulton Teachers Coll, POB 37100,Mail Code 3151, Phoenix, AZ 85069 USA. 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O., 2006, STRATEGY INSTRUCTION Mayes SD, 2006, LEARN INDIVID DIFFER, V16, P145, DOI 10.1016/j.lindif.2005.07.004 Montague M, 2008, LEARN DISABILITY Q, V31, P37 National Council of Teachers of Mathematics, 2002, PRINC STAND SCH MATH Odom SL, 2005, EXCEPT CHILDREN, V71, P137 Plavnick JB, 2011, J APPL BEHAV ANAL, V44, P747, DOI 10.1901/jaba.2011.44-747 Rapp JT, 2012, BEHAV INTERVENT, V27, P16, DOI 10.1002/bin.342 Rayner C, 2011, DEV NEUROREHABIL, V14, P339, DOI 10.3109/17518423.2011.606508 Rockwell SB, 2011, FOCUS AUTISM DEV DIS, V26, P87, DOI 10.1177/1088357611405039 Sansosti FJ, 2008, J POSIT BEHAV INTERV, V10, P162, DOI 10.1177/1098300708316259 U. S. Department of Education Office of Special Education Programs, 2011, IND DIS ED ACT IDEA van Garderen D, 2007, J LEARN DISABIL-US, V40, P540, DOI 10.1177/00222194070400060501 Volkmar F. R., 2009, J AUTISM DEV DISORD, V40, P149 Wang PS, 2009, EDUC TRAIN DEV DISAB, V44, P318 Waters HE, 2011, EDUC TRAIN AUTISM DE, V46, P544 Wei X, 2013, REM SPEC EDUC, V34, P154, DOI 10.1177/0741932512448253 Whitby PJS, 2009, EDUC TRAIN DEV DISAB, V44, P551 Whitby PJS, 2013, FOCUS AUTISM DEV DIS, V28, P78, DOI 10.1177/1088357612468764 Woodward J, 2002, J SPEC EDUC, V36, P89, DOI 10.1177/00224669020360020401 Xin YP, 1999, J SPEC EDUC, V32, P207 Zentall S. S., 2007, WHY IS MATH SO HARD, P219 NR 42 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2015 VL 50 IS 2 BP 172 EP 185 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700004 ER PT J AU Leaf, JB Leaf, R Alcalay, A Leaf, JA Ravid, D Dale, S Kassardjian, A Tsuji, K Taubman, M McEachin, J Oppenheim-Leaf, M AF Leaf, Justin B. Leaf, Ronald Alcalay, Aditt Leaf, Jeremy A. Ravid, Daniel Dale, Stephanie Kassardjian, Alyne Tsuji, Kathleen Taubman, Mitchell McEachin, John Oppenheim-Leaf, Misty TI Utility of Formal Preference Assessments for Individuals Diagnosed with Autism Spectrum Disorder SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID IDENTIFYING REINFORCERS; CHILDREN; BEHAVIOR; STIMULUS AB The systematic use of reinforcers is an essential component of behavioral intervention for individuals diagnosed with Autism Spectrum Disorder. Today, the use of rigorous formal preference assessments, including paired-preference assessments, are widely conducted to help determine which items to use as reinforcers during intervention. Although paired-preference assessments are widely used there is no experimental evidence whether extensive advance sampling actually produces higher rates of responding compared to in-the-moment analysis of reinforcer effects. The present study compared the rate of responding on a simple sorting task when participants were provided items that were determined as preferred via an extensive paired preference assessment to a teacher selecting items without the use of a paired preference assessment, but rather with an in-the-moment analysis of reinforcer effects. The results indicated no clear difference in the rate of responding, but there were clear differences in terms of efficiency. Clinical implications will be discussed. C1 [Leaf, Justin B.] Autism Partnership Fdn, Seal Beach, CA 90740 USA. Behav Therapy & Learning Ctr, Calgary, AB, Canada. RP Leaf, JB (reprint author), Autism Partnership Fdn, 200 Marina Dr, Seal Beach, CA 90740 USA. EM Jblautpar@aol.com CR Ayllon T., 1965, TOKEN EC MOTIVATIONA Cooper J. 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L., 2008, J APPL BEHAV ANAL, V41, P447 SCHREIBMAN L, 1975, J APPL BEHAV ANAL, V8, P91, DOI 10.1901/jaba.1975.8-91 WINDSOR J, 1994, RES DEV DISABIL, V15, P439, DOI 10.1016/0891-4222(94)90028-0 NR 16 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2015 VL 50 IS 2 BP 199 EP 212 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700006 ER PT J AU Rosenberg, N Congdon, M Schwartz, I Kamps, D AF Rosenberg, Nancy Congdon, Marissa Schwartz, Ilene Kamps, Debra TI Use of Say-Do Correspondence Training to Increase Generalization of Social Interaction Skills at Recess for Children with Autism Spectrum Disorder SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID HIGH-FUNCTIONING CHILDREN; INTERVENTIONS; EDUCATION; BEHAVIOR; PROGRAM AB Research suggests that while social skills groups in school settings can be effective for students with Autism Spectrum Disorder (ASD), generalization of the skills and behaviors learned in these groups to other settings can be problematic. This study assessed the use of a say-do correspondence intervention to increase generalization at recess of social interactions skills previously learned in a social skills group for students with ASD. The participants were three first graders who had participated in intensive social skills instruction for over a year but who were not generalizing their acquired skills to recess. The say-do correspondence involved the participants identifying before recess who they were going to talk to at recess and then receiving access to reinforcers after recess if they had talked to the student they had identified. A multiple-baseline across participants design was used to assess the impact of the intervention on the number of social exchanges between the child with ASD and other children during recess. Results showed that the number of social exchanges increased for all participants. Implications for practice in public school settings are discussed. C1 [Rosenberg, Nancy; Congdon, Marissa; Schwartz, Ilene] Univ Washington, Seattle, WA 98195 USA. [Kamps, Debra] Univ Kansas, Lawrence, KS 66045 USA. RP Rosenberg, N (reprint author), Univ Washington, Haring Ctr, Box 357925, Seattle, WA 98195 USA. EM nancyr@uw.edu FU Institute of Education Sciences, Department of Education [R324A090091] FX The research was funded by the Institute of Education Sciences, Department of Education (R324A090091). Opinions expressed herein are those of the authors and do not necessarily reflect the position of the funding agency. CR Ballard K. D., 1981, EXCEPT CHILDREN, V28, P55, DOI [10.1080/0156655810280106, DOI 10.1080/0156655810280106] Bauminger N, 2003, J AUTISM DEV DISORD, V33, P489, DOI 10.1023/A:1025827427901 Bellini S, 2007, REM SPEC EDUC, V28, P153, DOI 10.1177/07419325070280030401 Bevill-Davis A., 2004, J EARLY INTENSIVE BE, V1, P13 Giangreco MF, 1997, EXCEPT CHILDREN, V64, P7 GUEVREMONT DC, 1986, J APPL BEHAV ANAL, V19, P215, DOI 10.1901/jaba.1986.19-215 GUEVREMONT DC, 1986, J APPL BEHAV ANAL, V19, P99, DOI 10.1901/jaba.1986.19-99 Kamps D., 2014, J AUTISM DEV DISORD, V44, P1 KAZDIN AE, 1978, J CONSULT CLIN PSYCH, V46, P629, DOI 10.1037//0022-006X.46.4.629 Koegel LK, 2012, J POSIT BEHAV INTERV, V14, P220, DOI 10.1177/1098300712437042 Koegel LK, 2012, BEHAV MODIF, V36, P361, DOI 10.1177/0145445512445609 Lang R, 2011, RES AUTISM SPECT DIS, V5, P1296, DOI 10.1016/j.rasd.2011.02.012 Lee S. H., 2007, FOCUS AUTISM OTHER D, V22, P2, DOI DOI 10.1177/10883576070220010101 Lopata C, 2008, J AUTISM DEV DISORD, V38, P890, DOI 10.1007/s10803-007-0460-7 Malmgren K. W., 2006, J RES CHILDHOOD ED, V20, P301, DOI 10.1080/02568540609594569 May M. E., 2004, J BEHAV ED, V13, P267, DOI 10.1023/B:JOBE.0000044735.51022.5d Morrison RS, 2002, J EARLY INTERVENTION, V25, P58, DOI 10.1177/105381510202500106 National Professional Development Center on Autism Spectrum Disorders, EV BAS PRACT Owens G, 2008, J AUTISM DEV DISORD, V38, P1944, DOI 10.1007/s10803-008-0590-6 RISLEY TR, 1968, J APPL BEHAV ANAL, V1, P267, DOI 10.1901/jaba.1968.1-267 ROGERSWARREN A, 1976, J APPL BEHAV ANAL, V9, P335, DOI 10.1901/jaba.1976.9-335 Scruggs T. E., 1986, BEHAVIORAL DISORDERS, V11, P260 SCRUGGS TE, 1987, REM SPEC EDUC, V8, P24 White SW, 2007, J AUTISM DEV DISORD, V37, P1858, DOI 10.1007/s10803-006-0320-x WHITMAN TL, 1982, J APPL BEHAV ANAL, V15, P545, DOI 10.1901/jaba.1982.15-545 Yang NK, 2003, EDUC TRAIN MENT RET, V38, P405 NR 26 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2015 VL 50 IS 2 BP 213 EP 222 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700007 ER PT J AU Stroizer, S Hinton, V Flores, M Terry, L AF Stroizer, Shaunita Hinton, Vanessa Flores, Margaret Terry, LaTonya TI An Investigation of the Effects of CRA Instruction and Students with Autism Spectrum Disorder SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID CHILDREN AB Students with Autism Spectrum Disorders (ASD) have unique educational needs. The concrete representational abstract (CRA) instructional sequence has been shown effective in teaching students with mathematical difficulties. The purpose of this study was to examine the effects of the CRA sequence in teaching students with ASD. A multiple baseline across behavior design was used in assessing the effects of CRA to three elementary students with ASD over four weeks of instruction. A functional relation was demonstrated between CRA and three behaviors: addition with regrouping, subtraction with regrouping, and the multiplication facts zero through five. The results and implications are discussed further. C1 [Stroizer, Shaunita] Valdosta State Univ, Valdosta, GA USA. [Hinton, Vanessa; Flores, Margaret; Terry, LaTonya] Auburn Univ, Auburn, AL 36849 USA. RP Hinton, V (reprint author), Auburn Univ, Dept Special Educ Rehabil & Counseling, Haley Ctr 2084, Auburn, AL 36849 USA. EM vmh0002@tigermail.auburn.edu CR American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Boutot E. A., 2011, AUTISM SPECTRUM DISO Butler F. M., 2003, LEARNING DISABILITIE, V18, P99, DOI DOI 10.1111/1540-5826.00066 Centers for Disease Control and Prevention, 2012, PREV OF ASDS Connolly A. J., 2007, KEYMATH, V3rd Donaldson J. B., 2010, TEACHING EXCEPTIONAL, V42, P40 Flores M. M., 2009, PREVENTING SCH FAILU, V53, P145 Ganz J., 2011, TEACHING EXCEPTIONAL, V43, P8 Harris C. A., 1995, LEARNING DISABILITIE, V10, P180 Kaffar B. J., 2011, INVESTIGATIONS MATH, V4, P24 Kaufman A. S., 2004, KAUFMAN BRIEF INTELL Kroesbergen EH, 2003, REM SPEC EDUC, V24, P97, DOI 10.1177/07419325030240020501 Landry R, 2004, J CHILD PSYCHOL PSYC, V45, P1115, DOI 10.1111/j.1469-7610.2004.00304.x LYNN MR, 1986, NURS RES, V35, P382 Maccini P., 2000, ED TREATMENT CHILDRE, V23, P465 Maccini P., 2000, LEARNING DISABILITIE, V15, P10, DOI DOI 10.1207/SLDRP1501_2 MERCER CD, 1992, REM SPEC EDUC, V13, P19 Miller S. P., 1998, TREATMENT CHILDREN, V21, P22 Miller S. P., 2009, VALIDATED PRACTICES National Autism Center, 2009, EV BAS PRACT AUT SCH National Council of Teachers of Mathematics, 2000, PRINC STAND SCH MATH National Council of Teachers of Mathematics, 2006, CURR FOC POINTS PREK National Governors Association Center for Best Practices & the Council of Chief State School Officers, 2010, KEY SHIFTS MATH National Mathematics Advisory Panel, 2008, FDN SUCC FIN REP NAT Parker RI, 2011, BEHAV MODIF, V35, P303, DOI 10.1177/0145445511399147 Peterson S. K., 1988, LEARNING DISABILITIE, V4, P52 Poling A., 1995, FUNDAMENTALS BEHAV A Rice C., 2009, MORBIDITY MORTALITY U.S. Department of Education, 2002, NO CHILD LEFT DESKT Witzel B. S., 2003, LEARNING DISABILITIE, V3, P49, DOI DOI 10.1111/1540-5826.00068 NR 30 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2015 VL 50 IS 2 BP 223 EP 236 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI8JX UT WOS:000355019700008 ER PT J AU Ulke-Kurkcuoglu, B Bozkurt, F Cuhadar, S AF Ulke-Kurkcuoglu, Burcu Bozkurt, Funda Cuhadar, Selmin TI Effectiveness of Instruction Performed through Computer-Assisted Activity Schedules on On-Schedule and Role-Play Skills of Children with Autism Spectrum Disorder SO EDUCATIONAL SCIENCES-THEORY & PRACTICE LA English DT Article DE Autism spectrum disorder; Activity schedules; Role-play skills; Computer assisted; On-schedule ID PHOTOGRAPHIC ACTIVITY SCHEDULES; PRETEND PLAY; CHALLENGING BEHAVIOR; INCREASING PLAY; LEISURE SKILLS; DISABILITIES; ENGAGEMENT; TASK; CLASSROOM AB This study aims to investigate the effectiveness of the instruction process provided through computer-assisted activity schedules in the instruction of on-schedule and role-play skills to children with autism spectrum disorder. Herein, a multiple probe design with probe conditions across participants among single subject designs was used. Four children aged between four and ten participated in the study. The findings of the study showed that the instruction process provided through computer-assisted activity schedules has an effect upon the acquisition, maintenance, and generalization of the on-schedule and role-play skills of the children participating in the study. With respect to the social validity findings of the study, families and teachers gave positive opinions about the instruction process. In this paper, the findings obtained from the study are discussed and suggestions are made regarding implications and future research. C1 [Ulke-Kurkcuoglu, Burcu] Anadolu Univ, Res Inst Handicapped, TR-26470 Eskisehir, Turkey. [Bozkurt, Funda] Anadolu Univ, Fac Educ, Dept Special Educ, TR-26470 Eskisehir, Turkey. [Cuhadar, Selmin] Trakya Univ, Fac Educ, Dept Special Educ, Edirne, Turkey. RP Ulke-Kurkcuoglu, B (reprint author), Anadolu Univ, Res Inst Handicapped, Yunus Emre Campus, TR-26470 Eskisehir, Turkey. EM bulkekurkcuoglu@anadolu.edu.tr; fundab@anadolu.edu.tr; selmincuhadar@trakya.edu.tr CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Banda DR, 2008, EDUC TRAIN DEV DISAB, V43, P324 Barton E. E., 2012, YOUNG EXCEPTIONAL CH, V15, P5 Barton EE, 2010, INFANT YOUNG CHILD, V23, P247, DOI 10.1097/IYC.0b013e3181f22072 Barton EE, 2008, TOP EARLY CHILD SPEC, V28, P109, DOI 10.1177/0271121408318799 Betz A, 2008, J APPL BEHAV ANAL, V41, P237, DOI 10.1901/jaba.2008.41-237 BILLINGSLEY F, 1980, BEHAV ASSESS, V2, P229 Birkan B., 2013, OZEL EGITIM DERGISI, V14, P61 Bryan LC, 2000, J AUTISM DEV DISORD, V30, P553, DOI 10.1023/A:1005687310346 Carlile KA, 2013, EDUC TREAT CHILD, V36, P33 Cihak DF, 2011, RES AUTISM SPECT DIS, V5, P433, DOI 10.1016/j.rasd.2010.06.006 Cuhadar S, 2011, EDUC TRAIN AUTISM DE, V46, P386 Dauphin M, 2004, J POSIT BEHAV INTERV, V6, P238, DOI 10.1177/10983007040060040501 Haney M. R., 2013, UNDERSTANDING CHILDR Hobson JA, 2013, BRIT J DEV PSYCHOL, V31, P114, DOI 10.1111/j.2044-835X.2012.02083.x Kimball J., 2003, TEACHING EXCEPTIONAL, V36, P40 Kimball J., 2004, ED TREATMENT CHILDRE, V27, P280 Kircaali-Iftar G., 2012, OTIZM SPEKTRUM BOZUK, P17 Kircaali-Iftar G., 2007, OTIZM SPEKTRUM BOZUK Koroglu E., 2001, PSIK HAST TAN SIN KI Koyama T, 2011, RES DEV DISABIL, V32, P2235, DOI 10.1016/j.ridd.2011.05.003 KRANTZ PJ, 1993, J APPL BEHAV ANAL, V26, P137, DOI 10.1901/jaba.1993.26-137 Lequia J, 2012, RES AUTISM SPECT DIS, V6, P480, DOI 10.1016/j.rasd.2011.07.008 Liber DB, 2008, J AUTISM DEV DISORD, V38, P312, DOI 10.1007/s10803-007-0395-z Lifter K, 2011, INFANT YOUNG CHILD, V24, P225, DOI 10.1097/IYC.0b013e31821e995c Lovaas O. I., 2003, TEACHING INDIVIDUALS MACDUFF GS, 1993, J APPL BEHAV ANAL, V26, P89, DOI 10.1901/jaba.1993.26-89 Machalicek W, 2009, RES AUTISM SPECT DIS, V3, P547, DOI 10.1016/j.rasd.2008.11.003 Massey NG, 2000, EDUC TRAIN MENT RET, V35, P326 McClannahan L. E., 1999, ACTIVITY SCHEDULES C Morrison RS, 2002, J EARLY INTERVENTION, V25, P58, DOI 10.1177/105381510202500106 Naber FBA, 2008, J AUTISM DEV DISORD, V38, P857, DOI 10.1007/s10803-007-0454-5 Penington R. C., 2010, FOCUS AUTISM OTHER D, V25, P239 Phillips N., 2012, TEACHING PLAY CHILDR, V2nd Pierce JM, 2013, INT J DISABIL DEV ED, V60, P253, DOI 10.1080/1034912X.2013.812191 Rehfeldt RA, 2004, J APPL BEHAV ANAL, V37, P115, DOI 10.1901/jaba.2004.37-115 Rutherford MD, 2007, J AUTISM DEV DISORD, V37, P1024, DOI 10.1007/s10803-006-0240-9 Stromer R., 2006, FOCUS AUTISM OTHER D, V21, P14, DOI 10.1177/10883576060210010301 Tawney J. W., 1984, SINGLE SUBJECT RES S Tekin-Iftar E., 2006, OZEL EGITIMDE YANLIS, V2nd Tekin-Iftar E., 2012, EGITIM DAVRANIS BILI, P217 Wolfberg P. J., 1999, PLAY IMAGINATION CHI Wong C., 2014, EVIDENCE BASED PRACT NR 43 TC 0 Z9 0 PU EDAM PI ISTANBUL PA KISIKLI MH ALEMDAG CD YAN YOL SK, SBK IS MERKEZI NO 5, KAT 1 USKUDAR, ISTANBUL, 81190, TURKEY SN 1303-0485 EI 2148-7561 J9 EDUC SCI-THEOR PRACT JI Educ. Sci.-Theory Pract. PD JUN PY 2015 VL 15 IS 3 BP 671 EP 689 PG 19 WC Education & Educational Research SC Education & Educational Research GA CI2VK UT WOS:000354605300010 ER PT J AU Akmanoglu, N Kurt, O Kapan, A AF Akmanoglu, Nurgul Kurt, Onur Kapan, Alper TI Comparison of Simultaneous Prompting and Constant Time Delay Procedures in Teaching Children with Autism the Responses to Questions about Personal Information SO EDUCATIONAL SCIENCES-THEORY & PRACTICE LA English DT Article DE Autism spectrum disorder; Errorless teaching; Simultaneous prompting; Constant time delay ID SKILLS; DISABILITIES; RETARDATION AB The aim of the current study was to compare simultaneous prompting (SP) and constant time delay (CTD) in terms of their effectiveness and efficiency in teaching children with autism how to respond to questions about personal information. The adapted alternating treatments model was used in the study. Three male students with autism aged 4, 6, and 9, respectively, were included in the study. The findings of the study did not indicate any significant difference in two students with respect to the effectiveness of SP and CTD procedures. On the other hand, SP was observed to create more positive results and lead to a higher level of learning for the third participant. According to the findings, SP was more effective for one participant with respect to all the parameters studied. While SP was more efficient in the other two subjects in terms of incorrect responses, the difference regarding the instructional time to criterion for these two subjects was at a minimal level in favor of SP. C1 [Akmanoglu, Nurgul; Kurt, Onur; Kapan, Alper] Anadolu Univ, Res Inst Individuals Disabil, Eskisehir, Turkey. RP Kurt, O (reprint author), Anadolu Univ, Res Inst Individuals Disabil, Eskisehir, Turkey. EM nakmanoglu@anadolu.edu.tr; onurk@anadolu.edu.tr; akapan@anadolu.edu.tr CR Akmanoglu N, 2004, EDUC TRAIN DEV DISAB, V39, P326 Akmanoglu-Uludag N., 2005, EDUC TRAIN DEV DISAB, V40, P401 BILLINGSLEY F, 1980, BEHAV ASSESS, V2, P229 Bozkurt F, 2005, EDUC TRAIN DEV DISAB, V40, P390 Browder D. M., 2000, INSTRUCTION 7 DISABI, V5th, P453 Dippi-Hoy C., 2004, J SPEC EDUC, V38, P144 Dogoe M, 2009, EDUC TRAIN DEV DISAB, V44, P177 Fetko KS, 1999, EDUC TRAIN MENT RET, V34, P318 Gast D. L., 2010, SINGLE SUBJECT RES M GAST DL, 1988, EDUC TRAIN MENT RET, V23, P117 GIBSON AN, 1992, TOP EARLY CHILD SPEC, V12, P247 Head K. 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PD JUN PY 2015 VL 15 IS 3 BP 723 EP 737 PG 15 WC Education & Educational Research SC Education & Educational Research GA CI2VK UT WOS:000354605300013 ER PT J AU Skaper, SD Facci, L Fusco, M della Valle, MF Zusso, M Costa, B Giusti, P AF Skaper, Stephen D. Facci, Laura Fusco, Mariella della Valle, Maria Federica Zusso, Morena Costa, Barbara Giusti, Pietro TI Reply to: "Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives" Inflammopharmacology DOI:10.1007/s10787-014-0202-3 SO INFLAMMOPHARMACOLOGY LA English DT Editorial Material DE Neuropathic pain; Palmitoylethanolamide; Micronization; Excipients ID AUTISM SPECTRUM DISORDERS; 2-ARACHIDONOYLGLYCEROL; FORMULATION; LUTEOLIN; CHILDREN AB This is a reply to a recently published Commentary: "Palmitoylethanolamide: problems regarding micronization, ultra-micronization and additives" Inflammopharmacology DOI:10.1007/s10787-014-0202-3RefTarget Address="10.1007/s10787-014-0202-3" TargetType="DOI", written in relation to our review article: Skaper SD, Facci L, Fusco M, della Valle MF, Zusso M, Costa B, Giusti P (2014) "Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain" Inflammopharmacology 22:79-94 DOI:10.1007/s10787-013-0191-7RefTarget Address="10.1007/s10787-013-0191-7" TargetType="DOI". We believe that the Commentary by Kriek contains a number of erroneous statements and misinterpretations of the published scientific/medical literature which our reply shall elaborate on. Further, the writer of the Commentary has a direct connection to a company, JP Russell Science Ltd that sells palmitoylethanolamide. The take-home message of our review remains as originally stated: "Collectively, the findings presented here propose that palmitoylethanolamide merits further consideration as a disease-modifying agent for controlling inflammatory responses and related chronic and neuropathic pain". C1 [Skaper, Stephen D.; Facci, Laura; Zusso, Morena; Giusti, Pietro] Univ Padua, Padua, Italy. [Fusco, Mariella] Epitech Grp Srl, Sci Informat & Documentat Ctr, Saccolongo, PD, Italy. [della Valle, Maria Federica] Innovet Italia Srl, CeDIS Sci Informat & Documentat Ctr, Saccolongo, PD, Italy. [Costa, Barbara] Univ Milano Bicocca, Dept Biotechnol & Biosci, Milan, Italy. RP Skaper, SD (reprint author), Univ Padua, Padua, Italy. 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This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. MethodsParents of all Swedish 9-year-old twins born between 1992 and 2001 (n=19,130) underwent a telephone interview designed to screen for child psychiatric disorders, including ASD. To ensure full coverage of child psychiatric disorders, data were also retrieved from population-based health registers. We investigated the coexistence of eight psychiatric disorders known to coexist with ASDs in probands and their co-twins. ResultsHalf of the individuals with ASDs (50.3%) had four or more coexisting disorders and only 4% did not have any concomitant disorder. The healthy co-twin' in ASD discordant monozygotic twin pairs was very often (79% of boys and 50% of girls) affected by at least one non-ASD disorder. The corresponding figures for ASD discordant dizygotic twin pairs were significantly lower (46% of males and 30% of females). ConclusionsDetailed phenotypic descriptions including symptoms of problems associated with a wide range of child psychiatric disorders may aid in unraveling the genetic architecture of ASD and should guide the development of intervention strategies addressing each problem type specifically. C1 [Lundstrom, Sebastian; Kerekes, Nora; Anckarsater, Henrik] Univ Gothenburg, Ctr Eth Law & Mental Hlth, S-43141 Molndal, Sweden. [Lundstrom, Sebastian; Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Lundstrom, Sebastian; Kerekes, Nora] Swedish Prison & Probat Serv, R&D Unit, Gothenburg, Sweden. [Reichenberg, Abraham] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Reichenberg, Abraham] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Melke, Jonas] Univ Gothenburg, Dept Pharmacol, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden. [Rastam, Maria] Lund Univ, Dept Clin Sci Child & Adolescent Psychiat, Lund, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Lundstrom, S (reprint author), Univ Gothenburg, Ctr Eth Law & Mental Hlth, Wallins Gatan 8, S-43141 Molndal, Sweden. EM sebastian.lundstrom@neuro.gu.se FU Swedish Council for Working Life; Research Council of the Swedish National Alcohol Monopoly; Soderstrom-Konigska Foundation; ALF; Swedish Research Council FX The CATSS study was supported by the Swedish Council for Working Life, the Research Council of the Swedish National Alcohol Monopoly, Soderstrom-Konigska Foundation, and the funds under the ALF agreement and the Swedish Research Council. The funding sources had no involvement in study design, collection, analysis, interpretation of the data, and were not involved in the decision to submit this paper for publication. The authors have declared that they have no competing or potential conflicts of interest. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Anckarsater H, 2011, TWIN RES HUM GENET, V14, P495, DOI 10.1375/twin.14.6.495 Antshel KM, 2011, J DEV BEHAV PEDIATR, V32, P439, DOI 10.1097/DBP.0b013e318222355d Baird G, 2006, LANCET, V368, P210, DOI 10.1016/S0140-6736(06)69041-7 Bakkaloglu B, 2008, AM J HUM GENET, V82, P165, DOI 10.1016/j.ajhg.2007.09.017 Ballif BC, 2007, NAT GENET, V39, P1071, DOI 10.1038/ng2107 Belloso JM, 2007, EUR J HUM GENET, V15, P711, DOI 10.1038/sj.ejhg.5201824 Ben-Itzchak E, 2007, RES DEV DISABIL, V28, P287, DOI 10.1016/j.ridd.2006.03.002 Betancur C, 2011, BRAIN RES, V1380, P42, DOI 10.1016/j.brainres.2010.11.078 Coleman M., 2012, THE AUTISMS Cubo E, 2011, AN PEDIATR, V75, P40, DOI 10.1016/j.anpedi.2011.01.008 FOLSTEIN S, 1977, J CHILD PSYCHOL PSYC, V18, P297, DOI 10.1111/j.1469-7610.1977.tb00443.x Geschwind DH, 2011, TRENDS COGN SCI, V15, P409, DOI 10.1016/j.tics.2011.07.003 Gillberg C, 2010, RES DEV DISABIL, V31, P1543, DOI 10.1016/j.ridd.2010.06.002 Gillberg C, 2000, ACTA PSYCHIAT SCAND, V102, P321, DOI 10.1034/j.1600-0447.2000.102005321.x Hallett V, 2010, AM J PSYCHIAT, V167, P809, DOI 10.1176/appi.ajp.2009.09070990 Hansson SL, 2005, BRIT J PSYCHIAT, V187, P262, DOI 10.1192/bjp.187.3.262 Idring S, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0041280 Kerekes N., 2014, PEERJ, V22, pe359 Kopp S, 2010, J ATTEN DISORD, V14, P167, DOI 10.1177/1087054709332458 Larson T, 2013, BMC PSYCHIATRY, V13, DOI 10.1186/1471-244X-13-233 Larson T, 2010, BMC PSYCHIATRY, V10, DOI 10.1186/1471-244X-10-1 Leblond CS, 2012, PLOS GENET, V8, DOI 10.1371/journal.pgen.1002521 Lichtenstein P, 2010, AM J PSYCHIAT, V167, P1357, DOI 10.1176/appi.ajp.2010.10020223 Lundstrom S., 2013, J AUTISM DEV DISORDE Neale BM, 2012, NATURE, V485, P242, DOI 10.1038/nature11011 O'Roak BJ, 2011, NAT GENET, V43, P585, DOI 10.1038/ng.835 Pettersson E, 2013, J CHILD PSYCHOL PSYC, V54, P1356, DOI 10.1111/jcpp.12113 Pinto D, 2010, NATURE, V466, P368, DOI 10.1038/nature09146 Posthuma D, 2013, CURR OPIN NEUROL, V26, P111, DOI 10.1097/WCO.0b013e32835f19c3 Ronald A, 2011, AM J MED GENET B, V156B, P255, DOI 10.1002/ajmg.b.31159 Ronald A, 2008, J CHILD PSYCHOL PSYC, V49, P535, DOI 10.1111/j.1469-7610.2007.01857.x Rosenberg RE, 2009, ARCH PEDIAT ADOL MED, V163, P907, DOI 10.1001/archpediatrics.2009.98 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Stein MB, 2011, BIOL PSYCHIAT, V69, P825, DOI 10.1016/j.biopsych.2010.11.008 Strauss KA, 2006, NEW ENGL J MED, V354, P1370, DOI 10.1056/NEJMoa052773 Vernes SC, 2008, NEW ENGL J MED, V359, P2337, DOI 10.1056/NEJMoa0802828 Wang K, 2009, NATURE, V459, P528, DOI 10.1038/nature07999 Weiss LA, 2008, NEW ENGL J MED, V358, P667, DOI 10.1056/NEJMoa075974 Weiss LA, 2009, NATURE, V461, P802, DOI 10.1038/nature08490 NR 40 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUN PY 2015 VL 56 IS 6 BP 702 EP 710 DI 10.1111/jcpp.12329 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CI0XY UT WOS:000354464300011 PM 25279993 ER PT J AU Helles, A Gillberg, CI Gillberg, C Billstedt, E AF Helles, Adam Gillberg, Carina I. Gillberg, Christopher Billstedt, Eva TI Asperger syndrome in males over two decades: stability and predictors of diagnosis SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Asperger syndrome; diagnostic stability; autism spectrum disorder; pervasive developmental disorder; males; longitudinal study ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; DSM-IV-TR; CHILDHOOD; CHILDREN; SYMPTOMS; CRITERIA; ADULTS; INDIVIDUALS; ADOLESCENCE AB ObjectiveTo examine the diagnostic stability of a childhood diagnosis of Asperger Syndrome (AS) into adulthood in a prospective longitudinal study, and identify the predictors of stability. MethodsOne hundred males with AS diagnosed in childhood (T0) according to Gillberg's AS criteria, were followed up prospectively into adulthood over an average of 19years (range 13-26years). Fifty males (mean age 30years) participated in this second follow-up (T2) of the cohort. Seventy-six had participated in a previous follow-up (T1) at mean age 22years (47 participated in both follow-ups). Diagnosis at T2 was assessed using three sets of diagnostic criteria (Gillberg's AS criteria, DSM-IV Pervasive Developmental Disorder (PDD) and DSM-5 Autism Spectrum Disorder (ASD) criteria) and compared to previous assessments. Background predictors of diagnostic stability were analyzed. General functioning at T2 was assessed and compared to T1. ResultsThere was a decline in the stability of AS diagnosis over time, the rate dropping from 82% at T1 to 44% at T2, when using the Gillberg criteria. There was also a significant decrease in the rate of cases fulfilling any PDD diagnosis according to the DSM-IV, from 91% at T1 to 76% at T2 in the 47 cases followed up twice. Severity of autism spectrum symptoms at T1 was the main predictor of diagnostic stability at T2. Twenty percent of those meeting criteria for a PDD diagnosis according to DSM-IV, did not meet DSM-5 ASD criteria although they had marked difficulties in everyday life. ConclusionAsperger Syndrome, when considered as an ASD/PDD diagnosis, was fairly stable into adulthood, but there was a significant increase over time in cases no longer meeting criteria for an ASD diagnosis according to the DSM-IV, or AS according to the Gillberg criteria. Cases with a stable diagnosis showed significantly more core ASD symptoms in adolescence/young adulthood. C1 [Helles, Adam; Gillberg, Carina I.; Gillberg, Christopher; Billstedt, Eva] Gothenburg Univ, Gillberg Neuropsychiat Ctr, Inst Neurosci & Physiol, Sahlgrenska Acad, S-41119 Gothenburg, Sweden. RP Helles, A (reprint author), Gothenburg Univ, Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. EM adam.helles@gnc.gu.se FU Centre for Research and Development in Gavleborg; Child and Adolescent Habilitation Clinic in Gavle; VG Region Scientific Fund; Jerring Fund; Wilhelm and Martina Lundgren Foundation; Petter Silfverskiold Foundation; Golje Foundation; AnnMarie and Per Ahlqvist Foundation; Swedish Child Neuropsychiatry Science Foundation; Gillberg Neuropsychiatry Centre FX The study was supported by funding from: Centre for Research and Development in Gavleborg and the Child and Adolescent Habilitation Clinic in Gavle, VG Region Scientific Fund, the Jerring Fund, Wilhelm and Martina Lundgren Foundation, Petter Silfverskiold Foundation, Golje Foundation, AnnMarie and Per Ahlqvist Foundation, the Swedish Child Neuropsychiatry Science Foundation, and the Gillberg Neuropsychiatry Centre. The authors have declared that they have no potential or competing conflicts of interest. 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Child Psychol. Psychiatry PD JUN PY 2015 VL 56 IS 6 BP 711 EP 718 DI 10.1111/jcpp.12334 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CI0XY UT WOS:000354464300012 PM 25283685 ER PT J AU Zuckerman, KE Lindly, OJ Sinche, BK AF Zuckerman, Katharine Elizabeth Lindly, Olivia Jasmine Sinche, Brianna Kathleen TI Parental Concerns, Provider Response, and Timeliness of Autism Spectrum Disorder Diagnosis SO JOURNAL OF PEDIATRICS LA English DT Article ID UNITED-STATES; DEVELOPMENTAL CONCERNS; IDENTIFY CHILDREN; MEDICAL HOME; CARE; AGE; FAMILIES; SERVICES; DISPARITIES; RISK AB Objectives To assess differences between child age at first parental concern and age at first parental discussion of concerns with a health care provider among children with autism spectrum disorder (ASD) vs those with intellectual disability/developmental delay (ID/DD), and to assess whether provider response to parental concerns is associated with delays in ASD diagnosis. Study design Using nationally representative data from the 2011 Survey of Pathways to Diagnosis and Treatment, we compared child age at parent's first developmental concern with age at first discussion of concerns with a provider, and categorized provider response as proactive or reassuring/passive, among 1420 children with ASD and 2098 children with ID/DD. In the children with ASD, we tested the association between provider response type and years of diagnostic delay. Results Compared with children with ID/DD, children with ASD were younger when parents first had concerns and first discussed those concerns with a provider. Compared with parents of children with ID/DD, parents of children with ASD were less likely to receive proactive responses to their concerns and more likely to receive reassuring/passive responses. Among children with ASD, those with more proactive provider responses to concerns had shorter delays in ASD diagnosis compared with those with passive/reassuring provider responses. Conclusion Although parents of children with ASD have early concerns, delays in diagnosis are common, particularly when providers' responses are reassuring or passive, highlighting the need for targeted improvements in primary care. C1 [Zuckerman, Katharine Elizabeth; Lindly, Olivia Jasmine; Sinche, Brianna Kathleen] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Div Gen Pediat, Portland, OR 97239 USA. [Lindly, Olivia Jasmine] Oregon State Univ, Sch Publ Hlth, Corvallis, OR 97331 USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, CDRC 3203,707 SW Gaines Rd, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU Medical Research Foundation of Oregon; National Institute of Mental Health [1K23MH095828] FX Funded by the Medical Research Foundation of Oregon. K.Z. was funded by the National Institute of Mental Health (1K23MH095828). The authors declare no conflicts of interest. 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Pediatr. PD JUN PY 2015 VL 166 IS 6 BP 1431 EP + DI 10.1016/j.jpeds.2015.03.007 PG 10 WC Pediatrics SC Pediatrics GA CI8JI UT WOS:000355018200022 PM 25888348 ER PT J AU Kirsten, TB Queiroz-Hazarbassanov, N Bernardi, MM Felicio, LF AF Kirsten, Thiago B. Queiroz-Hazarbassanov, Nicolle Bernardi, Maria M. Felicio, Luciano F. TI Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure SO LIFE SCIENCES LA English DT Article DE Autistic-like effects; Maternal immune activation; Prenatal infection; Ultrasonic vocalizations; Gestation ID DEFICIT HYPERACTIVITY DISORDER; NEUROTROPHIC FACTOR; SPECTRUM DISORDERS; ULTRASONIC VOCALIZATION; INDUCED TERATOGENICITY; MATERNAL SEPARATION; MENTAL-RETARDATION; IMMUNE CHALLENGE; AMNIOTIC-FLUID; PROTEIN-LEVELS AB Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism. We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia. Materials and methods: We evaluated the effects of LPS and zinc on female reproductive performance. Communication, which is impaired in autism, was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker. Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction. Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls. Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments. The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway. (c) 2015 Elsevier Inc. All rights reserved. C1 [Kirsten, Thiago B.; Queiroz-Hazarbassanov, Nicolle; Felicio, Luciano F.] Univ Sao Paulo, Dept Pathol, Sch Vet Med, BR-05508270 Sao Paulo, SP, Brazil. [Kirsten, Thiago B.; Bernardi, Maria M.] Univ Estadual Paulista, Environm & Expt Pathol, BR-04026002 Sao Paulo, SP, Brazil. RP Kirsten, TB (reprint author), Univ Sao Paulo, Dept Pathol, Sch Vet Med, Av Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo, SP, Brazil. EM thik@outlook.com FU Sao Paulo Research Foundation (FAPESP) [2012/07007-8]; Sao Paulo Research Foundation [2009/51886-3]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [CAPES/Premio 1029/2014] FX This research was supported by the Sao Paulo Research Foundation (FAPESP grant 2012/07007-8 and thematic grant 2009/51886-3) and the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/Premio 1029/2014). 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PD JUN 1 PY 2015 VL 130 BP 12 EP 17 DI 10.1016/j.lfs.2015.02.027 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CI4XC UT WOS:000354756200003 PM 25817235 ER PT J AU Kiep, M Spek, AA Hoeben, L AF Kiep, Michelle Spek, Annelies A. Hoeben, Lisette TI Mindfulness-Based Therapy in Adults with an Autism Spectrum Disorder: Do Treatment Effects Last? SO MINDFULNESS LA English DT Article DE ASD; Mindfulness; Rumination; Psychological and physical well-being; Depression ID COGNITIVE-BEHAVIOR THERAPY; PERVASIVE DEVELOPMENTAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; PSYCHIATRIC-DISORDERS; ASPERGER SYNDROME; STRESS REDUCTION; MEDITATION; DEPRESSION; RUMINATION; ANXIETY AB Individuals with autism spectrum disorders (ASD) have a higher incidence of comorbid disorders in comparison with other patient groups. Empirical evidence on treatments targeting comorbid symptoms is however scarce. Earlier research showed that mindfulness-based therapy for individuals on the autism spectrum (MBT-AS) is effective in reducing symptoms of depression, anxiety, and rumination. In the current study, it was examined whether MBT-AS is effective in alleviating a variety of psychosomatic symptoms and whether these effects were still evident after 9 weeks. Fifty participants took part in a nine-week MBT-AS training. Self-reported symptoms were evaluated at three intervals: (1) before the first session, (2) after the last session, and (3) 9 weeks after the last session. Results showed that symptoms of anxiety, depression, agoraphobia, somatization, inadequacy in thinking and acting, distrust and interpersonal sensitivity, sleeping problems, and general psychological and physical well-being declined significantly during intervention. Positive affect increased, and rumination declined significantly during treatment. Hostility symptoms did not decline significantly during treatment. All symptoms remained stable between post intervention and follow-up. This would seem to indicate that MBT-AS is effective in reducing psychological and physical symptoms and keeping them stable over the longer term. Furthermore, the outcome indicates that rumination is an important mediating factor. In conclusion, MBT-AS appears to be an effective method for reducing a variety of symptoms, and treatment gains remain stable over the longer term. C1 [Kiep, Michelle; Spek, Annelies A.; Hoeben, Lisette] GGzE, Adult Autism Ctr, NL-5626 AB Eindhoven, Netherlands. RP Kiep, M (reprint author), GGzE, Adult Autism Ctr, POB 1418, NL-5626 AB Eindhoven, Netherlands. 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C. Castro, V. M. Blumenthal, S. R. Rosenfield, H. R. Murphy, S. N. Fava, M. Erb, J. L. Churchill, S. E. Kaimal, A. J. Doyle, A. E. Robinson, E. B. Smoller, J. W. Kohane, I. S. Perlis, R. H. TI Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system SO MOLECULAR PSYCHIATRY LA English DT Article ID PREGNANCY; DEPRESSION AB Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression. C1 [Clements, C. C.; Castro, V. M.; Blumenthal, S. R.; Rosenfield, H. R.; Doyle, A. E.; Robinson, E. B.; Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Clements, C. C.; Blumenthal, S. R.; Rosenfield, H. R.; Doyle, A. E.; Smoller, J. W.; Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Castro, V. M.; Murphy, S. N.] Partners HealthCare Syst, Partners Res Comp, Constitut Ctr 1, Boston, MA USA. [Castro, V. M.; Murphy, S. N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Castro, V. M.; Murphy, S. N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Erb, J. L.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Churchill, S. E.] Partners HealthCare Syst, Informat Syst, Boston, MA USA. [Kaimal, A. J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Robinson, E. B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genom Unit, Boston, MA 02114 USA. [Kohane, I. S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Psychiat, Simches Res Bldg MGH,185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org FU National Institute of Mental Health [5R01MH100286-02]; NIMH [R01MH086026]; Stanley Center for Psychiatric Research; NIH/National Library of Medicine [2U54LM008748] FX This work was supported through funding from the National Institute of Mental Health (5R01MH100286-02). Dr Perlis is supported by NIMH R01MH086026 and by the Stanley Center for Psychiatric Research. The i2b2 platform (PI: Kohane) is supported by award number 2U54LM008748 from the NIH/National Library of Medicine. We express our gratitude to the staff at the Massachusetts Registry of Vital Records and Statistics including Kevin Foster and Dean DiMartino. 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Psychiatr. PD JUN PY 2015 VL 20 IS 6 BP 727 EP 734 DI 10.1038/mp.2014.90 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CI6SB UT WOS:000354890200011 PM 25155880 ER PT J AU Bale, TL AF Bale, Tracy L. TI Epigenetic and transgenerational reprogramming of brain development SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID HIGH-FAT DIET; EARLY-LIFE STRESS; MATERNAL IMMUNE ACTIVATION; AUTISM SPECTRUM DISORDERS; PITUITARY-ADRENAL AXIS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2; CORTICOTROPIN-RELEASING HORMONE; GLUCOCORTICOID-RECEPTOR GENE; CENTRAL-NERVOUS-SYSTEM; PRENATAL STRESS AB Neurodevelopmental programming - the implementation of the genetic and epigenetic blueprints that guide and coordinate normal brain development - requires tight regulation of transcriptional processes. 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Rev. Neurosci. PD JUN PY 2015 VL 16 IS 6 BP 332 EP 344 DI 10.1038/nrn3818 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CI5PJ UT WOS:000354810000007 PM 25921815 ER PT J AU Lenz, KM McCarthy, MM AF Lenz, Kathryn M. McCarthy, Margaret M. TI A Starring Role for Microglia in Brain Sex Differences SO NEUROSCIENTIST LA English DT Review DE microglia; development; sex differences; hormone; inflammation; immune; cytokine; sex ID AUTISM SPECTRUM DISORDERS; PRENATAL IMMUNE CHALLENGE; PREGNANCY HORMONE ESTRIOL; ESTROGEN-RECEPTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; DEVELOPING RAT-BRAIN; MAST-CELLS; CEREBRAL-CORTEX; X-CHROMOSOME; HIPPOCAMPAL NEUROGENESIS AB Microglia, the resident innate immune cells in the brain, have long been understood to be crucial to maintenance in the nervous system, by clearing debris, monitoring for infiltration of infectious agents, and mediating the brain's inflammatory and repair response to traumatic injury, stroke, or neurodegeneration. A wave of new research has shown that microglia are also active players in many basic processes in the healthy brain, including cell proliferation, synaptic connectivity, and physiology. Microglia, both in their capacity as phagocytic cells and via secretion of many neuroactive molecules, including cytokines and growth factors, play a central role in early brain development, including sexual differentiation of the brain. In this review, we present the vast roles microglia play in normal brain development and how perturbations in the normal neuroimmune environment during development may contribute to the etiology of brain-based disorders. There are notable differences between microglia and neuroimmune signaling in the male and female brain throughout the life span, and these differences may contribute to the vast differences in the incidence of neuropsychiatric and neurological disorders between males and females. C1 [Lenz, Kathryn M.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Lenz, Kathryn M.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. [McCarthy, Margaret M.] Univ Maryland, Sch Med, Dept Pharmacol & Program Neurosci, Baltimore, MD 21201 USA. RP Lenz, KM (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave,Room 45, Columbus, OH 43210 USA. EM lenz.56@osu.edu FU National Insitute for Neurological Disorders and Stroke [F32NS076327]; National Institute for Mental Health [R01MH052716]; Ohio State University startup funds FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Insitute for Neurological Disorders and Stroke (F32NS076327), the National Institute for Mental Health (R01MH052716), and The Ohio State University startup funds. 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10.1016/S0168-9525(01)02446-5 Zhan Y, 2014, NAT NEUROSCI, V17, P400, DOI 10.1038/nn.3641 Zhong Y, 2010, BRAIN BEHAV IMMUN, V24, P874, DOI 10.1016/j.bbi.2010.01.007 NR 142 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD JUN PY 2015 VL 21 IS 3 BP 306 EP 321 DI 10.1177/1073858414536468 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI5DR UT WOS:000354773600011 PM 24871624 ER PT J AU Suarez, MA AF Suarez, Michelle Ann TI Multicomponent Treatment for Food Selectivity in Children: Description and Case Report SO NUTRITION IN CLINICAL PRACTICE LA English DT Article DE pediatrics; feeding and eating disorders of childhood; feeding behavior; food preferences; food selectivity ID PEDIATRIC FEEDING DISORDERS; AUTISM SPECTRUM DISORDERS; INTERVENTION; MOTHERS; MEAL AB Background: Food selectivity is common in children with and without developmental disabilities and can have negative implications for nutrition intake and family quality of life. The evidence base for effective treatment protocols is still developing. Methods: The purpose of this study was to describe a pilot, multicomponent treatment protocol for food selectivity and present several case examples using a retrospective chart review. Elements in the treatment manual included sensory integration and behavioral modification strategies, including systematic desensitization. Also, parents were educated on factors associated with food selectivity and strategies for increasing food acceptance during family meals. Results: Four children with food selectivity demonstrated increased food acceptance of previously refused foods. Incidence of negative behaviors, including gagging, vomiting, and aggressive behavior (eg, hitting, batting away spoon), during clinical meals was also evaluated. No aggressive behavior or vomiting was observed during treatment sessions, and gagging on foods at initial introduction was minimal. Conclusions: This descriptive study and case review provides information to inform treatment of food selectivity and may provide a catalyst for larger scale clinical trials. C1 [Suarez, Michelle Ann] Western Michigan Univ, Kalamazoo, MI 49008 USA. RP Suarez, MA (reprint author), Western Michigan Univ, CHHS, 1903 W Michigan Ave, Kalamazoo, MI 49008 USA. 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Clin. Pract. PD JUN PY 2015 VL 30 IS 3 BP 425 EP 431 DI 10.1177/0884533614553638 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CI5DN UT WOS:000354773200016 PM 25378354 ER PT J AU Shen, TJ Ji, F Yuan, ZQ Jiao, JW AF Shen, Tianjin Ji, Fen Yuan, Zengqiang Jiao, Jianwei TI CHD2 is Required for Embryonic Neurogenesis in the Developing Cerebral Cortex SO STEM CELLS LA English DT Article DE Embryonic stem cells; Progenitor cells; Neural differentiation; Proliferation; Self-renewal; Neural stem cell ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; PROGENITOR CELLS; GENE-EXPRESSION; SELF-RENEWAL; STEM-CELLS; REST; DIFFERENTIATION; PLURIPOTENCY; REPRESSOR AB Chromodomain helicase DNA-binding protein 2 (CHD2) has been associated with a broad spectrum of neurodevelopmental disorders, such as autism spectrum disorders and intellectual disability. However, it is largely unknown whether and how CHD2 is involved in brain development. Here, we demonstrate that CHD2 is predominantly expressed in Pax6(+) radial glial cells (RGs) but rarely expressed in Tbr2(+) intermediate progenitors (IPs). Importantly, the suppression of CHD2 expression inhibits the self-renewal of RGs and increases the generation of IPs and the production of neurons. CHD2 mediates these functions by directly binding to the genomic region of repressor element 1-silencing transcription factor (REST), thereby regulating the expression of REST. Furthermore, the overexpression of REST rescues the defect in neurogenesis caused by CHD2 knockdown. Taken together, these findings demonstrate an essential role of CHD2 in the maintenance of the RGs self-renewal levels, the subsequent generation of IPs, and neuronal output during neurogenesis in cerebral cortical development, suggesting that inactivation of CHD2 during neurogenesis might contribute to abnormal neurodevelopment. Stem Cells2015;33:1794-1806 C1 [Shen, Tianjin; Ji, Fen; Jiao, Jianwei] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China. [Yuan, Zengqiang] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China. [Shen, Tianjin] Univ Chinese Acad Sci, Beijing, Peoples R China. RP Jiao, JW (reprint author), Chinese Acad Sci, Inst Zool, Grp Neural Stem Cell & Neurogenesis, 1 Beichen West Rd, Beijing 100101, Peoples R China. EM jwjiao@ioz.ac.cn RI Jiao, Jianwei/I-1452-2013 OI Jiao, Jianwei/0000-0002-7893-0721 FU National Key Basic Research Program of China [2015CB964500, 2014CB964903, 2014CB964602]; National Science Foundation of China [31371477, 31300894]; Strategic Priority Research Program [XDA01020301] FX This work was supported by grants obtained from the National Key Basic Research Program of China (2015CB964500, 2014CB964903, and 2014CB964602), the National Science Foundation of China (31371477 and 31300894), and the Strategic Priority Research Program (XDA01020301). 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Evidence is mounting for the association between SLC25A12 variants (rs2056202 and rs2292813) and ASD risk, but the results are inconsistent. To clarify the effect of these two variants on ASD, a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to May 2014. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of association. A total of 775 cases, 922 controls, and 1289 families available from 8 studies concerning rs2056202, and 465 cases, 450 controls, and 1516 families available from 7 studies concerning rs2292813 were finally included. 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[Zhang, Zengyu] Hangzhou Normal Univ, Dept Paediat, Xiaoshan Hosp 1, Hangzhou, Zhejiang, Peoples R China. [Yu, Ke] Zhejiang Univ, Zhejiang California Int Nanosyst Inst, Hangzhou 310029, Zhejiang, Peoples R China. RP Liu, J (reprint author), Zhejiang Xiaoshan Hosp, Dept Clin Lab, Hangzhou 311202, Zhejiang, Peoples R China. EM xiaoshanry@163.com; yuke2009@gmail.com FU Xiaoshan Science and Technology Commission of Hangzhou City [2013303]; Health and Family Planning Commission of Zhejiang Province [2014kyB225] FX Grant sponsor: Xiaoshan Science and Technology Commission of Hangzhou City; Grant number: 2013303; Grant sponsor: Health and Family Planning Commission of Zhejiang Province; Grant number: 2014kyB225. 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Gai, Zhongtao TI Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE metabotropic glutamate receptor 7 gene (GRM7); autism spectrum disorders (ASDs); neuropsychiatric disorders ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COPY NUMBER VARIATION; RS3792452 POLYMORPHISM; AMYGDALA PLASTICITY; BIPOLAR DISORDER; VARIANTS; ASSOCIATION; SCHIZOPHRENIA; CHILDREN; BEHAVIOR AB GRM7, the gene encoding metabotropic glutamate receptor 7 (mGluR7), have been implicated in multiple neuropsychiatric disorders and shown to mediate excitatory synaptic neurotransmitter signaling and plasticity in the mammalian brain. Here we report a 303kb de novo deletion at band 3p26.1, disrupting five coding exons of GRM7 in a proband with autism spectrum disorder, and hyperactivity. Our exon transcriptome-mutation contingency index method shows that three of the exons within the breakpoint boundaries are under purifying selection and highly expressed in prenatal brain regions. Based on our results and a thorough review of the literature, we propose that haploinsufficiency of the GRM7 product (mGluR7) contributes to autism spectrum disorders and hyperactivity phenotype as seen in the patient described here. (c) 2015 Wiley Periodicals, Inc. C1 [Liu, Yi; Dong, Rui; Yang, Xiaomeng; Gai, Zhongtao] Shandong Univ, Pediat Res Inst, Qilu Childrens Hosp, Jinan 250022, Peoples R China. [Zhang, Yanqing; Zhao, Dongmei; Gai, Zhongtao] Shandong Univ, Pediat Hlth Care Inst, Qilu Childrens Hosp, Jinan 250022, Peoples R China. [Tammimies, Kristiina; Uddin, Mohammed; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. [Tammimies, Kristiina] Karolinska Inst, Ctr Neurodev Disorders, Karolinska Inst KIND, Pediat Neuropsychiat Unit,Dept Womens & Childrens, Stockholm, Sweden. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Scherer, SW (reprint author), Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada. EM stephen.scherer@sickkids.ca; gaizhongtaoi@sina.com FU GSK-CIHR FX The authors are grateful to the patients and their families for their contribution to the project. We would like to thank Shanghai Biotechnology Co, Shanghai Biochip National Engineering Research Center for technical support, as well as The Centre for Applied Genomics at the Hospital for Sick Children and the University of Toronto McLaughlin Centre. S.W.S. is supported by the GSK-CIHR Endowed Chair in Genome Sciences. 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J. Med. Genet. B PD JUN PY 2015 VL 168 IS 4 BP 258 EP 264 DI 10.1002/ajmg.b.32306 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA CI3IA UT WOS:000354640100004 PM 25921429 ER PT J AU Sokhadze, T El-Baz, AS Tasman, A Sears, L Wang, Y Casanova, MF AF Sokhadze, Tato El-Baz, Ayman S. Tasman, Allan Sears, Lonnie Wang, Yao Casanova, Manuel F. TI Combined Neuromodulation Therapy Integrating rTMS and EEG Biofeedback for Treatment of Children with Autism Spectrum Disorder SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Meeting Abstract DE Transcranial magnetic stimulation; Autism spectrum disorder; Prefrontal EEG biofeedback; Dorso-lateral prefrontal cortex EM tato.sokhadze@louisville.edu NR 0 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 EI 1573-3270 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD JUN PY 2015 VL 40 IS 2 BP 120 EP 120 PG 1 WC Psychology, Clinical SC Psychology GA CI1JA UT WOS:000354498700012 ER PT J AU Wang, Y Hensley, MK Casanova, MF Sokhadze, E AF Wang, Yao Hensley, Marie K. Casanova, Manuel F. Sokhadze, Estate (Tato) TI Prefrontal rTMS Treatment Effects on Autonomic Activity in Children with Autism SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Meeting Abstract DE Autism spectrum disorder; Transcranial magnetic stimulation; Children; Autonomic activity; Heart rate variability EM wangyao8488@gmail.com NR 0 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 EI 1573-3270 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD JUN PY 2015 VL 40 IS 2 BP 122 EP 122 PG 1 WC Psychology, Clinical SC Psychology GA CI1JA UT WOS:000354498700016 ER PT J AU Frederick, J Wang, Y Sokhadze, T Sears, L Tasman, A Casanova, MF AF Frederick, Jon Wang, Yao Sokhadze, Tato Sears, Lonnie Tasman, Allan Casanova, Manuel F. TI ERP and EEG Oscillations Study of Facial Expression Processing Deficits in Autism SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Meeting Abstract DE Event related potentials; Single trial induced EEG; Autism spectrum disorder; Emotional recognition EM psyphy2014@gmail.com NR 0 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 EI 1573-3270 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD JUN PY 2015 VL 40 IS 2 BP 129 EP 130 PG 2 WC Psychology, Clinical SC Psychology GA CI1JA UT WOS:000354498700031 ER PT J AU Hamilton, S AF Hamilton, Sheila TI Functional behavior assessment for people with autism: Making sense of senseless behavior SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Book Review CR GLASBERG BA, 2015, FUNCTIONAL BEHAV ASS NR 1 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0008-4174 EI 1911-9828 J9 CAN J OCCUP THER JI Can. J. Occup. Ther. PD JUN PY 2015 VL 82 IS 3 BP 204 EP 204 DI 10.1177/0008417415583109 PG 1 WC Rehabilitation SC Rehabilitation GA CI2IW UT WOS:000354570900011 ER PT J AU De Rubeis, S Buxbaum, JD AF De Rubeis, Silvia Buxbaum, Joseph D. TI Recent Advances in the Genetics of Autism Spectrum Disorder SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Autism spectrum disorder; Autism risk genes; Exome sequencing; Copy number variation; De novo variation; Heritability ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; NEURODEVELOPMENTAL DISORDERS; INTELLECTUAL DISABILITY; SYNAPTIC DEFECTS; PATERNAL ORIGIN; HUMAN BRAIN; RISK; VARIANTS; GENES AB Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with high prevalence in the population and a pronounced male preponderance. ASD has a strong genetic basis, but until recently, a large fraction of the genetic factors contributing to liability was still unknown. Over the past 3 years, high-throughput next-generation sequencing on large cohorts has exposed a heterogeneous and complex genetic landscape and has revealed novel risk genes. 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TI New Genes for Focal Epilepsies with Speech and Language Disorders SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Epilepsy-aphasia spectrum; Speech; Language; Gene; Landau-Kleffner syndrome; Epileptic encephalopathy with continuous spike-wave during sleep; Benign childhood epilepsy with centro-temporal spikes; GRIN2A; RBFOX genes; Copy number variants; Dysarthria; Speech dyspraxia; Oromotor dyspraxia; Continuous spike-wave in slow sleep; Rolandic; Atypical benign partial epilepsy; Autosomal dominant rolandic epilepsy with speech dyspraxia ID LANDAU-KLEFFNER-SYNDROME; BENIGN CHILDHOOD EPILEPSY; NMDA RECEPTOR SUBUNITS; ELECTRICAL STATUS EPILEPTICUS; IDIOPATHIC ROLANDIC EPILEPSY; CENTRO-TEMPORAL SPIKES; CENTROTEMPORAL SPIKES; MICRODELETION SYNDROME; ACQUIRED APHASIA; INHERITED SPEECH AB The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20 % of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes. C1 [Turner, Samantha J.; Morgan, Angela T.; Scheffer, Ingrid E.] Univ Melbourne, Dept Paediat, Royal Childrens Hosp, Parkville, Vic 3052, Australia. [Turner, Samantha J.; Morgan, Angela T.] Murdoch Childrens Res Inst, Language & Literacy Grp, Parkville, Vic, Australia. 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Morgan has received grants from the National Health and Medical Research Council (Career Development Award) and the Australian Research Council (Discovery Project).Ingrid E. Scheffer has received grants from the NHMRC (CI, Program Grant 2011-2015), the NIH (PI, Centres without Walls funding "Epi4K" 2011-2015) and the ARC (Discovery Grant 2012-2014). 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Neurol. Neurosci. Rep. PD JUN PY 2015 VL 15 IS 6 AR 35 DI 10.1007/s11910-015-0554-0 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CI0WD UT WOS:000354459100007 PM 25921602 ER PT J AU Ben-Sasson, A Amit-Ben-Simhon, H Meyer, S AF Ben-Sasson, Ayelet Amit-Ben-Simhon, Hemda Meyer, Sonya TI Cross-parent reliability in rating ASD markers in infants SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE ASD; autism; cross-parent; infant; reliability; screening ID CHILD-BEHAVIOR CHECKLIST; SPECTRUM DISORDER; AUTISTIC TRAITS; DISCREPANCIES; AGREEMENT; TODDLERS AB Objective: To investigate the congruence and discrepancies between mother and father reports of early autism spectrum disorders (ASD) markers. Methods: Mothers (n = 80) and fathers (n = 78) of 12-month-old infants (55% boys) completed the first year inventory (FYI), an ASD norm-referenced screening questionnaire. Mothers also completed the Infant Toddler Social Emotional Assessment (ITSEA). Results: There were significant and moderate intra-class correlations between mother and father reports for most FYI factors. Fathers' median FYI social-communication domain score was almost twice that of mothers. Mann-Whitney tests indicated that fathers rated their child significantly higher than mothers on the four FYI social-communication factors and on the sensory processing factor. Linear weighted kappa analyses indicated poor agreement on gaze-related and reactivity FYI items. FYI social-communication and sensory-regulatory factors showed significant correlations with corresponding ITSEA scores. Conclusions: Social-communication markers pose a greater challenge for consistent report across parents than sensory-regulatory markers. C1 [Ben-Sasson, Ayelet; Amit-Ben-Simhon, Hemda; Meyer, Sonya] Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-30905 Haifa, Israel. [Amit-Ben-Simhon, Hemda] Child Dev Ctr Maccabi Haifa, Haifa, Israel. [Meyer, Sonya] Child Dev Ctr Maccabi Hod Hasharon, Tel Aviv, Israel. RP Ben-Sasson, A (reprint author), Univ Haifa, Fac Social Welf & Hlth Sci, Dept Occupat Therapy, IL-30905 Haifa, Israel. EM asasson@univ.haifa.ac.il FU European international reintegration grant [203715] FX This study has been supported by a European international reintegration grant (# 203715). 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PD JUN PY 2015 VL 18 IS 3 BP 155 EP 161 DI 10.3109/17518423.2013.800164 PG 7 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA CH7KZ UT WOS:000354216600003 PM 23924084 ER PT J AU Castro, S Pinto, A AF Castro, Susana Pinto, Ana TI Matrix for assessment of activities and participation: Measuring functioning beyond diagnosis in young children with disabilities SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Engagement; environment; functioning patterns; ICF-CY; measure ID INTERNATIONAL CLASSIFICATION; HEALTH; ISSUES AB Objective: (i) To study the functioning patterns of young children with disabilities compared with typically developing children, using a new ICF-CY based tool - the Matrix for Assessment of Activities and Participation; (ii) study the factors that predict these functioning patterns. Methods: The MAAP tool was administered to three groups of children: (i) with autism, (ii) with other types of disabilities and (iii) typically developing. Results: Cluster analysis showed that children group according to the severity of their functioning profile and not according to the diagnostic category in which they were classified. Multiple regression analysis showed that a model comprising the environmental factors and the level of engagement in different routines of the child is a good predictor of these children's functioning patterns. Conclusion: These results support a functional approach to disability instead of the traditional medical model approach, underlining the role of engagement and environment in determining functioning. C1 [Castro, Susana; Pinto, Ana] Univ Porto, Fac Psychol & Educ Sci, P-4200135 Oporto, Portugal. RP Castro, S (reprint author), Univ Porto, Fac Psychol & Educ Sci, Rua Alfredo Allen, P-4200135 Oporto, Portugal. EM susanacastro161@gmail.com FU Fundacao para a a Ciencia e Tecnologia (FCT) FX The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper. The authors wish to thank Fundacao para a a Ciencia e Tecnologia (FCT) for funding this study. 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PD JUN PY 2015 VL 18 IS 3 BP 177 EP 189 DI 10.3109/17518423.2013.806963 PG 13 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA CH7KZ UT WOS:000354216600006 PM 23869963 ER PT J AU Adolfsson, M Fleischer, AS AF Adolfsson, Margareta Fleischer, Ann Simmeborn TI Applying the ICF to identify requirements for students with Asperger syndrome in higher education SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Asperger syndrome; higher education; ICF; requirement; student; support ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; INTERNATIONAL CLASSIFICATION; CORE SETS; DISABILITY; HEALTH; CHILDREN; YOUTH; CY; INTERVENTION AB Higher education requires more than academic skills and everyday student-life can be stressful. Students with Asperger syndrome (AS) may need support to manage their education due to difficulties in social functioning. Objective: As preparation for the development of a structured tool to guide student and coordinator dialogues at Swedish universities, this study aimed to identify ICF categories that reflect requirements in everyday student-life for students with AS. Methods: Using descriptive qualitative approach, information in documents reflecting the perspectives of university students, international classifications, user/health organisations and education authorities were linked to ICF codes. Results: In total, 114 ICF categories were identified, most of which related to learning, tasks and demands, communication and interactions. Conclusion: Students with AS need varying accommodations to be successful in higher education. In the future, ICF-based code sets, including demands on student roles, can be used as checklists to describe functioning and needs for support. C1 [Adolfsson, Margareta; Fleischer, Ann Simmeborn] Jonkoping Univ, Sch Educ & Commun, CHILD, SE-55111 Jonkoping, Sweden. 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Neurorehabil. PD JUN PY 2015 VL 18 IS 3 BP 190 EP 202 DI 10.3109/17518423.2013.819947 PG 13 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA CH7KZ UT WOS:000354216600007 PM 23957214 ER PT J AU Gerow, S Rispoli, M Boles, MB Neely, LC AF Gerow, Stephanie Rispoli, Mandy Boles, Margot B. Neely, Leslie C. TI An analysis of contingency statements in a DRO procedure: A case report SO DEVELOPMENTAL NEUROREHABILITATION LA English DT Article DE Autism; challenging behaviour; contingency statements; DRO; repetitive speech ID DIFFERENTIAL REINFORCEMENT; VOCAL STEREOTYPY; DISRUPTIVE BEHAVIOR; SELF-MANAGEMENT; AUTISM; CHILDREN; SCHEDULES; INSTRUCTION; CLASSROOM AB Objective: To examine latency to criterion for reduction of challenging behaviour with and without stating a contingency statement immediately prior to a DRO procedure. Method: An ABAC design in which A was baseline, B was used to evaluate the efficacy of a DRO procedure, and C was used to evaluate the efficacy of a DRO procedure with a contingency statement. Results: The DRO with the contingency statement intervention was associated with a shorter latency to behaviour change than the DRO procedure without the contingency statement. Discussion: These preliminary findings from this case study highlight the importance of examining the efficiency of behaviour change procedures. Directions for future research are provided. C1 [Gerow, Stephanie; Rispoli, Mandy; Boles, Margot B.; Neely, Leslie C.] Texas A&M Univ, Educ Psychol, College Stn, TX 77843 USA. RP Gerow, S (reprint author), Texas A&M Univ, Educ Psychol, College Stn, TX 77843 USA. 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PD JUN PY 2015 VL 18 IS 3 BP 203 EP 208 DI 10.3109/17518423.2013.809812 PG 6 WC Clinical Neurology; Pediatrics; Rehabilitation SC Neurosciences & Neurology; Pediatrics; Rehabilitation GA CH7KZ UT WOS:000354216600008 PM 23870002 ER PT J AU Katoh, M AF Katoh, Masaru TI Functional proteomics of the epigenetic regulators ASXL1, ASXL2 and ASXL3: a convergence of proteomics and epigenetics for translational medicine SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE acute myeloid leukemia; cardiovascular development; colorectal cancer; Forkhead-box transcription factor; hepatocellular carcinoma; melanoma; microsatellite instability; myelodysplastic syndrome; ovarian cancer; pancreatic cancer ID ADDITIONAL-SEX-COMBS; NUCLEAR RECEPTOR SUPERFAMILY; PROTEIN-PROTEIN INTERACTIONS; ACUTE MYELOID-LEUKEMIA; BOHRING-OPITZ SYNDROME; GENE IN-SILICO; PHD FINGER; MYELODYSPLASTIC SYNDROMES; MASS-SPECTROMETRY; BREAST-CANCER AB ASXL1, ASXL2 and ASXL3 are epigenetic scaffolds for BAP1, EZH2, NCOA1, nuclear receptors and WTIP. Here, functional proteomics of the ASXL family members are reviewed with emphasis on mutation spectra, the ASXM2 domain and the plant homeodomain (PHD) finger. Copy number gains of ASXL1 occur in chromosome 20q11.2 duplication syndrome and cervical cancer. Truncation mutations of ASXLs occur in autism, Bohring-Opitz and related syndromes, hematological malignancies and solid tumors, such as prostate cancer, breast cancer and high-grade glioma, which are gain-or loss-of-function mutations. The ASXM2 domain is a binding module for androgen receptor and estrogen receptor a, while the PHD finger is a ligand of WTIP LIM domains and a putative chromatin-binding module. Phylogenetic analyses of 139 human PHD fingers revealed that ASXL PHD fingers cluster with those of BPTF, DIDO, ING1, KDM5A (JARID1A), KMT2E (MLL5), PHF2, PHF8 and PHF23. The cell context-dependent epigenetic code of ASXLs should be deciphered to develop therapeutics for human diseases. C1 Natl Canc Ctr Japan, Dept Om Network, Tokyo 1040045, Japan. RP Katoh, M (reprint author), Natl Canc Ctr Japan, Dept Om Network, 5-1-1 Tsukiji Chuo Ward, Tokyo 1040045, Japan. EM mkatoh-kkr@umin.ac.jp FU Masaru Katoh's Fund FX This study was supported in part by a grant-in-aid for the Knowledgebase Project from the Masaru Katoh's Fund. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. 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Proteomics PD JUN PY 2015 VL 12 IS 3 BP 317 EP 328 DI 10.1586/14789450.2015.1033409 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CI2WZ UT WOS:000354610000009 PM 25835095 ER PT J AU Ochs, E AF Ochs, Elinor TI Corporeal Reflexivity and Autism SO INTEGRATIVE PSYCHOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Article DE Autism; Body; Stigma; Reflexivity; Perspective-taking ID MIND AB Ethnographic video recordings of high functioning children with autism or Aspergers Syndrome in everyday social encounters evidence their first person perspectives. High quality visual and audio data allow detailed analysis of children's bodies and talk as loci of reflexivity. Corporeal reflexivity involves displays of awareness of one's body as an experiencing subject and a physical object accessible to the gaze of others. Gaze, demeanor, actions, and sotto voce commentaries on unfolding situations indicate a range of moment-by-moment reflexive responses to social situations. Autism is associated with neurologically based motor problems (e.g. delayed action-goal coordination, clumsiness) and highly repetitive movements to self-soothe. These behaviors can provoke derision among classmates at school. Focusing on a 9-year-old girl's encounters with peers on the playground, this study documents precisely how autistic children can become enmeshed as unwitting objects of stigma and how they reflect upon their social rejection as it transpires. Children with autism spectrum disorders in laboratory settings manifest diminished understandings of social emotions such as embarrassment, as part of a more general impairment in social perspective-taking. Video ethnography, however, takes us further, into discovering autistic children's subjective sense of vulnerability to the gaze of classmates. C1 Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. RP Ochs, E (reprint author), Univ Calif Los Angeles, Dept Anthropol, 341 Haines Hall, Los Angeles, CA 90095 USA. EM eochs@anthro.ucla.edu FU Spencer Foundation for Educational and Related Research; project 'Autistic Children's Narrative Interactions at School and Home' FX This analysis has benefitted from years of dialogue and collaboration with Olga Solomon, whose continuing research on the lived worlds of children with autism spectrum disorders is source of inspiration. I am also grateful to Rachel Flamenbaum for her assistance in presenting the video and audio data for this study. This research is part of a larger study 'Socializing Autistic Children into the Rules of School and Family Life,' funded by the Spencer Foundation for Educational and Related Research (E. Ochs, Principal Investigator 2000-2003). The data were collected during a Spencer-funded project 'Autistic Children's Narrative Interactions at School and Home,' (E. Ochs and L. Capps, Co-Principal Investigators, 1997-2000). CR Agamben Giorgio, 1993, COMING COMMUNITY Agamben Giorgio, 1998, HOMOSACER SOVEREIGN AUSTIN John L., 1975, DO THINGS WORDS Baron-Cohen S., 2001, ESSENTIAL DIFFERENCE BARONCOHEN S, 1989, J CHILD PSYCHOL PSYC, V30, P285, DOI 10.1111/j.1469-7610.1989.tb00241.x BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Baron-Cohen S, 1999, EUR J NEUROSCI, V11, P1891, DOI 10.1046/j.1460-9568.1999.00621.x Bateson G, 1972, STEPS ECOLOGY MIND BOWLER DM, 1992, J CHILD PSYCHOL PSYC, V33, P877, DOI 10.1111/j.1469-7610.1992.tb01962.x Charman T, 1997, DEV PSYCHOL, V33, P781, DOI 10.1037//0012-1649.33.5.781 Dennett D. 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N., 1994, SELF AWARENESS ANIMA Ochs E, 2004, DISCOURSE STUD, V6, P147, DOI 10.1177/1461445604041766 Ochs E, 2010, ETHOS, V38, P69, DOI 10.1111/j.1548-1352.2009.01082.x Rutter M., 1989, J AUTISM DEV DISORD, V19, P383 Searle J., 1969, SPEECH ACTS ESSAY PH Shankey J., 2013, J CHILD LANG, V41, P275 Solomon O., 2011, LANGUAGE BODY HLTH Solomon O., 2012, CAMBRIDGE ANTHR, V30, P109, DOI [10.3167/ca.2012.300110, DOI 10.3167/CA.2012.300110] Taylor M, 1997, CHILD DEV, V68, P436, DOI 10.1111/j.1467-8624.1997.tb01950.x Vygotsky Lev Semyonovitch, 1978, MIND SOC DEV HIGHER Wechsler D., 1992, WECHSLER INTELLIGENC Wing L., 1997, AUTISM, V1, P13, DOI 10.1177/1362361397011004 Zahavi D., 2008, SUBJECTIVITY SELFHOO NR 37 TC 0 Z9 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-4502 EI 1936-3567 J9 INTEGR PSYCHOL BEHAV JI Integr. Psychol. Behav. Sci. PD JUN PY 2015 VL 49 IS 2 BP 275 EP 287 DI 10.1007/s12124-015-9306-6 PG 13 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA CI0BF UT WOS:000354399900012 PM 25939529 ER PT J AU Kryzak, LA Jones, EA AF Kryzak, Lauren A. Jones, Emily A. TI The Effect of Prompts within Embedded Circumscribed Interests to Teach Initiating Joint Attention in Children with Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Joint attention; Circumscribed interests; Generalization; Autism ID OF-THE-LITERATURE; YOUNG-CHILDREN; BEHAVIORS; INTERVENTION; COMMUNICATION; PLAY AB Joint attention occurs when two people engage in eye contact, verbalizations, or gestures between each other and a common object for the purpose of social interaction. Interventions which embedded participant's circumscribed interests (i.e., specific topics or themes of abnormal intensity) in materials found increases in joint attention without direct intervention. Previous joint attention intervention successfully taught three children with autism to respond to others' joint attention directives using interventions with circumscribed interest-related materials. However, initiating joint attention and generalization across materials and settings were not addressed. The current study investigated the effectiveness of prompt fading and reinforcement while engaging in circumscribed interest-related activities on initiating joint attention for three children with autism. All children acquired joint attention initiations; however, only two did so while engaging with circumscribed interest-related materials. Participants demonstrated variable generalization across activities, partners, and settings. Parents reported declines in circumscribed interest-related social interference from pre- to post-intervention. Results suggest teaching joint attention initiations using circumscribed interest-related materials to teach joint attention initiations may be an effective strategy for some children with autism. Future research implications are discussed. C1 [Kryzak, Lauren A.; Jones, Emily A.] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Kryzak, Lauren A.; Jones, Emily A.] CUNY, Grad Ctr, New York, NY 10016 USA. RP Kryzak, LA (reprint author), CUNY, Grad Ctr, 365 Fifth Ave, New York, NY 10016 USA. EM lauren.kryzak@qc.cuny.edu CR Acra C. F., 2006, DEV SOCIAL ENGAGEMEN, P81 American Psychiatric Association, 2013, DESK REF DIAGN CRIT Attwood T., 1998, ASPERGERS SYNDROME G BAKEMAN R, 1984, CHILD DEV, V55, P1278, DOI 10.2307/1129997 Baker M. 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Dev. Phys. Disabil. PD JUN PY 2015 VL 27 IS 3 BP 265 EP 284 DI 10.1007/s10882-014-9414-0 PG 20 WC Rehabilitation SC Rehabilitation GA CI1FC UT WOS:000354487000001 ER PT J AU Carlon, S Carter, M Stephenson, J AF Carlon, Sarah Carter, Mark Stephenson, Jennifer TI Decision-Making Regarding Early Intervention by Parents of Children with Autism Spectrum Disorder SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE ASD; Autism; Decision-making; Intervention; Parent; Treatment ID ALTERNATIVE MEDICINE; COMPLEMENTARY; EXPERIENCES; MODELS AB Seventy-five parents of preschool-age children with autism spectrum disorder (ASD) completed surveys designed to identify factors considered when selecting an intervention approach for their child and to elucidate the relative importance of those factors in the decision-making process. For decisions to use interventions, the most important factor related to the individual needs of the child. This factor and several others; including staff attributes, whether the intervention was ASD-specific, and intuition/gut feelings, were weighted more highly than research evidence in both decisions to use and to reject interventions. When the individual factors were grouped pragmatically, the category representing service characteristics, including staff attributes and whether the intervention was ASD-specific, was ranked significantly higher in importance than all other categories. Advice/recommendations from others have been reported in previous research as being frequently considered in parental decision-making. However, in the present study, advice and recommendations from others was rated significantly lower in importance than all other categories regardless of whether participants were considering using or rejecting an intervention. C1 [Carlon, Sarah; Carter, Mark; Stephenson, Jennifer] Macquarie Univ, Sydney, NSW 2109, Australia. 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PD JUN PY 2015 VL 27 IS 3 BP 285 EP 305 DI 10.1007/s10882-014-9415-z PG 21 WC Rehabilitation SC Rehabilitation GA CI1FC UT WOS:000354487000002 ER PT J AU McLay, L van der Meer, L Schafer, MCM Couper, L McKenzie, E O'Reilly, MF Lancioni, GE Marschik, PB Green, VA Sigafoos, J Sutherland, D AF McLay, Laurie van der Meer, Larah Schaefer, Martina C. M. Couper, Llyween McKenzie, Emma O'Reilly, Mark F. Lancioni, Giulio E. Marschik, Peter B. Green, Vanessa A. Sigafoos, Jeff Sutherland, Dean TI Comparing Acquisition, Generalization, Maintenance, and Preference Across Three AAC Options in Four Children with Autism Spectrum Disorder SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Augmentative and alternative communication; Autism spectrum disorder; Maintenance; Manual signing; Picture exchange; Preference; Generalization; Requesting; Speech-generating device ID SPEECH-GENERATING DEVICES; DEVELOPMENTAL-DISABILITIES; PICTURE EXCHANGE; COMMUNICATION MODES; INDIVIDUALS; LANGUAGE; REQUESTS; PECS AB We compared acquisition, generalization, maintenance, and preference for three AAC options. Four children with autism spectrum disorder were taught to use (a) a manual sign, (b) a picture exchange card, and (c) a speech-generating device to request toys. Intervention was staggered across children in a delayed multiple-probe design with acquisition and maintenance compared in an alternating treatments design. Generalization to new settings and people and preference for using each option were assessed. Three of the four children reached the acquisition criterion with each AAC option in 15 to 65 trials. One child learned to use the speech-generating device and picture exchange card in 20 and 40 trials, respectively, but failed to learn the manual sign. Two children showed generalization across settings and people with picture exchange and the speech-generating device and one child showed generalization with all three options. One child showed generalization across settings with the picture exchange card. Maintenance was relatively better with the speech-generating device and picture exchange card and the children most often chose the speech-generating device during the preference assessments. The results suggest comparable acquisition, but better generalization and maintenance with AAC options that involve selecting a graphic symbol. C1 [McLay, Laurie; Schaefer, Martina C. M.; Couper, Llyween; McKenzie, Emma; Sutherland, Dean] Univ Canterbury, Coll Educ, Sch Hlth Sci, Christchurch 1, New Zealand. [van der Meer, Larah; Green, Vanessa A.; Sigafoos, Jeff] Victoria Univ Wellington, Sch Educ, Wellington 6147, New Zealand. [O'Reilly, Mark F.] Univ Texas Austin, Meadows Ctr Preventing Educ Risk, Austin, TX 78712 USA. [Lancioni, Giulio E.] Univ Bari, Dept Neurosci & Sense Organs, Bari, Italy. [Marschik, Peter B.] Med Univ Graz, Inst Physiol, iDN Interdisciplinary Dev Neurosci, Graz, Austria. [Marschik, Peter B.] Karolinska Inst, Ctr Neurodev Disorders, Stockholm, Sweden. RP Sigafoos, J (reprint author), Victoria Univ Wellington, Sch Educ, POB 17-310, Wellington 6147, New Zealand. 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PD JUN PY 2015 VL 27 IS 3 BP 323 EP 339 DI 10.1007/s10882-014-9417-x PG 17 WC Rehabilitation SC Rehabilitation GA CI1FC UT WOS:000354487000004 ER PT J AU Miltenberger, CA Charlop, MH AF Miltenberger, Catherine A. Charlop, Marjorie H. TI The Comparative Effectiveness of Portable Video Modeling vs. Traditional Video Modeling Interventions with Children with Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Video modeling; Social-communication skills; Technology ID PRETEND PLAY; INTELLECTUAL DISABILITY; TEACHING-CHILDREN; STUDENTS; SKILLS; SELF; TECHNOLOGIES; BEHAVIORS; FUTURE AB Newly developed technologies are being incorporated into treatments for children with autism but there is only limited research examining how this affects child outcomes. In the present study, a multiple baseline design across children and an adapted alternating treatments design within child were used to compare the effectiveness of video modeling interventions implemented on the iPadA (R) to video modeling interventions implemented on the traditionally used television. Two targets were selected for each child and behaviors were randomly assigned to a treatment condition. Target behaviors were acquired and these behavior changes were found to be socially valid across treatment conditions. Four of the children required slightly more treatment sessions to acquire behaviors targeted on the iPadA (R). Generalization and maintenance were slightly higher following video modeling on the iPadA (R), but differences were inconsistent and unlikely to result in meaningfully different outcomes. These findings indicate that video modeling on the iPadA (R) does not result in improved child progress compared to traditional video modeling procedures. 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DeMand, Alexandra Shui, Amy TI Relationships Between Anxiety and Sleep and Feeding in Young Children with ASD SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Autism spectrum disorder; Anxiety; Sleep; Feeding ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; TYPICALLY DEVELOPING-CHILDREN; PRESCHOOL-CHILDREN; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; HABITS QUESTIONNAIRE; SENSORY SENSITIVITY; BEHAVIORAL-PROBLEMS; FOOD SELECTIVITY AB The purpose of this study was to describe anxiety symptoms in a large sample of young children (ages 2-6 years of age) with ASD and examine the relationship of anxiety with other characteristics. This study included 118 children with an average age of nearly 4 years. Parents completed reports of anxiety symptoms, sleep, and feeding. Regression modeling was used to determine if elevated anxiety symptoms were related to age, cognitive functioning, diagnostic status, sleep, and feeding behaviors. Anxiety symptoms were present in 16-19 % of the sample. Anxiety symptoms predicted more sleep disturbance and were associated with a higher likelihood of elevated score on the feeding measure. Anxiety symptoms are present in young children with ASD more than in young typically developing children. Moreover, anxiety symptoms predicted sleep disturbances and, less robustly, increase the chances of feeding problem. Directions for further study and intervention implications are discussed. C1 [Johnson, Cynthia R.] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh UPMC, Autism Ctr, Pittsburgh, PA 15213 USA. [DeMand, Alexandra] Univ Pittsburgh, Pittsburgh, PA USA. [Shui, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Johnson, CR (reprint author), Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh UPMC, Autism Ctr, 3420 5th Ave, Pittsburgh, PA 15213 USA. 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Dev. Phys. Disabil. PD JUN PY 2015 VL 27 IS 3 BP 359 EP 373 DI 10.1007/s10882-015-9419-3 PG 15 WC Rehabilitation SC Rehabilitation GA CI1FC UT WOS:000354487000006 ER PT J AU Malmberg, DB Charlop, MH Gershfeld, SJ AF Malmberg, Debra Berry Charlop, Marjorie H. Gershfeld, Sara J. TI A Two Experiment Treatment Comparison Study: Teaching Social Skills to Children with Autism Spectrum Disorder SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism Spectrum Disorder; Treatment comparison; Social skills; Social behavior; Video modeling; Social stories; Prompting ID TIME-DELAY; PERSPECTIVE-TAKING; IN-VIVO; VIDEO; STORIES; INTERVENTION; PLAY; BEHAVIOR; DESIGN; REINFORCEMENT AB The present study is a series of two experiments of treatment comparisons addressing the acquisition of social skills for children with Autism Spectrum Disorder (ASD). In Experiment 1, a multi-element design was used to assess the efficacy of video modeling as compared with Social Stories (TM) to teach various social skills to the children with ASD. Results from video modeling yielded positive and quick acquisition, consistent with previous literature. However, treatment with Social Stories did not. Upon close inspection of the Social Stories literature, it became apparent that most effective social stories interventions were treatment packages, which include well-tested behavioral procedures such as prompting. Therefore, Experiment 2 was designed to compare Social Stories with the components most often used in social stories treatment packages, such as prompting, parceled out, to assess variables functional for behavior change. A multiple baseline design across children was used. Results of Exp. 2 suggested that prompting was effective for the children in the present study. Results of both experiments are discussed in terms of relating these results to previous literature, and ultimately to recommending treatment for social skills for children with ASD. C1 [Malmberg, Debra Berry] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Charlop, Marjorie H.] Claremont Mckenna Coll, Dept Psychol, Claremont, CA 91711 USA. [Gershfeld, Sara J.] Scripps Coll, Dept Psychol, Claremont, CA 91711 USA. RP Malmberg, DB (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM dmalmberg@csun.edu FU College of Social and Behavioral Sciences, California State University, Northridge FX This research was supported by the College of Social and Behavioral Sciences, California State University, Northridge. 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TI Brief Component Analysis to Identify the Active Variable in the Maintenance of Tolerance for Delay of Reinforcement Intervention for an Adolescent with Autism SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Tolerance for delay of reinforcement; Explicit delay cue; General delay cue; Component analysis ID DEVELOPMENTAL-DISABILITIES; BEHAVIOR PROBLEMS; REDUCTION AB This study adopted a brief component analysis to examine the active variable in a tolerance for delay of reinforcement (TFD) intervention procedure to decrease tangible-maintained problem behavior for a male adolescent with autism. Antecedent-based functional analysis suggested that problem behavior occurred most when access to tangible items or activities was restricted. 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TI Autism Severity as a Predictor of Comorbid Conditions SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Severity; Comorbidity; Psychopathology; Challenging behaviors ID CHILDREN ASD-CC; SPECTRUM DISORDERS; CHALLENGING BEHAVIORS; PSYCHIATRIC-DISORDERS; DIAGNOSTIC FIDELITY; DSM-IV; RELIABILITY; SYMPTOMS; TODDLERS; CRITERIA AB The relationship between autism spectrum disorders (ASD) and comorbid disorders has become an increasingly popular area of study. This trend has been spurred by the recognition that many physical and psychological problems are present when a diagnosis of ASD has been confirmed. This paper studied comorbid psychopathology and challenging behaviors of 207 individuals diagnosed with ASD between 2 and 16 years of age. More severe symptoms of ASD resulted in more symptoms on multiple comorbidities. The implications of these data are discussed. 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L., 2007, AUTISM SPECTRUM DISO Matson JL, 2008, RES AUTISM SPECT DIS, V2, P237, DOI 10.1016/j.rasd.2007.06.003 Matson JL, 2009, RES DEV DISABIL, V30, P1317, DOI 10.1016/j.ridd.2009.05.008 Matson JL, 2012, J AUTISM DEV DISORD, V42, P1549, DOI 10.1007/s10803-012-1582-0 Matson JL, 2009, RES AUTISM SPECT DIS, V3, P345, DOI 10.1016/j.rasd.2008.08.002 Matson JL, 2009, RES DEV DISABIL, V30, P1107, DOI 10.1016/j.ridd.2009.06.003 Matson JL, 2008, J DEV PHYS DISABIL, V20, P155, DOI 10.1007/s10882-007-9086-0 Matson JL, 2009, J DEV PHYS DISABIL, V21, P253, DOI 10.1007/s10882-009-9140-1 Matson JL, 2007, J INTELLECT DEV DIS, V32, P39, DOI 10.1080/13668250601184689 Matson JL, 2012, J DEV PHYS DISABIL, V24, P403, DOI 10.1007/s10882-012-9278-0 Matson JL, 2008, J DEV PHYS DISABIL, V20, P327, DOI 10.1007/s10882-008-9100-1 Matson JL, 2010, RES DEV DISABIL, V31, P464, DOI 10.1016/j.ridd.2009.10.014 Matson JL, 2010, DEV NEUROREHABIL, V13, P72, DOI 10.3109/17518420903213576 Matson JL, 2009, RES DEV DISABIL, V30, P961, DOI 10.1016/j.ridd.2009.01.009 Matson JL, 2010, RES AUTISM SPECT DIS, V4, P300, DOI 10.1016/j.rasd.2009.10.001 Matson JL, 2008, RES AUTISM SPECT DIS, V2, P696, DOI 10.1016/j.rasd.2008.02.003 Matson JL, 2012, DEV NEUROREHABIL, V15, P185, DOI 10.3109/17518423.2012.672341 Matson JL, 2007, RES DEV DISABIL, V28, P341, DOI 10.1016/j.ridd.2005.12.004 Matson JL, 2005, RES DEV DISABIL, V26, P399, DOI 10.1016/j.ridd.2004.11.008 Matson JL, 2009, RES DEV DISABIL, V30, P1203, DOI 10.1016/j.ridd.2009.04.001 Mayes SD, 2012, RES AUTISM SPECT DIS, V6, P1, DOI 10.1016/j.rasd.2011.08.001 Neil N., 2014, CHILDREN YOUTH AUTIS Ollendick T., 2014, HDB AUTISM ANXIETY, P107 SCHOPLER E, 1980, J AUTISM DEV DISORD, V10, P91, DOI 10.1007/BF02408436 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Smith KRM, 2010, RES DEV DISABIL, V31, P1366, DOI 10.1016/j.ridd.2010.07.002 Thorson RT, 2012, RES AUTISM SPECT DIS, V6, P556, DOI 10.1016/j.rasd.2011.07.016 Tsai LKY, 2014, RES AUTISM SPECT DIS, V8, P1454, DOI 10.1016/j.rasd.2014.07.016 White S. 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Rubia, Katya TI Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD SO PSYCHOPHARMACOLOGY LA English DT Article DE ADHD; ASD; Motor response inhibition; Stop task; fMRI; Serotonin; Fluoxetine ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; AUTISTIC SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; RESPONSE-INHIBITION; TRYPTOPHAN DEPLETION; REPETITIVE BEHAVIOR; PLATELET SEROTONIN; ERROR-DETECTION AB Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders. We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine. Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls. Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD. The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders. C1 [Chantiluke, Kaylita; Santosh, Paramala; Rubia, Katya] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, MRC Ctr Social Genet & Dev Psychiat SGDP, London SE5 8AF, England. [Barrett, Nadia] South London & Maudsley NHS Trust, London, England. [Giampietro, Vincent; Brammer, Michael; Simmons, Andrew] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London SE5 8AF, England. [Simmons, Andrew] Kings Coll London, South London & Maudsley NHS Trust, NIHR Biomed Res Ctr Mental Hlth, London SE5 8AF, England. [Simmons, Andrew] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Murphy, Declan G.] Kings Coll London, Dept Forens & Dev Sci, London SE5 8AF, England. [Murphy, Declan G.] Kings Coll London, Inst Psychiat, Sackler Inst Translat Neurodev, London SE5 8AF, England. RP Rubia, K (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, MRC Ctr Social Genet & Dev Psychiat SGDP, 16 De Crespigny Pk,PO46, London SE5 8AF, England. EM katya.rubia@kcl.ac.uk RI Simmons, Andrew/B-8848-2008 OI Simmons, Andrew/0000-0003-2306-5811 FU Lilly FX Katya Rubia has received a funding from Lilly for another project and speaker's honoraria from Lilly, Shire and Novartis. Michael Brammer is a consultant for P1vital, Ltd, Oxford, UK. 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10.1007/s00213-014-3837-2 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CI1DG UT WOS:000354481000005 PM 25533997 ER PT J AU Ago, Y Condro, MC Tan, YV Ghiani, CA Colwell, CS Cushman, JD Fanselow, MS Hashimoto, H Waschek, JA AF Ago, Yukio Condro, Michael C. Tan, Yossan-Var Ghiani, Cristina A. Colwell, Christopher S. Cushman, Jesse D. Fanselow, Michael S. Hashimoto, Hitoshi Waschek, James A. TI Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist SO PSYCHOPHARMACOLOGY LA English DT Article DE VPAC2 receptor (VIPR2); Schizophrenia; Prepulse inhibition; PSD-95; Synaptophysin; Mouse ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; LONG-TERM POTENTIATION; SUPRACHIASMATIC NUCLEI; PREFRONTAL CORTEX; GENE-EXPRESSION; CEREBRAL-CORTEX; DENTATE GYRUS; MUTANT MICE; SCHIZOPHRENIA AB An abundance of genetic and epidemiologic evidence as well as longitudinal neuroimaging data point to developmental origins for schizophrenia and other mental health disorders. Recent clinical studies indicate that microduplications of VIPR2, encoding the vasoactive intestinal peptide (VIP) receptor VPAC2, confer significant risk for schizophrenia and autism spectrum disorder. Lymphocytes from patients with these mutations exhibited higher VIPR2 gene expression and VIP responsiveness (cAMP induction), but mechanisms by which overactive VPAC2 signaling may lead to these psychiatric disorders are unknown. We subcutaneously administered the highly selective VPAC2 receptor agonist Ro 25-1553 to C57BL/6 mice from postnatal day 1 (P1) to P14 to determine if overactivation of VPAC2 receptor signaling during postnatal brain maturation affects synaptogenesis and selected behaviors. Western blot analyses on P21 revealed significant reductions of synaptophysin and postsynaptic density protein 95 (PSD-95) in the prefrontal cortex, but not in the hippocampus in Ro 25-1553-treated mice. The same postnatally restricted treatment resulted in a disruption in prepulse inhibition of the acoustic startle measured in adult mice. No effects were observed in open-field locomotor activity, sociability in the three-chamber social interaction test, or fear conditioning or extinction. Overactivation of the VPAC2 receptor in the postnatal mouse results in a reduction in synaptic proteins in the prefrontal cortex and selective alterations in prepulse inhibition. These findings suggest that the VIPR2-linkage to mental health disorders may be due in part to overactive VPAC2 receptor signaling during a critical time of synaptic maturation. C1 [Ago, Yukio; Condro, Michael C.; Ghiani, Cristina A.; Fanselow, Michael S.; Waschek, James A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Ago, Yukio] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, Suita, Osaka 5650871, Japan. [Tan, Yossan-Var] Univ Rouen, INSERM Unite Mixte Rech U905 IRIB, F-76183 Rouen, France. [Colwell, Christopher S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Lab Circadian & Sleep Med, Los Angeles, CA 90095 USA. [Cushman, Jesse D.; Fanselow, Michael S.] Univ Calif Los Angeles, Brain Res Inst, Dept Psychol, Los Angeles, CA 90095 USA. [Hashimoto, Hitoshi] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Mol Neuropharmacol, Suita, Osaka 5650871, Japan. RP Waschek, JA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 635 Charles E Young Dr South, Los Angeles, CA 90095 USA. EM jwaschek@mednet.ucla.edu FU Simons Foundation; Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (Japan) [S2603]; National Institutes of Health [MH098506, HD04612] FX We thank Dr. Felix E. Schweizer (UCLA) and Dr. Thomas J. O'Dell (UCLA) for their kind gifts of anti-synaptophysin and anti-PSD-95 antibodies, respectively. This study was supported in part by grants from Simons Foundation, Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (Grant No. S2603, Japan) and National Institutes of Health (MH098506 and HD04612). 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However, how MIA affects offspring immune function remains unknown. Method of studyTo investigate the effect of MIA on the offspring, pregnant C57BL/6J mice were given an intraperitoneal injection of 50g/kg lipopolysaccharide (LPS) on gestational day 12.5. ResultsAdult LPS-treated offspring were hyper-reactive to LPS, and enhanced tumor necrosis factor- production was observed. CD4(+) T cells from LPS offspring had an elevated percentage of interferon (IFN)-(+)CD4(+) T cells and interleukin (IL)-17A(+)CD4(+) T cells in the spleen, IL-17A(+)CD4(+) T cells in the liver, and CD4(+)Foxp3(+) T cells in the spleen. LPS offspring CD4(+) T cells showed increased proliferation and an enhanced survival rate. DNA microarray analysis of resting LPS offspring CD4(+) T cells identified eight up-regulated genes, most of which encoded transcription factors. Quantitative liquid chromatography-mass spectrometry identified 18 up-regulated proteins in resting LPS offspring CD4(+) T cells and five up-regulated proteins in activated LPS offspring CD4(+) T cells, most of which participated in the PANTHER Gene Ontology metabolic process. ConclusionsOur results showed that MIA to LPS up-regulated proteins involved in metabolic process in CD4(+) T cells from LPS offspring that might contribute to the hyperactivated immune response of adult LPS offspring. C1 [Luan, Rong; Cheng, Hao; Liu, Hui; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China. [Hao, Jianlei; Yin, Zhinan] Jinan Univ, Int Immunol Ctr, Biomed Translat Res Inst, Guangzhou, Guangdong, Peoples R China. [Li, Lin; Yang, Jinghua] Shandong Univ, Caner Res Ctr, Jinan 250100, Shandong, Peoples R China. [Li, Lin] Binzhou Med Univ, Period Dept, Yantai, Shandong, Peoples R China. [Zhao, Qiang] Nankai Univ, Coll Life Sci, Dept Zool & Dev Biol, Tianjin 300071, Peoples R China. RP Yin, ZN (reprint author), Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China. EM zhinan.yin@yale.edu RI ahmed, Jamila/E-8653-2015 FU National High Technology Research and Development Program of China [SS2014AA021601]; Major Program of the National Natural Science Foundation of China [31230025]; International Science and Technology Cooperation Program of China [2010DFB34000]; National Basic Research Grant of China [2010CB529100]; National Natural Science Foundation of China [31170858, 31370883, 31000400]; Natural Science Foundation of Tianjin [12JCYBJC15700] FX This work was supported by the National High Technology Research and Development Program of China Grant SS2014AA021601 (863Program), Major Program of the National Natural Science Foundation of China Grant 31230025 (to Dr. Zhinan Yin), International Science and Technology Cooperation Program of China Grant 2010DFB34000 (to Dr. Zhinan Yin), and National Basic Research Grant of China 2010CB529100. This work was also supported by National Natural Science Foundation of China Grants 31170858 and 31370883 (to Dr. Liqing Zhao) and 31000400 (to Dr. Zhenzhou Wu) and Natural Science Foundation of Tianjin Grant 12JCYBJC15700 (to Dr. Qiang Zhao). 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Psychol. PD JUN PY 2015 VL 50 IS 3 BP 169 EP 172 DI 10.1111/ap.12080 PG 4 WC Psychology, Multidisciplinary SC Psychology GA CH3UO UT WOS:000353956100001 ER PT J AU Tanchanco, L De Vera, M Bernal, S Bengzon, A AF Tanchanco, L. De Vera, M. Bernal, S. Bengzon, A. TI EFFECT OF MESENCHYMAL STEM CELL TREATMENT ON AUTISM SPECTRUM DISORDER SO CYTOTHERAPY LA English DT Meeting Abstract C1 [Tanchanco, L.; De Vera, M.; Bernal, S.; Bengzon, A.] Med City Hosp, Pasig, Philippines. [Tanchanco, L.; De Vera, M.; Bengzon, A.] Ateneo Sch Med & Publ Hlth, Pasig, Philippines. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PD JUN PY 2015 VL 17 IS 6 SU S MA 134 BP S39 EP S40 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA CH6JK UT WOS:000354142700125 ER PT J AU Treasure, J Stein, D Maguire, S AF Treasure, Janet Stein, Daniel Maguire, Sarah TI Has the time come for a staging model to map the course of eating disorders from high risk to severe enduring illness? An examination of the evidence SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Review DE biological markers; early intervention; eating disorders; epidemiology; outcome ID RANDOMIZED CONTROLLED-TRIAL; INTERPERSONAL MAINTENANCE MODEL; AUTISM SPECTRUM DISORDERS; FEMALE COLLEGE-STUDENTS; SEVERE ANOREXIA-NERVOSA; FAMILY-BASED TREATMENT; BULIMIA-NERVOSA; FOLLOW-UP; PREVENTION PROGRAM; EARLY INTERVENTION AB AimTo examine the evidence to support using a staging heuristic for eating disorders, suggesting that the diagnosis of an eating disorder follows a trajectory across the life course. Specifically, to examine whether high-risk markers and prodromal features presenting in childhood and adolescence can later transition to the full manifestation of the illness in early adulthood, and whether over time, the illness can be described as becoming severe and enduring, often resistant to treatment. MethodsWe conducted a comprehensive literature search on the MEDLINE, PubMed, PsycINFO, EMBASE and Cochrane databases from using the following terms: staging, duration of illness, early intervention, developmental epidemiology, neurobiological marker, phenotype, partial syndrome, severe enduring, chronic, prospective, longitudinal, cohort, epidemiology, adolescent, adult with anorexia nervosa, bulimia nervosa, binge eating disorder, eating disorder. The evidence was organized according to the staging heuristic defined by McGorry. ResultsEvidence from epidemiological studies, neuropsychological findings, treatment responsivity and prognosis, support a specific staging trajectory for anorexia nervosa in that there is a longitudinal trajectory with evidence of neurobiological progression and evidence that interventions matched to stage of illness may optimize the benefit. There is less data at the moment to support such a model for bulimia nervosa and binge eating disorder. ConclusionThe staging heuristic is a useful model for anorexia nervosa in terms of providing prognostic information and stage matched interventions. Although the evidence is encouraging, further research is needed before a similar model could be applied for bulimia nervosa and binge eating disorder. C1 [Treasure, Janet] Kings Coll London, Inst Psychiat, Eating Disorders Res Unit PO59, London SE5 8AF, England. [Stein, Daniel] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Stein, Daniel] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Maguire, Sarah] Univ Sydney, Ctr Eating & Dieting Disorders, Boden Inst, Sydney, NSW 2006, Australia. RP Treasure, J (reprint author), Kings Coll London, Inst Psychiat, Eating Disorders Res Unit, P059,103 Denmark Hill, London SE5 8AF, England. 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Novarino, Gaia Engels, Hartmut TI Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID 3P DELETION SYNDROME; FUNCTION MUTATIONS; CRITICAL REGION; PATIENT; FEATURES; GENETICS; SYSTEMS; AUTISM; DOMAIN AB Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. C1 [Kuechler, Alma; Luedecke, Hermann-Josef; Czeschik, Johanna Christina; Wieczorek, Dagmar] Univ Duisburg Essen, Inst Humangenet, Univ Klinikum Essen, Essen, Germany. [Zink, Alexander M.; Cremer, Kirsten; Aretz, Stefan; Maylahn, Carina; Wohlleber, Eva; Engels, Hartmut] Univ Bonn, Inst Human Genet, D-53105 Bonn, Germany. [Wieland, Thomas; Gundlach, Jasmin; Schwarzmayr, Thomas; Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Salviati, Leonardo; Pinato, Claudia; Clementi, Maurizio] Univ Padua, Clin Genet Unit, Dept Salute Donna & Bambino, Padua, Italy. [Magini, Pamela] Univ Bologna, UO Genet Med, Dipartimento Sci Med & Chirug DIMEC, Bologna, Italy. [Najafi, Kimia; Kariminejad, Roxana] Kariminejad Najmabadi Pathol & Genet Ctr, Tehran, Iran. [Zweier, Christiane; Endele, Sabine] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Tamburrino, Federica; Mazzanti, Laura] Univ Bologna, Policlin S Orsola Malpighi, Ambulatorio Auxol Sindromol & Malattie Rare, Dipartimento Sci Med & Chirug DIMEC, Bologna, Italy. [Schlessinger, Avner] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Schlessinger, Avner] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Novarino, Gaia] IST Austria, Klosterneuburg, Austria. RP Engels, H (reprint author), Univ Bonn, Inst Human Genet, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM hartmut.engels@uni-bonn.de RI ahmed, Jamila/E-8653-2015 FU German Ministry of Research and Education (German Mental Retardation Network) as part of the National Genome Research Network [01GS08164, 01GS08167, 01GS08163]; European Commission's FP7 CHERISH programme [223692] FX We are grateful to the patients and their families for participating in this study. We thank the 'German Mental Retardation Network' (MRNET) and Sabine Kaya, Daniela Falkenstein and Mike Liu for their excellent technical assistance. This work was supported in part by the German Ministry of Research and Education (grant numbers 01GS08164, 01GS08167, 01GS08163, German Mental Retardation Network) as part of the National Genome Research Network and by the European Commission's FP7 CHERISH programme (grant number 223692). 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TI MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDER; 2Q23.1 MICRODELETION; DEVELOPMENTAL DELAY; GENE; RAI1; CLOCK; MUTATIONS; PHENOTYPE; FEATURES; DUPLICATION AB Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders. C1 [Mullegama, Sureni V.; Gu, Yanghong; Nelson, David L.; Elsea, Sarah H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Elsea, Sarah H.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA. RP Elsea, SH (reprint author), Baylor Coll Med, Dept Mol & Human Genet, One Baylor Plaza,NAB2015, Houston, TX 77030 USA. EM elsea@bcm.edu FU Fondation Jerome Lejeune; Smith-Magenis Syndrome Research Foundation; resources from Virginia Commonwealth University; Baylor College of Medicine; Jan and Dan Duncan Neurological Research Institute at the Texas Children's Hospital FX We are grateful to PRISMS and to the 2q23.1 Facebook group and all of the study participants and their families for their cooperation in this study. We thank the Fondation Jerome Lejeune and the Smith-Magenis Syndrome Research Foundation for funding portions of this study. This work was supported, in part, by the resources from Virginia Commonwealth University, Baylor College of Medicine, and the Jan and Dan Duncan Neurological Research Institute at the Texas Children's Hospital. 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TI Two male adults with pathogenic AUTS2 variants, including a two-base pair deletion, further delineate the AUTS2 syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUTISM-SUSCEPTIBILITY-CANDIDATE-2 AUTS2; TRANSLOCATION BREAKPOINT; INTELLECTUAL DISABILITY; DEVELOPMENTAL DELAY; SPECTRUM DISORDERS; GENE; PATIENT; AUTISM AB AUTS2 syndrome is characterized by low birth weight, feeding difficulties, intellectual disability, microcephaly and mild dysmorphic features. All affected individuals thus far were caused by chromosomal rearrangements, variants at the base pair level disrupting AUTS2 have not yet been described. Here we present the full clinical description of two affected men with intragenic AUTS2 variants (one two-base pair deletion in exon 7 and one deletion of exon 6). Both variants are de novo and are predicted to cause a frameshift of the full-length transcript but are unlikely to affect the shorter 30 transcript starting in exon 9. The similarities between the phenotypes of both men are striking and further support that AUTS2 syndrome is a single gene disorder. C1 [Beunders, Gea; Voorhoeve, Els; Groffen, Alexander J.; Meijers-Heijboer, Elizabeth J.; Sistermans, Erik A.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands. [de Munnik, Sonja A.; Nillesen, Willy M.; Yntema, Helger G.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Van der Aa, Nathalie; Kooy, R. Frank] Univ Antwerp Hosp, Dept Med Genet, Antwerp, Belgium. [Ceulemans, Berten] Univ Antwerp Hosp, Dept Neurol Paediat Neurol, Antwerp, Belgium. RP Sistermans, EA (reprint author), Vrije Univ Amsterdam, Med Ctr, Genome Diagnost, Boechorststr 7,J376, NL-1081 BT Amsterdam, Netherlands. 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J. Hum. Genet. PD JUN PY 2015 VL 23 IS 6 BP 803 EP 807 DI 10.1038/ejhg.2014.173 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CI1BG UT WOS:000354474600020 PM 25205402 ER PT J AU Vojinovic, D Adams, HHH van der Lee, SJ Ibrahim-Verbaas, CA Brouwer, R van den Hout, MCGN Oole, E van Rooij, J Uitterlinden, A Hofman, A van IJcken, WFJ Aartsma-Rus, A van Ommen, GB Ikram, MA van Duijn, CM Amin, N AF Vojinovic, Dina Adams, Hieab H. H. van der Lee, Sven J. Ibrahim-Verbaas, Carla A. Brouwer, Rutger van den Hout, Mirjam C. G. N. Oole, Edwin van Rooij, Jeroen Uitterlinden, Andre Hofman, Albert van IJcken, Wilfred F. J. Aartsma-Rus, Annemieke van Ommen, GertJan B. Ikram, M. Arfan van Duijn, Cornelia M. Amin, Najaf TI The dystrophin gene and cognitive function in the general population SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; AUTISM SPECTRUM DISORDER; GABA(A) RECEPTORS; WIDE ASSOCIATION; SEQUENCING DATA; BRAIN; EXPRESSION; CHILDREN; PERFORMANCE; MALES AB The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1x10(-4)), rs147546024: A>G showed strong association (beta = 1.786, P-value = 2.56 x 10(-4)) with block-design test in the ERF study, while another variant rs1800273: G>A showed suggestive association (beta = -0.465, P-value = 0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024: A>G is an intronic variant, whereas rs1800273: G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values = 0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations. C1 [Vojinovic, Dina; Adams, Hieab H. H.; van der Lee, Sven J.; Ibrahim-Verbaas, Carla A.; Uitterlinden, Andre; Hofman, Albert; Ikram, M. Arfan; van Duijn, Cornelia M.; Amin, Najaf] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Vojinovic, Dina] Univ Belgrade, Sch Med, Clin Neurol & Psychiat Children & Youth, Belgrade, Serbia. [Adams, Hieab H. H.; Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. [Brouwer, Rutger; van den Hout, Mirjam C. G. N.; Oole, Edwin; van IJcken, Wilfred F. J.] Erasmus MC, Ctr Biom, Rotterdam, Netherlands. [van Rooij, Jeroen; Uitterlinden, Andre] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Uitterlinden, Andre; van Duijn, Cornelia M.] Netherlands Consortium Hlth Aging & Natl Genom In, Leiden, Netherlands. [Aartsma-Rus, Annemieke; van Ommen, GertJan B.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [van Ommen, GertJan B.; van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, NL-3000 CA Rotterdam, Netherlands. RP Vojinovic, D (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM d.vojinovic@erasmusmc.nl FU European Commission FP6 STRP grant [018947 (LSHG-CT-2006-01947)]; European Community's Seventh Framework Program (FP7)/European Commission under program 'Quality of Life and Management of the Living Resources' of 5th Framework Program [HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; Russian Foundation for Basic Research [NWO-RFBR 047.017.043]; ZonMw grant [91111025]; Ministry of Science of Serbia [175083]; Hersenstichting Nederland [F2013(1)-28]; Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in Elderly [01493- 015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project [050-060-810]; Netherlands Consortium for Healthy Ageing (NCHA); Erasmus Medical Center and Erasmus University, Rotterdam; Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for the Health Research and Development (ZonMw) FX Erasmus Rucphen Family study: The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Program (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the program 'Quality of Life and Management of the Living Resources' of 5th Framework Program (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, J Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. Dina Vojinovic is supported by the Ministry of Science of Serbia (grant number 175083). Najaf Amin is supported by the Hersenstichting Nederland (project number F2013(1)-28).Rotterdam study: The generation and management of GWAS genotype data for the Rotterdam Study are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011 and 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (01493- 015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810 and Netherlands Consortium for Healthy Ageing (NCHA). We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database, and Karol Estrada and Maksim V Struchalin for their support in creation and analysis of imputed data. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. 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J. Hum. Genet. PD JUN PY 2015 VL 23 IS 6 BP 837 EP 843 DI 10.1038/ejhg.2014.183 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CI1BG UT WOS:000354474600025 PM 25227141 ER PT J AU Witmer, SE Nasamran, A Parikh, PJ Schmitt, HA Clinton, MC AF Witmer, Sara E. Nasamran, Amy Parikh, Purvi J. Schmitt, Heather A. Clinton, Marianne C. TI Using Parents and Teachers to Monitor Progress Among Children With ASD: A Review of Intervention Research SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE assessment; autism spectrum disorders; behavior; communication; socialization ID CURRICULUM-BASED MEASUREMENT; GENERAL-EDUCATION CLASSROOM; AUTISM SPECTRUM DISORDER; TERM SUCCESSFUL TREATMENT; SOCIAL-SKILLS; STUDENT-ACHIEVEMENT; ASPERGER-SYNDROME; LEAST PROMPTS; YOUNG-CHILD; BEHAVIOR AB Despite growing knowledge of the effectiveness of various interventions for children with autism spectrum disorders (ASD), it is never clear whether a particular intervention will be effective for a specific child with ASD. Careful monitoring of an individual child's progress is necessary to know whether an intervention is effective. In this review, we examined intervention research studies focused on children with ASD in Grades K-12 that involve parents, teachers, and other school staff as data collectors. We describe the strategies that have been used in the 40 identified research studies to monitor progress in the areas of behavior and social communication. The results highlight monitoring strategies that may be helpful for parents and teachers to apply, and the discussion provides related suggestions to guide future research and practice. C1 [Witmer, Sara E.; Nasamran, Amy; Schmitt, Heather A.; Clinton, Marianne C.] Michigan State Univ, E Lansing, MI 48824 USA. [Parikh, Purvi J.] Univ Detroit Mercy, Detroit, MI 48221 USA. RP Witmer, SE (reprint author), Michigan State Univ, 620 Farm Lane,Rm 434, E Lansing, MI 48824 USA. EM sbolt@msu.edu CR Akmanoglu N, 2011, AUTISM, V15, P205, DOI 10.1177/1362361309352180 Akmanoglu-Uludag N, 2005, EDUC TRAIN DEV DISAB, V40, P401 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Baker L. M., 2010, CLIN CASE STUDIES, V9, P218, DOI 10.1177/1534650110372253 Banda D. R., 2006, EDUC TREAT CHILD, V29, P507 Barry L. 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Disabil. PD JUN PY 2015 VL 30 IS 2 BP 67 EP 85 DI 10.1177/1088357614525659 PG 19 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA CH4RW UT WOS:000354021600001 ER PT J AU Knight, VF Wood, CL Spooner, F Browder, DM O'Brien, CP AF Knight, Victoria F. Wood, Charles L. Spooner, Fred Browder, Diane M. O'Brien, Christopher P. TI An Exploratory Study Using Science eTexts With Students With Autism Spectrum Disorder SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE supported electronic text; digital text; teaching science content; universal design for learning; explicit instruction; ASD and intellectual disability ID SEVERE DEVELOPMENTAL-DISABILITIES; READING-COMPREHENSION; LEARNING-DISABILITIES; INSTRUCTION; TECHNOLOGY; CHILDREN; INDIVIDUALS; STRATEGIES; ABILITY; SKILLS AB Supported electronic text (eText), or text altered to provide support, may promote comprehension of science content for students with disabilities. According to the Center for Applied Special Technology, Book Builder uses supported eText to promote reading for meaning for all students. Students with autism spectrum disorder experience difficulty comprehending science content because of the extensive amount of background knowledge required in conjunction with difficulties understanding abstract and figurative language. Investigations on the most effective methods for reading comprehension and teaching science to this population are equally limited. In this pilot study, feasibility was supported in high levels of treatment fidelity and teacher- and student-reported satisfaction. A multiple probe across participants with an embedded ABCD design was used to evaluate various modifications of Book Builder on measures of vocabulary, literal comprehension, and application questions. Considerations for students with ASD, limitations, and recommendations for future research conclude the article. C1 [Knight, Victoria F.] Vanderbilt Univ, Nashville, TN 37203 USA. [Wood, Charles L.; Spooner, Fred; Browder, Diane M.; O'Brien, Christopher P.] Univ N Carolina, Charlotte, NC 28223 USA. RP Knight, VF (reprint author), Vanderbilt Univ, Peabody Coll, Dept Special Educ, One Magnolia Circle, Nashville, TN 37203 USA. EM victoria.f.knight@vanderbilt.edu FU University of Oregon [554902]; National Center for Supported eText Dissertation Grants Program; U.S. Department of Education, Institute of Education Sciences [R324AQ080014] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Support for this research was provided in part by Grant No. 554902 from the University of Oregon, National Center for Supported eText Dissertation Grants Program awarded to the University of North Carolina at Charlotte, and by Grant No. R324AQ080014 from the U.S. Department of Education, Institute of Education Sciences, awarded to the University of North Carolina at Charlotte. 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Disabil. PD JUN PY 2015 VL 30 IS 2 BP 86 EP 99 DI 10.1177/1088357614559214 PG 14 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA CH4RW UT WOS:000354021600002 ER PT J AU Siegel, EB Lien, SE AF Siegel, Ellin B. Lien, Susan E. TI Using Photographs of Contrasting Contextual Complexity to Support Classroom Transitions for Children With Autism Spectrum Disorders SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; iPad; augmented input; contextual photographs ID ACTIVITY SCHEDULES; SINGLE-SUBJECT; DESIGN AB A single-subject, alternating treatment study compared the impact of two types of photograph displays of contrasting contextual complexity. The study examined the impact of high-context and no-context photographs, displayed on an iPad, on the ability of three preschool children with autism spectrum disorder (ASD) to transition to play activities. The influence of the two photograph types on the children's duration of transition time, number of prompts required, and type of prompts were measured. Results indicated that both photograph types provided helpful support for the children's transition time to play activities. Results for duration of transition time and number of prompts required during transitions suggest that the participant with more challenging needs performed more quickly and independently using high-context photographs. Results suggest the photographs that have contextual information matched to a child's needs can provide salient information and support their transition to activities in familiar settings. C1 [Siegel, Ellin B.; Lien, Susan E.] Univ Nebraska, Lincoln, NE 68583 USA. RP Siegel, EB (reprint author), Univ Nebraska, Dept Special Educ & Commun Disorders, 355 Barkley Mem Ctr, Lincoln, NE 68583 USA. 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PD JUN PY 2015 VL 30 IS 2 BP 100 EP 114 DI 10.1177/1088357614559211 PG 15 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA CH4RW UT WOS:000354021600003 ER PT J AU Lopata, C Toomey, JA Thomeer, ML McDonald, CA Fox, JD Smith, RA Meichenbaum, DL Volker, MA Lee, GK Lipinski, AM AF Lopata, Christopher Toomey, Jennifer A. Thomeer, Marcus L. McDonald, Christin A. Fox, Jeffery D. Smith, Rachael A. Meichenbaum, David L. Volker, Martin A. Lee, Gloria K. Lipinski, Alanna M. TI Community Trial of a Comprehensive Psychosocial Treatment for HFASDs SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE community effectiveness trial; manualized treatment; community replication; comprehensive psychosocial intervention; high-functioning autism spectrum disorders ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; SOCIAL-SKILLS INTERVENTIONS; ASPERGERS-SYNDROME; CHILDREN; EFFICACY; INDIVIDUALS AB This community effectiveness trial examined the feasibility and efficacy of a comprehensive psychosocial treatment for 28 children, aged 7 to 10 years with high-functioning autism spectrum disorders (HFASDs). Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition skills, interest expansion, and interpretation of non-literal language skills. A behavioral program was instituted to foster skills acquisition and reduce ASD symptoms and problem behaviors. Feasibility was supported in high levels of fidelity and satisfaction. Significant improvements were found for the children's non-literal language skills and parent ratings of target social and communicative skills, broader social performance, and ASD symptoms. Secondary staff ratings corroborated parent ratings. Results suggest that the treatment, when administered by a community agency, was feasible and yielded positive outcomes similar to prior randomized clinical trials (RCTs). C1 [Lopata, Christopher; Thomeer, Marcus L.; Lipinski, Alanna M.] Canisius Coll, Inst Autism Res, Buffalo, NY 14208 USA. [Toomey, Jennifer A.; Meichenbaum, David L.] Summit Educ Resources, Getzville, NY USA. [McDonald, Christin A.; Smith, Rachael A.; Volker, Martin A.; Lee, Gloria K.; Lipinski, Alanna M.] SUNY Buffalo, Buffalo, NY 14260 USA. [McDonald, Christin A.] Nationwide Childrens Hosp, Columbus, OH USA. [Fox, Jeffery D.] Autism Serv Inc, Williamsville, NY USA. 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PD JUN PY 2015 VL 30 IS 2 BP 115 EP 125 DI 10.1177/1088357614525662 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA CH4RW UT WOS:000354021600004 ER PT J AU Stevens, WD Tessler, MH Peng, CS Martin, A AF Stevens, W. Dale Tessler, Michael Henry Peng, Cynthia S. Martin, Alex TI Functional Connectivity Constrains the Category-Related Organization of Human Ventral Occipitotemporal Cortex SO HUMAN BRAIN MAPPING LA English DT Article DE functional MRI; resting-state; tools; objects; scenes; parahippocampal place area; hemispheric asymmetry; lateralization; concepts; localization ID FUSIFORM FACE AREA; SELECTIVE CORTICAL REGIONS; AUTISM SPECTRUM DISORDERS; GLOBAL SIGNAL REGRESSION; RESTING HUMAN BRAIN; HUMAN OBJECT AREAS; WORD FORM AREA; MANIPULATABLE OBJECTS; TEMPORAL CORTEX; INDIVIDUAL VARIABILITY AB One of the most robust and oft-replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category-related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category-relevant properties may be a major contributing factor. To test this hypothesis, we used a multicategory functional magnetic resonance imaging (MRI) localizer to individually define category-related brain regions of interest (ROIs) in a large group of subjects (n=33). We then used these ROIs in resting-state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category-preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category-preference, as defined by the functional localizer. Importantly, a tool-preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common toolsposterior middle temporal gyrus (involved in perception of nonbiological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs)relative to other category-related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category-relevant properties constrains the category-related organization of VOTC. Hum Brain Mapp 36:2187-2206, 2015. (c) Published 2015. This article is a U.S. Government work and is in the public domain in the USA. C1 [Stevens, W. Dale; Tessler, Michael Henry; Peng, Cynthia S.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Stevens, WD (reprint author), York Univ, Dept Psychol, Sherman Hlth Sci Res Ctr, 281 Ian Macdonald Blvd, Toronto, ON M3J 1P3, Canada. EM stevensd@yorku.ca FU National Institute of Mental Health, National Institutes of Health, Division of Intramural Research FX Contract grant sponsor: The National Institute of Mental Health, National Institutes of Health, Division of Intramural Research. 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Brain Mapp. PD JUN PY 2015 VL 36 IS 6 BP 2187 EP 2206 DI 10.1002/hbm.22764 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CH4AF UT WOS:000353972000013 PM 25704493 ER PT J AU Valk, SL Di Martino, A Milham, MP Bernhardt, BC AF Valk, Sofie L. Di Martino, Adriana Milham, Michael P. Bernhardt, Boris C. TI Multicenter Mapping of Structural Network Alterations in Autism SO HUMAN BRAIN MAPPING LA English DT Article DE ASD; ABIDE; neocortex; connectivity; medial PFC; connectome ID DORSOLATERAL PREFRONTAL CORTEX; SURFACE-BASED ANALYSIS; CORTICAL THICKNESS; SPECTRUM DISORDERS; WHITE-MATTER; ORBITOFRONTAL CORTEX; CEREBRAL-CORTEX; NEURAL BASIS; BRAIN; MRI AB Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions primarily characterized by abnormalities in social cognition. Abundant previous functional MRI studies have shown atypical activity in networks encompassing medial prefrontal cortex (mPFC) and medial parietal regions corresponding to posterior cingulate cortex and precuneus (PCC/PCU). Conversely, studies assessing structural brain anomalies in ASD have been rather inconsistent. The current work evaluated whether structural changes in ASD can be reliability detected in a large multicenter dataset. Our comprehensive structural MRI framework encompassed cortical thickness mapping and structural covariance analysis based on three independent samples comprising individuals with ASD and controls (n=220), selected from the Autism Brain Imaging Data Exchange open-access database. Surface-based analysis revealed increased cortical thickness in ASD relative to controls in mPFC and lateral prefrontal cortex. Clusters encompassing mPFC were embedded in altered inter-regional covariance networks, showing decreased covariance in ASD relative to controls primarily to PCC/PCU and inferior parietal regions. Cortical thickness increases and covariance reductions in ASD were consistent, yet of variable effect size, across the different sites evaluated and measurable both in children and adults. Our multisite study shows regional and network-level structural alterations in mPFC in ASD that, possibly, relate to atypical socio-cognitive functions in this condition. Hum Brain Mapp 36:2364-2373, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Valk, Sofie L.; Bernhardt, Boris C.] Max Planck Inst Human Cognit & Brain Sci, Dept Social Neurosci, D-04301 Leipzig, Germany. [Di Martino, Adriana] NYU, Langone Med Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA. [Di Martino, Adriana] NYU, Langone Med Ctr, Ctr Child Study, Autism Spectrum Disorder Res Program, New York, NY USA. [Milham, Michael P.] Child Mind Inst, New York, NY USA. [Milham, Michael P.] NYU, Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. [Bernhardt, Boris C.] Montreal Neurol Hosp & Inst, Brain Imaging Ctr, Montreal, PQ, Canada. RP Bernhardt, BC (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Social Neurosci, Stephanstr 1a, D-04301 Leipzig, Germany. EM bernhardt@cbs.mpg.de FU NIH (NYU site) [K23MH087770, R21MH084126, R01MH081218, R01HD065282]; Autism Speaks; Stavros Niarchos Foundation; Leon Levy Foundation; Autism Speaks (PITT site) [04593]; KO1 NIMH [MH081191]; NIMH [MH67924]; NIH [HD55748]; National Institutes of Health [K08 MH092697, RO1MH080826, P50MH60450, T32DC008553, R01NS34783]; Autism Speaks Mentor-based Predoctoral Fellowship (USM site) [1677]; University of Utah Multidisciplinary Research Seed Grant; NRSA Predoctoral Fellowship [F31 DC010143]; Ben B. and Iris M. Margolis Foundation; Jeanne Timmins Costello Award of the Montreal Neurological Institute and Hospital; CIHR; International Max Planck Research School Stipend, IMPRS NeuroCom FX Contract grant sponsor: NIH (NYU site); Contract grant numbers: K23MH087770, R21MH084126, R01MH081218, R01HD065282; Contract grant sponsor(s): Autism Speaks, The Stavros Niarchos Foundation, The Leon Levy Foundation, an endowment provided by Phyllis Green and Randolph Cowen; Contract grant sponsor: Autism Speaks (PITT site); Contract grant number: 04593; Contract grant sponsor: KO1 NIMH; Contract grant number: MH081191; Contract grant sponsor: NIMH; Contract grant number: MH67924; Contract grant sponsor: NIH; Contract grant number: HD55748; Contract grant sponsor: National Institutes of Health; Contract grant number(s): K08 MH092697, RO1MH080826, P50MH60450, T32DC008553, R01NS34783; Contract grant sponsor: Autism Speaks Mentor-based Predoctoral Fellowship (USM site); Contract grant number: 1677; Contract grant sponsor: University of Utah Multidisciplinary Research Seed Grant; Contract grant sponsor: NRSA Predoctoral Fellowship; Contract grant number: F31 DC010143; Contract grant sponsor: Ben B. and Iris M. Margolis Foundation; Contract grant sponsor: Jeanne Timmins Costello Award of the Montreal Neurological Institute and Hospital and CIHR (to B.C.B.); Contract grant sponsor: International Max Planck Research School Stipend, IMPRS NeuroCom (to S.L.V.). 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Brain Mapp. PD JUN PY 2015 VL 36 IS 6 BP 2364 EP 2373 DI 10.1002/hbm.22776 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CH4AF UT WOS:000353972000025 PM 25727858 ER PT J AU St Pourcain, B Haworth, CMA Davis, OSP Wang, K Timpson, NJ Evans, DM Kemp, JP Ronald, A Price, T Meaburn, E Ring, SM Golding, J Hakonarson, H Plomin, R Smith, GD AF St Pourcain, Beate Haworth, C. M. A. Davis, O. S. P. Wang, Kai Timpson, Nicholas J. Evans, David M. Kemp, John P. Ronald, Angelica Price, Tom Meaburn, Emma Ring, Susan M. Golding, Jean Hakonarson, Hakon Plomin, R. Smith, George Davey TI Heritability and genome-wide analyses of problematic peer relationships during childhood and adolescence SO HUMAN GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DIFFICULTIES QUESTIONNAIRE; GENETIC INFLUENCES; YOUNG ADULTHOOD; ASSOCIATION; ADJUSTMENT; STRENGTHS; TRAITS; METAANALYSIS; POPULATION AB Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N currency sign 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h (2) currency sign 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r (g) = 0.30). GCTA (ALSPAC: N currency sign 5,608, TEDS: N currency sign 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h (2)(Meta) currency sign 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) currency sign 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N currency sign 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P currency sign 0.03). Single variant signals (P currency sign 10(-5)) were followed up in TEDS (N currency sign 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N (Pedigrees) = 793; ACC: N (Cases) = 1,453/N (Controls) = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence. C1 [St Pourcain, Beate; Timpson, Nicholas J.; Evans, David M.; Kemp, John P.; Ring, Susan M.; Smith, George Davey] Univ Bristol, MRC IEU, Bristol BS8 2BN, Avon, England. [St Pourcain, Beate] Univ Bristol, Sch Oral & Dent Sci, Bristol BS8 2BN, Avon, England. [St Pourcain, Beate] Univ Bristol, Sch Expt Psychol, Bristol BS8 2BN, Avon, England. [St Pourcain, Beate; Timpson, Nicholas J.; Evans, David M.; Kemp, John P.; Ring, Susan M.; Golding, Jean; Smith, George Davey] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Haworth, C. M. A.] Univ Warwick, Dept Psychol, Coventry CV4 7AL, W Midlands, England. [Haworth, C. M. A.; Davis, O. S. P.; Plomin, R.] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Davis, O. S. P.] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England. [Wang, Kai; Hakonarson, Hakon] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Wang, Kai] Univ So Calif, ZilkhaNeurogenet Inst, Los Angeles, CA USA. [Wang, Kai] Univ So Calif, Dept Psychiat, Los Angeles, CA USA. [Evans, David M.; Kemp, John P.] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia. [Ronald, Angelica; Meaburn, Emma] Univ London, Dept Psychol Sci, London, England. [Price, Tom] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Golding, Jean] Univ Bristol, Ctr Child & Adolescent Hlth, Bristol BS8 2BN, Avon, England. RP St Pourcain, B (reprint author), Univ Bristol, MRC IEU, Oakfield House, Bristol BS8 2BN, Avon, England. EM beate.stpourcain@bristol.ac.uk FU UK Medical Research Council; Wellcome Trust [WT092731/Z/10/Z, WT083431MA]; University of Bristol; Medical Research Council Integrative Epidemiology Unit [MC_UU_12013/1-9]; Medical Research Council New Investigator Award (MRC) [G0800582]; UK Medical Research Council [G0901245, G19/2]; U.S. National Institutes of Health [HD044454, HD059215]; Wellcome Trust Case Control Consortium [085475/B/08/Z, 085475/Z/08/Z]; British Academy; Sir Henry Wellcome Fellowship from the Wellcome Trust [WT088984]; European Research Council [295366]; National Institute of Mental Health [1U24MH081810]; [23] FX The UK Medical Research Council and the Wellcome Trust (WT092731/Z/10/Z), and the University of Bristol provided core support for ALSPAC, and Autism Speaks (7132) provided support for the analysis of autistic-trait related data. This work was also supported by the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/1-9). DME is supported by a Medical Research Council New Investigator Award (MRC G0800582). JPK is funded by a Wellcome Trust 4-year PhD studentship (WT083431MA).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. 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 23 and Me.We are enormously grateful to the twins, parents and the twins' teachers who have supported the Twins Early Development Study (TEDS) for the past 18 years. The Twins Early Development Study (TEDS) is supported by a program grant from the UK Medical Research Council (G0901245, and previously G0500079), with additional support from the U.S. National Institutes of Health (HD044454, HD059215). Genome-wide genotyping was made possible by grants from the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z, 085475/Z/08/Z). C. M. A. Haworth was supported by a research fellowship from the British Academy. O. S. P. Davis was supported by a Sir Henry Wellcome Fellowship from the Wellcome Trust (WT088984). R. Plomin was supported by a research professorship from the UK Medical Research Council (G19/2) and a European Research Council Advanced Investigator Award (295366).We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participants of the AGRE and ACC resources. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). 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Genet. PD JUN PY 2015 VL 134 IS 6 BP 539 EP 551 DI 10.1007/s00439-014-1514-5 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CH7DQ UT WOS:000354196200002 PM 25515860 ER PT J AU Davis, JM Quick, VBS Sikela, JM AF Davis, J. M. Quick, V. B. Searles Sikela, J. M. TI Replicated linear association between DUF1220 copy number and severity of social impairment in autism SO HUMAN GENETICS LA English DT Article ID HEAD CIRCUMFERENCE; SPECTRUM DISORDERS; EVOLUTION; CHILDREN; ABNORMALITIES; DUPLICATIONS; GENETICS; DOMAINS; 1Q21.1; GROWTH AB Sequences encoding DUF1220 protein domains exhibit an exceptional human-specific increase in copy number and have been associated with several phenotypes related to brain size. Autism is a highly heritable and heterogeneous condition characterized behaviorally by social and communicative impairments, and increased repetitive and stereotyped behavior. Given the accelerated brain growth pattern observed in many individuals with autism, and the association between DUF1220 subtype CON1 copy number and brain size, we previously investigated associations between CON1 copy number and autism-related symptoms. We determined that CON1 copy number increase is associated with increasing severity of all three behavioral features of autism. The present study sought to replicate these findings in an independent population (N = 166). Our results demonstrate a replication of the linear relationship between CON1 copy number and the severity of social impairment in individuals with autism as measured by Autism Diagnostic Interview-Revised Social Diagnostic Score, such that with each additional copy of CON1 Social Diagnostic Score increased 0.24 points (SE = 0.11, p = 0.036). We also identified an analogous trend between CON1 copy number and Communicative Diagnostic Score, but did not replicate the relationship between CON1 copy number and Repetitive Behavior Diagnostic Score. Interestingly, these associations appear to be most pronounced in multiplex children. These results, representing the first replication of a gene dosage relationship with the severity of a primary symptom of autism, lend further support to the possibility that the same protein domain family implicated in the evolutionary expansion of the human brain may also be involved in autism severity. C1 [Davis, J. M.; Quick, V. B. Searles; Sikela, J. M.] Univ Colorado, Dept Biochem & Mol Genet & Human Med Genet & Gen, Sch Med, Med Scientist Training Program, Aurora, CO 80045 USA. [Davis, J. M.; Quick, V. B. Searles; Sikela, J. M.] Univ Colorado, Sch Med, Neurosci Program, Aurora, CO 80045 USA. [Davis, J. M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. RP Sikela, JM (reprint author), Univ Colorado, Dept Biochem & Mol Genet & Human Med Genet & Gen, Sch Med, Med Scientist Training Program, Anschutz Med Campus, Aurora, CO 80045 USA. EM James.Sikela@ucdenver.edu FU NIH [R01 MH081203]; SFARI from Simons Foundation for Autism Research [309230]; Colorado Clinical and Translational Science Institute (CCTSI) Award [TL1 TR001081] FX Funding for this work was provided by NIH grant R01 MH081203 (JMS), by SFARI Pilot Grant 309230 from the Simons Foundation for Autism Research (JMS), and by a Colorado Clinical and Translational Science Institute (CCTSI) Award TL1 TR001081 (VBSQ). We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. We also thank Nathan Anderson for excellent technical assistance. 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Wang, Jun Huang, Dongsheng Chen, Jian-Min Wang, Yiming TI Characterization of 26 deletion CNVs reveals the frequent occurrence of micro-mutations within the breakpoint-flanking regions and frequent repair of double-strand breaks by templated insertions derived from remote genomic regions SO HUMAN GENETICS LA English DT Article ID STRUCTURAL VARIATION; INHERITED DISEASE; GENE CONVERSION; MECHANISMS; REARRANGEMENTS; REPLICATION; EVOLUTION; SPECTRUM; SIGNATURES; VARIANTS AB Copy number variations (CNVs) have increasingly been reported to cause, or predispose to, human disease. However, a large fraction of these CNVs have not been accurately characterized at the single-base-pair level, thereby hampering a better understanding of the mutational mechanisms underlying CNV formation. Here, employing a composite pipeline method derived from various inference-based programs, we have characterized 26 deletion CNVs [including three novel pathogenic CNVs involving an autosomal gene (EXT2) causing hereditary osteochondromas and an X-linked gene (CLCN5) causing Dent disease, as well as 23 CNVs previously identified by inference from a cohort of Canadian autism spectrum disorder families] to the single-base-pair level of accuracy from whole-genome sequencing data. We found that breakpoint-flanking micro-mutations (within 22 bp of the breakpoint) are present in a significant fraction (5/26; 19 %) of the deletion CNVs. This analysis also provided evidence that a recently described error-prone form of DNA repair (i.e., repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome) not only causes human genetic disease but also impacts on human genome evolution. Our findings illustrate the importance of precise CNV breakpoint delineation for understanding the underlying mutational mechanisms and have implications for primer design in relation to the detection of deletion CNVs in clinical diagnosis. C1 [Wang, Ye; Hu, Bin; Yuan, Ping; Li, Fucheng; Jing, Xiangyi; Wang, Yiming] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Med Genet, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Ye; Hu, Bin; Yuan, Ping; Li, Fucheng; Jing, Xiangyi; Wang, Yiming] Sun Yat Sen Univ, Ctr Genome Res, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Ye; Su, Peiqiang] Sun Yat Sen Univ, Dept Orthoped, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China. [Zhu, Wenjuan; Li, Qibin; Wang, Jun; Wang, Yiming] BGI, Shenzhen 518083, Peoples R China. [Yuan, Ping] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Guangzhou 510120, Guangdong, Peoples R China. [Li, Jiangchao; Guan, Xinyuan] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, Guangzhou 510060, Guangdong, Peoples R China. [Li, Jiangchao] Guangdong Pharmaceut Univ, Vasc Biol Res Inst, Guangzhou 510006, Guangdong, Peoples R China. [Guan, Xinyuan] Univ Hong Kong, Dept Clin Oncol, Hong Kong 999077, Hong Kong, Peoples R China. [Jing, Xiangyi; Li, Ru; Zhang, Yongling] Guangzhou Med Univ, Prenatal Diagnost Ctr, Guangzhou Women & Children Med Ctr, Guangzhou 510623, Guangdong, Peoples R China. [Ferec, Claude; Chen, Jian-Min] INSERM, U1078, F-29218 Brest, France. [Ferec, Claude; Chen, Jian-Min] Etab Francais Sang EFS Bretagne, F-29218 Brest, France. [Ferec, Claude; Chen, Jian-Min] Univ Bretagne Occidentale, Fac Med & Sci Sante, F-29238 Brest, France. [Ferec, Claude] CHU Brest, Hop Morvan, Lab Genet Mol & Histocompatibilite, F-29609 Brest, France. [Cooper, David N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. [Wang, Jun] Univ Copenhagen, Dept Biol, Copenhagen, Denmark. [Huang, Dongsheng] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Orthoped, Guangzhou 510120, Guangdong, Peoples R China. RP Huang, DS (reprint author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Orthoped, Guangzhou 510120, Guangdong, Peoples R China. EM huangdongshen18@hotmail.com; Jian-Min.Chen@univ-brest.fr; ywzhong@hotmail.com RI ahmed, Jamila/E-8653-2015 FU National Natural Science Foundation of China [31271342, 81371908, 81071703]; Ministry of Education of China [20110171110047]; Sun Yat-Sen University [10ykyc07]; Basic Research Funds of the key Universities of China [11ykzd10]; Institute National de la Sante et de la Recherche Medicale (INSERM), France; BIOBASE GmbH; Cardiff University; [NCET-12-0564] FX This work was supported by the National Natural Science Foundation of China [No. 31271342, No. 81371908, No. 81071703], the Ministry of Education of China [20110171110047], the Sun Yat-Sen University [No. 10ykyc07], the NCET-12-0564 program and the Basic Research Funds of the key Universities of China [11ykzd10], and the Institute National de la Sante et de la Recherche Medicale (INSERM), France. DNC receives financial support from BIOBASE GmbH through a license agreement with Cardiff University. 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Takayanagi, Ryoichi Kano, Masanobu Goetz, Magdalena Hirase, Hajime Tanaka, Kohichi TI Astroglial Glutamate Transporter Deficiency Increases Synaptic Excitability and Leads to Pathological Repetitive Behaviors in Mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; NMDA RECEPTOR ANTAGONISTS; TOURETTE-SYNDROME; ANIMAL-MODELS; MUTANT MICE; GLAST; CIRCUITRY; AUTISM; PATHOPHYSIOLOGY; SCHIZOPHRENIA AB An increase in the ratio of cellular excitation to inhibition (E/I ratio) has been proposed to underlie the pathogenesis of neuropsychiatric disorders, such as autism spectrum disorders (ASD), obsessive-compulsive disorder (OCD), and Tourette's syndrome (TS). A proper E/I ratio is achieved via factors expressed in neuron and glia. In astrocytes, the glutamate transporter GLT1 is critical for regulating an E/I ratio. 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C1 [Aida, Tomomi; Yoshida, Junichi; Iino, Yusuke; Soma, Miho; Bai, Ning; Ito, Yukiko; Cui, Wanpeng; Aizawa, Hidenori; Yanagisawa, Michiko; Tanaka, Kohichi] Tokyo Med & Dent Univ, Med Res Inst, Lab Mol Neurosci, Tokyo 1138510, Japan. [Nomura, Masatoshi; Takayanagi, Ryoichi] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. [Tanimura, Asami; Kano, Masanobu] Univ Tokyo, Grad Sch Med, Dept Neurophysiol, Tokyo, Japan. [Nagai, Terumi; Takata, Norio] RIKEN, Brain Sci Inst, Lab Neuron Glia Circuitry, Saitama, Japan. [Tanaka, Kenji F.; Hirase, Hajime] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. [Goetz, Magdalena] Univ Munich, Inst Physiol, Physiol Genom, D-80539 Munich, Germany. [Tanaka, Kohichi] JST, CREST, Saitama, Japan. [Tanaka, Kohichi] Tokyo Med & Dent Univ, Ctr Brain Integrat Res, Tokyo 1138510, Japan. RP Tanaka, K (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Lab Mol Neurosci, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan. EM tanaka.aud@mri.tmd.ac.jp RI ahmed, Jamila/E-8653-2015 FU Strategic Research Program for Brain Sciences (SRPBS) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); MEXT [22700328]; Moritani Scholarship Foundation; Medical Research Institute (MRI), of TMDU; MRI of TMDU FX This work was supported by the Strategic Research Program for Brain Sciences (SRPBS) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT, to KT and MK). Additional support was provided by a Grant-in-Aid for Science Research (22700328 to TA) from MEXT, grants to TA from The Moritani Scholarship Foundation, a grant to JY from the Medical Research Institute (MRI), of TMDU, and the Joint Usage/Research Program of the MRI of TMDU to KFT. The authors declare no conflict of interest. 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Rats communicate in the ultrasonic range by means of ultrasonic vocalizations (USV). Depending on developmental stage and affective state, rats emit various distinct types of USV, with appetitive 50-kHz USV being induced by positive social interactions, like juvenile social play, probably serving an affiliative communicative function, namely to (re)establish or induce social proximity. In rats and mice selectively bred for low (LAB) and high (HAB) anxietyrelated behavior, the emission of isolation-induced distress USV during maternal deprivation as pups correlates with innate high levels of hypothalamic AVP availability. Moreover, male LAB and HAB rats express deficits in social approach towards conspecifics, together with high and/or abnormal forms of aggression when confronted with harmless opponents, possibly due to a lack of social communication skills. The aim of this study was therefore (1) to investigate and characterize social play behavior and concomitant pro-social 50-kHz USV emission in male and female, juvenile LAB and HAB rats and to compare them to non-selected Wistar (NAB) rats; and (2) to link these findings pharmacologically to the central AVP system via applying an AVP la receptor (V1aR) antagonist (0.75 mu g; Manning compound) or synthetic AVP (1 ng) into the lateral ventricle of male juvenile NAB rats. Our results show that reduced social play behavior in highly anxious male and female, juvenile HAB rats is accompanied by low amounts of pro-social 50-kHzUSV, as compared to respective LAB and NAB rats, possibly reflecting a lack of positive affective states in expectation of or following social interactions in these individuals. Secondly, although synthetic AVP did not alter social play behavior and pro-social 50-kHz USV, we demonstrated for the first time that a blockade of the central AVP system not only reduces juvenile social play behavior, but at the same time pro-social 50-kHz USV emission rates, indicating an involvement of the social neuropeptide in regulating affiliative communication in rodents. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lukas, Michael] Univ Regensburg, Fac Biol, Behav & Mol Neurobiol, D-93053 Regensburg, Germany. [Woehr, Markus] Univ Marburg, Fac Psychol, Behav Neurosci, D-35032 Marburg, Germany. RP Lukas, M (reprint author), Univ Regensburg, Fac Biol, Behav & Mol Neurobiol, Univ Str 31, D-93053 Regensburg, Germany. EM Michael.Lukas@ur.de; woehrm@staff.uni-marburg.de FU German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [WO 1732/1-1] FX This work was supported in part by a grant from the German Research Foundation to MW (Deutsche Forschungsgemeinschaft, DFG; WO 1732/1-1). Resources had no further role in study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the manuscript for publication. 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We created a probabilistic model to separately estimate stimulus and individual differences in behavioral data from 165 individuals viewing up to 14 different McGurk stimuli. The noisy encoding of disparity (NED) model characterizes stimuli by their audiovisual disparity and characterizes individuals by how noisily they encode the stimulus disparity and by their disparity threshold for perceiving the illusion. The model accurately described perception of the McGurk effect in our sample, suggesting that differences between individuals are stable across stimulus differences. The most important benefit of the NED model is that it provides a method to compare multisensory integration across individuals and groups without the confound of stimulus differences. An added benefit is the ability to predict frequency of the McGurk effect for stimuli never before seen by an individual. C1 [Magnotti, John F.; Beauchamp, Michael S.] Univ Texas Houston, Med Sch Houston, Dept Neurobiol & Anat, Houston, TX 77030 USA. RP Magnotti, JF (reprint author), Univ Texas Houston, Med Sch Houston, Dept Neurobiol & Anat, 6431 Fannin St,Suite G550, Houston, TX 77030 USA. EM john.magnotti@gmail.com; michael.s.beauchamp@gmail.com FU NIH [R01NS065395] FX This research was supported by NIH R01NS065395 to MSB. We thank Wei Ji Ma and xaq pitkow for helpful comments. 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Bull. Rev. PD JUN PY 2015 VL 22 IS 3 BP 701 EP 709 DI 10.3758/s13423-014-0722-2 PG 9 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA CH7FA UT WOS:000354199800009 PM 25245268 ER PT J AU Santiesteban, I Shah, P White, S Bird, G Heyes, C AF Santiesteban, Idalmis Shah, Punit White, Sarah Bird, Geoffrey Heyes, Cecilia TI Mentalizing or submentalizing in a communication task? Evidence from autism and a camera control SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Perspective-taking; Mentalizing; Submentalizing; Object-centered spatial coding; Director task; Autism ID HIGH-FUNCTIONING AUTISM; PERSPECTIVE-TAKING; MIND; SPECTRUM; ADULTS AB In the director task (DT), participants are instructed to move objects within a grid of shelves while ignoring those objects that cannot be seen by a human figure, the "director," located beyond the shelves. It is widely assumed that, since they are explicitly instructed to do, participants use mentalizing in this communicative task; they represent what the director can see, and therefore the DT provides important information about how and when mentalizing is used in adult life. We tested this view against a "submentalizing" hypothesis suggesting that DT performance depends on object-centered spatial coding, without mentalizing. As predicted by the submentalizing account, we found that DT performance was unchanged when the director was replaced by an inanimate object, a camera, and that participants with autism spectrum disorders were unimpaired, relative to matched control participants, in both the director and camera conditions. In combination with recent critical analyses of "implicit mentalizing," these findings support the view that adults use mentalizing sparingly in psychological experiments and in everyday life. C1 [Santiesteban, Idalmis; Shah, Punit] Univ London, Dept Psychol Sci, London WC1E 7HX, England. [Shah, Punit; Bird, Geoffrey] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [White, Sarah; Bird, Geoffrey] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Heyes, Cecilia] Univ Oxford, All Souls Coll, Oxford OX1 4AL, England. RP Santiesteban, I (reprint author), Univ London, Dept Psychol Sci, Malet St, London WC1E 7HX, England. EM i.santiesteban@bbk.ac.uk FU Economic and Social Research Council [ES/H013504/1] FX The authors thank Iroise Dumontheil for providing helpful feedback on an earlier version of the manuscript. This work was supported by an Economic and Social Research Council studentship [ES/H013504/1] awarded to I.S. 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We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2 mg/kg) was given to the experimental group (VPA_AST, n = 10) while saline was given to the control group (VPA, n = 10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autismlike features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity. (C) 2015 Elsevier B.V. All rights reserved. C1 [Al-Amin, Md. Mamun; Rahman, Md. Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Reza, Hasan Mahmud] North South Univ, Dept Pharmaceut Sci, Dhaka 1229, Bangladesh. RP Reza, HM (reprint author), Plot 15,Block B, Dhaka 1229, Bangladesh. 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Brain Res. PD JUN 1 PY 2015 VL 286 BP 112 EP 121 DI 10.1016/j.bbr.2015.02.041 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG8XS UT WOS:000353599600018 PM 25732953 ER PT J AU Thinnes, FP AF Thinnes, Friedrich P. TI Phosphorylation, nitrosation and plasminogen K3 modulation make VDAC-1 lucid as part of the extrinsic apoptotic pathway-Resulting thesis: Native VDAC-1 indispensible for finalisation of its 3D structure SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE Porin; VRAC; Cystic fibrosis; Alzheimers disease; Autism; Malaria ID DEPENDENT ANION CHANNEL; HUMAN B-LYMPHOCYTES; MITOCHONDRIAL OUTER-MEMBRANE; PEPTIDE-SPECIFIC ANTIBODIES; HUMAN PORIN; TYPE-1 VDAC; PLASMA-MEMBRANE; VERTEBRATE PORIN; SKELETAL-MUSCLE; CYSTIC-FIBROSIS AB Native and recombinant VDAC preparations differ in their acetylation, phosphorylation and nitrosation state; additionally, proteineous modulators are missing in the latter. They thus vary in channel characteristics, as can be taken from comparative black lipid bilayer experiments. Furthermore, the multi-compartment expression makes expect even differing native VDAC-1 molecules. Recent structural work on mammalian VDAC-1 has only used recombinant material, refolded from Escherichia coli inclusion bodies. While this approach established the basic three-dimensional structure of VDAC-1, a ss-barrel set up by nineteen ss-pleated sheets, dissent is on positioning and movements of its free N-terminal helical peptide stretch preceding E-pleated sheet-1. A synopsis of data concerning posttranslational modifications, cytotopology and physiology of native VDAC-1, from my point of view, suggests that the finalisation of its three-dimensional structure will need native channel preparations to be studied. Concerning relevance, recent evidence on the regulation of cell membrane-integrated VDAC-1 by posttranslational modifications and proteineous modulators, taken together with experimental demonstrations that VDAC-1 is involved in cell volume regulation, it thus may be part of the extrinsic apoptotic pathway can hopefully help to understand some relevant medical syndromes, e.g. cystic fibrosis, Alzheimer's disease, autism and malaria. (C) 2015 Elsevier B.V. All rights reserved. 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Biophys. Acta-Biomembr. PD JUN PY 2015 VL 1848 IS 6 BP 1410 EP 1416 DI 10.1016/j.bbamem.2015.02.031 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CH0YE UT WOS:000353747500016 ER PT J AU Feuerriegel, D Churches, O Hofmann, J Keage, HAD AF Feuerriegel, Daniel Churches, Owen Hofmann, Jessica Keage, Hannah A. D. TI The N170 and face perception in psychiatric and neurological disorders: A systematic review SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE N170; VPP; M170; Systematic review; Event-related potentials; Face perception ID EVENT-RELATED POTENTIALS; AUTISM SPECTRUM DISORDER; EMOTIONAL FACIAL EXPRESSIONS; AFFECT RECOGNITION DEFICITS; BRAIN POTENTIALS; BIPOLAR DISORDER; PARKINSONS-DISEASE; SOCIAL PHOBIA; ERP EVIDENCE; NEUROPHYSIOLOGICAL RESPONSES AB Objective: To systematically evaluate evidence for configural and affective face processing abnormalities as measured by the N170 and Vertex Positive Potential (VPP) event-related potential components, and analogous M170 magnetoencephalography (MEG) component, in neurological and psychiatric disorders. Methods: 1251 unique articles were identified using PsychINFO and PubMed databases. Sixty-seven studies were selected for review, which employed various tasks to measure the N170, M170 or VPP; the 13 neurological/psychiatric conditions were Attention-Deficit Hyperactivity Disorder (ADHD), Alcohol Dependence, Alzheimer's Disease, Autism Spectrum Disorders (ASDs), Bipolar Disorder, Bulimia Nervosa, Fibromyalgia, Huntington's Disease, Major Depressive Disorder, Parkinson's Disease, Prosopagnosia, Schizophrenia and Social Phobia. Results: Smaller N170 and VPP amplitudes to faces compared to healthy controls were consistently reported in Schizophrenia but not in ASDs. In Schizophrenia N170 and VPP measures were not correlated with clinical symptoms. Findings from other disorders were highly inconsistent; however, reported group differences were almost always smaller amplitudes or slower latencies to emotional faces in disordered groups regardless of diagnosis. Conclusions: Results suggest that N170/VPP abnormalities index non-specific facial affect processing dysfunction in these neurological and psychiatric conditions, reflecting social impairments being broadly characteristic of these groups. Significance: The N170 and analogous components hold promise as diagnostic and treatment monitoring biomarkers for social dysfunction. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Feuerriegel, Daniel; Hofmann, Jessica; Keage, Hannah A. D.] Univ S Australia, Cognit Neurosci Lab, Adelaide, SA 5001, Australia. [Churches, Owen] Flinders Univ S Australia, Brain & Cognit Lab, Adelaide, SA 5001, Australia. RP Feuerriegel, D (reprint author), Univ S Australia, Sch Psychol Social Work & Social Policy, Cognit Neurosci Lab, St Bernards Rd, Adelaide, SA 5001, Australia. EM Daniel.Feuerriegel@Unisa.edu.au FU Australian National Health and Medical Research Council Training Award [568890] FX H.A.D.K. was supported by an Australian National Health and Medical Research Council Training Award (568890). We thank Dr Mark Kohler for his support within the UniSA Cognitive Neuroscience Laboratory. 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Neurophysiol. PD JUN PY 2015 VL 126 IS 6 BP 1141 EP 1158 DI 10.1016/j.clinph.2014.09.015 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH1ME UT WOS:000353785000011 PM 25306210 ER PT J AU Ricketts, J Dockrell, JE Patel, N Charman, T Lindsay, G AF Ricketts, Jessie Dockrell, Julie E. Patel, Nita Charman, Tony Lindsay, Geoff TI Do children with specific language impairment and autism spectrum disorders benefit from the presence of orthography when learning new spoken words? SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE Specific language impairment; Autism spectrum disorders; Word learning; Vocabulary; Vocabulary acquisition; Orthographic facilitation; Orthography ID READING-COMPREHENSION; BEGINNING READERS; MNEMONIC VALUE; SIMPLE VIEW; ACQUISITION; CONSISTENCY; DISABILITY; HYPOTHESIS; KNOWLEDGE; MEANINGS AB This experiment investigated whether children with specific language impairment (SLI), children with autism spectrum disorders (ASD), and typically developing children benefit from the incidental presence of orthography when learning new oral vocabulary items. Children with SLI, children with ASD, and typically developing children (n = 27 per group) between 8 and 13 years of age were matched in triplets for age and nonverbal reasoning. Participants were taught 12 mappings between novel phonological strings and referents; half of these mappings were trained with orthography present and half were trained with orthography absent. Groups did not differ on the ability to learn new oral vocabulary, although there was some indication that children with ASD were slower than controls to identify newly learned items. During training, the ASD, SLI, and typically developing groups benefited from orthography to the same extent. In supplementary analyses, children with SLI were matched in pairs to an additional control group of younger typically developing children for nonword reading. Compared with younger controls, children with SLI showed equivalent oral vocabulary acquisition and benefit from orthography during training. Our findings are consistent with current theoretical accounts of how lexical entries are acquired and replicate previous studies that have shown orthographic facilitation for vocabulary acquisition in typically developing children and children with ASD. We demonstrate this effect in SLI for the first time. The study provides evidence that the presence of orthographic cues can support oral vocabulary acquisition, motivating intervention approaches (as well as standard classroom teaching) that emphasize the orthographic form. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ricketts, Jessie] Univ London, Dept Psychol, Royal Holloway, Egham TW20 0EX, Surrey, England. [Dockrell, Julie E.] UCL, UCL Inst Educ, London WC1H 0AL, England. [Patel, Nita] City Univ London, Div Language & Commun Sci, London EC1V 0HB, England. [Charman, Tony] Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England. [Lindsay, Geoff] Univ Warwick, Ctr Educ Dev Appraisal & Res, Coventry CV4 7AL, W Midlands, England. RP Ricketts, J (reprint author), Univ London, Dept Psychol, Royal Holloway, Egham TW20 0EX, Surrey, England. EM jessie.ricketts@rhul.ac.uk FU UK Department for Education as part of the Better Communication Research Programme FX We acknowledge the support of all the students, their families, and their schools. We are also grateful to Olympia Palikara and Mia Travlos for assistance with data collection. This research was funded by the UK Department for Education as part of the Better Communication Research Programme (https://www.gov.uk/governmentiorganisationsidepartment-for-education/se ries/better-communication-research-programme, accessed 28 August 2014). 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Exp. Child Psychol. PD JUN PY 2015 VL 134 BP 43 EP 61 DI 10.1016/j.jecp.2015.01.015 PG 19 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA CH0SZ UT WOS:000353734000004 PM 25795987 ER PT J AU Perez-Gonzalez, LA Diaz, E Fernandez-Garcia, S Baizan, C AF Antonio Perez-Gonzalez, Luis Diaz, Elvira Fernandez-Garcia, Silvia Baizan, Cristina TI Stimuli with identical contextual functions taught independently become functionally equivalent SO LEARNING & BEHAVIOR LA English DT Article DE Contextual control; Stimulus relations; Stimulus equivalence; Associative learning; Functional equivalence; Language; Verbal behavior ID 2ND-ORDER CONDITIONAL DISCRIMINATIONS; LEARNING-SET; CHILDREN; SAMPLE; REINFORCEMENT; EXPANSION; PIGEONS; ADULTS AB A novel learning process that does not require stimulus associations was explored in humans. The hypothesis was that two contextual stimuli taught in separate settings, with different stimuli, become equivalent if they accomplish identical functions with regard to the relations between the stimuli presented with them. The procedure consisted of : (a) first teaching an AB conditional discrimination (e.g., match A1 to B1 and A2 to B2) and then teaching a second-order XAB conditional discrimination in which X1 indicated performing the same selections as in AB and X2 indicated selecting the alternative comparison (e.g., match A1 to B2 and A2 to B1); (b) repeating the procedure with completely new stimuli, YHJ, in which the functions of the Y stimuli were identical to those of X; and (c) conducting a final probe under extinction to verify the equivalence between the X and the Y stimuli. Three experiments were conducted to explore the process and to rule out the influence of alternative variables. Out of these, 13 of the 14 participants matched the stimuli to the same contextual functions. Thus, the hypothesis was verified. These results demonstrate that humans are able to match stimuli according to their functions in relation to other stimuli. This process may be very much involved in language; for example, understanding that words or clauses that have been learned in separate contexts and with separate stimuli share the same meaning. Understanding this process may help to identify learning or developmental problems, such as those shown by persons with autism, and help to treat them. C1 [Antonio Perez-Gonzalez, Luis] Univ Oviedo, Dept Psychol, Oviedo 33003, Spain. [Diaz, Elvira; Fernandez-Garcia, Silvia; Baizan, Cristina] Univ Oviedo, Sch Psychol, Oviedo 33003, Spain. RP Perez-Gonzalez, LA (reprint author), Univ Oviedo, Dept Psychol, Plaza Feijoo S-N,Despacho 209, Oviedo 33003, Spain. EM laperez@uniovi.es FU Ministerio de Ciencia e Innovacion, Spain [PSI2009-08644] FX This research was supported by grant PSI2009-08644 from the Ministerio de Ciencia e Innovacion, Spain, to the first author, who directed the study. The other three authors contributed approximately equally. The authors thank two anonymous reviewers of previous versions of the manuscript, and Jeanne Speakman for editing the manuscript. CR Carpentier F, 2002, PSYCHOL REC, V52, P351 Carpentier F, 2002, PSYCHOL REC, V52, P139 Carpentier F, 2000, PSYCHOL REC, V50, P671 HARLOW HF, 1949, PSYCHOL REV, V56, P51, DOI 10.1037/h0062474 Honey RC, 1999, J EXP PSYCHOL ANIM B, V25, P324, DOI 10.1037//0097-7403.25.3.324 Junior J. L., 2001, COMPORTAMENTO COGNIC, P401 Junior J. 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PD JUN PY 2015 VL 43 IS 2 BP 113 EP 128 DI 10.3758/s13420-014-0166-6 PG 16 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA CH1WZ UT WOS:000353814600002 PM 25673100 ER PT J AU Gupta, SC Yadav, R Pavuluri, R Morley, BJ Stairs, DJ Dravid, SM AF Gupta, Subhash C. Yadav, Roopali Pavuluri, Ratnamala Morley, Barbara J. Stairs, Dustin J. Dravid, Shashank M. TI Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity SO NEUROPHARMACOLOGY LA English DT Article DE Glutamate; Dendritic spine; GRID1; GluD1; GluN2B ID CANDIDATE GENES; PRESYNAPTIC DIFFERENTIATION; PREFRONTAL CORTEX; SYNAPSE FORMATION; LIM-KINASE; RECEPTOR; AUTISM; PLASTICITY; COFILIN; NEURONS AB The glutamate delta-1 (GluD1) receptor is highly expressed in the forebrain. We have previously shown that loss of GluD1 leads to social and cognitive deficits in mice, however, its role in synaptic development and neurotransmission remains poorly understood. Here we report that GluD1 is enriched in the medial prefrontal cortex (mPFC) and GluD1 knockout mice exhibit a higher dendritic spine number, greater excitatory neurotransmission as well as higher number of synapses in mPFC. In addition abnormalities in the LIMK1-cofilin signaling, which regulates spine dynamics, and a lower ratio of GluN2A/GluN2B expression was observed in the mPFC in GluD1 knockout mice. Analysis of the GluD1 knockout CA1 hippocampus similarly indicated the presence of higher spine number and synapses and altered LIMK1-cofilin signaling. We found that systemic administration of an N-methyl-D-aspartate (NMDA) receptor partial agonist D-cycloserine (DCS) at a high-dose, but not at a low-dose, and a GluN2B-selective inhibitor Ro-25-6981 partially normalized the abnormalities in LIMK1-cofilin signaling and reduced excess spine number in mPFC and hippocampus. The molecular effects of high-dose DCS and GluN2B inhibitor correlated with their ability to reduce the higher stereotyped behavior and depression-like behavior in GluD1 knockout mice. Together these findings demonstrate a critical requirement for GluD1 in normal spine development in the cortex and hippocampus. Moreover, these results identify inhibition of GluN2B-containing receptors as a mechanism for reducing excess dendritic spines and stereotyped behavior which may have therapeutic value in certain neurodevelopmental disorders such as autism. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Gupta, Subhash C.; Yadav, Roopali; Pavuluri, Ratnamala; Dravid, Shashank M.] Creighton Univ, Dept Pharmacol, Omaha, NE 68178 USA. [Stairs, Dustin J.] Creighton Univ, Dept Psychol, Omaha, NE 68178 USA. [Morley, Barbara J.] Boys Town Natl Res Hosp, Neurochem Lab, Omaha, NE 68178 USA. RP Dravid, SM (reprint author), Creighton Univ, Sch Med, Dept Pharmacol, 2500 Calif Plaza, Omaha, NE 68178 USA. EM ShashankDravid@creighton.edu FU Health Future Foundation; Faculty Development Award [LB692]; EPSCoR Award; National Institute of Health (NIH) [1R21MH098270]; NE DHHS [2014-08]; National Center for Research Resources [G20RR024001] FX This work was supported by Health Future Foundation (SMD), LB692 Faculty Development Award (SMD), EPSCoR Award (SMD, BJM), National Institute of Health (NIH) #1R21MH098270 (SMD) and a grant from NE DHHS (Stem Cell 2014-08). The project was also supported by G20RR024001 from National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. We thank Dr. Suneet Mehrotra and Dr. Thomas F. Murray for providing technical support and resources for Gene Gun and Imaris analysis. 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B. Hauser-Cram, P. Crossman, M. K. TI Relationship dimensions of the 'Down syndrome advantage' SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE behavioural phenotypes; Down syndrome; intellectual disability; parents ID YOUNG-CHILDREN; PRESCHOOL-CHILDREN; BEHAVIOR PROBLEMS; PARENTING STRESS; SYNDROME SPECIFICITY; INTELLECTUAL DISABILITY; MATERNAL DIRECTIVENESS; DEVELOPMENTAL DELAY; MOTHERS; AUTISM AB BackgroundSome researchers have proposed an advantage' for parents of children with Down syndrome over parents of children with other intellectual disabilities, especially in relation to experiencing less parenting stress. Others have maintained that these differences are an artefact of demographic and related differences. This study extends the investigation of possible differences in dimensions of parenting stress and also examines whether differences exist in maternal and child contingent responsiveness during mother-child interaction in these two groups. MethodMothers of children with Down syndrome (n=43) and undifferentiated developmental disabilities (n=54) completed measures of children's adaptive functioning and behaviour problems, parenting stress and maternal social support. Observers rated the contingent interactions between mothers and children using the Nursing Child Assessment Teaching Scale. ResultsOnce mother's age, education and social support as well as child adaptive functioning and behaviour problems were considered, neither parent nor child related parenting stress demonstrated an advantage for parents of children with Down syndrome. However, a Down syndrome advantage' was apparent for both maternal and child contingent responsiveness after accounting for maternal demographic and contextual variables and child attributes. ConclusionsChildren with Down syndrome and their mothers have more positive interactions than children with other developmental disabilities, both in terms of the responsiveness of mothers and of child responses contingent on maternal behaviour. These findings suggest that both children with Down syndrome themselves and their mothers are contributing to a Down syndrome advantage. C1 [Mitchell, D. B.] Colby Sawyer Coll, Social Sci & Educ, New London, NH 03257 USA. [Hauser-Cram, P.] Boston Coll, Counseling Dev & Educ Psychol Dept, Chestnut Hill, MA 02167 USA. [Crossman, M. K.] Brandeis Univ, Lurie Inst Disabil Policy, Heller Sch Social Policy & Management, Waltham, MA USA. [Crossman, M. K.] Boston Children Hosp, Boston, MA USA. RP Mitchell, DB (reprint author), Colby Sawyer Coll, Social Sci & Educ, 541 Main St,Colgate 309, New London, NH 03257 USA. EM darcy.b.mitchell@colby-sawyer.edu FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC08956]; NIMH/NIH [R25 MH071286]; LEND grant, Maternal Child and Health Bureau [T73MH00020] FX The Early Intervention Collaborative Study (EICS) is funded by Grant No. R40 MC08956 through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. Additional partial support for manuscript preparation was provided by NIMH/NIH R25 MH071286 and LEND grant T73MH00020, Maternal Child and Health Bureau. This study was approved by the Institutional Review Board at Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467. We wish to thank the many children and families who have participated in this investigation. CR Abbeduto L, 2004, AM J MENT RETARD, V109, P237, DOI 10.1352/0895-8017(2004)109<237:PWACIM>2.0.CO;2 Abidin R. 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P., 2000, NEURONS NEIGHBORHOOD Slonims V, 2006, AM J MENT RETARD, V111, P273, DOI 10.1352/0895-8017(2006)111[273:AOMIII]2.0.CO;2 Sparrow S, 1984, VINELAND ADAPTIVE BE Stoneman Z, 2007, J INTELL DISABIL RES, V51, P1006, DOI 10.1111/j.1365-2788.2007.01012.x Trevarthen C, 2001, J CHILD PSYCHOL PSYC, V42, P3, DOI 10.1017/S0021963001006552 Warren SF, 2007, MENT RETARD DEV D R, V13, P330, DOI 10.1002/mrdd.20177 Widaman K. F., 1996, STRUCTURE ADAPTIVE B, DOI [10.1037/10203-006, DOI 10.1037/10203-006] WISHART JG, 1990, J MENT DEFIC RES, V34, P409 NR 64 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD JUN PY 2015 VL 59 IS 6 BP 506 EP 518 DI 10.1111/jir.12153 PG 13 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA CG4GG UT WOS:000353242900002 PM 25070618 ER PT J AU Minnes, P Perry, A Weiss, JA AF Minnes, P. Perry, A. Weiss, J. A. TI Predictors of distress and well-being in parents of young children with developmental delays and disabilities: the importance of parent perceptions SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE coping; developmental disability; parent stress; young children ID INTELLECTUAL DISABILITY; PRESCHOOL-CHILDREN; BEHAVIOR PROBLEMS; POSITIVE PERCEPTIONS; FAMILY IMPACT; SELF-EFFICACY; MENTAL-HEALTH; MOTHERS; EMPOWERMENT; AUTISM AB BackgroundMoving from family-centred to child-centred models of service delivery can be stressful for parents as their young children with developmental delays and disabilities transition into school. The purpose of this paper was to explore and compare predictors of both distress and well-being in parents during this transition period. MethodsA sample of 155 mothers of 113 boys and 42 girls participated in the study. The mean age of the children was 4.9 years and their diagnoses included autism spectrum disorder (52%); unspecified intellectual disability/developmental delay (26%); Down syndrome (12%); other genetic conditions (4%) and other diagnoses (6%). Participants completed surveys primarily online focusing on child characteristics, family resources, parent coping strategies, parental distress and positive gain. ResultsMultiple regression analyses were conducted to determine predictors of parent reported distress and positive gain. Parent coping variables were the strongest predictors of both positive gain and parental distress, with reframing emerging as a predictor of positive gain and parent empowerment emerging as a predictor of both greater positive gain and lower parental distress. ConclusionsThe results of this study highlight not only the importance of including positive as well as negative outcomes in research with parents but also the importance of including parent characteristics such as coping strategies (e.g. reframing and empowerment/self-efficacy) as potential predictors of outcome in such studies. C1 [Minnes, P.] Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. [Perry, A.; Weiss, J. A.] York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada. RP Minnes, P (reprint author), Queens Univ, Psychol, 62 Arch St,32 Newcourt Pl, Kingston, ON K7L 3N6, Canada. EM patricia.minnes@queensu.ca FU Canadian Institutes for Health Research [94788] FX This research was funded by the Canadian Institutes for Health Research (Grant #94788) Data for this study were collected as part of the Canadian Institutes for Health Research Team HELPS Inc: Health Education and Learning Partnerships Promoting Social Inclusion of Children with Developmental Delays and Disabilities. 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A., 2003, J DEV DISABILITIES, V10, P129 Wildenger LK, 2011, J CHILD FAM STUD, V20, P387, DOI 10.1007/s10826-010-9403-6 Zimmerman MA, 1995, AM J COMMUN PSYCHOL, V23, P581, DOI 10.1007/BF02506983 Zimmerman MA, 1998, REHABIL PSYCHOL, V43, P3, DOI 10.1037//0090-5550.43.1.3 NR 52 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 EI 1365-2788 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD JUN PY 2015 VL 59 IS 6 BP 551 EP 560 DI 10.1111/jir.12160 PG 10 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA CG4GG UT WOS:000353242900006 PM 25169777 ER PT J AU Griffith, GM Hastings, RP Petalas, MA Lloyd, TJ AF Griffith, G. M. Hastings, R. P. Petalas, M. A. Lloyd, T. J. TI Mothers' expressed emotion towards children with autism spectrum disorder and their siblings SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE ASD; autism; expressed emotion; family; mothers; siblings ID MENTAL-HEALTH STATUS; FRAGILE-X-SYNDROME; BEHAVIOR PROBLEMS; INTELLECTUAL DISABILITY; DOWN-SYNDROME; DEVELOPMENTAL DISABILITY; PSYCHOLOGICAL IMPACT; RELATIONSHIP QUALITY; SYNDROME SPECIFICITY; PRESCHOOL-CHILDREN AB BackgroundExpressed emotion (EE) is a construct used to measure the emotional climate within families. EE is of interest to researchers in the field of autism spectrum disorder (ASD) because of its putative implications for child development. The aim was to explore whether maternal EE differs towards a child with ASD and a non-disabled sibling. MethodsWe adopted a within-family design with 143 mothers of children with ASD and a non-disabled sibling. EE was measured using the Five-Minute Speech Sample. ResultsWilcoxon signed-rank tests were utilised. Mothers were coded as significantly more critical and less warm towards their child with ASD than towards the sibling. There were no significant differences in maternal emotional overinvolvement or overall EE towards the child with ASD and a sibling. ConclusionsThe data support the results of previous research suggesting that EE is linked to the relationship a mother has with individual children, rather than being evidence of the character disposition of mothers. More research is needed to understand the emotional dimensions of parent-child relationships in families with children with ASD. C1 [Griffith, G. M.; Lloyd, T. J.] Bangor Univ, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales. [Hastings, R. P.] Univ Warwick, CEDAR, Warwick, England. [Petalas, M. A.] Mental Healthcare UK Ltd, Llangwyfan, Denbigh, England. RP Griffith, GM (reprint author), Bangor Univ, Psychol, Briganita Bldg,Penrhalt Rd, Bangor LL57 2AS, Gwynedd, Wales. EM g.m.griffith@bangor.ac.uk FU Bangor University; National Autistic Society Cymru; European Social Fund FX This research was supported in part by funding from Bangor University, the National Autistic Society Cymru and the European Social Fund, objective 1 area funding. No conflict of interest is declared. 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Intell. Disabil. Res. PD JUN PY 2015 VL 59 IS 6 BP 580 EP 587 DI 10.1111/jir.12178 PG 8 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA CG4GG UT WOS:000353242900009 PM 25521064 ER PT J AU Omori, M Yamamoto, J AF Omori, Mikimasa Yamamoto, Jun-ichi TI Spelling Instruction by Stimulus Pairing in Japanese Students with Autism Spectrum Disorders: Effects of Stimulus Presentation Order SO PSYCHOLOGICAL RECORD LA English DT Article DE Stimulus pairing procedure; Stimulus relations; Spelling; Autism spectrum disorders ID EQUIVALENCE-RELATIONS; TO-SAMPLE; DISABILITIES; CHILDREN; DISCRIMINATION; INDIVIDUALS; FAMILIARITY; ATTENTION; SKILLS; SELF AB Students with autism spectrum disorder (ASD) often have difficulties in learning stimulus relations in spelling. Using the two-stimulus pairing procedure, we examined the emergence of stimulus relations between Japanese and English words by comparing the spelling performance of five students with ASD with that of five typically developing students. In the Japanese-English pairing procedure, a Japanese word was presented first, followed by its English translation, and in the English-Japanese pairing, an English word was presented first, followed by its Japanese translation. Training effects were evaluated with a sign test and analysis of variance. All the students correctly spelled the English words in both procedures. The Japanese-English pairing procedure required fewer training blocks than the English-Japanese pairing procedure. In the Japanese-English pairing, students with ASD required fewer training blocks than typically developing students. 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Rec. PD JUN PY 2015 VL 65 IS 2 BP 401 EP 410 DI 10.1007/s40732-014-0114-z PG 10 WC Psychology, Multidisciplinary SC Psychology GA CG5OL UT WOS:000353341500015 ER PT J AU Casey, AF Quenneville-Himbeault, G Normore, A Davis, H Martell, SG AF Casey, Amanda Faith Quenneville-Himbeault, Gabriel Normore, Alexa Davis, Hanna Martell, Stephen G. TI A Therapeutic Skating Intervention for Children With Autism Spectrum Disorder SO PEDIATRIC PHYSICAL THERAPY LA English DT Article DE activities of daily living; autism spectrum disorder; child; human; male; motor skills; physical activity; postural balance ID PHYSICAL-ACTIVITY; DISABILITIES; INDIVIDUALS; EXERCISE AB Purpose: The purpose of this study was to evaluate the effects of a highly structured therapeutic skating intervention on motor outcomes and functional capacity in 2 boys with autism spectrum disorder aged 7 and 10 years. Methods: This multiple-baseline, single-subject study assigned participants to three 1-hour skating sessions per week for 12 weeks focusing on skill and motor development. Multiple data points assessed (a) fidelity to the intervention and (b) outcomes measures including the Pediatric Balance Scale, Timed Up and Go, floor to stand, Six-Minute Walk Test, goal attainment, and weekly on-ice testing. Results: Improvements were found in balance, motor behavior, and functional capacity by posttest with gains remaining above pretest levels at follow-up. Conclusions: Therapeutic skating may produce physical benefits for children with autism spectrum disorder and offer a viable, inexpensive community-based alternative to other forms of physical activity. C1 [Casey, Amanda Faith; Quenneville-Himbeault, Gabriel; Normore, Alexa; Davis, Hanna; Martell, Stephen G.] St Francis Xavier Univ, Dept Human Kinet, Antigonish, NS B2G 2R6, Canada. 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Phys. Ther. PD SUM PY 2015 VL 27 IS 2 BP 170 EP 177 DI 10.1097/PEP.0000000000000139 PG 8 WC Pediatrics; Rehabilitation SC Pediatrics; Rehabilitation GA CE8EW UT WOS:000352075400017 PM 25822357 ER PT J AU Bhat, A Bubela, D AF Bhat, Anjana Bubela, Deborah TI Commentary on "A Therapeutic Skating Intervention for Children With Autism Spectrum Disorder" SO PEDIATRIC PHYSICAL THERAPY LA English DT Editorial Material C1 [Bhat, Anjana] Univ Delaware, Phys Therapy Program, Newark, DE 19716 USA. [Bhat, Anjana; Bubela, Deborah] Univ Connecticut, Phys Therapy Program, Storrs, CT USA. RP Bhat, A (reprint author), Univ Delaware, Phys Therapy Program, Newark, DE 19716 USA. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0898-5669 EI 1538-005X J9 PEDIATR PHYS THER JI Pediatr. Phys. Ther. PD SUM PY 2015 VL 27 IS 2 BP 177 EP 177 DI 10.1097/PEP.0000000000000140 PG 1 WC Pediatrics; Rehabilitation SC Pediatrics; Rehabilitation GA CE8EW UT WOS:000352075400018 PM 25822358 ER PT J AU Good, B Fang, L AF Good, Bethany Fang, Lin TI Promoting Smart and Safe Internet Use Among Children with Neurodevelopmental Disorders and Their Parents SO CLINICAL SOCIAL WORK JOURNAL LA English DT Article DE Internet safety; Cyber bullying; Digital literacy; Digital citizenship; Autism spectrum; Learning disabilities; Mental health; Group therapy; ADHD ID AUTISM SPECTRUM DISORDERS; LEARNING-DISABILITIES; MENTAL-HEALTH; ADOLESCENTS; ONLINE; PREVALENCE; YOUTH; VICTIMIZATION; COMMUNICATION; ADDICTION AB Technological devices and the internet have become standard tools used by young people in their social, recreational and educational contexts. The utility of digital technology continues to expand and influence the ways young people socialize, learn about the world and develop and experiment with identity. The ability to remain in one's own home while also connecting with others can be perceived as safer than venturing out in the offline world; however, there are a variety of risks associated with online activities. Some youth may be more at risk of harm than others, such as youth with neurodevelopmental disorders including learning disabilities (LDs), autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD). There is an instinct for adults to be protective of children who struggle with disabilities, leading some parents to take an overprotective approach to their child's internet use. Parents can play a significant role in helping their children navigate the pitfalls associated with online use while enjoying the benefits it provides. In this paper, we discuss the characteristics of young people with neurodevelopmental disorders that may cause difficulties online and review the opportunities and risks associated with internet use. We then discuss ways for parents to provide effective and balanced guidance on internet use for their child by reviewing the literature and offering concepts on digital literacies. The paper ends with a proposed intergenerational, parent-child group intervention that aims to help parents safeguard young people from online harms and offers opportunities for healthy online participation. C1 [Good, Bethany; Fang, Lin] Univ Toronto, Factor Inwentash Fac Social Work, Toronto, ON M5S 1V4, Canada. RP Good, B (reprint author), Univ Toronto, Factor Inwentash Fac Social Work, 246 Bloor St West, Toronto, ON M5S 1V4, Canada. 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Soc. Work J. PD JUN PY 2015 VL 43 IS 2 SI SI BP 179 EP 188 DI 10.1007/s10615-015-0519-4 PG 10 WC Social Work SC Social Work GA CE5WG UT WOS:000351905800008 ER PT J AU Crespi, BJ Hurd, PL AF Crespi, Bernard J. Hurd, Peter L. TI Genetically based correlates of serum oxytocin and testosterone in autism and schizotypy SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Testosterone; Oxytocin; Autism; Schizotypy; Social cognition ID INTRANASAL OXYTOCIN; PERSONALITY-DISORDER; ASPERGER-SYNDROME; PLASMA OXYTOCIN; HORMONE-LEVELS; RECEPTOR GENE; HUMAN BRAIN; SCHIZOPHRENIA; AMYGDALA; BEHAVIOR AB The hormones oxytocin and testosterone have been implicated in autism spectrum and schizophrenia-spectrum cognition and disorders, but their roles in mediating these psychological phenotypes remain largely unknown. We genotyped a large set of healthy individuals for loci that represent established genetic indicators of serum testosterone and oxytocin levels, and tested for associations of these genetic indices of hormone levels with self-report measures of autistic and schizotypal cognition. A low genetic index of testosterone, a high genetic index of oxytocin, and/or a low ratio of testosterone to oxytocin indices were positively correlated with high imagination (by the Autism Quotient) and high positive and total schizotypy (by the Schizotypal Personality Questionnaire). The genetic indices for oxytocin, and testosterone relative to oxytocin, also showed significant correlations with a metric of positive schizotypy relative to autism, implicating higher oxytocin and lower testosterone in increased positively-schizotypal traits combined with decreased autism-associated traits. These results link genetic indicators of serum hormone levels with measures of schizotypy and autism among healthy individuals. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Crespi, Bernard J.] Simon Fraser Univ, Dept Biol, Burnaby, BC V5A 1S6, Canada. [Hurd, Peter L.] Univ Alberta, Dept Psychol, Edmonton, AB T6G 2R3, Canada. [Hurd, Peter L.] Univ Alberta, Ctr Neurosci, Edmonton, AB T6G 2R3, Canada. RP Crespi, BJ (reprint author), Simon Fraser Univ, Dept Biol, Burnaby, BC V5A 1S6, Canada. EM crespi@sfu.ca FU Natural Science and Engineering Research Council of Canada FX We are grateful to the Natural Science and Engineering Research Council of Canada for support, and to the Editor and three anonymous reviewers for helpful comments. 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Individ. Differ. PD JUN PY 2015 VL 79 BP 39 EP 43 DI 10.1016/j.paid.2015.01.052 PG 5 WC Psychology, Social SC Psychology GA CE2OG UT WOS:000351654300008 ER PT J AU Gallitto, E Leth-Steensen, C AF Gallitto, Elena Leth-Steensen, Craig TI Autistic traits and adult attachment styles SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Autism-Spectrum Quotient; Attachment avoidance; Attachment anxiety; BIS/BAS; Personality ID SPECTRUM QUOTIENT AQ; HIGH-FUNCTIONING AUTISM; MENTAL-RETARDATION; ASPERGER-SYNDROME; SOCIAL DEFICITS; CHILDREN; DISORDER; RESPONSES; LONELINESS; PHENOTYPE AB This study examined the relationship between autistic traits and adult attachment styles in a non-clinical sample of 326 university students. Multiple regression analysis was used to predict both attachment avoidance and attachment anxiety from levels of self-reported autistic traits. A significant unique relationship between autistic traits and attachment avoidance was found after controlling for all Big-Five personality traits, BIS/BAS, gender, and current relationship status. Hence, individuals who report more autistic-like behaviours, especially with respect to communication difficulties, are less likely to report sharing high levels of emotional closeness with romantic partners. On the other hand, no unique relationship between autistic traits and attachment anxiety was present. (c) 2015 Elsevier Ltd. All rights reserved. C1 [Gallitto, Elena] Univ Ottawa, Sch Psychol, Ottawa, ON K1N 6N5, Canada. [Leth-Steensen, Craig] Carleton Univ, Dept Psychol, Ottawa, ON K1S 5B6, Canada. RP Gallitto, E (reprint author), Univ Ottawa, Sch Psychol, 136 Jean Jacques Lussier Vanier Hall, Ottawa, ON K1N 6N5, Canada. 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PD JUN PY 2015 VL 79 BP 63 EP 67 DI 10.1016/j.paid.2015.01.032 PG 5 WC Psychology, Social SC Psychology GA CE2OG UT WOS:000351654300012 ER PT J AU Alrahbeni, T Sartor, F Anderson, J Miedzybrodzka, Z McCaig, C Muller, B AF Alrahbeni, Tahani Sartor, Francesca Anderson, Jihan Miedzybrodzka, Zosia McCaig, Colin Mueller, Berndt TI Full UPF3B function is critical for neuronal differentiation of neural stem cells SO MOLECULAR BRAIN LA English DT Article DE Autism; Schizophrenia; X-linked intellectual disability; Nonsense-mediated mRNA decay; UPF3B mutation; UPF1; Tethered function assay; qPCR; Arhgap24; Atf4; Protein localisation ID MESSENGER-RNA DECAY; NONSENSE-MEDIATED DECAY; EXON JUNCTION COMPLEX; MENTAL-RETARDATION; PREFRONTAL CORTEX; NMD; MUTATIONS; PATHWAY; GENE; SCHIZOPHRENIA AB Background: Mutation in the UPF3B gene on chromosome X is implicated in neurodevelopmental disorders including X-linked intellectual disability, autism and schizophrenia. The protein UPF3B is involved in the nonsense-mediated mRNA decay pathway (NMD) that controls mRNA stability and functions in the prevention of the synthesis of truncated proteins. Results: Here we show that NMD pathway components UPF3B and UPF1 are down-regulated during differentiation of neural stem cells into neurons. Using tethered function assays we found that UPF3B missense mutations described in families with neurodevelopmental disorders reduced the activity of UPF3B protein in NMD. In neural stem cells, UPF3B protein was detected in the cytoplasm and in the nucleus. Similarly in neurons, UPF3B protein was detected in neurites, the somatic cytoplasm and in the nucleus. In both cell types nuclear UPF3B protein was enriched in the nucleolus. Using GFP tagged UPF3B proteins we found that the missense mutations did not affect the cellular localisation. Expression of missense mutant UPF3B disturbed neuronal differentiation and reduced the complexity of the branching of neurites. Neuronal differentiation was similarly affected in the presence of the NMD inhibitor Amlexanox. The expression of mutant UPF3B proteins lead to a subtle increase in mRNA levels of selected NMD targets. Conclusions: Together our findings indicate that, despite the down-regulation of NMD factors, functional NMD is critical for neuronal differentiation. We propose that the neurodevelopmental phenotype of UPF3B missense mutation is caused by impairment of NMD function altering neuronal differentiation. C1 [Alrahbeni, Tahani; Sartor, Francesca; Anderson, Jihan; McCaig, Colin; Mueller, Berndt] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. [Miedzybrodzka, Zosia] Med Genet, Aberdeen AB25 2ZD, Scotland. RP Muller, B (reprint author), Univ Aberdeen, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland. EM b.mueller@abdn.ac.uk FU Tenovus Scotland [G11-06]; Moonlight Prowl; Saudi Arabian Ministry of Higher Education via King Abdullah Program; Medical Research Scotland [PhD-654-2012]; Dundee Cell Products FX We thank Fred H Gage (Salk Institute, La Jolla, CA, USA) for HCN-A94 cells and Niels Gehring (University of Cologne, Germany) for constructs. We gratefully acknowledge Tenovus Scotland (Project Grant G11-06), Moonlight Prowl (FS) and the Saudi Arabian Ministry of Higher Education via King Abdullah Program for Scholarships for support (TA). JA is supported by a PhD studentship from Medical Research Scotland (PhD-654-2012) and Dundee Cell Products. 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Brain PD MAY 27 PY 2015 VL 8 AR 33 DI 10.1186/s13041-015-0122-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CI9FG UT WOS:000355075200001 PM 26012578 ER PT J AU Mannik, K Magi, R Mace, A Guyatt, AL Shihab, HA Maillard, AM Alavere, H Kolk, A Reigo, A Mihailov, E Leitsalu, L Ferreira, AM Noukas, M Teumer, A Salvi, E Cusi, D Mcgue, M Iacono, WG Gaunt, T Beckmann, JS Jacquemont, S Kutalik, Z Pankratz, N Timpson, N Metspalu, A Reymond, A AF Maennik, Katrin Maegi, Reedik Mace, Aurelien Guyatt, Anna L. Shihab, Hashem A. Maillard, Anne M. Alavere, Helene Kolk, Anneli Reigo, Anu Mihailov, Evelin Leitsalu, Liis Ferreira, Anne-Maud Noukas, Margit Teumer, Alexander Salvi, Erika Cusi, Daniele McGue, Matt Iacono, William G. Gaunt, Tomr. Beckmann, Jacques S. Jacquemont, Sebastien Kutalik, Zoltan Pankratz, Nathan Timpson, Nicholas Metspalu, Andres Reymond, Alexandre TI Copy Number Variations and Cognitive Phenotypes in Unselected Populations SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHROMOSOME 16P11.2; GENOMIC DISORDERS; GENE-EXPRESSION; VARIANTS; ASSOCIATION; INTELLIGENCE; AUTISM; DISEASE; ABILITY; OBESITY AB IMPORTANCE The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency <= 0.05%; size >= 250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS The population biobank of Estonia contains 52 000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health-and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, <= 0.05%; >= 250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P = 1.06e-04) among 248 (>= 250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (>= 1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P = .005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P = 1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health. C1 [Maennik, Katrin; Ferreira, Anne-Maud; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Maennik, Katrin; Maegi, Reedik; Alavere, Helene; Kolk, Anneli; Reigo, Anu; Mihailov, Evelin; Leitsalu, Liis; Noukas, Margit; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Mace, Aurelien; Maillard, Anne M.; Jacquemont, Sebastien; Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland. [Mace, Aurelien; Ferreira, Anne-Maud; Beckmann, Jacques S.; Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland. [Pankratz, Nathan] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Guyatt, Anna L.; Shihab, Hashem A.; Gaunt, Tomr.; Timpson, Nicholas] Univ Bristol, Sch Social & Community Med, Bristol Genet Epidemiol Labs, Bristol, Avon, England. [Shihab, Hashem A.; Gaunt, Tomr.; Timpson, Nicholas] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Kolk, Anneli] Tartu Univ Hosp, Childrens Clin, Dept Neurol & Neurorehabil, Tartu, Estonia. [Leitsalu, Liis; Noukas, Margit; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Teumer, Alexander] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Salvi, Erika; Cusi, Daniele] Univ Milan, Dept Hlth Sci, Milan, Italy. [Cusi, Daniele] Italian Natl Res Council, Inst Biomed Technol, Milan, Italy. [McGue, Matt; Iacono, William G.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Kutalik, Zoltan] Lausanne Univ Hosp CHUV, Inst Social & Prevent Med, Lausanne, Switzerland. RP Reymond, A (reprint author), Univ Lausanne, Ctr Integrat Genom, Genopode Bldg, CH-1015 Lausanne, Switzerland. EM alexandre.reymond@unil.ch FU Swiss Scientific Exchange New Member State of the European Union Program; Wellcome Trust [102433/Z/13/Z]; SNSF [31003A_160203]; SNSF Sinergia grant [CRSII33-133044]; Simons Foundation Autism Research Initiative [SFARI274424]; Leenaards Foundation Prizes; European Commission [278913, 306031, 313010]; Center of Excellence in Genomics (EXCEGEN); University of Tartu [SP1GVARENG]; Estonian Research Council [IUT20-60]; US Public Health Service grants from the National Institute on Alcohol Abuse and Alcoholism [AA09367, AA11886]; National Institute on Drug Abuse [DA05147, DA13240, DA024417]; National Institute of Mental Health [MH066140] FX Dr Mannik is a grantee of a scholarship from the Swiss Scientific Exchange New Member State of the European Union Program. Ms Guyatt is funded by a PhD studentship from the Wellcome Trust (grant 102433/Z/13/Z). Dr Jacquemont is a Bursary Professor of the Swiss National Science Foundation (SNSF). This study is supported by 2 SNSF grants (31003A_160203, Drs Reymond, and Kutalik), a specific 16p11.2 SNSF Sinergia grant (CRSII33-133044, Dr Reymond), the Simons Foundation Autism Research Initiative (SFARI274424, Dr Reymond), Leenaards Foundation Prizes (Drs Jacquemont, Reymond, and Kutalik), European Commission Framework Program 7 grants (278913, 306031, and 313010) (Dr Metspalu), Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG, Dr Metspalu), Estonian Research Council Grant (IUT20-60, Dr Metspalu), US Public Health Service grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886, Dr Pankratz), the National Institute on Drug Abuse (DA05147, DA13240, and DA024417, Dr Pankratz), and the National Institute of Mental Health (MH066140, Dr Pankratz). 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PD MAY 26 PY 2015 VL 313 IS 20 BP 2044 EP 2054 DI 10.1001/jama.2015.4845 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CJ0DC UT WOS:000355142400018 PM 26010633 ER PT J AU Itahashi, T Yamada, T Watanabe, H Nakamura, M Ohta, H Kanai, C Iwanami, A Kato, N Hashimoto, R AF Itahashi, Takashi Yamada, Takashi Watanabe, Hiromi Nakamura, Motoaki Ohta, Haruhisa Kanai, Chieko Iwanami, Akira Kato, Nobumasa Hashimoto, Ryu-ichiro TI Alterations of local spontaneous brain activity and connectivity in adults with high-functioning autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Resting-state functional magnetic resonance imaging; Spontaneous activity; Local connectivity; Amplitude of low-frequency fluctuation ID SENTENCE COMPREHENSION; ALZHEIMERS-DISEASE; NETWORK CENTRALITY; ASPERGERS SYNDROME; SYMPTOM SEVERITY; SOCIAL DEFICITS; FUSIFORM GYRUS; GRAY-MATTER; QUOTIENT AQ; CORTEX AB Background: Previous autism research has hypothesized that abnormalities of functional connectivity in autism spectrum disorder (ASD) may vary with the spatial distance between two brain regions. Although several resting-state functional magnetic resonance imaging (rsfMRI) studies have extensively examined long-range (or distant) connectivity in the adult ASD brain, short-range (or local) connectivity has been investigated in less depth. Furthermore, the possible relationship between functional connectivity and brain activity level during the resting state remains unclear. Methods: We acquired rsfMRI data from 50 adults with high-functioning ASD and 50 matched controls to examine the properties of spontaneous brain activity using measures of local and distant connectivity together with a measure of the amplitude of brain activity, known as fractional amplitude of low-frequency fluctuation (fALFF). The two connectivity measures were calculated using a common graph-theoretic framework. We also examined the spatial overlaps between these measures and possible relationships of these disrupted functional measures with autistic traits assessed by the Autism-Spectrum Quotient (AQ). Results: Compared to the controls, participants with ASD exhibited local over-connectivity in the right superior frontal gyrus and middle frontal gyrus, accompanied by local under-connectivity in the bilateral fusiform gyri (FG) and right middle temporal gyrus (MTG). On the other hand, we did not find any significant alterations in distant connectivity. Participants with ASD also exhibited reduced fALFF in the right middle occipital gyrus, lingual gyrus, and FG. Further conjunction and spatial overlap analyses confirmed that the spatial pattern of reduced fALFF substantially overlapped with that of local under-connectivity, demonstrating the co-occurrence of disrupted connectivity and spontaneous activity level in the right inferior occipital gyrus, posterior MTG (pMTG), and FG. Finally, within the ASD group, disrupted local connectivity in the right pMTG significantly correlated with the "social interaction" subscale score of the AQ. Conclusions: These findings revealed local functional disruptions in the occipital and temporal regions, especially the right FG and pMTG, in the form of co-occurrence of spontaneous brain activity level and local connectivity, which may underline social and communicative dysfunctions in adult ASD. C1 [Itahashi, Takashi; Yamada, Takashi; Watanabe, Hiromi; Ohta, Haruhisa; Kanai, Chieko; Kato, Nobumasa; Hashimoto, Ryu-ichiro] Showa Univ, Med Inst Dev Disabil Res, Setagaya Ku, Tokyo, Japan. [Yamada, Takashi; Watanabe, Hiromi; Nakamura, Motoaki; Ohta, Haruhisa; Iwanami, Akira] Showa Univ, Sch Med, Dept Psychiat, Setagaya Ku, Tokyo 142, Japan. [Yamada, Takashi] ATR Brain Informat Commun Res Lab Grp, Kyoto, Japan. [Nakamura, Motoaki] Kinko Hosp, Kanagawa Psychiat Ctr, Yokohama, Kanagawa, Japan. [Hashimoto, Ryu-ichiro] Tokyo Metropolitan Univ, Dept Language Sci, Grad Sch Humanities, Hachioji, Tokyo, Japan. RP Hashimoto, R (reprint author), Showa Univ, Med Inst Dev Disabil Res, Setagaya Ku, 6-11-11 Kita Karasuyama, Tokyo, Japan. EM dbridges50@gmail.com FU Japan Society for the Promotion of Science (JSPS) [25870738]; Ministry of Education, Culture, Sports, Science, and Technology of Japan [23118003] FX This study is the result of "Development of BMI Technologies for Clinical Application" carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was also supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Young Scientists (B) (25870738 to T.I.) and by a Grant-in-Aid for Scientific Research on Innovative Areas (23118003; Adolescent Mind and Self-Regulation to R.H.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. 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They show variable clinical expressivity, being associated with different disorders, and incomplete penetrance. However, due to its very low frequency, the full variety of clinical outcomes associated with each one of these CNVs is unknown. Current methods for detection of CNVs are labor intensive, expensive or not suitable for high throughput analysis. Quantitative interspecies competitive PCR linked to variant minisequencing and detection by mass-spectrometry may overcome these limitations. Here, we present two multiplex assays based on this method to screen for eleven psychiatric risk CNVs, such as 1q21, 16p11.2, 3q29, or 16p13.11 regions, among others. The assays were tested in our collection of 514 schizophrenia patients. Results were compared with MLPA at two CNVs. Additional positive results were confirmed by exome sequencing. A total of fourteen patients were CNV carriers. The method presents high sensitivity and specificity, showing its utility as a cheap, accurate, high throughput screening tool for recurrent CNVs. The method may be very useful for management of psychiatric patients as well as screening of different collections of samples to better identify the full spectrum of clinical variability. (C) 2015 Elsevier B.V. All rights reserved. C1 [Rodriguez-Lopez, Julio; Carrera, Noa; Arrojo, Manuel; Amigo, Jorge; Paramo, Mario; Paz, Eduardo; Agra, Santiago; Ramos-Rios, Ramon; Brenlla, Julio; Carracedo, Angel; Costas, Javier] Inst Invest Sanitaria IDIS Santiago de Compostela, Serv Galego Saude SERGAS, Santiago De Compostela, Spain. [Rodriguez-Lopez, Julio; Carrera, Noa; Sobrino, Beatriz; Carracedo, Angel] Fdn Pabl Galega Med Xenom, Santiago De Compostela, Spain. [Arrojo, Manuel; Paramo, Mario; Paz, Eduardo; Agra, Santiago; Ramos-Rios, Ramon; Brenlla, Julio] Complexo Hospt Univ Santiago de Compostela, Serv Psiquiatr, Serv Galego Saude SERGAS, Santiago De Compostela, Spain. [Amigo, Jorge; Carracedo, Angel] Univ Santiago Compostela, Grp Med Xenom, Santiago De Compostela, Spain. RP Costas, J (reprint author), Hosp Clin Univ, Inst Invest Sanitaria IDIS Santiago de Compostela, Grp Xenet Psiquiatr, Edificio Consultas,Andar 2,Despacho 15, E-15706 Santiago De Compostela, Spain. EM javier.costas.costas@sergas.es RI Costas, Javier/B-5016-2008 OI Costas, Javier/0000-0003-0306-3990 FU Instituto de Salud Carlos III/FEDER [CP11/00163] FX This work was supported by grant CP11/00163 from Instituto de Salud Carlos III/FEDER to JC. Genotyping was performed at the Santiago de Compostela node of Centro Nacional de Genotipado. We thank Maria Torres and Juan Ansede for their technical assistance. 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Athymic nude mice have been employed for tumorigenic research for decades; however, the relationships between the gut microbiome and host's response in drug treatment to the grafted tumors have not been explored. In this study, we analyzed the fecal microbiome of nonxenograft and xenograft nude mice treated with phytosaponins from a popular medicinal plant, Gynostemma pentaphyllum (Gp). Analysis of enterobacterial repetitive intergenic consensus (ERIC)-PCR data showed that the microbiota profile of xenograft mice departed from that of the nonxenograft mice. After ten days of treatment with Gp saponins (GpS), the microbiota of the treated mice was closer to the microbiota at Day 0 before the implantation of the tumor. Data obtained from 16S pyrosequencing of fecal samples reiterates the differences in microbiome between the nonxenograft and xenograft mice. GpS markedly increased the relative abundance of Clostridium cocleatum and Bacteroides acidifaciens, for which the beneficial effects on the host have been well documented. This study, for the first time, characterizes the properties of gut microbiome in nude mice responding to tumor implant and drug treatment. We also demonstrate that dietary saponins such as GpS can potentially regulate the gut microbial ecosystem by increasing the number of symbionts. Interestingly, this regulation of the gut ecosystem might, at least in part, be responsible for or contribute to the anticancer effect of GpS. C1 [Hsiao, W. L. Wendy] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Chen, Lei; Tai, William C. S.; Hsiao, W. L. Wendy] Hong Kong Baptist Univ, Sch Chinese Med, Ctr Canc & Inflammat Res, Kowloon, Hong Kong, Peoples R China. [Brar, Manreetpal S.; Leung, Frederick C. C.] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China. 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Angelaki, Dora E. TI Self-motion perception in autism is compromised by visual noise but integrated optimally across multiple senses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autism; multisensory integration; noise; coherence; Bayesian ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; MULTISENSORY INTEGRATION; HEADING PERCEPTION; VESTIBULAR SIGNALS; CHILDREN; COHERENCE; DEFICITS; FORM; INFORMATION AB Perceptual processing in autism spectrum disorder (ASD) is marked by superior low-level task performance and inferior complex-task performance. This observation has led to theories of defective integration in ASD of local parts into a global percept. Despite mixed experimental results, this notion maintains widespread influence and has also motivated recent theories of defective multisensory integration in ASD. Impaired ASD performance in tasks involving classic random dot visual motion stimuli, corrupted by noise as a means to manipulate task difficulty, is frequently interpreted to support this notion of global integration deficits. By manipulating task difficulty independently of visual stimulus noise, here we test the hypothesis that heightened sensitivity to noise, rather than integration deficits, may characterize ASD. We found that although perception of visual motion through a cloud of dots was unimpaired without noise, the addition of stimulus noise significantly affected adolescents with ASD, more than controls. Strikingly, individuals with ASD demonstrated intact multisensory (visual-vestibular) integration, even in the presence of noise. Additionally, when vestibular motion was paired with pure visual noise, individuals with ASD demonstrated a different strategy than controls, marked by reduced flexibility. This result could be simulated by using attenuated (less reliable) and inflexible (not experience-dependent) Bayesian priors in ASD. These findings question widespread theories of impaired global and multisensory integration in ASD. Rather, they implicate increased sensitivity to sensory noise and less use of prior knowledge in ASD, suggesting increased reliance on incoming sensory information. C1 [Zaidel, Adam; Angelaki, Dora E.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Goin-Kochel, Robin P.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Zaidel, Adam] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. RP Zaidel, A (reprint author), Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. EM adam.zaidel@biu.ac.il; angelaki@bcm.edu FU Simons Foundation [SFARI 247992] FX We thank Eric Raap and Alan Lin for help with data collection. This work was supported by Simons Foundation Grant SFARI 247992 (to D.E.A.). 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Natl. Acad. Sci. U. S. A. PD MAY 19 PY 2015 VL 112 IS 20 BP 6461 EP 6466 DI 10.1073/pnas.1506582112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CI4OD UT WOS:000354729500069 PM 25941373 ER PT J AU Uddin, M Codner, D Hasan, SMM Scherer, SW O'Rielly, DD Rahman, P AF Uddin, Mohammed Codner, Dianne Hasan, S. M. Mahmud Scherer, Stephen W. O'Rielly, Darren D. Rahman, Proton TI Integrated Genomics Identifies Convergence of Ankylosing Spondylitis with Global Immune Mediated Disease Pathways SO SCIENTIFIC REPORTS LA English DT Article ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; CYTOKINE PRODUCTION; T-CELLS; VARIANTS; NETWORK; POLYMORPHISMS; PHENOTYPE; PSORIASIS; REVEALS AB Ankylosing spondylitis(AS), a highly heritable complex inflammatory arthritis. Although, a handful of non-HLA risk loci have been identified, capturing the unexplained genetic contribution to AS pathogenesis remains a challenge attributed to additive, pleiotropic and epistatic-interactions at the molecular level. Here, we developed multiple integrated genomic approaches to quantify molecular convergence of non-HLA loci with global immune mediated diseases. We show that non-HLA genes are significantly sensitive to deleterious mutation accumulation in the general population compared with tolerant genes. Human developmental proteomics (prenatal to adult) analysis revealed that proteins encoded by non-HLA AS risk loci are 2-fold more expressed in adult hematopoietic cells. Enrichment analysis revealed AS risk genes overlap with a significant number of immune related pathways (p < 0.0001 to 9.8 x 10(-12)). Protein-protein interaction analysis revealed non-shared AS risk genes are highly clustered seeds that significantly converge (empirical; p < 0.01 to 1.6 x 10(-4)) into networks of global immune mediated disease risk loci. We have also provided initial evidence for the involvement of STAT(2/3) in AS pathogenesis. Collectively, these findings highlight molecular insight on non-HLA AS risk loci that are not exclusively connected with overlapping immune mediated diseases; rather a component of common pathophysiological pathways with other immune mediated diseases. This information will be pivotal to fully explain AS pathogenesis and identify new therapeutic targets. C1 [Uddin, Mohammed; Scherer, Stephen W.] Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Codner, Dianne; Hasan, S. M. Mahmud; O'Rielly, Darren D.; Rahman, Proton] Mem Univ Newfoundland, Fac Med, St John, NF, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Rahman, P (reprint author), Mem Univ Newfoundland, Fac Med, St John, NF, Canada. 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Crawford, Jessica D. Szebeni, Attila Szebeni, Katalin Ordway, Gregory A. TI NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Pyramidal neurons; Astrocytes; Cingulate; Autism; Glutamate receptors ID TYROSINE PROTEIN-KINASE; HIGH-FUNCTIONING AUTISM; FRAGILE-X-SYNDROME; GENE-EXPRESSION; NEUROTROPHIC FACTOR; MESSENGER-RNA; MOUSE MODEL; RAT-BRAIN; TRKB; CHILDREN AB Background: The anterior cingulate cortex (ACC) is a brain area involved in modulating behavior associated with social interaction, disruption of which is a core feature of autism spectrum disorder (ASD). Functional brain imaging studies demonstrate abnormalities of the ACC in ASD as compared to typically developing control patients. However, little is known regarding the cellular basis of these functional deficits in ASD. Pyramidal neurons in the ACC are excitatory glutamatergic neurons and key cellular mediators of the neural output of the ACC. This study was designed to investigate the potential role of ACC pyramidal neurons in ASD brain pathology. Methods: Postmortem ACC tissue from carefully matched ASD and typically developing control donors was obtained from two national brain collections. Pyramidal neurons and surrounding astrocytes were separately collected from layer III of the ACC by laser capture microdissection. Isolated RNA was subjected to reverse transcription and endpoint PCR to determine gene expression levels for 16 synaptic genes relevant to glutamatergic neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann area 10) to examine those genes demonstrating differences in expression in the ACC comparing typically developing and ASD donors. Results: The level of NTRK2 expression was robustly and significantly lower in pyramidal neurons from ASD donors as compared to typically developing donors. Levels of expression of GRIN1, GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors, but statistical significance for these latter genes did not survive correction for multiple comparisons. No significant expression differences of any genes were found in astrocytes laser captured from the same neocortical area. In addition, expression levels of NTRK2 and other synaptic genes were normal in pyramidal neurons laser captured from the prefrontal cortex. Conclusions: These studies demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through which neurotrophic factors modify differentiation, plasticity, and synaptic transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby contribute to abnormal neuronal activity and disrupt social behavior mediated by this brain region. C1 [Chandley, Michelle J.] E Tennessee State Univ, Coll Publ Hlth, Dept Hlth Sci, Johnson City, TN 37614 USA. [Crawford, Jessica D.; Szebeni, Attila; Szebeni, Katalin; Ordway, Gregory A.] E Tennessee State Univ, James H Quillen Coll Med, Dept Biomed Sci, Johnson City, TN 37614 USA. RP Ordway, GA (reprint author), E Tennessee State Univ, James H Quillen Coll Med, Dept Biomed Sci, POB 70582, Johnson City, TN 37614 USA. EM ordway@etsu.edu FU Autism Speaks pilot grant [7330]; National Institutes of Health [RR030651] FX The authors are grateful to the families who made the choice to consent to donate brain tissue. This invaluable contribution will support many years of ASD research. Human brain tissue was obtained from the Autism Speaks Autism Tissue Program, the Harvard Brain Tissue Resource, and the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. Written informed consent was obtained from the subject's next of kin for publication of their individual details in this manuscript. The consent forms are held by the above mentioned brain banks and are available for review by the Editor-in-Chief. Autism Speaks pilot grant #7330 and the National Institutes of Health RR030651 supported this research. 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Autism PD MAY 16 PY 2015 VL 6 AR 28 DI 10.1186/s13229-015-0023-2 PG 12 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CI6HP UT WOS:000354859700001 PM 26000162 ER PT J AU Uno, Y Uchiyama, T Kurosawa, M Aleksic, B Ozaki, N AF Uno, Yota Uchiyama, Tokio Kurosawa, Michiko Aleksic, Branko Ozaki, Norio TI Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder SO VACCINE LA English DT Article DE Autism Spectrum Disorder; Risk factor; Measles-Mumps-Rubella vaccine; Thimerosal; Case-control study; Environmental factors ID INFLAMMATORY-BOWEL-DISEASE; CHILD-HEALTH-HANDBOOK; MMR VACCINE; COMMUNICATION DISORDERS; DIAGNOSTIC INTERVIEW; METAANALYSIS; COMPLICATIONS; MERCURY AB Objective: This case-control study investigated the relationship between the risk of Autism Spectrum Disorder (ASD) onset, and early exposure to the combined Measles-Mumps-Rubella (MMR) vaccine and thimerosal consumption measured from vaccinations in the highly genetically homogenous Japanese population. Methods: Vaccination histories at 1, 3, 6, 12, 18, 24, and 36 months from birth were investigated in ASD cases (189 samples), and controls (224 samples) matching age and sex in each case. Crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to determine relationship between MMR vaccination and ASD. The differences in mean values of the thimerosal dosage between cases and controls were analyzed using an unpaired t-test. MMR vaccination and thimerosal dosage were also investigated using a conditional multiple-regression model. Results: There were no significant differences in MMR vaccination and thimerosal dosage between cases and controls at any age. Furthermore, the ORs (95% CIs) of MMR vaccination and thimerosal dosage associated with ASD in the conditional multiple regression model were, respectively, 0.875(0.345-2.222) and 1.205(0.862-1.683) at age 18 months, 0.724(0.421-1.243) and 1.343(0.997-1.808) at 24 months, and 1.040(0.648-1.668) and 0.844(0.632-1.128) at 36 months. Thus, there were no significant differences. Conclusions: No convincing evidence was found in this study that MMR vaccination and increasing thimerosal dose were associated with an increased risk of ASD onset. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Uno, Yota] Nagoya Univ, Grad Sch Med, Dept Child & Adolescent Psychiat, Showa Ku, Nagoya, Aichi 4668550, Japan. [Uno, Yota; Uchiyama, Tokio] Yokohama Psychodev Clin, Dept Psychiat, Tsuzuki Ku, Yokohama, Kanagawa 2240032, Japan. [Uchiyama, Tokio] Fukushima Univ, Grad Sch, Dept Fac Human Dev, Fukushima, Fukushima 9601248, Japan. [Kurosawa, Michiko] Juntendo Univ, Grad Sch Med, Dept Epidemiol & Environm Hlth, Bunkyo Ku, Tokyo 1138421, Japan. [Aleksic, Branko; Ozaki, Norio] Nagoya Univ, Grad Sch Med, Dept Psychiat, Showa Ku, Nagoya, Aichi 4668550, Japan. RP Uno, Y (reprint author), Nagoya Univ, Grad Sch Med, Dept Child & Adolescent Psychiat, Showa Ku, Tsurumai Cho 65, Nagoya, Aichi 4668550, Japan. EM yota_u@ypdc.net; tokiouch@ca2.so-net.ne.jp; mic@med.juntendo.ac.jp; branko@med.nagoya-u.ac.jp; ozaki-n@med.nagoya-u.ac.jp FU Ministry of Health, Labor and Welfare of Japan [H22-Psychiatry-General-016]; Ministry of Education, Culture, Sports, Science and Technology of Japan FX The authors are grateful to Associate Professor Masahiko Ando, Nagoya University Hospital, for his advice and checking of statistical analyses. This study is the result of research grants from the Ministry of Health, Labor and Welfare of Japan (H22-Psychiatry-General-016), and "Integrated research on neuropsychiatric disorders" carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. 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Indeed, a growing body of evidence indicates that glial cells interact extensively with neurons both chemically (e.g., through neurotransmitters, neurotrophic factors, and cytokines) and physically (e.g., through gap junctions), supporting a role for these cells as likely significant modifiers not only of neural function in brain development but also disease pathobiology. Since questions have lingered as to whether glial dysfunction plays a primary role in the biology of neuropsychiatric disorders or a role related solely to their support of neuronal physiology in these diseases, informative and predictive animal models have been developed over the last decade. In this article, we review recent findings uncovered using glia-specific genetically modified mice with which we can evaluate both the causation of glia dysfunction and its potential role in neuropsychiatric disorders such as autism and schizophrenia. 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Neurosci. PD MAY 15 PY 2015 VL 9 AR 154 DI 10.3389/fncel.2015.00154 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CI5NS UT WOS:000354804400001 PM 26029044 ER PT J AU Wang, YT Sung, PY Lin, PL Yu, YW Chung, RH AF Wang, Yi-Ting Sung, Pei-Yuan Lin, Peng-Lin Yu, Ya-Wen Chung, Ren-Hua TI A multi-SNP association test for complex diseases incorporating an optimal P-value threshold algorithm in nuclear families SO BMC GENOMICS LA English DT Article ID CONTRASTING LINKAGE-DISEQUILIBRIUM; DISTANCE-BASED REGRESSION; GENOME-WIDE ASSOCIATION; HAPLOTYPE SIMILARITY; TRANSMISSION/DISEQUILIBRIUM TEST; GENERAL PEDIGREES; AUTISM; RISK; TOOL; SIMULATION AB Background: Genome-wide association studies (GWAS) have become a common approach to identifying single nucleotide polymorphisms (SNPs) associated with complex diseases. As complex diseases are caused by the joint effects of multiple genes, while the effect of individual gene or SNP is modest, a method considering the joint effects of multiple SNPs can be more powerful than testing individual SNPs. The multi-SNP analysis aims to test association based on a SNP set, usually defined based on biological knowledge such as gene or pathway, which may contain only a portion of SNPs with effects on the disease. Therefore, a challenge for the multi-SNP analysis is how to effectively select a subset of SNPs with promising association signals from the SNP set. Results: We developed the Optimal P-value Threshold Pedigree Disequilibrium Test (OPTPDT). The OPTPDT uses general nuclear families. A variable p-value threshold algorithm is used to determine an optimal p-value threshold for selecting a subset of SNPs. A permutation procedure is used to assess the significance of the test. We used simulations to verify that the OPTPDT has correct type I error rates. Our power studies showed that the OPTPDT can be more powerful than the set-based test in PLINK, the multi-SNP FBAT test, and the p-value based test GATES. We applied the OPTPDT to a family-based autism GWAS dataset for gene-based association analysis and identified MACROD2-AS1 with genome-wide significance (p-value= 2.5 x 10(-6)). Conclusions: Our simulation results suggested that the OPTPDT is a valid and powerful test. The OPTPDT will be helpful for gene-based or pathway association analysis. The method is ideal for the secondary analysis of existing GWAS datasets, which may identify a set of SNPs with joint effects on the disease. C1 [Wang, Yi-Ting; Sung, Pei-Yuan] Natl Tsing Hua Univ, Inst Stat, Hsinchu, Taiwan. [Lin, Peng-Lin] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu, Taiwan. [Yu, Ya-Wen; Chung, Ren-Hua] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan. RP Chung, RH (reprint author), Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan. EM rchung@nhri.org.tw FU Medical Research Council [G0601030]; Wellcome Trust [075491/Z/04]; National Health Research Institutes [PH-103-PP-15]; National Science Council in Taiwan [NSC 102-2221-E-400-001-MY2] FX We are grateful to the National Center for High-performance Computing in Taiwan for computer time and facilities. The datasets used for the analysis described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number, phs000267.v4.p2. Submission of the data, phs000267.v4.p2, to dbGaP was provided by Dr. Bernie Devlin on behalf of the Autism Genome Project (AGP). Collection and submission of the data to dbGaP were supported by a grant from the Medical Research Council (G0601030) and the Wellcome Trust (075491/Z/04), Anthony P. Monaco, P.I., University of Oxford. This work was funded by grants from the National Health Research Institutes (PH-103-PP-15) and National Science Council (NSC 102-2221-E-400-001-MY2) in Taiwan. 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TI Wavelet methodology to improve single unit isolation in primary motor cortex cells SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Wavelet transform; Statistical thresholding; Spike sorting; Single units; Principal component analysis; Neuronal cell isolation ID EEG-BASED DIAGNOSIS; FUZZY SYNCHRONIZATION LIKELIHOOD; PRINCIPAL COMPONENT ANALYSIS; NEURAL NETWORK METHODOLOGY; AUTISM SPECTRUM DISORDER; ALZHEIMERS-DISEASE; SEIZURE DETECTION; SPIKE DETECTION; EXTRACELLULAR RECORDINGS; ALGORITHM AB The proper isolation of action potentials recorded extracellularly from neural tissue is an active area of research in the fields of neuroscience and biomedical signal processing. This paper presents an isolation methodology for neural recordings using the wavelet transform (WT), a statistical thresholding scheme, and the principal component analysis (PCA) algorithm. The effectiveness of five different mother wavelets was investigated: biorthogonal, Daubachies, discrete Meyer, symmetric, and Coifman; along with three different wavelet coefficient thresholding schemes: fixed form threshold, Stein's unbiased estimate of risk, and minimax; and two different thresholding rules: soft and hard thresholding. The signal quality was evaluated using three different statistical measures: mean-squared error, root-mean squared, and signal to noise ratio. The clustering quality was evaluated using two different statistical measures: isolation distance, and L-ratio. This research shows that the selection of the mother wavelet has a strong influence on the clustering and isolation of single unit neural activity, with the Daubachies 4 wavelet and minimax thresholding scheme performing the best. (C) 2015 Published by Elsevier B.V. C1 [Ortiz-Rosario, Alexis; Adeli, Hojjat; Buford, John A.] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Civil & Environm Engn & Geodet Sci, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43210 USA. [Adeli, Hojjat] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. [Buford, John A.] Ohio State Univ, Sch Hlth & Rehabil Sci, Div Phys Therapy, Columbus, OH 43210 USA. RP Adeli, H (reprint author), Ohio State Univ, Dept Biomed Engn, 470 Hitchcock Hall,2070 Neil Ave, Columbus, OH 43210 USA. EM adeli.1@osu.edu FU NIH NINDS [R01 NS37822] FX The authors thank Rebecca Slattery, Thomas Hirschauer and Amanda Jellick for assistance in collecting the data used in this research. This work was supported partially by NIH NINDS R01 NS37822. 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Surprisingly, non-human animal studies of the neural substrates of this form of multisensory integration have been somewhat sparse until very recently, and this may be due in part to a relative paucity of viable testing methods. Here we review the historical development and use of various "crossmodal" cognition tasks for non-human primates and rodents, focusing on tests of "rossmodal object recognition", the ability to recognize an object across sensory modalities. Such procedures have great potential to elucidate the cognitive and neural bases of object representation as it pertains to perception and memory. Indeed, these studies have revealed roles in crossmodal cognition for various brain regions (e.g., prefrontal and temporal cortices) and neurochemical systems (e.g., acetylcholine). A recent increase in behavioral and physiological studies of crossmodal cognition in rodents augurs well for the future of this research area, which should provide essential information about the basic mechanisms of object representation in the brain, in addition to fostering a better understanding of the causes of, and potential treatments for, cognitive deficits in human diseases characterized by atypical multisensory integration. (C) 2014 Elsevier B.V. All rights reserved. C1 [Winters, Boyer D.] Univ Guelph, Dept Psychol, Guelph, ON N1G 2W1, Canada. Univ Guelph, Collaborat Neurosci Program, Guelph, ON N1G 2W1, Canada. RP Winters, BD (reprint author), Univ Guelph, Dept Psychol, Guelph, ON N1G 2W1, Canada. 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Brain Res. PD MAY 15 PY 2015 VL 285 SI SI BP 118 EP 130 DI 10.1016/j.bbr.2014.09.039 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG2CU UT WOS:000353083300012 PM 25286314 ER PT J AU Grayson, B Leger, M Piercy, C Adamson, L Harte, M Neill, JC AF Grayson, Ben Leger, Marianne Piercy, Chloe Adamson, Lisa Harte, Michael Neill, Joanna C. TI Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Object recognition; Alzheimer's disease; Schizophrenia; Parkinson's disease; Autistic spectrum disorder; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; HIPPOCAMPAL CELL-PROLIFERATION; PRENATAL IMMUNE ACTIVATION; ENVIRONMENTAL RISK-FACTORS; AUTISM SPECTRUM DISORDERS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MEMORY DEFICITS AB The novel object recognition test (NOR) test is a two trial cognitive paradigm that assesses recognition memory. Recognition memory is disturbed in a range of human disorders and NOR is widely used in rodents for investigating deficits in a variety of animal models of human conditions where cognition is impaired. It possesses several advantages over more complex tasks that involve lengthy training procedures and/or food or water deprivation. It is quick to administer, non-rewarded, provides data quickly, cost effective and most importantly, ethologically relevant as it relies on the animal's natural preference for novelty. A PubMed search revealed over 900 publications in rats and mice using this task over the past 3 years with 34 reviews in the past 10 years, demonstrating its increasing popularity with neuroscientists. Although it is widely used in many disparate areas of research, no articles have systematically examined this to date, which is the subject of our review. We reveal that NOR may be used to study recognition memory deficits that occur in Alzheimer's disease and schizophrenia, where research is extensive, in Parkinson's disease and Autism Spectrum Disorders (ASD) where we observed markedly reduced numbers of publications. In addition, we review the use of NOR to study cognitive deficits induced by traumatic brain injury and cancer chemotherapy, not disorders per se, but situations in which cognitive deficits dramatically reduce the quality of life for those affected, see Fig. 1 for a summary. Our review reveals that, in all these animal models, the NOR test is extremely useful for identification of the cognitive deficits observed, their neural basis, and for testing the efficacy of novel therapeutic agents. Our conclusion is that NOR is of considerable value for cognitive researchers of all disciplines and we anticipate that its use will continue to increase due to its versatility and several other advantages, as detailed in this review. (C) 2014 Elsevier B.V. All rights reserved. C1 [Grayson, Ben; Leger, Marianne; Piercy, Chloe; Adamson, Lisa; Harte, Michael; Neill, Joanna C.] Univ Manchester, Manchester Pharm Sch, Manchester M13 9PT, Lancs, England. RP Grayson, B (reprint author), Univ Manchester, Manchester Pharm Sch, Manchester M13 9PT, Lancs, England. 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PD MAY 15 PY 2015 VL 285 SI SI BP 176 EP 193 DI 10.1016/j.bbr.2014.10.025 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG2CU UT WOS:000353083300017 PM 25447293 ER PT J AU Kastner, A Begemann, M Michel, TM Everts, S Stepniak, B Bach, C Poustka, L Becker, J Banaschewski, T Dose, M Ehrenreich, H AF Kaestner, Anne Begemann, Martin Michel, Tanja Maria Everts, Sarah Stepniak, Beata Bach, Christiane Poustka, Luise Becker, Joachim Banaschewski, Tobias Dose, Matthias Ehrenreich, Hannelore TI Autism beyond diagnostic categories: characterization of autistic phenotypes in schizophrenia SO BMC PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Positive and negative syndrome scale; Autism diagnostic observation schedule; Diagnostics; Autism quotient; Empathy quotient; Adults ID OBSERVATION SCHEDULE; SPECTRUM DISORDER; COGNITIVE PERFORMANCE; PSYCHIATRIC-DISORDERS; FUNCTIONING AUTISM; GENERAL-POPULATION; CLOZAPINE RESPONSE; ASPERGER-SYNDROME; BIPOLAR DISORDER; GENETIC OVERLAP AB Background: Behavioral phenotypical continua from health to disease suggest common underlying mechanisms with quantitative rather than qualitative differences. Until recently, autism spectrum disorders and schizophrenia were considered distinct nosologic entities. However, emerging evidence contributes to the blurring of symptomatic and genetic boundaries between these conditions. The present study aimed at quantifying behavioral phenotypes shared by autism spectrum disorders and schizophrenia to prepare the ground for biological pathway analyses. Methods: Specific items of the Positive and Negative Syndrome Scale were employed and summed up to form a dimensional autism severity score (PAUSS). The score was created in a schizophrenia sample (N = 1156) and validated in adult high-functioning autism spectrum disorder (ASD) patients (N = 165). To this end, the Autism Diagnostic Observation Schedule (ADOS), the Autism (AQ) and Empathy Quotient (EQ) self-rating questionnaires were applied back to back with the newly developed PAUSS. Results: PAUSS differentiated between ASD, schizophrenia and a disease-control sample and substantially correlated with the Autism Diagnostic Observation Schedule. Patients with ADOS scores >= 12 obtained highest, those with scores <7 lowest PAUSS values. AQ and EQ were not found to vary dependent on ADOS diagnosis. ROC curves for ADOS and PAUSS resulted in AuC values of 0.9 and 0.8, whereas AQ and EQ performed at chance level in the prediction of ASD. Conclusions: This work underscores the convergence of schizophrenia negative symptoms and autistic phenotypes. PAUSS evolved as a measure capturing the continuous nature of autistic behaviors. The definition of extreme-groups based on the dimensional PAUSS may permit future investigations of genetic constellations modulating autistic phenotypes. C1 [Kaestner, Anne; Begemann, Martin; Everts, Sarah; Stepniak, Beata; Becker, Joachim; Ehrenreich, Hannelore] Max Planck Inst Expt Med, Clin Neurosci, D-37075 Gottingen, Germany. [Begemann, Martin; Ehrenreich, Hannelore] DFG Res Ctr Nanoscale Microscopy & Mol Physiol Br, Gottingen, Germany. [Michel, Tanja Maria] Univ Southern Denmark, Inst Clin Res, Dept Psychiat, Odense, Denmark. [Bach, Christiane; Poustka, Luise; Banaschewski, Tobias] Cent Inst Mental Hlth, Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany. [Dose, Matthias] Kbo Isar Amper Klinikum Taufkirchen, Taufkirchen, Vils, Germany. RP Ehrenreich, H (reprint author), Max Planck Inst Expt Med, Clin Neurosci, Hermann Rein Str 3, D-37075 Gottingen, Germany. EM ehrenreich@em.mpg.de FU Max Planck Society; Max Planck Forderstiftung; DFG (CNMPB); EXTRABRAIN EU-FP7; EU-AIMS; Innovative Medicines Initiative Joint Undertaking [115300]; European Union's Seventh Framework Programme (FP7); EFPIA companies; Autism Speaks FX This work was supported by the Max Planck Society, the Max Planck Forderstiftung, the DFG (CNMPB), EXTRABRAIN EU-FP7, 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. We are indebted to all individuals participating in the studies, and to all collaborating schizophrenia and autism centers for their support. We are grateful to all colleagues who contributed over the last decade to the GRAS and validation sample data collection. 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The effects of these two peptides are meditated by their specific receptors, which are encoded by the oxytocin receptor (OXTR) and arginine vasopressin receptor 1a genes (AVPR1A), respectively. In several species, polymorphisms in these genes have been linked to various behavioural traits. Little, however, is known about whether positive selection acts on sequence variants in genes influencing variation in human behaviours. Results: We identified, in both neuroreceptor genes, signatures of balancing selection in the cis-regulative acting sequences such as transcription factor binding and enhancer sequences, as well as in a transcriptional repressor sequence motif. Additionally, in the intron 3 of the OXTR gene, the SNP rs59190448 appears to be under positive directional selection. For rs59190448, only one phenotypical association is known so far, but it is in high LD' (>0.8) with loci of known association; i.e., variants associated with key pro-social behaviours and mental disorders in humans. Conclusions: Only for one SNP on the OXTR gene (rs59190448) was a sign of positive directional selection detected with all three methods of selection detection. For rs59190448, however, only one phenotypical association is known, but rs59190448 is in high LD' (>0.8), with variants associated with important pro-social behaviours and mental disorders in humans. We also detected various signatures of balancing selection on both neuroreceptor genes. C1 [Schaschl, Helmut; Huber, Susanne; Schaefer, Katrin; Windhager, Sonja; Wallner, Bernard; Fieder, Martin] Univ Vienna, Dept Anthropol, Vienna, Austria. [Wallner, Bernard] Univ Vienna, Cognit Sci Platform, Vienna, Austria. [Wallner, Bernard] Univ Vienna, Dept Behav Biol, Vienna, Austria. RP Fieder, M (reprint author), Univ Vienna, Dept Anthropol, Vienna, Austria. EM martin.fieder@univie.ac.at RI Wallner, Bernard/B-1089-2009 FU University of Vienna, Faculty of Life Sciences; University of Vienna [IP 547011] FX The R Core Team for the statistical computing environment, the 1000 Genomes Project, as well as LOSITAN, BAYESCAN, and FLK. Furthermore, we thank Michael Stachowitsch and the anonymous reviewers for valuable comments on the manuscript. We would also like to thank Horst Seidler for his continuing support. This work was supported by Young Investigator Award 2013 University of Vienna, Faculty of Life Sciences, to SW; Emerging Field "Comparative Human Life History: A Multilevel Approach", University of Vienna, Faculty of Life Sciences, to KS; Back-to-Research Grant, University of Vienna, to SH; and Investitionsprojekt IP 547011, University of Vienna, to MF. The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation. We thank the anonymous reviewers for their very comments that significantly improved the manuscript. 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Biol. PD MAY 13 PY 2015 VL 15 AR 85 DI 10.1186/s12862-015-0372-7 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA CH7YL UT WOS:000354252600001 PM 25968600 ER PT J AU Gockley, J Willsey, AJ Dong, S Dougherty, JD Constantino, JN Sanders, SJ AF Gockley, Jake Willsey, A. Jeremy Dong, Shan Dougherty, Joseph D. Constantino, John N. Sanders, Stephan J. TI The female protective effect in autism spectrum disorder is not mediated by a single genetic locus SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Sex bias; Female protective effect; GWAS ID DE-NOVO MUTATIONS; GENERAL-POPULATION; RISK; TRAITS; EPIDEMIOLOGY; ASSOCIATION; RECURRENCE; EXPRESSION; VARIANTS; RESOURCE AB Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. Methods: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. Results: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. Conclusions: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE. C1 [Gockley, Jake; Willsey, A. Jeremy; Dong, Shan; Sanders, Stephan J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Willsey, A. Jeremy; Sanders, Stephan J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Dong, Shan] Peking Univ, State Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. [Dougherty, Joseph D.; Constantino, John N.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA. [Dougherty, Joseph D.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. 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TI Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism SO MOLECULAR AUTISM LA English DT Article DE Autism; RORA expression; Transcriptional targets; Sex differences; Postmortem brain tissues; Mouse brain ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; FETAL TESTOSTERONE; GENE-EXPRESSION; NEURONAL DEVELOPMENT; MENTAL-RETARDATION; ABNORMAL-BEHAVIOR; DENDRITIC GROWTH; PURKINJE-CELLS; ALPHA AB Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant impairment in reciprocal social interactions and communication coupled with stereotyped, repetitive behaviors and restricted interests. Although genomic and functional studies are beginning to reveal some of the genetic complexity and underlying pathobiology of ASD, the consistently reported male bias of ASD remains an enigma. We have recently proposed that retinoic acid-related orphan receptor alpha (RORA), which is reduced in the brain and lymphoblastoid cell lines of multiple cohorts of individuals with ASD and oppositely regulated by male and female hormones, might contribute to the sex bias in autism by differentially regulating target genes, including CYP19A1 (aromatase), in a sex-dependent manner that can also lead to elevated testosterone levels, a proposed risk factor for autism. Methods: In this study, we examine sex differences in RORA and aromatase protein levels in cortical tissues of unaffected and affected males and females by re-analyzing pre-existing confocal immunofluorescence data from our laboratory. We further investigated the expression of RORA and its correlation with several of its validated transcriptional targets in the orbital frontal cortex and cerebellum as a function of development using RNAseq data from the BrainSpan Atlas of the Developing Human Brain. In a pilot study, we also analyzed the expression of Rora and the same transcriptional targets in the cortex and cerebellum of adult wild-type male and female C57BL/6 mice. Results: Our findings suggest that Rora/RORA and several of its transcriptional targets may exhibit sexually dimorphic expression in certain regions of the brain of both mice and humans. Interestingly, the correlation coefficients between Rora expression and that of its targets are much higher in the cortex of male mice relative to that of female mice. A strong positive correlation between the levels of RORA and aromatase proteins is also seen in the cortex of control human males and females as well as ASD males, but not ASD females. Conclusions: Based on these studies, we suggest that disruption of Rora/RORA expression may have a greater impact on males, since sex differences in the correlation of RORA and target gene expression indicate that RORA-deficient males may experience greater dysregulation of genes relevant to ASD in certain brain regions during development. C1 [Hu, Valerie W.; Sarachana, Tewarit; Kocher, Kristen M.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Sarachana, Tewarit] Chulalongkorn Univ, Fac Allied Hlth Sci, Dept Clin Chem, Bangkok, Thailand. [Sherrard, Rachel M.] Univ Paris 06, Univ Paris 04, Inst Biol Paris Seine, CNRS,UMR Biol Adaptat & Aging 8256, F-75005 Paris, France. RP Hu, VW (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, 2300 Eye St NW, Washington, DC 20037 USA. EM valhu@gwu.edu RI ahmed, Jamila/E-8653-2015 FU Higher Educational Strategic Scholarship for Frontier Research Network (SFR scholarship) from the Office of the Commission on Higher Education of the Royal Thai Government, Thailand, through the Faculty of Allied Health Sciences, Chulalongkorn University; NIEHS [R21 ES023061-01] FX We wish to thank the families of all of the brain donors for their invaluable gift to autism research and the Autism Tissue Program (San Diego, CA, USA) for making frozen human brain tissues available for this work through the Harvard Brain Tissue Resource Center (Harvard University, Boston, MA, USA). We also thank the Allen Institute for Brain Science (Seattle, WA, USA) and all the members of the consortium working on the brain mapping project for making the RNAseq expression data of the human brain publicly available. This study was supported in part by generous gifts from the Ireland Family Foundation (Chapel Hill, NC, USA) and the LIFE Foundation (Aspen, CO, USA), and by a grant from the NIEHS (R21 ES023061-01). None of the funding sources played any role in the study design, collection, analysis, and interpretation of data, writing of the manuscript, or decision to submit this study for publication. TS was a predoctoral student in the Institute for Biomedical Sciences at the George Washington University, who was supported by the Higher Educational Strategic Scholarship for Frontier Research Network (SFR scholarship) from the Office of the Commission on Higher Education of the Royal Thai Government, Thailand, through the Faculty of Allied Health Sciences, Chulalongkorn University. 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Autism PD MAY 13 PY 2015 VL 6 AR 7 DI 10.1186/2040-2392-6-7 PG 18 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CH9JI UT WOS:000354351400002 PM 26056561 ER PT J AU Lai, MC Baron-Cohen, S Buxbaum, JD AF Lai, Meng-Chuan Baron-Cohen, Simon Buxbaum, Joseph D. TI Understanding autism in the light of sex/gender SO MOLECULAR AUTISM LA English DT Editorial Material ID SPECTRUM DISORDERS; SEX-DIFFERENCES; ANOREXIA-NERVOSA; TRAITS; CHILDREN; POPULATION; GENDER; ADULTS; IDENTIFICATION; FEMALES C1 [Lai, Meng-Chuan; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Lai, Meng-Chuan; Baron-Cohen, Simon] Cambridgeshire & Peterborough NHS Fdn Trust, Chitra Sethia Autism Ctr, CLASS Clin, Cambridge CB21 5EF, England. [Lai, Meng-Chuan] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10051, Taiwan. [Lai, Meng-Chuan] Coll Med, Taipei 10051, Taiwan. 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Autism PD MAY 13 PY 2015 VL 6 DI 10.1186/s13229-015-0021-4 PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CH9JC UT WOS:000354350800001 PM 25973161 ER PT J AU Mandy, W Tchanturia, K AF Mandy, Will Tchanturia, Kate TI Do women with eating disorders who have social and flexibility difficulties really have autism? A case series SO MOLECULAR AUTISM LA English DT Article DE Eating disorders; anorexia nervosa; Autism spectrum disorder (ASD); gender differences; Autism Diagnostic Observation Schedule (ADOS); clinical interview ID ANOREXIA-NERVOSA; SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; FUNCTIONING AUTISM; ASPERGER-SYNDROME; ADOLESCENTS; TRAITS; ONSET; METAANALYSIS; CHILDREN AB Background: Many women with eating disorders (EDs) have social impairments and difficulties with flexibility. It is unclear to what extent these are manifestations of an underlying autism spectrum disorder (ASD); or whether they are instead the consequence of starvation, anxiety, low mood or obsessive compulsive disorder, all of which are highly prevalent in EDs. The resolution of this clinically and theoretically important uncertainty will require the use of gold-standard ASD assessment measures. To date these have not been employed in ED research. This case series is the first report of a well-validated, direct-observational measure of ASD, the Autism Diagnostic Observation Schedule (ADOS), being administered to women with EDs. We aimed to learn about the feasibility of the ADOS in this population, and to contribute to debates about whether a sub-group with EDs really have ASD. Methods: Ten women (mean age = 26.4 years, range = 19 to 38 years) who had a suspected ASD due to social and flexibility difficulties and were receiving treatment for ED (seven anorexia, two ED not otherwise specified, one bulimia) at a specialist service (four inpatient, six outpatient) received an ADOS Module 4 assessment. Results: All 10 participants completed all activities of the ADOS Module 4. Five scored in the ASD range on the ADOS diagnostic algorithm. An additional two were judged likely to have ASD, even though they scored below the ADOS's diagnostic threshold. This was on the basis of clinical observation, participant self-report and parent report. The seven women who we estimated to have ASD all reported autistic difficulties prior to the onset of their ED. They commonly described longstanding non-autistic neurodevelopmental problems, including dyslexia, dyspraxia and epilepsy. Only one had a childhood diagnosis of ASD. Conclusions: A substantial proportion of women with EDs who present with social and flexibility difficulties may have an unrecognised ASD, indicated by a constellation of autistic difficulties that appears to predate the onset of their eating problems. The ADOS is a useful component of an ASD assessment for adult women with ED. C1 [Mandy, Will] UCL, Res Dept Clin Educ & Hlth Psychol, London WC1E 6BT, England. [Tchanturia, Kate] Kings Coll London, Inst Psychiat, Psychol Med, London WC2R 2LS, England. [Tchanturia, Kate] South London & Maudsley NHS Trust, Psychol Med Clin Acad Grp, London, England. [Tchanturia, Kate] Illia State Univ, Tbilisi, Rep of Georgia. RP Mandy, W (reprint author), UCL, Res Dept Clin Educ & Hlth Psychol, Gower St, London WC1E 6BT, England. EM w.mandy@ucl.ac.uk FU Maudsley Charity 'Health in Mind' FX KT would like to thank the Maudsley Charity 'Health in Mind' for their funding support. KT and WM thank the participants of this study, and the clinical team at Maudsley Eating Disorder Adult National Service: Nikola Kern, Catia Acosta, Danielle Glennon, Eli Doris, Caroline Fleming, Elaine Smith and Victoria Mountford. 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Autism PD MAY 13 PY 2015 VL 6 AR 6 DI 10.1186/2040-2392-6-6 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CH9JI UT WOS:000354351400001 PM 26056560 ER PT J AU Nordahl, CW Iosif, AM Young, GS Perry, LM Dougherty, R Lee, A Li, D Buonocore, MH Simon, T Rogers, S Wandell, B Amaral, DG AF Nordahl, Christine Wu Iosif, Ana-Maria Young, Gregory S. Perry, Lee Michael Dougherty, Robert Lee, Aaron Li, Deana Buonocore, Michael H. Simon, Tony Rogers, Sally Wandell, Brian Amaral, David G. TI Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Connectivity; Diffusion tensor imaging; Longitudinal; MRI; White matter ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; WHITE-MATTER; MRI DATA; FRONTAL-CORTEX; YOUNG-CHILDREN; DIFFUSION; BRAIN; ENLARGEMENT; SIZE AB Background: Abnormalities in the corpus callosum have been reported in individuals with autism spectrum disorder (ASD), but few studies have evaluated young children. Sex differences in callosal organization and diffusion characteristics have also not been evaluated fully in ASD. Methods: Structural and diffusion-weighted images were acquired in 139 preschool-aged children with ASD (112 males/27 females) and 82 typically developing (TD) controls (53 males/29 females). Longitudinal scanning at two additional annual time points was carried out in a subset of these participants. Callosal organization was evaluated using two approaches: 1) diffusion tensor imaging (DTI) tractography to define subregions based on cortical projection zones and 2) as a comparison to previous studies, midsagittal area analysis using Witelson subdivisions. Diffusion measures of callosal fibers were also evaluated. Results: Analyses of cortical projection zone subregions revealed sex differences in the patterns of altered callosal organization. Relative to their sex-specific TD counterparts, both males and females with ASD had smaller regions dedicated to fibers projecting to superior frontal cortex, but patterns differed in callosal subregions projecting to other parts of frontal cortex. While males with ASD had a smaller callosal region dedicated to the orbitofrontal cortex, females with ASD had a smaller callosal region dedicated to the anterior frontal cortex. There were also sex differences in diffusion properties of callosal fibers. While no alterations were observed in males with ASD relative to TD males, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were all increased in females with ASD relative to TD females. Analyses of Witelson subdivisions revealed a decrease in midsagittal area of the corpus callosum in both males and females with ASD but no regional differences in specific subdivisions. Longitudinal analyses revealed no diagnostic or sex differences in the growth rate or change in diffusion measures of the corpus callosum from 3 to 5 years of age. Conclusions: There are sex differences in the pattern of altered corpus callosum neuroanatomy in preschool-aged children with ASD. C1 [Nordahl, Christine Wu; Iosif, Ana-Maria; Young, Gregory S.; Lee, Aaron; Li, Deana; Simon, Tony; Rogers, Sally; Amaral, David G.] Univ Calif Davis, Sch Med, MIND Inst, Sacramento, CA 95817 USA. [Nordahl, Christine Wu; Young, Gregory S.; Lee, Aaron; Li, Deana; Simon, Tony; Rogers, Sally; Amaral, David G.] Univ Calif Davis, Sch Med, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Iosif, Ana-Maria] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Perry, Lee Michael; Wandell, Brian] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Dougherty, Robert] Stanford Univ, Ctr Cognit & Neurobiol Imaging, Stanford, CA 94305 USA. [Buonocore, Michael H.] Univ Calif Davis, Sch Med, Dept Radiol, Sacramento, CA 95817 USA. RP Nordahl, CW (reprint author), Univ Calif Davis, Sch Med, MIND Inst, 2805 50th St, Sacramento, CA 95817 USA. EM crswu@ucdavis.edu FU National Institute of Mental Health [R01 MH089626, U24 MH081810, R00 MH085099]; UC Davis MIND Institute; MIND Institute Intellectual and Developmental Disabilities Research Center [U54 HD079125] FX The authors would like to acknowledge Adam Wandell, Robert Scholz, and Sarah Liston for their expert technical assistance and the Autism Phenome Project staff for helping with the logistics of family visits and data collection. We especially thank all of the families and children who participated in the study. This work was supported by the National Institute of Mental Health (R01 MH089626, U24 MH081810, R00 MH085099) and the UC Davis MIND Institute. Statistical support was provided by the MIND Institute Intellectual and Developmental Disabilities Research Center (U54 HD079125). 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Autism PD MAY 13 PY 2015 VL 6 AR 26 DI 10.1186/s13229-015-0005-4 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CH9JC UT WOS:000354350800003 PM 25973163 ER PT J AU Werling, DM Geschwind, DH AF Werling, Donna M. Geschwind, Daniel H. TI Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins SO MOLECULAR AUTISM LA English DT Article DE Female protective model; Sex differences; Multiplex families; AGRE; Recurrence risk; Interbirth interval ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; GENOME-WIDE; SUSCEPTIBILITY LOCI; RESOURCE EXCHANGE; RISK LOCI; LINKAGE; EPIDEMIOLOGY; REPLICATION; SIBLINGS AB Background: Autism spectrum disorders (ASDs) are more prevalent in males, suggesting a multiple threshold liability model in which females are, on average, protected by sex-differential mechanisms. Under this model, autistic females are predicted to carry a more penetrant risk variant load than males and to share this greater genetic liability with their siblings. However, reported ASD recurrence rates have not demonstrated significantly increased risk to siblings of affected girls. Here, we characterize recurrence patterns in multiplex families from the Autism Genetics Resource Exchange (AGRE) to determine if risk in these families follows a female protective model. Methods: We assess recurrence rates and quantitative traits in full siblings from 1,120 multiplex nuclear families and concordance rates in 305 twin pairs from AGRE. We consider the first two affected children per family, and one randomly selected autistic twin per pair, as probands. We then compare recurrence rates and phenotypes between males and females and between twin pairs or families with at least one female proband (female-containing (FC)) versus those with only male probands (male-only (MO)). Results: Among children born after two probands, we observe significantly higher recurrence in males (47.5%) than in females (21.1%; relative risk, RR = 2.25; adjusted P = 6.22e-08) and in siblings of female (44.3%) versus siblings of male probands (30.4%; RR = 1.46; adj. P = 0.036). This sex-differential recurrence is also robust in dizygotic twin pairs (males = 61.5%, females = 19.1%; RR = 3.23; adj. P = 7.66e-09). Additionally, we find a significant negative relationship between interbirth interval and ASD recurrence that is driven by children in MO families. Conclusions: By classifying families as MO or FC using two probands instead of one, we observe significant recurrence rate differences between families harboring sex-differential familial liability. However, a significant sex difference in risk to children within FC families suggests that female protective mechanisms are still operative in families carrying high genetic risk loads. Furthermore, the male-specific relationship between shorter interbirth intervals and increased ASD risk is consistent with a potentially greater contribution from environmental factors in males versus higher genetic risk in affected females and their families. Understanding the mechanisms driving these sex-differential risk profiles will be useful for treatment development and prevention. C1 [Werling, Donna M.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Neurogenet Program, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobehav Genet, Semel Inst, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza, Los Angeles, CA 90095 USA. EM dhg@mednet.ucla.edu FU National Institute of Mental Health (NIMH) [1U24MH081810]; NIMH [F31 MH093086]; ACE Network grant [RO1 MH100027]; ACE Center grant [R01 MH071425] FX We gratefully acknowledge resources provided by the Autism Genetics Resource Exchange (AGRE) collection and the participating families, as well as Clara M. Lajonchere and Eve Landa. Thank you also to Jennifer Lowe for the assistance with data acquisition and management. 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Autism PD MAY 13 PY 2015 VL 6 AR 27 DI 10.1186/s13229-015-0004-5 PG 14 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CH9JC UT WOS:000354350800004 PM 25973164 ER PT J AU Vogt, D Cho, KKA Lee, AT Sohal, VS Rubenstein, JLR AF Vogt, Daniel Cho, Kathleen K. A. Lee, Anthony T. Sohal, Vikaas S. Rubenstein, John L. R. TI The Parvalbumin/Somatostatin Ratio Is Increased in Pten Mutant Mice and by Human PTEN ASD Alleles SO CELL REPORTS LA English DT Article ID AUTISM SPECTRUM DISORDERS; CORTICAL INTERNEURONS; NEURODEVELOPMENTAL DISORDERS; GAMMA-OSCILLATIONS; TENSIN HOMOLOG; MOUSE MODEL; CELLS; BRAIN; ABNORMALITIES; INHIBITION AB Mutations in the phosphatase PTEN are strongly implicated in autism spectrum disorder (ASD). Here, we investigate the function of Pten in cortical GABAergic neurons using conditional mutagenesis in mice. Loss of Pten results in a preferential loss of SST+ interneurons, which increases the ratio of parvalbumin/somatostatin (PV/SST) interneurons, ectopic PV+ projections in layer I, and inhibition onto glutamatergic cortical neurons. Pten mutant mice exhibit deficits in social behavior and changes in electroencephalogram (EEG) power. Using medial ganglionic eminence (MGE) transplantation, we test for cell-autonomous functional differences between human PTEN wild-type (WT) and ASD alleles. The PTEN ASD alleles are hypomorphic in regulating cell size and the PV/SST ratio in comparison to WT PTEN. This MGE transplantation/complementation assay is efficient and is generally applicable for functional testing of ASD alleles in vivo. C1 [Vogt, Daniel; Cho, Kathleen K. A.; Lee, Anthony T.; Sohal, Vikaas S.; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. [Rubenstein, John L. R.] Univ Calif San Francisco, Neurosci Program, San Francisco, CA 94158 USA. [Vogt, Daniel; Rubenstein, John L. R.] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA. [Cho, Kathleen K. A.; Lee, Anthony T.; Sohal, Vikaas S.] Univ Calif San Francisco, Ctr Integrat Neurosci, San Francisco, CA 94143 USA. [Cho, Kathleen K. A.; Lee, Anthony T.; Sohal, Vikaas S.] Univ Calif San Francisco, Sloan Swartz Ctr Theoret Neurobiol, San Francisco, CA 94143 USA. RP Vogt, D (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. EM daniel.vogt@ucsf.edu; john.rubenstein@ucsf.edu FU Autism Speaks; Weston Havens Foundation; NIMH [R01 MH081880, R37 MH049428, R01 MH100292]; International Mental Health Research Organization; NIH [DP2 MH100011]; NARSAD Young Investigator Award from the Brain and Behavior Foundation; Medical Scientist Training Program grant from NIGMS [GM07618]; Nina Ireland; Staglin Family FX This work was supported by grants to J.L.R.R. from Autism Speaks, Nina Ireland, Weston Havens Foundation, NIMH R01 MH081880, and NIMH R37 MH049428. V.S.S. was supported by the Staglin Family and International Mental Health Research Organization, NIH DP2 MH100011, and NIMH R01 MH100292. K.K.A.C. was supported by a NARSAD Young Investigator Award from the Brain and Behavior Foundation. A.T.L. was supported by a Medical Scientist Training Program grant from NIGMS (GM07618). J.L.R.R. is a founding member and consultant for Neurona Therapeutics. 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Cell. Neurosci. PD MAY 12 PY 2015 VL 9 AR 183 DI 10.3389/fncel.7015.00183 PG 4 WC Neurosciences SC Neurosciences & Neurology GA CI5NL UT WOS:000354803700001 PM 26029053 ER PT J AU Varea, O Martin-de-Saavedra, MD Kopeikina, KJ Schurmann, B Fleming, HJ Fawcett-Patel, JM Bach, A Jang, S Peles, E Kim, E Penzes, P AF Varea, Olga Martin-de-Saavedra, Maria Dolores Kopeikina, Katherine J. Schuermann, Britta Fleming, Hunter J. Fawcett-Patel, Jessica M. Bach, Anthony Jang, Seil Peles, Elior Kim, Eunjoon Penzes, Peter TI Synaptic abnormalities and cytoplasmic glutamate receptor aggregates in contactin associated protein-like 2/Caspr2 knockout neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CNTNAP2; synapse; AMPA; GluA1; schizophrenia ID AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; CNTNAP2; SCHIZOPHRENIA; GENE; SYNAPSES; EPILEPSY; ADHESION; CONTACTIN-ASSOCIATED-PROTEIN-LIKE-2; METAANALYSIS AB Central glutamatergic synapses and the molecular pathways that control them are emerging as common substrates in the pathogenesis of mental disorders. Genetic variation in the contactin associated protein-like 2 (CNTNAP2) gene, including copy number variations, exon deletions, truncations, single nucleotide variants, and polymorphisms have been associated with intellectual disability, epilepsy, schizophrenia, language disorders, and autism. CNTNAP2, encoded by Cntnap2, is required for dendritic spine development and its absence causes disease-related phenotypes in mice. However, the mechanisms whereby CNTNAP2 regulates glutamatergic synapses are not known, and cellular phenotypes have not been investigated in Cntnap2 knockout neurons. Here we show that CNTNAP2 is present in dendritic spines, as well as axons and soma. Structured illumination superresolution microscopy reveals closer proximity to excitatory, rather than inhibitory synaptic markers. CNTNAP2 does not promote the formation of synapses and cultured neurons from Cntnap2 knockout mice do not show early defects in axon and dendrite outgrowth, suggesting that CNTNAP2 is not required at this stage. However, mature neurons from knockout mice show reduced spine density and levels of GluA1 subunits of AMPA receptors in spines. Unexpectedly, knockout neurons show large cytoplasmic aggregates of GluA1. Here we characterize, for the first time to our knowledge, synaptic phenotypes in Cntnap2 knockout neurons and reveal a novel role for CNTNAP2 in GluA1 trafficking. Taken together, our findings provide insight into the biological roles of CNTNAP2 and into the pathogenesis of CNTNAP2-associated neuropsychiatric disorders. C1 [Varea, Olga; Martin-de-Saavedra, Maria Dolores; Kopeikina, Katherine J.; Schuermann, Britta; Fleming, Hunter J.; Fawcett-Patel, Jessica M.; Bach, Anthony; Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. [Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Jang, Seil; Kim, Eunjoon] Korea Adv Inst Sci & Technol, Dept Neurosci, Taejon 305701, South Korea. [Kim, Eunjoon] Inst for Basic Sci Korea, Ctr Synapt Brain Dysfunct, Taejon 305701, South Korea. [Peles, Elior] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Penzes, P (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. EM p-penzes@northwestern.edu FU NIH National Institute of Mental Health [MH097216]; Institute for Basic Science [IBS-R002-D1]; NIH Grant [NS50220, 1S10OD016342-01]; National Cancer Institute Cancer Center Support Grant [P30 CA060553] FX We thank Drs. Teng-Leong Chew and Joshua Zachary Rappoport for help with SIM imaging. This work was supported by Grant MH097216 from the NIH National Institute of Mental Health (to P.P.), IBS-R002-D1 from Institute for Basic Science (to E.K.), German Research Foundation Research Fellowship SCHU2710/1-1 (to B.S.), and NIH Grant NS50220 (to E.P.). SIM imaging work was performed at the Northwestern University Center for Advanced Microscopy, which is generously supported by National Cancer Institute Cancer Center Support Grant P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. SIM imaging was performed on a Nikon N-SIM system, purchased through the support of NIH Grant 1S10OD016342-01. 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Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2015 VL 112 IS 19 BP 6176 EP 6181 DI 10.1073/pnas.1423205112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CH9XS UT WOS:000354390600082 PM 25918374 ER PT J AU Xia, WL Liu, YL Jiao, JW AF Xia, Wenlong Liu, YanLi Jiao, Jianwei TI GRM7 Regulates Embryonic Neurogenesis via CREB and YAP SO STEM CELL REPORTS LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; CELL-PROLIFERATION; PROGENITOR PROLIFERATION; CORTICAL DEVELOPMENT; PKC PHOSPHORYLATION; MAMMALIAN BRAIN; DIFFERENTIATION; TRANSCRIPTION; BROMODEOXYURIDINE; BIOLOGY AB Metabotropic glutamate receptor 7 (GRM7) has recently been identified to be associated with brain developmental defects, such as attention deficit hyperactivity disorder (ADHD) and autism. However, the function of GRM7 during brain development remains largely unknown. Here, we used gain-and loss-of-function strategies to investigate the role of GRM7 in early cortical development. We demonstrate that Grm7 knockdown increases neural progenitor cell (NPC) proliferation, decreases terminal mitosis and neuronal differentiation, and leads to abnormal neuronal morphology. GRM7 regulates the phosphorylation of cyclic AMP response element-binding protein (CREB) and the expression of Yes-associated protein (YAP) by directly interacting with CaM, which subsequently regulates the expression of CyclinD1 and ultimately affects early cortical development. These defects in neurogenesis are ameliorated by Grm7 overexpression, Creb knockdown, or Yap knockdown. Thus, our findings indicate that GRM7 signaling via CREB and YAP is necessary for neurogenesis in the brain. C1 [Xia, Wenlong; Liu, YanLi; Jiao, Jianwei] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China. [Xia, Wenlong] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. RP Jiao, JW (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China. EM jwjiao@ioz.ac.cn RI Jiao, Jianwei/I-1452-2013 OI Jiao, Jianwei/0000-0002-7893-0721 FU National Key Basic Research Program of China [2015CB964501, 2014CB964903]; Strategic Priority Research Program [XDA01020301]; National Science Foundation of China [31371477] FX We thank Junhua Lv and Feng Liu for technical help. This work was supported by grants from the National Key Basic Research Program of China (2015CB964501 and 2014CB964903), Strategic Priority Research Program (XDA01020301), and the National Science Foundation of China (31371477). 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PD MAY 12 PY 2015 VL 4 IS 5 BP 795 EP 810 DI 10.1016/j.stemcr.2015.03.004 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CI0DO UT WOS:000354406400004 PM 25921811 ER PT J AU Rahbar, MH Samms-Vaughan, M Dickerson, AS Loveland, KA Ardjomand-Hessabi, M Bressler, J Shakespeare-Pellington, S Grove, ML 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. Boerwinkle, Eric TI Factors associated with blood lead concentrations of children in Jamaica SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING LA English DT Article DE Children; Jamaica; food; road traffic; lead; risk factors ID AUTISM SPECTRUM DISORDERS; ARSENIC CONCENTRATIONS; DRINKING-WATER; TRACE-ELEMENTS; HEAVY-METALS; MEXICO-CITY; EXPOSURE; FISH; CONSUMPTION; SEDIMENTS AB Lead is a heavy metal known to be detrimental to neurologic, physiologic, and behavioral health of children. Previous studies from Jamaica reported that mean lead levels in soil are four times that of lead levels in some other parts of the world. Other studies detected lead levels in fruits and root vegetables, which were grown in areas with lead contaminated soil. In this study, we investigate environmental factors associated with blood lead concentrations in Jamaican children. The participants in this study comprised 125 typically developing (TD) children (ages 2-8years) who served as controls in an age- and sex-matched case-control study that enrolled children from 2009-2012 in Jamaica. We administered a questionnaire to assess demographic and socioeconomic information as well as potential exposures to lead through food. Using General Linear Models (GLMs), we identified factors associated with blood lead concentrations in Jamaican children. The geometric mean blood lead concentration (GMBLC) in the sample of children in this study was 2.80 mu g dL(-1). In univariable GLM analyses, GMBLC was higher for children whose parents did not have education beyond high school compared to those whose parents had attained this level (3.00 mu g dL(-1) vs. 2.31 mu g dL(-1); P = 0.05), children living near a high traffic road compared to those who did not (3.43 mu g dL(-1) vs. 2.52 mu g dL(-1); P < 0.01), and children who reported eating ackee compared to those who did not eat this fruit (2.89 mu g dL(-1) vs. 1.65 mu g dL(-1); P < 0.05). In multivariable analysis, living near a high traffic road was identified as an independent risk factor for higher adjusted GMBLC (3.05 mu g dL(-1) vs. 2.19 mu g dL(-1); P = 0.01). While our findings indicate that GMBLC in Jamaican children has dropped by at least 62% during the past two decades, children living in Jamaica still have GMBLC that is twice that of children in more developed countries. In addition, we have identified significant risk factors for higher blood lead concentrations in Jamaican children. We believe increasing awareness among parents regarding these risk factors could potentially lead to a lower level of lead exposure in Jamaican children. C1 [Rahbar, Mohammad H.; Boerwinkle, Eric] Univ Texas Sch Publ Hlth Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Rahbar, Mohammad H.] Univ Texas Hlth Sci Ctr Houston, Sch Med, 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, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design BERD Core, Houston, TX 77030 USA. [Samms-Vaughan, Maureen; Shakespeare-Pellington, Sydonnie] Univ W Indies, Dept Child & Adolescent Hlth, Kingston 7, Jamaica. [Loveland, Katherine A.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Med Sch Houston, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Bressler, Jan; Grove, Megan L.; Boerwinkle, Eric] Univ Texas Sch Publ Hlth Houston, Ctr Human Genet, Houston, TX USA. RP Rahbar, MH (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design BERD Core, 6410 Fannin St,UT Profess Bldg,Suite 1100-05, 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]; Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS); NIH Centers for Translational Science Award (NIH CTSA) grant [UL1 RR024148]; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS) [UL1 TR000371] 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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PD MAY 12 PY 2015 VL 50 IS 6 BP 529 EP 539 DI 10.1080/10934529.2015.994932 PG 11 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA CF1PU UT WOS:000352320600001 PM 25837555 ER PT J AU Gdalyahu, A Lazaro, M Penagarikano, O Golshani, P Trachtenberg, JT Gescwind, DH AF Gdalyahu, Amos Lazaro, Maria Penagarikano, Olga Golshani, Peyman Trachtenberg, Joshua T. Gescwind, Daniel H. TI The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study SO PLOS ONE LA English DT Article ID STRUCTURAL PLASTICITY; LONG-TERM; EXPERIENCE; CORTEX; NEOCORTEX; SYNAPSES; CONTACTIN-ASSOCIATED-PROTEIN-LIKE-2; IMPLICATE; DYNAMICS; EPILEPSY AB The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry. C1 [Gdalyahu, Amos; Trachtenberg, Joshua T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol,Brain Res Inst, Integrat Ctr Learning & Memory,Semel Inst Neurosc, Los Angeles, CA 90095 USA. [Lazaro, Maria; Penagarikano, Olga; Golshani, Peyman; Gescwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet & Neurobehav Genet, Dept Neurol,Semel Inst Neurosci & Behav, Los Angeles, CA 90095 USA. RP Gdalyahu, A (reprint author), Tel Aviv Univ, Dept Neurobiol, IL-69978 Tel Aviv, Israel. EM amos.gdalyahu@gmail.com FU ACE Network [5RO1MH081754, RO1MH10027] FX Funding: This work was supported by ACE Network grant 5RO1MH081754 and the renewal RO1MH10027. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Dunaevsky, Anna TI Deficit in Motor Training-Induced Clustering, but Not Stabilization, of New Dendritic Spines in fmr1 Knock-Out Mice SO PLOS ONE LA English DT Article ID FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; MOUSE MODEL; MESSENGER-RNAS; CGG-REPEAT; AUTISM; CORTEX; IDENTIFICATION AB Fragile X Syndrome is the most common inherited intellectual disability, and Fragile X Syndrome patients often exhibit motor and learning deficits. It was previously shown that the fmr1 knock-out mice, a common mouse model of Fragile X Syndrome, recapitulates this motor learning deficit and that the deficit is associated with altered plasticity of dendritic spines. Here, we investigated the motor learning-induced turnover, stabilization and clustering of dendritic spines in the fmr1 knock-out mouse using a single forelimb reaching task and in vivo multiphoton imaging. We report that fmr1 knock-out mice have deficits in motor learning-induced changes in dendritic spine turnover and new dendritic spine clustering, but not the motor learning-induced long-term stabilization of new dendritic spines. These results suggest that a failure to establish the proper synaptic connections in both number and location, but not the stabilization of the connections that are formed, contributes to the motor learning deficit seen in the fmr1 knock-out mouse. C1 [Reiner, Benjamin C.; Dunaevsky, Anna] Univ Nebraska, Med Ctr, Munroe Meyer Inst, Dept Dev Neurosci, Omaha, NE 68182 USA. RP Dunaevsky, A (reprint author), Univ Nebraska, Med Ctr, Munroe Meyer Inst, Dept Dev Neurosci, Omaha, NE 68182 USA. EM adunaevsky@unmc.edu FU National Institute of Child Health and Human Development [R01 HD67218] FX This work was supported by the National Institute of Child Health and Human Development R01 HD67218 to A.D. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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The typical phenotype includes neonatal hypotonia, moderate to severe intellectual disability, absent or delayed speech, minor dysmorphic features and autism or autistic-like behaviour. Recently, point mutations or micro-deletions of the SHANK3 gene have been identified, accompanied by a phenotype different from the initial clinically description in Phelan McDermid syndrome. Case presentation: Here we present two case studies with similar psychiatric and genetic diagnosis as well as similar clinical history and evolution. The two patients were diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioural disorders after a stressful event during adolescence. Interestingly, both patients presented mutation/ microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and methylphenidate) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioural symptoms and allowed patients to recover their pre-catatonia level of functioning, without significant side effects. Conclusion: These cases support the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to catatonia-like deterioration for which lithium use could be an efficient treatment. Therefore, these cases provide an important contribution to the field of autism research, clinical genetics and possible pharmacological answers. C1 [Serret, Sylvie; Thuemmler, Susanne; Dor, Emmanuelle; Vesperini, Stephanie; Santos, Andreia; Askenazy, Florence] Univ Nice Sophia Antipolis, CoBTek EA7276, Childrens Hosp Nice CHU Lenval, Univ Child & Adolescent Psychiat Dept,Autism Reso, F-06189 Nice, France. RP Serret, S (reprint author), Univ Nice Sophia Antipolis, CoBTek EA7276, Childrens Hosp Nice CHU Lenval, Univ Child & Adolescent Psychiat Dept,Autism Reso, F-06189 Nice, France. EM serret.s@pediatrie-chulenval-nice.fr CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Bonaglia MC, 2011, PLOS GENET, V7, P7 Bush G, 1996, ACTA PSYCHIAT SCAND, V93, P129, DOI 10.1111/j.1600-0447.1996.tb09814.x Busner Joan, 2007, Psychiatry (Edgmont), V4, P28 Cipriani A, 2013, BMC PSYCHIATRY, V13, DOI 10.1186/1471-244X-13-212 Denayer A, 2012, MOL SYNDROMOL, V3, P14, DOI DOI 10.1159/000339119 Durand CM, 2007, NAT GENET, V39, P25, DOI 10.1038/ng1933 Kumar RA, 2009, CURR NEUROL NEUROSCI, V9, P188, DOI 10.1007/s11910-009-0029-2 Leblond C, 2014, PLOS GENET, V10, P9 Lord C., 2000, AUTISM DIAGNOSTIC OB Perez-Martinez DA, 2009, NEUROLOGIA, V24, P143 Phelan K, 2012, MOL SYNDROMOL, V2-5, P186, DOI DOI 10.1159/000334260 Rutter M., 2003, ADI R AUTISM DIAGNOS Sparrow S, 1984, VINELAND ADAPTATIVE Verhoeven WMA, 2012, NEUROPSYCH DIS TREAT, V8, P175, DOI 10.2147/NDT.S30506 Verhoeven WMA, 2013, AM J MED GENET A, V161A, P158, DOI 10.1002/ajmg.a.35597 Wang XM, 2014, MOL AUTISM, V5, DOI 10.1186/2040-2392-5-30 Wang XM, 2014, DEV NEUROBIOL, V74, P123, DOI 10.1002/dneu.22084 Wing L, 2006, INT REV NEUROBIOL, V72, P21, DOI 10.1016/S0074-7742(05)72002-X NR 19 TC 0 Z9 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD MAY 7 PY 2015 VL 15 AR 107 DI 10.1186/s12888-015-0490-1 PG 6 WC Psychiatry SC Psychiatry GA CH9JO UT WOS:000354352100002 PM 25947967 ER PT J AU Migliavacca, E Golzio, C Mannik, K Blumenthal, I Oh, EC Harewood, L Kosmicki, JA Loviglio, MN Giannuzzi, G Hippolyte, L Maillard, AM Alfaiz, AA van Haelst, MM Andrieux, J Gusella, JF Daly, MJ Beckmann, JS Jacquemont, S Talkowski, ME Katsanis, N Reymond, A AF Migliavacca, Eugenia Golzio, Christelle Maennik, Katrin Blumenthal, Ian Oh, Edwin C. Harewood, Louise Kosmicki, Jack A. Loviglio, Maria Nicla Giannuzzi, Giuliana Hippolyte, Loyse Maillard, Anne M. Alfaiz, Ali Abdullah van Haelst, Mieke M. Andrieux, Joris Gusella, James F. Daly, Mark J. Beckmann, Jacques S. Jacquemont, Sebastien Talkowski, Michael E. Katsanis, Nicholas Reymond, Alexandre CA 16p11 2 European Consortium TI A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY NUMBER VARIATION; DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDER; SPINAL MUSCULAR-ATROPHY; SPATIAL WORKING-MEMORY; JOUBERT-SYNDROME; CHROMOSOME 16P11.2; PRIMARY CILIUM; CENTROSOMAL PROTEIN; SCHIZOPHRENIA AB The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11.2 CNVs. Transcript perturbations correlated with clinical endophenotypes and were enriched for genes associated with ASDs, abnormalities of head size, and ciliopathies. Ciliary gene expression was also perturbed in orthologous mouse models, raising the possibility that ciliary dysfunction contributes to 16p11.2 pathologies. In support of this hypothesis, we found structural ciliary defects in the CA1 hippocampal region of 16p11.2 duplication mice. Moreover, by using an established zebrafish model, we show genetic interaction between KCTD13, a key driver of the mirrored neuroanatomical phenotypes of the 16p11.2 CNV, and ciliopathy-associated genes. Overexpression of BBS7 rescues head size and neuroanatomical defects of kctd13 morphants, whereas suppression or overexpression of CEP290 rescues phenotypes induced by KCTD13 under-or overexpression, respectively. Our data suggest that dysregulation of ciliopathy genes contributes to the clinical phenotypes of these CNVs. C1 [Migliavacca, Eugenia; Maennik, Katrin; Harewood, Louise; Loviglio, Maria Nicla; Giannuzzi, Giuliana; Alfaiz, Ali Abdullah; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Migliavacca, Eugenia; Alfaiz, Ali Abdullah; Beckmann, Jacques S.] SIB, CH-1015 Lausanne, Switzerland. [Golzio, Christelle; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Golzio, Christelle; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Maennik, Katrin] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Blumenthal, Ian; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kosmicki, Jack A.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kosmicki, Jack A.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Hippolyte, Loyse; Maillard, Anne M.; Beckmann, Jacques S.; Jacquemont, Sebastien] Lausanne Univ Hosp CHUV, Serv Med Genet, CH-1011 Lausanne, Switzerland. [van Haelst, Mieke M.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 AB Utrecht, Netherlands. [Andrieux, Joris] CHRU Lille, Inst Genet Med, Hop Jeanne de Flandre, F-59037 Lille, France. [Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland. RP Katsanis, N (reprint author), Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA. EM katsanis@cellbio.duke.edu; alexandre.reymond@unil.ch FU Swiss Scientific Exchange NMS Program; Swiss National Science Foundation (SNSF); Brain and Behavior Research Foundation; Saudi Arabian National Guard Health Affairs; Simons Foundation [SFARI274424, SFARI239983, SFARI238504, SFARI240021]; Swiss National Science Foundation [31003A_160203]; SNSF [CRIS FN CRSII33-133044]; Leenaards Foundation Prize; NIH [P50MH094260, MH095867]; Nancy Lurie Marks Family Foundation FX We thank the members of the Lausanne Genomic Technologies Facility, Patrick Meylan, and Alexandre Thiery for technical help. We are grateful to all the families participating to the Simons Variation in Individuals Project (Simons VIP), as well as to the Simons VIP working group. K.M. was awarded a scholarship from the Swiss Scientific Exchange NMS Program, S.J. is recipient of a Bursary Professor fellowship of the Swiss National Science Foundation (SNSF), and C.G., E.C.O., and M.E.T. are grantees of NARSAD Young Investigator Grants from the Brain and Behavior Research Foundation. A. A. A. was awarded a scholarship from the Saudi Arabian National Guard Health Affairs. This work is supported by the Simons Foundation (grants SFARI274424 to A.R., SFARI239983 to N.K., SFARI238504 to M.E.T., and SFARI240021 to J.F.G.), the Swiss National Science Foundation (grant 31003A_160203 to A.R.), a specific SNSF Sinergia grant (CRIS FN CRSII33-133044 to A.R.), the Leenaards Foundation Prize (S.J. and A.R.), by NIH P50MH094260 (N.K.) and MH095867 (M.E.T.), and the Nancy Lurie Marks Family Foundation (J.F.G. and M.E.T.). N.K. is a Distinguished Brumley Professor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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J. Hum. Genet. PD MAY 7 PY 2015 VL 96 IS 5 BP 784 EP 796 DI 10.1016/j.ajhg.2015.04.002 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CH7AZ UT WOS:000354189300009 PM 25937446 ER PT J AU Barrer, L Gimenez, G AF Barrer, Laurence Gimenez, Guy TI First time description of dismantling phenomenon SO FRONTIERS IN PSYCHOLOGY LA English DT Review DE countertransference; autistic disorder; dismantling; metapsychology; defense mechanism AB Dismantling is a complex psychic phenomenon, which is not easy to define, and little interest has been shown in the subject. The authors of this paper want to demonstrate that dismantling is the main defense mechanism in autism, bringing about de-consensus of senses. The effects perceived in a child with autistic disorder are passivity and lack of thought. The authors' purpose here is to define the dismantled state and reveal its underlying process. 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Psychol. PD MAY 5 PY 2015 VL 6 AR 510 DI 10.3389/fpsyg.2015.00510 PG 5 WC Psychology, Multidisciplinary SC Psychology GA CI5PC UT WOS:000354809100001 PM 25999871 ER PT J AU Clausi, S Coricelli, G Pisotta, I Pavone, EF Lauriola, M Molinari, M Leggio, M AF Clausi, Silvia Coricelli, Giorgio Pisotta, Iolanda Pavone, Enea Francesco Lauriola, Marco Molinari, Marco Leggio, Maria TI Cerebellar damage impairs the self-rating of regret feeling in a gambling task SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE choice behavior; cortico-cerebellar circuits; emotion; gambling; self-monitoring; social cognition; autism spectrum disorders; alexithymia ID DECISION-MAKING; ORBITOFRONTAL CORTEX; EMOTION; DISAPPOINTMENT; AUTISM; BRAIN; SCHIZOPHRENIA; NEUROANATOMY; COGNITION; NETWORKS AB Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17-60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects' choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. 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PD MAY 4 PY 2015 VL 21 IS 3 BP 379 EP 398 DI 10.1080/09297049.2014.906569 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA CI9SC UT WOS:000355109100007 PM 24754365 ER PT J AU Fawkes, DB Malow, BA Weiss, SK Reynolds, AM Loh, A Adkins, KW Wofford, DD Wyatt, AD Goldman, SE AF Fawkes, Diane B. Malow, Beth A. Weiss, Shelly K. Reynolds, Ann M. Loh, Alvin Adkins, Karen W. Wofford, Deborah D. Wyatt, Amanda D. Goldman, Suzanne E. TI Conducting Actigraphy Research in Children With Neurodevelopmental Disorders-A Practical Approach SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID PRACTICE PARAMETERS; WRIST ACTIGRAPHY; SLEEP DISORDERS; AUTISM; ADOLESCENTS; INSOMNIA; SPECTRUM; UPDATE; HOME AB The literature has been highly informative for when to use actigraphy and its validity in pediatric research. However, minimal literature exists on how to perform actigraphy, especially in special populations. We determined whether providing actigraphy training to parents and coordinators increased the nights of actigraphy data that could be scored. We compared two studies in children with autism spectrum disorders, one of which provided a basic level of training in a single-site trial and the other of which provided more detailed training to parents and coordinators in a multisite trial. There was an increase in scorable nights in the multisite trial containing a one-hour structured parent training session. Our results support the use of educational tools in clinical trials that use actigraphy. C1 [Fawkes, Diane B.; Malow, Beth A.; Adkins, Karen W.; Wofford, Deborah D.; Wyatt, Amanda D.; Goldman, Suzanne E.] Vanderbilt Univ, Dept Neurol, Sleep Disorders Div, Sch Med, Nashville, TN 37232 USA. [Malow, Beth A.; Goldman, Suzanne E.] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA. [Weiss, Shelly K.] Univ Toronto, Hosp Sick Children, Toronto, ON M5S 1A1, Canada. [Reynolds, Ann M.] Univ Colorado Denver, Dept Pediat, Anschutz Med Campus, Aurora, CO USA. [Reynolds, Ann M.] Univ Colorado, Sch Med, Aurora, CO USA. [Loh, Alvin] Univ Toronto, Pediat, Toronto, ON, Canada. [Loh, Alvin] Surrey Pl Ctr, Toronto, ON M5S 2C2, Canada. RP Fawkes, DB (reprint author), Vanderbilt Univ, Dept Neurol, Sleep Disorders Div, 1161 21st Ave South,Room A-0118, Nashville, TN 37232 USA. EM diane.b.fawkes@vanderbilt.edu FU U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054]; Organization for Autism Research; CTSA from the National Center for Advancing Translational Sciences [UL1TR000445] FX The authors report no conflicts of interest or financial relationships relevant to this article. This research was conducted as part of the Autism Speaks Autism Treatment Network. Further support came from a cooperative agreement (UA3 MC 11054) from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. Additional support was provided by the Organization for Autism Research and CTSA award No. UL1TR000445 from the National Center for Advancing Translational Sciences. The views expressed in this publication do not necessarily reflect the views of Autism Speaks, Inc. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. 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PD MAY 4 PY 2015 VL 13 IS 3 BP 181 EP 196 DI 10.1080/15402002.2013.854245 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CH0QR UT WOS:000353727800002 PM 24669845 ER PT J AU Seigfried-Spellar, KC O'Quinn, CL Treadway, KN AF Seigfried-Spellar, Kathryn C. O'Quinn, Casey L. Treadway, Kellin N. TI Assessing the relationship between autistic traits and cyberdeviancy in a sample of college students SO BEHAVIOUR & INFORMATION TECHNOLOGY LA English DT Article DE computer crime; autism; Asperger syndrome; hacking; cybercrime; cyberbullying; personality ID SYNDROME/HIGH-FUNCTIONING AUTISM; SPECTRUM QUOTIENT AQ; ASPERGER-SYNDROME; COMPUTER; VALIDITY; BEHAVIOR AB Case studies suggest a relationship between Asperger syndrome (AS) and computer hacking. The current study examined whether characteristics associated with AS were significantly related to hacking, cyberbullying, identity theft, and virus writing. Two hundred and ninety-six university undergraduate students completed an Internet-based anonymous survey measuring self-reported computer deviant behaviour and characteristics associated with AS (autism-spectrum quotient; AQ). Of the 296 university students, 179 (60%) engaged in some form of computer deviant behaviour, but only 2 (0.01%) yielded clinically significant scores according to the AQ. Contrary to the authors' expectations, hackers did not score higher on the AQ compared to non-computer hackers. However, virus writers, identity thieves, and cyberbullies scored higher on the AQ compared to their computer non-deviant counterparts. In addition, individuals who engaged in hacking, identity theft, cyberbullying, and virus writing scored higher on the AQ and reported poorer social skills, poorer communication, and poorer imagination compared to all other individuals engaging in computer deviant behaviours. Considerations for future research and study limitations are discussed. C1 [Seigfried-Spellar, Kathryn C.; O'Quinn, Casey L.; Treadway, Kellin N.] Univ Alabama, Dept Criminal Justice, Tuscaloosa, AL 35487 USA. RP Seigfried-Spellar, KC (reprint author), Univ Alabama, Dept Criminal Justice, 410 Farrah Hall,Box 870320 Mailing, Tuscaloosa, AL 35487 USA. 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D., 1999, Security Management, V43 Vandebosch H, 2008, CYBERPSYCHOL BEHAV, V11, P499, DOI 10.1089/cpb.2007.0042 Woodbury-Smith MR, 2005, J AUTISM DEV DISORD, V35, P331, DOI 10.1007/s10803-005-3300-7 NR 31 TC 0 Z9 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0144-929X EI 1362-3001 J9 BEHAV INFORM TECHNOL JI Behav. Inf. Technol. PD MAY 4 PY 2015 VL 34 IS 5 BP 533 EP 542 DI 10.1080/0144929X.2014.978377 PG 10 WC Computer Science, Cybernetics; Ergonomics SC Computer Science; Engineering GA CD1EZ UT WOS:000350818600009 ER PT J AU Clarke, CE Dixon, GN Holton, A McKeever, BW AF Clarke, Christopher E. Dixon, Graham N. Holton, Avery McKeever, Brooke Weberling TI Including "Evidentiary Balance" in News Media Coverage of Vaccine Risk SO HEALTH COMMUNICATION LA English DT Article ID UNCERTAINTY; INFORMATION; JOURNALISM; AUTISM; REPRESENTATIONS; COMMUNICATION; PERCEPTIONS; CREDIBILITY; CONTROVERSY; SCIENTISTS AB Journalists communicating risk-related uncertainty must accurately convey scientific evidence supporting particular conclusions. Scholars have explored how "balanced" coverage of opposing risk claims shapes uncertainty judgments. In situations where a preponderance of evidence points to a particular conclusion, balanced coverage reduces confidence in such a consensus and heightens uncertainty about whether a risk exists. Using the autism-vaccine controversy as a case study, we describe how journalists can cover multiple sides of an issue and provide insight into where the strength of evidence lies by focusing on "evidentiary balance." Our results suggest that evidentiary balance shapes perceived certainty that vaccines are safe, effective, and not linked to autism through the mediating role of a perception that scientists are divided about whether a link exists. Deference toward science, moreover, moderates these relationships under certain conditions. We discuss implications for journalism practice and risk communication. C1 [Clarke, Christopher E.] George Mason Univ, Dept Commun, Fairfax, VA 20031 USA. [Dixon, Graham N.] Washington State Univ, Murrow Coll Commun, Pullman, WA 99164 USA. [Holton, Avery] Univ Utah, Dept Commun, Salt Lake City, UT 84112 USA. [McKeever, Brooke Weberling] Univ S Carolina, Sch Journalism & Mass Commun, Columbia, SC 29208 USA. RP Clarke, CE (reprint author), George Mason Univ, Dept Commun, 4400 Univ Dr,MS 3D6, Fairfax, VA 20031 USA. 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F., 2013, INTRO MEDIATION MODE Holton A., 2011, ELECT J COMMUNICATIO, V21, P1 Holton A., 2014, COMMUNICATION RES RE, V32, P33, DOI [10.1080/08824096.2013.843165, DOI 10.1080/08824096.2013.843165] Jensen JD, 2008, HUM COMMUN RES, V34, P347, DOI 10.1111/j.1468-2958.2008.00324.x Jensen JD, 2011, J HEALTH COMMUN, V16, P486, DOI 10.1080/10810730.2010.546491 Jensen JD, 2012, PUBLIC UNDERST SCI, V21, P689, DOI 10.1177/0963662510387759 Kennedy A, 2011, HEALTH AFFAIR, V30, P1151, DOI 10.1377/hlthaff.2011.0396 Mebane F, 2003, J HEALTH COMMUN, V8, P50, DOI 10.1080/1081730390224875 Powell M, 2007, PUBLIC UNDERST SCI, V16, P323, DOI 10.1177/0963662507074491 Ryan M., 2001, J MASS MEDIA ETHICS, V16, P3, DOI 10.1207/S15327728JMME1601_2 Schmitt KM, 2004, COMMUN RES, V31, P623, DOI 10.1177/0093650205269390 NR 37 TC 0 Z9 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PD MAY 4 PY 2015 VL 30 IS 5 BP 461 EP 472 DI 10.1080/10410236.2013.867006 PG 12 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA CB5LC UT WOS:000349667500005 PM 25010352 ER PT J AU Fernandez, MAF Puentes, AA AF Fernandez Fernandez, M. A. Amado Puentes, A. TI The importance of being careful with the concepts on autism spectrum disorders SO ANALES DE PEDIATRIA LA Spanish DT Letter C1 [Fernandez Fernandez, M. A.] Inst Andaluz Neurol Pediat, Area Neurol Pediat, Seville, Spain. [Amado Puentes, A.] Complejo Hosp Univ Vigo, Serv Pediat, Unidad Neurol Pediait, Vigo, Spain. RP Fernandez, MAF (reprint author), Inst Andaluz Neurol Pediat, Area Neurol Pediat, Seville, Spain. EM drlolo13@hotmail.com; amadopuentes@gmail.com CR Alonso Canal L, 2014, AN PEDIAT BARC CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Mari-Bauset S, 2014, J CHILD NEUROL Sponheim E, 2006, TIDSSKR NOR LAEGEFOR, V25, P1475 NR 4 TC 0 Z9 0 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 1695-4033 EI 1696-4608 J9 AN PEDIATR JI An. Pediatr. PD MAY PY 2015 VL 82 IS 5 BP 372 EP 372 DI 10.1016/j.anpedi.2014.09.016 PG 1 WC Pediatrics SC Pediatrics GA CI8ZF UT WOS:000355059500017 PM 25510842 ER PT J AU Canal, LA Zaragoza, CI AF Alonso Canal, L. Isasi Zaragoza, C. TI Gluten-free, casein-free diet in autism spectrum disorders; different perspectives SO ANALES DE PEDIATRIA LA Spanish DT Letter C1 [Alonso Canal, L.] Hosp San Rafael, Serv Gastroenterol Pediat, Madrid, Spain. [Isasi Zaragoza, C.] Hosp Puerta Hierro Majadahonda, Serv Reumatol, Madrid, Spain. RP Canal, LA (reprint author), Hosp San Rafael, Serv Gastroenterol Pediat, Madrid, Spain. EM lauraalonso02@hotmail.com CR de Magistris L, 2010, J PEDIATR GASTR NUTR, V51, P418, DOI 10.1097/MPG.0b013e3181dcc4a5 Pennesi CM, 2012, NUTR NEUROSCI, V15, P85, DOI 10.1179/1476830512Y.0000000003 Troncone R, 2011, J INTERN MED, V269, P582, DOI 10.1111/j.1365-2796.2011.02385.x Vandenplas Yvan, 2014, Pediatr Gastroenterol Hepatol Nutr, V17, P1, DOI 10.5223/pghn.2014.17.1.1 NR 4 TC 0 Z9 0 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 1695-4033 EI 1696-4608 J9 AN PEDIATR JI An. Pediatr. PD MAY PY 2015 VL 82 IS 5 BP 373 EP 373 DI 10.1016/j.anpedi.2014.10.011 PG 1 WC Pediatrics SC Pediatrics GA CI8ZF UT WOS:000355059500018 ER PT J AU Schwartzman, JS Velloso, RD D'Antino, MEF Santos, S AF Schwartzman, Jose Salomao Velloso, Renata de Lima Fama D'Antino, Maria Eloisa Santos, Silvana TI The eye-tracking of social stimuli in patients with Rett syndrome and autism spectrum disorders: a pilot study SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Article DE Rett syndrome; autism spectrum disorders; social cognition; eye tracking ID CHILDREN; MECP2; MUTATION; OXYTOCIN; FEATURES; REGION AB Objective: To compare visual fixation at social stimuli in Rett syndrome (RT) and autism spectrum disorders (ASD) patients. Method: Visual fixation at social stimuli was analyzed in 14 RS female patients (age range 4-30 years), 11 ASD male patients (age range 4-20 years), and 17 children with typical development (TD). Patients were exposed to three different pictures (two of human faces and one with social and non-social stimuli) presented for 8 seconds each on the screen of a computer attached to an eye-tracker equipment. Results: Percentage of visual fixation at social stimuli was significantly higher in the RS group compared to ASD and even to TD groups. Conclusion: Visual fixation at social stimuli seems to be one more endophenotype making RS to be very different from ASD. C1 [Schwartzman, Jose Salomao; Fama D'Antino, Maria Eloisa] Univ Presbiteriana Mackenzie, Programa Posgrad Disturbios Desenvolvimento, Sao Paulo, SP, Brazil. [Velloso, Renata de Lima] Univ Presbiteriana Mackenzie, Clin Transtornos Espectro Autismo, Sao Paulo, SP, Brazil. [Santos, Silvana] Assoc Brasileira Sindrome Rett Sao Paulo Abre Te, Div Informacao & Pesquisa, Sao Paulo, SP, Brazil. RP Schwartzman, JS (reprint author), Rua Franca Pinto 941, BR-04016034 Sao Paulo, SP, Brazil. 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Neuro-Psiquiatr. PD MAY PY 2015 VL 73 IS 5 BP 402 EP 407 DI 10.1590/0004-282X20150033 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CJ2KL UT WOS:000355313200006 PM 26017205 ER PT J AU Lee, PF Thomas, RE Lee, PA AF Lee, Patrick F. Thomas, Roger E. Lee, Patricia A. TI Approach to autism spectrum disorder Using the new DSM-V diagnostic criteria and the CanMEDS-FM framework SO CANADIAN FAMILY PHYSICIAN LA English DT Review ID CHILDREN AB Objective To review the diagnostic criteria for autism spectrum disorder (ASD) from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), and to develop an approach to managing ASD using the CanMEDS-Family Medicine (CanMEDS-FM) framework. Sources of information The DSM-V from the American Psychiatric Association, published in May 2013, provides new diagnostic criteria for ASD. The College of Family Physicians of Canada's CanMEDS-FM framework provides a blueprint that can guide the complex management of ASD. We used data from the Centers for Disease Control and Prevention to determine the prevalence of ASD, and we used the comprehensive systematic review and meta-analysis completed by the UK National Institute for Health and Care Excellence for their guidelines on ASD to assess the evidence for more than 100 interventions. Main message The prevalence of ASD was 1 in 88 in 2008 in the United States according to data from the Centers for Disease Control and Prevention. The ASD classification in the fourth edition of the DSM included autism, Asperger syndrome, pervasive developmental disorder, and childhood disintegrative disorder. The new DSM-V revision incorporates all these disorders into one ASD umbrella term with different severity levels. The management of ASD is complex and requires a multidisciplinary team effort and continuity of care. The CanMEDS-FM roles provide a framework for management. Conclusion Family physicians are the key leaders of the multidisciplinary care team for ASD, and the CanMEDS-FM framework provides a comprehensive guide to help manage a child with ASD and to help the child's family. C1 [Lee, Patrick F.; Thomas, Roger E.] Univ Calgary, Family Med, Calgary, AB T2N 1N4, Canada. [Lee, Patrick F.; Thomas, Roger E.] Univ Calgary, Fac Med, Calgary, AB T2N 1N4, Canada. [Lee, Patricia A.] Univ Calgary, Emergency Med Residency Program, Calgary, AB T2N 1N4, Canada. RP Lee, PF (reprint author), Univ Calgary, Family Med, Calgary, AB T2N 1N4, Canada. 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Neuropsychopharmacol. PD MAY PY 2015 VL 25 IS 5 SI SI BP 682 EP 702 DI 10.1016/j.euroneuro.2014.01.009 PG 21 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CI8WO UT WOS:000355052600005 PM 24857313 ER PT J AU Jedrzejewska-Szczerska, M Karpienko, K Landowska, A AF Jedrzejewska-Szczerska, Malgorzata Karpienko, Katarzyna Landowska, Agnieszka TI System supporting behavioral therapy for children with autism SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES LA English DT Article DE Autism spectrum disorder; biomedical sensors; physiological parameters; sensor network ID HYPERVENTILATION SYNDROME; DISORDER; SENSORS; STRESS AB In this paper, a system supporting behavioral therapy for autistic children is presented. The system consists of sensors network, base station and a brooch indicating person's emotional states. The system can be used to measure values of physiological parameters that are associated with changes in the emotional state. In the future, it can be useful to inform the autistic child and the therapist about the emotional state of the interlocutor objectively, on the basis of performed measurements. The selected physiological parameters were chosen during the experiment which was designed and conducted by authors. In this experiment, a group of volunteers under controlled conditions was exposed to a stressful situation caused by the picture or sound. For each of the volunteers, a set of physiological parameters, was recorded, including: skin conductance, heart rate, peripheral temperature, respiration rate and electromyography. The bio-statistical analysis allowed us to discern the proper physiological parameters that are most associated to changes due to emotional state of a patient, such as: skin conductance, temperatures and respiration rate. This allowed us to design electronic sensors network for supporting behavioral therapy for children with autism. C1 [Jedrzejewska-Szczerska, Malgorzata] Gdansk Univ Technol, Fac Elect Telecommun & Informat, Dept Metrol & Optoelect, PL-80233 Gdansk, Poland. [Karpienko, Katarzyna; Landowska, Agnieszka] Gdansk Univ Technol, Fac Elect Telecommun & Informat, Dept Software Engn, PL-80233 Gdansk, Poland. RP Karpienko, K (reprint author), Gdansk Univ Technol, Fac Elect Telecommun & Informat, Dept Software Engn, Gabriela Narutowicza St 11-12, PL-80233 Gdansk, Poland. EM k.karpienko@pro.wp.pl FU Foundation for Polish Science [48/UD/SKILLS/2014]; National Centre for Research and Development, Poland; DS Programs of the Faculty of Electronics, Telecommunications and Informatics, Gdansk University of Technology; European Cooperation in Science and Technology (COST) Action [TD1309] FX This study was partially supported by the Foundation for Polish Science under grant No. 48/UD/SKILLS/2014 and the National Centre for Research and Development, Poland under grant titled: "Automated therapy monitoring for children with developmental disorders of autism spectrum", as well as DS Programs of the Faculty of Electronics, Telecommunications and Informatics, Gdansk University of Technology, and European Cooperation in Science and Technology (COST) Action TD1309. 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PD MAY PY 2015 VL 8 IS 3 SI SI AR 1541008 DI 10.1142/S1793545815410084 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA CJ3JQ UT WOS:000355379600009 ER PT J AU Wang, KS Tonarelli, S Luo, XG Wang, L Su, BD Zuo, LJ Mao, CX Rubin, L Briones, D Xu, C AF Wang, Ke-Sheng Tonarelli, Silvina Luo, Xingguang Wang, Liang Su, Brenda Zuo, Lingjun Mao, ChunXiang Rubin, Lewis Briones, David Xu, Chun TI Polymorphisms within ASTN2 gene are associated with age at onset of Alzheimer's disease SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Alzheimer's disease; Genome-wide association; Age of onset; ASTN2; Logrank test; Single-nucleotide polymorphisms ID GENOME-WIDE ASSOCIATION; OF-ONSET; LOCI; SCHIZOPHRENIA; LINKAGE; NUMBER; PREVALENCE; DISORDER; SPECTRUM; FAMILY AB Alzheimer's disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K single-nucleotide polymorphisms (SNPs) panel and the FBAT-logrank statistic. We observed 10 SNPs associated with AAO in AD with p < 2 x 10(-3). The most significant hit within a known gene, the neuronal protein astrotactin 2 (ASTN2), was SNP rs1334071 (p = 8.74 x 10(-4)). ASTN2 has been implicated in several neuropsychiatric disorders, including cognitive disorders, autism and schizophrenia. We then conducted a replication study focusing on ASTN2 gene in a Canadian sample of 791 AD patients and 782 controls using the logrank test. Five ASTN2 SNPs (highest association is rs16933774 with p = 0.0053) showed associations with AAO in this Canadian sample (p < 0.05). Furthermore, Kaplan-Meier survival analysis of SNP rs16933774 showed that the AAO of AD in individuals heterozygous for AG genotype of rs16933774 (median of AAO = 68.5 years) was approximately 4.5 years earlier than those individuals having the AA genotype (median of AAO = 73 years). In conclusion, a significant association of ASTN2 genetic variants with AAO of AD in two independent samples demonstrates a role for ASTN2 in the pathogenesis of AD. Future functional studies of this gene may help to characterize the genetic architecture of the AAO of AD. Genetic factors in AAO may be a critical factor for early AD intervention and prevention efforts. C1 [Wang, Ke-Sheng; Wang, Liang] E Tennessee State Univ, Coll Publ Hlth, Dept Biostat & Epidemiol, Johnson City, TN USA. [Tonarelli, Silvina; Briones, David] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Psychiat, El Paso, TX USA. [Luo, Xingguang; Zuo, Lingjun] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Su, Brenda] Harbin Med Univ, Coll Bioinformat Sci, Harbin, HeiLongJing, Peoples R China. [Su, Brenda] Harbin Med Univ, Coll Technol, Harbin, HeiLongJing, Peoples R China. [Mao, ChunXiang; Rubin, Lewis; Xu, Chun] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Pediat, El Paso, TX 79905 USA. RP Xu, C (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Pediat, El Paso, TX 79905 USA. EM chun.xu@ttuhsc.edu FU National Institute on Drug Abuse (NIDA) [K01 DA029643]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R21 AA021380, R21 AA020319]; National Alliance for Research on Schizophrenia and Depression (NARSAD) Award [17616]; ABMRF/The Foundation for Alcohol Research; Division of Neuroscience, NIA; Genetic Consortium for Late-Onset Alzheimer's Disease as part of the Division of Neuroscience, NIA FX This work was supported in part by National Institute on Drug Abuse (NIDA) grant K01 DA029643, National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R21 AA021380 and R21 AA020319, the National Alliance for Research on Schizophrenia and Depression (NARSAD) Award 17616 (L.Z.) and ABMRF/The Foundation for Alcohol Research (L.Z.). We acknowledge the NIH GWAS Data Repository, the Contributing Investigator(s) who contributed the phenotype data and DNA samples from his/her original study, and the primary funding organization that supported the contributing study "National Institute on Aging (NIA) Late-Onset Alzheimer's Disease Genetics Initiative: The Multiplex Family Study". The NIA dataset used for 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 00160.v1.p1 through dbGaP accession number: phs000160.v1.p1. Funding support for the "Genetic Consortium for Late-Onset Alzheimer's Disease" was provided through the Division of Neuroscience, NIA. The Genetic Consortium for Late-Onset Alzheimer's Disease includes a genome-wide association study funded as part of the Division of Neuroscience, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Genetic Consortium for Late-Onset Alzheimer's Disease. We also acknowledge the NIH GWAS Data Repository, the Contributing Investigator(s) who contributed the phenotype data and DNA samples from his/her original study and the primary funding organization that supported the contributing study "Multi-Site Collaborative Study for Genotype-Phenotype Associations in Alzheimer's disease and longitudinal follow-up of Genotype-Phenotype Associations in Alzheimer's disease and Neuroimaging component of Genotype-Phenotype Associations in Alzheimer's disease". The genotypic and associated phenotypic data used in the study, "Multi-Site Collaborative Study for Genotype-Phenotype Associations in Alzheimer's Disease (GenADA)" were provided by the GlaxoSmithKline, R&D Limited. The datasets used for analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000219.v1.p1. 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Neural Transm. PD MAY PY 2015 VL 122 IS 5 BP 701 EP 708 DI 10.1007/s00702-014-1306-z PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CJ2WD UT WOS:000355344500009 PM 25410587 ER PT J AU Lukic, A Uphill, J Brown, CA Beck, J Poulter, M Campbell, T Adamson, G Hummerich, H Whitfield, J Ponto, C Zerr, I Lloyd, SE Collinge, J Mead, S AF Lukic, Ana Uphill, James Brown, Craig A. Beck, John Poulter, Mark Campbell, Tracy Adamson, Gary Hummerich, Holger Whitfield, Jerome Ponto, Claudia Zerr, Inga Lloyd, Sarah E. Collinge, John Mead, Simon TI Rare structural genetic variation in human prion diseases SO NEUROBIOLOGY OF AGING LA English DT Article DE Prion; CNV; CJD; Kuru; GWAS ID CREUTZFELDT-JAKOB-DISEASE; GENOME-WIDE ASSOCIATION; RISK-FACTORS; VARIANT; KURU; PRNP; MUTATIONS; GENOTYPE; SCRAPIE; 16P11.2 AB Prion diseases are a diverse group of neurodegenerative conditions, caused by the templated misfolding of prion protein. Aside from the strong genetic risk conferred by multiple variants of the prion protein gene (PRNP), several other variants have been suggested to confer risk in the most common type, sporadic Creutzfeldt-Jakob disease (sCJD) or in the acquired prion diseases. Large and rare copy number variants (CNVs) are known to confer risk in several related disorders including Alzheimer's disease (at APP), schizophrenia, epilepsy, mental retardation, and autism. Here, we report the first genome-wide analysis for CNV-associated risk using data derived from a recent international collaborative association study in sCJD (n = 1147 after quality control) and publicly available controls (n = 5427). We also investigated UK patients with variant Creutzfeldt-Jakob disease (n = 114) and elderly women from the Eastern Highlands of Papua New Guinea who proved highly resistant to the epidemic prion disease kuru, who were compared with healthy young Fore population controls (n = 395). There were no statistically significant alterations in the burden of CNVs >100, >500, or >1000 kb, duplications, or deletions in any disease group or geographic region. After correction for multiple testing, no statistically significant associations were found. A UK blood service control sample showed a duplication CNV that overlapped PRNP, but these were not found in prion disease. Heterozygous deletions of a 30 region of the PARK2 gene were found in 3 sCJD patients and no controls (p = 0.001, uncorrected). A cell-based prion infection assay did not provide supportive evidence for a role for PARK2 in prion disease susceptibility. These data are consistent with a modest impact of CNVs on risk of late-onset neurologic conditions and suggest that, unlike APP, PRNP duplication is not a causal high-risk mutation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lukic, Ana; Uphill, James; Brown, Craig A.; Beck, John; Poulter, Mark; Campbell, Tracy; Adamson, Gary; Hummerich, Holger; Whitfield, Jerome; Lloyd, Sarah E.; Collinge, John; Mead, Simon] UCL Inst Neurol, MRC Prion Unit, London WC1N 3BG, England. [Ponto, Claudia; Zerr, Inga] Univ Gottingen, Dept Neurol, Gottingen, Germany. [Ponto, Claudia; Zerr, Inga] German Ctr Neurodegenrat Dis DZNE, Gottingen, Germany. RP Mead, S (reprint author), UCL Inst Neurol, MRC Prion Unit, Queen Sq, London WC1N 3BG, England. EM s.mead@prion.ucl.ac.uk FU Medical Research Council; Department of Health (England); Biomedical Research Centre, University College London Hospitals NHS Trust; Robert Koch-Institute through funds of the Federal Ministry of Health [1369-341] FX The authors are grateful for advice on statistical genetics from Professor David Balding and Vincent Plagnol from UCL. This study was funded by the Medical Research Council. Many patients were recruited by the National Prion Monitoring Cohort study which was funded by the Department of Health (England) and subsequently the Biomedical Research Centre, University College London Hospitals NHS Trust. In Germany, the study was funded by the Robert Koch-Institute through funds of the Federal Ministry of Health (grant no. 1369-341). 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Aging PD MAY PY 2015 VL 36 IS 5 BP 2004 EP U20 DI 10.1016/j.neurobiolaging.2015.01.011 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CI9PA UT WOS:000355100900021 ER PT J AU Nomi, JS Uddin, LQ AF Nomi, Jason S. Uddin, Lucina Q. TI Face processing in autism spectrum disorders: From brain regions to brain networks SO NEUROPSYCHOLOGIA LA English DT Review DE Autism; Faces; fMRI; Connectivity; Social cognition; Eye gaze ID HIGH-FUNCTIONING AUTISM; SUPERIOR TEMPORAL SULCUS; VOXEL PATTERN-ANALYSIS; HUMAN NEURAL SYSTEM; SOCIAL BRAIN; TYPICAL DEVELOPMENT; FACIAL EXPRESSIONS; ASPERGER-SYNDROME; FUSIFORM GYRUS; EYE GAZE AB Autism spectrum disorder (ASD) is characterized by reduced attention to social stimuli including the human face. This hypo-responsiveness to stimuli that are engaging to typically developing individuals may result from dysfunctioning motivation, reward, and attention systems in the brain. Here we review an emerging neuroimaging literature that emphasizes a shift from focusing on hypo-activation of isolated brain regions such as the fusiform gyms, amygdala, and superior temporal sulcus in ASD to a more holistic approach to understanding face perception as a process supported by distributed cortical and subcortical brain networks. We summarize evidence for atypical activation patterns within brain networks that may contribute to social deficits characteristic of the disorder. We conclude by pointing to gaps in the literature and future directions that will continue to shed light on aspects of face processing in autism that are still under-examined. In particular, we highlight the need for more developmental studies and studies examining ecologically valid and naturalistic social stimuli. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Nomi, Jason S.; Uddin, Lucina Q.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. 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Lerche, H Kapser, C Schankin, CJ Kunz, WS Surges, R Elger, CE Gaus, V Schmitz, B Helbig, I Muhle, H Stephani, U Klein, KM Rosenow, F Neubauer, BA Reinthaler, EM Zimprich, F Feucht, M Moller, RS Hjalgrim, H De Jonghe, P Suls, A Lieb, W Franke, A Strauch, K Gieger, C Schurmann, C Schminke, U Nurnberg, P Sander, T AF Lal, Dennis Ruppert, Ann-Kathrin Trucks, Holger Schulz, Herbert de Kovel, Carolien G. Trenite, Dorothee Kasteleijn-Nolst Sonsma, Anja C. M. Koeleman, Bobby P. Lindhout, Dick Weber, Yvonne G. Lerche, Holger Kapser, Claudia Schankin, Christoph J. Kunz, Wolfram S. Surges, Rainer Elger, Christian E. Gaus, Verena Schmitz, Bettina Helbig, Ingo Muhle, Hiltrud Stephani, Ulrich Klein, Karl M. Rosenow, Felix Neubauer, Bernd A. Reinthaler, Eva M. Zimprich, Fritz Feucht, Martha Moller, Rikke S. Hjalgrim, Helle De Jonghe, Peter Suls, Arvid Lieb, Wolfgang Franke, Andre Strauch, Konstantin Gieger, Christian Schurmann, Claudia Schminke, Ulf Nuernberg, Peter Sander, Thomas CA EPICURE Consortium TI Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies SO PLOS GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDER; COPY NUMBER VARIANTS; GENOME-WIDE ASSOCIATION; OF-FUNCTION MUTATIONS; EPILEPTIC ENCEPHALOPATHY; DEVELOPMENTAL DELAY; INTELLECTUAL DISABILITY; 15Q13.3 MICRODELETIONS; 16P13.11 PREDISPOSE; COMMON EPILEPSIES AB Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (>= 400 kb) and rare (<1%) autosomal microdeletions with high calling confidence (>= 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10(-17)) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10(-18), OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10(-12), OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes. C1 [Lal, Dennis; Ruppert, Ann-Kathrin; Trucks, Holger; Schulz, Herbert; Nuernberg, Peter] Univ Cologne, CCG, D-50931 Cologne, Germany. [Lal, Dennis; Nuernberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. [Lal, Dennis; Neubauer, Bernd A.] Univ Med Ctr Giessen & Marburg, Dept Neuropediat, Giessen, Germany. [Lal, Dennis; Ruppert, Ann-Kathrin; Trucks, Holger; Schulz, Herbert; de Kovel, Carolien G.; Trenite, Dorothee Kasteleijn-Nolst; Sonsma, Anja C. M.; Koeleman, Bobby P.; Lindhout, Dick; Weber, Yvonne G.; Lerche, Holger; Kapser, Claudia; Schankin, Christoph J.; Kunz, Wolfram S.; Surges, Rainer; Elger, Christian E.; Gaus, Verena; Schmitz, Bettina; Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich; Klein, Karl M.; Rosenow, Felix; Reinthaler, Eva M.; Zimprich, Fritz; Feucht, Martha; Moller, Rikke S.; Hjalgrim, Helle; De Jonghe, Peter; Suls, Arvid; Nuernberg, Peter; Sander, Thomas; EPICURE Consortium] EPICURE Consortium, Utrecht, Netherlands. [de Kovel, Carolien G.; Sonsma, Anja C. M.; Koeleman, Bobby P.; Lindhout, Dick] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Lindhout, Dick] SEIN Epilepsy Inst Netherlands, Hoofddorp, Netherlands. [Weber, Yvonne G.; Lerche, Holger] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Tubingen, Germany. [Kapser, Claudia; Schankin, Christoph J.] Univ Munich Hosp Grosshadern, Dept Neurol, Munich, Germany. [Kunz, Wolfram S.; Surges, Rainer; Elger, Christian E.] Univ Clin Bonn, Dept Epileptol, Bonn, Germany. [Gaus, Verena; Schmitz, Bettina] Charite, Campus Virchow Clin, Dept Neurol, D-13353 Berlin, Germany. [Schmitz, Bettina] Vivantes Humboldt Klinikum, Dept Neurol, Berlin, Germany. [Helbig, Ingo; Muhle, Hiltrud; Stephani, Ulrich] Univ Med Ctr Schleswig Holstein, Dept Neuropediat, Kiel, Germany. [Klein, Karl M.; Rosenow, Felix] Univ Marburg, Dept Neurol, Epilepsy Ctr Hessen, Marburg, Germany. [Klein, Karl M.; Rosenow, Felix] Goethe Univ Frankfurt, Dept Neurol, Epilepsy Ctr Frankfurt Rhein Main, D-60054 Frankfurt, Germany. [Reinthaler, Eva M.; Zimprich, Fritz] Med Univ Vienna, Dept Neurol, Vienna, Austria. [Feucht, Martha] Med Univ Vienna, Dept Pediat & Neonatol, Vienna, Austria. [Moller, Rikke S.; Hjalgrim, Helle] Danish Epilepsy Ctr, Dept Neurol, Dianalund, Denmark. [Moller, Rikke S.; Hjalgrim, Helle] Univ Southern Denmark, Inst Reg Hlth Serv, Odense, Denmark. [De Jonghe, Peter; Suls, Arvid] Univ Antwerp VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium. [De Jonghe, Peter; Suls, Arvid] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium. [Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany. [Lieb, Wolfgang] Univ Kiel, Biobank Popgen, Kiel, Germany. [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Strauch, Konstantin; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Munich, Germany. [Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Schurmann, Claudia] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Schminke, Ulf] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Dept Neurol, Greifswald, Germany. [Nuernberg, Peter] Univ Cologne, CMMC, D-50931 Cologne, Germany. RP Lal, D (reprint author), Univ Cologne, CCG, D-50931 Cologne, Germany. EM sandert@uni-koeln.de FU European Community [LSHM-CT-2006-037315, 602531]; German Research Foundation (DFG) within the EUROCORES Programme EuroEPINOMICS [Le1030/11-1, NU50/8-1, SA434/5-1, SA434/4-2]; German Federal Ministry of Education and Research, National Genome Research Network [NGFNplus: EMINet] [01GS08120, 01GS08123]; Netherlands National Epilepsy Fund [04-08]; Netherlands Organization for Scientific Research [917.66.315]; Fund for Scientific Research Flanders (FWO); PopGen biobank; German Federal Ministry of Education and Research [01EY1103]; Helmholtz Zentrum Munchen - German Research Center for Environmental Health - German Federal Ministry of Education and Research; State of Bavaria; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0701, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania FX This work was supported by grants from the European Community [FP6 Integrated Project EPICURE, grant LSHM-CT-2006-037315 to BPK, HL, and TS; and FP7 Project DESIRE, grant 602531 to TS], the German Research Foundation (DFG) within the EUROCORES Programme EuroEPINOMICS [grants Le1030/11-1 to HL, NU50/8-1 to PN, SA434/5-1 & SA434/4-2 to TS], the German Federal Ministry of Education and Research, National Genome Research Network [NGFNplus: EMINet, grants 01GS08120 to TS, and 01GS08123 to HL], The Netherlands National Epilepsy Fund [grant 04-08 to BPK], The Netherlands Organization for Scientific Research [grant 917.66.315 to BPK and CGdK], the Fund for Scientific Research Flanders (FWO) [grant to PDJ], and the PopGen biobank [grant to AF]. AS is a postdoctoral fellow of the Fund for Scientific Research Flanders (FWO). The PopGen project received infrastructure support through the German Research Foundation excellence cluster "Inflammation at Interfaces" (EXC306/2). The PopGen 2.0 network is supported by a grant from the German Federal Ministry of Education and Research (01EY1103). The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum Munchen - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria; this research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research Net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0701), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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PD MAY PY 2015 VL 11 IS 5 AR e1005226 DI 10.1371/journal.pgen.1005226 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA CJ2HQ UT WOS:000355305200039 PM 25950944 ER PT J AU Van Damme, T Sabbe, B van West, D Simons, J AF Van Damme, Tine Sabbe, Bernard van West, Dirk Simons, Johan TI Motor abilities of adolescents with a disruptive behavior disorder: The role of comorbidity with ADHD SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Motor abilities; Disruptive behavior disorder; ADHD; Adolescent; Bruininks-Oseretsky test of motor proficiency ID DEVELOPMENTAL COORDINATION DISORDER; DEFICIT-HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; AUTISM SPECTRUM DISORDER; 6-YEAR-OLD CHILDREN; GENDER-DIFFERENCES; PHYSICAL-FITNESS; ATTENTION; PERFORMANCE; AGE AB The aim of this study was to explore the incidence, type and severity of motor impairment in male adolescents with a disruptive behavior disorder (DBD) and evaluate the role of comorbid ADHD. The Bruininks-Oseretsky test of motor proficiency, Second Edition was administered to examine a detailed motor profile and to compare the motor abilities of individuals with DBD (n = 99) to those of controls (n = 87). Additional subgroup analyses were conducted within the clinical population and encompassed (1) analyzing differences in motor profiles between individuals diagnosed with oppositional defiant disorder (ODD) or conduct disorder (CD) and (2) comparing the motor profiles of individuals with or without comorbid ADHD. The results indicated that individuals with a DBD showed a mixed motor impairment profile. Even after controlling for IQ, the DBD group obtained significantly lower scores in comparison to controls. The ODD and CD subgroups showed a similar motor profile. Presence of comorbid ADHD did not produce major differences in the motor profile. As approximately 79% of the adolescents with a DBD suffered from motor impairment, motor ability needs to be adequately addressed in research as well as in clinical practice. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Van Damme, Tine; Sabbe, Bernard; van West, Dirk] Univ Antwerp, Collaborat Antwerp Psychiat Res Inst, Fac Med & Hlth Sci, B-2610 Antwerp, Belgium. [Van Damme, Tine; van West, Dirk] ZNA, Univ Ctr Child & Adolescent Psychiat Antwerp, B-2020 Antwerp, Belgium. [van West, Dirk] Vrije Univ Brussel, Dept Clin & Lifespan Psychol, Fac Psychol, B-1050 Brussels, Belgium. [Simons, Johan] Katholieke Univ Leuven, Dept Rehabil Sci, Fac Kinesiol & Rehabil Sci, B-3001 Heverlee, Belgium. RP Van Damme, T (reprint author), Collaborat Antwerp Psychiat Res Inst, Univ Pl 1, B-2610 Antwerp, Belgium. 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TI The independent use of self-instructions for the acquisition of untrained multi-step tasks for individuals with an intellectual disability: A review of the literature SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Review DE Intellectual disability; Self-instruction; Self-prompting; Student-directed; Self-directed ID PERSONAL DIGITAL ASSISTANT; SEVERELY HANDICAPPED ADOLESCENTS; AUTISM SPECTRUM DISORDERS; DAILY LIVING SKILLS; PICTURE PROMPTS; YOUNG-ADULTS; DEVELOPMENTAL-DISABILITIES; VOCATIONAL TASKS; COOKING SKILLS; STUDENTS AB Systematic instruction on multi-step tasks (e.g., cooking, vocational skills, personal hygiene) is common for individuals with an intellectual disability. Unfortunately, when individuals with disabilities turn 22-years-old, they no longer receive services in the public school system in most states and systematic instruction often ends (Bouck, 2012). Rather than focusing instructional time on teacher-delivered training on the acquisition of specific multi-step tasks, teaching individuals with disabilities a pivotal skill, such as using self-instructional strategies, may be a more meaningful use of time. By learning self-instruction strategies that focus on generalization, individuals with disabilities can continue acquiring novel multi-step tasks in post-secondary settings and remediate skills that are lost over time. This review synthesizes the past 30 years of research related to generalized self-instruction to learn multi-step tasks, provides information about the types of self-instructional materials used, the ways in which participants received training to use them, and concludes with implications for practitioners and recommendations for future research. Published by Elsevier Ltd. C1 [Smith, Katie A.; Shepley, Sally B.; Alexander, Jennifer L.; Ayres, Kevin M.] Univ Georgia, Athens, GA 30602 USA. 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PD MAY PY 2015 VL 40 BP 19 EP 30 DI 10.1016/j.ridd.2015.01.010 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI6XD UT WOS:000354906600003 ER PT J AU Davidson, C O'Hare, A Mactaggart, F Green, J Young, D Gillberg, C Minnis, H AF Davidson, Claire O'Hare, Anne Mactaggart, Fiona Green, Jonathan Young, David Gillberg, Christopher Minnis, Helen TI Social relationship difficulties in autism and reactive attachment disorder: Improving diagnostic validity through structured assessment SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Reactive attachment disorder; Autism spectrum disorder; Indiscriminate friendliness; Social relationships; Differential diagnosis; Observation ID SPECTRUM DISORDERS; CHILDREN; PREVALENCE; BEHAVIORS; ASSOCIATION; POPULATION; ADOPTEES; DEFICITS; ALCOHOL AB Background: Autism Spectrum Disorder (ASD) versus Reactive Attachment Disorder (RAD) is a common diagnostic challenge for clinicians due to overlapping difficulties with social relationships. RAD is associated with neglect or maltreatment whereas ASD is not: accurate differential diagnosis is therefore critical. Very little research has investigated the relationship between the two, and it is unknown if standardised measures are able to discriminate between ASD and RAD. The current study aimed to address these issues. Methods: Fifty eight children with ASD, and no history of maltreatment, were group matched on age with 67 children with RAD. Group profiles on multi-informant measures of RAD were investigated and group differences explored. Discriminant function analysis determined assessment features that best discriminated between the two groups. Results: Although, according to parent report, children with ASD presented with significantly fewer indiscriminate friendliness behaviours compared to the RAD group (p < 0.001), 36 children with ASD appeared to meet core RAD criteria. However, structured observation clearly demonstrated that features were indicative of ASD and not RAD for all but 1 of these 36 children. Conclusions: Children with RAD and children with ASD may demonstrate similar social relationship difficulties but there appears to be a difference in the social quality of the interactions between the groups. In most cases it was possible to differentiate between children with ASD and children with RAD via structured observation. Nevertheless, for a small proportion of children with ASD, particularly those whose difficulties may be more subtle, our current standardised measures, including structured observation, may not be effective in differentiating RAD from ASD. (C) 2015 Published by Elsevier Ltd. C1 [Davidson, Claire; Gillberg, Christopher; Minnis, Helen] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland. [O'Hare, Anne] Univ Edinburgh, Dept Child Life & Hlth, Edinburgh, Midlothian, Scotland. [Mactaggart, Fiona] North Edinburgh Team, Child & Adolescent Mental Hlth Serv, Edinburgh Connect & North Edinburgh Team, Edinburgh, Midlothian, Scotland. [Green, Jonathan] Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England. [Young, David] Univ Strathclyde, Dept Math & Stat, Glasgow, Lanark, Scotland. [Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. RP Davidson, C (reprint author), Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland. EM claire.davidson@glasgow.ac.uk; aohare@ed.ac.uk; Fiona.Mactaggart@nhslothian.scot.nhs.uk; Jonathan.Green@manchester.co.uk; David.Young@strath.ac.uk; christopher.gillberg@gnc.gu.se FU Chief Scientist Office (Scotland) [CZH/4/651]; Sick Kids Friends Foundation FX We are grateful to all participating families, and to the following people who helped with rating of research instruments: Ashley Cameron, Manju Haridas, Franciske Evans, Helen Dawson, Saman Khan, Shubha Hegde, Sadia Mohammad, Laxmi Kathuria and Christine Clark. We are also grateful to Susan Davidson and Irene O'Neill for administrative support, to the Edinburgh RHSC Clinical Research Facility for use of their facilities and to the funders: the Chief Scientist Office (Scotland CZH/4/651) and the Sick Kids Friends Foundation. 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Dev. Disabil. PD MAY PY 2015 VL 40 BP 63 EP 72 DI 10.1016/j.ridd.2015.01.007 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI6XD UT WOS:000354906600007 PM 25754456 ER PT J AU Limoges, E Bolduc, C Berthiaume, C Mottron, L Godbout, R AF Limoges, Elyse Bolduc, Christianne Berthiaume, Claude Mottron, Laurent Godbout, Roger TI Relationship between poor sleep and daytime cognitive performance in young adults with autism (vol 34, pg 1322, 2013) SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Correction C1 [Limoges, Elyse; Bolduc, Christianne; Berthiaume, Claude; Godbout, Roger] Hop Riviere des Prairies, Sleep Lab & Clin, Montreal, PQ H1E 1A4, Canada. [Limoges, Elyse; Bolduc, Christianne; Mottron, Laurent; Godbout, Roger] Hop Riviere des Prairies, Ctr Rech Fernand Seguin, Montreal, PQ H1E 1A4, Canada. [Mottron, Laurent] Hop Riviere des Prairies, Autism Clin, Montreal, PQ H1E 1A4, Canada. [Mottron, Laurent; Godbout, Roger] Univ Montreal, Dept Psychiat, Downtown Branch, Montreal, PQ H1E 1A4, Canada. RP Godbout, R (reprint author), Hop Riviere des Prairies, Sleep Lab & Clin, 7070 Perras Blvd, Montreal, PQ H1E 1A4, Canada. EM roger.godbout@umontreal.ca CR Limoges E, 2013, RES DEV DISABIL, V34, P1322, DOI 10.1016/j.ridd.2013.01.013 NR 1 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 MAY PY 2015 VL 40 BP 73 EP 73 DI 10.1016/j.ridd.2015.03.001 PG 1 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CI6XD UT WOS:000354906600008 ER PT J AU Overgaauw, S van Duijvenvoorde, ACK Moor, BG Crone, EA AF Overgaauw, Sandy van Duijvenvoorde, Anna C. K. Moor, Bregtje Gunther Crone, Eveline A. TI A longitudinal analysis of neural regions involved in reading the mind in the eyes SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE social brain; longitudinal design; mentalizing; adolescence; development ID TEST-RETEST RELIABILITY; INFERIOR FRONTAL GYRUS; ASPERGER-SYNDROME; EARLY ADULTHOOD; ADOLESCENCE; AUTISM; BRAIN; FMRI; METAANALYSIS; CHILDHOOD AB The ability to perceive social intentions from people's eyes is present from an early age, yet little is known about whether this skill is fully developed in childhood or that subtle changes may still occur across adolescence. This fMRI study investigated the ability to read mental states by using an adapted version of the Reading the Mind in the Eyes task within adolescents (aged 12-19 years) over a 2-year test-retest interval. This longitudinal setup provides the opportunity to study both stability over time as well as age-related changes. The behavioral results showed that participants who performed well in the mental state condition at the first measurement also performed well at the second measurement. fMRI results revealed positive test-retest correlations of neural activity in the right superior temporal sulcus and right inferior frontal gyrus for the contrast mental state > control, suggesting stability within individuals over time. Besides stability of activation, dorsal medial prefrontal cortex showed a dip in mid-adolescence for the mental state > control condition and right inferior frontal gyrus decreased linearly with age for the mental state > control condition. These findings underline changes in the slope of the developmental pattern depending on age, even in the existence of relatively stable activation in the social brain network. C1 [Overgaauw, Sandy; van Duijvenvoorde, Anna C. K.; Moor, Bregtje Gunther; Crone, Eveline A.] Leiden Univ, Dept Dev Psychol, NL-2333 AK Leiden, Netherlands. [Overgaauw, Sandy; van Duijvenvoorde, Anna C. K.; Crone, Eveline A.] Leiden Inst Brain & Cognit, Leiden, Netherlands. RP Overgaauw, S (reprint author), Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands. EM s.overgaauw.2@fsw.leidenuniv.nl FU European Research Council [ERC-2010-StG-263234] FX We would like to acknowledge the Autism Research Centre for the use of the 'Reading the Mind in the Eyes task'. We are grateful to Wouter van der Horst and Marthe de Jong for assistance in recruiting participants and for assistance in scanning. Eveline A. Crone was supported by a starting grant of the European Research Council (ERC-2010-StG-263234). CR Achenbach TM, 1991, MANUAL CHILD BEHAV C Adams R. 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Cogn. Affect. Neurosci. PD MAY PY 2015 VL 10 IS 5 BP 619 EP 627 DI 10.1093/scan/nsu095 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CJ1ZM UT WOS:000355283700001 PM 25062837 ER PT J AU Franklin, C Gattas, M Dossetor, D Lennox, N AF Franklin, C. Gattas, M. Dossetor, D. Lennox, N. TI AUTISM SPECTRUM DISORDER: ESSENTIALS FOR PSYCHIATRISTS SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Franklin, C.; Lennox, N.] Univ Queensland, MRI UQ, Queensland Ctr Intellectual & Dev Disabil, Brisbane, Qld, Australia. [Gattas, M.] Wesley Med Ctr, Brisbane Genet, Brisbane, Qld, Australia. [Gattas, M.] Royal Brisbane & Womens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia. [Dossetor, D.] Sydney Childrens Hosp Network, Sydney, NSW, Australia. [Dossetor, D.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 15 EP 15 PG 1 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500034 ER PT J AU Gattas, M AF Gattas, M. TI GENETICS AND AUTISM SPECTRUM DISODER SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Gattas, M.] Wesley Med Ctr, Brisbane Genet, Brisbane, Qld, Australia. [Gattas, M.] Royal Brisbane & Womens Hosp, Genet Hlth Queensland, Brisbane, Qld, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 15 EP 16 PG 2 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500035 ER PT J AU Lennox, N AF Lennox, N. TI PHYSICAL HEALTH IN AUTISM: COMMON CONDITIONS AND THEIR MANAGEMENT SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Lennox, N.] Univ Queensland, Queensland Ctr Intellectual & Dev Disabil, Brisbane, Qld, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 16 EP 16 PG 1 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500037 ER PT J AU Franklin, C AF Franklin, C. TI MENTAL HEALTH IN ADULTS WITH AUTISM SPECTRUM DISORDER SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Franklin, C.] Univ Queensland, Queensland Ctr Intellectual & Dev Disabil, Brisbane, Qld, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 17 EP 17 PG 1 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500038 ER PT J AU Bird, P AF Bird, P. TI AUTISM SPECTRUM DISORDERS - NEW TREATMENTS SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Bird, P.] Gosforth Clin, Maroochydore, Australia. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 38 EP 38 PG 1 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500095 ER PT J AU Jayawardena, V Kisely, S Perera, H AF Jayawardena, V. Kisely, S. Perera, H. TI CAREGIVER BURDEN AND DEPRESSION AMONG CAREGIVERS OF AUTISM PRESENTING TO A SPECIALIST CHILD MENTAL HEALTH SERVICE IN SRI LANKA SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Jayawardena, V.] West Moreton Hosp & Hlth Serv, Ipswich, Qld, Australia. [Kisely, S.] Univ Queensland, Herston, Qld, Australia. [Perera, H.] Univ Colombo, Dept Psychol Med, Colombo, Sri Lanka. NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2015 VL 49 SU 1 BP 68 EP 68 PG 1 WC Psychiatry SC Psychiatry GA CI0OU UT WOS:000354437500174 ER PT J AU Kondapalli, LA Barnhart, KB AF Kondapalli, L. A. Barnhart, K. B. TI Prospective Cohort Study of Autism, Neurodevelopment, and Behavior in Young Children Conceived by Assisted Reproductive Technology (ART): Cause for Concern or Reassurance? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Kondapalli, L. A.] Colorado Ctr Reprod Med, Lone Tree, CO USA. [Kondapalli, L. A.; Barnhart, K. B.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2015 VL 103 IS 5 MA S12 BP 357 EP 357 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CI4SD UT WOS:000354742400016 ER PT J AU Boukhris, T Muanda-Tsobo, F Berard, A AF Boukhris, T. Muanda-Tsobo, F. Berard, A. TI Antidepressant, Especially SSRI Use, during Pregnancy and the Risk of Autism Spectrum Disorder: A Meta-Analysis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Boukhris, T.; Muanda-Tsobo, F.; Berard, A.] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada. [Berard, A.] CHU St Justine, Res Ctr, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2015 VL 103 IS 5 MA P19 BP 411 EP 411 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CI4SD UT WOS:000354742400119 ER PT J AU Colvert, E Tick, B McEwen, F Stewart, C Curran, SR Woodhouse, E Gillan, N Hallett, V Lietz, S Garnett, T Ronald, A Plomin, R Rijsdijk, F Happe, F Bolton, P AF Colvert, Emma Tick, Beata McEwen, Fiona Stewart, Catherine Curran, Sarah R. Woodhouse, Emma Gillan, Nicola Hallett, Victoria Lietz, Stephanie Garnett, Tracy Ronald, Angelica Plomin, Robert Rijsdijk, Fruehling Happe, Francesca Bolton, Patrick TI Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample SO JAMA PSYCHIATRY LA English DT Article ID GENERAL-POPULATION; GENETIC INFLUENCES; BROADER PHENOTYPE; TRAITS; CHILDHOOD; PAIRS; SCHIZOPHRENIA; INHERITANCE; ENVIRONMENT; PREVALENCE AB IMPORTANCE Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population. OBJECTIVES To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD. DESIGN, SETTING, AND PARTICIPANTS We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs). MAIN OUTCOMES AND MEASURES Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis. RESULTS On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]). CONCLUSIONS AND RELEVANCE The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD. C1 [Colvert, Emma; Tick, Beata; McEwen, Fiona; Ronald, Angelica; Plomin, Robert; Rijsdijk, Fruehling; Happe, Francesca; Bolton, Patrick] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [McEwen, Fiona; Bolton, Patrick] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child & Adolescent Psychiat, London SE5 8AF, England. [Stewart, Catherine; Gillan, Nicola; Garnett, Tracy; Bolton, Patrick] Maudsley Hosp & Inst Psychiat, South London & Maudsley NHS Fdn Trust, London SE5 8AZ, England. [Stewart, Catherine; Curran, Sarah R.; Hallett, Victoria] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, London SE5 8AF, England. [Curran, Sarah R.] Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9RH, E Sussex, England. [Curran, Sarah R.] Sussex Partnership NHS Fdn Trust, Worthing, W Sussex, England. [Woodhouse, Emma] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Forens & Neurodev Sci, London SE5 8AF, England. [Lietz, Stephanie] UCL, Res Dept Clin Educ & Hlth Psychol, London, England. [Ronald, Angelica] Univ London, Dept Psychol Sci, London, England. RP Tick, B (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, Crespigny Pk, London SE5 8AF, England. EM beata.b.tick@kcl.ac.uk FU UK Medical Research Council (MRC) [G0901245, G0500079]; MRC [G0500870, MR/J500380/1]; National Institute for Health Research; Biomedical Research Centre in Mental Health at South London and Maudsley NHS Trust; Autism Speaks grant FX The Twins Early Development Study (TEDS) is supported by program grant G0901245 (previously G0500079) from the UK Medical Research Council (MRC). The Social Relationship Study was supported by grant G0500870 from the MRC. 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Gunnes, Nina Hirtz, Deborah Lie, Kari Kveim Magnus, Per Reichborn-Kjennerud, Ted Roth, Christine Schjolberg, Synnve Stoltenberg, Camilla Suren, Pal Susser, Ezra Lipkin, W. Ian TI Association of Maternal Report of Infant and Toddler Gastrointestinal Symptoms With Autism Evidence From a Prospective Birth Cohort SO JAMA PSYCHIATRY LA English DT Article ID SPECTRUM DISORDERS; YOUNG-CHILDREN; LANGUAGE DELAY; SEROTONIN; INDIVIDUALS; DYSFUNCTION; MET; DIAGNOSIS; PATTERNS; SYSTEM AB IMPORTANCE Gastrointestinal (GI) comorbidities are frequently described in association with autism spectrum disorder (ASD). However, the prevalence of GI disturbances and the age at which such problems first appear are unclear, and their specificity for ASD compared with other neurodevelopmental disorders is uncertain. OBJECTIVE To compare maternal report of GI symptoms during the first 3 years of life in children with ASD, developmental delay (DD), and typical development (TD). DESIGN, SETTING, AND PARTICIPANTS This large prospective cohort study consists of participants in the Norwegian Mother and Child Cohort Study. During a 10-year period (January 1, 1999, through December 31, 2008), women throughout Norway were recruited at the first prenatal ultrasonographic visit (approximately 18 weeks' gestation). The study enrolled 95 278 mothers, 75 248 fathers, and 114 516 children. Our analyses are based on MoBa data released through October 1, 2013, and NPR diagnoses registered through December 31, 2012, and include children born from January 1, 2002, through December 31, 2008, with completed age 18- and 36-month questionnaires. EXPOSURES We defined 3 groups of children: children with ASD (n = 195), children with DD and delayed language and/or motor development (n = 4636), and children with TD (n = 40 295). MAIN OUTCOMES AND MEASURES The GI symptoms were based on maternal report of constipation, diarrhea, and food allergy/intolerance. RESULTS Children with ASD were at significantly increased odds of maternally reported constipation (adjusted odds ratio [aOR], 2.7; 95% CI, 1.9-3.8; P < .001) and food allergy/intolerance (aOR, 1.7; 95% CI, 1.1-2.6; P = .01) in the 6- to 18-month-old age period and diarrhea (aOR, 2.3; 95% CI, 1.5-3.6; P < .001), constipation (aOR, 1.6; 95% CI, 1.2-2.3; P < .01), and food allergy/intolerance (aOR, 2.0; 95% CI, 1.3-3.1; P < .01) in the 18- to 36-month-old age period compared with children with TD. Similar results for these symptom categories were observed in comparisons with children with DD, but ORs were slightly lower. Mothers of children with ASD were significantly more likely to report 1 or more GI symptom in either the 6- to 18-month or the 18-to 36-month-old age period and more than twice as likely to report at least 1 GI symptom in both age periods compared with mothers of children with TD or DD. CONCLUSIONS AND RELEVANCE In this large prospective cohort, maternally reported GI symptoms are more common and more often persistent during the first 3 years of life in children with ASD than in children with TD or DD. C1 [Bresnahan, Michaeline; Hornig, Mady; Roth, Christine; Susser, Ezra; Lipkin, W. Ian] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hornig, Mady; Schultz, Andrew F.; Lipkin, W. Ian] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10032 USA. [Gunnes, Nina; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Roth, Christine; Schjolberg, Synnve; Stoltenberg, Camilla; Suren, Pal] Norwegian Inst Publ Hlth, Oslo, Norway. [Hirtz, Deborah] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Reichborn-Kjennerud, Ted] Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway. RP Bresnahan, M (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 622W168th St,Room 809, New York, NY 10032 USA. EM mab29@columbia.edu FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS47537]; Research Council of Norway [189457, 190694, 196452] FX This research was supported by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, and grant NS47537 from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (Dr Lipkin). The following grants from the Research Council of Norway have provided support to the ABC in general: 189457, 190694, and 196452. CR Altaf MA, 2008, DEV DISABIL RES REV, V14, P87, DOI 10.1002/ddrr.15 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bauman ML, 2010, NEUROTHERAPEUTICS, V7, P320, DOI 10.1016/j.nurt.2010.06.001 Buie T, 2010, PEDIATRICS, V125, pS1, DOI 10.1542/peds.2009-1878C Campbell DB, 2006, P NATL ACAD SCI USA, V103, P16834, DOI 10.1073/pnas.0605296103 Campbell DB, 2009, PEDIATRICS, V123, P1018, DOI 10.1542/peds.2008-0819 Campbell DB, 2008, AUTISM RES, V1, P159, DOI 10.1002/aur.27 Chaidez V, 2014, J AUTISM DEV DISORD, V44, P1117, DOI 10.1007/s10803-013-1973-x Chandana SR, 2005, INT J DEV NEUROSCI, V23, P171, DOI 10.1016/j.ijdevneu.2004.08.002 Chandler S, 2013, J AUTISM DEV DISORD, V43, P2737, DOI 10.1007/s10803-013-1768-0 Coury Daniel L, 2012, Pediatrics, V130 Suppl 2, pS160, DOI 10.1542/peds.2012-0900N Dale PS, 2003, J SPEECH LANG HEAR R, V46, P544, DOI 10.1044/1092-4388(2003/044) Eggesbo M, 2001, ALLERGY, V56, P393, DOI 10.1034/j.1398-9995.2001.056005393.x Emond A, 2010, PEDIATRICS, V126, pE337, DOI 10.1542/peds.2009-2391 Fleiss J, 2003, STAT METHODS RATES P, V3rd Gaspar P, 2003, NAT REV NEUROSCI, V4, P1002, DOI 10.1038/nrn1256 Gershon MD, 2007, GASTROENTEROLOGY, V132, P397, DOI 10.1053/j.gastro.2006.11.002 Gorrindo P, 2012, AUTISM RES, V5, P101, DOI 10.1002/aur.237 Hornig M, 2013, CURR OPIN RHEUMATOL, V25, P488, DOI 10.1097/BOR.0b013e32836208de Ibrahim SH, 2009, PEDIATRICS, V124, P680, DOI 10.1542/peds.2008-2933 Jackson PB, 2009, AUTISM RES, V2, P232, DOI 10.1002/aur.87 Leboyer M, 1999, BIOL PSYCHIAT, V45, P158, DOI 10.1016/S0006-3223(97)00532-5 Levy SE, 2007, BIOL PSYCHIAT, V61, P492, DOI 10.1016/j.biopsych.2006.07.013 LORD C, 1994, J AUTISM DEV DISORD, V24, P659, DOI 10.1007/BF02172145 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Magnus P, 2006, INT J EPIDEMIOL, V35, P1146, DOI 10.1093/ije/dyl170 Motil KJ, 1999, J PEDIATR GASTR NUTR, V29, P31, DOI 10.1097/00005176-199907000-00010 Mouridsen SE, 2010, CHILD CARE HLTH DEV, V36, P437, DOI 10.1111/j.1365-2214.2009.01021.x Nelson HD, 2006, PEDIATRICS, V117, pE298, DOI 10.1154/peds.2005-1467 Onore C, 2012, BRAIN BEHAV IMMUN, V26, P383, DOI 10.1016/j.bbi.2011.08.007 Roth C, 2011, JAMA-J AM MED ASSOC, V306, P1566, DOI 10.1001/jama.2011.1433 Sandhu B, 2009, ARCH DIS CHILD, V94, P497, DOI 10.1136/adc.2008.148866 Singh VK, 1997, BIOL PSYCHIAT, V41, P753, DOI 10.1016/S0006-3223(96)00522-7 Sleigh G, 2004, ARCH DIS CHILD, V89, P534 Sparrow SS, 2005, VINELAND ADAPTIVE BE Squires J, 1997, J PEDIATR PSYCHOL, V22, P313, DOI 10.1093/jpepsy/22.3.313 Stoltenberg C, 2010, MOL PSYCHIATR, V15, P676, DOI 10.1038/mp.2009.143 Suren P, 2014, PEDIATRICS, V133, pE1128, DOI 10.1542/peds.2013-3664 Veldhuizen S, ACAD PEDIATR, DOI [10.1016/j.acap.2014.08.002, DOI 10.1016/J.ACAP.2014.08.002] Williams BL, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0024585 World Health Organization, 1993, MENT DIS GLOSS GUID Zhou X, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0027428 NR 42 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 MAY PY 2015 VL 72 IS 5 BP 466 EP 474 DI 10.1001/jamapsychiatry.2014.3034 PG 9 WC Psychiatry SC Psychiatry GA CH6YC UT WOS:000354181400009 PM 25806498 ER PT J AU Selten, JP Lundberg, M Rai, D Magnusson, C AF Selten, Jean-Paul Lundberg, Michael Rai, Dheeraj Magnusson, Cecilia TI Risks for Nonaffective Psychotic Disorder and Bipolar Disorder in Young People With Autism Spectrum Disorder A Population-Based Study SO JAMA PSYCHIATRY LA English DT Article ID SOCIAL DEFEAT HYPOTHESIS; PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; SCHIZOPHRENIA; CHILDHOOD; ASSOCIATION; CHILDREN; ADULTS; INTELLIGENCE; EXPERIENCES AB IMPORTANCE Whether individuals with autism spectrum disorder (ASD) are at increased risk for nonaffective psychotic disorder (NAPD) or bipolar disorder (BD) is unknown. OBJECTIVE To test whether the risks for NAPD and BD in individuals with ASD are increased and whether these risks are higher than those of their siblings not diagnosed as having ASD. DESIGN, SETTING, AND PARTICIPANTS We performed a nested case-control study of all individuals 17 years or younger who ever resided in Stockholm County, Sweden, from January 1, 2001, through December 31, 2011 (Stockholm Youth Cohort). We included cohort members ever diagnosed as having ASD (n = 9062) and their full siblings never diagnosed as having ASD. Each case was matched with 10 control individuals of the same sex born during the same month and year. Using Swedish registers, cases, siblings, and controls were followed up until December 31, 2011. By then, the oldest individuals had reached the age of 27 years. EXPOSURES Autism spectrum disorder, registered before age 16 or 28 years. We distinguished between ASD with and without intellectual disability (ID). MAIN OUTCOMES AND MEASURES We calculated odds ratios (ORs) for NAPD and BD adjusted for age, sex, population density of place of birth, personal or parental history of migration, hearing impairment, parental age, parental income, parental educational level, and parental history of psychiatric disorder. RESULTS The adjusted ORs for NAPD and BD for cases with non-ID ASD registered before age 16 years were 5.6 (95% CI, 3.3-8.5) and 5.8 (95% CI, 3.9-8.7), respectively; the adjusted ORs for cases with ID ASD were 3.5 (95% CI, 2.0-6.0) and 1.8 (95% CI, 0.8-4.1). The adjusted ORs for NAPD and BD in cases with non-ID ASD registered before age 28 years were 12.3 (95% CI, 9.5-15.9) and 8.5 (95% CI, 6.5-11.2), respectively; for cases with ID ASD, these ORs were 6.4 (95% CI, 4.2-9.8) and 2.0 (95% CI, 1.0-3.9), respectively. The ORs for NAPD and BD for the nonautistic full siblings of cases for whom ASD was registered before age 16 years, adjusted for hearing loss, were 1.8 (95% CI, 1.1-2.7) and 1.7 (95% CI, 1.1-2.6), respectively. CONCLUSIONS AND RELEVANCE A diagnosis of ASD is associated with a substantially increased risk for NAPD and BD. This finding contributes to our understanding of these disorders and has implications for the management of ASD. C1 [Selten, Jean-Paul] Maastricht Univ, Sch Mental Hlth & Neurosci, NL-6200 MD Maastricht, Netherlands. [Selten, Jean-Paul] Rivierduinen Psychiat Inst, NL-2333 ZZ Leiden, Netherlands. [Lundberg, Michael; Magnusson, Cecilia] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden. [Selten, Jean-Paul; Magnusson, Cecilia] Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden. [Rai, Dheeraj] Univ Bristol, Sch Social & Community Med, Ctr Acad Mental Hlth, Bristol, Avon, England. 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Levy, Brynn Kiryluk, Krzysztof Wuttke, Matthias Abraham, Alison G. Kaskel, Frederick Koettgen, Anna Warady, Bradley A. Furth, Susan L. Wong, Craig S. Gharavi, All G. TI Genomic imbalances in pediatric patients with chronic kidney disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COPY-NUMBER VARIANTS; CHROMOSOMAL MICROARRAY; DEVELOPMENTAL DELAY; PROSPECTIVE COHORT; DISORDERS; CHILDREN; AUTISM; ASSOCIATION; POPULATION; GENES AB BACKGROUND. There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown. METHODS. We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in MD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD. RESULTS. We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeobox B (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 x 10(-20)). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease. CONCLUSION. A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for common forms of pediatric nephropathy. Detection of pathogenic imbalances has practical implications for personalized diagnosis and health monitoring in this population. C1 [Verbitsky, Miguel; Sanna-Cherchi, Simone; Fasel, David A.; Kiryluk, Krzysztof; Gharavi, All G.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Pathol, New York, NY USA. [Levy, Brynn] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USA. [Wuttke, Matthias; Koettgen, Anna] Univ Freiburg, Med Ctr, Dept Nephrol, D-79106 Freiburg, Germany. [Abraham, Alison G.; Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kaskel, Frederick] Albert Einstein Coll Med, Div Pediat Nephrol, New York, NY USA. [Warady, Bradley A.] Childrens Mercy Hosp, Div Pediat Nephrol, Kansas City, MO 64108 USA. [Furth, Susan L.] Univ Penn, Childrens Hosp Philadelphia, Perelmen Sch Med, Dept Pediat,Div Nephrol, Philadelphia, PA 19104 USA. [Furth, Susan L.] Univ Penn, Childrens Hosp Philadelphia, Perelmen Sch Med, Dept Epidemiol,Div Nephrol, Philadelphia, PA 19104 USA. [Wong, Craig S.] Univ New Mexico, Childrens Hosp, Albuquerque, NM 87131 USA. RP Wong, CS (reprint author), Univ New Mexico, Childrens Hosp, Div Pediat Nephrol, MSC10-55901, Albuquerque, NM 87131 USA. EM cwong@salud.unm.edu; ag2239@columbia.edu FU NIH; National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute FX This work was supported by the NIH, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute. 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Clin. Invest. PD MAY PY 2015 VL 125 IS 5 BP 2171 EP 2178 DI 10.1172/1080877 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CH5JK UT WOS:000354071700036 PM 25893603 ER PT J AU Fukai, R Hiraki, Y Yofune, H Tsurusaki, Y Nakashima, M Saitsu, H Tanaka, F Miyake, N Matsumoto, N AF Fukai, Ryoko Hiraki, Yoko Yofune, Hiroko Tsurusaki, Yoshinori Nakashima, Mitsuko Saitsu, Hirotomo Tanaka, Fumiaki Miyake, Noriko Matsumoto, Naomichi TI A case of autism spectrum disorder arising from a de novo missense mutation in POGZ SO JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETICS; GENES AB Autism spectrum disorder (ASD) is a clinically heterogeneous psychiatric disorder with various genetic backgrounds. Here, we report a novel mutation in the pogo transposable element-derived protein with zinc finger domain gene (POGZ) identified by triobased whole exome sequencing. To date, a total of seven de novo POGZ mutations in ASD have been reported. POGZ contains a total of five functional domains, and this study reports the first de novo missense mutation in the centromere protein B-like DNA-binding domain. POGZ is highly expressed in the human fetal brain and is involved in mitosis and the regulation of neuronal proliferation. Therefore its loss-of-function or pathogenic missense mutations are likely to be causative of ASD. C1 [Fukai, Ryoko; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan. [Fukai, Ryoko; Tanaka, Fumiaki] Yokohama City Univ, Grad Sch Med, Dept Neurol & Stroke Med, Yokohama, Kanagawa 2360004, Japan. [Hiraki, Yoko] Hiroshima Municipal Ctr Child Hlth & Dev, Hiroshima, Japan. [Yofune, Hiroko] Hiroshima City Hokubu Ctr Childrens Treatment & G, Hiroshima, Japan. RP Miyake, N (reprint author), Yokohama City Univ, Grad Sch Med, Dept Human Genet, Kanazawa Ku, Fukuura 3-9, Yokohama, Kanagawa 2360004, Japan. EM nmiyake@yokohama-cu.ac.jp; naomat@yokohama-cu.ac.jp FU Ministry of Health, Labour and Welfare of Japan; Japan Science and Technology Agency; Strategic Research Program for Brain Sciences; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science; Takeda Science Foundation; Hayashi Memorial Foundation for Female Natural Scientists FX We thank the patient's family for participating in this work. This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan (HS, N Matsumoto, N Miyake), the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency (N Matsumoto), the Strategic Research Program for Brain Sciences (N Matsumoto) and a Grant-in-Aid for Scientific Research on Innovative areas-(Transcription cycle)-from the Ministry of Education, Culture, Sports, Science and Technology of Japan (N Matsumoto), Grants-in-Aid for Scientific Research (A) and (B) from the Japan Society for the Promotion of Science (HS, N Miyake, N Matsumoto), the Takeda Science Foundation (N Matsumoto, N Miyake), the Yokohama Foundation for Advancement of Medical Science (N Miyake) and the Hayashi Memorial Foundation for Female Natural Scientists (N Miyake). 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Hum. Genet. PD MAY PY 2015 VL 60 IS 5 BP 277 EP 279 DI 10.1038/jhg.2015.13 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CI8IO UT WOS:000355016200008 PM 25694107 ER PT J AU Duerden, EG Taylor, MJ Lee, M McGrath, PA Davis, KD Roberts, SW AF Duerden, Emma G. Taylor, Margot J. Lee, Minha McGrath, Patricia A. Davis, Karen D. Roberts, S. Wendy TI Decreased Sensitivity to Thermal Stimuli in Adolescents With Autism Spectrum Disorder: Relation to Symptomatology and Cognitive Ability SO JOURNAL OF PAIN LA English DT Article DE Cognition; pain; perception; autism; human ID WARM FIBERS; COMMUNICATION DISORDERS; DIAGNOSTIC INTERVIEW; INCREMENTAL CHANGES; BRAIN POTENTIALS; SKIN TEMPERATURE; PAIN THRESHOLDS; BETA-ENDORPHIN; REACTION-TIMES; NERVE BLOCK AB Social communication deficits and repetitive behaviors are established characteristics of autism spectrum disorder (ASD) and the focus of considerable study. Alterations in pain sensitivity have been widely noted clinically but remain understudied and poorly understood. The ASD population may be at greater risk for having their pain undermanaged, especially in children with impaired cognitive ability and limited language skills, which may affect their ability to express pain. Given that sensitivity to noxious stimuli in adolescents with ASD has not been systematically assessed, here we measured warm and cool detection thresholds and heat and cold pain thresholds in 20 high-functioning adolescents with ASD and 55 typically developing adolescents using a method-of-limits quantitative sensory testing protocol. Adolescents with ASD had a loss of sensory function for thermal detection (P < .001, both warm and cool detection thresholds) but not pain threshold (P > .05, both heat and cold pain thresholds) in comparison to controls, with no evidence for significant age or sex effects (P > .05). Intelligence quotients and symptomatology were significantly correlated with a loss of some types of thermal perception in the ASD population (ie, warm detection threshold, cool detection threshold, and heat pain threshold; P < .05). Decreased thermal sensitivity in adolescents with ASD may be associated with cognitive impairments relating to attentional deficits. Our findings are consistent with previous literature indicating an association between thermal perception and cortical thickness in brain regions involved in somatosensation, cognition, and salience detection. Further brain-imaging research is needed to determine the neural mechanisms underlying thermal perceptual deficits in adolescents with ASD. Perspective: We report quantitative evidence for altered thermal thresholds in adolescents with ASD. Reduced sensitivity to warmth, coolness, and heat pain was related to impaired cognitive ability. Caregivers and clinicians should consider cognitive ability when assessing and managing pain in adolescents with ASD. (C) 2015 by the American Pain Society C1 [Duerden, Emma G.; Taylor, Margot J.; Lee, Minha] Hosp Sick Children, Dept Diagnost Imaging, Toronto, ON M5G 1X8, Canada. [Duerden, Emma G.; Roberts, S. Wendy] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada. [Taylor, Margot J.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Taylor, Margot J.; Davis, Karen D.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Duerden, Emma G.] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. [Taylor, Margot J.; Davis, Karen D.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [McGrath, Patricia A.] Pain Innovat Inc, London, ON, Canada. [Davis, Karen D.] Univ Hlth Network, Toronto Western Res Inst, Div Brain Imaging & Behav Syst Neurosci, Toronto, ON, Canada. RP Duerden, EG (reprint author), Hosp Sick Children, Div Neurol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. 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Pain PD MAY PY 2015 VL 16 IS 5 BP 463 EP 471 DI 10.1016/j.jpain.2015.02.001 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CH6KA UT WOS:000354144300007 PM 25704841 ER PT J AU Boulet, SL Mehta, A Kissin, DM Warner, L Kawwass, JF Jamieson, DJ AF Boulet, Sheree L. Mehta, Akanksha Kissin, Dmitry M. Warner, Lee Kawwass, Jennifer F. Jamieson, Denise J. TI Trends in Use of and Reproductive Outcomes Associated With Intracytoplasmic Sperm Injection SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Since its introduction in 1992, intracytoplasmic sperminjection (ICSI) has been increasingly used in patients without severe male factor infertility despite the lack of clear evidence of a benefit over conventional in vitro fertilization (IVF). Compared with pregnancies resulting from conventional IVF, pregnancies resulting from the use of ICSI are associated with 1.5 to 4 times increased risk of chromosomal abnormalities, birth defects, intellectual disabilities, imprinting disorders, and autism. Intracytoplasmic sperm injection is considerably more expensive than conventional IVF. The aim of this retrospective observational study was to assess national trends and reproductive outcomes of fresh IVF cycles associated with the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use. Although only fresh embryos were transferred, it is unlikely that outcomes for frozen-thawed embryos would differ. Data were obtained from the US National Assisted Reproductive Technology Surveillance System for all fresh and ICSI cycles performed during 1996 to 2012. The primary study outcomes were (1) trends in use of ICSI during 1996 to 2012 with respect to male factor infertility, unexplained infertility, maternal age 38 years or older, low oocyte yield (<5 oocytes retrieved), and 2 or more prior assisted reproductive technology cycles and no prior live birth, and (2) reproductive outcomes during 2008 to 2012 for conventional IVF and ICSI cycles, stratified by the presence or absence of male factor infertility. A total of 1,395,634 fresh IVF cycles were identified between 1996 and 2012; 908,767 (65.1%) used ICSI, and 486,867 cycles (34.9%) used conventional IVF. Male factor infertility was identified in 499,135 (35.8%) of fresh cycles. During 2006 to 2012, ICSI use among cycles with male factor infertility increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < 0.001), whereas its use for those without male factor infertility increased from 15.4% (4,197/27,191) to 66.9% (42,321/63,250) (P < 0.001). During 2008 to 2012, 494,907 fresh IVF cycles were identified, 74.6% of which used ICSI. Male factor infertility was reported in 35.7% (176,911/494,907) of fresh cycles. The risk for multiple births among these cycles was significantly lower in those undergoing ICSI compared with conventional IVF (30.9% vs 34.2%); the adjusted relative risk (RR) was 0.87, with a 95% confidence interval (CI) of 0.83 to 0.91. Compared with conventional IVF, ICSI use among cycles without male factor infertility (n = 317,996) was associated with lower rates of implantation (23.0% vs 25.2%; adjusted RR, 0.93; 95% CI, 0.91-0.95), live birth (36.5% vs 39.2%; adjusted RR, 0.95; 95% CI, 0.93-0.97), and multiple live births (30.1% vs 31.0%; adjusted RR, 0.93; 95% CI, 0.91-0.95). These findings show that ICSI use among fresh IVF cycles in the United States increased from 36.4% to 76.2% between 1996 and 2012. The largest relative increase occurred in cycles without male factor infertility. The data show no improvement in postfertilization reproductive outcomes with use of ICSI over conventional IVF in the absence of male factor infertility, irrespective of male factor infertility diagnosis. C1 [Boulet, Sheree L.; Mehta, Akanksha; Kissin, Dmitry M.; Warner, Lee; Kawwass, Jennifer F.; Jamieson, Denise J.] Emory Univ, Sch Med, Div Reprod Hlth, Ctr Dis Control & Prevent, Atlanta, GA 30322 USA. [Mehta, Akanksha] Emory Univ, Sch Med, Dept Urol, Atlanta, GA USA. [Kissin, Dmitry M.; Kawwass, Jennifer F.; Jamieson, Denise J.] Emory Univ, Sch Med, Dept Obstet & Gynecol, Atlanta, GA USA. RP Boulet, SL (reprint author), Emory Univ, Sch Med, Div Reprod Hlth, Ctr Dis Control & Prevent, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2015 VL 70 IS 5 BP 325 EP 326 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CI4MZ UT WOS:000354725300016 ER PT J AU Bernard, LP Zhang, HY AF Bernard, Laura P. Zhang, Huaye TI MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism SO PLOS ONE LA English DT Article ID LONG-TERM POTENTIATION; DENDRITIC SPINE MORPHOLOGY; SYNAPTIC PLASTICITY; PROTEIN-KINASE; PHOSPHORYLATION; POLARITY; PSD-95; LKB1; NEURONS; SYNAPTOGENESIS AB The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs), are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer's disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA), through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse. C1 [Bernard, Laura P.; Zhang, Huaye] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Zhang, HY (reprint author), Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. EM huaye.zhang@rutgers.edu FU National Institutes of Health grant [NS065183]; Rutgers Robert Wood Johnson Medical School FX This work was supported by National Institutes of Health grant NS065183 and startup funds from the Rutgers Robert Wood Johnson Medical School to H.Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Brown, Tiara S. TI A Strategy to Increase the Social Interactions of 3-Year-Old Children With Disabilities in an Inclusive Classroom SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE developmental delay; disability populations; peer-mediated; intervention strategies; social skills; peer interactions; play ID HEAD-START CHILDREN; PRESCHOOL-CHILDREN; PRETEND PLAY; COMMUNICATION INTERVENTION; LANGUAGE IMPAIRMENT; PEER INTERVENTION; SPECIAL-EDUCATION; AUTISM; SKILLS AB The current study evaluated the play behaviors of children with disabilities (e.g., developmental delays, specific language impairment) who participated in a social communication intervention targeting skills such as initiations, responses, name use, proximity, and turn-taking. Three children who were enrolled in an inclusive classroom met the inclusion criteria. A multiple baseline design was used to determine the effects of the intervention. 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W., 1984, SINGLE SUBJECT RES S Tsai MH, 2013, CHILD YOUTH SERV REV, V35, P25, DOI 10.1016/j.childyouth.2012.10.016 Wong C, 2012, J AUTISM DEV DISORD, V42, P2152, DOI 10.1007/s10803-012-1467-2 Zimmerman I., 2002, PRESCHOOL LANGUAGE S, V4th NR 62 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-1214 EI 1538-4845 J9 TOP EARLY CHILD SPEC JI Top. Early Child. Spec. Educ. PD MAY PY 2015 VL 35 IS 1 BP 4 EP 14 DI 10.1177/0271121414554210 PG 11 WC Education, Special SC Education & Educational Research GA CI1BI UT WOS:000354474800001 ER PT J AU Lieberman-Betz, RG AF Lieberman-Betz, Rebecca G. TI A Systematic Review of Fidelity of Implementation in Parent-Mediated Early Communication Intervention SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Review DE intervention; families; training; parents; communication/language; intervention strategies; parent-child interaction ID RANDOMIZED CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDERS; YOUNG-CHILDREN; LANGUAGE INTERVENTION; DEVELOPMENTAL DELAYS; TREATMENT INTEGRITY; PRESCHOOL-CHILDREN; TEACHING PARENTS; JOINT ATTENTION; SUPPORT STRATEGIES AB This article examined the reporting of four elements of fidelity of implementation (FOI) in parent-mediated early communication treatment studies. Thirty-five studies were reviewed to extract information regarding reporting of dosage, adherence, quality, and participant responsiveness for both practitioners and parents involved in parent-delivered communication treatment for children birth to 6 years of age. Results indicate relatively low reporting practices across the four elements of FOI for both practitioners and parents. Most studies (71%) reported dosage at the practitioner level (e.g., number and length of parent-training sessions), while few studies (14%) reported dosage at the parent level (i.e., amount of intervention implemented by parents outside of treatment sessions). Results also found 60% of studies reported adherence for parent implementation, but only 34% of studies reported adherence for practitioners. Implications for low reporting in the research literature, as well as recommendations for future reporting and research on FOI, are provided. C1 [Lieberman-Betz, Rebecca G.] Univ Georgia, Athens, GA 30602 USA. RP Lieberman-Betz, RG (reprint author), Univ Georgia, Coll Educ, Dept Commun Sci & Special Educ, 565 Aderhold Hall, Athens, GA 30602 USA. 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PD MAY PY 2015 VL 38 IS 5 BP 264 EP 272 DI 10.1016/j.tins.2015.02.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CI8TZ UT WOS:000355045900003 ER PT J AU Rutishauser, U Mamelak, AN Adolphs, R AF Rutishauser, Ueli Mamelak, Adam N. Adolphs, Ralph TI The primate amygdala in social perception - insights from electrophysiological recordings and stimulation SO TRENDS IN NEUROSCIENCES LA English DT Review ID DEEP BRAIN-STIMULATION; POSTTRAUMATIC-STRESS-DISORDER; EMOTIONAL FACIAL EXPRESSIONS; MEDIAL PREFRONTAL CORTEX; MONKEY AMYGDALA; SINGLE NEURONS; ELECTRICAL-STIMULATION; HUMAN HIPPOCAMPUS; TEMPORAL-LOBE; QUANTITATIVE METAANALYSIS AB The role of the amygdala in emotion and social perception has been intensively investigated primarily through studies using functional magnetic resonance imaging (fMRI). Recently, this topic has been examined using single-unit recordings in both humans and monkeys, with a focus on face processing. The findings provide novel insights, including several surprises: amygdala neurons have very long response latencies, show highly nonlinear responses to whole faces, and can be exquisitely selective for very specific parts of faces such as the eyes. In humans, the responses of amygdala neurons correlate with internal states evoked by faces, rather than with their objective features. Current and future studies extend the investigations to psychiatric illnesses such as autism, in which atypical face processing is a hallmark of social dysfunction. C1 [Rutishauser, Ueli; Mamelak, Adam N.] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Rutishauser, Ueli] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Rutishauser, Ueli; Adolphs, Ralph] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Rutishauser, Ueli] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. 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NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1748-1708 EI 1748-1716 J9 ACTA PHYSIOL JI Acta Physiol. PD MAY PY 2015 VL 214 SU 700 SI SI MA P-02-005 BP 23 EP 23 PG 1 WC Physiology SC Physiology GA CI1TY UT WOS:000354528800067 ER PT J AU Sappok, T Diefenbacher, A Gaul, I Bolte, S AF Sappok, Tanja Diefenbacher, Albert Gaul, Isabell Bolte, Sven TI Validity of the Social Communication Questionnaire in Adults With Intellectual Disabilities and Suspected Autism Spectrum Disorder SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE diagnostics; intellectual developmental disability; autism spectrum disorders; Social Communication Questionnaire ID DIAGNOSTIC OBSERVATION SCHEDULE; PERVASIVE DEVELOPMENTAL DISORDERS; PRESCHOOL-CHILDREN; MENTAL-RETARDATION; ADI-R; RISK; CLASSIFICATION; IDENTIFICATION; PREVALENCE; INSTRUMENT AB This study examined the validity of the Social Communication Questionnaire (SCQ) to identify autism spectrum disorder (ASD) in 151 adults with intellectual disabilities (ID) in Germany. Sensitivities and specificities for ASD were 98/47% for the SCQ-current version and 92/22% for the SCQ-lifetime version. Sensitivities and specificities were increased to 89/66% and 78/48% by adjusting the recommended cut-points. The SCQ-current score correlated with the Scale for Pervasive Developmental Disorders in Mentally Retarded Persons and the Autism Diagnostic Observation Schedule, whereas the SCQ-lifetime score correlated with the Autism Diagnostic Interview-Revised. Our findings support the use of the SCQ-current version for ASD screening in adults with ID, although the SCQ-lifetime version should be used with caution in this population. C1 [Sappok, Tanja; Diefenbacher, Albert; Gaul, Isabell] Evangel Krankenhaus Konigin Elisabeth Herzberge, Dept Psychiat Psychotherapy & Psychosomat, Berlin, Germany. [Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, S-10401 Stockholm, Sweden. RP Sappok, T (reprint author), Ev Krankenhaus Konigin Elisabeth Herzberge, Dept Psychiat, Herzbergstr 79, D-10365 Berlin, Germany. EM tanja.sappok@t-online.de FU Swedish Research Council FX We are grateful to the participants and their caregivers for participating in the study and to the clinicians who helped with data collection for standardized ASD assessments. We appreciate Manuel Heinrich for his thorough data search of the charts, data entry, data analysis support, and the layout of the tables and figures. We also thank Heika Kaiser, who thoroughly performed the PDD-MRS, ADOS, and ADI-R evaluations. Sven Bolte was supported by the Swedish Research Council. 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Ouyang, Lijing TI Emergency Department and Inpatient Hospitalizations for Young People With Fragile X Syndrome SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE intellectual disability; fragile X syndrome; adolescents; health care; health status ID CARE SENSITIVE CONDITIONS; HEALTH-CARE; PARENT SURVEY; EPILEPSY; TRANSITION; PREVALENCE; SEIZURES; CHILDREN; DISABILITIES; ADOLESCENTS AB We compared hospital encounters between adolescents and young adults with fragile X syndrome (FXS) to peers with intellectual disability (ID) from other causes, autism spectrum disorder (ASD), and a comparison group without these conditions matched by gender, age, and insurance coverage. Those with FXS, ASD, or ID were more likely to have had hospital encounters. In terms of age groups, we found mental illness hospitalizations decreased during adulthood as compared to adolescence for those with FXS, and we found that for conditions unrelated to FXS (e.g., respiratory, genitourinary, gastroenteritis, and pneumonia) adolescents had higher rates of hospitalization compared to their peers with FXS, ID, or ASD. We analyzed epilepsy, common among people with FXS and designated as an ambulatory care sensitive condition that can be treated outside the hospital, and found that people with FXS, ID, and ASD had higher odds of hospitalization due to epilepsy in both age groups than did the comparison group. C1 [McDermott, Suzanne; Hardin, James W.; Tong, Xin] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Royer, Julie A.] Univ S Carolina, South Carolina Revenue & Fiscal Affairs Off, Columbia, SC 29208 USA. [Mann, Joshua R.] Univ S Carolina, Sch Med, Columbia, SC 29208 USA. [Ozturk, Orgul D.] Univ S Carolina, Moore Sch Business, Columbia, SC 29208 USA. [Ouyang, Lijing] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP McDermott, S (reprint author), Univ S Carolina, Dept Epidemiol & Biostat, Arnold Sch Publ Hlth, 915 Greene St, Columbia, SC 29208 USA. EM smcdermo@mailbox.sc.edu FU Centers for Disease Control and Prevention FX This research was supported by a cooperative agreement from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, the South Carolina Budget and Control Board Division of Research and Statistics, the South Carolina Department of Health and Human Services, the South Carolina Public Employee Benefit Authority, the South Carolina Department of Education, or the South Carolina Department of Social Services. 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Goh, Yi Shuen TI High-Precision Visual Long-Term Memory in Children With High-Functioning Autism SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism; visual long-term memory; face memory ID SPATIAL WORKING-MEMORY; SPECTRUM DISORDERS; FACE RECOGNITION; FAMILIAR FACE; INTACT; CAPACITY; OBJECTS AB Domain-general theories of autism rest on evidence that the disorder impacts not only social communication skills but also nonsocial functions such as memory. Yet recognition memory deficits have been inconsistently documented, especially for stimuli other than faces and sentences. Here we tested school-age children with high-functioning autism (ASD) and IQ, and age-matched comparison children on a visual long-term memory task involving more than 100 photographs of objects, faces, cats, houses, and abstract stimuli. Children viewed each photograph for 2 s. After a 10-min filled delay, we assessed recognition memory for object category as well as for specific exemplars. Data supported the presence of a high-capacity and high-precision visual memory in children with ASD. Both category memory and exemplar memory accuracies were above 90% for categories for which a single exemplar had been encoded. When more exemplars per category were encoded, category memory improved, but exemplar memory declined. An exception was face memory, which remained highly accurate even after many faces had been encoded. Our study provided no evidence that visual memory in general, and face memory in particular, is impaired in children with ASD. C1 [Jiang, Yuhong V.; Palm, Bryce E.; DeBolt, Michaela C.; Goh, Yi Shuen] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Jiang, YHV (reprint author), Univ Minnesota, Dept Psychol, S251 Elliott Hall,75 East River Rd, Minneapolis, MN 55455 USA. 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Abnorm. Psychol. PD MAY PY 2015 VL 124 IS 2 BP 447 EP 456 DI 10.1037/abn0000022 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA CH8WP UT WOS:000354317100021 PM 25436998 ER PT J AU Aman, MG Arnold, LE Hollway, JA AF Aman, Michael G. Arnold, L. Eugene Hollway, Jill A. TI Assessing Change in Core Autism Symptoms: Challenges for Pharmacological Studies SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material ID TRIALS C1 [Aman, Michael G.; Arnold, L. Eugene; Hollway, Jill A.] Ohio State Univ, Nisonger Ctr OCEDD, Columbus, OH 43210 USA. RP Aman, MG (reprint author), Ohio State Univ, Psychol, Nisonger Ctr OCEDD, 1581 Dodd Dr, Columbus, OH 43210 USA. 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PD MAY 1 PY 2015 VL 25 IS 4 BP 282 EP 285 DI 10.1089/cap.2015.28999.mga PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA CI1UT UT WOS:000354531100002 PM 25978740 ER PT J AU Cochran, DM Sikoglu, EM Hodge, SM Edden, RAE Foley, A Kennedy, DN Moore, CM Frazier, JA AF Cochran, David M. Sikoglu, Elif M. Hodge, Steven M. Edden, Richard A. E. Foley, Ann Kennedy, David N. Moore, Constance M. Frazier, Jean A. TI Relationship among Glutamine, gamma-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MESSENGER-RNA LEVELS; GABA CONCENTRATION; PREFRONTAL CORTEX; POSTMORTEM BRAIN; CINGULATE CORTEX; FRONTAL-CORTEX; SYSTEM; ABNORMALITIES AB Objective: An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13-17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition. Methods: Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy (H-1-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher-Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr). Results: There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=-0.62, p=0.001) and IQ (rho=-0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=-0.34, p=0.09). Conclusions: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups. C1 [Cochran, David M.; Sikoglu, Elif M.; Hodge, Steven M.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; Frazier, Jean A.] Univ Massachusetts, Sch Med, Child & Adolescent NeuroDev Initiat, Worcester, MA 01655 USA. [Cochran, David M.; Sikoglu, Elif M.; Hodge, Steven M.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; Frazier, Jean A.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Sikoglu, Elif M.; Moore, Constance M.] Univ Massachusetts, Sch Med, Ctr Comparat NeuroImaging, Worcester, MA 01655 USA. [Edden, Richard A. E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Edden, Richard A. E.] Kennedy Krieger Inst, M Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. [Moore, Constance M.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Frazier, Jean A.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. RP Cochran, DM (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 55 Lake Ave N,S7-434, Worcester, MA 01655 USA. EM david.cochran@umassmemorial.org FU American Psychiatric Institute for Research and Education; Janssen Pharmaceutica; American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award; University of Massachusetts Medical School Department of Psychiatry Career Development and Research Office award; UMASS Intellectual and Developmental Disabilities Research Center (National Institutes of Health [NIH]/National Institute of Child Health and Human Development [NICHD]) [5P30 HD004147-39]; National Institute of Mental Health (NIMH) [MH073998]; University of Massachusetts Medical School; NIH [R01 EB016089, P41 EB015909] FX This work was supported by a grant from the American Psychiatric Institute for Research and Education and Janssen Pharmaceutica, an American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award, a University of Massachusetts Medical School Department of Psychiatry Career Development and Research Office award, the UMASS Intellectual and Developmental Disabilities Research Center (National Institutes of Health [NIH]/National Institute of Child Health and Human Development [NICHD] 5P30 HD004147-39), National Institute of Mental Health (NIMH) to C.M.M. (MH073998), and startup funds to C.M.M. from the University of Massachusetts Medical School. This work applies tools developed under NIH grants R01 EB016089 and P41 EB015909; R.A.E.E. also received salary support from these grants. Mr. Hodge served as the statistical expert for this research. 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TI Aberrant Behaviors and Co-occurring Conditions as Predictors of Psychotropic Polypharmacy among Children with Autism Spectrum Disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID POPULATION-BASED SURVEILLANCE; MEDICATION USE; FOSTER-CARE; DRUG-USE; PREVALENCE; PATTERNS; IDENTIFICATION; COLLABORATION; ADHERENCE; NETWORK AB Objectives: The purpose of this study was to identify rates and predictors of psychotropic medication polypharmacy among Medicaid-eligible children in South Carolina with autism spectrum disorder (ASD) from 2000 to 2008. Methods: Population-based surveillance data were linked with state Medicaid records to obtain a detailed demographic, behavioral, educational, clinical, and diagnostic data set for all Medicaid-eligible 8-year-old children (n=629) who were identified and diagnosed with ASD using standardized criteria. Polypharmacy was defined as having interclass psychotropic medication claims overlapping for >= 30 consecutive days at any time during the 2-year study period. Multivariable logistic regression was used to model predictors of any polypharmacy, and for the three most common combinations. Results: Overall, 60% (n=377) used any psychotropic medication, and 41% (n=153) of those had interclass polypharmacy. Common combinations were attention-deficit/hyperactivity disorder (ADHD) medications with an antidepressant (A/AD), antipsychotic (A/AP) or a mood stabilizer (A/MS). Black children had lower odds of any polypharmacy, as did those eligible for Medicaid because of income or being foster care versus those eligible because of disability. There were no significant associations between polypharmacy and social deficits in ASD for any combination, although children with communication deficits diagnostic of ASD had lower odds of any polypharmacy and A/AP polypharmacy. Children with argumentative, aggressive, hyperactive/impulsive, or self-injurious aberrant behaviors had higher odds of polypharmacy, as did children with diagnosed co-occurring ADHD, anxiety or mood disorders, or conduct/oppositional defiant disorder (ODD) in Medicaid records. Conclusions: Future research is warranted to investigate how child-level factors impact combination psychotropic medication prescribing practices and outcomes in ASD. C1 [Logan, Sarah L.] Med Univ S Carolina, Dept Healthcare Leadership & Management, Charleston, SC 29425 USA. [Carpenter, Laura; Charles, Jane] Med Univ S Carolina, Div Dev & Behav Pediat, Dept Pediat, Charleston, SC 29425 USA. [Leslie, R. Scott] Univ Calif San Diego, Dept Family Prevent Med, San Diego, CA 92103 USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Hollings Canc Ctr, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Nicholas, Joyce S.] Centra Neurosci Inst, Lynchburg, VA USA. RP Logan, SL (reprint author), Med Univ S Carolina, Dept Healthcare Leadership & Management, 151B Rutledge Ave,Room 415, Charleston, SC 29425 USA. EM logans@musc.edu FU Centers for Disease Control (CDC) [CDC-RFA-DD06-601] FX This work was supported by the Centers for Disease Control (CDC) Grant #CDC-RFA-DD06-601. CR Aman MG, 2005, J CHILD ADOL PSYCHOP, V15, P116, DOI 10.1089/cap.2005.15.116 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Bilder D, 2009, PEDIATRICS, V123, P1293, DOI 10.1542/peds.2008-0927 Centers for Disease Control, 2009, MMWR-MORBID MORTAL W, V56, P1 Centers for Disease Control, 2012, MMWR-MORBID MORTAL W, V61, P1 Charles JM, 2008, INT J PSYCHIAT MED, V38, P133, DOI 10.2190/PM.38.2.a Dawson G, 2010, PEDIATRICS, V125, pE17, DOI 10.1542/peds.2009-0958 dosReis S, 2005, J CHILD ADOL PSYCHOP, V15, P68, DOI 10.1089/cap.2005.15.68 dosReis S, 2011, PEDIATRICS, V128, pE1459, DOI 10.1542/peds.2010-2970 Durkin MS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011551 Durkin MS, 2008, AM J EPIDEMIOL, V168, P1268, DOI 10.1093/aje/kwn250 Erickson CA, 2007, PEDIATR ANN, V36, P575 Esbensen AJ, 2009, J AUTISM DEV DISORD, V39, P1339, DOI 10.1007/s10803-009-0750-3 Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 Kalkbrenner AE, 2010, EPIDEMIOLOGY, V21, P631, DOI 10.1097/EDE.0b013e3181e65d76 Karve S, 2008, MED CARE, V46, P1125, DOI 10.1097/MLR.0b013e31817924d2 King LB, 2008, 18 AEP, V18 Levy SE, 2010, J DEV BEHAV PEDIATR, V31, P267, DOI 10.1097/DBP.0b013e3181d5d03b Logan SL, 2012, ANN EPIDEMIOL, V22, P1, DOI 10.1016/j.annepidem.2011.10.007 Mandell DS, 2009, AM J PUBLIC HEALTH, V99, P493, DOI 10.2105/AJPH.2007.131243 Mandell DS, 2008, PEDIATRICS, V121, pE441, DOI 10.1542/peds.2007-0984 Martin A, 1999, J AM ACAD CHILD PSY, V38, P923, DOI 10.1097/00004583-199907000-00024 Montes Guillermo, 2009, Pediatrics, V124 Suppl 4, pS407, DOI 10.1542/peds.2009-1255L Moore TR, 2009, J AUTISM DEV DISORD, V39, P1173, DOI 10.1007/s10803-009-0729-0 Myers SM, 2007, EXPERT OPIN PHARMACO, V8, P1579, DOI 10.1517/14656566.811.1579 Myers SM, 2007, PEDIATRICS, V120, P1162, DOI 10.1542/peds.2007-2362 Nicholas JS, 2009, ANN EPIDEMIOL, V19, P808, DOI 10.1016/j.annepidem.2009.04.005 Nicholas JS, 2008, ANN EPIDEMIOL, V18, P130, DOI 10.1016/i.annepidem.2007.10.013 Nicholas JS, 2012, DISABIL HEALTH J, V5, P185, DOI 10.1016/j.dhjo.2012.03.004 Pinborough-Zimmerman J., 2009, MATERN CHILD HLTH J, V14, P392 Powell K, 2010, J PEDIATR-US, V156, P420, DOI 10.1016/j.jpeds.2009.09.068 Rice CE, 2007, PAEDIATR PERINAT EP, V21, P179, DOI 10.1111/j.1365-3016.2007.00801.x Riddle MA, 2001, J CHILD PSYCHOL PSYC, V42, P73, DOI 10.1017/S0021963001006576 Rogers SJ, 2008, J CLIN CHILD ADOLESC, V37, P8, DOI 10.1080/15374410701817808 Rosenberg R, 2009, J AUTISM DEV DISORD, V40, P342 Rubin DM, 2009, PEDIATRICS, V124, pE305, DOI 10.1542/peds.2008-3713 Safer DJ, 2003, AM J PSYCHIAT, V160, P438, DOI 10.1176/appi.ajp.160.3.438 Shattuck PT, 2009, J AM ACAD CHILD PSY, V48, P474, DOI 10.1097/CHI.0b013e31819b3848 Shattuck PT, 2007, MENT RETARD DEV D R, V13, P129, DOI 10.1002/mrdd.20143 Spencer D, 2013, PEDIATRICS, V132, P833, DOI 10.1542/peds.2012-3774 Stevens J, 2009, J CHILD ADOL PSYCHOP, V19, P289, DOI 10.1089/cap.2008.0129 Van Naarden Braun K, 2008, AUTISM RES, V1, P265 Wiggins LD, 2009, AUTISM, V13, P357, DOI 10.1177/1362361309105662 Yeargin-Allsopp M, 2008, PEDIATRICS, V121, P547, DOI 10.1542/peds.2007-1270 Yeargin-Allsopp M, 2003, JAMA-J AM MED ASSOC, V289, P49, DOI 10.1001/jama.289.1.49 Zito JM, 2003, ARCH PEDIAT ADOL MED, V157, P17 NR 46 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 MAY 1 PY 2015 VL 25 IS 4 BP 323 EP 336 DI 10.1089/cap.2013.0119 PG 14 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA CI1UT UT WOS:000354531100007 PM 25919445 ER PT J AU Fiks, AG Mayne, SL Song, LH Steffes, J Liu, WW McCarn, B Margolis, B Grimes, A Gotlieb, E Localio, R Ross, ME Grundmeier, RW Wasserman, R Leslie, LK AF Fiks, Alexander G. Mayne, Stephanie L. Song, Lihai Steffes, Jennifer Liu, Weiwei McCarn, Banita Margolis, Benyamin Grimes, Alan Gotlieb, Edward Localio, Russell Ross, Michelle E. Grundmeier, Robert W. Wasserman, Richard Leslie, Laurel K. TI Changing Patterns of Alpha Agonist Medication Use in Children and Adolescents 2009-2011 SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; PRACTICE PARAMETER; AGGRESSIVE-CHILDREN; TIC DISORDERS; CLONIDINE; ADHD; GUANFACINE; EFFICACY AB Objectives: The purpose of this study was to describe rates and patterns of long- and short-acting alpha agonist use for behavioral problems in a primary care population following Food and Drug Administration (FDA) approval of the long-acting alpha agonists guanfacine and clonidine. Methods: Children and adolescents 4-18 years of age, who received an alpha agonist prescription between 2009 and 2011, were identified from a sample of 45 United States primary care practices in two electronic health record-based research networks. Alpha agonist receipt was identified using National Drug Codes and medication names. The proportion of subjects receiving long- and short-acting prescriptions in each year was calculated and examined with respect to reported mental health diagnoses, and whether indications for use were on-label, had evidence from clinical trials, or had no trial evidence. Results: In a cohort of 282,875 subjects, 27,671 (10%) received any psychotropic medication and only 4,227 subjects (1.5%) received at least one prescription for an alpha agonist, most commonly a short-acting formulation (83%). Only 20% of alpha agonist use was on-label (use of long-acting formulations for attention-deficit/hyperactivity disorder [ADHD]). Most subjects (68%) received alpha agonists for indications with evidence of efficacy from clinical trials but no FDA approval, primarily short-acting formulations for ADHD and autism; 12% received alpha agonists for diagnoses lacking randomized clinical trial evidence in children, including sleep disorders and anxiety, or for which there was no documented mental health diagnosis. Rates of long-acting alpha agonist use increased more than 20-fold from 0.2% to 4%, whereas rates of short-acting alpha agonist use grew only slightly between 2009 and 2011 from 10.6% to 11.3%. Conclusions: Alpha agonist use was uncommon in this population, and most subjects received short-acting forms for conditions that were off-label, but with clinical trial evidence. The safety and efficacy of use for conditions, including sleep disorders and anxiety, lacking evidence from randomized trials, warrant further investigation. C1 [Fiks, Alexander G.] Childrens Hosp Philadelphia, Pediat Res Consortium, Philadelphia, PA 19104 USA. [Fiks, Alexander G.; Grundmeier, Robert W.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Fiks, Alexander G.; Mayne, Stephanie L.; Song, Lihai] Childrens Hosp Philadelphia, Ctr Pediat Clin Effectiveness, Philadelphia, PA 19104 USA. [Fiks, Alexander G.; Mayne, Stephanie L.; Song, Lihai] Childrens Hosp Philadelphia, PolicyLab, Philadelphia, PA 19104 USA. [Fiks, Alexander G.; Steffes, Jennifer; Liu, Weiwei; McCarn, Banita; Grimes, Alan; Gotlieb, Edward; Wasserman, Richard; Leslie, Laurel K.] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Fiks, Alexander G.; Grundmeier, Robert W.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Margolis, Benyamin] US Hlth Resources & Serv Adm, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. [Localio, Russell; Ross, Michelle E.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Wasserman, Richard] Univ Vermont, Coll Med, Burlington, VT USA. [Leslie, Laurel K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Fiks, AG (reprint author), Childrens Hosp Philadelphia, 3535 Market Suite,Room 1546, Philadelphia, PA 19104 USA. EM fiks@email.chop.edu FU Maternal and Child Health Bureau, Health Resources and Services Administration, United States Department of Health and Human Services (HHS) through the American Recovery and Reinvestment Act [UB5MC2O286]; American Academy of Pediatrics; Maternal and Child Health Bureau [R40MC245943] FX This research was supported by cooperative agreement UB5MC2O286 from the Maternal and Child Health Bureau, Health Resources and Services Administration, United States Department of Health and Human Services (HHS) through the American Recovery and Reinvestment Act of 2009 and the American Academy of Pediatrics. The research was also supported by grant number R40MC245943 from the Maternal and Child Health Bureau. The findings and conclusions are those of the authors and do not necessarily represent the views of HHS or the authors' affiliated institutions. 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Child Adolesc. Psychopharmacol. PD MAY 1 PY 2015 VL 25 IS 4 BP 362 EP 367 DI 10.1089/cap.2014.0122 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA CI1UT UT WOS:000354531100011 PM 25919708 ER PT J AU Harfterkamp, M van der Meer, D van der Loo-Neus, G Buitelaar, JK Minderaa, RB Hoekstra, PJ AF Harfterkamp, Myriam van der Meer, Dennis van der Loo-Neus, Gigi Buitelaar, Jan K. Minderaa, Ruud B. Hoekstra, Pieter J. TI No Evidence for Predictors of Response to Atomoxetine Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Letter ID PERVASIVE DEVELOPMENTAL DISORDERS; OPEN-LABEL; EFFICACY; ADHD; HYPERACTIVITY; PLACEBO; SAFETY C1 [Harfterkamp, Myriam; van der Meer, Dennis; Minderaa, Ruud B.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [van der Loo-Neus, Gigi; Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. RP Harfterkamp, M (reprint author), Univ Med Ctr Groningen, Dept Psychiat, Child & Adolescent Psychiat Ctr, Hanzepl 1, NL-9717 ER Groningen, Netherlands. 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Child Adolesc. Psychopharmacol. PD MAY 1 PY 2015 VL 25 IS 4 BP 372 EP 375 DI 10.1089/cap.2014.0142 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA CI1UT UT WOS:000354531100013 PM 25919900 ER PT J AU Raja, M AF Raja, Michele TI Did Mozart suffer from Asperger syndrome? SO JOURNAL OF MEDICAL BIOGRAPHY LA English DT Article ID HIGH-FUNCTIONING AUTISM; DEVELOPMENTAL DISORDER; SCATOLOGICAL DISORDER; TOURETTE-SYNDROME; HANDEDNESS; TICS; DELUSIONS; BEHAVIOR; CHILDREN; BELIEFS AB The most reliable biographies of Mozart highlight elements that are compatible with current diagnostic criteria for Asperger syndrome including qualitative impairment in social interaction and stereotyped and repetitive motor mannerisms. Furthermore, numerous features are documented including difficulty in communicating his emotional state and in inferring the mental state of his interlocutors, motor clumsiness, specific skills and genius, left-handedness, special sense of humour, physical developmental abnormalities, bizarre thinking, overvalued ideas and delusions. C1 [Raja, Michele] Santo Spirito Hosp, Psychiat Intens Care Unit, Rome, Italy. [Raja, Michele] Hosp Med Sch Rome, Psychopharmacol & Psychiat Semeiot, Rome, Italy. RP Raja, M (reprint author), Via Prisciano 26, I-00136 Rome, Italy. 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Med. Biogr. PD MAY PY 2015 VL 23 IS 2 BP 84 EP 92 DI 10.1177/0967772013503763 PG 9 WC History & Philosophy Of Science SC History & Philosophy of Science GA CI2FJ UT WOS:000354560300003 PM 24585598 ER PT J AU Croft, S Stride, C Maughan, B Rowe, R AF Croft, Simone Stride, Christopher Maughan, Barbara Rowe, Richard TI Validity of the Strengths and Difficulties Questionnaire in Preschool-Aged Children SO PEDIATRICS LA English DT Article ID PSYCHOMETRIC PROPERTIES; MEASUREMENT INVARIANCE; COMMUNITY SAMPLE; FIT INDEXES; VERSION; PARENT; SDQ; RELIABILITY; ALPHA AB BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen for child mental health problems and measure common forms of psychopathology in 4-to 16-year-olds. Using longitudinal data, we examined the validity of a version adapted for 3-to 4-year-olds. METHODS: We used SDQ data from 16 659 families collected by the Millennium Cohort Study, which charts the development of children born throughout the United Kingdom during 2000-2001. Parents completed the preschool SDQ when children were aged 3 and the standard SDQ at ages 5 and 7. The SDQ's internal factor structure was assessed by using confirmatory factor analysis, with a series of competing models and extensions used to determine construct, convergent, and discriminant validity and measurement invariance over time. Predictive validity was evaluated by examining the relationships of age 3 SDQ scores with age 5 diagnostic measures of attention-deficit/hyperactivity disorder, autism spectrum disorder/Asperger syndrome, and teacher-reported measures of personal, social, and emotional development. RESULTS: Confirmatory factor analysis supported a 5-factor measurement model. Internal reliability of subscales ranged from omega = 0.66 (peer problems) to omega = 0.83 (hyperactivity). Item-factor structures revealed measurement invariance over time. Strong positive correlations between ages 3 and 5 SDQ scores were not significantly different from correlations between age 5 and 7 scores. Conduct problems and hyperactivity subscales independently predicted developmental and clinical outcomes 2 years later. CONCLUSIONS: Satisfactory psychometric properties of the adapted preschool version affirm its utility as a screening tool to identify 3-to 4-year-olds with emotional and behavioral difficulties. C1 [Croft, Simone; Rowe, Richard] Univ Sheffield, Dept Psychol, Sheffield S10 2TP, S Yorkshire, England. [Stride, Christopher] Univ Sheffield, Inst Work Psychol, Sheffield S10 2TP, S Yorkshire, England. [Maughan, Barbara] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Res Ctr, London, England. RP Croft, S (reprint author), Univ Sheffield, Dept Psychol, Western Bank, Sheffield S10 2TP, S Yorkshire, England. EM s.e.croft@sheffield.ac.uk RI Rowe, Richard/B-8477-2008 FU Economic and Social Research Council [ES/J500215/1] FX This work was supported by an Economic and Social Research Council PhD studentship (ES/J500215/1), awarded to Ms Croft and supervised by Drs Rowe and Stride. 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TI Maternal Prepregnancy Body Mass Index and Child Psychosocial Development at 6 Years of Age SO PEDIATRICS LA English DT Article ID DIFFICULTIES QUESTIONNAIRE; INTELLECTUAL DISABILITY; PSYCHOMETRIC PROPERTIES; COGNITIVE-DEVELOPMENT; WEIGHT-GAIN; PREGNANCY; OBESITY; ASSOCIATIONS; TRENDS; RISK AB BACKGROUND: Both obesity and developmental disabilities have increased in recent decades. Limited studies suggest associations between maternal prepregnancy obesity and child neurodevelopment. METHODS: The Infant Feeding Practices Study II, a US nationally distributed longitudinal study of maternal health and infant health and feeding practices, was conducted from 2005 to 2007. In 2012, mothers were recontacted for information on their children's health and development. We examined associations between maternal prepregnancy BMI and child psychosocial development in 1311 mother-child pairs included in this follow-up study. Children's development was assessed by maternal report of child psychosocial difficulties from the Strengths and Difficulties Questionnaire, past developmental diagnoses, and receipt of special needs services. RESULTS: Adjusting for sociodemographic factors, children of obese class II/III mothers (BMI > 35.0) had increased odds of emotional symptoms (adjusted odds ratio [aOR] 2.24; 95% confidence interval [CI], 1.27-3.98), peer problems (aOR 2.07; 95% CI, 1.26-3.40), total psychosocial difficulties (aOR 2.17; 95% CI, 1.24-3.77), attention-deficit/hyperactivity disorder diagnosis (aOR 4.55; 95% CI, 1.80-11.46), autism or developmental delay diagnosis (aOR 3.13; 95% CI, 1.10-8.94), receipt of speech language therapy (aOR 1.93; 95% CI, 1.18-3.15), receipt of psychological services (aOR 2.27; 95% CI, 1.09-4.73), and receipt of any special needs service (aOR 1.99; 95% CI, 1.33-2.97) compared with children of normal weight mothers (BMI 18.5-24.9). Adjustment for potential causal pathway factors including pregnancy weight gain, gestational diabetes, breastfeeding duration, postpartum depression, and child's birth weight did not substantially affect most estimates. CONCLUSIONS: Children whose mothers were severely obese before pregnancy had increased risk for adverse developmental outcomes. C1 [Jo, Heejoo; Schieve, Laura A.] Ctr Dis Control & Prevent, Div Birth Defects & Dev Disabil, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Li, Ruowei; Lind, Jennifer N.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA 30333 USA. [Lind, Jennifer N.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA. [Jo, Heejoo] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Sharma, Andrea J.] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA 30333 USA. 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These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. Method: The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. Results: The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. Conclusion: The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process. C1 [Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge] Univ Marburg, Klin Kinder & Jugendpsychiat Psychosomat & Psycho, D-35039 Marburg, Germany. RP Kamp-Becker, I (reprint author), Univ Marburg, Klin Kinder & Jugendpsychiat Psychosomat & Psycho, Hans Sachs Str 6, D-35039 Marburg, Germany. EM kampbeck@med.uni-marburg.de CR Baron-Cohen S, 2000, J ROY SOC MED, V93, P521 Bolte S., 2008, SKALA ERFASSUNG SOZI Bolte S, 2006, DIAGNOSTISCHES INTER Bolte S., 2006, FRAGEBOGEN SOZIALEN Bolte S, 2011, J AUTISM DEV DISORD, V41, P66, DOI 10.1007/s10803-010-1024-9 Bortz J., 2006, FORSCHUNGSMETHODEN E Cholemkery H, 2014, EUR CHILD ADOLES PSY, V23, P81, DOI 10.1007/s00787-013-0427-5 Cholemkery H, 2014, J AUTISM DEV DISORD, V44, P1168, DOI 10.1007/s10803-013-1979-4 Collin L, 2013, RES DEV DISABIL, V34, P1505, DOI 10.1016/j.ridd.2013.01.008 Corsello CM, 2013, J CHILD PSYCHOL PSYC, V54, P178, DOI 10.1111/j.1469-7610.2012.02607.x Dumont-Mathieu T, 2005, MENT RETARD DEV D R, V11, P253, DOI 10.1002/mrdd.20072 Eaves LC, 2006, AUTISM, V10, P229, DOI 10.1177/1362361306063288 Georgiades S, 2013, J CHILD PSYCHOL PSYC, V54, P206, DOI 10.1111/j.1469-7610.2012.02588.x Gotham K, 2008, J AM ACAD CHILD PSY, V47, P642, DOI 10.1097/CHI.0b013e31816bffb7 Groves R.M., 2009, SURVEY METHODOLOGY Grzadzinski R, 2011, J AUTISM DEV DISORD, V41, P1178, DOI 10.1007/s10803-010-1135-3 Hoffmann W, 2013, RES DEV DISABIL, V34, P640, DOI 10.1016/j.ridd.2012.09.013 Hosmer DW, 2000, APPL LOGISTIC REGRES, V2nd Hus V, 2013, J CHILD PSYCHOL PSYC, V54, P216, DOI 10.1111/j.1469-7610.2012.02589.x Ivarsson T, 2008, J ANXIETY DISORD, V22, P969, DOI 10.1016/j.janxdis.2007.10.003 Johnson S, 2011, ARCH DIS CHILD, V96, P73, DOI 10.1136/adc.2010.194795 Jones RM, 2013, BEHAV BRAIN RES, V251, P113, DOI 10.1016/j.bbr.2012.10.037 Kamp-Becker I, 2005, Z KINDER JUG-PSYCH, V33, P15, DOI 10.1024/1422-4917.33.1.15 Kamp-Becker I, 2012, Z KINDER JUG-PSYCH, V40, P341, DOI 10.1024/1422-4917/a000191 Kamp-Becker I, 2013, AUTISM, V17, P87, DOI 10.1177/1362361311408932 Kamp-Becker I, 2010, KINDH ENTWICKL, V19, P144, DOI 10.1026/0942-5403/a000019 Kamp-Becker I, 2010, KINDH ENTWICKL, V19, P168, DOI 10.1026/0942-5403/a000021 Kim SH, 2010, AUTISM RES, V3, P162, DOI 10.1002/aur.142 Kjellmer L, 2012, RES DEV DISABIL, V33, P172, DOI 10.1016/j.ridd.2011.09.003 Le Couteur A, 2008, J AUTISM DEV DISORD, V38, P362, DOI 10.1007/s10803-007-0403-3 Lord C, 1997, J AUTISM DEV DISORD, V27, P501, DOI 10.1023/A:1025873925661 Lord C, 2012, J CHILD PSYCHOL PSYC, V53, P490, DOI 10.1111/j.1469-7610.2012.02547.x Lord C, 2006, ARCH GEN PSYCHIAT, V63, P694, DOI 10.1001/archpsyc.63.6.694 Lord C., 2000, AUTISM DIAGNOSTIC OB Margraf J., 2009, LEHRBUCH VERHALTENST, V1, P339 Mayes SD, 2012, RES AUTISM SPECT DIS, V6, P277, DOI 10.1016/j.rasd.2011.05.009 McConachie H, 2005, J AUTISM DEV DISORD, V35, P167, DOI 10.1007/s10803-005-1995-0 Moricke E, 2010, EUR CHILD ADOLES PSY, V19, P659, DOI 10.1007/s00787-010-0103-y Oosterling I, 2010, J CHILD PSYCHOL PSYC, V51, P1260, DOI 10.1111/j.1469-7610.2010.02246.x Pelphrey KA, 2011, J CHILD PSYCHOL PSYC, V52, P631, DOI 10.1111/j.1469-7610.2010.02349.x Rithl D., 2004, DIAGNOSTISCHE BEABAC Ronald A, 2010, J ABNORM CHILD PSYCH, V38, P185, DOI 10.1007/s10802-009-9366-5 Rutter M., 2003, AUTISM DIAGNOSTIC IN Rutter M., 2003, SOCIAL COMMUNICATION Schanding GT, 2012, J AUTISM DEV DISORD, V42, P1705, DOI 10.1007/s10803-011-1412-9 Schwenck Christina, 2014, Atten Defic Hyperact Disord, V6, P221, DOI 10.1007/s12402-014-0147-9 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Sinzig J, 2011, Z KINDER JUG-PSYCH, V39, P91, DOI 10.1024/1422-4917/a000095 Skase D. H., 2005, BRIT J PSYCHIAT, V187, P568 Snow AV, 2008, AUTISM, V12, P627, DOI 10.1177/1362361308097116 Steinhausen HC, 2013, Z KINDER JUG-PSYCH, V41, P419, DOI 10.1024/1422-4917/a000258 Sunita M. A., 2013, J PAEDIATR CHILD H, V49, P438 Taurines Regina, 2012, Atten Defic Hyperact Disord, V4, P115, DOI 10.1007/s12402-012-0086-2 Tyson KE, 2012, J AUTISM DEV DISORD, V42, P1477, DOI 10.1007/s10803-011-1386-7 Wall DP, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0043855 NR 55 TC 0 Z9 0 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 1422-4917 EI 1664-2880 J9 Z KINDER JUG-PSYCH JI Z. Kinder-und Jugendpsy. Psychother. PD MAY PY 2015 VL 43 IS 3 BP 207 EP 219 DI 10.1024/1422-4917/a000354 PG 13 WC Psychiatry SC Psychiatry GA CI2OK UT WOS:000354586700006 ER PT J AU Cermak, SA Duker, LIS Williams, ME Lane, CJ Dawson, ME Borreson, AE Polido, JC AF Cermak, Sharon A. Duker, Leah I. Stein Williams, Marian E. Lane, Christianne Joy Dawson, Michael E. Borreson, Ann E. Polido, Jose C. TI Feasibility of a Sensory-Adapted Dental Environment for Children With Autism SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE child development disorders, pervasive; dental care; environment; occupational therapy; sensation disorders; stress, physiological ID HEALTH-CARE NEEDS; SPECTRUM DISORDERS; ORAL CARE; ANXIETY; ADAPTATION; RISK AB OBJECTIVE. To provide an example of an occupational therapy feasibility study and evaluate the implementation of a randomized controlled pilot and feasibility trial examining the impact of a sensory-adapted dental environment (SADE) to enhance oral care for children with autism spectrum disorder (ASD). METHOD. Twenty-two children with ASD and 22 typically developing children, ages 6-12 yr, attended a dental clinic in an urban hospital. Participants completed two dental cleanings, 3-4 mo apart, one in a regular environment and one in a SADE. Feasibility outcome measures were recruitment, retention, accrual, dropout, and protocol adherence. Intervention outcome measures were physiological stress, behavioral distress, pain, and cost. RESULTS. We successfully recruited and retained participants. Parents expressed satisfaction with re'search study participation. Dentists stated that the intervention could be incorporated in normal practice. Intervention outcome measures favored the SADE condition. CONCLUSION. Preliminary positive benefit of SADE in children with ASD warrants moving forwa.rd with a large-scale clinical trial. C1 [Cermak, Sharon A.] Univ So Calif, Herman Ostrow Sch Dent, Mrs TH Chan Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. [Duker, Leah I. Stein; Borreson, Ann E.] Univ So Calif, Herman Ostrow Sch Dent, Div Occupat Sci & Occupat Therapy, Los Angeles, CA USA. [Williams, Marian E.] Univ So Calif, Keck Sch Med, Univ Ctr Excellence Dev Disabil, Clin Pediat,Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Lane, Christianne Joy] Univ So Calif, Dept Prevent Med, Div Biostat, Los Angeles, CA 90089 USA. [Dawson, Michael E.] Univ So Calif, Dept Psychol, Dana & David Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA. [Polido, Jose C.] Univ So Calif, Childrens Hosp Los Angeles, Dent, Los Angeles, CA USA. [Polido, Jose C.] Univ So Calif, Herman Ostrow Sch Dent, Clin Dent, Los Angeles, CA USA. RP Cermak, SA (reprint author), Univ So Calif, Herman Ostrow Sch Dent, Mrs TH Chan Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. EM cermak@usc.edu FU National Institute of Dental and Craniofacial Research [1R34DE022263-01]; University of Southern California Ostrow School of Dentistry; Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [T32HD064578] FX This study was funded by the National Institute of Dental and Craniofacial Research (1R34DE022263-01; Sharon Cermak, principal investigator), by a seed grant from the University of Southern California Ostrow School of Dentistry, and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (T32HD064578; Florence Clark, principal investigator). We thank the University of Southern California Mrs. T. H. Chan Division of Occupational Science and Occupational Therapy for its continued support; Michele Shapiro and Anat Baniel from Beit Issie Shapiro, Ra'nana, Israel, for their original research on sensory adaptations in the dental environment and for providing consultation throughout this project; Trudy Mallinson for her assistance with Rasch analysis in developing the CDBRS coding scale; Mae Aghili for her participation and skill in performing the study dental cleanings; Irina Zamora for assistance in confirming diagnosis of children with ASD; Elyse Peterson and Lauren St. Hilaire for their assistance in psychometric testing of the CDBRS, data collection, and interrater reliability assessments of measures; and Daniela Florindez, our bilingual research assistant. Our ClinicalTrials.gov identifier is NCT02077985. CR Ayres A. 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J. Occup. Ther. PD MAY-JUN PY 2015 VL 69 IS 3 DI 10.5014/ajot.2015.013714 PG 10 WC Rehabilitation SC Rehabilitation GA CH5JI UT WOS:000354071500002 ER PT J AU Kirby, AV Little, LM Schultz, B Baranek, GT AF Kirby, Anne V. Little, Lauren M. Schultz, Beth Baranek, Grace T. TI Observational Characterization of Sensory Interests, Repetitions, and Seeking Behaviors SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE child behavior; child development disorders, pervasive; developmental disabilities; observation; sensation ID AUTISM SPECTRUM DISORDERS; TYPICALLY DEVELOPING-CHILDREN; YOUNG-CHILDREN; DEVELOPMENTAL DELAYS; PROFILE; LIFE; DISABILITIES; MODULATION; PATTERNS; FEATURES AB Sensory interests, repetitions; and seeking behaviors (SIRS) are common among children with autism spectrum disorder (ASD) and other developmental disabilities (DD) and involve unusual actions that intensify or reinforce a sensory experience. Researchers and practitioners typically use parent-report measures or informal clinical observations to understand the presence and nature of SIRS. In this study, we used a scoring supplement to the Sensory Processing Assessment for Young Children, an observational measure, to characterize SIRS across three groups of children those with ASD (n = 40), DD (n = 37), and typical development (n = 39). Group differences were identified in frequency and intensity of overall SIRS, complexity of SIRS, and incidence of particular types of SIRS (i.e., posturing, sighting, proprioceptive seeking, spinning). Facial affect was also explored and found to be primarily neutral during engagement in SIRS across groups. Implications for practice and future research are discussed. C1 [Kirby, Anne V.; Schultz, Beth] Univ N Carolina, Dept Allied Hlth Sci, Div Occupat Sci & Occupat Therapy, Chapel Hill, NC 27599 USA. [Little, Lauren M.] Univ Kansas, Med Ctr, Dept Occupat Therapy Educ, Kansas City, KS USA. [Baranek, Grace T.] Univ N Carolina, Dept Allied Hlth Sci, Div Occupat Sci & Occupat Therapy, Res, Chapel Hill, NC USA. RP Kirby, AV (reprint author), Univ N Carolina, Dept Allied Hlth Sci, Div Occupat Sci & Occupat Therapy, Chapel Hill, NC 27599 USA. EM avkirby@gmail.com FU National Institute for Child Health and Human Development [R01-HD42168] FX This research was supported by a grant from the National Institute for Child Health and Human Development (R01-HD42168). This study also received core support for participant recruitment through the North Carolina Autism Research Registry (P30-HD03110). The authors thank staff and students at the Sensory Experiences Project as well as the families whose participation made this study possible. CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Ausderau K, 2014, J AUTISM DEV DISORD, V44, P915, DOI 10.1007/s10803-013-1945-1 Baranek G. T., 2009, SENSORY EXPERI UNPUB Baranek G. T., 1999, SENSORY PROCES UNPUB Baranek GT, 2007, AM J MENT RETARD, V112, P233, DOI 10.1352/0895-8017(2007)112[233:HSPIYC]2.0.CO;2 Baranek GT, 1999, J AUTISM DEV DISORD, V29, P213, DOI 10.1023/A:1023080005650 Baranek GT, 2013, DEV PSYCHOPATHOL, V25, P307, DOI 10.1017/S0954579412001071 Becker K. A., 2003, HIST STANFORD BINET Ben-Sasson A, 2009, J AUTISM DEV DISORD, V39, P1, DOI 10.1007/s10803-008-0593-3 Ben-Sasson A, 2007, AM J OCCUP THER, V61, P584 Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Boyd BA, 2010, AUTISM RES, V3, P78, DOI 10.1002/aur.124 Dunn W, 1997, AM J OCCUP THER, V51, P490 Dunn W, 2001, AM J OCCUP THER, V55, P608 Dunn W., 1999, SENSORY PROFILE Engel-Yeger B, 2011, BRIT J OCCUP THER, V74, P456, DOI 10.4276/030802211X13182481841868 Ermer J, 1998, AM J OCCUP THER, V52, P283 Field A., 2009, DISCOVERING STAT USI FLEISS JL, 1973, EDUC PSYCHOL MEAS, V33, P613, DOI 10.1177/001316447303300309 Higashida N., 2013, THE REASON I JUMP Juberg DR, 2001, PEDIATRICS, V107, P135, DOI 10.1542/peds.107.1.135 Lane AE, 2010, J AUTISM DEV DISORD, V40, P112, DOI 10.1007/s10803-009-0840-2 Lane S. J., 2013, WILLARD SPACKMANS OC, P816 Le Couteur A., 2003, AUTISM DIAGNOSTIC IN Leekam SR, 2007, J AUTISM DEV DISORD, V37, P894, DOI 10.1007/s10803-006-0218-7 Lord C., 1999, AUTISM DIAGNOSTIC OB MacDonald R, 2007, RES DEV DISABIL, V28, P266, DOI 10.1016/j.ridd.2006.01.004 Militerni R, 2002, EUR CHILD ADOLES PSY, V11, P210, DOI 10.1007/s00787-002-0279-x Miller LJ, 2007, AM J OCCUP THER, V61, P135 Mullen E, 1995, MULLEN SCALES EARLY Pasamanick B., 1974, GESELL AMATRUDAS DEV Pfeiffer B, 2005, AM J OCCUP THER, V59, P335 Reynolds S, 2011, J AUTISM DEV DISORD, V41, P1496, DOI 10.1007/s10803-010-1173-x Roid G., 1997, LEITER INT PERFORMAN Roid G. H., 2003, STANFORD BINET INTEL Schopler E., 1988, CHILDHOOD AUTISM RAT Sparrow S, 1984, VINELAND ADAPTIVE BE Sullivan L. E., 2009, SAGE GLOSSARY SOCIAL Sullivan MW, 2003, INFANT YOUNG CHILD, V16, P120 Tomchek SD, 2007, AM J OCCUP THER, V61, P190 Volkmar F., 2014, HDB AUTISM, P378 Watling RL, 2001, AM J OCCUP THER, V55, P416 Watt N, 2008, J AUTISM DEV DISORD, V38, P1518, DOI 10.1007/s10803-007-0532-8 Zwaigenbaum L, 2005, INT J DEV NEUROSCI, V23, P143, DOI 10.1016/j.ijdevneu.2004.05.001 NR 44 TC 0 Z9 0 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 EI 1943-7676 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2015 VL 69 IS 3 DI 10.5014/ajot.2015.015081 PG 9 WC Rehabilitation SC Rehabilitation GA CH5JI UT WOS:000354071500001 ER PT J AU Reynolds, S Lane, SJ Mullen, B AF Reynolds, Stacey Lane, Shelly J. Mullen, Brian TI Effects of Deep Pressure Stimulation on Physiological Arousal SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE adaptation, physiological; arousal; autonomic nervous system; pressure; touch ID DEFICIT HYPERACTIVITY DISORDER; COGNITIVE-ENERGETIC MODEL; ON-TASK BEHAVIOR; SENSORY OVERRESPONSIVITY; WEIGHTED VEST; CHILDREN; ATTENTION; AUTISM AB Deep pressure stimulation has been used in therapeutic practice because of the assumption that it changes physiological arousal. The purpose of this study was to test the effects of deep pressure stimulation, applied with a Vayu Vest (Therapeutic Systems), on both autonomic arousal and performance in a normative adult sample. A repeated-measures, repeated-baseline design was used with participants completing a performance test before and after deep pressure application. A convenience sample of 50 adults participated in the study. Results showed that wearing the Vayu Vest for even short periods of time reduced sympathetic arousal and non stimulus-driven electrical occurrences. Concomitant increases in parasympathetic arousal were found. Performance improvements were noted after wearing the Vayu Vest, potentially because of changes in arousal. We conclude that deep pressure stimulation is capable of eliciting changes in autonomic arousal and may be a useful modality in diagnostic groups seen by occupational therapy practitioners. C1 [Reynolds, Stacey; Lane, Shelly J.] Virginia Commonwealth Univ, Dept Occupat Therapy, Richmond, VA 23284 USA. [Mullen, Brian] Therapeut Syst, Amherst, MA USA. RP Reynolds, S (reprint author), Virginia Commonwealth Univ, Dept Occupat Therapy, Richmond, VA 23284 USA. EM reynoldsse3@vcu.edu FU Virginia Commonwealth University's Presidential Research Quest Fund; Virginia Commonwealth University's Kathryn Lawrence Dragas Memorial Scholarship Fund FX We would like to acknowledge Sara Taylor and Alison Travers, who worked as research assistants on this project. Funding for this study was provided by Virginia Commonwealth University's Presidential Research Quest Fund and Kathryn Lawrence Dragas Memorial Scholarship Fund. CR Abdi H., 2010, ENCY RES DESIGN, P545 Angeles Fernandez-Gil M., 2010, SEMINARS ULTRASOUND, V31, P196 Ayres A. J., 1972, SENSORY INTEGRATION Champagne T, 2011, WORK, V38, P67, DOI 10.3233/WOR-2011-1105 Dunn W., 2002, ADULT ADOLESCENT SEN Edelson SM, 1999, AM J OCCUP THER, V53, P145 Fertel-Daly D, 2001, AM J OCCUP THER, V55, P629 Field T, 2010, INFANT BEHAV DEV, V33, P115, DOI 10.1016/j.infbeh.2009.12.004 Grossman P, 2007, BIOL PSYCHOL, V74, P263, DOI 10.1016/j.biopsycho.2005.11.014 Hare TA, 2008, BIOL PSYCHIAT, V63, P927, DOI 10.1016/j.biopsych.2008.03.015 Hodgetts S, 2011, J AUTISM DEV DISORD, V41, P805, DOI 10.1007/s10803-010-1104-x Kessler RC, 2005, ARCH GEN PSYCHIAT, V62, P617, DOI 10.1001/archpsyc.62.6.617 Kimball JG, 2007, AM J OCCUP THER, V61, P406 Lane SJ, 2012, AM J OCCUP THER, V66, P595, DOI 10.5014/ajot.2012.004523 Lin HY, 2014, AM J OCCUP THER, V68, P149, DOI 10.5014/ajot.2014.009365 Mullen B., 2008, OCCUPATIONAL THERAPY, V24, P65 Pfeiffer B, 2005, AM J OCCUP THER, V59, P335 Reynolds S, 2010, J ATTEN DISORD, V13, P468, DOI 10.1177/1087054708329906 Sergeant J, 2000, NEUROSCI BIOBEHAV R, V24, P7, DOI 10.1016/S0149-7634(99)00060-3 Sergeant JA, 2005, BIOL PSYCHIAT, V57, P1248, DOI 10.1016/j.bps.2004.09.010 Tomchek SD, 2007, AM J OCCUP THER, V61, P190 VandenBerg NL, 2001, AM J OCCUP THER, V55, P621 Withersty David J, 2005, Psychiatry (Edgmont), V2, P47 NR 23 TC 0 Z9 0 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 EI 1943-7676 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2015 VL 69 IS 3 AR 6903350010 DI 10.5014/ajot.2015.015560 PG 5 WC Rehabilitation SC Rehabilitation GA CH5JI UT WOS:000354071500014 ER PT J AU Kigar, SL Chang, LZ Auger, AP AF Kigar, Stacey L. Chang, Liza Auger, Anthony P. TI Gadd45b is an epigenetic regulator of juvenile social behavior and alters local pro-inflammatory cytokine production in the rodent amygdala SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Amygdala; Gadd45b; Methylation; Epigenetics; Social play; Reelin; MeCP2; Adra2a; Cytokines; Development ID SPONTANEOUSLY HYPERTENSIVE-RATS; ACTIVE DNA DEMETHYLATION; ANXIETY-LIKE BEHAVIOR; LONG-TERM-MEMORY; VASOPRESSIN EXPRESSION; PLAY-BEHAVIOR; BRAIN; MECP2; INTERLEUKIN-6; RECEPTOR AB Precise regulation of the epigenome during perinatal development is critical to the formation of species-typical behavior later in life. Recent data suggests that Gadd45b facilitates active DNA demethylation by recruiting proteins involved in base excision repair (BER), which will catalyze substitution of 5-methylcytosine (5mC) for an unmodified cytosine. While a role for Gadd45b has been implicated in both hippocampal and amygdalar learning tasks, to the best of our knowledge, no study has been done investigating the involvement of Gadd45b in neurodevelopmental programming of social behavior. To address this, we used a targeted siRNA delivery approach to transiently knock down Gadd45b expression in the neonatal rat amygdala. We chose to examine social behavior in the juvenile period, as social deficits associated with neurodevelopmental disorders tend to emerge in humans at an equivalent age. We find that neonatal Gadd45b knock-down results in altered juvenile social behavior and reduced expression of several genes implicated in psychiatric disorders, including methyl-CpG-binding protein 2 (MeCP2), Reelin, and brain derived neurotrophic factor (BDNF). We furthermore report a novel role for Gadd45b in the programmed expression of alpha(2)-adrenoceptor (Adra2a). Consistent with Gadd45b's role in the periphery, we also observed changes in the expression of pro-inflammatory cytokines interleukin-6 (Il-6) and interleukin-1 beta (Il-1beta) in the amygdala, which could potentially mediate or exacerbate effects of Gadd45b knockdown on the organization of social behavior. These data suggest a prominent role for Gadd45b in the epigenetic programming of complex juvenile social interactions, and may provide insight into the etiology of juvenile behavioral disorders such as ADHD, autism, and/or schizophrenia. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kigar, Stacey L.] Univ Wisconsin, Mol & Cellular Pharmacol Program, Madison, WI 53706 USA. [Chang, Liza; Auger, Anthony P.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Auger, Anthony P.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. RP Auger, AP (reprint author), 1202 W,Johnson St, Madison, WI 53706 USA. EM apauger@wisc.edu FU NIH [T32 GM008688]; NSF [IOS-112207] FX This work supported by NIH #T32 GM008688 to S.L.K. and NSF IOS-112207 to A.P.A. 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Immun. PD MAY PY 2015 VL 46 BP 60 EP 69 DI 10.1016/j.bbi.2015.02.018 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CH0ZO UT WOS:000353751100009 PM 25728234 ER PT J AU Wu, WL Adams, CE Stevens, KE Chow, KH Freedman, R Patterson, PH AF Wu, Wei-Li Adams, Catherine E. Stevens, Karen E. Chow, Ke-Huan Freedman, Robert Patterson, Paul H. TI The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Maternal immune activation (MIA); Maternal infection; Poly(I:C); Nicotinic acetylcholine receptor alpha 7 subunit (alpha 7AChR, CHRNA7, Chrna7); Choline supplementation; Interleukin-6 (IL-6); Schizophrenia; Autism ID FETAL-BRAIN-DEVELOPMENT; CHOLINE SUPPLEMENTATION; GENE-EXPRESSION; ADULT PSYCHOPATHOLOGY; C57BL/6 SUBSTRAINS; SENSORY INHIBITION; ANIMAL-MODELS; MOUSE; SCHIZOPHRENIA; AUTISM AB Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (alpha 7nAChR) associated with schizophrenia in clinical studies,and rodent models. This study investigates the role of alpha 7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective alpha 7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal-placental-fetal axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (Il6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of Il6 in Chrna7 mutant mice. We found that the basal level of Il6 was higher in Chrna7 mutant fetal brain, which suggests that alpha 7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7(+/-) offspring. The Chrna7(+/-) offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that alpha 7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wu, Wei-Li; Chow, Ke-Huan; Patterson, Paul H.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Adams, Catherine E.] Denver VA Med Ctr, Denver, CO 80220 USA. [Adams, Catherine E.; Stevens, Karen E.; Freedman, Robert] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Wu, WL (reprint author), MC 156-29,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM wlwu@caltech.edu FU NIH Conte Center Award, United States [NIH 5P50MH086383-04]; Autism Speaks, United States [7670]; National Science Council, Taiwan [NSC 101-2917-I-564-039] FX We acknowledge Laura Rodriguez for administrative assistance; Jan Ko, Elaine Y. Hsiao and Natalia Malkova for technical assistance; Lorena C. Sandoval, Kwan F. Lee and Jaime Rodriguez for caring for the animals. This work was supported by NIH Conte Center Award, United States (to P.H.P.; NIH 5P50MH086383-04), Autism Speaks, United States (to P.H.P; #7670), and postdoctoral fellowship from National Science Council, Taiwan (to W.-L.W.; NSC 101-2917-I-564-039). 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Immun. PD MAY PY 2015 VL 46 BP 192 EP 202 DI 10.1016/j.bbi.2015.02.005 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CH0ZO UT WOS:000353751100023 PM 25683697 ER PT J AU Zerbo, O Leong, A Barcellos, L Bernal, P Fireman, B Croen, LA AF Zerbo, Ousseny Leong, Albin Barcellos, Lisa Bernal, Pilar Fireman, Bruce Croen, Lisa A. TI Immune mediated conditions in autism spectrum disorders SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Autism spectrum disorder; Allergies; Autoimmune disease; Asthma ID EARLY-CHILDHOOD AUTISM; AUTOIMMUNE-DISEASES; CHILDREN; BRAIN; PREVALENCE; PSORIASIS; AUTOANTIBODIES; IMMUNOGLOBULIN; HEALTH; ASTHMA AB We conducted a case-control study among members of Kaiser Permanente Northern California (KPNC) born between 1980 and 2003 to determine the prevalence of immune-mediated conditions in individuals with autism, investigate whether these conditions occur more often than expected, and explore the timing of onset relative to autism diagnosis. Cases were children and young adults with at least two autism diagnoses recorded in outpatient records (n = 5565). Controls were children without autism randomly sampled at a ratio of 5 to I, matched to cases on birth year, sex, and length of KPNC membership (n = 27,825). The main outcomes - asthma, allergies, and autoimmune diseases - were identified from KPNC inpatient and outpatient databases. Chi-square tests were used to evaluate case-control differences. Allergies and autoimmune diseases were diagnosed significantly more often among children with autism than among controls (allergy: 20.6% vs. 17.7%, Crude odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.13-1.31; autoimmune disease: 1% vs. 0.76%, OR = 1.36, 95% CI 1.01-1.83), and asthma was diagnosed significantly less often (13.7% vs. 15.9%; OR = 0.83, 95% CI 0.76-0.90). Psoriasis occurred more than twice as often in cases than in controls (0.34% vs. 0.15%; OR = 2.35, 95% CI 1.36-4.08). Our results support previous observations that children with autism have elevated prevalence of specific immune-related comorbidities. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zerbo, Ousseny; Fireman, Bruce; Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Leong, Albin] Kaiser Permanente No Calif, Roseville Med Ctr, Oakland, CA 94612 USA. [Barcellos, Lisa] Univ Calif Berkeley, Sch Publ Hlth, Genet Epidemiol & Genom Lab, Div Epidemiol, Berkeley, CA 94720 USA. [Bernal, Pilar] Kaiser Permanente No Calif, San Jose Med Ctr, Oakland, CA 94612 USA. RP Zerbo, O (reprint author), Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. EM ousseny.x.zerbo@kp.org FU Kaiser Foundation Research Institute; National Institute of Environmental Health Sciences [3R01ES016669] FX The work was funded in part by the Kaiser Foundation Research Institute and Grant 3R01ES016669 from National Institute of Environmental Health Sciences. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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PD MAY PY 2015 VL 46 BP 232 EP 236 DI 10.1016/j.bbi.2015.02.001 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CH0ZO UT WOS:000353751100027 PM 25681541 ER PT J AU Koch, SV Larsen, JT Mouridsen, SE Bentz, M Petersen, L Bulik, C Mortensen, PB Plessen, KJ AF Koch, Susanne V. Larsen, Janne T. Mouridsen, Svend E. Bentz, Mette Petersen, Liselotte Bulik, Cynthia Mortensen, Preben B. Plessen, Kerstin J. TI Autism spectrum disorder in individuals with anorexia nervosa and in their first- and second-degree relatives: Danish nationwide register-based cohort-study SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR PSYCHIATRIC-DISORDERS; EATING-DISORDERS; RISK-FACTORS; GENDER-DIFFERENCES; BIPOLAR DISORDER; TRAITS; ONSET; SCHIZOPHRENIA; FAMILY; DEPRESSION AB Background Clinical and population-based studies report increased prevalence of autism spectrum disorders (ASD) in individuals with anorexia nervosa and in their relatives. No nationwide study has yet been published on co-occurrence of these disorders. Aims To investigate comorbidity of ASD in individuals with anorexia nervosa, and aggregation of ASD and anorexia nervosa in their relatives. Method In Danish registers we identified all individuals born in 1981-2008, their parents, and full and half siblings, and linked them to data on hospital admissions for psychiatric disorders. Results Risk of comorbidity of ASD in probands with anorexia nervosa and aggregation of ASD in families of anorexia nervosa probands were increased. However, the risk of comorbid and familial ASD did not differ significantly from comorbid and familial major depression or any psychiatric disorder in anorexia nervosa probands. Conclusions We confirm aggregation of ASD in probands with anorexia nervosa and in their relatives; however, the relationship between anorexia nervosa and ASD appears to be nonspecific. (C) The Royal College of Psychiatrists 2015. C1 [Koch, Susanne V.; Plessen, Kerstin J.] Univ Copenhagen, Mental Hlth Ctr Child & Adolescent Psychiat, Copenhagen Reg, DK-2100 Copenhagen, Denmark. [Koch, Susanne V.; Plessen, Kerstin J.] Univ Copenhagen, Inst Clin Med, Fac Hlth Sci, DK-2100 Copenhagen, Denmark. [Larsen, Janne T.; Petersen, Liselotte; Mortensen, Preben B.] Univ Aarhus, Natl Ctr Register Based Res, Sch Business & Social Sci, Aarhus, Denmark. [Larsen, Janne T.; Mortensen, Preben B.] Aarhus Univ, Lundbeck Fdn Initiat Integrat Psychiat Res, iPsych, Dept Biomed,Fac Hlth, DK-8000 Aarhus C, Denmark. [Mouridsen, Svend E.; Bentz, Mette] Mental Hlth Ctr Child & Adolescent Psychiat, Copenhagen Reg, Copenhagen, Denmark. [Petersen, Liselotte] Aarhus Univ, Fac Hlth, Dept Biomed, iPsych, DK-8000 Aarhus C, Denmark. [Petersen, Liselotte] Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark. [Bulik, Cynthia] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. 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J. Psychiatry PD MAY PY 2015 VL 206 IS 5 BP 401 EP 407 DI 10.1192/bjp.bp.114.153221 PG 7 WC Psychiatry SC Psychiatry GA CH6PA UT WOS:000354157300008 PM 25657359 ER PT J AU Staal, WG Langen, M van Dijk, S Mensen, VT Durston, S AF Staal, Wouter G. Langen, Marieke van Dijk, Sarai Mensen, Vincent T. Durston, Sarah TI DRD3 gene and striatum in autism spectrum disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID REPETITIVE BEHAVIOR; SYMPTOMS AB A single-nucleotide polymorphism (SNP) of the DRD3 gene (rs167771) was recently associated with autism spectrum disorders (ASD). Different polymorphisms of rs167771 corresponded to varying degrees of stereotyped behaviour. As DRD3 receptors are relatively overexpressed in the striatum, we investigated whether striatal volume was related to these polymorphisms in autism. We assessed volumes of caudate nucleus and putamen in 86 participants with ASD (mean age 15.3 years). 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Preclinical models with strong endophenotypes relevant to cognitive dysfunctions offer a valuable resource for therapeutic development. However, improved assays to test higher order cognition are needed. We employed touchscreen technology to design a complex transitive inference (TI) assay that requires cognitive flexibility and relational learning. C57BL/6J (B6) mice with good cognitive skills and BTBR T +tf/J (BTBR), a model of ASD with cognitive deficits, were evaluated in simple and complex touchscreen assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR displayed deficits on components of TI, when 4 stimuli pairs were interspersed, which required flexible integrated knowledge. BTBR displayed impairment on the A > E inference, analogous to the A > E deficit in ASD. B6 and BTBR mice both reached criterion on the B > D comparison, unlike the B > D impairment in schizophrenia. 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In the LgDel mouse, optimal acquisition, execution, and reversal of a visually guided discrimination task, comparable to executive function tasks in primates including humans, are compromised; however, there is significant individual variation in degree of impairment. The task relies critically on the integrity of circuits in medial anterior frontal cortical regions. Accordingly, we analyzed neuronal changes that reflect previously defined 22q11DSrelated alterations of cortical development in the medial anterior frontal cortex of the behaviorally characterized LgDel mice. Interneuron placement, synapse distribution, and projection neuron frequency are altered in this region. The magnitude of one of these changes, layer 2/ 3 projection neuron frequency, is a robust predictor of behavioral performance: it is substantially and selectively lower in animals with the most significant behavioral deficits. These results parallel correlations of volume reduction and altered connectivity in comparable cortical regions with diminished executive function in 22q11DS patients. Apparently, 22q11 deletion alters behaviorally relevant circuits in a distinct cortical region that are essential for cognitive function. C1 [Meechan, D. W.; Fralish, M. S.; Maynard, T. M.; LaMantia, A. -S.] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. [Rutz, H. L. H.; Rothblat, L. A.] George Washington Univ, Dept Psychol, Washington, DC 20037 USA. [Meechan, D. W.; Rutz, H. L. H.; Fralish, M. S.; Maynard, T. M.; Rothblat, L. A.; LaMantia, A. -S.] George Washington Univ, GW Inst Neurosci, Washington, DC 20037 USA. RP LaMantia, AS (reprint author), George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. EM lamantia@gwu.edu FU National Institutes of Health [R01 HD042182] FX This work was supported by the National Institutes of Health (R01 HD042182; A.-S.L.). 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TI Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates SO CORTEX LA English DT Article DE Autism; MRI; DTI; Spectroscopy; Multimodal neuroimaging; Classification ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE-SPECTROSCOPY; CORTICAL THICKNESS ANALYSIS; HIGH-FUNCTIONING AUTISM; SURFACE-BASED ANALYSIS; AGE 2 YEARS; N-ACETYLASPARTATE; IN-VIVO; MINICOLUMNAR PATHOLOGY; GEOMETRICALLY ACCURATE AB Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multi-modal imaging to better inform on the neural characteristics most relevant to the disorder. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Libero, Lauren E.; DeRamus, Thomas P.; Kana, Rajesh K.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Lahti, Adrienne C.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Deshpande, Gopikrishna] Auburn Univ, Dept Elect & Comp Engn, MRI Res Ctr, Auburn, AL 36849 USA. [Deshpande, Gopikrishna] Auburn Univ, Dept Psychol, Auburn, AL 36849 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 College of Arts and Sciences Interdisciplinary Innovation Award FX This study was funded by the UAB College of Arts and Sciences Interdisciplinary Innovation Award to RK. The authors would also like to thank Dr. Meredith Reid and David White for their assistance with the 1H-MRS aspect of this project. The authors would also like to thank Dr. Jason Yeatman, Dr. Franco Pestilli, Dr. Brian Wendell, and the Stanford Vision and Imaging Science and Technology Laboratory for providing access to the mrDiffusion and AFQ software, and their assistance with these resources. 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Jones, Emily J. H. Gliga, Teodora TI Brain adaptation and alternative developmental trajectories SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CRITICAL PERIOD PLASTICITY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; DIFFERENTIAL SUSCEPTIBILITY; VISUAL-CORTEX; FRAGILE-X; NEURODEVELOPMENTAL DISORDERS; BIOLOGICAL SENSITIVITY; HOMEOSTATIC PLASTICITY; LANGUAGE-ACQUISITION AB Resilience and adaptation in the face of early genetic or environmental risk has become a major interest in child psychiatry over recent years. However, we still remain far from an understanding of how developing human brains as a whole adapt to the diffuse and widespread atypical synaptic function that may be characteristic of some common developmental disorders. The first part of this paper discusses four types of whole-brain adaptation in the face of early risk: redundancy, reorganization, niche construction, and adjustment of developmental rate. 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PD MAY PY 2015 VL 27 IS 2 SI SI BP 425 EP 442 DI 10.1017/S0954579415000073 PG 18 WC Psychology, Developmental SC Psychology GA CH5WR UT WOS:000354107000007 PM 25997763 ER PT J AU Gandin, I Faletra, F Faletra, F Carella, M Pecile, V Ferrero, GB Biamino, E Palumbo, P Palumbo, O Bosco, P Romano, C Belcaro, C Vozzi, D d'Adamo, AP AF Gandin, Ilaria Faletra, Flavio Faletra, Francesca Carella, Massimo Pecile, Vanna Ferrero, Giovanni B. Biamino, Elisa Palumbo, Pietro Palumbo, Orazio Bosco, Paolo Romano, Corrado Belcaro, Chiara Vozzi, Diego d'Adamo, Adamo P. TI Excess of runs of homozygosity is associated with severe cognitive impairment in intellectual disability SO GENETICS IN MEDICINE LA English DT Article DE inbreeding; intellectual disability; runs of homozygosity ID MENTAL-RETARDATION; SEQUENCING REVEALS; DISORDERS AB Purpose: The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees. Methods: We investigated (i) the runs of homozygosity distribution between syndromic and nonsyndromic ID (ii) the effect of runs of homozygosity on the ID degree, using the intelligence quotient score. Results: Our data revealed no significant differences in the first analysis; instead we detected significantly larger runs of homozygosity stretches in severe ID compared to nonsevere ID cases (P = 0.007), together with an increase of the percentage of genome covered by runs of homozygosity (P = 0.03). Conclusion: In accord with the recent findings regarding autism and other neurological disorders, this study reveals the important role of autosomal recessive variants in intellectual disability. The amount of homozygosity seems to modulate the degree of cognitive impairment despite the intellectual disability cause. C1 [Gandin, Ilaria; Belcaro, Chiara; d'Adamo, Adamo P.] Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy. [Faletra, Flavio; Faletra, Francesca; Pecile, Vanna; Vozzi, Diego; d'Adamo, Adamo P.] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Carella, Massimo; Palumbo, Pietro; Palumbo, Orazio] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, San Giovanni Rotondo, Italy. [Ferrero, Giovanni B.; Biamino, Elisa] Univ Turin, Dept Pediat, I-10124 Turin, Italy. [Bosco, Paolo] Oasi Inst Res Mental Retardat & Brain Aging IRCCS, Troina, Italy. [Romano, Corrado] IRCCS Assoc Oasi Maria Santissima, Unit Pediat & Med Genet, Troina, Italy. RP d'Adamo, AP (reprint author), Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy. EM adadamo@units.it FU [33/2011] FX The authors thank Stefania Cappellani, Lisa Cleva, and Anna Morgan. This study was made possible by the financial support of the Research Project n.33/2011 "identification of new genes involved in intellectual disability." 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TI Effects of a Professional Development Package to Prepare Special Education Paraprofessionals to Implement Evidence-Based Practice SO JOURNAL OF SPECIAL EDUCATION LA English DT Article DE professional development; paraprofessionals; video modeling; coaching; treatment fidelity ID AUTISM SPECTRUM DISORDERS; TIME-DELAY; STUDENTS; DISABILITIES; COMMUNICATION; PARAEDUCATORS; STRATEGIES; SETTINGS; SCIENCE AB Although paraprofessionals have become an increasingly integral part of special education services, most paraprofessionals lack training in evidence-based instructional strategies. We used a randomized contolled experimental design to examine the efficacy of a professional development training package and its individual components to equip 25 paraprofessionals to implement constant time delay. The effect of the training package on implementation fidelity was statistically significant and large in magnitude (d = 2.67; p < .001). Video modeling and coaching components were effective, although the effect of coaching alone (d = 2.23; p < .01) was larger than video modeling alone (d = .55; p = .18). Recommendations for further refining effective professional development opportunities for special education paraprofessionals are offered along with discussion of future research needs. C1 [Brock, Matthew E.; Carter, Erik W.] Vanderbilt Univ, Nashville, TN 37203 USA. RP Brock, ME (reprint author), Vanderbilt Univ, Dept Special Educ, PMB 228, Nashville, TN 37203 USA. EM matthew.e.brock@vanderbilt.edu FU Tennessee Department of Education to Vanderbilt University (CFDA) [84.027A] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Partial support for this project was provided by a grant from the Tennessee Department of Education to Vanderbilt University (CFDA No. 84.027A). 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PD MAY PY 2015 VL 49 IS 1 BP 39 EP 51 DI 10.1177/0022466913501882 PG 13 WC Education, Special SC Education & Educational Research GA CH4GB UT WOS:000353990800004 ER PT J AU Balakas, K Gallaher, CS Tilley, C AF Balakas, Karen Gallaher, Carol S. Tilley, Carra TI Optimizing Perioperative Care for CHILDREN AND ADOLESCENTS with Challenging Behaviors SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Article DE Adaptation; Children; Developmental disabilities; Perioperative ID AUTISM SPECTRUM DISORDERS; NEEDS; SURGERY AB Pediatric perioperative nurses care for a wide variety of children and adolescents, some of whom have special developmental or behavioral needs. Providing care for this vulnerable population can be challenging because they may not express their level of pain or anxiety through behaviors commonly observed in typically developing children. This quality improvement project was conducted. to enhance perioperative care delivered to children with challenging behaviors and to their families. A screening tool to individualize the plan of care was developed to identify specific behaviors, triggers, and communication patterns of these children prior to hospitalization. Interventions were identified to address these behaviors that could be used by nurses, child life specialists, and occupational therapists. Partnering with parents and other members of the interprofessional healthcare team has resulted in best practice care planning for these children, ensuring a much more successful perioperative experience for patients and families. Findings from parent surveys demonstrate that by using the tool, nurses and other team members are able to minimize stressors and implement interventions specific to the child. As a result, the adaptive care planning tool has expanded beyond the perioperative area and is now being used by direct care nurses, support staff, nurse practitioners, and physicians across the organization. C1 [Balakas, Karen] St Louis Childrens Hosp, St Louis, MO 63178 USA. [Gallaher, Carol S.; Tilley, Carra] St Louis Childrens Hosp, Perioperat Serv, St Louis, MO 63178 USA. RP Balakas, K (reprint author), St Louis Childrens Hosp, St Louis, MO 63178 USA. 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J. Matern.-Child Nurs. PD MAY-JUN PY 2015 VL 40 IS 3 BP 153 EP 159 DI 10.1097/NMC.0000000000000124 PG 7 WC Nursing SC Nursing GA CH6PO UT WOS:000354158700005 PM 25594693 ER PT J AU Suzuki, AM Griesi-Oliveira, K Machado, CDF Vadasz, E Zachi, EC Passos-Bueno, MR Sertie, AL AF Suzuki, A. M. Griesi-Oliveira, K. De Oliveira Freitas Machado, C. Vadasz, E. Zachi, E. C. Passos-Bueno, M. R. Sertie, A. L. TI Altered mTORC1 signaling in multipotent stem cells from nearly 25% of patients with nonsyndromic autism spectrum disorders SO MOLECULAR PSYCHIATRY LA English DT Letter C1 [Suzuki, A. M.; Griesi-Oliveira, K.; Zachi, E. C.; Passos-Bueno, M. R.] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisa Genoma Humano & Celulas Tronco, Sao Paulo, Brazil. [Griesi-Oliveira, K.; De Oliveira Freitas Machado, C.; Sertie, A. L.] Hosp lsraelita Albert Einstein, Ctr Pesquisa Expt, Sao Paulo, Brazil. [Vadasz, E.] Univ Sao Paulo, Inst Psiquiatria, Hosp Clin, Fac Med, Sao Paulo, Brazil. 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Psychiatr. PD MAY PY 2015 VL 20 IS 5 BP 550 EP 552 DI 10.1038/mp.2014.175 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CH0JS UT WOS:000353706400003 ER PT J AU Bacon, C Schneider, M Le Magueresse, C Froehlich, H Sticht, C Gluch, C Monyer, H Rappold, GA AF Bacon, C. Schneider, M. Le Magueresse, C. Froehlich, H. Sticht, C. Gluch, C. Monyer, H. Rappold, G. A. TI Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour SO MOLECULAR PSYCHIATRY LA English DT Article ID ESSENTIAL TRANSCRIPTIONAL REGULATOR; DE-NOVO MUTATIONS; INTELLECTUAL DISABILITY; RECOGNITION MEMORY; LANGUAGE DISORDER; SPECTRUM DISORDER; MICE; DEFICITS; SPEECH; ABNORMALITIES AB Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-) mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance. C1 [Bacon, C.; Froehlich, H.; Rappold, G. A.] Heidelberg Univ, Fac Med, Dept Human Mol Genet, D-69120 Heidelberg, Germany. [Bacon, C.; Le Magueresse, C.; Froehlich, H.; Monyer, H.; Rappold, G. A.] Heidelberg Univ, Interdisciplinary Ctr Neurosci IZN, D-69120 Heidelberg, Germany. [Schneider, M.; Gluch, C.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol,Res Grp Dev Neuropsychopharm, D-69120 Heidelberg, Germany. [Le Magueresse, C.; Monyer, H.] Heidelberg Univ, Fac Med, Dept Clin Neurobiol, D-69120 Heidelberg, Germany. [Le Magueresse, C.; Monyer, H.] German Canc Res Ctr, Heidelberg, Germany. [Le Magueresse, C.] Univ Paris 06, INSERM, UMR S 839, Paris, France. [Sticht, C.] Heidelberg Univ, Med Res Ctr, Mannheim, Germany. RP Rappold, GA (reprint author), Heidelberg Univ, Dept Human Mol Genet, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. EM gudrun.rappold@med.uni-heidelberg.de FU Deutsche Forschungsgemeinschaft [Ra 380/15-1] FX We thank Professor Gunther Schutz for for providing the Cre deleter mice and Dr Phil Tucker for the floxed Foxp1 mice. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Ra 380/15-1). Gudrun A. Rappold is a member of the CellNetworks Cluster of Excellence. 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PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2015 VL 20 IS 5 BP 640 EP 646 DI 10.1038/mp.2014.77 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CH0JS UT WOS:000353706400015 PM 25092245 ER PT J AU Lugnegard, T Hallerback, MU Gillberg, C AF Lugnegard, Tove Hallerback, Maria Unenge Gillberg, Christopher TI Asperger syndrome and schizophrenia: Overlap of self-reported autistic traits using the Autism-spectrum Quotient (AQ) SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Article DE Asperger syndrome; Autism spectrum; Autism-spectrum quotient; Autistic traits; Schizophrenia ID NEURODEVELOPMENTAL HYPOTHESIS; PERSONALITY-TRAITS; GENERAL-POPULATION; DISORDERS; ADULTS; PHENOTYPE; EPIDEMIOLOGY; ASSOCIATION; EXPERIENCES; SCHIZOTYPY AB Background: In clinical practice, the differential diagnosis of Asperger syndrome (AS) versus schizophrenia can be a challenge. Some self-report instruments-such as the Autism-spectrum Quotient (AQ)-have been portrayed as proxies for the diagnosis of AS. However, it has not been demonstrated to what extent autistic traits-as measured by the AQ-separate AS from schizophrenia. Aim: To examine the AS-schizophrenia discriminating ability of the AQ. Method: The AQ is a 50-item self-administered questionnaire (with score range 0-50) for measuring "autistic traits" in adults. Here, it was completed by 136 individuals: 36 with schizophrenic psychosis, 51 with AS and 49 non-clinical comparison cases. A receiver operating characteristic (ROC) analysis for the total AQ score was performed to examine the discriminating power of the instrument. Result: Both individuals with schizophrenia and individuals with AS scored significantly higher on AQ than the non-clinical group. The mean total AQ score (+/- standard deviation) of the AS group (26.7 +/- 8.9; range 9-44) was significantly higher than that of the schizophrenia group (22.7 +/- 6.2; range 10-35) (P = 0.041). However, when using the full Likert scale for scoring, the difference did not reach significance. In the ROC analysis of total AQ scores for AS versus schizophrenia, the area under the curve (AUC) was 0.65 (P = 0.02). Conclusion: Although mean AQ scores separated AS and schizophrenia at a group comparison level, significant overlap of AQ scores across the two diagnostic groups clearly reduces the discriminating power of the AQ in the separation of schizophrenia from AS. C1 [Lugnegard, Tove; Hallerback, Maria Unenge] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden. [Lugnegard, Tove] Cent Hosp Karlstad, Dept Psychiat, S-65185 Karlstad, Sweden. [Hallerback, Maria Unenge] Cent Hosp Karlstad, Dept Child & Adolescent Psychiat, S-65185 Karlstad, Sweden. [Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Child & Adolescent Psychiat, Gothenburg, Sweden. RP Lugnegard, T (reprint author), Cent Hosp Karlstad, Dept Psychiat, S-65185 Karlstad, Sweden. 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CR Hacking I., 2015, PHILOS ISSUES PSYCHI NR 1 TC 0 Z9 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0952-8229 J9 PSYCHOLOGIST JI Psychologist PD MAY PY 2015 VL 28 IS 5 BP 343 EP 343 PG 1 WC Psychology, Multidisciplinary SC Psychology GA CH3MT UT WOS:000353935500009 ER PT J AU Weisberg, DS AF Weisberg, Deena Skolnick TI Pretend play SO WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE LA English DT Review ID OF-MIND DEVELOPMENT; MENTAL TIME-TRAVEL; YOUNG-CHILDREN; SYMBOLIC PLAY; INDIVIDUAL-DIFFERENCES; REALITY CONFUSIONS; OBJECT PLAY; AUTISM; PRESCHOOLERS; LANGUAGE AB Pretend play is a form of playful behavior that involves nonliteral action. Although on the surface this activity appears to be merely for fun, recent research has discovered that children's pretend play has connections to important cognitive and social skills, such as symbolic thinking, theory of mind, and counterfactual reasoning. The current article first defines pretend play and then reviews the arguments and evidence for these three connections. Pretend play has a nonliteral correspondence to reality, hence pretending may provide children with practice with navigating symbolic relationships, which may strengthen their language skills. Pretend play and theory of mind reasoning share a focus on others' mental states in order to correctly interpret their behavior, hence pretending and theory of mind may be mutually supportive in development. Pretend play and counterfactual reasoning both involve representing nonreal states of affairs, hence pretending may facilitate children's counterfactual abilities. These connections make pretend play an important phenomenon in cognitive science: Studying children's pretend play can provide insight into these other abilities and their developmental trajectories, and thereby into human cognitive architecture and its development. WIREs Cogn Sci 2015, 6:249-261. doi: 10.1002/wcs.1341 For further resources related to this article, please visit the . Conflict of interest: The author has declared no conflicts of interest for this article. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Weisberg, DS (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. 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PD MAY-JUN PY 2015 VL 6 IS 3 BP 249 EP 261 DI 10.1002/wcs.1341 PG 13 WC Psychology, Experimental SC Psychology GA CH2WP UT WOS:000353886000005 ER PT J AU Feldman, HM Blum, NJ Gahman, AE Shults, J AF Feldman, Heidi M. Blum, Nathan J. Gahman, Amy E. Shults, Justine CA DBPNet Steering Comm TI Diagnosis of Attention-deficit/Hyperactivity Disorder by Developmental Pediatricians in Academic Centers: A DBPNet Study SO ACADEMIC PEDIATRICS LA English DT Article DE attention-deficit/hyperactivity disorder; comorbidity; DBPNet; developmental-behavioral pediatrics; diagnosis; stimulants ID CLINICAL-PRACTICE GUIDELINE; DEFICIT HYPERACTIVITY DISORDER; PRIMARY-CARE; US CHILDREN; ADHD AB OBJECTIVE: To describe the developmental-behavioral pediatricians (DBPs), patients, and clinical practices used in the diagnostic assessments of attention-deficit/hyperactivity disorder (ADHD) within all 12 academic medical centers comprising Developmental-Behavioral Pediatrics Research Network (DBPNet). METHODS: Between December 2011 and June 2012, all DBPs who evaluated children with ADHD or autism spectrum disorders were asked to complete a diagnostic encounter survey form for up to 10 consecutive new cases that resulted in the diagnosis of ADHD or autism spectrum disorder. Fifty-two clinicians returned one or more forms for children diagnosed with ADHD (n = 211). RESULTS: DBPs were generally experienced full-time academics. Children were 76.3% male, 62.3% white, 24.5% African American, and 20.7% Hispanic. Mean child age was 8.0 + 3.1 years. DBPs reviewed parent ratings of behavior in 84.4% and teacher ratings in 69.2% of cases. They reviewed or completed at least one developmental assessment in 79.2% of cases: intelligence (60.2%), academic (57.8%), fine motor or visual motor (39.3%), speech/language (34.6%), or adaptive skills (28.9%). They made the diagnosis of coexisting conditions in 82.7% of cases, including learning disabilities (31.8%), speech/language disorders (31.8%), anxiety (14.2%), externalizing disorders (10.9%), and sleep disorders (9.5%). Among 146 children not medicated before the visit, stimulant medications were initiated in 15 children (10.2%). CONCLUSIONS: Within DBPNet, DBPs were highly likely to complete comprehensive assessments of ADHD that went beyond the requirements of primary care practice guidelines. They typically identified coexisting developmental and learning conditions. They did. not typically prescribe medication at the end of diagnostic encounters. C1 [Feldman, Heidi M.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. [Blum, Nathan J.; Gahman, Amy E.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Blum, Nathan J.; Shults, Justine] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Feldman, HM (reprint author), Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM hfeldman@stanford.edu FU Maternal Child Health Bureau (Combating Autism Act), Health Resources and Services, Department of Health and Human Services) [UA3MC20218] FX DBPNet is supported by cooperative agreement UA3MC20218 from the Maternal Child Health Bureau (Combating Autism Act of 2006), Health Resources and Services, Department of Health and Human Services (project director, Nathan J. Blum, MD). The DBPNet Steering Committee would like to thank the following individuals, who also contributed to the development of the study: Daniel Coury, MD; Christopher Forrest, MD, PhD; Connie Kasai, PhD; and Amy Kratchman, BS. In addition, we would like to thank David Schonfeld, MD who helped initiate this study at Cincinnati Children's Hospital Medical Center and all of the physicians at DBPNet sites who voluntarily completed the encounter forms for this study. 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Pediatr. PD MAY-JUN PY 2015 VL 15 IS 3 BP 282 EP 288 PG 7 WC Pediatrics SC Pediatrics GA CH2MQ UT WOS:000353859700006 PM 25441653 ER PT J AU Blanken, LME Mous, SE Ghassabian, A Muetzel, RL Schoemaker, NK El Marroun, H van der Lugt, A Jaddoe, VWV Hofman, A Verhulst, FC Tiemeier, H White, T AF Blanken, Laura M. E. Mous, Sabine E. Ghassabian, Akhgar Muetzel, Ryan L. Schoemaker, Nikita K. El Marroun, Hanan van der Lugt, Aad Jaddoe, Vincent W. V. Hofman, Albert Verhulst, Frank C. Tiemeier, Henning White, Tonya TI Cortical Morphology in 6-to 10-Year Old Children With Autistic Traits: A Population-Based Neuroimaging Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUPERIOR TEMPORAL SULCUS; SURFACE-AREA; DIAGNOSTIC INTERVIEW; SPECTRUM DISORDERS; BRAIN; THICKNESS; GYRIFICATION; CHILDHOOD; TRAJECTORIES; NETWORK AB Objective: Recent evidence suggests that symptoms of social impairment in autism spectrum disorder (ASD) form a spectrum that extends into the general population. However, it is unclear whether the neuroanatomy of ASD also shows a similar continuum in the general population. Therefore, the goat of the present study was to investigate the relationship between cortical morphology and autistic traits along a continuum in a large population-based sample of young children. Method: The study included 717 children, aged 6-10 years, who are participants in the Generation R Study, a large population-based cohort. Autistic traits were measured using the Social Responsiveness Scale when the children were approximately 6 years old. High-resolution MRI was obtained, and morphological measures of the cortex, including cortical thickness and gyrification, were quantified brain-wide. Results: Children with more autistic traits showed widespread areas of decreased gyrification. After excluding children with the highest autistic traits and confirmed ASD, the association remained present in a large cluster involving the left hemisphere temporal and precuneus regions. Comparable, but nonsignificant effects when comparing a small sample of confirmed ASD case subjects with age- and gender-matched control subjects were observed. Conclusions: Differences in cortical morphology related to autistic traits along a continuum in a large population-based sample of school-aged children were found. Part of these differences remained after excluding the most severely affected children. These findings lend support to an extension of the neurobiology of autistic traits to the general population. C1 [White, Tonya] Erasmus Med Ctr Sophia, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands. Erasmus Med Ctr Sophia, Generat Study Grp R, Rotterdam, Netherlands. Leiden Univ, Ctr Child & Family Studies, Leiden, Netherlands. Erasmus MC, Dept Radiol, Rotterdam, Netherlands. Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. RP White, T (reprint author), Erasmus Med Ctr Sophia, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands. EM t.white@erasmusmc.nl FU FP7 grant Action FP-7 Health Innovation [602768]; ZonMw TOP [91211021]; Erasmus Medical Center-Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development (ZonMw); Netherlands Organization for Scientific Research; Ministry of Health, Welfare and Sport; GE Healthcare; Dutch Medical Research Council (ZonMW); European Union Research Support FP7 Program for Pediatric Conduct Disorder; Sophia Foundation for Scientific Research FX Supported by the FP7 grant Action FP-7 Health Innovation 2013 (number, 602768) (to Dr. Tiemeier) and by ZonMw TOP (project number, 91211021) (to Dr. White). The general design of the Generation R Study is supported by the Erasmus Medical Center-Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research, and the Ministry of Health, Welfare and Sport. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond.Dr. van der Lugt has received research grant support from and served on the speaker's bureau of GE Healthcare. Dr. Verhulst receives royalties from the Dutch version of the Achenbach System of Empirically Based Assessment. Dr. Tiemeier has received research grant support from the Dutch Medical Research Council (ZonMW), the European Union Research Support FP7 Program for Pediatric Conduct Disorder, and the Sophia Foundation for Scientific Research. All other authors report no financial relationships with commercial interests. 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J. Psychiat. PD MAY PY 2015 VL 172 IS 5 BP 479 EP 486 DI 10.1176/appi.ajp.2014.14040482 PG 8 WC Psychiatry SC Psychiatry GA CH2FM UT WOS:000353841100015 PM 25585034 ER PT J AU Cheng, W Rolls, ET Gu, HG Zhang, J Feng, JF AF Cheng, Wei Rolls, Edmund T. Gu, Huaguang Zhang, Jie Feng, Jianfeng TI Autism: reduced connectivity between cortical areas involved in face expression, theory of mind, and the sense of self SO BRAIN LA English DT Article DE Autistic spectrum disorder; behavioural neurology; neuropsychiatry imaging social cognition; temporal lobe ID SUPERIOR TEMPORAL SULCUS; SPECTRUM DISORDERS; FUNCTIONAL CONNECTIVITY; SOCIAL BRAIN; CORTEX; NEURONS; MONKEY; NETWORK; PARCELLATION; INFORMATION AB Whole-brain voxel-based unbiased resting state functional connectivity was analysed in 418 subjects with autism and 509 matched typically developing individuals. We identified a key system in the middle temporal gyrus/superior temporal sulcus region that has reduced cortical functional connectivity (and increased with the medial thalamus), which is implicated in face expression processing involved in social behaviour. This system has reduced functional connectivity with the ventromedial prefrontal cortex, which is implicated in emotion and social communication. The middle temporal gyrus system is also implicated in theory of mind processing. We also identified in autism a second key system in the precuneus/superior parietal lobule region with reduced functional connectivity, which is implicated in spatial functions including of oneself, and of the spatial environment. It is proposed that these two types of functionality, face expression-related, and of one's self and the environment, are important components of the computations involved in theory of mind, whether of oneself or of others, and that reduced connectivity within and between these regions may make a major contribution to the symptoms of autism. C1 [Cheng, Wei; Zhang, Jie; Feng, Jianfeng] Fudan Univ, Ctr Computat Syst Biol, Shanghai 200433, Peoples R China. [Rolls, Edmund T.; Feng, Jianfeng] Univ Warwick, Dept Comp Sci, Coventry CV4 7AL, W Midlands, England. [Rolls, Edmund T.] Oxford Ctr Computat Neurosci, Oxford, England. [Gu, Huaguang] Tongji Univ, Sch Aerosp Engn & Appl Mech, Shanghai 200092, Peoples R China. RP Feng, JF (reprint author), Univ Warwick, Dept Comp Sci, Coventry CV4 7AL, W Midlands, England. EM Jianfeng.Feng@warwick.ac.uk RI Gu, Huaguang/E-3562-2013; ahmed, Jamila/E-8653-2015 OI Gu, Huaguang/0000-0003-0815-1447; FU Royal Society Wolfson Research Merit Award; National Centre for Mathematics and Interdisciplinary Sciences (NCMIS) of the Chinese Academy of Sciences; Key Program of National Natural Science Foundation of China [91230201]; National High Technology Research and Development Program of China [2015AA020507]; National Natural Science Foundation of China [61271396, 11471081, 11101429]; National Science Foundation of China [NSFC 61104143, 61104224]; special Funds for Major State Basic Research Projects of China [2015CB856003] FX J.F. is a Royal Society Wolfson Research Merit Award holder. The research was partially supported by the National Centre for Mathematics and Interdisciplinary Sciences (NCMIS) of the Chinese Academy of Sciences and Key Program of National Natural Science Foundation of China (No. 91230201); and National High Technology Research and Development Program of China under grant No. 2015AA020507, by grants from the National Natural Science Foundation of China Grant 61271396, 11471081 and 11101429 to W.C. J.Z. is supported by National Science Foundation of China (NSFC 61104143 and 61104224), and special Funds for Major State Basic Research Projects of China (2015CB856003). 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Zetino, Manuel Garel, Keri-Lee A. Herbert, Martha R. Hamalainen, Matti S. Kenet, Tal TI Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale SO BRAIN LA English DT Article DE magnetoencephalography; coherence; biomarker; steady-state; vibrotactile; mu-rhythm; autism spectrum disorder ID SPACE SEPARATION METHOD; SURFACE-BASED ANALYSIS; TOP-DOWN MODULATION; SPECTRUM DISORDERS; BRAIN CONNECTIVITY; EVOKED-RESPONSES; CORTICAL SURFACE; EEG-DATA; COORDINATE SYSTEM; MU RHYTHM AB Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-a rhythm. In contrast, the mu-beta rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-beta was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism. C1 [Khan, Sheraz; Michmizos, Konstantinos; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Kenet, Tal] Harvard Univ, Sch Med, Dept Neurol, MGH, Boston, MA 02115 USA. [Khan, Sheraz; Michmizos, Konstantinos; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hamalainen, Matti S.; Kenet, Tal] MGH MIT Harvard, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. [Hamalainen, Matti S.] Harvard Univ, Sch Med, Dept Radiol, MGH, Boston, MA 02115 USA. [Hamalainen, Matti S.] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Espoo, Finland. RP Kenet, T (reprint author), Massachusetts Gen Hosp, 149 13th St CNY 2275, Charlestown, MA 02129 USA. EM tal@nmr.mgh.harvard.edu FU Nancy Lurie Marks Family Foundation; Autism Speaks; Simons Foundation [SFARI 239395]; National Institute of Child Health and Development [R01HD073254]; National Centre for Research Resources [P41EB015896]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; Cognitive Rhythms Collaborative: A Discovery Network [NFS 1042134] FX This work was supported by grants from the Nancy Lurie Marks Family Foundation (T.K., S.K.), Autism Speaks (T.K.), The Simons Foundation (SFARI 239395, T.K.), The National Institute of Child Health and Development (R01HD073254, T.K.), The National Centre for Research Resources (P41EB015896, M.S.H.), National Institute for Biomedical Imaging and Bioengineering (5R01EB009048, M.S.H.), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, M.S.H.). Article needs to be deposited in PMC. 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However, the molecular mechanisms underlying its role in ASD remain unclear. In the present study, a murine model with ASD-like phenotypes was induced by intra-medial amygdala injection of N-methyl-d-aspartate, and it was used to investigate the role of OXT in behaviour regulation. Behavioural tests were performed to verify the ASD-like phenotypes of N-methyl-d-aspartate-treated mice, and the results showed that mice with bilateral medial amygdala lesions presented significant behavioural deficits, including impaired learning and memory and increased anxiety and depression. We also observed a notably decreased level of OXT in both the plasma and the hypothalamus of medial amygdala-lesioned mice, and the extracellular signal-regulated kinase (ERK) was activated. Further studies demonstrated that the administration of OXT alleviated ASD-like symptoms and significantly inhibited phosphorylation of ERK; the inhibitory effect was similar to that of U0126, an ERK signalling inhibitor. In addition, OXT administration modulated the expression of downstream proteins of the ERK signalling pathway, such as cyclic adenosine monophosphate response element binding and c-fos. Taken together, our data indicate that OXT plays an important role in ameliorating behavioural deficits in an ASD-like mouse model, which was mediated by inhibiting the ERK signalling pathway and its downstream proteins. C1 [Wang, Yu; Zhao, Shanshan; Wu, Zhe; Feng, Yu; Zhao, Chuansheng; Zhang, Chaodong] China Med Univ, Affiliated Hosp 1, Dept Neurol, Shenyang 110001, Peoples R China. RP Zhang, CD (reprint author), China Med Univ, Affiliated Hosp 1, Dept Neurol, 155 North Nanjing St, Shenyang 110001, Peoples R China. EM cmu1hzhangchaodong@163.com RI ahmed, Jamila/E-8653-2015 FU National Natural Science Foundation of China [81371456] FX This study was supported by a grant from the National Natural Science Foundation of China (No.: 81371456). 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PD MAY PY 2015 VL 19 IS 3 BP 386 EP 387 DI 10.1016/j.ejpn.2015.01.009 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA CG9CM UT WOS:000353612000021 PM 25725507 ER PT J AU Davidovitch, M Levit-Binnun, N Golan, D Manning-Courtney, P AF Davidovitch, Michael Levit-Binnun, Nava Golan, Dafna Manning-Courtney, Patricia TI Late Diagnosis of Autism Spectrum Disorder After Initial Negative Assessment by a Multidisciplinary Team SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism; autism spectrum disorder; diagnosis; diagnostic evaluation; late diagnosis ID AGE; POPULATION; PREVALENCE AB Objective: Describe a cohort of children who received a diagnosis of autism spectrum disorder (ASD) after age 6 and after having undergone a comprehensive multidisciplinary assessment before the age of 6, through which they were not diagnosed with ASD. Methods: Extensive chart review of patients' electronic medical records comprised a representative population-based registry of patients seen during 2004 to 2011. The study focused only on the cohort of children who were diagnosed with ASD after the age of 6 but were not diagnosed with ASD at an earlier age. The charts were reviewed for the number of developmental assessments completed and the clinician's diagnostic impressions. The charts were also examined for documentation of ASD-suggestive features pulled directly from the text of the evaluators' reports. Results: A total of 221 patients (189 males) were diagnosed with ASD after age 6 although their initial comprehensive developmental evaluations before the age of 6 were negative for ASD. The study cohort underwent a total of 1028 developmental evaluations before the age of 6, with initial diagnostic impressions that included language deficits (70%), motor difficulties (67%), attention problems (46%), and cognitive difficulties (42%). Less than half of the cohort had ASD-suggesting features documented in their initial assessment. Conclusions: Subsequent late diagnosis of ASD after an initial ASD-negative comprehensive assessment is a common clinical experience. Reasons for this scenario may include evolving diagnosis as well as missed and overdiagnosed cases of ASD. C1 [Davidovitch, Michael] Maccabi Healthcare Serv, Div Med, Child Dev, IL-6812509 Tel Aviv, Israel. [Davidovitch, Michael; Levit-Binnun, Nava] Interdisciplinary Ctr IDC, Sch Psychol, Sagol Inst Appl Neurosci, Herzliyya, Israel. [Golan, Dafna] Maccabi Healthcare Serv, Hashfela & Jerusalem Dist, Child Dev, Jerusalem, Israel. 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Lord, Catherine TI Depressive and Anxiety Symptom Trajectories From School Age Through Young Adulthood in Samples With Autism Spectrum Disorder and Developmental Delay SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism spectrum disorder; depression; anxiety; growth curve; Child Behavior Checklist ID MENTAL-RETARDATION; INTELLECTUAL DISABILITY; PSYCHIATRIC COMORBIDITY; MALADAPTIVE BEHAVIORS; ASPERGER SYNDROME; ADOLESCENTS; CHILDREN; PSYCHOPATHOLOGY; PEOPLE; YOUTH AB Objective: The objectives of this study were to model growth in anxiety and depressive symptoms from late school age through young adulthood in individuals with autism spectrum disorder (ASD) and controls with developmental delay (DD), and to assess relationships among internalizing growth patterns, participant characteristics, baseline predictors, and distal outcomes. Method: Data were collected between ages 6 and 24 years in 165 participants (n = 109 with ASD; n = 56 with non-spectrum DD), most of whom received diagnostic evaluations in both childhood and early adulthood. Questionnaires were collected approximately every 3 to 6 months between ages 9 and 24 years. Parent-rated Child Behavior Checklist (CBCL), Adult Behavior Checklist (ABCL), and Developmental Behaviour Checklist anxiety-and depression-related subscale distributions were modeled with mixed-effects Poisson models, covarying diagnosis, age, verbal IQ (VIQ), gender, and significant 2- and 3-way interactions. Results: Anxiety was positively associated with VIQ, and controlling for VIQ, both anxiety and depressive symptoms were greater in ASD than non-spectrum participants. Female gender predicted greater increases over time in anxiety and depressive symptoms for both diagnostic groups. Lower maternal education was associated with increasing internalizing symptoms in a subset of less verbal individuals with ASD. In exploratory post hoc analyses, internalizing symptoms were associated with poorer emotional regulation in school age, and with lower life satisfaction and greater social difficulties in early adulthood. Conclusion: Findings support previous claims that individuals with ASD are at particular risk for affect- and anxiety-specific problems. Although symptom levels in females increase at a faster rate throughout adolescence, males with ASD appear to have elevated levels of depressive symptoms in school age that are maintained into young adulthood. C1 [Gotham, Katherine] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Brunwasser, Steven M.] Vanderbilt Univ, Kennedy Ctr, Nashville, TN 37235 USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Dev Brain, New York, NY USA. 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PD MAY PY 2015 VL 54 IS 5 BP 369 EP 376 DI 10.1016/j.jaac.2015.02.005 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CG9WE UT WOS:000353670000007 PM 25901773 ER PT J AU Valluy, J Bicker, S Aksoy-Aksel, A Lackinger, M Sumer, S Fiore, R Wust, T Seffer, D Metge, F Dieterich, C Wohr, M Schwarting, R Schratt, G AF Valluy, Jeremy Bicker, Silvia Aksoy-Aksel, Ayla Lackinger, Martin Sumer, Simon Fiore, Roberto Wuest, Tatjana Seffer, Dominik Metge, Franziska Dieterich, Christoph Woehr, Markus Schwarting, Rainer Schratt, Gerhard TI A coding-independent function of an alternative Ube3a transcript during neuronal development SO NATURE NEUROSCIENCE LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; ANGELMAN-SYNDROME; MESSENGER-RNAS; GENE UBE3A; NEUROPSYCHIATRIC DISORDERS; IN-VIVO; MICRORNAS; SYNAPSE; AUTISM; DENDRITOGENESIS AB The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent synapse development and plasticity. Ube3a mutations cause Angelman syndrome and have been associated with autism spectrum disorders (ASD). However, the biological significance of alternative Ube3a transcripts generated in mammalian neurons remains unknown. We report here that Ube3a1 RNA, a transcript that encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant dendrite growth and promotes spine maturation in rat hippocampal neurons. Surprisingly, Ube3a1 RNA function was independent of its coding sequence but instead required a unique 3' untranslated region and an intact microRNA pathway. Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134, suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA. Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo is abolished in mice lacking miR-134. Taken together, our results define a noncoding function of an alternative Ube3a transcript in dendritic protein synthesis, with potential implications for Angelman syndrome and ASD. C1 [Valluy, Jeremy; Bicker, Silvia; Aksoy-Aksel, Ayla; Lackinger, Martin; Sumer, Simon; Fiore, Roberto; Schratt, Gerhard] Univ Marburg, Inst Physiol Chem, Biochem Pharmacol Ctr Marburg, D-35032 Marburg, Germany. [Wuest, Tatjana] Heidelberg Univ, Interdisciplinary Ctr Neurosci, SFB Jr Grp 488, Heidelberg, Germany. [Seffer, Dominik; Woehr, Markus; Schwarting, Rainer] Univ Marburg, Behav Neurosci Expt & Biol Psychol, D-35032 Marburg, Germany. [Metge, Franziska; Dieterich, Christoph] Max Planck Inst Biol Ageing, Computat RNA Biol Lab, Cologne, Germany. RP Schratt, G (reprint author), Univ Marburg, Inst Physiol Chem, Biochem Pharmacol Ctr Marburg, D-35032 Marburg, Germany. EM schratt@staff.uni-marburg.de FU European Research Council; European Union FP7 ("EpimiRNA"); Deutsche Forschungsgemeinschaft (DFG) [SFB593, FOR2107:SCHR 1136/3-1]; Universitatsklinikum Giessen-Marburg; DFG [FOR2107, SCHW 559/14-1, WO 1732/4-1]; Von Behring-Rontgen-Foundation [62-0004] FX We acknowledge technical assistance of U. Beck, E. Becker, R. Gondrum, G. Jarosch, H. Kaiser and H. Rippberger. This work was funded by grants from the European Research Council (Starting Grant "Neuromir"), the European Union FP7 ("EpimiRNA"), the Deutsche Forschungsgemeinschaft (DFG) (SFB593, FOR2107:SCHR 1136/3-1) and the Universitatsklinikum Giessen-Marburg to G.S., the DFG (FOR2107) to R.S. (SCHW 559/14-1) and M.W. (WO 1732/4-1) and the Von Behring-Rontgen-Foundation (62-0004) to S.B. 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Neurosci. PD MAY PY 2015 VL 18 IS 5 BP 666 EP + DI 10.1038/nn.3996 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CG9LN UT WOS:000353636900013 PM 25867122 ER PT J AU Holmes, GL Tian, CJ Hernan, AE Flynn, S Camp, D Barry, J AF Holmes, Gregory L. Tian, Chengju Hernan, Amanda E. Flynn, Sean Camp, Devon Barry, Jeremy TI Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Epilepsy; Sociability; Power spectrum; Development; Coherence; Voltage correlations ID AUTISM SPECTRUM DISORDERS; LONG-TERM POTENTIATION; HIPPOCAMPAL-PREFRONTAL NETWORK; NEONATAL SEIZURES; TUBEROUS SCLEROSIS; RECURRENT SEIZURES; THETA-OSCILLATIONS; INBRED STRAINS; EEG COHERENCE; 1ST YEAR AB There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) days 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-P25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of Ea toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. (C) 2015 Elsevier Inc. All rights reserved. C1 [Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT 05405 USA. RP Holmes, GL (reprint author), 95 Carrigan Dr,Stafford 118, Burlington, VT 05405 USA. EM Gregory.holmes@uvm.edu FU National Institute of Health [NS074450, NS073083]; Emmory R. Shapses Research Fund; Michael J. Pietroniro Research Fund; NIH from the COBRE Program of the National Center for Research Resources [P30 RR032135]; National Institute of General Medical Sciences [P30 GM 103498] FX This study has beensupported by the National Institute of Health grants NS074450, NS074450 and NS073083, the Emmory R. Shapses Research Fund and Michael J. Pietroniro Research Fund to GLH and NIH grant number P30 RR032135 from the COBRE Program of the National Center for Research Resources and P30 GM 103498 from the National Institute of General Medical Sciences. 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Dis. PD MAY PY 2015 VL 77 BP 204 EP 219 DI 10.1016/j.nbd.2015.02.015 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CG9CO UT WOS:000353612200018 PM 25766676 ER PT J AU Lawson, RA Papadakis, AA Higginson, CI Barnett, JE Wills, MC Strang, JF Wallace, GL Kenworthy, L AF Lawson, Rachel A. Papadakis, Alison A. Higginson, Christopher I. Barnett, Jeffrey E. Wills, Meagan C. Strang, John F. Wallace, Gregory L. Kenworthy, Lauren TI Everyday Executive Function Impairments Predict Comorbid Psychopathology in Autism Spectrum and Attention Deficit Hyperactivity Disorders SO NEUROPSYCHOLOGY LA English DT Article DE autism; ADHD; executive function; aggression; anxiety/depression ID OBSESSIVE-COMPULSIVE DISORDER; DEFICIT/HYPERACTIVITY DISORDER; PERSEVERATIVE COGNITION; DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; ACADEMIC-ACHIEVEMENT; UNIPOLAR DEPRESSION; ASPERGER-SYNDROME; WORKING-MEMORY; CHILDREN AB Objective: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) both have psychiatric comorbidities and distinctive profiles of executive dysfunction. Although there is evidence that executive function (EF) plays a role in the expression of specific behaviors and psychiatric symptoms, it is not known whether specific EF deficits in ASD and ADHD may be pathways to comorbidities in the disorders. This study examines whether parent reported problems with flexibility in ASD and inhibition in ADHD mediate the disorders' associations with anxiety/depression and oppositional/ aggressive behavior, respectively. Method: Parent report data from the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL) were obtained for 125 children (70 ASD, 55 ADHD Hyperactive/Impulsive or Combined type) as part of a neuropsychological assessment. Diagnostic status, BRIEF Shift (shifting/flexibility) and Inhibit (behavioral inhibition) scale scores, and CBCL Anxious/Depressed (anxiety/depression) and Aggressive Behavior (oppositionality/aggression) scale scores were analyzed with a path analysis to investigate the relation of flexibility and inhibition to comorbid symptoms in children with ASD and ADHD. Results: In a path model with good fit ASD predicted greater inflexibility which predicted greater anxiety/depression, while ADHD predicted greater disinhibition that predicted greater aggression, consistent with our mediational hypotheses. Unexpectedly, the greater inflexibility associated with ASD also predicted greater aggression. Conclusions: Findings support the importance of everyday EF problems in ASD and ADHD as predictors of comorbid psychopathology and as crucial intervention targets for potential prevention and mitigation of comorbid symptoms. C1 [Lawson, Rachel A.; Papadakis, Alison A.; Higginson, Christopher I.; Barnett, Jeffrey E.] Loyola Univ Maryland, Dept Psychol, Baltimore, MD 21210 USA. [Wills, Meagan C.; Strang, John F.; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD USA. [Wallace, Gregory L.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC 20052 USA. RP Lawson, RA (reprint author), Loyola Univ Maryland, Dept Psychol, 4501 N Charles St, Baltimore, MD 21210 USA. EM rachel.lawson112@gmail.com FU Isadore and Bertha Gudelsky Foundation; Frederick and Elizabeth Singer Foundation FX LK receives financial compensation for use of the Behavior Rating Inventory of Executive Function (BRIEF). This research was supported by the Isadore and Bertha Gudelsky Foundation, and the Frederick and Elizabeth Singer Foundation. We thank the families of the participants and the diagnostic team that characterized the participants for their efforts over the years. 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Amestoy, Anouck Bouvard, Manuel P. Demany, Laurent TI A Late-Emerging Auditory Deficit in Autism SO NEUROPSYCHOLOGY LA English DT Article DE autism spectrum disorder; echoic memory; auditory development; periodicity detection ID SHORT-TERM-MEMORY; SPECTRUM DISORDERS; DEVELOPMENTAL TRAJECTORIES; PITCH DISCRIMINATION; TEMPORAL RESOLUTION; SIGNAL-DETECTION; ECHOIC MEMORY; TONE PITCH; CHILDREN; NOISE AB Objective: Individuals with autism spectrum disorders (ASD) show enhanced perceptual and memory abilities in the domain of pitch, but also perceptual deficits in other auditory domains. The present study investigated their skills with respect to "echoic memory," a form of short-term sensory memory intimately tied to auditory perception, using a developmental perspective. Method: We tested 23 high-functioning participants with ASD and 26 typically developing (TD) participants, distributed in two age groups (children vs. young adults; mean ages: similar to 11 and similar to 21 years). By means of an adaptive psychophysical procedure, we measured the longest period for which periodic (i.e., repeated) noise could be reliably discriminated from nonperiodic (i.e., plain random) noise. On each experimental trial, a single noise sample was presented to the participant, who had to classify this sound as periodic or nonperiodic. Results: The TD adults performed, on average, much better than the other three groups, who performed similarly overall. As a function of practice, the measured thresholds improved for the TD participants, but did not change for the ASD participants. Thresholds were not correlated to performance in a test assessing verbal memory. The variance of the participants' response biases was larger among the ASD participants than among the TD participants. Conclusion: The results mainly suggest that echoic memory takes a long time to fully develop in TD humans, and that this development stops prematurely in persons with ASD. C1 [Erviti, Mayalen; Semal, Catherine; Amestoy, Anouck; Bouvard, Manuel P.; Demany, Laurent] CNRS, F-75700 Paris, France. [Erviti, Mayalen] Univ Bordeaux, Talence, France. [Semal, Catherine] Inst Polytech Bordeaux, Bordeaux, France. [Wright, Beverly A.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. [Amestoy, Anouck; Bouvard, Manuel P.; Demany, Laurent] Univ Bordeaux, UMR CNRS 5287, Inst Neurosci Cognit & Integrat Aquitaine, Talence, France. RP Demany, L (reprint author), Univ Bordeaux 2, BP 63,146 Rue Leo Saignat, F-33076 Bordeaux, France. EM laurent.demany@u-bordeaux.fr FU Fondation de France [UB 032143] FX This study was supported by the Fondation de France (UB 032143) and is part of the doctoral thesis of author Mayalen Erviti. 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TI A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: Current state and future research opportunities SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Positron emission tomography (PET); Single-photon emission computed tomography (SPECT); Neuroimaging; Molecular imaging; Autism spectrum disorder ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; PERVASIVE DEVELOPMENTAL DISORDERS; SEROTONIN TRANSPORTER BINDING; CHILDHOOD AUTISM; GLUCOSE-METABOLISM; ASPERGER-SYNDROME; INFANTILE-AUTISM; BRAIN SPECT; MICROGLIAL ACTIVATION AB Non-invasive positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are techniques used to quantify molecular interactions, biological processes and protein concentration and distribution. In the central nervous system, these molecular imaging techniques can provide critical insights into neurotransmitter receptors and their occupancy by neurotransmitters or drugs. In recent years, there has been an increase in the number of studies that have investigated neurotransmitters in autism spectrum disorder (ASD), while earlier studies mostly focused on cerebral blood flow and glucose metabolism. The underlying and contributing mechanisms of ASD are largely undetermined and ASD diagnosis relies on the behavioral phenotype. Discovery of biochemical endophenotypes would represent a milestone in autism research that could potentially lead to ASD subtype stratification and the development of novel therapeutic drugs. This review characterizes the prior use of molecular imaging by PET and SPECT in ASD, addresses methodological challenges and highlights areas of future opportunity for contributions from molecular imaging to understand ASD pathophysiology. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zuercher, Nicole R.; Bhanot, Anisha; Hooker, Jacob M.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Zuercher, Nicole R.; Hooker, Jacob M.] Harvard Univ, Sch Med, Boston, MA USA. [McDougle, Christopher J.] MassGen Hosp Children, Dept Pediat, Lurie Ctr Autism, Lexington, MA USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Hooker, JM (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Suite 2301, Charlestown, MA 02129 USA. EM hooker@martinos.org FU Robert E. and Donna Landreth Fund for the Study of Neuroinflammation in Autism; Autism Speaks Meixner Translational Postdoctoral Fellowship [9258] FX The authors acknowledge support from the Robert E. and Donna Landreth Fund for the Study of Neuroinflammation in Autism. Nicole R. Zurcher was funded by an Autism Speaks Meixner Translational Postdoctoral Fellowship (#9258). The authors would like to thank Nouchine Hadjikhani for helpful comments on an earlier version of the manuscript and Regan Butterfield for discussions regarding Fig. 1. 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PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAY PY 2015 VL 52 BP 56 EP 73 DI 10.1016/j.neubiorev.2015.02.002 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG8YJ UT WOS:000353601300005 PM 25684726 ER PT J AU Naaijen, J Lythgoe, DJ Amiri, H Buitelaar, JK Glennon, JC AF Naaijen, Jilly Lythgoe, David J. Amiri, Houshang Buitelaar, Jan K. Glennon, Jeffrey C. TI Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: A review of magnetic resonance spectroscopy studies SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Magnetic resonance spectroscopy; Compulsivity; Impulsivity; ADHD; Autism; OCD; Glutamate; GABA ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; DEFICIT HYPERACTIVITY DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SYMPTOM SEVERITY; METABOLITE ALTERATIONS; PROTON SPECTROSCOPY; PREFRONTAL CORTEX; MAJOR DEPRESSION; HEALTHY CONTROLS AB Compulsivity and impulsivity are cross-disorder traits observed in autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Aberrant fronto-striatal glutamatergic signalling is core to the understanding of compulsive and impulsive disorders. In this review, the glutamate (Glu) neurochemistry of fronto-striatal circuits in paediatric and adult ASD, ADHD and OCD, as described in 59 studies, is outlined from the perspective of proton magnetic resonance spectroscopy (H-1 MRS). Despite the methodological inconsistencies between studies, two observations stand out that form possible hypotheses for future studies. Firstly, a possible increase in Glx (combination of Glu, glutamine and GABA) in the striatum across ADHD, OCD and ASD. Secondly, an increased Glx signal in the anterior cingulate cortex in paediatric ASD and ADHD but a lower Glx signal in adult ASD and ADHD. This suggests neurodevelopmental changes in fronto-striatal glutamatergic circuits across the lifespan. Future studies should incorporate more homogeneous samples, perform MRS at field strengths of at least 3 Tesla and provide much more precise and standardized information on methods to improve our understanding of fronto-striatal glutamatergic transmission in compulsive and impulsive syndromes. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Naaijen, Jilly; Amiri, Houshang; Buitelaar, Jan K.; Glennon, Jeffrey C.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 EZ Nijmegen, Netherlands. [Lythgoe, David J.] Kings Coll London, Dept Neuroimaging, Inst Psychiat, London SE5 8AF, England. [Amiri, Houshang] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6500 HB Nijmegen, Netherlands. [Amiri, Houshang] Kerman Univ Med Sci, Inst Neuropharmacol, Neurosci Res Ctr, Kerman, Iran. [Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, NL-6525 GC Nijmegen, Netherlands. RP Naaijen, J (reprint author), Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Geert Grootepl Noord 10,Huispost 126, NL-6525 EZ Nijmegen, Netherlands. EM j.naaijen@donders.ru.nl; david.lythgoe@kcl.ac.uk; amiri.houshang@gmail.com; jan.buitelaar@radboudumc.nl; jeffrey.glennon@radboudumc.nl RI ahmed, Jamila/E-8653-2015 FU European Community [278948] FX The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) TACTICS under grant agreement no. 278948. 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PD MAY PY 2015 VL 52 BP 74 EP 88 DI 10.1016/j.neubiorev.2015.02.009 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG8YJ UT WOS:000353601300006 PM 25712432 ER PT J AU Zantomio, D Chana, G Laskaris, L Testa, R Everall, I Pantelis, C Skafidas, E AF Zantomio, Daniela Chana, Gursharan Laskaris, Liliana Testa, Renee Everall, Ian Pantelis, Christos Skafidas, Efstratios TI Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article DE mGluR5; Glutamate; Autism spectrum disorder; Neurodevelopment; GRM5; Neuroinflammation; Microglia ID METABOTROPIC GLUTAMATE-RECEPTOR; AUTISM SPECTRUM DISORDERS; FRAGILE-X-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; LONG-TERM POTENTIATION; RETT-SYNDROME; MOUSE MODEL; MICROGLIAL ACTIVATION; PROTEIN-SYNTHESIS; CENTRAL MECHANISM AB The pathogenesis of Autism Spectrum Disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, and syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zantomio, Daniela] Austin Hlth, Dept Haematol, Heidelberg, Vic, Australia. [Zantomio, Daniela; Chana, Gursharan; Laskaris, Liliana; Skafidas, Efstratios] Univ Melbourne, Ctr Neural Engn, Parkville, Vic 3052, Australia. [Chana, Gursharan; Laskaris, Liliana; Everall, Ian; Pantelis, Christos; Skafidas, Efstratios] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. [Testa, Renee; Pantelis, Christos] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Parkville, Vic 3052, Australia. [Testa, Renee; Pantelis, Christos] Melbourne Hlth, Parkville, Vic, Australia. [Testa, Renee] Monash Univ, Dept Psychol, Clayton, Vic 3168, Australia. [Chana, Gursharan; Everall, Ian; Pantelis, Christos; Skafidas, Efstratios] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Skafidas, Efstratios] Ctr Integrat Brain Funct, Melbourne, Vic, Australia. RP Skafidas, E (reprint author), Univ Melbourne, Ctr Neural Engn, Carlton, Vic 3053, Australia. EM sskaf@unimelb.edu.au FU NHMRC [628386]; NASRAD Distinguish Investigator Award (Brain & Behavior Research Foundation, US) [18722] FX Prof Christos Pantelis was supported by a NHMRC Senior Principal Research Fellowship (ID: 628386) and NASRAD Distinguish Investigator Award (Brain & Behavior Research Foundation, US, Grant ID: 18722). 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Biobehav. Rev. PD MAY PY 2015 VL 52 BP 172 EP 177 DI 10.1016/j.neubiorev.2015.02.006 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG8YJ UT WOS:000353601300012 PM 25704074 ER PT J AU Van der Hallen, R Evers, K Brewaeys, K Van den Noortgate, W Wagemans, J AF Van der Hallen, Ruth Evers, Kris Brewaeys, Katrien Van den Noortgate, Wim Wagemans, Johan TI Global Processing Takes Time: A Meta-Analysis on Local-Global Visual Processing in ASD SO PSYCHOLOGICAL BULLETIN LA English DT Article DE autism spectrum disorder; developmental disorders; meta-analysis; perception; vision science ID HIGH-FUNCTIONING AUTISM; EMBEDDED FIGURES TASK; SUPERIOR DISEMBEDDING PERFORMANCE; WEAK CENTRAL COHERENCE; SPECTRUM DISORDERS; ASPERGER-SYNDROME; ORIENTED PERCEPTION; GESTALT PSYCHOLOGY; VISUOSPATIAL TASKS; PUBLICATION BIAS AB What does an individual with autism spectrum disorder (ASD) perceive first: the forest or the trees? In spite of 30 years of research and influential theories like the weak central coherence (WCC) theory and the enhanced perceptual functioning (EPF) account, the interplay of local and global visual processing in ASD remains only partly understood. Research findings vary in indicating a local processing bias or a global processing deficit, and often contradict each other. We have applied a formal meta-analytic approach and combined 56 articles that tested about 1,000 ASD participants and used a wide range of stimuli and tasks to investigate local and global visual processing in ASD. Overall, results show no enhanced local visual processing nor a deficit in global visual processing. Detailed analysis reveals a difference in the temporal pattern of the local-global balance, that is, slow global processing in individuals with ASD. Whereas task-dependent interaction effects are obtained, gender, age, and IQ of either participant groups seem to have no direct influence on performance. Based on the overview of the literature, suggestions are made for future research. C1 [Van der Hallen, Ruth; Brewaeys, Katrien; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Van der Hallen, Ruth; Wagemans, Johan] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Leuven, Belgium. [Evers, Kris] UPC KU Leuven, Expt Psychol Lab, Leuven Autism Res LAuRes, Louvain, Belgium. [Evers, Kris] UPC KU Leuven, Child & Adolescent Psychiat, Louvain, Belgium. [Van den Noortgate, Wim] Katholieke Univ Leuven, Methodol Educ Sci, B-3000 Leuven, Belgium. RP Van der Hallen, R (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. EM ruth.vanderhallen@ppw.kuleuven.be FU Methusalem grant by the Flemish Government [METH/08/02] FX The authors would like to thank everybody who has devoted time to reading and commenting this article, in particular the three anonymous reviewers. This research was funded by a Methusalem grant awarded to Johan Wagemans by the Flemish Government (METH/08/02). 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Bull. PD MAY PY 2015 VL 141 IS 3 BP 549 EP 573 DI 10.1037/bul0000004 PG 25 WC Psychology; Psychology, Multidisciplinary SC Psychology GA CH0PR UT WOS:000353725000003 PM 25420221 ER PT J AU Blackford, JU Williams, LE Heckers, S AF Blackford, J. U. Williams, L. E. Heckers, S. TI Neural correlates of out-group bias predict social impairment in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; fMRI; Habituation; Social functioning ID AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; HUMAN AMYGDALA; HABITUATION; RECOGNITION; SELF; HIPPOCAMPUS; PERCEPTION; STIMULI; FACES AB Background: Social impairments are a hallmark feature of schizophrenia and are a key predictor of functional disability. Deficits in social information processing likely underlie social impairment; however, this relationship is understudied. We previously demonstrated that patients with schizophrenia fail to habituate to neutral faces, providing evidence for an alteration in basic social information processing. It remains unknown whether patients with schizophrenia also show deficits in processing of more complex social information. Outgroup bias provides an excellent opportunity to test complex social information processing because the bias requires basic face processing skills, the ability to discriminate between groups, as well as the ability to categorize oneself into a salient social group. Methods: Study participants were 23 patients with schizophrenia and 21 controls. Using functional magnetic resonance imaging, habituation of response to 120 s of repeated presentations of faces was assessed in participants who viewed either same-gender faces or opposite-gender faces. The interaction between face gender (same/opposite) and group was examined in three key regions: amygdala, hippocampus, and visual cortex. Social impairment was measured using the PANSS and correlations between social impairment and out-group effect (main effect of face type) were performed in patients. Results: Patients with schizophrenia had aberrant neural responses to opposite-gender faces (interaction, p < .05 corrected). Healthy controls showed an immediate heightened response to opposite-gender faces relative to same-gender faces; but in patients this effect was substantially delayed (similar to 70 s). In patients with schizophrenia, the out-group bias was significantly correlated with social impairment. Patients with no social impairment showed a heightened neural response to opposite-gender faces after 30 s, whereas patients with mild-moderate social impairment failed to ever show a heightened response. Conclusion: Alterations in neural responses during out-group processing predicted degree of social impairment in patients with schizophrenia; thus, neural responses to opposite-gender faces may provide a novel measure for studies of treatment response and disease outcome. (C) 2015 Elsevier B.V. All rights reserved. C1 [Blackford, J. U.; Heckers, S.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Williams, L. E.] Univ ofWisconsin, Wisconsin Psychiat Inst & Clin, Dept Psychiat, Madison, WI 53719 USA. RP Blackford, JU (reprint author), 1601 23rd Ave South,Suite 3057J, Nashville, TN 37212 USA. EM j.blackford@vanderbilt.edu FU National Institute of Mental Health [R01 MH070560, K01 MH083052]; National Center for Research Resources [UL1 RR024975-01, 2 UL1 TR000445-06] FX This work was supported by the National Institute of Mental Health (R01 MH070560 to SH; K01 MH083052 to JUB), and the National Center for Research Resources (grant UL1 RR024975-01, now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445-06, to LEW). The NIMH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. 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Res. PD MAY PY 2015 VL 164 IS 1-3 BP 203 EP 209 DI 10.1016/j.schres.2015.03.019 PG 7 WC Psychiatry SC Psychiatry GA CG5MX UT WOS:000353337100030 PM 25864952 ER PT J AU Rahkonen, P Lano, A Pesonen, AK Heinonen, K Raikkonen, K Vanhatalo, S Autti, T Valanne, L Andersson, S Metsaranta, M AF Rahkonen, Petri Lano, Aulikki Pesonen, Anu-Katriina Heinonen, Kati Raikkonen, Katri Vanhatalo, Sampsa Autti, Taina Valanne, Leena Andersson, Sture Metsaranta, Marjo TI Atypical sensory processing is common in extremely low gestational age children SO ACTA PAEDIATRICA LA English DT Article DE Autism spectrum disorder; Neonate; Patent ductus arteriosus ligation; Preterm; Sensory processing ID PATENT DUCTUS-ARTERIOSUS; BIRTH-WEIGHT INFANTS; PRETERM INFANTS; NEURODEVELOPMENTAL OUTCOMES; SURGICAL CLOSURE; PARALYSIS; EVOLUTION; PROFILES; AUTISM AB AimAtypical sensory processing is common in children born extremely prematurely. We investigated sensory processing abilities in extremely low gestational age (ELGA) children and analysed associated neonatal risk factors, neuroanatomical findings and neurodevelopmental outcome. MethodsWe carried out a prospective study of 44 ELGA children, including 42 who had undergone brain magnetic resonance imaging (MRI) at term-equivalent age, when they were 2years of corrected age. Their sensory processing abilities were assessed with the Infant/Toddler Sensory Profile questionnaire and their neurodevelopmental with a structured Hempel neurological examination, Griffiths Mental Developmental Scales and Bayley Scales of Infant and Toddler Development Third Edition. ResultsSensory profiles were definitely or probably atypical (<-1 SD) in half of the ELGA children, and the most common behavioural pattern was low registration (23%). Sensation seeking was associated with abnormalities in grey and/or white matter in the brain MRI (p<0.01). Atypical oral sensory processing was associated with surgical closure of the patent ductus arteriosus (p=0.02, adjusted p<0.01). ConclusionAtypical sensory processing in ELGA children was common, and children with neonatal neuroanatomical lesions tended to present specific behavioural responses to sensory stimuli. Surgical closure of the patent ductus arteriosus may predispose infants to feeding problems due to atypical oral sensory processing. C1 [Rahkonen, Petri; Andersson, Sture; Metsaranta, Marjo] Univ Helsinki, Childrens Hosp, Dept Pediat, Helsinki, Finland. [Lano, Aulikki] Univ Helsinki, Childrens Hosp, Dept Child Neurol, Helsinki, Finland. [Pesonen, Anu-Katriina; Heinonen, Kati; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Vanhatalo, Sampsa] Univ Helsinki, Childrens Hosp, Dept Clin Neurophysiol, Helsinki, Finland. [Autti, Taina; Valanne, Leena] Univ Helsinki, Med Imaging Ctr, Helsinki, Finland. RP Rahkonen, P (reprint author), Univ Helsinki, Childrens Hosp, POB 281, Helsinki 00029, Hus, Finland. EM petri.rahkonen@hus.fi FU Jenny and Antti Wihuri Foundation; Academy of Finland (Centre of Excellence Program); Finnish Medical Foundation; Finska Lakaresallskapet; Helsinki University Central Hospital; Foundation for Pediatric Research; Paivikki and Sakari Sohlberg Foundation; Emil Aaltonen Foundation; Signe and Ane Gyllenberg Foundation; Maud Kuistila Memorial Foundation; Arvo and Lea Ylppo Foundation; Orion Research Foundation FX The study was financially supported by the Jenny and Antti Wihuri Foundation, the Academy of Finland (Centre of Excellence Program), the Finnish Medical Foundation, Finska Lakaresallskapet, the Helsinki University Central Hospital Research Grants, the Foundation for Pediatric Research, the Paivikki and Sakari Sohlberg Foundation, the Emil Aaltonen Foundation, the Signe and Ane Gyllenberg Foundation, the Maud Kuistila Memorial Foundation, the Arvo and Lea Ylppo Foundation and the Orion Research Foundation. 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J. Hum. Biol. PD MAY-JUN PY 2015 VL 27 IS 3 BP 339 EP 343 DI 10.1002/ajhb.22644 PG 5 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA CG4ZZ UT WOS:000353299400007 PM 25327626 ER PT J AU Lo, ST Collin, PJL Hokken-Koelega, ACS AF Lo, S. T. Collin, P. J. L. Hokken-Koelega, A. C. S. TI Psychiatric Disorders in Children with Prader-Willi Syndrome-Results of a 2-Year Longitudinal Study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Prader-Willi syndrome; psychiatric disorders; psychosis; oppositional defiant disorder; compulsions ID MATERNAL UNIPARENTAL DISOMY; AUTISM SPECTRUM DISORDER; GROWTH-HORMONE TREATMENT; COMPULSIVE BEHAVIOR; PEOPLE; ADULTS; ILLNESS; ADOLESCENTS; PREVALENCE; SYMPTOMS AB Psychiatric disorders such as psychosis are highly prevalent in adults with Prader-Willi syndrome (PWS). However, knowledge about the presence and progression of psychiatric disorders in children with PWS is very limited. Sixty-one children with PWS aged 7-17 years were tested using the Diagnostic Interview Schedule for Children (DISC) and Compulsive Behaviour Checklist (CBC), and 38/61 were retested after 2 years. Prevalence of psychiatric disorders and the association with age, gender, genetic subtype, and total IQ were assessed. In addition, occurrence and characteristics of compulsions were determined. Prior to the study, two boys were known with psychotic symptoms and treated with antipsychotics. At baseline, none scored positive for psychotic disorder. During the follow-up, only one boy with known psychotic symptoms required a dose adjustment of his antipsychotic medication. After 2 years, none of the children had a psychotic disorder according to the DISC. Oppositional defiant disorder (ODD) was the most common diagnosis and present in 20% of children with PWS, and this was not associated with age (=-0.081, P=0.546), gender (=0.013, P=0.923), genetic subtype (=-0.073, P=0.584), or total IQ (=-0.150, P=0.267). The most common compulsions were hoarding and fixed hygiene sequences. In our large group of 61 children with PWS, the majority had no psychotic disorder and no progression was found during 2-year follow-up. ODD was present in 20% of children. No changes in the prevalence of psychiatric disorders were found during the 2-year follow-up study and genetic subtype was not related to psychosis, depression, or ODD. (c) 2015 Wiley Periodicals, Inc. C1 [Lo, S. T.; Hokken-Koelega, A. C. S.] Dutch Growth Res Fdn, Rotterdam, Netherlands. [Lo, S. T.; Hokken-Koelega, A. C. S.] Sophia Childrens Univ Hosp, Erasmus Univ Med Ctr, Dept Pediat, Subdiv Endocrinol, NL-3016 AH Rotterdam, Netherlands. [Collin, P. J. L.] Koraalgroep, Sittard, Netherlands. RP Lo, ST (reprint author), Sophia Childrens Univ Hosp, Erasmus Univ Med Ctr, Dept Pediat, Subdiv Endocrinol, Westzeedijk 106, NL-3016 AH Rotterdam, Netherlands. EM s.lo@kindengroei.nl FU Dutch Prader-Willi Fund; Fund NutsOhra; Dutch Growth Research Foundation FX Grant sponsor: Dutch Prader-Willi Fund; Grant sponsor: Fund NutsOhra; Grant sponsor: Dutch Growth Research Foundation. 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J. Med. Genet. A PD MAY PY 2015 VL 167A IS 5 BP 983 EP 991 DI 10.1002/ajmg.a.36998 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CG3HY UT WOS:000353171900003 PM 25712902 ER PT J AU Garcia-Santiago, FA Martinez-Glez, V Santos, F Garcia-Minaur, S Mansilla, E Meneses, AG Rosell, J Granero, AP Vallespin, E Fernandez, L Sierra, B Oliver-Bonet, M Palomares, M de Torres, ML Mori, MA Nevado, J Heath, KE Delicado, A Lapunzina, P AF Amalia Garcia-Santiago, Fe Martinez-Glez, Victor Santos, Fernando Garcia-Minaur, Sixto Mansilla, Elena Gonzalez Meneses, Antonio Rosell, Jordi Perez Granero, Angeles Vallespin, Elena Fernandez, Luis Sierra, Blanca Oliver-Bonet, Maria Palomares, Maria Luisa de Torres, Maria Angeles Mori, Maria Nevado, Julian Heath, Karen E. Delicado, Alicia Lapunzina, Pablo TI Analysis of Invdupdel(8p) Rearrangement: Clinical, Cytogenetic and Molecular Characterization SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE invdupdel(8p); inversion; duplication; deletion; chromosome 8; genomic rearrangement; FISH; chromosomal microarray ID IN-SITU HYBRIDIZATION; DUP DEL(8P); INVERTED DUPLICATION; CLEFT-LIP; INVERSION; AUTISM; 8P; MECHANISM; EPILEPSY; MUSCLE AB Inverted duplication 8p associated with deletion of the short arms of chromosome 8 (invdupdel[8p]) is a relatively uncommon complex chromosomal rearrangement, with an estimated incidence of 1 in 10,000-30,000 live borns. The chromosomal rearrangement consists of a deletion of the telomeric region (8p23-pter) and an inverted duplication of the 8p11.2-p22 region. Clinical manifestations of this disorder include severe to moderate intellectual disability and characteristic facial features. In most cases, there are also CNS associated malformations and congenital heart defects. In this work, we present the cytogenetic and molecular characterization of seven children with invdupdel(8p) rearrangements. Subsequently, we have carried out genotype-phenotype correlations in these seven patients. The majority of our patients carry a similar deletion but different size of duplications; the latter probably explaining the phenotypic variability among them. We recommend that complete clinical evaluation and detailed chromosomal microarray studies should be undertaken, enabling appropriate genetic counseling. (c) 2015 Wiley Periodicals, Inc. C1 [Amalia Garcia-Santiago, Fe; Mansilla, Elena; Luisa de Torres, Maria; Delicado, Alicia] Hosp Univ La Paz, Inst Genet Med & Mol INGEMM, IdiPAZ, Cytogenet Unit, Madrid 28046, Spain. [Martinez-Glez, Victor; Vallespin, Elena; Fernandez, Luis; Palomares, Maria; Angeles Mori, Maria; Nevado, Julian] Hosp Univ La Paz, Inst Genet Med & Mol INGEMM, IdiPAZ, Funct & Struct Genom Unit, Madrid 28046, Spain. [Santos, Fernando; Garcia-Minaur, Sixto; Lapunzina, Pablo] Hosp Univ La Paz, Inst Genet Med & Mol INGEMM, IdiPAZ, Clin Gent Unit, Madrid 28046, Spain. [Heath, Karen E.] Hosp Univ La Paz, Inst Genet Med & Mol INGEMM, IdiPAZ, Mol Endocrinol Unit, Madrid 28046, Spain. [Martinez-Glez, Victor; Santos, Fernando; Garcia-Minaur, Sixto; Mansilla, Elena; Rosell, Jordi; Vallespin, Elena; Fernandez, Luis; Palomares, Maria; Luisa de Torres, Maria; Angeles Mori, Maria; Nevado, Julian; Heath, Karen E.; Delicado, Alicia; Lapunzina, Pablo] ISCIII, Ctr Invest Biomed Red Enfermedades Raras, CIBERER, Madrid, Spain. [Gonzalez Meneses, Antonio] Hosp Virgen del Rocio, Dysmorphol Unit, Seville, Spain. [Rosell, Jordi; Perez Granero, Angeles; Sierra, Blanca] Hosp Son Espases, Genet Unit, Palma De Mallorca, Spain. [Oliver-Bonet, Maria] Hosp Son Espases, Res Unit, Palma de Mallorca, Spain. RP Garcia-Santiago, FA (reprint author), Hosp Univ La Paz, Inst Genet Med & Mol INGEMM, IdiPAZ, Paseo Castellana 261, Madrid 28046, Spain. EM feamalia.garcia@salud.madrid.org CR Baulac S, 2008, ARCH NEUROL-CHICAGO, V65, P943, DOI 10.1001/archneur.65.7.943 Benazet JD, 2009, CSH PERSPECT BIOL, V1, DOI 10.1101/cshperspect.a001339 Buysse K, 2009, EUR J MED GENET, V52, P31, DOI 10.1016/j.ejmg.2008.10.007 Caglayan AO, 2009, GENET COUNSEL, V20, P333 Chien WH, 2010, CLIN GENET, V78, P449, DOI 10.1111/j.1399-0004.2010.01395.x DEDIESMULDERS CEM, 1995, AM J MED GENET, V59, P369, DOI 10.1002/ajmg.1320590318 Devriendt K, 1999, AM J HUM GENET, V64, P1119, DOI 10.1086/302330 Fisch GS, 2011, BEHAV GENET, V41, P373, DOI 10.1007/s10519-011-9447-4 Floridia G, 1996, AM J HUM GENET, V58, P785 Giglio S, 2001, AM J HUM GENET, V68, P874, DOI 10.1086/319506 Glancy M, 2009, EUR J HUM GENET, V17, P37, DOI 10.1038/ejhg.2008.133 GUO WJ, 1995, AM J MED GENET, V58, P230, DOI 10.1002/ajmg.1320580307 Hand M, 2010, AM J MED GENET A, V152A, P2827, DOI 10.1002/ajmg.a.33669 Hippenmeyer S, 2002, NEURON, V36, P1035, DOI 10.1016/S0896-6273(02)01101-7 Lemmens K, 2004, CIRCULATION, V109, P324, DOI 10.1161/01.CIR.0000114521.88547.5E McEachern MJ, 2000, ANNU REV GENET, V34, P331, DOI 10.1146/annurev.genet.34.1.331 Mehmet A, 2010, PEDIATR INT, V52, P2 Nucaro A, 2011, CLIN GENET, V79, P394, DOI 10.1111/j.1399-0004.2010.01548.x Riley BM, 2007, AM J MED GENET A, V143A, P846, DOI 10.1002/ajma.a.31673 Riley BM, 2007, P NATL ACAD SCI USA, V104, P4512, DOI 10.1073/pnas.0607956104 Rodriguez-Revenga L, 2013, GENE, V521, P82, DOI 10.1016/j.gene.2013.02.043 Shimokawa O, 2004, AM J MED GENET A, V128A, P133, DOI 10.1002/ajmg.a.30063 Sugawara H, 2003, GENOMICS, V82, P238, DOI 10.1016/S0888-7543(03)00108-3 Vallespin E, 2013, AM J MED GENET A, V161, P1950, DOI 10.1002/ajmg.a.35960 Vermeesch JR, 2003, J MED GENET, V40, DOI 10.1136/jmg.40.8.e93 Yu S, 2010, CYTOGENET GENOME RES, V129, P265, DOI 10.1159/000315887 NR 26 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2015 VL 167A IS 5 BP 1018 EP 1025 DI 10.1002/ajmg.a.36879 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CG3HY UT WOS:000353171900008 PM 25712135 ER PT J AU Louw, JJ Corveleyn, A Jia, YJ Hens, G Gewillig, M Devriendt, K AF Louw, Jacoba J. Corveleyn, Anniek Jia, Yaojuan Hens, Greet Gewillig, Marc Devriendt, Koenraad TI MEIS2 Involvement in Cardiac Development, Cleft Palate, and Intellectual Disability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE cleft palate; cleft lip; cardiopathy; heart; intellectual disability; next generation sequencing (NGS) ID HINDBRAIN BOUNDARY; GENE-EXPRESSION; ZEBRAFISH; DELETION; DEFECT; 15Q14; DELAY AB MEIS2 has been associated with cleft palate and cardiac septal defects as well as varying degrees of intellectual disability. We present a female patient with a more severe phenotype compared to previous reported patients. She has multiple congenital malformations; cleft palate and congenital heart defect characterized by septal defects and aortic coarctation. She has severe feeding problems, facial dysmorphism, severely delayed gross motor and verbal development, and autism spectrum disorder. Facial dysmorphism consisting of bitemporal narrowing, arched and laterally extended eyebrows, mild upslanting palpebral fissures, deep-set eyes, a tented upper lip, thin upper vermilion, full lower vermilion, broad first ray of hands and feet, a gap between the first and second toes, and syndactyly of toe II-III. Exome sequencing revealed a non-frameshift deletion (c.998_1000del:p.Arg333del) of three base pairs in the MEIS2 homeodomain. The more severe phenotype is most probably due to dominant-negative mechanisms. This is the first report showing a de novo small intragenic mutation in MEIS2 and further confirms the important role of this gene in normal development. (c) 2015 Wiley Periodicals, Inc. C1 [Louw, Jacoba J.; Gewillig, Marc] Univ Hosp Leuven, Dept Congenital & Pediat Cardiol, Leuven, Belgium. [Louw, Jacoba J.; Corveleyn, Anniek; Jia, Yaojuan; Devriendt, Koenraad] Katholieke Univ Leuven, Univ Hosp Leuven, Ctr Human Genet, Leuven, Belgium. [Hens, Greet] Univ Hosp Leuven, Dept Ear Nose & Throat, Leuven, Belgium. RP Devriendt, K (reprint author), Ctr Human Genet, Herestr 49, B-3000 Leuven, Belgium. EM koenraad.devriendt@uzleuven.be FU H. Van Itterbeek; Eddy Merckx; FU Leuven [GOA/12/015] FX Grant sponsor: H. Van Itterbeek; Grant sponsor: Eddy Merckx; Grant sponsor: FU Leuven; Grant number: GOA/12/015. CR Agoston Z, 2009, DEVELOPMENT, V136, P3311, DOI 10.1242/dev.037770 Chen CP, 2008, EUR J MED GENET, V51, P368, DOI 10.1016/j.ejmg.2008.02.011 Crowley MA, 2010, AM J MED GENET A, V152A, P1326, DOI 10.1002/ajmg.a.33375 Erdogan F, 2007, AM J MED GENET A, V143A, P172, DOI 10.1002/ajmg.a.31541 Garg V, 2003, NATURE, V424, P443, DOI 10.1038/nature01827 Glickman NS, 2002, SEMIN CELL DEV BIOL, V13, P507, DOI 10.1016/S1084-9521(02)00104-0 Johansson S, 2014, AM J MED GENET A, V164, P1622, DOI 10.1002/ajmg.a.36498 Krissinel E, 2007, J MOL BIOL, V372, P774, DOI 10.1016/j.jmb.2007.05.022 Paige SL, 2012, CELL, V151, P221, DOI 10.1016/j.cell.2012.08.027 Shim S, 2007, MOL CELL BIOL, V27, P1614, DOI 10.1128/MCB.01429-06 Vennemann A, 2008, BRAIN RES, V1206, P33, DOI 10.1016/j.brainres.2008.01.100 Waskiewicz AJ, 2001, DEVELOPMENT, V128, P4139 Zerucha T, 2001, MECH DEVELOP, V102, P247, DOI 10.1016/S0925-4773(01)00299-4 NR 13 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2015 VL 167A IS 5 BP 1142 EP 1146 DI 10.1002/ajmg.a.36989 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CG3HY UT WOS:000353171900025 PM 25712757 ER PT J AU Doyle-Thomas, KAR Lee, W Foster, NEV Tryfon, A Ouimet, T Hyde, KL Evans, AC Lewis, J Zwaigenbaum, L Anagnostou, E AF Doyle-Thomas, Krissy A. R. Lee, Wayne Foster, Nicholas E. V. Tryfon, Ana Ouimet, Tia Hyde, Krista L. Evans, Alan C. Lewis, John Zwaigenbaum, Lonnie Anagnostou, Evdokia CA NeuroDevNet ASD Imaging Grp TI Atypical Functional Brain Connectivity during Rest in Autism Spectrum Disorders SO ANNALS OF NEUROLOGY LA English DT Article ID DEFAULT MODE NETWORK; SENTENCE COMPREHENSION; REVISED VERSION; CORTEX; UNDERCONNECTIVITY; TASK; FMRI; ABNORMALITIES; COMMUNICATION; HYPOTHESIS AB ObjectiveConnectivity atypicalities in autism spectrum disorders (ASD) have been extensively proposed. The default mode network (DMN) is critical in this study, given the insight it provides for long-distance connectivity, and the importance of regions in this network for introspection and social emotion processing, areas affected in ASD. However, study of this network has largely been limited to adults; research earlier in development is lacking. The objective of this study was to examine DMN connectivity in children/adolescents with ASD. MethodsA total of 115 children/adolescents, aged 6 to 17 years (71 males with ASD and 44 group age-matched TD males) were included in these analyses. We examined group differences in (1) functional connectivity between the posterior cingulate cortex and regions across the brain, (2) connectivity within the DMN as a function of age and intelligence quotient (IQ), and (3) the association between DMN connectivity and empathic accuracy. ResultsIndividuals with ASD, relative to controls, showed either stronger or weaker connectivity between the posterior cingulate cortex (PCC) and DMN regions, depending on the region, but also showed stronger connectivity with non-DMN regions. A significant group-by-age interaction was observed in functional connectivity between the PCC and medial prefrontal cortex; connectivity increased with age in controls, but decreased in individuals with ASD. No effects of IQ were found. There was a significant group difference in the relation between DMN connectivity and empathic accuracy. InterpretationDifferences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities. Ann Neurol 2015;77:866-876 C1 [Doyle-Thomas, Krissy A. R.; Anagnostou, Evdokia] Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Toronto, ON, Canada. [Doyle-Thomas, Krissy A. R.; Anagnostou, Evdokia] Univ Toronto, Dept Pediat, Toronto, ON M4G 1R8, Canada. [Lee, Wayne] Hosp Sick Children, Diagnost Imaging, Toronto, ON M5G 1X8, Canada. [Foster, Nicholas E. V.; Tryfon, Ana; Ouimet, Tia; Hyde, Krista L.] Univ Montreal, Int Lab Brain Mus & Sound Res, Montreal, PQ, Canada. [Foster, Nicholas E. V.; Tryfon, Ana; Ouimet, Tia; Hyde, Krista L.] McGill Univ, Fac Med, Montreal, PQ, Canada. [Evans, Alan C.; Lewis, John] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. RP Anagnostou, E (reprint author), Univ Toronto, Bloorview Res Inst, Holland Bloorview Kids Rehabil Hosp, 150 Kilgour Rd, Toronto, ON M4G 1R8, Canada. EM eanagnostou@hollandbloorview.ca FU NeuroDevNet FX This research was supported by NeuroDevNet. 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Neurol. PD MAY PY 2015 VL 77 IS 5 BP 866 EP 876 DI 10.1002/ana.24391 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG4EF UT WOS:000353235400014 PM 25707715 ER PT J AU Srinivasjois, R Rao, S Patole, S AF Srinivasjois, Ravisha Rao, Shripada Patole, Sanjay TI Probiotic supplementation in children with autism spectrum disorder SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Letter ID NEURODEVELOPMENTAL DISORDERS; MICROBIOTA C1 [Srinivasjois, Ravisha] Joondalup Hlth Campus, Dept Neonatol & Paediat, Perth, WA 6027, Australia. [Rao, Shripada] King Edward Mem Hosp Women, Dept Neonatal Paediat, Perth, WA, Australia. [Patole, Sanjay] Princess Margaret Hosp Children, Dept Neonatal Paediat, Perth, WA, Australia. RP Srinivasjois, R (reprint author), Joondalup Hlth Campus, Dept Paediat, Specialist Med Ctr, Suite 204, Perth, WA 6027, Australia. EM srinivasjoisr@ramsayhealth.com.au CR Adams JB, 2011, BMC GASTROENTEROL, V11, DOI 10.1186/1471-230X-11-22 de Theije CGM, 2014, BRAIN BEHAV IMMUN, V37, P197, DOI 10.1016/j.bbi.2013.12.005 Gilbert JA, 2013, CELL, V155, P1446, DOI 10.1016/j.cell.2013.11.035 Hsiao EY, 2013, CELL, V155, P1451, DOI 10.1016/j.cell.2013.11.024 Kaluzna-Czaplinska J, 2012, NUTRITION, V28, P124, DOI 10.1016/j.nut.2011.08.002 Macfabe Derrick, 2013, Glob Adv Health Med, V2, P52, DOI 10.7453/gahmj.2013.089 OCEBM Levels of Evidence Working Group, 2009, OXF 2011 LEV EV Parracho H. M. R. T., 2010, International Journal of Probiotics and Prebiotics, V5, P69 Tomova A, 2015, PHYSIOL BEHAV, V138, P179, DOI 10.1016/j.physbeh.2014.10.033 NR 9 TC 0 Z9 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 EI 1468-2044 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD MAY PY 2015 VL 100 IS 5 DI 10.1136/archdischild-2014-308002 PG 2 WC Pediatrics SC Pediatrics GA CG3DX UT WOS:000353159300023 ER PT J AU Davidson, J Gringras, P Fairhurst, C Simpson, J AF Davidson, Joseph Gringras, Paul Fairhurst, Charlie Simpson, John TI Physical and neurodevelopmental outcomes in children with single-ventricle circulation SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID LEFT-HEART SYNDROME; QUALITY-OF-LIFE; AUTISM-SPECTRUM; BRAIN-DEVELOPMENT; NORWOOD PROCEDURE; FONTAN OPERATION; CARDIAC-SURGERY; GROWTH; PREVALENCE; INFANTS AB Objective To investigate longer-term physical and neurodevelopmental outcomes of patients with hypoplastic left heart syndrome (HLHS) compared with other patients with functionally single-ventricle circulation surviving beyond the age of 10 years. Design A retrospective, observational study from a UK tertiary centre for paediatric cardiology. Results 58 patients with HLHS and 44 non-HLHS patients with single-ventricle physiology were included. Subjective reduction in exercise tolerance was reported in 72% (95% CI 61% to 84%) of patients with HLHS and 45% (31% to 60%) non-HLHS patients. Compared with non-HLHS patients, educational concerns were reported more frequently in patients with HLHS, 41% (29% to 54%) vs 23% (10% to 35%), as was a diagnosis of a behaviour disorder (autism or attention deficit hyperactivity disorder) 12% (4% to 21%) vs 0%, and referral to other specialist services 67% (55% to 79%) vs 48% (33% to 63%). Conclusions Within a group of young people with complex congenital heart disease, those with HLHS are likely to have worse physical, psychological and educational outcomes. C1 [Davidson, Joseph] Kings Coll London, Sch Med, London WC2R 2LS, England. [Gringras, Paul; Fairhurst, Charlie] Guys & St Thomas NHS Fiundat Trust, Evelina London Childrens Hosp, Dept Paediat Neurol, London, England. 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Dis. Child. PD MAY PY 2015 VL 100 IS 5 BP 495 EP 499 DI 10.1136/archdischild-2014-306934 PG 5 WC Pediatrics SC Pediatrics GA CG3DX UT WOS:000353159300020 PM 25398447 ER PT J AU Moore, DJ AF Moore, David J. TI Acute pain experience in individuals with autism spectrum disorders: A review SO AUTISM LA English DT Review DE autism spectrum disorder; autism; autistic; pain; sensory differences ID TACTILE PERCEPTION; INFANTILE-AUTISM; BETA-ENDORPHIN; CHILDREN; ADULTS; ABNORMALITIES; COMMUNICATION; ADOLESCENTS; EXPRESSION; CHILDHOOD AB In addition to the diagnostic criteria for autism spectrum disorder, a number of clinically important comorbid complaints, including sensory abnormalities, are also discussed. One difference often noted in these accounts is hyposensitivity to pain; however, evidence for this is limited. The purpose of the current review therefore was to examine sensitivity to pain of individuals with autism spectrum disorder. This review is interested in reports which consider differences in subjective experience of pain (i.e. different pain thresholds) and differences in behavioural response to pain (i.e. signs of pain-related distress). Studies were included if they were conducted with human subjects, included a clearly diagnosed autism spectrum disorder population and reported data pertaining to pain experience relative to the neurotypical population. Studies were classified as being self/parent report, clinical observations, observations of response to medical procedures or experimental examination of pain. Both self/parent report and clinical observations appeared to report hyposensitivity to pain, whereas observations of medical procedures and experimental manipulation suggested normal or hypersensitive responses to pain. This review suggests that contrary to classical reports, individuals with autism spectrum disorder do not appear to have systematically altered pain responses or thresholds. More systematic experimental examination of this area is needed to understand responses to pain of individuals with autism spectrum disorder. C1 [Moore, David J.] Liverpool John Moores Univ, Liverpool L3 3AF, Merseyside, England. RP Moore, DJ (reprint author), Liverpool John Moores Univ, Dept Nat Sci & Psychol, Liverpool L3 3AF, Merseyside, England. 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autism spectrum quotient; autism; character; endophenotype; personality; temperament ID DEFICIT-HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; SUBSTANCE USE DISORDERS; PERSONALITY-TRAITS; PSYCHOBIOLOGICAL MODEL; QUOTIENT AQ; ADHD; COMORBIDITY; RELIABILITY; DYSFUNCTION AB Autism spectrum disorder and attention deficit/hyperactivity disorder overlap in several ways, raising questions about the nature of this comorbidity. Rommelse et al. published an innovative review of candidate endophenotypes for autism spectrum disorder and attention deficit/hyperactivity disorder in cognitive and brain domains. They found that all the endophenotypic impairments that were reviewed in attention deficit/hyperactivity disorder were also present in autism spectrum disorder, suggesting a continuity model with attention deficit/hyperactivity disorder as a light form of autism spectrum disorder. Using existing data, 75 adults with autism spectrum disorder and 53 with attention deficit/hyperactivity disorder were directly compared on autistic symptoms with the autism spectrum quotient, and on the endophenotypic measure of temperament and character, using the Abbreviated (Dutch: Verkorte) Temperament and Character Inventory. Based on the hypothesis that attention deficit/hyperactivity disorder and autism spectrum disorder are disorders on a continuous spectrum, autism spectrum quotient scores and abbreviated Temperament and Character Inventory scores were expected to be different from normal controls in both disorders in a similar direction. In addition, the autism spectrum quotient and abbreviated Temperament and Character Inventory scores were expected to be closely correlated. These conditions applied to only two of the seven Abbreviated Temperament and Character Inventory scales (harm avoidance and self-directedness), suggesting that temperament and character as an endophenotype of autism spectrum disorder and attention deficit/hyperactivity disorder provides only partial support for the continuity hypothesis of autism spectrum disorder and attention deficit/hyperactivity disorder. C1 [Sizoo, Bram B.] Dimence, Ctr Dev Disorders, NL-7400 GC Deventer, Netherlands. [van der Gaag, Rutger Jan] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands. [van den Brink, Wim] Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands. RP Sizoo, BB (reprint author), Dimence, Ctr Dev Disorders, POB 5003, NL-7400 GC Deventer, Netherlands. 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Despite the multiple studies focusing on social skills interventions, only some have focused specifically on problem-solving skills and have not targeted workplace adaptation training in the adult population. This study describes preliminary data from a group format manual-based intervention, the Interpersonal Problem-Solving for Workplace Adaptation Programme, aimed at improving the cognitive and metacognitive process of social problem-solving skills focusing on typical social situations in the workplace based on mediation as the main strategy. A total of 50 adults with Asperger syndrome received the programme and were compared with a control group of typical development. The feasibility and effectiveness of the treatment were explored. Participants were assessed at pre-treatment and post-treatment on a task of social problem-solving skills and two secondary measures of socialisation and work profile using self- and caregiver-report. Using a variety of methods, the results showed that scores were significantly higher at post-treatment in the social problem-solving task and socialisation skills based on reports by parents. Differences in comparison to the control group had decreased after treatment. The treatment was acceptable to families and subject adherence was high. The Interpersonal Problem-Solving for Workplace Adaptation Programme appears to be a feasible training programme. C1 [Bonete, Saray; Dolores Calero, Maria; Fernandez-Parra, Antonio] Univ Granada, E-18071 Granada, Spain. [Bonete, Saray] Univ Francisco Vitoria, Madrid 28223, Spain. RP Bonete, S (reprint author), Univ Francisco Vitoria, Ctra Pozuelo Majadahonda Km 1-800, Madrid 28223, Spain. EM s.bonete.prof@ufv.es FU University of Granada FPU Plan Propio grant FX This project was partially supported by the University of Granada FPU Plan Propio grant. 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TI The influence of maternal language responsiveness on the expressive speech production of children with autism spectrum disorders: A microanalysis of mother-child play interactions SO AUTISM LA English DT Article DE autism spectrum disorders; responsiveness; speech ID PARENT VERBAL RESPONSIVENESS; JOINT ATTENTION; COMMUNICATION; INTERVENTION; BEHAVIORS; PRESCHOOLERS; ABILITIES; TODDLERS; STIMULI; PREDICT AB Adult responsiveness is related to language development both in young typically developing children and in children with autism spectrum disorders, such that parents who use more responsive language with their children have children who develop better language skills over time. This study used a micro-analytic technique to examine how two facets of maternal utterances, relationship to child focus of attention and degree of demandingness, influenced the immediate use of appropriate expressive language of preschool-aged children with autism spectrum disorders (n = 28) and toddlers with typical development (n = 16) within a naturalistic mother-child play session. Mothers' use of follow-in demanding language was most likely to elicit appropriate expressive speech in both children with autism spectrum disorders and children with typical development. For children with autism spectrum disorders, but not children with typical development, mothers' use of orienting cues conferred an additional benefit for expressive speech production. 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Myhre, Anne M. Sponheim, Eili TI Exploring the agreement between questionnaire information and DSM-IV diagnoses of comorbid psychopathology in children with autism spectrum disorders SO AUTISM LA English DT Article DE autism spectrum disorders; children; Child Behavior Check List; DSM-IV disorders; psychiatric comorbidity ID PERVASIVE DEVELOPMENTAL DISORDERS; HIGH-FUNCTIONING AUTISM; PSYCHIATRIC-DISORDERS; BEHAVIOR CHECKLIST; ASPERGER-SYNDROME; YOUNG-PEOPLE; INTERVIEW; VALIDITY; ANXIETY; ADOLESCENTS AB Autism spectrum disorders are often comorbid with other psychiatric symptoms and disorders. However, identifying psychiatric comorbidity in children with autism spectrum disorders is challenging. We explored how a questionnaire, the Child Behavior Check List, agreed with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV)-based semi-structured interview, the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS). The sample comprised 55 children and adolescents (age 6 to 18 years) with autism spectrum disorders, including the main autism spectrum disorder subgroups and the broad range of cognitive and language functioning. High rate of psychopathology was found both through questionnaire and interview assessment. Using predefined Child Behavior Check List cutoffs, we found good agreement between the Child Behavior Check List and the Kiddie-SADS for identifying attention deficit/hyperactivity disorder, depressive disorders, and oppositional defiant disorder. However, overall the specificity of the Child Behavior Check List was low. The Child Behavior Check List was not useful for identifying anxiety disorders. The Child Behavior Check List may capture core symptoms of autism spectrum disorders as well as comorbid psychopathology, and clinicians should be aware that the Child Behavior Check List may be unspecific when used in children and adolescents with autism spectrum disorders. C1 [Gjevik, Elen; Andreassen, Ole A.; Myhre, Anne M.; Sponheim, Eili] Oslo Univ Hosp, N-0424 Oslo, Norway. [Gjevik, Elen; Sandstad, Berit; Andreassen, Ole A.; Myhre, Anne M.] Univ Oslo, N-0316 Oslo, Norway. RP Gjevik, E (reprint author), Oslo Univ Hosp, Div Mental Hlth & Addict, Res Unit, POB 4959, N-0424 Oslo, Norway. EM elen.gjevik@medisin.uio.no FU University of Oslo; Oslo University Hospital; Research Council of Norway [213694] FX The current project was funded by the University of Oslo, Oslo University Hospital, and the Research Council of Norway (#213694). CR Achenbach TM, 2001, MANUAL ASEBA SCH AGE American Psychiatric Association APA, 2013, DIAGN STAT MAN MENT, V5th Antshel KM, 2011, J DEV BEHAV PEDIATR, V32, P439, DOI 10.1097/DBP.0b013e318222355d Bellina M, 2013, EUR CHILD ADOLES PSY, V22, P235, DOI 10.1007/s00787-012-0343-0 Biederman J, 2010, J DEV BEHAV PEDIATR, V31, P485, DOI 10.1097/DBP.0b013e3181e56ddd Biederman J, 2008, J ATTEN DISORD, V12, P76, DOI 10.1177/1087054707299404 Brereton AV, 2006, J AUTISM DEV DISORD, V36, P863, DOI 10.1007/s10803-006-0125-y de Bruin EI, 2007, J AUTISM DEV DISORD, V37, P877, DOI 10.1007/s10803-006-0215-x Gadow KD, 2006, J AUTISM DEV DISORD, V36, P271, DOI 10.1007/s10803-005-0060-3 Gjevik E, 2011, J AUTISM DEV DISORD, V41, P761, DOI 10.1007/s10803-010-1095-7 Hartley SL, 2008, J INTELL DISABIL RES, V52, P819, DOI 10.1111/j.1365-2788.2008.01065.x Herring S, 2006, J INTELL DISABIL RES, V50, P874, DOI 10.1111/j.1365-2788.2006.00904.x Hurtig T, 2009, AUTISM, V13, P583, DOI 10.1177/1362361309335719 Joshi G, 2010, J AUTISM DEV DISORD, V40, P1361, DOI 10.1007/s10803-010-0996-9 Kanne SM, 2009, J AUTISM DEV DISORD, V39, P856, DOI 10.1007/s10803-009-0694-7 Kanne SM, 2011, J AUTISM DEV DISORD, V41, P926, DOI 10.1007/s10803-010-1118-4 Kaufman J, 1997, J AM ACAD CHILD PSY, V36, P980, DOI 10.1097/00004583-199707000-00021 Kornor H, 2012, PSYKTESTBARN Krol NPCM, 2006, J CLIN CHILD ADOLESC, V35, P127, DOI 10.1207/s15374424jccp3501_11 Kuusikko S, 2008, J AUTISM DEV DISORD, V38, P1697, DOI 10.1007/s10803-008-0555-9 Lecavalier L, 2011, AUTISM, V15, P527, DOI 10.1177/1362361310391115 Lecavalier L, 2009, J AUTISM DEV DISORD, V39, P278, DOI 10.1007/s10803-008-0622-2 Lecavalier L, 2006, J INTELL DISABIL RES, V50, P172, DOI 10.1111/j.1365-2788.2005.00732.x Leyfer OT, 2006, J AUTISM DEV DISORD, V36, P849, DOI 10.1007/s10803-006-0123-0 Lord C, 1997, J AUTISM DEV DISORD, V27, P501, DOI 10.1023/A:1025873925661 Mattila ML, 2010, J AUTISM DEV DISORD, V40, P1080, DOI 10.1007/s10803-010-0958-2 Mazefsky CA, 2011, J PSYCHOPATHOL BEHAV, V33, P31, DOI 10.1007/s10862-010-9198-1 McPheeters ML, 2011, PEDIATRICS, V127, pE1312, DOI 10.1542/peds.2011-0427 Mukaddes NM, 2010, WORLD J BIOL PSYCHIA, V11, P964, DOI 10.3109/15622975.2010.507785 Novik TS, 1999, EUR CHILD ADOLES PSY, V8, P247 Ooi YP, 2011, J AUTISM DEV DISORD, V41, P1147, DOI 10.1007/s10803-010-1015-x Pandolfi V, 2012, RES AUTISM SPECT DIS, V6, P96, DOI 10.1016/j.rasd.2011.03.009 Pandolfi V, 2009, J AUTISM DEV DISORD, V39, P986, DOI 10.1007/s10803-009-0716-5 Posey DJ, 2007, BIOL PSYCHIAT, V61, P538, DOI 10.1016/j.biopsych.2006.09.028 Reaven J, 2012, J CHILD PSYCHOL PSYC, V53, P410, DOI 10.1111/j.1469-7610.2011.02486.x Roid G., 1997, LEITER INT PERFORMAN Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Sukhodolsky DG, 2008, J ABNORM CHILD PSYCH, V36, P117, DOI 10.1007/s10802-007-9165-9 Witwer AN, 2012, J AUTISM DEV DISORD, V42, P1949, DOI 10.1007/s10803-012-1442-y NR 39 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD MAY PY 2015 VL 19 IS 4 BP 433 EP 442 DI 10.1177/1362361314526003 PG 10 WC Psychology, Developmental SC Psychology GA CG1IK UT WOS:000353026100005 PM 24637430 ER PT J AU Andersen, PN Skogli, EW Hovik, KT Geurts, H Egeland, J Oie, M AF Andersen, Per N. Skogli, Erik W. Hovik, Kjell T. Geurts, Hilde Egeland, Jens Oie, Merete TI Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: Results from a 2-year longitudinal study SO AUTISM LA English DT Article DE Asperger's syndrome; attention-deficit; hyperactivity disorder; autism spectrum disorder; development; pervasive developmental disorder-not otherwise specified; working memory ID SCHOOL-AGE-CHILDREN; EXECUTIVE FUNCTION; SPECTRUM DISORDERS; ASPERGER-SYNDROME; DEVELOPMENTAL DISORDERS; TOTAL POPULATION; ADOLESCENTS; ADHD; SCHIZOPHRENIA; RELIABILITY AB The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder. C1 [Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Oie, Merete] Innlandet Hosp Trust, N-2629 Lillehammer, Norway. [Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Oie, Merete] Univ Oslo, N-0316 Oslo, Norway. [Geurts, Hilde] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands. [Geurts, Hilde] Dr Leo Kannerhuis, Nijmegen, Netherlands. [Egeland, Jens] Vestfold Hosp Trust, Tonsberg, Norway. RP Andersen, PN (reprint author), Innlandet Hosp Trust, Div Mental Hlth Care, N-2629 Lillehammer, Norway. EM pernoan@gmail.com FU Innlandet Hospital Trust [150170]; Regional Resource Center for Autism, ADHD, Tourette's syndrome and Narcolepsy, Oslo University Hospital [150182] FX The work was supported by grants from Innlandet Hospital Trust (grant number 150170) and from Regional Resource Center for Autism, ADHD, Tourette's syndrome and Narcolepsy, Oslo University Hospital (grant number 150182). 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This study investigated face processing in adolescents with autism spectrum disorders using the Thatcher illusion, a perceptual phenomenon exhibiting inversion effects' that characterize typical face processing. While previous studies used a limited range of face orientations, we measured perception of normality/grotesqueness of faces at seven orientations ranging from upright to inverted to allow for a detailed comparison of both reaction time and error by orientation profiles. We found that, like their typically developing peers, adolescents with autism spectrum disorders show strong inversion effects whereby reaction times were longer and error rates greater at inverted when compared to upright orientations. Additionally, the adolescents with autism spectrum disorders, like their peers in the typically developing group, show a marked nonlinearity in the error by orientation profile. 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Results from two standard explicit Theory of Mind tasks are mixed: Individuals with autism spectrum disorders did not differ from neurotypical adults in their performance in the Strange Stories Test, but scored significantly lower on the Reading the Mind in the Eyes Test. Furthermore, in an implicit false-belief task, individuals with autism spectrum disorders differed from neurotypical adults in false belief-congruent anticipatory looking. However, this group difference disappeared by (1) providing participants with the outcome of a false belief-based action and (2) subsequently repeating this test trial. Although the tendency to fixate the false belief-congruent location significantly increased from the first to the second test trial in individuals with autism spectrum disorders, it differed in neither test trial from chance. These findings support the notion of an implicit Theory of Mind deficit in autism spectrum disorders, but give rise to the idea that anticipatory looking behaviors in autism spectrum disorders may be affected by experience. Additionally, the pattern of results from implicit and explicit Theory of Mind measures supports the theory of two independent Theory of Mind reasoning systems. C1 [Schuwerk, Tobias; Vuori, Maria; Sodian, Beate] Univ Munich, D-80802 Munich, Germany. RP Schuwerk, T (reprint author), Univ Munich, Dept Psychol, Leopoldstr 13, D-80802 Munich, Germany. EM tobias.schuwerk@psy.lmu.de FU Volkswagen Foundation (Research group "The social brain") FX This research was funded by a grant from the Volkswagen Foundation (Research group "The social brain"). 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Despite the obvious importance of this issue for children with autism spectrum disorder, the literature on gestures in autism is scarce and contradictory. The purpose of this study was to analyze gestural communication in children with autism spectrum disorder during spontaneous mother-child interaction. Participants were children with autism spectrum disorder (n = 20), Down's syndrome (n = 20), and typical development (n = 20) and their mothers. Children's mean developmental age was 24.16 months (standard deviation = 1.45 months) and did not differ across the groups. Gestural communication was analyzed with a specific coding scheme allowing a quantitative and qualitative analysis of gestural production. 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Roberts, Wendy Stoddart, Kevin P. Zwaigenbaum, Lonnie TI Autism comes to the hospital: The experiences of patients with autism spectrum disorder, their parents and health-care providers at two Canadian paediatric hospitals SO AUTISM LA English DT Article DE autism spectrum disorder; health care; hospital; medical; paediatric; qualitative methods ID DEVELOPMENTAL-DISABILITIES; MEDICAL CONDITIONS; CHILDREN; MANAGEMENT; EXPENDITURES; ADOLESCENTS; BEHAVIOR AB Youth with autism spectrum disorder are a vulnerable, often poorly understood patient group, who may experience periodic and chronic health challenges, in addition to their primary developmental social and communication problems. Developmental and behavioural challenges can complicate management of acute health-care needs. To date, there is an absence of empirical research exploring the hospital experiences of children and youth with autism spectrum disorder, their families and their health-care providers. Therefore, the purpose of this study was to understand these experiences in order to inform hospital-based care. A total of 42 participants were interviewed (youth with autism spectrum disorder, their parents and health-care providers) at one of two Canadian paediatric hospitals, representing 20 distinct cases of patients with autism spectrum disorder. Results from the qualitative analyses indicated that patients with autism spectrum disorder faced several challenges in the context of health-care delivery in the hospital setting, as did their families and health-care provider team. Problems identified included communication and sensory challenges, and the degree of flexibility of health-care providers and the hospital organization. Supportive health-care providers were those who acknowledged parents as experts, inquired about the requirements of patients with autism spectrum disorder and implemented strategies that accommodated the unique clinical presentation of the individual patient. These recommendations have wide-reaching utility for hospital and health-care practices involving this patient group. C1 [Muskat, Barbara; Burnham Riosa, Priscilla; Roberts, Wendy] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Muskat, Barbara; Roberts, Wendy; Stoddart, Kevin P.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Nicholas, David B.] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Stoddart, Kevin P.] Redpath Ctr, Toronto, ON, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Edmonton, AB T6G 2M7, Canada. [Zwaigenbaum, Lonnie] Glenrose Rehabil Hosp, Edmonton, AB, Canada. RP Muskat, B (reprint author), Hosp Sick Children, Dept Social Work, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. 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H. TI The implications of de novo coding mutations in simplex autism families SO CLINICAL GENETICS LA English DT Editorial Material ID SPECTRUM C1 [Utami, K. H.] Translat Lab Genet Med TLGM, Agcy Sci, Res & Technol, Singapore, Singapore. RP Utami, KH (reprint author), Translat Lab Genet Med TLGM, Agcy Sci, Res & Technol, Singapore, Singapore. RI ahmed, Jamila/E-8653-2015 CR Iossifov I, 2014, NATURE, V515, P216, DOI 10.1038/nature13908 Iossifov I, 2012, NEURON, V74, P285, DOI 10.1016/j.neuron.2012.04.009 Michaelson JJ, 2012, CELL, V151, P1431, DOI 10.1016/j.cell.2012.11.019 O'Roak BJ, 2012, NATURE, V485, P246, DOI 10.1038/nature10989 NR 4 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9163 EI 1399-0004 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2015 VL 87 IS 5 BP 428 EP 429 DI 10.1111/cge.12582 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA CF8GS UT WOS:000352794800005 PM 25753786 ER PT J AU Lane, RD Hsu, CH Locke, DEC Ritenbaugh, C Stonnington, CM AF Lane, Richard D. Hsu, Chiu-Hsieh Locke, Dona E. C. Ritenbaugh, Cheryl Stonnington, Cynthia M. TI Role of theory of mind in emotional awareness and alexithymia: Implications for conceptualization and measurement SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Theory of mind; Alexithymia; Affective agnosia; Emotional awareness; Somatic symptom disorders ID ASPERGER-SYNDROME; AUTISM; SCALE; SOMATIZATION; RECOGNITION; VALIDATION; DEPRESSION; SELF AB The goal of this study was to determine whether alexithymia, which is characterized by difficulty in recognizing and describing emotions, is associated with impairments in the ability to mentally represent emotional states. We studied 89 outpatients including 29 conversion disorder patients, 30 functional somatic syndrome [e.g. fibromyalgia] patients and 30 medical controls. Groups did not differ on affective or cognitive Theory of Mind (TOM) measures, the Levels of Emotional Awareness Scale (LEAS) or the Twenty-Item Toronto Alexithymia Scale (TAS20) after adjusting for Positive and Negative Affect Scale (PANAS) variables. Across all patients, LEAS but not TAS-20 correlated positively with affective and cognitive ToM measures after adjusting for PANAS scores. Impairments in ToM functioning influence LEAS performance but not TAS-20 scores. These findings support the distinction between a milder "anomia" form of alexithymia associated with impaired emotion naming and a more severe "agnosia" form associated with impaired mental representation of emotion. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lane, Richard D.] Univ Arizona, Dept Psychiat Psychol & Neurosci, Tucson, AZ 85724 USA. 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Post-error slowing and the difference in Error-Related Negativity amplitude between correct and incorrect responses (ERNdiff) were used to index error-monitoring ability. Overall, ERNdiff increased with age. On the Gender Task, individuals with ASD had a smaller ERNdiff than individuals with typical development; however, on the Affect Task, there were no significant diagnostic group differences on ERNdiff. Individuals with ASD may have ERN amplitudes similar to those observed in individuals with typical development in more social contexts compared to less social contexts due to greater consequences for errors, more effortful processing, and/or reduced processing efficiency in these contexts. Across all participants, more post-error slowing on the Affect Task was associated with better social cognitive skills. C1 [McMahon, Camilla M.] 3C Inst, Cary, NC 27513 USA. [Henderson, Heather A.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada. RP McMahon, CM (reprint author), 3C Inst, 1901 N Harrison Ave,Suite 200, Cary, NC 27513 USA. EM camillam@live.com FU National Institute of Health (NIH) [R01MH071273, T32MH073124]; Institute of Education Sciences, US Department of Education [DED-R305C050052] FX This research was supported by the National Institute of Health (NIH), through Grants R01MH071273 and T32MH073124, and the Institute of Education Sciences, US Department of Education, through Grant DED-R305C050052. The opinions expressed are those of the authors and do not represent views of NIH or the US Department of Education. The authors thank Michael Alessandri, Jessica Alvarez, Alexis Bitting, Diana Borrero, Jeffrey Brosco, Elektra Burgos, Jessica Cardenas, Raphaelle Cuenod, Irene Daboin, Cristina De Armas, Stephanie Dickinson, Michaela Gaffley, Bridget Gamber, Allyson Hodgkins, Mark Jaime, Nicole Kojkowski, Krystal Lago, Peggy Laguerre, Javier Lopez-Calderon, Adam McMahon, Daniel Messinger, Leena Mohapatra, Lisa Newell, Kimie Ono, Jessica Smolarz, and Marygrace Yale-Kaiser for their contributions. 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Sci. PD MAY PY 2015 VL 18 IS 3 BP 389 EP 403 DI 10.1111/desc.12220 PG 15 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA CG1SJ UT WOS:000353054000003 PM 25066088 ER PT J AU Popp, B Stove, SI Endele, S Myklebust, LM Hoyer, J Sticht, H Azzarello-Burri, S Rauch, A Arnesen, T Reis, A AF Popp, Bernt Stove, Svein I. Endele, Sabine Myklebust, Line M. Hoyer, Juliane Sticht, Heinrich Azzarello-Burri, Silvia Rauch, Anita Arnesen, Thomas Reis, Andre TI De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID N-TERMINAL ACETYLTRANSFERASE; LENZ MICROPHTHALMIA SYNDROME; AUTISM SPECTRUM DISORDERS; COFFIN-LOWRY-SYNDROME; ALPHA-ACETYLTRANSFERASE; INTELLECTUAL DISABILITY; SEQUENCING DATA; HUMAN GENOME; COMPLEX; ARD1 AB Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity. C1 [Popp, Bernt; Endele, Sabine; Hoyer, Juliane; Reis, Andre] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany. [Stove, Svein I.; Myklebust, Line M.; Arnesen, Thomas] Univ Bergen, Dept Mol Biol, Bergen, Norway. [Stove, Svein I.; Arnesen, Thomas] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway. [Sticht, Heinrich] Univ Erlangen Nurnberg, Inst Biochem, D-91054 Erlangen, Germany. [Azzarello-Burri, Silvia; Rauch, Anita] Univ Zurich, Inst Med Genet, Schlieren, Switzerland. RP Reis, A (reprint author), Univ Erlangen Nurnberg, Inst Human Genet, Schwabachanlage 10, D-91054 Erlangen, Germany. EM andre.reis@uk-erlangen.de FU German Intellectual Disability Network (MRNET) through German Ministry of Research and Education [01GS08160]; Swiss National Science Foundation [SNF 320030_135669]; Research Council of Norway; Norwegian Cancer Society; Bergen Research Foundation (BFS); Western Norway Health Authorities FX We are grateful to the families involved in this study for their participation. We thank Angelika Diem and Daniela Schweitzer for excellent technical assistance and Steffen Uebe and Arif Ekici for assistance in NGS. This manuscript is part of a doctoral thesis of Bernt Popp. We thank the Novocraft Technologies Company for granting a trial license of novoalignCS. This study was supported in part by the German Intellectual Disability Network (MRNET) through a grant from the German Ministry of Research and Education to Andre Reis (01GS08160), by a grant from the Swiss National Science Foundation (SNF 320030_135669) to Anita Rauch and by the Research Council of Norway, the Norwegian Cancer Society, Bergen Research Foundation (BFS) and the Western Norway Health Authorities to Thomas Arnesen. 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J. Hum. Genet. PD MAY PY 2015 VL 23 IS 5 BP 602 EP 609 DI 10.1038/ejhg.2014.150 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1JF UT WOS:000353028200010 PM 25099252 ER PT J AU Vergult, S Dheedene, A Meurs, A Faes, F Isidor, B Janssens, S Gautier, A Le Caignec, C Menten, B AF Vergult, Sarah Dheedene, Annelies Meurs, Alfred Faes, Fran Isidor, Bertrand Janssens, Sandra Gautier, Agnes Le Caignec, Cedric Menten, Bjorn TI Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and intellectual disability SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEPENDENT CALCIUM-CHANNELS; LINKED MENTAL-RETARDATION; COPY NUMBER VARIANTS; BIPOLAR DISORDER; WIDE ASSOCIATION; MUTATION; IDENTIFICATION; SUBUNIT; PICCOLO; PROTEIN AB Voltage-gated calcium channels have an important role in neurotransmission. Aberrations affecting genes encoding the alpha subunit of these channels have been associated with epilepsy and neuropsychiatric disorders such as autism or schizophrenia. Here we report three patients with a genomic aberration affecting the CACNA2D1 gene encoding the alpha 2 delta subunit of these voltage-gated calcium channels. All three patients present with epilepsy and intellectual disability pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical features. Besides these characteristics, patient 2 also presents with obesity with hyperinsulinism, which is very likely to be caused by deletion of the CD36 gene. C1 [Vergult, Sarah; Dheedene, Annelies; Janssens, Sandra; Menten, Bjorn] Univ Ghent, Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Meurs, Alfred] Univ Ghent, Ghent Univ Hosp, Dept Neurol, Lab Clin & Expt Neurophysiol Neurobiol & Neuropsy, B-9000 Ghent, Belgium. [Faes, Fran] Ghent Univ Hosp, Ctr Ontwikkelingsstoornissen COS, Ghent, Belgium. [Isidor, Bertrand; Le Caignec, Cedric] Inst Biol, Serv Genet Med, Nantes, France. [Gautier, Agnes] CHU Nantes, Serv Pediat, F-44035 Nantes 01, France. RP Menten, B (reprint author), Univ Ghent, Ghent Univ Hosp, Ctr Med Genet, Pintelaan 185, B-9000 Ghent, Belgium. EM Bjorn.Menten@Ugent.be FU Research Foundation-Flanders (FWO); Special Research Fund (BOF) from Ghent University; Belgian State, Prime Minister's Office, Science Policy Programming (IUAP); Wellcome Trust FX We are indebted to the patients and their parents. We thank Willy Lissens for the X-inactivation assay and Lies Vantomme for expert technical assistance. Sarah Vergult was supported by a PhD fellowship of the Research Foundation-Flanders (FWO) and is now supported by a postdoctoral grant from the Special Research Fund (BOF) from Ghent University. 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TI Developmental Links Between Disobedient Behavior and Social Classroom Relationships in Boys With Psychiatric Disorders in Special Education SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Behavior problems; Teacher-child relationship; Peer relations; Special education; EBD ID TEACHER-CHILD RELATIONSHIPS; AUTISM SPECTRUM DISORDERS; PEER RELATIONSHIPS; EXTERNALIZING BEHAVIOR; EMOTIONAL ADJUSTMENT; RECIPROCAL RELATIONS; STUDENT RELATIONSHIP; SCHOOL ADJUSTMENT; SELF-PERCEPTIONS; AGGRESSION AB In mainstream education, positive relationships with teachers and peers have been found to positively influence children's behavioral development. However, high levels of classroom behavior problems may hinder the formation of such positive relationships. Therefore, findings from mainstream education cannot be generalized to special education. The present study investigated the developmental links between disobedience and positive as well as negative relationships with teachers and peers among boys in restrictive special educational settings. At three assessment waves across one school year, teacher-reports of teacher-child closeness and conflict, and peer-reports of peer acceptance, rejection and disobedience were collected among 340 boys (mean age = 10.1 years, SD = 1.58, range = 5-13) with psychiatric disorders receiving special education. Autoregressive cross-lagged models were fitted to explore the nature of these developmental links. The impact of boys' age was examined using multiple group analyses. Findings supported the importance of teacher-child conflict, but not closeness, and positive and negative peer relationships for the development of boys' disobedience, with a stronger effect of negative than positive relationships. 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Lee, Chi-Chun Audhkhasi, Kartik Narayanan, Shrikanth TI Applying Machine Learning to Facilitate Autism Diagnostics: Pitfalls and Promises SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism diagnostic observation schedule; Autism diagnostic interview; Machine learning; Signal processing; Autism; Diagnosis ID SPECTRUM DISORDERS; OBSERVATION SCHEDULE; CLASSIFICATION; INTERVIEW; ACCURACY; BRAIN AB Machine learning has immense potential to enhance diagnostic and intervention research in the behavioral sciences, and may be especially useful in investigations involving the highly prevalent and heterogeneous syndrome of autism spectrum disorder. However, use of machine learning in the absence of clinical domain expertise can be tenuous and lead to misinformed conclusions. To illustrate this concern, the current paper critically evaluates and attempts to reproduce results from two studies (Wall et al. in Transl Psychiatry 2(4):e100, 2012a; PloS One 7(8), 2012b) that claim to drastically reduce time to diagnose autism using machine learning. Our failure to generate comparable findings to those reported by Wall and colleagues using larger and more balanced data underscores several conceptual and methodological problems associated with these studies. We conclude with proposed best-practices when using machine learning in autism research, and highlight some especially promising areas for collaborative work at the intersection of computational and behavioral science. C1 [Bone, Daniel; Audhkhasi, Kartik; Narayanan, Shrikanth] Univ So Calif, SAIL, Los Angeles, CA 90089 USA. [Goodwin, Matthew S.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Black, Matthew P.] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Lee, Chi-Chun] Natl Tsing Hua Univ, Dept Elect Engn, Hsinchu 30013, Taiwan. RP Bone, D (reprint author), Univ So Calif, SAIL, 3710 McClintock Ave, Los Angeles, CA 90089 USA. EM dbone@usc.edu RI ahmed, Jamila/E-8653-2015 FU NSF [1029035]; NIH [P50 DC013027, R01 DC012774]; Alfred E. Mann Innovation in Engineering Fellowship FX This work was supported by funds from NSF Award 1029035, "Computational Behavioral Science: Modeling, Analysis, and Visualization of Social and Communicative Behavior'', NIH grants P50 DC013027 and R01 DC012774, and the Alfred E. Mann Innovation in Engineering Fellowship. The authors are grateful to Shanping Qiu for her efforts in acquiring and preparing the BID data for analysis. 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E., 2014, J SPEECH LANGUAGE HE Ye Z., 2012, P 2012 ACM C UB COMP, P699 NR 37 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1121 EP 1136 DI 10.1007/s10803-014-2268-6 PG 16 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200001 PM 25294649 ER PT J AU Carlisle, GK AF Carlisle, Gretchen K. TI The Social Skills and Attachment to Dogs of Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Dogs; Children; Attachment; Social skills ID OWNERSHIP; THERAPY; PET AB Children with Autism Spectrum Disorder (ASD) have deficits in social skills, and interaction with service dogs has been associated with increased social skills for children with ASD. In this telephone survey of 70 parents of children with ASD, children owning dogs had greater Mean scores for social skills, using the Social Skills Improvement System Rating Scale, while those with some type of pet (not excluding dogs) had significantly greater skills for subscale item "assertion". Parents described their children as attached to their dogs. Children owning dogs completed the Companion Animal Bonding Scale, and reported strong bonding with dogs. These findings suggest children with ASD may bond with their dogs, and pet ownership may be associated with increased social skills. C1 Univ Missouri, Coll Vet Med, Res Ctr Human Anim Interact, Columbia, MO 65211 USA. RP Carlisle, GK (reprint author), Univ Missouri, Coll Vet Med, Res Ctr Human Anim Interact, Clydesdale Annex 2,900 East Campus Dr, Columbia, MO 65211 USA. EM carlislegk@missouri.edu FU Sigma Theta Tau-Alpha Iota Chapter FX The author acknowledges the University of Missouri Thompson Center for Autism and Neurodevelopmental Disorders for the use of their data set in recruitment. A grant to support this study was awarded from Sigma Theta Tau-Alpha Iota Chapter. This paper was prepared from the author's doctoral dissertation, acknowledging the support of her dissertation committee members, Dr. Rebecca A. Johnson, Dr. Lawrence Ganong, Dr. Debra Gayer and Dr. Micah Mazurek. A poster presentation of the data was made at the Midwest Nursing Research Society conference in Chicago, Illinois on March, 2013. CR American Psychiatric Association, 2013, DIAGNOSTIC AND STATI American Veterinary Medical Association, 2012, US PET OWNERSHIP DEM Berry A, 2013, J ALTERN COMPLEM MED, V19, P73, DOI 10.1089/acm.2011.0835 Bryant B. K., 1990, Anthrozoös, V3, P253 Burrows KE, 2008, QUAL HEALTH RES, V18, P1642, DOI 10.1177/1049732308327088 Carlisle G. 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PD MAY PY 2015 VL 45 IS 5 BP 1137 EP 1145 DI 10.1007/s10803-014-2267-7 PG 9 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200002 PM 25308197 ER PT J AU Crutchfield, SA Mason, RA Chambers, A Wills, HP Mason, BA AF Crutchfield, Stephen A. Mason, Rose A. Chambers, Angela Wills, Howard P. Mason, Benjamin A. TI Use of a Self-monitoring Application to Reduce Stereotypic Behavior in Adolescents with Autism: A Preliminary Investigation of I-Connect SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Self-monitoring; Stereotypic behavior; Technology-based application ID MANAGEMENT TREATMENT PACKAGE; REPETITIVE BEHAVIORS; SPECTRUM DISORDER; CHILDREN; STUDENTS; SKILLS; MODEL; REINFORCEMENT; INTERVENTIONS; DISABILITIES AB Many students with autism engage in a variety of complex stereotypic behaviors, impacting task completion and interfering with social opportunities. Self-monitoring is an intervention with empirical support for individuals with ASD to increase behavioral repertoires and decrease behaviors that are incompatible with successful outcomes. However, there is limited evidence for its utility for decreasing stereotypy, particularly for adolescents in school settings. This study evaluated the functional relationship between I-Connect, a technology-delivered self-monitoring program, and decreases in the level of stereotypy for two students with ASD in the school setting utilizing a withdrawal design with an embedded multiple baseline across participants. Both students demonstrated a marked decrease in stereotypy with the introduction of the self-monitoring application. Results and implications for practice and future research will be discussed. C1 [Crutchfield, Stephen A.; Mason, Rose A.; Wills, Howard P.; Mason, Benjamin A.] Univ Kansas, Juniper Gardens Childrens Project, Kansas City, KS 66101 USA. [Chambers, Angela] Univ Kansas, Sch Educ, Dept Special Educ, Lawrence, KS 66045 USA. RP Crutchfield, SA (reprint author), Univ Kansas, Juniper Gardens Childrens Project, 444 Minnesota Ave, Kansas City, KS 66101 USA. EM stephencrutchfield@ku.edu; rosemason519@gmail.com FU U.S. Department of Education, Institute of Education Sciences [R324B100004]; National Institute on Disability and Rehabilitation Research [H133A130032]; Office of Special Education Programs [H327A100082]; I-CONNECT PLUS: Enhancing Community Participation for Adolescents and Adults with ASD Using Online Instruction, Coaching, and Accessible Self-Management Technologies [H133A130032] FX The authors disclosed receipt of the following financial support for the research, and/or publication of this article: This research was supported in part by grants from the U.S. Department of Education, Institute of Education Sciences (R324B100004), the National Institute on Disability and Rehabilitation Research (H133A130032), and the Office of Special Education Programs (H327A100082). The opinions expressed in this article are not necessarily reflective of the positions of the U.S. Department of Education. This research was supported in part by the Research Grant No. H133A130032, I-CONNECT PLUS: Enhancing Community Participation for Adolescents and Adults with ASD Using Online Instruction, Coaching, and Accessible Self-Management Technologies. CR Agran M, 2005, EDUC TRAIN DEV DISAB, V40, P3 American Psychiatric and Association, 2012, DIAGN STAT MAN MENT Boyd BA, 2012, J AUTISM DEV DISORD, V42, P1236, DOI 10.1007/s10803-011-1284-z Bracken B. A., 1998, UNIVERSAL NONVERBAL Bregman J. D., 2012, ED STUDENTS AUTISM S, P13 Cervantes PE, 2014, RES AUTISM SPECT DIS, V8, P502, DOI 10.1016/j.rasd.2014.01.008 Cooper J. 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Westerlund, Joakim Bejerot, Susanne TI Autism Spectrum Disorders and Self-reports: Testing Validity and Reliability Using the NEO-PI-R SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Self report; Psychometrics; Validation; Personality tests ID QUOTIENT AQ; DEPRESSION; INTERVIEW; ADULTS; SCALE; BIAS; PERSONALITY; POPULATION; VALIDATION; CHILDREN AB Although self-reported measures are frequently used to assess adults with autism spectrum disorders (ASD), the validity of self-reports is under-researched in ASD. The core symptoms of ASD may negatively affect the psychometric properties of self-reported measures. The aim of the present study was to test the validity and reliability of self-reported data using the NEO personality inventory-revised (NEO-PI-R). Forty-eight adults with ASD and 53 controls completed the NEO-PI-R and a psychiatric interview. Results indicate satisfactory internal consistency of the NEO-PI-R, a satisfactory factor structure, predicted correlations with clinician ratings in the ASD group, and predicted differences in personality between the ASD group and controls. In conclusion, the present results support the use of self-reported measures when assessing adults with ASD . C1 [Hesselmark, Eva; Eriksson, Jonna M.; Bejerot, Susanne] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Hesselmark, Eva; Bejerot, Susanne] St Gorans Sjukhus, Norra Stockholm Psykiatri, S-11281 Stockholm, Sweden. [Westerlund, Joakim] Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. RP Hesselmark, E (reprint author), St Gorans Sjukhus, Norra Stockholm Psykiatri, Patientvagen 2,3Tr, S-11281 Stockholm, Sweden. EM eva.hesselmark@ki.se FU St Goran Foundation; Swedish Society of Medicine; Thuring Foundation FX The authors want to express their gratitude towards all participants who agreed to sign up for the study and to Dr. Sabina Bonde who assisted in some of the assessments. Technical support was provided by Christina Arlinde and Ann Lindgren. This study was supported by the St Goran Foundation, The Swedish Society of Medicine and the Thuring Foundation. 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This cross-sectional study used the Parent Observation of Early Markers Scale (POEMS, Feldman et al. in J Autism Dev Disord 42:13-12, 2012) to identify early signs of ASD in 69 ASD high-risk (older sibling diagnosed with ASD) and 69 sex and aged-matched ASD low-risk second-born or later infants (no family history of ASD) between 6 and 36 months of age. Family sociodemographic comparisons were also made between the risk groups. The high-risk children had significantly more elevated POEMS items than the low-risk children at 12, 18, 24, 30 and 36 months of age, even when the children subsequently diagnosed with ASD were removed from the analyses. Families of the high-risk group had older parents, lower family income and fewer mothers working out of the home than the low-risk group. These sociodemographic variables were not significantly correlated with POEMS scores. The results suggest that high-risk infants may show signs of the broader ASD phenotype as early as 12 months of age that may be unrelated to observed sociodemographic family differences. C1 [Feldman, Maurice A.; Hendry, Amanda M.; Ward, Rebecca A.] Brock Univ, Ctr Appl Disabil Studies, St Catharines, ON L2S 3A1, Canada. [Hudson, Melissa; Liu, Xudong] Queens Univ, Genom Lab Ongwanada, Kingston, ON K7M 8A6, Canada. RP Feldman, MA (reprint author), Brock Univ, Ctr Appl Disabil Studies, 500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada. EM mfeldman@brocku.ca; hendry_amanda@hotmail.com; bward@brocku.ca; melissa.hudson@queensu.ca; liux@queensu.ca FU CIHR Interdisciplinary Health Research Team [RT-43820]; Ongwanada FX This work was supported by CIHR Interdisciplinary Health Research Team grant (RT-43820) to the Autism Spectrum Disorders Canadian-American Research Consortium (ASD-CARC: www.autismresearch.ca) and funding from Ongwanada. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1167 EP 1175 DI 10.1007/s10803-014-2277-5 PG 9 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200005 PM 25326257 ER PT J AU Haigh, SM Heeger, DJ Dinstein, I Minshew, N Behrmann, M AF Haigh, Sarah M. Heeger, David J. Dinstein, Ilan Minshew, Nancy Behrmann, Marlene TI Cortical Variability in the Sensory-Evoked Response in Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; fMRI; Sensory-evoked; Variability ID HIGH-FUNCTIONING AUTISM; INTRAINDIVIDUAL VARIABILITY; DEVELOPMENTAL NEUROBIOLOGY; DIAGNOSTIC INTERVIEW; SPECTRUM DISORDERS; BINOCULAR-RIVALRY; BRAIN; CHILDREN; EPILEPSY; CONNECTIVITY AB Previous findings have shown that individuals with autism spectrum disorder (ASD) evince greater intra-individual variability (IIV) in their sensory-evoked fMRI responses compared to typical control participants. We explore the robustness of this finding with a new sample of high-functioning adults with autism. Participants were presented with visual, somatosensory and auditory stimuli in the scanner whilst they completed a one-back task. While ASD and control participants were statistically indistinguishable with respect to behavioral responses, the new ASD group exhibited greater IIV relative to controls. We also show that the IIV was equivalent across hemispheres and remained stable over the duration of the experiment. This suggests that greater cortical IIV may be a replicable characteristic of sensory systems in autism. C1 [Haigh, Sarah M.; Behrmann, Marlene] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Haigh, Sarah M.; Minshew, Nancy] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Heeger, David J.] NYU, Dept Psychol, New York, NY 10003 USA. [Heeger, David J.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Dinstein, Ilan] Ben Gurion Univ Negev, Dept Psychol, IL-84105 Beer Sheva, Israel. [Minshew, Nancy] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. RP Haigh, SM (reprint author), Univ Pittsburgh, Dept Psychiat, Suite 420 Oxford Bldg, Pittsburgh, PA 15213 USA. EM haighsm@upmc.edu RI ahmed, Jamila/E-8653-2015 FU Simons Foundation Autism Research Initiative [177638]; NIH/NICHD [HD055748] FX The research described here was supported by a Grant from the Simons Foundation Autism Research Initiative (177638) to DH and MB, and a NIH/NICHD Grant (HD055748) to NJM. The authors thank Ryan Egan for helping with participant recruitment and fMRI testing. We also thank the staff at the Center for Excellence in Autism Research at the University of Pittsburgh for recruitment and assessment of participants. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1176 EP 1190 DI 10.1007/s10803-014-2276-6 PG 15 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200006 PM 25326820 ER PT J AU van Asselt-Goverts, AE Embregts, PJCM Hendriks, AHC Wegman, KM Teunisse, JP AF van Asselt-Goverts, A. E. Embregts, P. J. C. M. Hendriks, A. H. C. Wegman, K. M. Teunisse, J. P. TI Do Social Networks Differ? Comparison of the Social Networks of People with Intellectual Disabilities, People with Autism Spectrum Disorders and Other People Living in the Community SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Intellectual disabilities; Autism; Social network; Satisfaction; Wishes ID QUALITY-OF-LIFE; HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; SUPPORT; ADULTS; CHILDREN; INDIVIDUALS; FRIENDSHIP; MILD; ADOLESCENTS AB The aim of this study was to determine the similarities and differences in social network characteristics, satisfaction and wishes with respect to the social network between people with mild or borderline intellectual disabilities (ID), people with autism spectrum disorders (ASD) and a reference group. Data were gathered from 105 young adults living independently in the community. The social networks of people with ID and ASD are more restricted than those of the reference group. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1191 EP 1203 DI 10.1007/s10803-014-2279-3 PG 13 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200007 PM 25326258 ER PT J AU Bouck, EC Joshi, GS AF Bouck, Emily C. Joshi, Gauri S. TI Does Curriculum Matter for Secondary Students with Autism Spectrum Disorders: Analyzing the NLTS2 SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Secondary; Education; Functional curriculum; Post-school outcomes ID NATIONAL LONGITUDINAL TRANSITION; YOUNG-ADULTS; POSTSCHOOL OUTCOMES; HIGH-SCHOOL; EMPLOYMENT; DISABILITIES; YOUTH; INSTRUCTION; EDUCATION; SKILLS AB A common presumption of secondary education is that what occurs in-school impacts students after they exit school. Previous researchers found transition-services received in school by students with autism spectrum disorder predicted their post-school success with regards to employment and independent living. 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PD MAY PY 2015 VL 45 IS 5 BP 1204 EP 1212 DI 10.1007/s10803-014-2281-9 PG 9 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200008 PM 25326821 ER PT J AU Knight, VF Sartini, E AF Knight, Victoria F. Sartini, Emily TI A Comprehensive Literature Review of Comprehension Strategies in Core Content Areas for Students with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Evidence-based practice; Content areas; Comprehension; Math; ELA; Science ID SEVERE DEVELOPMENTAL-DISABILITIES; COOPERATIVE LEARNING GROUPS; READING-COMPREHENSION; INTELLECTUAL DISABILITY; GRAPHIC ORGANIZERS; INTEGRATION STRATEGY; QUESTION GENERATION; NORMAL-CHILDREN; TEACH SCIENCE; YOUNG-ADULTS AB Understanding text can increase access to educational, vocational, and recreational activities for individuals with autism spectrum disorder (ASD); however, limited research has been conducted investigating instructional practices to remediate or compensate for these comprehension challenges. The current comprehensive literature review expanded previous reviews and evaluated research quality using Reichow (Evidence-based practices and treatments for children with autism, pp 25-39. doi:10.1007/978-1-4419-6975-0_2, 2011) criteria for identifying evidence-based practices. Three questions guided the review: (a) Which approaches to comprehension instruction have been investigated for students with ASD?; (b) Have there been a sufficient number of acceptable studies using a particular strategy to qualify as an evidence-based practice for teaching comprehension across the content areas?; and (c) What can educators learn from the analysis of high quality studies? Of the 23 studies included in the review, only 13 achieved high or adequate ratings. Results of the review suggest that both response-prompting procedures (e.g., model-lead-test, time delay, system of least prompts,) and visual supports (e.g., procedural facilitators) can increase comprehension skills in content areas of ELA, math, and science. Authors conclude with a discussion of (a) research-based examples of how to use effective approaches, (b) implications for practitioners, and (c) limitations and future research. C1 [Knight, Victoria F.] Vanderbilt Univ, Dept Special Educ, Nashville, TN 37203 USA. [Sartini, Emily] Univ Kentucky, Lexington, KY USA. RP Knight, VF (reprint author), Vanderbilt Univ, Dept Special Educ, GPC 228,230 Appleton Pl, Nashville, TN 37203 USA. EM victoria.f.knight@vanderbilt.edu; emily.sartini@uky.edu CR Allor JH, 2010, EDUC TRAIN AUTISM DE, V45, P3 American Psychiatric Association, 2013, DIAGN STAT MAN MENT Armstrong T. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1213 EP 1229 DI 10.1007/s10803-014-2280-x PG 17 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200009 PM 25331325 ER PT J AU Lai, KYC Leung, PWL Mo, FYM Lee, MMC Shea, CKS Chan, GFC Che, KKI Luk, ESL Mak, ADP Warrington, R Skuse, D AF Lai, Kelly Y. C. Leung, Patrick W. L. Mo, Flora Y. M. Lee, Marshall M. C. Shea, Caroline K. S. Chan, Grace F. C. Che, Kiti K. I. Luk, Ernest S. L. Mak, Arthur D. P. Warrington, Richard Skuse, David TI Validation of the Developmental, Dimensional and Diagnostic Interview (3Di) Among Chinese Children in a Child Psychiatry Clinic in Hong Kong SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; 3Di; Chinese; Validation ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TWIN SAMPLE; POPULATION; VALIDITY; TRAITS; ADHD; HERITABILITY; SYMPTOMS AB Autism spectrum disorder (ASD) is a disorder with high levels of co-morbidities. The Developmental, Dimensional and Diagnostic Interview (3Di) is a relatively new instrument designed to provide dimensional as well as categorical assessment of autistic behaviours among children with normal intelligence. Its sound psychometric properties and relatively short administration time make it a versatile instrument. The 3Di was translated into Chinese (Cantonese) and its applicability among 194 clinic children was examined. Results found excellent reliability and validity, and achieved a sensitivity of 95 % and specificity of 77 %. It was able to capture the diagnosis of ASD among children presenting with attention deficit hyperactivity disorder. However, although the disorder of ASD is considered universal, the use of a western instrument in a Chinese context should also take note of cultural influences that may impact on the manifestation of its symptoms. C1 [Lai, Kelly Y. C.; Luk, Ernest S. L.; Mak, Arthur D. P.] Chinese Univ Hong Kong, Dept Psychiat, Shatin, Hong Kong, Peoples R China. [Leung, Patrick W. L.] Chinese Univ Hong Kong, Dept Psychol, Shatin, Hong Kong, Peoples R China. [Mo, Flora Y. M.; Lee, Marshall M. C.; Shea, Caroline K. S.; Chan, Grace F. C.; Che, Kiti K. I.] Alice Ho Miu Ling Nethersole Hosp, Dept Psychiat, Tai Po, Hong Kong, Peoples R China. [Warrington, Richard; Skuse, David] Inst Child Hlth, London, England. RP Lai, KYC (reprint author), Chinese Univ Hong Kong, Dept Psychiat, Shatin, Hong Kong, Peoples R China. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1230 EP 1237 DI 10.1007/s10803-014-2284-6 PG 8 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200010 PM 25326822 ER PT J AU Waite, J Moss, J Beck, SR Richards, C Nelson, L Arron, K Burbidge, C Berg, K Oliver, C AF Waite, Jane Moss, Joanna Beck, Sarah R. Richards, Caroline Nelson, Lisa Arron, Kate Burbidge, Cheryl Berg, Katy Oliver, Chris TI Repetitive Behavior in Rubinstein-Taybi Syndrome: Parallels with Autism Spectrum Phenomenology SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Rubinstein-Taybi syndrome; Autism spectrum disorder (ASD); Repetitive behavior; Ritualistic behavior ID PRADER-WILLI-SYNDROME; FRAGILE-X SYNDROMES; STEREOTYPED BEHAVIORS; DOWN-SYNDROME; CHILDREN; PREVALENCE; DISORDERS; DEFICITS; PEOPLE; ASSOCIATIONS AB Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS. C1 [Waite, Jane; Moss, Joanna; Beck, Sarah R.; Richards, Caroline; Arron, Kate; Oliver, Chris] Univ Birmingham, Sch Psychol, Cerebra Ctr Neurodev Disorders, Birmingham B15 2TT, W Midlands, England. [Moss, Joanna] UCL, Inst Cognit Neurosci, London, England. [Nelson, Lisa] Royal Derby Hosp, Derbyshire Childrens Hosp, Dept Clin Psychol, Derby, England. 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PD MAY PY 2015 VL 45 IS 5 BP 1238 EP 1253 DI 10.1007/s10803-014-2283-7 PG 16 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200011 PM 25491025 ER PT J AU Yoder, P Watson, LR Lambert, W AF Yoder, Paul Watson, Linda R. Lambert, Warren TI Value-Added Predictors of Expressive and Receptive Language Growth in Initially Nonverbal Preschoolers with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Spoken language; Useful speech; Predictors; Nonverbal; Longitudinal ID DIAGNOSTIC OBSERVATION SCHEDULE; CHILD-DIRECTED SPEECH; COMMUNICATIVE DEVELOPMENT INVENTORY; YOUNG-CHILDREN; FOLLOW-UP; JOINT ATTENTION; SOCIAL COGNITION; PHYSIOLOGICAL-RESPONSES; TYPICAL DEVELOPMENT; SYMBOLIC PLAY AB Eighty-seven preschoolers with autism spectrum disorders who were initially nonverbal (under 6 words in language sample and under 21 parent-reported words said) were assessed at five time points over 16 months. Statistical models that accounted for the intercorrelation among nine theoretically- and empirically-motivated predictors, as well as two background variables (i.e., cognitive impairment level, autism severity), were applied to identify value-added predictors of expressive and receptive spoken language growth and outcome. The results indicate that responding to joint attention, intentional communication, and parent linguistic responses were value-added predictors of both expressive and receptive spoken language growth. In addition, consonant inventory was a value-added predictor of expressive growth; early receptive vocabulary and autism severity were value-added predictors of receptive growth. C1 [Yoder, Paul] Vanderbilt Univ, Special Educ, Nashville, TN 37235 USA. [Watson, Linda R.] Univ N Carolina, Speech & Hearing Sci, Chapel Hill, NC USA. [Lambert, Warren] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37235 USA. RP Yoder, P (reprint author), Vanderbilt Univ, Special Educ, 221 Kirkland Hall, Nashville, TN 37235 USA. EM Paul.Yoder@vanderbilt.edu FU National Institute for Deafness and other Communication Disorders [NIDCD R01 DC006893]; National Institute for Child Health and Disorders (NICHD) through the Vanderbilt Kennedy Center [P30HD15052]; Carolina Institute for Developmental Disabilities [P30HD03110] FX This research was funded by National Institute for Deafness and other Communication Disorders (NIDCD R01 DC006893) and supported by the National Institute for Child Health and Disorders (NICHD) through the Vanderbilt Kennedy Center (P30HD15052) and the Carolina Institute for Developmental Disabilities (P30HD03110). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We are very grateful to our wonderful staff (Elizabeth Gardner, Nicole Thompson, Paula McIntyre, Ariel Schwartz, Tricia Paulley, Kristen Fite, Maura Tourian, Ann Firestine, Lucy Stefani, Olivia Fairchild, Amanda Haskins, Danielle Kopkin, and Kathleen Berry), the families who trust us with their precious children, and Tiffany Woynaroski, who edited drafts of this manuscript. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1254 EP 1270 DI 10.1007/s10803-014-2286-4 PG 17 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200012 PM 25344152 ER PT J AU Wiggins, LD Reynolds, A Rice, CE Moody, EJ Bernal, P Blaskey, L Rosenberg, SA Lee, LC Levy, SE AF Wiggins, Lisa D. Reynolds, Ann Rice, Catherine E. Moody, Eric J. Bernal, Pilar Blaskey, Lisa Rosenberg, Steven A. Lee, Li-Ching Levy, Susan E. TI Using Standardized Diagnostic Instruments to Classify Children with Autism in the Study to Explore Early Development SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE ADI-R; ADOS; Autism; Classification; Phenotypes; Study methods ID SOCIAL COMMUNICATION QUESTIONNAIRE; SPECTRUM DISORDERS; OBSERVATION SCHEDULE; ADI-R; PRESCHOOL-CHILDREN; INTERVIEW; VALIDITY; ADOS; AGE AB The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome. C1 [Wiggins, Lisa D.; Rice, Catherine E.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Reynolds, Ann; Moody, Eric J.; Rosenberg, Steven A.] Univ Colorado, Sch Med, Aurora, CO USA. [Bernal, Pilar] Kaiser Permanente No Calif, San Jose Med Ctr, Autism Spectrum Disorders Ctr, San Jose, CA USA. [Blaskey, Lisa; Levy, Susan E.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Ctr Autism Res, Philadelphia, PA 19104 USA. [Lee, Li-Ching] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wiggins, LD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd MS E-86, Atlanta, GA 30333 USA. EM lwiggins@cdc.gov FU Centers for Disease Control and Prevention, Colorado Department of Public Health [U10DD000180]; Kaiser Foundation Research Institute (CA) [U10DD000181]; University of Pennsylvania [U10DD000182]; Johns Hopkins University [U10DD000183]; University of North Carolina at Chapel Hill [U10DD000184]; Michigan State University [U10DD000498] FX We would like to thank Lisa Croen, Julie Daniels, Ellen Giarelli, Rebecca Landa, Cordelia Robinson, Diana Schendel, Amy Sims, and Patrick Thompson for their contributions to the development of the SEED final classification algorithm and/or comments on previous versions of this paper. We would also like to thank Aimee Alexander, Rebecca Cantrell, and Laura Schieve for their assistance with data cleaning and the SEED principal investigators, co-principal investigators, project coordinators, project staff, and children and families who participated in this research. This publication was supported by six cooperative agreements from the Centers for Disease Control and Prevention: Cooperative Agreement Number U10DD000180, Colorado Department of Public Health; Cooperative Agreement Number U10DD000181, Kaiser Foundation Research Institute (CA); Cooperative Agreement Number U10DD000182, University of Pennsylvania; Cooperative Agreement Number U10DD000183, Johns Hopkins University; Cooperative Agreement Number U10DD000184, University of North Carolina at Chapel Hill; and Cooperative Agreement Number U10DD000498, Michigan State University. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 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PD MAY PY 2015 VL 45 IS 5 BP 1271 EP 1280 DI 10.1007/s10803-014-2287-3 PG 10 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200013 PM 25348175 ER PT J AU Dillen, C Steyaert, J Op de Beeck, HP Boets, B AF Dillen, Claudia Steyaert, Jean Op de Beeck, Hans P. Boets, Bart TI Visual Processing in Adolescents with Autism Spectrum Disorder: Evidence from Embedded Figures and Configural Superiority Tests SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Embedded figures test; Configural superiority effect; Vision ID HIGH-FUNCTIONING AUTISM; WEAK CENTRAL COHERENCE; DISEMBEDDING PERFORMANCE; ASPERGER-SYNDROME; COGNITIVE-STYLE; TASK-PERFORMANCE; CHILDREN; ATTENTION; INDIVIDUALS; PERCEPTION AB The embedded figures test has often been used to reveal weak central coherence in individuals with autism spectrum disorder (ASD). Here, we administered a more standardized automated version of the embedded figures test in combination with the configural superiority task, to investigate the effect of contextual modulation on local feature detection in 23 adolescents with ASD and 26 matched typically developing controls. On both tasks both groups performed largely similarly in terms of accuracy and reaction time, and both displayed the contextual modulation effect. This indicates that individuals with ASD are equally sensitive compared to typically developing individuals to the contextual effects of the task and that there is no evidence for a local processing bias in adolescents with ASD. C1 [Dillen, Claudia; Steyaert, Jean; Boets, Bart] Univ Leuven KU Leuven, Dept Neurosci, Child & Adolescent Psychiat, B-3000 Leuven, Belgium. [Dillen, Claudia; Op de Beeck, Hans P.] Katholieke Univ Leuven, Biol Psychol, Dept Psychol, B-3000 Leuven, Belgium. [Dillen, Claudia; Steyaert, Jean; Boets, Bart] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Leuven, Belgium. RP Boets, B (reprint author), Univ Leuven KU Leuven, Dept Neurosci, Child & Adolescent Psychiat, Herestr 49,Box 7003, B-3000 Leuven, Belgium. EM bart.boets@ppw.kuleuven.be FU KU Leuven Research Council [IDO/10/003] FX The research was financed by a Grant of the KU Leuven Research Council (IDO/10/003). Bart Boets is a postdoctoral research fellow of the Research Foundation Flanders. We thank Lynn Herremans, Franca Geerlings and Kaat Alaerts for assistance with data collection, and all children and families for participating in the study. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1281 EP 1290 DI 10.1007/s10803-014-2288-2 PG 10 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200014 PM 25342435 ER PT J AU Palmer, CJ Paton, B Enticott, PG Hohwy, J AF Palmer, Colin J. Paton, Bryan Enticott, Peter G. Hohwy, Jakob TI 'Subtypes' in the Presentation of Autistic Traits in the General Adult Population SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic traits; Autism-spectrum quotient; Cluster analysis; Subgroups; Factor analysis ID SPECTRUM QUOTIENT AQ; MECHANICAL TURK; INDIVIDUAL-DIFFERENCES; FAMILY-HISTORY; ILLUSION; TWIN; RELIABILITY; COMPONENTS; BEHAVIORS; PHENOTYPE AB The present study examined the presentation of autistic traits in a large adult population sample (n = 2,343). Cluster analysis indicated two subgroups with clearly distinguishable trait profiles. One group (n = 1,059) reported greater social difficulties and lower detail orientation, while the second group (n = 1,284) reported lesser social difficulties and greater detail orientation. We also report a three-factor solution for the autism-spectrum quotient, with two, related, social-themed factors (Sociability and Mentalising) and a third non-social factor that varied independently (Detail Orientation). These results indicate that different profiles of autistic characteristics tend to occur in the adult nonclinical population. Research into nonclinical variance in autistic features may benefit by considering social- and detail-related trait domains independently. C1 [Palmer, Colin J.; Paton, Bryan; Hohwy, Jakob] Monash Univ, Dept Philosophy, Cognit & Philosophy Lab, Melbourne, Vic 3800, Australia. [Paton, Bryan] Monash Univ, Monash Biomed Imaging, Melbourne, Vic 3800, Australia. [Paton, Bryan] Monash Univ, Sch Psychol Sci, Melbourne, Vic 3800, Australia. 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PD MAY PY 2015 VL 45 IS 5 BP 1302 EP 1317 DI 10.1007/s10803-014-2290-8 PG 16 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200016 PM 25351828 ER PT J AU Yoshimura, S Sato, W Uono, S Toichi, M AF Yoshimura, Sayaka Sato, Wataru Uono, Shota Toichi, Motomi TI Impaired Overt Facial Mimicry in Response to Dynamic Facial Expressions in High-Functioning Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders (ASD); Dynamic facial expression; Facial mimicry; Reciprocal social interaction ID RATING-SCALE; TOKYO VERSION; PERCEPTION; CHILDREN; RECOGNITION; IMITATION; VOLUNTARY; IDENTITY; EMOTION; SYSTEM AB Previous electromyographic studies have reported that individuals with autism spectrum disorders (ASD) exhibited atypical patterns of facial muscle activity in response to facial expression stimuli. However, whether such activity is expressed in visible facial mimicry remains unknown. 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RP Yoshimura, S (reprint author), Kyoto Univ, Grad Sch Med, Dept Neurodev Psychiat Habilitat & Rehabil, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan. EM yoshimurasayaka@gmail.com RI ahmed, Jamila/E-8653-2015 FU JSPS FX The authors thank all participants for their participation in the experiment and Ms. Minemoto and Ms. Yokoyama for their technical assistance. This study was supported by funds from the JSPS Funding Program for Next Generation World-Leading Researchers and the Organization for Promoting Developmental Disorder Research. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Beall PM, 2008, J EXP CHILD PSYCHOL, V101, P206, DOI 10.1016/j.jecp.2008.04.004 Blairy S, 1999, J NONVERBAL BEHAV, V23, P5, DOI 10.1023/A:1021370825283 CACIOPPO JT, 1986, J PERS SOC PSYCHOL, V50, P260, DOI 10.1037//0022-3514.50.2.260 CACIOPPO JT, 1992, PERS SOC PSYCHOL B, V18, P515, DOI 10.1177/0146167292185001 Cappella J. 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PD MAY PY 2015 VL 45 IS 5 BP 1318 EP 1328 DI 10.1007/s10803-014-2291-7 PG 11 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200017 PM 25374131 ER PT J AU Brennan, L Barton, M Chen, CM Green, J Fein, D AF Brennan, Laura Barton, Marianne Chen, Chi-Ming Green, James Fein, Deborah TI Detecting Subgroups in Children Diagnosed with Pervasive Developmental Disorder - Not Otherwise Specified SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE PDD-NOS; Cluster analysis; DSM 5; ASD; Subgroups ID AUTISM SPECTRUM DISORDER; MODIFIED CHECKLIST; CHILDHOOD AUTISM; CLUSTER-ANALYSIS; AGE; VALIDATION; INTERVIEW; TODDLERS; CRITERIA; CHAT AB Hierarchical cluster analyses were used to detect three subgroups in a sample of children with pervasive developmental disorder-not otherwise specified (PDD-NOS) evaluated at ages 2 and 4. At age 2, Cluster 1 demonstrated few autism symptoms and high cognitive scores; 60 % no longer met criteria for PDD at 4. Cluster 2 exhibited more autism symptoms and lower cognitive scores at 2; 89.5 % met criteria for ASD at 4. Cluster 3 had the lowest cognitive scores and most impaired social/communication skills at 2, but no repetitive behaviors; 60 % diagnosed with Autistic Disorder at 4. Results shed light on outcomes for different PDD-NOS types and raise questions regarding the increased importance of repetitive behaviors in DSM-5. C1 [Brennan, Laura; Barton, Marianne; Chen, Chi-Ming; Green, James; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. RP Brennan, L (reprint author), Univ Connecticut, Dept Psychol, 406 Babbidge Rd,Unit 1020, Storrs, CT 06269 USA. EM laura.brennan@uconn.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [RO1 HD039961] FX We are extremely grateful to all the children and families for their participation and to the pediatrician sites, as well as Birth-to-Three providers within Connecticut and Massachusetts, who assisted and continue to assist our study. We would like to extend sincere thanks to members of the Early Detection Advisory Board, especially Thyde Dumont-Mathieu, M.D., Ho-Wen Hsu, M.D., and Mark Greenstein, M.D., for their sage advice and support. We would also like to thank the clinicians, graduate students, undergraduate research assistants, and research assistants whose work has been invaluable to the study. This study is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (RO1 HD039961). 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TI Identifying the Associated Factors of Mediation and Due Process in Families of Students with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE School; Litigation; Advocacy; Family-school partnership; Internalizing behaviors; Inclusion ID DEVELOPMENTAL-DISABILITIES; PARENTING STRESS; CHILDREN; SCHOOL; MOTHERS; PARTNERSHIPS; ADVOCACY; SERVICES; IMPACT AB Compared to families of students with other types of disabilities, families of students with autism spectrum disorder (ASD) are significantly more likely to enact their procedural safeguards such as mediation and due process. However, we do not know which school, child, and parent characteristics are associated with the enactment of safeguards. For this study, 507 parents of students with ASD responded to a national web-based survey. 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However, their reported prevalence varies between studies and their co-occurrence is unknown. We determined the prevalence of SIS in a large group of 254 autistic individuals and searched for PP in 46 of these autistic individuals and 46 intelligence and age-matched typically developing controls. The prevalence of SIS among autistic individuals was 62.5 % and that of PP was 58 % (13 % in controls). The prevalence of SIS increased with intelligence and age. The existence of an SIS in a particular modality was not associated with the presence of a PP in the same modality. This suggests that talents involve an experience-dependent component in addition to genetically defined alterations of perceptual encoding. C1 [Meilleur, Andree-Anne S.; Jelenic, Patricia; Mottron, Laurent] Univ Montreal, Hop Riviere des Prairies, Ctr Excellence Pervas Dev Disorders CETEDUM, Montreal, PQ H1E 1A4, Canada. RP Meilleur, AAS (reprint author), Univ Montreal, Hop Riviere des Prairies, Ctr Excellence Pervas Dev Disorders CETEDUM, 7070 Perras Blvd, Montreal, PQ H1E 1A4, Canada. EM ameilleur009@gmail.com; patricia.jelenic.hrdp@ssss.gouv.qc.ca; 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 the CIHR (L.M., 171795); Autism Speaks Foundation (L.M., 2706); and the Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (CGS-D)(A-A.S.M.). We also thank the statistician Claude Berthiaume for his advice and availability, the HRDP autism research group for comments on the manuscript, and our research assistant Chloe Paquin-Hodge for testing the participants. CR Aram D. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1354 EP 1367 DI 10.1007/s10803-014-2296-2 PG 14 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200020 PM 25374134 ER PT J AU Hedley, D Brewer, N Young, R AF Hedley, Darren Brewer, Neil Young, Robyn TI The Effect of Inversion on Face Recognition in Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Eye tracking; Face inversion effect; Face perception; Face processing; Face recognition ID ASPERGER-SYNDROME; FUNCTIONING AUTISM; FIXATION PATTERNS; CHILDREN; INDIVIDUALS; MEMORY; IDENTITY; INFORMATION; PERCEPTION; MECHANISMS AB Face identity recognition has widely been shown to be impaired in individuals with autism spectrum disorders (ASD). In this study we examined the influence of inversion on face recognition in 26 adults with ASD and 33 age and IQ matched controls. Participants completed a recognition test comprising upright and inverted faces. Participants with ASD performed worse than controls on the recognition task but did not show an advantage for inverted face recognition. Both groups directed more visual attention to the eye than the mouth region and gaze patterns were not found to be associated with recognition performance. These results provide evidence of a normal effect of inversion on face recognition in adults with ASD. C1 [Hedley, Darren; Brewer, Neil; Young, Robyn] Flinders Univ S Australia, Adelaide, SA 5001, Australia. [Hedley, Darren] Emerson Coll, Dept Commun Sci & Disorders, Boston, MA 02116 USA. RP Hedley, D (reprint author), Emerson Coll, Dept Commun Sci & Disorders, 120 Boylston St, Boston, MA 02116 USA. EM DarrenHedley@gmail.com FU Australian Research Council (ARC) [LE0882562]; ARC [DP1093210]; Flinders University Research Grant; Flinders University Research Scholarship (FURS) FX This research was supported by (a) Australian Research Council (ARC) LE0882562 to Neil Brewer, Robyn Young et al., and ARC DP1093210 to Neil Brewer et al., (b) a Flinders University Research Grant to Robyn Young and Neil Brewer, and (c) a Flinders University Research Scholarship (FURS) to Darren Hedley. Portions of the research in this paper use the Computer Vision Laboratory (CVL) Face Database, University of Ljubljana, Slovenia (Peer 2011; Solina et al. 2003). 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TI Toward a Best-Practice Protocol for Assessment of Sensory Features in ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Perceptual disorders; Sensory function; Sensory disorders; Symptom assessment; Best practices ID AUTISM SPECTRUM DISORDERS; EVENT-RELATED POTENTIALS; FUNCTIONING AUTISM; MULTISENSORY INTEGRATION; OVER-RESPONSIVITY; ASPERGER-SYNDROME; YOUNG-CHILDREN; DEVELOPMENTAL-DISABILITIES; EXPERIENCES QUESTIONNAIRE; TYPICAL DEVELOPMENT AB Sensory difficulties are a commonly occurring feature of autism spectrum disorders and are now included as one manifestation of the 'restricted, repetitive patterns of behavior, interests, or activities' diagnostic criteria of the DSM5 necessitating guidelines for comprehensive assessment of these features. To facilitate the development of such guidelines, this paper provides an overview of the literature on sensory features in autism spectrum disorder. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1380 EP 1395 DI 10.1007/s10803-014-2299-z PG 16 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200022 PM 25374136 ER PT J AU Nakao, S Scott, JM Masterson, EE Chi, DL AF Nakao, Sy Scott, JoAnna M. Masterson, Erin E. Chi, Donald L. TI Non-traumatic Dental Condition-Related Emergency Department Visits and Associated Costs for Children and Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Emergency department visits; Non-traumatic dental conditions; Dental costs ID MEDICAID-ENROLLED CHILDREN; HEALTH-CARE EXPENDITURES; ORAL-HEALTH; DEVELOPMENTAL-DISABILITY; WISCONSIN MEDICAID; EXPERIENCES; COMMUNITY; DIAGNOSIS; PROGRAM; PEOPLE AB We analyzed 2010 US National Emergency Department Sample data and ran regression models to test the hypotheses that individuals with ASD are more likely to have non-traumatic dental condition (NTDC)-related emergency department (ED) visits and to incur greater costs for these visits than those without ASD. There were nearly 2.3 million NTDC-related ED visits in 2010. Less than 1.0 % (children) and 2.1 % (adults) of all ED visits were for NTDC. There was no significant difference in NTDC-related ED visits or costs for children by ASD status. Adults with ASD had significantly lower odds of NTDC-related ED visits (OR 0.39; 95 % CI 0.29, 0.52; p < 0.001) but incurred significantly greater mean costs for NTDC-related ED visits (p < 0.006) than did adults without ASD. C1 [Nakao, Sy; Masterson, Erin E.; Chi, Donald L.] Univ Washington, Sch Dent, Dept Oral Hlth Sci, Seattle, WA 98195 USA. [Scott, JoAnna M.] Univ Washington, Sch Dent, Dept Pediat Dent, Seattle, WA 98195 USA. RP Chi, DL (reprint author), Univ Washington, Sch Dent, Dept Oral Hlth Sci, Box 357475, Seattle, WA 98195 USA. EM dchi@uw.edu FU National Institute of Dental and Craniofacial Research (NIDCR); National Institutes of Health (NIH) [TL1TR000422, K08DE020856]; Health Resources and Services Administration (HRSA) [R40MC26198] FX This research was made possible by the National Institute of Dental and Craniofacial Research (NIDCR) and National Institutes of Health (NIH) Grant Numbers TL1TR000422 and K08DE020856 and Health Resources and Services Administration (HRSA) Grant Number R40MC26198. 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PD MAY PY 2015 VL 45 IS 5 BP 1396 EP 1407 DI 10.1007/s10803-014-2298-0 PG 12 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200023 PM 25374135 ER PT J AU Finn, L Ramasamy, R Dukes, C Scott, J AF Finn, Lisa Ramasamy, Rangasamy Dukes, Charles Scott, John TI Using WatchMinder to Increase the On-Task Behavior of Students with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Self-monitoring; Tactile prompting; WatchMinder; Self-graphing; Classroom intervention ID SELF-MANAGEMENT; CHILDREN; STRATEGIES; CLASSROOM; TEACHERS AB This study assessed the use of WatchMinder (TM), a vibrating prompt watch, and self-graphing on the on-task behavior of students with autism spectrum disorder in an elementary special education setting. Using a multiple baseline across subjects design, results showed an immediate increase in on-task behavior when the intervention was introduced. Participants maintained high levels of on-task behavior during the follow-up phase. Implications for expanded self-monitoring treatment packages are discussed. C1 [Finn, Lisa; Ramasamy, Rangasamy; Dukes, Charles; Scott, John] Florida Atlantic Univ, Coll Educ, Dept Except Student Educ, Boca Raton, FL 33431 USA. RP Finn, L (reprint author), Florida Atlantic Univ, Coll Educ, Dept Except Student Educ, 777 Glades Rd, Boca Raton, FL 33431 USA. EM lisa.finn@palmbeachschools.org CR Amato-Zech NA, 2006, PSYCHOL SCHOOLS, V43, P211, DOI 10.1002/pits.20137 Anderson A, 2004, AUSTRALASIAN J SPECI, V28, P30, DOI 10.1080/1030011040280204 Anson HM, 2008, BEHAV RES METHODS, V40, P1106, DOI 10.3758/BRM.40.4.1106 Bjorklund D. F, 2012, CHILDRENS THINKING C BLICK DW, 1987, LEARN DISABILITY Q, V10, P203, DOI 10.2307/1510493 Briesch AM, 2009, SCHOOL PSYCHOL QUART, V24, P106, DOI 10.1037/a0016159 Callahan K., 1999, J POSIT BEHAV INTERV, V1, P117, DOI 10.1177/109830079900100206 Farrell C. 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B., 2014, SINGLE SUBJECT RES A Sebag R, 2010, TEACHING EXCEPTIONAL, V42, P22 Soares DA, 2009, BEHAV INTERVENT, V24, P171, DOI 10.1002/bin.283 TRAMMEL DL, 1994, J LEARN DISABIL, V27, P75 Van Hulle A, 2006, BRAIN INJURY, V20, P101, DOI 10.1080/02699050500309684 Wilkinson LA, 2008, INTERV SCH CLIN, V43, P150, DOI 10.1177/1053451207311613 NR 26 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1408 EP 1418 DI 10.1007/s10803-014-2300-x PG 11 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200024 PM 25377769 ER PT J AU Graham, SA Abbott, AE Nair, A Lincoln, AJ Muller, RA Goble, DJ AF Graham, Sarah A. Abbott, Angela E. Nair, Aarti Lincoln, Alan J. Mueller, Ralph-Axel Goble, Daniel J. TI The Influence of Task Difficulty and Participant Age on Balance Control in ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorder; Balance control; Sensorimotor integration; Postural control; Center of pressure ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; HIGH-FUNCTIONING AUTISM; POSTURAL CONTROL; DEVELOPMENTAL-CHANGES; REPETITIVE BEHAVIOR; CHILDREN; ADOLESCENTS; SINGLE; STANCE AB Impairments in sensorimotor integration are reported in Autism Spectrum Disorder (ASD). Poor control of balance in challenging balance tasks is one suggested manifestation of these impairments, and is potentially related to ASD symptom severity. Reported balance and symptom severity relationships disregard age as a potential covariate, however, despite its involvement in balance development. We tested balance control during increasingly difficult balance conditions in children with ASD and typically developing peers, and investigated relationships between balance control and diagnostic/symptom severity metrics for participants with ASD, including age as a covariate. Balance deficits in ASD were exacerbated by stance alterations, but were not related to symptom severity when age was considered. These findings support impaired balance in ASD, especially in challenging conditions, but question a link between balance and symptom severity. C1 [Graham, Sarah A.; Goble, Daniel J.] San Diego State Univ, Coll Hlth & Human Serv, Sch Exercise & Nutr Sci, San Diego, CA 92182 USA. [Abbott, Angela E.; Nair, Aarti; Mueller, Ralph-Axel] San Diego State Univ, Dept Psychol, Coll Sci, San Diego, CA 92182 USA. [Lincoln, Alan J.] Alliant Int Univ, Calif Sch Profess Psychol, Dept Clin Psychol, San Diego, CA 92131 USA. RP Goble, DJ (reprint author), San Diego State Univ, Coll Hlth & Human Serv, Sch Exercise & Nutr Sci, 5500 Campanile Dr, San Diego, CA 92182 USA. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1419 EP 1427 DI 10.1007/s10803-014-2303-7 PG 9 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200025 PM 25381191 ER PT J AU Zhou, P Crain, S Gao, LQ Tang, Y Jia, MX AF Zhou, Peng Crain, Stephen Gao, Liqun Tang, Ye Jia, Meixiang TI The Use of Grammatical Morphemes by Mandarin-Speaking Children with High Functioning Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Grammatical morphology; Temporal processing; Event structure; Language development ID RECEPTIVE LANGUAGE DISORDER; EARLY ADULT LIFE; SPECTRUM DISORDERS; FOLLOW-UP; IMPAIRMENT; TENSE; ACQUISITION; PHENOTYPES; OUTCOMES; PROSODY AB The present study investigated the production of grammatical morphemes by Mandarin-speaking children with high functioning autism. Previous research found that a subgroup of English-speaking children with autism exhibit deficits in the use of grammatical morphemes that mark tense. In order to see whether this impairment in grammatical morphology can be generalised to children with autism from other languages, the present study examined whether or not high-functioning Mandarin-speaking children with autism also exhibit deficits in using grammatical morphemes that mark aspect. The results show that Mandarin-speaking children with autism produced grammatical morphemes significantly less often than age-matched and IQ-matched TD peers as well as MLU-matched TD peers. The implications of these findings for understanding the grammatical abilities of children with autism were discussed. C1 [Zhou, Peng; Crain, Stephen] Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, Dept Cognit Sci, Sydney, NSW 2109, Australia. [Gao, Liqun; Tang, Ye] Beijing Language & Culture Univ, Beijing 100083, Peoples R China. [Jia, Meixiang] Peking Univ Sixth Hosp, Beijing 100083, Peoples R China. RP Zhou, P (reprint author), Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, Dept Cognit Sci, Sydney, NSW 2109, Australia. EM peng.zhou@mq.edu.au RI ahmed, Jamila/E-8653-2015 FU Macquarie University; ARC Centre of Excellence in Cognition and its Disorders [CE110001021] FX This research was supported by a Macquarie University Research Fellowship to the first author and also the ARC Centre of Excellence in Cognition and its Disorders (CE110001021). The authors are grateful to Dr. Joshua John Diehl and three anonymous reviewers for their insightful comments and suggestions on an earlier version of the paper. The authors would also like to thank the children and the teachers at the Rehabilitation and Education Centre for Children with Autism affiliated with the Peking University Sixth Hospital, Beijing, China, for their assistance and support in running the experiments. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1437 EP 1450 DI 10.1007/s10803-014-2306-4 PG 14 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200027 PM 25384720 ER PT J AU Goin-Kochel, RP Mire, SS Dempsey, AG AF Goin-Kochel, Robin P. Mire, Sarah S. Dempsey, Allison G. TI Emergence of Autism Spectrum Disorder in Children from Simplex Families: Relations to Parental Perceptions of Etiology SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorder; Regression; Parent perceptions; Simons Simplex Collection ID DEVELOPMENTAL REGRESSION; RUBELLA VACCINATION; UNITED-STATES; RISK-FACTORS; MEASLES; MUMPS; POPULATION; CPEA; PHENOTYPE; BELIEFS AB Current research describes a four-category scheme of Autism Spectrum Disorder (ASD) onset: early, regressive, plateau, delay + regression. To replicate prevalence of different onset types, ASD onset (per the Autism Diagnostic Interview-Revised) was examined in a large North American sample; for a subset, parents' causal beliefs were ascertained via the Revised Illness Perception Questionnaire to examine potential associations with ASD-onset types. Onset rates were similar across samples, with a slightly higher proportion of children in the subsample categorized with regression. Top-rated causes of ASD were genetics, brain structure, will of God, toxins in vaccines, and environmental pollution. Parents reporting regression more often believed that toxins in vaccines caused ASD. Influences on treatment selection and broader public-health ramifications are discussed. C1 [Goin-Kochel, Robin P.] Baylor Coll Med, Houston, TX 77030 USA. [Goin-Kochel, Robin P.] Texas Childrens Hosp, Autism Ctr, Houston, TX 77054 USA. [Mire, Sarah S.] Univ Houston, Houston, TX USA. [Dempsey, Allison G.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. RP Goin-Kochel, RP (reprint author), Texas Childrens Hosp, Autism Ctr, 8080 N Stadium Dr,Suite 180, Houston, TX 77054 USA. EM kochel@bcm.edu FU Simons Foundation [SFARIto SSC-15] FX This work was supported by a grant from the Simons Foundation (SFARIto SSC-15 to R. Goin-Kochel and A. Beaudet). We are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, E. Wijsman). We appreciate obtaining access to phenotypic data on SFARI Base. Approved researchers can obtain the SSC population dataset described in this study (https://ordering.base.sfari.org/similar to browse_collection/archive[sfari_collection_v14_1]/ui:view()) by applying at https://base.sfari.org. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1451 EP 1463 DI 10.1007/s10803-014-2310-8 PG 13 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200028 PM 25398603 ER PT J AU Goldman, S DeNigris, D AF Goldman, Sylvie DeNigris, Danielle TI Parents' Strategies to Elicit Autobiographical Memories in Autism Spectrum Disorders, Developmental Language Disorders and Typically Developing Children SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Parent-child conversation; Past event; Recall ID HIGH-FUNCTIONING CHILDREN; VERBAL RESPONSIVENESS; MULTIPLE-INCIDENCE; JOINT ATTENTION; YOUNG-CHILDREN; SELF; COMMUNICATION; BEHAVIORS; TODDLERS; DEFICITS AB Conversations about the past support the development of autobiographical memory. Parents' strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD, n = 11). We focused on the prevalence of directives versus enrichment of events. Groups did not differ in number of events, length, and total turns. However, parents of children with ASD produced more direct questions, corrections, and unrelated turns than parents of TD children. Results highlight how parents adjusted their conversational style to their child's communication difficulties to maximize interactions and how these strategies may affect the development of personal conversations. C1 [Goldman, Sylvie] Albert Einstein Coll Med, Rose F Kennedy Intellectual & Dev Disabil Res Ctr, Saul R Korey Dept Neurol, Dept Pediat, Bronx, NY 10461 USA. [DeNigris, Danielle] CUNY, Grad Ctr, Dept Psychol, New York, NY 10016 USA. RP Goldman, S (reprint author), Columbia Univ, Med Ctr, GH Sergievski Ctr, 622 West 168th St,PH18-331, New York, NY 10032 USA. EM sg3253@cumc.columbia.edu FU Einstein/Montefiore Autism Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) [P30HD071593] FX Sylvie Goldman was supported by the Einstein/Montefiore Autism Center and by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under Award Number P30HD071593. Portions of this manuscript were presented at The International Meeting for Autism Research (IMFAR) in Atlanta, Georgia 2014. We thank the children and their parents for their participation. We are thankful to Dr Katherine Nelson for her insightful comments on a previous version of the manuscript and for her unconditional support. 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1464 EP 1473 DI 10.1007/s10803-014-2271-y PG 10 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200029 PM 25312278 ER PT J AU Reese, RM Jamison, TR Braun, M Wendland, M Black, W Hadorn, M Nelson, EL Prather, C AF Reese, R. Matthew Jamison, T. Rene Braun, Matt Wendland, Maura Black, William Hadorn, Megan Nelson, Eve-Lynn Prather, Carole TI Brief Report: Use of Interactive Television in Identifying Autism in Young Children: Methodology and Preliminary Data SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Telemedicine; Underserved populations; Assessment; Evaluation ID HEALTH-CARE NEEDS; SPECTRUM DISORDER; TELEMEDICINE; DIAGNOSIS AB Children living in rural and underserved areas experience decreased access to health care services and are often diagnosed with autism at a later age compared to those living in urban or suburban areas. This study examines the utility and validity of an ASD assessment protocol conducted via video conferencing (VC). Participants (n = 17) included families with young children (2.5-6 years) requesting an evaluation for ASD in an interdisciplinary clinic. We randomly assigned families to complete an additional evaluation either in-person or via VC prior to their clinic appointment and compared diagnostic impressions to their interdisciplinary clinic evaluation. Results demonstrate excellent inter-rater agreement on diagnoses between clinicians in the VC setting and the interdisciplinary team, which suggests VC may be a viable method to increase access to autism diagnostic services, and ultimately early intervention, for families in rural and underserved areas. C1 [Reese, R. Matthew; Jamison, T. Rene; Braun, Matt; Wendland, Maura; Hadorn, Megan; Prather, Carole] Univ Kansas, Med Ctr, Ctr Child Hlth & Dev, Kansas City, KS 66160 USA. [Black, William] Univ Missouri, Kansas City, KS USA. [Nelson, Eve-Lynn] Univ Kansas, Med Ctr, Ctr TeleMed & TeleHlth, Kansas City, KS 66160 USA. RP Jamison, TR (reprint author), Univ Kansas, Med Ctr, Ctr Child Hlth & Dev, 3901 Rainbow Blvd,Mailstop 4003, Kansas City, KS 66160 USA. EM rjamison@kumc.edu FU National Institute Of Mental Health of the National Institutes of Health [R21MH098133]; Department of Defense Autism Concept Grant [W81XWH-08-1-0233] FX Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number R21MH098133. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study is based on pilot data from a previous study (Reese et al. 2013) supported by a Department of Defense Autism Concept Grant (Number W81XWH-08-1-0233). CR American Academy of Pediatrics, 2006, AAP AUT SCREEN GUID American Academy of Pediatrics, 2006, DEV SURV SCREEN Barretro A, 2006, J APPL BEHAV ANAL, V39, P333, DOI 10.1901/jaba.2006.173-04 Carbone PS, 2010, AM FAM PHYSICIAN, V81, P453 Centers for Disease Control and Prevention, 2014, SURVEILLANCE SUMMARI, V63, P1 Dawson G, 2008, DEV PSYCHOPATHOL, V20, P775, DOI 10.1017/S0954579408000370 Farmer JE, 2001, CLIN PEDIATR, V40, P93, DOI 10.1177/000992280104000205 Filipek PA, 2000, NEUROLOGY, V55, P468 Heitzman-Powell LS, 2014, FOCUS AUTISM DEV DIS, V29, P23, DOI 10.1177/1088357613504992 Interagency Autism Coordinating Committee (IACC), 2013, INT AUT COORD COMM S Lauritsen MB, 2014, J AUTISM DEV DISORD, V44, P394, DOI 10.1007/s10803-013-1875-y Lord C., 2012, AUTISM DIAGNOSTIC 1 Mandell DS, 2007, J AUTISM DEV DISORD, V37, P1795, DOI 10.1007/s10803-006-0314-8 Marcin JP, 2004, PEDIATRICS, V113, P1, DOI 10.1542/peds.113.1.1 Nesbitt T. S., 2006, ENHANCING MENTAL HLT Newschaffer CJ, 2005, PEDIATRICS, V115, pE277, DOI 10.1542/peds.2004-1958 Reese RM, 2013, TELEMED E-HEALTH, V19, P671, DOI 10.1089/tmj.2012.0312 Rutter M., 2003, AUTISM DIAGNOSTIC II NR 18 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1474 EP 1482 DI 10.1007/s10803-014-2269-5 PG 9 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200030 PM 25331323 ER PT J AU Faughn, C Marrus, N Shuman, J Ross, SR Constantino, JN Pruett, JR Povinelli, DJ AF Faughn, Carley Marrus, Natasha Shuman, Jeremy Ross, Stephen R. Constantino, John N. Pruett, John R., Jr. Povinelli, Daniel J. TI Brief Report: Chimpanzee Social Responsiveness Scale (CSRS) Detects Individual Variation in Social Responsiveness for Captive Chimpanzees SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Comparative cognition; Autism; Social Responsiveness Scale; Chimpanzee; Nonhuman primate ID PAN-TROGLODYTES PERSONALITY; RECIPROCITY; COGNITION; INTERCHANGE; DOMINANCE; MIND AB Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human-chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness Scale (CSRS). Here, we augment our prior CSRS sample with 25 zoo chimpanzees at three sites: combined N = 54. The CSRS demonstrated strong interrater reliability, and low-ranked chimpanzees, on average, displayed higher CSRS scores. The CSRS continues to discriminate variation in chimpanzee social responsiveness, and the association of higher scores with lower chimpanzee social standing has implications for the relationship between autistic traits and human social status. Continued comparative investigations of social responsiveness will enhance our understanding of underlying impairments in ASD, improve early diagnosis, and inform future therapies. C1 [Faughn, Carley] Univ Louisiana Lafayette, Inst Cognit Sci, Lafayette, LA 70504 USA. [Marrus, Natasha; Pruett, John R., Jr.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Shuman, Jeremy] Indiana State Univ, Clin Psychol, Terre Haute, IN 47809 USA. [Ross, Stephen R.] Lincoln Pk Zoo, Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL USA. [Constantino, John N.] Washington Univ, Sch Med, Dept Psychiat, Child Div, St Louis, MO 63110 USA. [Constantino, John N.] Washington Univ, Sch Med, Pediat, St Louis, MO 63110 USA. [Povinelli, Daniel J.] Univ Louisiana Lafayette, Dept Biol, Lafayette, LA 70504 USA. RP Pruett, JR (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 So Euclid Ave,Campus Box 8134, St Louis, MO 63110 USA. EM carley.faughn@gmail.com; pruettj@psychiatry.wustl.edu FU James S. McDonnell Centennial Fellowship; [K12 EY016336] FX We would like to thank the Species Survival Plan for Chimpanzees, the Lester E. Fisher Center for the Study and Conservation of Apes and the animal care staff at the Lincoln Park Zoo, the North Carolina Zoo, the Knoxville Zoo, the Primate Rescue Center, and the St. Louis Zoo. This research was supported by K12 EY016336 (JRP) and a James S. McDonnell Centennial Fellowship (DJP). 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Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1483 EP 1488 DI 10.1007/s10803-014-2273-9 PG 6 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200031 PM 25312279 ER PT J AU Shumer, DE Roberts, AL Reisner, SL Lyall, K Austin, SB AF Shumer, Daniel E. Roberts, Andrea L. Reisner, Sari L. Lyall, Kristen Austin, S. Bryn TI Brief Report: Autistic Traits in Mothers and Children Associated with Child's Gender Nonconformity SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Gender; Gender identity; Gender nonconformity; Transgender ID IDENTITY DISORDER; SOCIAL RESPONSIVENESS; POSTTRAUMATIC STRESS; SPECTRUM DISORDERS; ASPERGER-SYNDROME; RISK; ANDROGENS; VARIANCE; ABUSE AB We examined relationships between autistic traits in children, mothers, and fathers and gender nonconformity (GNC) in children using data from the Nurses' Health Study II and the Growing Up Today Study 1. Autistic traits of mothers, fathers and children were measured using the Social Responsiveness Scale (SRS). GNC in children was measured using questions from the Recalled Childhood Gender Identity/Gender Role Questionnaire. In multivariable analyses increase in child's SRS score was associated with increased odds (OR 1.35; p = 0.03) of being in a higher GNC category. Increase in maternal SRS score was also associated with increased odds (OR 1.46; p = 0.005) of the child being in a higher GNC category. Paternal SRS scores were not related to child's GNC category. C1 [Shumer, Daniel E.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Roberts, Andrea L.; Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.] Fenway Inst, Boston, MA USA. [Lyall, Kristen] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lyall, Kristen] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Austin, S. Bryn] Boston Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. [Austin, S. Bryn] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Austin, S. Bryn] Harvard Univ, Sch Med, Boston, MA USA. RP Austin, SB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM Daniel.shumer@childrens.harvard.edu; bryn.austin@childrens.harvard.edu FU National Institute of Health (NIH) [CA50385, T32MH073124-08, P60AR047782, HD057368, R01ES017-04]; Autism Speaks Grants [1788, 2210]; United States Department of Defense [W81XWH-08-1-0499]; United States Army Medical Research and Material Command (USAMRMC) [A-14917]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [1T32HD075727-01]; Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau [HRSA 6T71-MC00009] FX The Nurses' Health Study II and the Growing Up Today Study are ongoing studies conducted at the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard School of Public Health, and Harvard Medical School. The work reported in this manuscript was supported by the National Institute of Health (NIH) Grants CA50385, T32MH073124-08, P60AR047782, HD057368, and R01ES017-04, Autism Speaks Grants 1788 and 2210, the United States Department of Defense Grant W81XWH-08-1-0499, and the United States Army Medical Research and Material Command (USAMRMC) Grant A-14917. D. E. Shumer is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 1T32HD075727-01. S.B. Austin is supported by the Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, HRSA 6T71-MC00009. 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PD MAY PY 2015 VL 45 IS 5 BP 1489 EP 1494 DI 10.1007/s10803-014-2292-6 PG 6 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200032 PM 25358249 ER PT J AU Shiozawa, BJ AF Shiozawa, Brian J. TI It's About Time for Autism Reform Legislation in Utah SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Insurance; Legislation; Reform; Applied behavioral analysis AB On 3 April 2014, Governor Gary Herbert signed into law a health insurance reform bill that requires private insurers to cover autism therapy. Specifically, SB57 requires state-regulated health plans to cover applied behavior analysis (ABA) therapy. While early diagnosis and intervention can reduce the long-term cost of autism, families are finding themselves bankrupt in order to pay for ABA therapy. Currently, 37 states, and the District of Columbia have enacted insurance reform laws. Ensuring that children with autism receive proper therapy is a serious public health issue. Utah was right to pass reform legislation because it properly benefits and safeguards the interests of affected children in promoting their well-being and participation in society. C1 Mendoza Soldier Family Care Clin, William Beaumont Army Med Ctr, Ft Bliss, TX 79916 USA. RP Shiozawa, BJ (reprint author), Mendoza Soldier Family Care Clin, William Beaumont Army Med Ctr, 11335 SSG Sims St, Ft Bliss, TX 79916 USA. EM brian.shiozawa@gmail.com CR Autism Society, 2014, BUDG CRIS ADV NEWS Autism Speaks, 2014, 35 UT EN AUT INS REF Autism Speaks, 2014, SALT LAK MAY PROP UT Autism Speaks, 2014, NEW RES FINDS ANN CO Autism Speaks, 2014, STAT IN MAP ADV NEWS May H., 2014, SALT LAKE TRIBUNE Missouri Department of Insurance Financial Institutions and Professional Registration, 2014, INS COV AUT TREAT AP Stewart K., 2014, SALT LAKE TRIBUNE NR 8 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2015 VL 45 IS 5 BP 1495 EP 1496 DI 10.1007/s10803-014-2302-8 PG 2 WC Psychology, Developmental SC Psychology GA CG6JS UT WOS:000353407200033 PM 25395093 ER PT J AU Luo, SY Huang, W Xia, QP Du, Q Wu, LQ Duan, RH AF Luo, Shiyu Huang, Wen Xia, Qiuping Du, Qian Wu, Lingqian Duan, Ranhui TI Mutational Analyses of the FMR1 Gene in Chinese Pediatric Population of Fragile X Suspects: Low Tolerance for Point Mutation SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE FMR1 mutation; deletion; Chinese pediatrics AB CGG repeat expansion is the most common cause of fragile X syndrome. Numerous efforts have been made to identify novel mutations in patients with intellectual disability, developmental delay, and/or autism. To evaluate the mutational spectrum in the at-risk Chinese population, 60 pediatric patients presenting fragile X traits but normal-sized CGG repeats were sequenced for all 17 exons and regulatory regions in FMR1. A c.879A>C mutation, reported to alter a neighboring splicing, was detected in a severely retarded male and his normal mother. However, the exon junction appears unaffected. A 237-kb deletion covering the entire FMR1 was identified to cause moderate intellectual disability and marked hyperactivity in an 8-year-old boy. The 5 and 3 breakpoints were buried in the surrounding long interspersed and short interspersed elements, respectively. In general, missense mutations do not commonly cause fragile X syndrome, whereas deletions should be considered with caution in patient referrals presenting with developmental delay and/or ordinary retardation. C1 [Luo, Shiyu; Huang, Wen; Xia, Qiuping; Du, Qian; Wu, Lingqian; Duan, Ranhui] Cent S Univ, State Key Lab Med Genet, Xiangya Sch Med, Changsha 410078, Hunan, Peoples R China. RP Duan, RH (reprint author), Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China. EM wulingqian@sklmg.edu.cn; duanranhui@sklmg.edu.cn RI ahmed, Jamila/E-8653-2015 FU National Key Basic Research Program of China [2012CB944600]; National Natural Science Foundation of China [81071028, 81172513]; National Key Technology R&D Program of China [2012BAI09B05]; Program for New Century Excellent Talents in University [NCET-10-0832] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants from the National Key Basic Research Program of China (grant 2012CB944600), National Natural Science Foundation of China (grant 81071028, 81172513), National Key Technology R&D Program of China (grant 2012BAI09B05), Program for New Century Excellent Talents in University (grant NCET-10-0832). CR Coffee B, 2008, AM J MED GENET A, V146A, P1358, DOI 10.1002/ajmg.a.32261 Collins SC, 2010, AM J MED GENET A, V152A, P2512, DOI 10.1002/ajmg.a.33626 DEBOULLE K, 1993, NAT GENET, V3, P31, DOI 10.1038/ng0193-31 Gronskov K, 2011, EUR J HUM GENET, V19, P489, DOI 10.1038/ejhg.2010.223 Guo Yizhen, 2000, ACTA ACAD MED SINICA, V22, P85 Hagerman R, 2010, MOL AUTISM, V1, DOI 10.1186/2040-2392-1-12 Myrick LK, 2014, EUR J HUM GENET Shinahara Kumi, 2004, Journal of Medical Investigation, V51, P52, DOI 10.2152/jmi.51.52 Tarleton J, 2002, J MED GENET, V39, P196, DOI 10.1136/jmg.39.3.196 Wells RD, 2009, J BIOL CHEM, V284, P7407, DOI 10.1074/jbc.R800024200 NR 10 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2015 VL 30 IS 6 BP 803 EP 806 DI 10.1177/0883073814538508 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA CG8SZ UT WOS:000353584100023 PM 24963073 ER PT J AU Rosqvist, HB Brownlow, C O'Dell, L AF Rosqvist, Hanna Bertilsdotter Brownlow, Charlotte O'Dell, Lindsay TI 'An Association for All'-Notions of the Meaning of Autistic Self-Advocacy Politics within a Parent-Dominated Autistic Movement SO JOURNAL OF COMMUNITY & APPLIED SOCIAL PSYCHOLOGY LA English DT Article DE self-advocacy; autism; identity; Asperger syndrome; parents ID DISABILITY AB In this paper, we seek to explore the tensions between advocacy and self advocacy autistic movements in a Swedish context with a special focus on the meanings that enable the production of particular understandings of autism and the autistic subject. Drawing on articles written for the Swedish advocacy magazine Empowerment written for and by people with autism, the discourse analysis explores two competing discourses: a reformist and a radical. The reformist discourse underlines a goal of (political) representation expressed in Empowerment. It may be understood as an important part of producing a legitimate autistic political subject-positioned as a full member, with a full membership-within a parent-dominated autistic advocacy movement. The reformist discourse can be viewed as a result of a negotiation, where full membership is conditioned on the parents' terms and granted on specific terms. These include working together (neuro-inclusively), advocacy based on interest rather than identity/position as a specific target/member group, agreement upon a definition of autism as a disability (a deficit) a person has rather than an identity. In relation to this, an alternative legitimate autistic subject is produced through invoking the counter-hegemonic radical discourse. Such a narrative produces the Asperger' or Aspie'. Here, the full membership' refers to a sense of identification with sense of belonging to and being at home with other people with autism. It contains a certain amount of autistic solidarity within the group of adults with autism. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Rosqvist, Hanna Bertilsdotter] Umea Univ, Dept Social Work, S-90187 Umea, Sweden. [Brownlow, Charlotte] Univ So Queensland, Sch Psychol Counselling & Community, Toowoomba, Qld 4350, Australia. [O'Dell, Lindsay] Open Univ, Fac Hlth & Social Care, Milton Keynes MK7 6AA, Bucks, England. RP Rosqvist, HB (reprint author), Umea Univ, Dept Social Work, S-90187 Umea, Sweden. 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Ziviani, Jenny Dodrill, Pamela TI Multidisciplinary Intervention for Childhood Feeding Difficulties SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE autism spectrum disorders; feeding difficulties; intervention; nutrition; weight ID AUTISM SPECTRUM DISORDERS; FAILURE-TO-THRIVE; CHILDREN; GROWTH; BEHAVIORS; OUTCOMES; INFANCY AB Objective: The aim of the study was to determine whether operant conditioning (OC) or systematic desensitization (SysD) intervention resulted in more improvements in dietary variety/intake, and more reductions in difficult mealtime behaviors. Methods: Children 2 to 6 years with autism spectrum disorder or with a nonmedically complex history were recruited. Feeding difficulties were confirmed based on clinical assessment. Participants were randomized to receive 10 OC or SysD sessions (parents could opt for intervention once per week, or intensively within a week). Immersive parent education was delivered across both arms. A 3-month review was provided to measure outcomes postintervention. Results: In total, 68 participants (87%) completed the study. There were no significant differences in outcome measures between the OC and SysD intervention groups from baseline to 3-month review. When the data were combined across both groups, however, significant improvements in primary outcome measures were observed (P < 0.05). Although not statistically significant, it was considered clinically significant that participants in the OC arm demonstrated more increases in dietary variety (mean difference 3.3 foods, 95% confidence interval -0.1 to 6.8, P = 0.06) compared with the SysD arm. There were limited differences in response observed between the autism spectrum disorder and nonmedically complex history groups, and the intensive and weekly arms. Conclusions: Favorable results were observed regardless of intervention, intensity, or etiological group. Results suggest that, when delivered to a protocol by experienced therapists and coupled with parent education, these 2 intervention approaches are effective. Further research is required in exploring these interventions across other subgroups, and examining outcomes for longer periods. C1 [Marshall, Jeanne; Hill, Rebecca J.] Univ Queensland, Childrens Nutr Res Ctr, Royal Childrens Hosp, Brisbane, Qld, Australia. [Ware, Robert S.] Univ Queensland, Royal Childrens Hosp, Child Hlth Res Ctr, Brisbane, Qld, Australia. [Ziviani, Jenny] Univ Queensland, Royal Childrens Hosp, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. [Dodrill, Pamela] Univ Queensland, Royal Childrens Hosp, Childrens Hlth Queensland, Brisbane, Qld, Australia. RP Marshall, J (reprint author), Lady Cilento Childrens Hosp, Speech Pathol Dept, Level 7,501 Stanley St, South Brisbane, Qld 4101, Australia. EM j.marshall@uq.edu.au RI Ware, Robert/B-2024-2014 OI Ware, Robert/0000-0002-6129-6736 FU Queensland Children's Medical Research Institute, University of Queensland; Children's Health Queensland FX The study was supported by Queensland Children's Medical Research Institute, University of Queensland, and Children's Health Queensland. 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PD MAY PY 2015 VL 60 IS 5 BP 680 EP 687 DI 10.1097/MPG.0000000000000669 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA CG6LA UT WOS:000353410900028 PM 25534777 ER PT J AU Stewart, SB Greene, DJ Lessov-Schlaggar, CN Church, JA Schlaggar, BL AF Stewart, Stephanie B. Greene, Deanna J. Lessov-Schlaggar, Christina N. Church, Jessica A. Schlaggar, Bradley L. TI Clinical Correlates of Parenting Stress in Children with Tourette Syndrome and in Typically Developing Children SO JOURNAL OF PEDIATRICS LA English DT Article ID PREVALENCE; DISORDER; MOTHERS; AUTISM; SCALE AB Objective To determine the impact of tic severity in children with Tourette syndrome on parenting stress and the impact of comorbid attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) symptomatology on parenting stress in both children with Tourette syndrome and typically developing children. Study design Children with diagnosed Tourette syndrome (n = 74) and tic-free typically developing control subjects (n = 48) were enrolled in a cross-sectional study. Results Parenting stress was greater in the group with Tourette syndrome than the typically developing group. Increased levels of parenting stress were related to increased ADHD symptomatology in both children with Tourette syndrome and typically developing children. Symptomatology of OCD was correlated with parenting stress in Tourette syndrome. Parenting stress was independent of tic severity in patients with Tourette syndrome. Conclusions For parents of children with Tourette syndrome, parenting stress appears to be related to the child's ADHD and OCD comorbidity and not to the severity of the child's tic. Subthreshold ADHD symptomatology also appears to be related to parenting stress in parents of typically developing children. These findings demonstrate that ADHD symptomatology impacts parental stress both in children with and without a chronic tic disorder. C1 [Stewart, Stephanie B.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Stewart, Stephanie B.; Greene, Deanna J.; Lessov-Schlaggar, Christina N.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Greene, Deanna J.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Church, Jessica A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Stewart, SB (reprint author), Washington Univ, Sch Med, Dept Neurol, 4525 Scott Ave, St Louis, MO 63110 USA. EM stewarts@npg.wustl.edu FU National Institute on Drug Abuse (NIDA) [T32 DA007261]; National Institute of Neurological Disorders and Stroke (NINDS) [F32 NS065649]; National Institute of Mental Health (NIMH) [R21 Q3MH091512]; Intellectual and Developmental Disabilities Research Center at Washington University National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) [P30 HD062171] FX Funded by National Institute on Drug Abuse (NIDA) (T32 DA007261 [to S.S.]), National Institute of Neurological Disorders and Stroke (NINDS) (F32 NS065649 [to J.C.]), National Institute of Mental Health (NIMH) (R21 Q3MH091512 [to B.S.]), and the Intellectual and Developmental Disabilities Research Center at Washington University (National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) (P30 HD062171). The authors declare no conflicts of interest. 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Pediatr. PD MAY PY 2015 VL 166 IS 5 BP 1297 EP U539 DI 10.1016/j.jpeds.2015.01.041 PG 9 WC Pediatrics SC Pediatrics GA CG6DW UT WOS:000353387100039 PM 25769235 ER PT J AU Van Battum, EY Brignani, S Pasterkamp, RJ AF Van Battum, Eljo Y. Brignani, Sara Pasterkamp, R. Jeroen TI Axon guidance proteins in neurological disorders SO LANCET NEUROLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; CONGENITAL MIRROR MOVEMENTS; TEMPORAL-LOBE EPILEPSY; AUTISM SPECTRUM DISORDERS; ONSET ALZHEIMERS-DISEASE; CENTRAL-NERVOUS-SYSTEM; HORIZONTAL GAZE PALSY; MOTOR-NEURON DISEASE; PARKINSON-DISEASE; SEMAPHORIN 3A AB Many neurological disorders are characterised by structural changes in neuronal connections, ranging from presymptomatic synaptic changes to the loss or rewiring of entire axon bundles. The molecular mechanisms that underlie this perturbed connectivity are poorly understood, but recent studies suggest a role for axon guidance proteins. Axon guidance proteins guide growing axons during development and control structural plasticity of synaptic connections in adults. Changes in expression or function of these proteins might induce pathological changes in neural circuits that predispose to, or cause, neurological diseases. For some neurological disorders, such as midline crossing disorders, investigators have identified causative mutations in genes for axon guidance. However, for most other disorders, evidence is correlative and further studies are needed to confirm the pathological role of defects in proteins for axon guidance. Importantly, further insight into how dysregulation of axon guidance proteins causes disease will help the development of therapeutic strategies for neurological disorders. C1 [Van Battum, Eljo Y.; Brignani, Sara; Pasterkamp, R. Jeroen] Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, NL-3584 CG Utrecht, Netherlands. RP Pasterkamp, RJ (reprint author), Univ Med Ctr Utrecht, Dept Translat Neurosci, Brain Ctr Rudolf Magnus, NL-3584 CG Utrecht, Netherlands. EM r.j.pasterkamp@umcutrecht.nl FU Dutch Epilepsy Fund; Prinses Beatrix Fund; International Parkinson Fund; European Union [289581]; Collaborative project Epi-miRNA [FP7-HEALTH-2013-INNOVATION-1]; CTMM, the Center for Translational Molecular Medicine, project EMINENCE [01C-204] FX Our work was supported by the Dutch Epilepsy Fund, the Prinses Beatrix Fund, the International Parkinson Fund, the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7) 2007-2013 under REA grant agreement number 289581 (NPlast), and the FP7-HEALTH-2013-INNOVATION-1 Collaborative project Epi-miRNA. Our work was partly performed within the framework of CTMM (to RJP), the Center for Translational Molecular Medicine, project EMINENCE (01C-204). 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PD MAY PY 2015 VL 14 IS 5 BP 532 EP 546 DI 10.1016/S1474-4422(14)70257-1 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA CG6SY UT WOS:000353433900013 ER PT J AU Laxman, DJ McBride, BA Jeans, LM Dyer, WJ Santos, RM Kern, JL Sugimura, N Curtiss, SL Weglarz-Ward, JM AF Laxman, Daniel J. McBride, Brent A. Jeans, Laurie M. Dyer, W. Justin Santos, Rosa M. Kern, Justin L. Sugimura, Niwako Curtiss, Sarah L. Weglarz-Ward, Jenna M. TI Father Involvement and Maternal Depressive Symptoms in Families of Children with Disabilities or Delays SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Depression; Disability related studies; Family and mental illness; Families with disabled members; Fathers level and quality of child-care involvement ID DEVELOPMENTAL DELAY; YOUNG-CHILDREN; PRESCHOOL-CHILDREN; PARENTING STRESS; MOTHERS; AUTISM; ASSOCIATIONS; METAANALYSIS; PERCEPTIONS; PREDICTORS AB This study examined the longitudinal association between fathers' early involvement in routine caregiving, literacy, play, and responsive caregiving activities at 9 months and maternal depressive symptoms at 4 years. Data for 3,550 children and their biological parents were drawn from the Early Childhood Longitudinal Study-Birth Cohort data set. Analyses in a structural equation modeling framework examined whether the association between father involvement and maternal depressive symptoms differed for families of children with autism spectrum disorder (ASD) and for families of children with other disabilities or delays from families of children who were typically developing. Results indicated that father literacy and responsive caregiving involvement were associated with lower levels of depressive symptoms for mothers of children with ASD. These findings indicate that greater father involvement may benefit families of children with ASD and highlight the need to support and encourage service providers to work with fathers. C1 [Laxman, Daniel J.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [McBride, Brent A.; Santos, Rosa M.; Kern, Justin L.; Sugimura, Niwako; Curtiss, Sarah L.; Weglarz-Ward, Jenna M.] Univ Illinois, Urbana, IL 61801 USA. [Jeans, Laurie M.] St Ambrose Univ, Davenport, IA USA. [Dyer, W. Justin] Brigham Young Univ, Provo, UT 84602 USA. RP Laxman, DJ (reprint author), Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. EM dlaxman@Waisman.Wisc.edu FU Institute for Education Sciences of the U.S. Department of Education [R324A120174]; Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [T32HD007489, P30HD003352] FX This research was supported by a grant from the Institute for Education Sciences of the U.S. Department of Education to B. McBride, R. Santos, S. Hong, and W. J. Dyer (R324A120174). This research was also supported in part by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Numbers T32HD007489 and P30HD003352. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Institute for Education Sciences or the National Institutes of Health. 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PD MAY PY 2015 VL 19 IS 5 BP 1078 EP 1086 DI 10.1007/s10995-014-1608-7 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CG0SM UT WOS:000352978500016 PM 25326111 ER PT J AU Fujiwara, H Yassin, W Murai, T AF Fujiwara, Hironobu Yassin, Walid Murai, Toshiya TI Neuroimaging studies of social cognition in schizophrenia SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review DE magnetic resonance imaging; multimodal imaging; quality of life; schizophrenia; social cognition ID EMOTIONAL FACIAL EXPRESSIONS; VOXEL-BASED MORPHOMETRY; WHITE-MATTER INTEGRITY; FRONTAL-LOBE PATHOLOGY; HUMAN AMYGDALA; GRAY-MATTER; NORMAL ADULTS; MIND; RECOGNITION; AUTISM AB Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology. C1 [Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya] Kyoto Univ, Grad Sch Med, Dept Psychiat, Kyoto 6068507, Japan. [Fujiwara, Hironobu] Kyoto Univ Hosp, Integrated Clin Educ Ctr, Kyoto 606, Japan. RP Murai, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Psychiat, Sakyo Ku, Shogoinkawahara Cho 54, Kyoto 6068507, Japan. EM murai@kuhp.kyoto-u.ac.jp RI ahmed, Jamila/E-8653-2015 FU Japan Society for the Promotion of Science [22220003, 23390290, 23118004]; Ministry of Education, Culture, Sports, Science and Technology, Japan FX The authors declare no conflict of interest. This study was funded by a Grant-in-Aid for Scientific Research (S) (22220003), a Grant-in-Aid for Scientific Research (B) (23390290), and a Grant-in-Aid for Scientific Research on Innovative Areas (23118004), from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology, Japan. H.F. wrote the first draft of the manuscript, critically reviewed it, and approved the final manuscript as submitted. W.Y. managed the literature search, contributed to the writing of the manuscript, critically reviewed it, and approved the final manuscript as submitted. T.M. supervised, reviewed, and edited the manuscript, and approved it as submitted. 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We then consider how diffusion dynamics through interaction at critical focal points, in tandem with exogenous shocks, could have shaped the spatial dynamics of autism in California. We achieve these goals through an empirically calibrated simulation model of the whole population of 3- to 9-year-olds in California. We show that in the absence of interaction at these fociprincipally malls and schoolswe would not observe an autism epidemic. We also explore the idea that epigenetic changes affecting one generation in the distal past could shape the precise spatial patterns we observe among the next generation. C1 [Liu, Kayuet] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90024 USA. [Bearman, Peter S.] Columbia Univ, Paul F Lazarsfeld Ctr Social Sci, New York, NY 10027 USA. RP Bearman, PS (reprint author), Columbia Univ, 701b Knox Hall,622 W 122nd St, New York, NY 10027 USA. EM psb17@columbia.edu FU National Institutes of Health (NIH) Director's Pioneer Award program, part of the NIH Roadmap for Medical Research [1 DP1 OD003635-01] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is supported by the National Institutes of Health (NIH) Director's Pioneer Award program, part of the NIH Roadmap for Medical Research (Grant 1 DP1 OD003635-01). 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PD MAY PY 2015 VL 44 IS 2 SI SI BP 272 EP 305 DI 10.1177/0049124112460369 PG 34 WC Social Sciences, Mathematical Methods; Sociology SC Mathematical Methods In Social Sciences; Sociology GA CG3UD UT WOS:000353204200004 ER PT J AU Tamouza, R Bennabi, M Delorme, R Fortier, C Marzais, F Gaman, A Charron, D Bourgeron, T Leboyer, M Tamouza, R AF Tamouza, Ryad Bennabi, Meriem Delorme, Richard Fortier, Catherine Marzais, Francois Gaman, Alexandru Charron, Dominique Bourgeron, Thomas Leboyer, Marion Tamouza, Ryad TI HLA-CLASS II GENETIC SIGNATURES IN AUTISM SPECTRUM DISORDERS SO TISSUE ANTIGENS LA English DT Meeting Abstract CT European-Federation-for-Immunogenetics Conference CY APR 26-29, 2015 CL Geneva, SWITZERLAND SP European Federat Immunogenet C1 [Tamouza, Ryad; Tamouza, Ryad] Jean Dausset Lab, Paris, France. [Tamouza, Ryad; Bennabi, Meriem; Tamouza, Ryad] INSERM, UMRS 1160, Paris, France. [Delorme, Richard] Hop Robert Debre, DHU Protect Serv Psychiat Enfant & Adolescent, F-75019 Paris, France. [Fortier, Catherine; Marzais, Francois; Charron, Dominique] St Louis Hosp, Jean Dausset Lab, Paris, France. [Gaman, Alexandru] FondaMental Fdn, Creteil, France. [Bourgeron, Thomas] Inst Pasteur, Dept Genet Humaine & Fonct Cognit, Paris, France. [Leboyer, Marion] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. EM tamouza.ryad@gmail.com NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 EI 1399-0039 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2015 VL 85 IS 5 MA P20 BP 337 EP 337 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA CF9SN UT WOS:000352907000097 ER PT J AU Tamouza, R Bennabi, M Delorme, R Fortier, C Marzais, F Gaman, A Charron, D Bourgeron, T Leboyer, M Tamouza, R AF Tamouza, Ryad Bennabi, Meriem Delorme, Richard Fortier, Catherine Marzais, Francois Gaman, Alexandru Charron, Dominique Bourgeron, Thomas Leboyer, Marion Tamouza, Ryad TI CLEC7A (DECTIN-1) POLYMOPHISMS IN AUTISM SPECTRUM DISORDERS: GENETIC RISK FACTORS AND GENETIC DISEASE SPECIFIERS SO TISSUE ANTIGENS LA English DT Meeting Abstract CT European-Federation-for-Immunogenetics Conference CY APR 26-29, 2015 CL Geneva, SWITZERLAND SP European Federat Immunogenet C1 [Tamouza, Ryad; Tamouza, Ryad] Jean Dausset Lab, Paris, France. [Bennabi, Meriem] INSERM, UMRS 1160, Paris, France. [Bennabi, Meriem] St Louis Hosp, INSERM, U1160, Paris, France. [Delorme, Richard] Hop Robert Debre, Dept Pediat Psychiat, F-75019 Paris, France. [Fortier, Catherine; Marzais, Francois; Charron, Dominique] St Louis Hosp, Jean Dausset Lab, Paris, France. [Gaman, Alexandru] FondaMental Fdn, Creteil, France. [Bourgeron, Thomas] Pasteur Inst Paris, Dept Genet & Cognit Funct, Paris, France. [Leboyer, Marion] Hop Henri Mondor, Dept Psychiat, F-94010 Creteil, France. EM tamouza.ryad@gmail.com NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 EI 1399-0039 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2015 VL 85 IS 5 MA P39 BP 344 EP 344 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA CF9SN UT WOS:000352907000116 ER PT J AU Choi, US Kim, SY Sim, HJ Lee, SY Park, SY Jeong, JS Seol, KI Yoon, HW Jhung, K Park, JI Cheon, KA AF Choi, Uk-Su Kim, Sun-Young Sim, Hyeon Jeong Lee, Seo-Young Park, Sung-Yeon Jeong, Joon-Sup Seol, Kyeong In Yoon, Hyo-Woon Jhung, Kyungun Park, Jee-In Cheon, Keun-Ah TI Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study SO YONSEI MEDICAL JOURNAL LA English DT Article DE ASDs; social reward leaning; fMRI ID DIAGNOSTIC INTERVIEW; INFORMATION; CORTEX AB Purpose: We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). Materials and Methods: 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. Results: ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyms. Conclusion: These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs. C1 [Choi, Uk-Su; Park, Sung-Yeon; Jeong, Joon-Sup] Gachon Univ Med & Sci, Neurosci Res Inst, Inchon, South Korea. [Kim, Sun-Young; Sim, Hyeon Jeong; Lee, Seo-Young; Seol, Kyeong In; Park, Jee-In; Cheon, Keun-Ah] Yonsei Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Coll Med, Seoul 120752, South Korea. [Kim, Sun-Young; Sim, Hyeon Jeong; Lee, Seo-Young; Seol, Kyeong In; Park, Jee-In; Cheon, Keun-Ah] Yonsei Univ, Inst Behav Sci Med, Yonsei Autism Lab, Coll Med, Seoul 120752, South Korea. [Yoon, Hyo-Woon] Daegu Cyber Univ, Dept Art Therapy, Daegu, South Korea. [Jhung, Kyungun] Konyang Univ, Dept Psychiat, Coll Med, Taejon, South Korea. RP Cheon, KA (reprint author), Yonsei Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Coll Med, 50-1 Yonsei Ro, Seoul 120752, South Korea. EM kacheon@yuhs.ac RI ahmed, Jamila/E-8653-2015 FU Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI12C0021 (A120029), HI12C0245 (A120296)]; Yonsei University College of Medicine [6-2010-0139] FX This work was supported by a research grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [Grant number: HI12C0021 (A120029), HI12C0245 (A120296)] and by a faculty research grant from Yonsei University College of Medicine for 2010 (6-2010-0139). 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Bisphenol A (BPA), a widely used chemical in the plastic containers and in the linings of food and beverage cans, has been suggested to play a possible causative role in some developmental disorders. Here, we report behavioral modifications in Drosophila melanogaster following early exposure to BPA, which may suggest BPA as an environmental risk factor for the behavioral impairments that are the basis of diagnosis of autism and ADHD. In an open field assay with perinatally BPA-exposed and vehicle-treated control Drosophila, different parameters of locomotion (distance traveled, walking speed, spatial movement, mobility, turn angle, angular velocity and meander) were analyzed using the ethovision software. We also examined the repetitive and social interaction behaviors in these flies. In an open field assay, we identified disturbances in the locomotion patterns of BPA-exposed Drosophila that may relate to the decision-making and the motivational state of the animal. An increase in repetitive behavior was observed as an increase in the grooming behavior of Drosophila following BPA exposure. Furthermore, we also observed abnormal social interaction by the BPA-exposed flies in a social setting. These results demonstrate the effect of the environmentally prevalent risk agent BPA on the behavior of Drosophila, and suggest the practicability and the ease of using Drosophila as a model in the studies of neurobehavioral developmental disorders. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kaur, Kulbir; Chauhan, Ved; Chauhan, Abha] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA. [Kaur, Kulbir] CUNY, Grad Ctr, Biol Neurosci Grad Program, New York, NY 10016 USA. [Kaur, Kulbir] Ctr Dev Neurosci & Dev Disabil, Staten Isl, NY 10314 USA. [Simon, Anne F.] Univ Western Ontario, Fac Sci, Dept Biol, London, ON N6A 3K7, Canada. 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Brain Res. PD MAY 1 PY 2015 VL 284 BP 77 EP 84 DI 10.1016/j.bbr.2015.02.001 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CF6NB UT WOS:000352672300010 PM 25660202 ER PT J AU Weisman, O Agerbo, E Carter, CS Harris, JC Uldbjerg, N Henriksen, TB Thygesen, M Mortensen, PB Leckman, JF Dalsgaard, S AF Weisman, Omri Agerbo, Esben Carter, C. Sue Harris, James C. Uldbjerg, Niels Henriksen, Tine B. Thygesen, Malene Mortensen, Preben B. Leckman, James F. Dalsgaard, Soren TI Oxytocin-augmented labor and risk for autism in males SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Pitocin; Autism; Labor; Augmentation; Gender bias; Birth cohort ID SPECTRUM DISORDERS; PITOCIN INDUCTION; WOMEN; GENE; ASSOCIATION; VASOPRESSIN; INFERENCE; CHILDREN; HUMANS; OXTR AB The use of synthetic oxytocin (OT) to induce and/or augment labor and delivery is on the rise. Maternal exposure to OT during birth may have adverse effects on the infant's development, including increased risk for autism. Yet, studies that test this biologically plausible association and whether it is modified by sex are limited and show inconsistent findings. To this end, we conducted an epidemiological analysis, including all singleton live births in Denmark between 2000 and 2009 (N=557,040), with a follow-up through 2012. A total of 2110 children in this cohort were subsequently diagnosed with autistic disorder according to the ICD-10-DCR. Augmentation of labor with OT was modestly associated with an increased risk for autism in males (HR 1.13; 95% CI, 1.00-1.26; P=0.04), but not in females (0.99; 0.77-1.27; P=0.95). Among males exposed to OT augmentation, 560 were subsequently diagnosed with autistic disorder, and among those not exposed, 1177 met criteria for autism (incidence rate 103.2 and 81.4 per 100,000 person-years, respectively). Our findings suggest a modest association between OT-augmented labor and risk for autism in males. However, given the known benefits of using synthetic OT during labor and delivery caution is warranted when interpreting the findings. Future studies should also investigate dose-dependent effect of OT on infant's development. (C) 2015 Elsevier B.V. All rights reserved. C1 [Weisman, Omri; Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Agerbo, Esben; Thygesen, Malene; Mortensen, Preben B.; Dalsgaard, Soren] Aarhus Univ, Sch Business & Social Sci, Dept Econ & Business, Natl Ctr Register Based Res, Aarhus, Denmark. [Agerbo, Esben; Mortensen, Preben B.; Dalsgaard, Soren] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark. [Agerbo, Esben; Mortensen, Preben B.; Dalsgaard, Soren] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark. [Agerbo, Esben; Thygesen, Malene] Aarhus Univ, Dept Econ & Business, CIRRAU Ctr Integrated Register Based Res, Aarhus, Denmark. [Carter, C. Sue] Indiana Univ, Kinsey Inst, Bloomington, IN USA. [Harris, James C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Harris, James C.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Uldbjerg, Niels] Aarhus Univ, Dept Clin Med Obstet & Gynecol, Aarhus, Denmark. [Henriksen, Tine B.] Aarhus Univ Hosp, Dept Pediat, Perinatal Epidemiol Res Unit, Skejby, Denmark. [Dalsgaard, Soren] Hosp Telemark, Dept Child & Adolescent Psychiat, Kragero, Norway. RP Weisman, O (reprint author), Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. EM omri.weisman@yale.edu RI Agerbo, Esben /A-2645-2012 OI Agerbo, Esben /0000-0002-2849-524X FU Lundbeck Foundation; Centre For Integrated Register-Based Research at Aarhus University (CIRRAU); Fulbright; Rothschild Fellowships FX SD and EA are grateful for the financial support provided by The Lundbeck Foundation, and the Centre For Integrated Register-Based Research at Aarhus University (CIRRAU). The work conducted by OW is supported by the Fulbright and the Rothschild Fellowships. 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NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 751 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501344 ER PT J AU Wang, H Liang, S Wang, MQ Gao, JQ Sun, CH Wang, J Xia, W Wu, SY Sumner, SJ Zhang, FY Sun, CH Wu, LJ AF Wang, Han Liang, Shuang Wang, Maoqing Gao, Jingquan Sun, Caihong Wang, Jia Xia, Wei Wu, Shiying Sumner, Susan J. Zhang, Fengyu Sun, Changhao Wu, Lijie TI Metabolomics Study of Autism for Biomarker Discovery in Han Chinese Population SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; serum biomarker; diagnosis; metabolomics; ultra-performance liquid chromatography quadrupol C1 [Wang, Han; Liang, Shuang; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Wu, Lijie] Harbin Med Univ, Sch Publ Hlth, Dept Child & Adolescent Hlth, Harbin, Peoples R China. [Wang, Maoqing; Sun, Changhao] Harbin Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Harbin, Peoples R China. [Wu, Shiying] SAS Inst Inc, Adv Analyt Div, Cary, NC USA. [Sumner, Susan J.] Res Triangle Inst, Syst & Translat Sci, Res Triangle Pk, NC 27709 USA. [Zhang, Fengyu] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 763 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501356 ER PT J AU Watson, KK Miller, S Hannah, E Kovac, M Damiano, C Sabatino, A Turner-Brown, L Sasson, N Platt, M Dichter, GS AF Watson, Karli K. Miller, Stephanie Hannah, Eleanor Kovac, Megan Damiano, Cara Sabatino, Antionette Turner-Brown, Lauren Sasson, Noah Platt, Michael Dichter, Gabriel S. TI Autism Pay-per-view: Evidence for Differential Implicit Reward Value of Social and Nonsocial Stimuli in Children with Autism from an Econometric Choice Task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism spectrum disorder; behavioral econometrics; restricted interests; social C1 [Watson, Karli K.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA. [Miller, Stephanie; Hannah, Eleanor; Kovac, Megan; Damiano, Cara; Sabatino, Antionette; Turner-Brown, Lauren] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA. [Sasson, Noah] Univ Texas Dallas, Sch Behav & Brain Sci, Dallas, TX 75230 USA. [Platt, Michael] Duke Univ, Neurobiol, Durham, NC USA. [Dichter, Gabriel S.] Univ N Carolina, Psychiat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 532 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207501126 ER PT J AU Stadlbauer, U Labouesse, MA Dong, E Grayson, D Guidotti, A Meyer, U AF Stadlbauer, Ulrike Labouesse, Marie A. Dong, Erbo Grayson, Dennis Guidotti, Alessandro Meyer, Urs TI Transgenerational Transmission and Modification of Behavioral Deficits Induced by Prenatal Immune Activation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; Epigenetics; Immune System; Maternal Infection; Schizophrenia C1 [Stadlbauer, Ulrike; Labouesse, Marie A.; Meyer, Urs] Swiss Fed Inst Technol, Physiol & Behav Lab, Schwerzenbach, Switzerland. [Dong, Erbo; Grayson, Dennis; Guidotti, Alessandro] Univ Illinois, Coll Med, Dept Psychiat, Inst Psychiat, Chicago, IL USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 24 BP 9S EP 9S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500025 ER PT J AU Bohorquez, D White, RS Port, RG Carlson, GC AF Bohorquez, Dominique White, Rachel S. Port, Russel G. Carlson, Gregory C. TI Disruption of Amygdalar Functional Connectivity in PCDH10 Haploinsufficient Mice (Pcdh10+/-) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; Amygdala; Voltage Sensitive Dye Imaging; Electrophysiology; Protocadherin-10 C1 [Bohorquez, Dominique; White, Rachel S.; Port, Russel G.; Carlson, Gregory C.] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 143 BP 52S EP 52S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500136 ER PT J AU Ameis, S Croarkin, P Blumberger, D Drmic, I Desarkar, P Mabbott, D Szatmari, P Daskalakis, J AF Ameis, Stephanie Croarkin, Paul Blumberger, Daniel Drmic, Irene Desarkar, Pushpal Mabbott, Donald Szatmari, Peter Daskalakis, Jeff TI TMS for Executive Function Deficits in Youth with Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism Spectrum Disorder; Executive Functioning; Repetitive Transcranial Magnetic Stimulation; Brain Imaging; Clinical Trial C1 [Ameis, Stephanie; Szatmari, Peter] Ctr Addict & Mental Hlth, Child Youth & Family, Toronto, ON, Canada. [Ameis, Stephanie] Hosp Sick Children, Psychiat, Toronto, ON M5G 1X8, Canada. [Croarkin, Paul] Mayo Clin, Childrens Ctr, Rochester, MN USA. [Blumberger, Daniel; Daskalakis, Jeff] Ctr Addict & Mental Hlth, Temerty Ctr Therapeut Brain Intervent, Toronto, ON, Canada. [Drmic, Irene; Mabbott, Donald] Hosp Sick Children, Psychol, Toronto, ON M5G 1X8, Canada. [Desarkar, Pushpal] Ctr Addict & Mental Hlth, Dual Diag, Toronto, ON, Canada. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 181 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500174 ER PT J AU Damiano, C Miller, S Hannah, E Kovac, M Aloi, J Cockrell, D Dunlap, K Burrus, C Kinsey, E Bizzell, J Dichter, GS AF Damiano, Cara Miller, Stephanie Hannah, Eleanor Kovac, Megan Aloi, Joseph Cockrell, Dillon Dunlap, Kaitlyn Burrus, Caley Kinsey, Elizabeth Bizzell, Joshua Dichter, Gabriel S. TI Neural Mechanisms of Uncertainty Processing in Children with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism spectrum disorder; insistence on sameness; uncertainty; functional MRI C1 [Damiano, Cara; Miller, Stephanie; Hannah, Eleanor; Kovac, Megan; Aloi, Joseph; Cockrell, Dillon; Dunlap, Kaitlyn; Burrus, Caley; Kinsey, Elizabeth; Bizzell, Joshua] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA. [Dichter, Gabriel S.] Univ N Carolina, Psychiat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 183 BP 68S EP 69S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500176 ER PT J AU Vellingiri, B Subramaniam, M Meyyazhagan, A Krishnan, P Iyer, M AF Vellingiri, Balachandar Subramaniam, Mohanadevi Meyyazhagan, Arun Krishnan, Padmavathy Iyer, Mahalaxmi TI Peripheral Blood Markers of Homocysteine, Paraoxonase1 (PON1) Activity and Oxidative Stress in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; antioxidant protein; homocysteine; human paraoxonase; glutathione peroxidase C1 [Vellingiri, Balachandar; Meyyazhagan, Arun; Krishnan, Padmavathy; Iyer, Mahalaxmi] Bharathiar Univ, Zool, Coimbatore, Tamil Nadu, India. [Subramaniam, Mohanadevi] Dankook Univ, Anim Sci, Yongin, South Korea. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 184 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500177 ER PT J AU Ou, JJ Guo, H Hyde, TM Xia, K Hu, ZM Kleinman, JE Weinberger, DR Zhao, JP Zhang, FY AF Ou, Jianjun Guo, Hui Hyde, Thomas M. Xia, Kun Hu, Zhengmao Kleinman, Joel E. Weinberger, Daniel R. Zhao, Jingping Zhang, Fengyu TI ULK4 Genetic Variants Associate with risk of Autism and Its Gene Expression in Human Postmortem brains SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; ULK4; Genetic Variants; Postmortem brains C1 [Ou, Jianjun; Zhao, Jingping] Cent S Univ, Mental Hlth Inst, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Guo, Hui; Xia, Kun; Hu, Zhengmao] Cent S Univ, State Key Lab Med Genet, Changsha, Hunan, Peoples R China. [Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel R.; Zhang, Fengyu] Johns Hopkins Sch Med, Lieber Inst Brain Dev, Baltimore, MD USA. [Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Neurol, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Genom Med, Baltimore, MD USA. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 227 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500220 ER PT J AU Shen, YD Xun, GL Dong, HX Ou, JJ Xia, K Zhao, JP AF Shen, Yidong Xun, Guanglei Dong, Huixi Ou, Jianjun Xia, Kun Zhao, Jingping TI Association and Gene-gene Interactions Study of Reelin Signaling Pathway Related Genes with Autism in Chinese Han Population SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism; Reelin; Gene-Gene interaction C1 [Shen, Yidong; Xun, Guanglei; Dong, Huixi; Ou, Jianjun; Xia, Kun; Zhao, Jingping] Cent S Univ, Mental Hlth Inst, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 228 BP 87S EP 87S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500221 ER PT J AU Park, MTM Raznahan, A Shaw, P Gogtay, N Chakravarty, MM AF Park, Min Tae M. Raznahan, Armin Shaw, Philip Gogtay, Nitin Chakravarty, M. Mallar TI Shared Cerebellar Phenotypes in Autism Spectrum Disorders and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Cerebellum; Autism; Schizophrenia; MRI C1 [Park, Min Tae M.; Chakravarty, M. Mallar] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ, Canada. [Raznahan, Armin; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Shaw, Philip] NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 268 BP 103S EP 104S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500261 ER PT J AU Khundrakpam, B Lewis, J Kostopoulos, P Evans, A AF Khundrakpam, Budhachandra Lewis, John Kostopoulos, Penelope Evans, Alan TI Altered Cortical Trajectories in Autism Spectrum Disorders: Relation to Symptomatology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Autism spectrum disorders; Cortical trajectories; Neuroimaging; Symptom severity; Behavior C1 [Khundrakpam, Budhachandra; Lewis, John; Kostopoulos, Penelope; Evans, Alan] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 270 BP 104S EP 105S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500263 ER PT J AU Vasa, RA Tang, XY Crocetti, D Miller, MI Mostofsky, SH AF Vasa, Roma A. Tang, Xiaoying Crocetti, Deana Miller, Michael I. Mostofsky, Stewart H. TI Amygdala and Hippocampal Morphology in Children with High Functioning Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE autism spectrum disorders; amygdala; hippoccampal; morphology; children C1 [Vasa, Roma A.; Crocetti, Deana; Mostofsky, Stewart H.] Kennedy Krieger Inst, Ctr Neurodev & Imaging Res, Baltimore, MD USA. [Tang, Xiaoying; Miller, Michael I.] Johns Hopkins Univ, Ctr Imaging Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 269 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500262 ER PT J AU Cochran, DM Kennedy, DN Hodge, S Frazier, JA AF Cochran, David M. Kennedy, David N. Hodge, Steven Frazier, Jean A. TI Altered Striatal Resting-State Connectivity to Sensory and Language Processing Cortical Areas in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE autism; resting state fMRI; neuroimaging; striatum; functional connectivity C1 [Cochran, David M.; Kennedy, David N.; Hodge, Steven; Frazier, Jean A.] Univ Massachusetts, Sch Med, Psychiat, Worcester, MA USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 273 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207500266 ER PT J AU Rannals, MD Cerceo-Page, S Campbell, M Hamersky, G Gallo, R Shin, JH Hyde, TM Kleinman, J Jaffe, AE Weinberger, DR Maher, BJ AF Rannals, Matthew D. Cerceo-Page, Stephanie Campbell, Morganne Hamersky, Gregory Gallo, Ryan Shin, Joo Heon Hyde, Thomas M. Kleinman, Joel Jaffe, Andrew E. Weinberger, Daniel R. Maher, Brady J. TI The Schizophrenia and Autism Spectrum Disorder Gene TCF4 Regulates the Intrinsic Excitability of Prefrontal Neurons SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE schizophrenia; autism; TCF4; animal model; electrophysiology C1 [Rannals, Matthew D.; Cerceo-Page, Stephanie; Campbell, Morganne; Hamersky, Gregory; Gallo, Ryan; Maher, Brady J.] Lieber Inst Brain Dev, Dev Electrophysiol, Baltimore, MD USA. [Shin, Joo Heon; Kleinman, Joel; Jaffe, Andrew E.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Genet Epigenet & Bioinformat, Baltimore, MD USA. [Hyde, Thomas M.] Lieber Inst Brain Dev, Neuropathol, Baltimore, MD USA. [Maher, Brady J.] Johns Hopkins Sch Med, Psychiat & Behav Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 859 BP 308S EP 308S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502060 ER PT J AU Boisgontier, J Beggiato, A Toro, R Duchesnay, E Poupon, C Amsellem, F Katz, J Petit, J Monnet, D D'Albis, MA Delphine, D Aline, L Le Dudal, K Scimia, N Lettelier, L Leboyer, M Bourgeron, T Elmaleh, M Sebag, G Germanaud, D Delorme, R Houenou, J AF Boisgontier, Jennifer Beggiato, Anita Toro, Roberto Duchesnay, Edouard Poupon, Cyril Amsellem, Frederique Katz, Julien Petit, Julie Monnet, David D'Albis, Marc Antoine Delphine, Duclap Aline, Lefebvre Le Dudal, Katia Scimia, Nelly Lettelier, Laurence Leboyer, Marion Bourgeron, Thomas Elmaleh, Monique Sebag, Guy Germanaud, David Delorme, Richard Houenou, Josselin TI Fronto-occipital Disconnectivity as a Familial Risk Marker of Autism Spectrum Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE autism spectrum disorders; first-degree relatives; diffusion tensor imaging; magnetic resonance; genetic C1 [Boisgontier, Jennifer; Katz, Julien; Petit, Julie; Monnet, David; D'Albis, Marc Antoine; Houenou, Josselin] Hop Henri Mondor, INSERM, U955, Equipe Equipe Psychopathol & Genet Malad Psychiat, F-94010 Creteil, France. [Beggiato, Anita; Toro, Roberto; Bourgeron, Thomas] Inst Pasteur, Human Genet & Cognit Funct, Paris, France. [Duchesnay, Edouard] CEA Saclay, I2BM, Neurospin, UNATI, F-91191 Gif Sur Yvette, France. [Poupon, Cyril; Delphine, Duclap] CEA Saclay, I2BM, Neurospin, UNIRS, F-91191 Gif Sur Yvette, France. [Amsellem, Frederique; Elmaleh, Monique; Sebag, Guy] Robert Debre Hosp, Dept Pediat Imaging, Paris, France. [Aline, Lefebvre] CHU Caen, Esquirol Ctr, F-14000 Caen, France. [Le Dudal, Katia] Hop Henri Mondor, AP HP, CIC 1430, F-94010 Creteil, France. [Scimia, Nelly; Lettelier, Laurence; Germanaud, David; Delorme, Richard] Robert Debre Hosp, Chils & Adolescent Psychiat Unit, Paris, France. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1004 BP 363S EP 364S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502197 ER PT J AU Featherstone, RE Liang, YL Nagy, L Shin, R Kogan, JH Matsumoto, M Siegel, SJ AF Featherstone, Robert E. Liang, Yuling Nagy, Lauren Shin, Rick Kogan, Jeffery H. Matsumoto, Mitsuyuki Siegel, Steven J. TI Baclofen Restores Excitatory-inhibitory Balance in 15q13.3 Deletion Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE EEG; Gamma oscillation; Autism; Copy number variation; GABA C1 [Featherstone, Robert E.; Liang, Yuling; Nagy, Lauren; Siegel, Steven J.] Univ Penn, Psychiat Translat Neurosci, Philadelphia, PA 19104 USA. [Shin, Rick; Kogan, Jeffery H.] Astellas Res Inst Amer LLC, CNS, Skokie, IL USA. [Matsumoto, Mitsuyuki] Astellas Res Inst Japan LLC, CNS, Tokyo, Japan. RI ahmed, Jamila/E-8653-2015 NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1092 BP 399S EP 399S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502285 ER PT J AU Page, SC Rannals, MD Campbell, MN Briley, A Gallo, RA Mayfield, B Phan, BN Weinberger, DR Maher, BJ AF Page, Stephanie C. Rannals, Matthew D. Campbell, Morganne N. Briley, Aaron Gallo, Ryan A. Mayfield, Brent Phan, BaDoi N. Weinberger, Daniel R. Maher, Brady J. TI The Schizophrenia and Autism Associated Gene, Transcription Factor 4, Regulates Cortical Column Formation in the Prefrontal Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the Society-of-Biological-Psychiatry on Stress, Emotion, Neurodevelopment and Psychopathology CY MAY 14-16, 2015 CL Toronto, CANADA SP Soc Biol Psychiat DE Transcription Factor 4; Neural Differentiation; Neural Migration C1 [Page, Stephanie C.; Rannals, Matthew D.; Campbell, Morganne N.; Briley, Aaron; Gallo, Ryan A.; Mayfield, Brent; Phan, BaDoi N.; Maher, Brady J.] Lieber Inst Brain Dev, Div Dev Electrophysiol, Baltimore, MD USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Genet Epigenet & Bioinformat, Baltimore, MD USA. [Weinberger, Daniel R.; Maher, Brady J.] Johns Hopkins Sch Med, Psychiat & Behav Sci, Baltimore, MD USA. [Weinberger, Daniel R.; Maher, Brady J.] Johns Hopkins Sch Med, Neurosci, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Genet Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 SU S MA 1136 BP 416S EP 416S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CF0BM UT WOS:000352207502328 ER PT J AU Esan, F Chester, V Gunaratna, IJ Hoare, S Alexander, RT AF Esan, Fola Chester, Verity Gunaratna, Ignatius J. Hoare, Sudeep Alexander, Regi T. TI The Clinical, Forensic and Treatment Outcome Factors of Patients with Autism Spectrum Disorder Treated in a Forensic Intellectual Disability Service SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE autistic spectrum disorder; comorbidity; forensic; intellectual disability; learning disability; treatment outcomes ID ASPERGERS-SYNDROME; OFFENDING BEHAVIOR; VIOLENCE; ADULTS; SAMPLE; LAW AB Background To describe the characteristics of those with autism spectrum disorder (ASD) treated within a forensic intellectual disability hospital and to compare them with those without ASD. Method Service evaluation of a cohort of 138 patients treated over a 6-year period. Results Of the 138, 42 had an ASD. Personality disorders and harmful use or dependence on drugs were significantly lower in the ASD group. The ASD group was less likely to be subject to criminal sections or restriction orders. Self-harm was significantly higher in the ASD group. There were no differences in the length of stay and direction of care pathway. Conclusions Although the ASD and non-ASD groups differ on clinical and forensic characteristics, their treatment outcomes appear similar. This suggests that the diagnostic category of ASD alone may be inadequate in predicting the treatment outcome. There is a case to identify distinct typologies within the ASD group. C1 [Esan, Fola; Chester, Verity; Gunaratna, Ignatius J.; Hoare, Sudeep; Alexander, Regi T.] Partnerships Care Learning Disabil Serv, Diss IP22 1BA, Norfolk, England. [Alexander, Regi T.] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England. RP Alexander, RT (reprint author), Partnerships Care Learning Disabil Serv, St Johns House,Lion Rd, Diss IP22 1BA, Norfolk, England. EM regi.alexander@-btinternet.com CR Alexander R. 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TI Research Review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Review DE Autism spectrum disorder; attention-deficit; hyperactivity disorder; Caesarean section ID PERINATAL RISK-FACTORS; INFANTILE-AUTISM; HYPERACTIVITY DISORDER; NEONATAL FACTORS; DELIVERY; CHILDREN; COMPLICATIONS; POPULATION; MICROBIOTA; ASSOCIATION AB BackgroundGiven the growing prevalence of birth by Caesarean section (CS) worldwide, it is important to understand any long-term effects CS delivery may have on a child's development. We assessed the impact of mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). MethodsWe conducted a systematic review of the literature in PubMed, Embase, CINAHL, PsycINFO and Web of Science up to 28 February 2014. No publication date, language, location or age restrictions were employed. ResultsThirteen studies reported an adjusted estimate for CS-ASD, producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40). Two studies reported an adjusted estimate for CS-ADHD, producing a pooled OR of 1.07 (95% CI: 0.86, 1.33). ConclusionsDelivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of CS implies that even a small increase in the odds of disorders, such as ASD or ADHD, may have a large impact on the society as a whole. This warrants further investigation. C1 [Curran, Eileen A.; O'Neill, Sinead M.; Kenny, Louise C.; Khashan, Ali S.] Natl Univ Ireland Univ Coll Cork, Dept Obstet & Gynaecol, Irish Ctr Fetal & Neonatal Translat Res INFANT, Cork, Ireland. [O'Neill, Sinead M.] Cork Univ, Matern Hosp, Anu Res Ctr, Dept Obstet & Gynaecol,Natl Perinatal Epidemiol C, Cork, Ireland. [Cryan, John F.] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Dept Anat & Neurosci, Cork, Ireland. [Dinan, Timothy G.] Natl Univ Ireland Univ Coll Cork, Dept Psychiat, Alimentary Pharmabiot Ctr, Cork, Ireland. [Khashan, Ali S.; Kearney, Patricia M.] Natl Univ Ireland Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland. RP Curran, EA (reprint author), Cork Univ, Matern Hosp, 5th Floor, Cork, Ireland. EM ecurran@ucc.ie FU Science Foundation Ireland (SFI) [12\RC\2272] FX This work was carried out at The Irish Centre for Fetal and Neonatal Translational Research (INFANT) (Science Foundation Ireland (SFI) funded Centre, Grant number 12 vertical bar RC vertical bar 2272). The authors have declared that they have no competing or potential conflicts of interest. CR Al-Jammas I. 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Child Psychol. Psychiatry PD MAY PY 2015 VL 56 IS 5 BP 500 EP 508 DI 10.1111/jcpp.12351 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CF4YQ UT WOS:000352560900002 PM 25348074 ER PT J AU Hirschler-Guttenberg, Y Golan, O Ostfeld-Etzion, S Feldman, R AF Hirschler-Guttenberg, Yael Golan, Ofer Ostfeld-Etzion, Sharon Feldman, Ruth TI Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorder; emotion regulation; emotional reactivity; mothering; fathering ID SELF-REGULATION; EMPIRICAL-EVIDENCE; CHILDREN; EXPRESSION; STRATEGIES; SYNCHRONY; ANGER; TEMPERAMENT; RECOGNITION; CHILDHOOD AB BackgroundChildren with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. MethodsForty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. ResultsDuring free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. ConclusionFindings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality, rather than increased negative reactivity and self-regulatory efforts, emerges as the consistent element associated with ER processes in this group. C1 [Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth] Bar Ilan Univ, Dept Psychol, IL-52900 Ramat Gan, Israel. [Golan, Ofer] Assoc Children Risk, Tel Aviv, Israel. [Feldman, Ruth] Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. RP Feldman, R (reprint author), Bar Ilan Univ, Dept Psychol, IL-52900 Ramat Gan, Israel. EM Feldman@mail.biu.ac.il RI ahmed, Jamila/E-8653-2015 FU Association for Children at Risk, Ramat-Hen, Israel; US-Israel Bi-National Science Foundation FX The study was supported by the Association for Children at Risk, Ramat-Hen, Israel and by the US-Israel Bi-National Science Foundation. 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H., 2007, CHILD DEV, V78, P597 Yirmiya N, 2006, MOL PSYCHIATR, V11, P488, DOI 10.1038/sj.mp.4001812 Zwaigenbaum L, 2013, BEHAV BRAIN RES, V251, P133, DOI 10.1016/j.bbr.2013.04.004 Zwaigenbaum L, 2005, INT J DEV NEUROSCI, V23, P143, DOI 10.1016/j.ijdevneu.2004.05.001 NR 52 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAY PY 2015 VL 56 IS 5 BP 530 EP 539 DI 10.1111/jcpp.12311 PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CF4YQ UT WOS:000352560900005 PM 25123380 ER PT J AU de Vries, M Prins, PJM Schmand, BA Geurts, HM AF de Vries, Marieke Prins, Pier J. M. Schmand, Ben A. Geurts, Hilde M. TI Working memory and cognitive flexibility-training for children with an autism spectrum disorder: a randomized controlled trial SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Executive functioning; working memory; flexibility; cognitive training; autism ID QUALITY-OF-LIFE; SOCIAL RESPONSIVENESS SCALE; GENERIC CORE SCALES; EXECUTIVE FUNCTION; DIAGNOSTIC INTERVIEW; PRESCHOOL-CHILDREN; ADHD; TASK; PEDSQL(TM)-4.0; VALIDITY AB BackgroundPeople with autism spectrum disorders (ASDs) experience executive function (EF) deficits. There is an urgent need for effective interventions, but in spite of the increasing research focus on computerized cognitive training, this has not been studied in ASD. Hence, we investigated two EF training conditions in children with ASD. MethodsIn a randomized controlled trial, children with ASD (n=121, 8-12years, IQ>80) were randomly assigned to an adaptive working memory (WM) training, an adaptive cognitive flexibility-training, or a non-adaptive control training (mock-training). Braingame Brian, a computerized EF-training with game-elements, was used. Outcome measures (pretraining, post-training, and 6-week-follow-up) were near-transfer to trained EFs, far-transfer to other EFs (sustained attention and inhibition), and parent's ratings of daily life EFs, social behavior, attention deficit hyperactivity disorder (ADHD)-behavior, and quality of life. ResultsAttrition-rate was 26%. Children in all conditions who completed the training improved in WM, cognitive flexibility, attention, and on parent's ratings, but not in inhibition. There were no significant differential intervention effects, although children in the WM condition showed a trend toward improvement on near-transfer WM and ADHD-behavior, and children in the cognitive flexibility condition showed a trend toward improvement on near-transfer flexibility. ConclusionAlthough children in the WM condition tended to improve more in WM and ADHD-behavior, the lack of differential improvement on most outcome measures, the absence of a clear effect of the adaptive training compared to the mock-training, and the high attrition rate suggest that the training in its present form is probably not suitable for children with ASD. C1 [de Vries, Marieke; Prins, Pier J. M.; Schmand, Ben A.; Geurts, Hilde M.] Univ Amsterdam, NL-1018 XA Amsterdam, Netherlands. [de Vries, Marieke; Geurts, Hilde M.] Dutch Autism & ADHD Res Ctr, Amsterdam, Netherlands. [Schmand, Ben A.] Acad Med Ctr Amsterdam, Amsterdam, Netherlands. [Geurts, Hilde M.] Dr Leo Kannerhuis, Amsterdam, Netherlands. RP de Vries, M (reprint author), Univ Amsterdam, Dept Psychol, Brain & Cognit, Weesperpl 4, NL-1018 XA Amsterdam, Netherlands. EM m.devries@uva.nl FU University of Amsterdam FX The study was approved by the ethics committee of the Academic Medical Center Amsterdam (METC 2010-185), and registered in the Dutch trial register (NL32255.018.10). Study funding was provided by the University of Amsterdam. P.J.M.P. is member of the foundation Gaming and Training, a nonprofit organization that develops and evaluates online interventions, such as EF training, for youth mental health care. The other authors have declared that they have no competing or potential conflicts of interest. The authors thank all the children and their parents for participating in the study; the students for testing the participants; and the mental health care institutions for helping with patient recruitment. 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M., 2001, ASSESSMENT CHILDREN Shipstead Z, 2012, J APPL RES MEM COGN, V1, P185, DOI 10.1016/j.jarmac.2012.06.003 Shipstead Z, 2012, PSYCHOL BULL, V138, P628, DOI 10.1037/a0027473 Smidts D., 2009, BRIEF EXECUTIEVE FUN Smith EE, 1999, SCIENCE, V283, P1657, DOI 10.1126/science.283.5408.1657 Stichter JP, 2010, J AUTISM DEV DISORD, V40, P1067, DOI [10.1007/s10803-010-0959-1, 10.1007/s10803-010-0968-0] Thorell LB, 2009, DEVELOPMENTAL SCI, V12, P106, DOI 10.1111/j.1467-7687.2008.00745.x Varni JW, 2001, MED CARE, V39, P800, DOI 10.1097/00005650-200108000-00006 Varni JW, 2003, AMBUL PEDIATR, V3, P329, DOI 10.1367/1539-4409(2003)003<0329:TPAAPP>2.0.CO;2 World Health Organisation, 1992, ICD 10 CLASS MENT BE Zinke K, 2012, FRONT HUM NEUROSCI, V6, DOI 10.3389/fnhum.2012.00041 NR 74 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAY PY 2015 VL 56 IS 5 BP 566 EP 576 DI 10.1111/jcpp.12324 PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CF4YQ UT WOS:000352560900009 PM 25256627 ER PT J AU Jones, RM Risi, S Wexler, D Anderson, D Corsello, C Pickles, A Lord, C AF Jones, Rebecca M. Risi, Susan Wexler, Diana Anderson, Deborah Corsello, Christina Pickles, Andrew Lord, Catherine TI How interview questions are placed in time influences caregiver description of social communication symptoms on the ADI-R SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorders; ADI-R; parent report; longitudinal; diagnosis ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; SEVERITY; SCORES; SCHEDULE; CHILDREN; AGE AB BackgroundCaregiver report is crucial for the diagnosis of childhood onset psychiatric disorders, particularly autism. Three experiments were conducted to determine whether caregiver reports of past and current behaviors are affected by question timing and ordering. MethodsUsing the Autism Diagnostic Interview - Revised (ADI-R), two studies systematically varied the order in which caregivers were asked about behaviors. In a third study, descriptions of children's current behaviors at age 5 were compared to retrospective descriptions of behaviors at age 5 collected at age 10. ResultsCaregivers, who were first asked about a history of symptoms, described less severe past and present behavior than caregivers reporting current behaviors as well as caregivers reporting current and history of symptoms together. Caregivers retrospectively reported more severe behaviors for age 5 when their children were age 10 than they had when their children were age 5. ConclusionsCaregivers describe past behaviors differently depending on whether they are asked about current symptoms first. Methods of caregiver reporting can influence interpretations of symptom severity with effects on diagnoses and research findings. C1 [Jones, Rebecca M.; Wexler, Diana; Anderson, Deborah; Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, Ctr Autism & Dev Brain, White Plains, NY 10605 USA. [Risi, Susan] Eastern Michigan Univ, Autism Collaborat Ctr, Ypsilanti, MI 48197 USA. [Corsello, Christina] Rady Childrens Hosp, San Diego, CA USA. [Pickles, Andrew] Kings Coll London, Inst Psychiat, Dept Biostat, London WC2R 2LS, England. RP Jones, RM (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, Ctr Autism & Dev Brain, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM rej2004@med.cornell.edu RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU National Institute of Mental Health [NIMH RO1 MH081873-04, 1R01HD073975-01]; Autism Speaks Meixner Fellowship [7608]; Health Resources Services Administration [HRSA UA3-MC-11055] FX This study was funded by the National Institute of Mental Health (NIMH RO1 MH081873-04 and 1R01HD073975-01), Autism Speaks Meixner Fellowship (7608), and the Health Resources Services Administration (HRSA UA3-MC-11055). CR American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th American Psychiatric Association, 2013, DIAGN STAT MAN MENT Angold A, 2000, J AM ACAD CHILD PSY, V39, P39, DOI 10.1097/00004583-200001000-00015 Dunn L. M., 1997, PEABODY PICTURE VOCA, V3rd Elliott C. 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Child Psychol. Psychiatry PD MAY PY 2015 VL 56 IS 5 BP 577 EP 585 DI 10.1111/jcpp.12325 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CF4YQ UT WOS:000352560900010 PM 25243378 ER PT J AU Maffini, MV Neltner, TG AF Maffini, Maricel V. Neltner, Thomas G. TI Brain drain: the cost of neglected responsibilities in evaluating cumulative effects of environmental chemicals SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID PUBLIC-HEALTH; DISABILITIES AB Developmental disabilities affect millions of people and have a great impact on their lives, their families and the societies where they live. The prevalence of disorders such as autism, attention deficit hyperactivity disorder as well as subclinical decrements in brain function cannot be explained solely as genetic diseases. Exposures to environmental chemicals, especially during prenatal and early postnatal life, are one likely explanation for some of the decrements. The current chemical risk assessment approach is typically based on the toxicity caused by a single chemical on a variety of organs without acknowledging additional exposures to other chemicals also affecting the same organ or system. We identified more than 300 chemicals allowed in food that may have potential harmful effects on the developing brain. Each individual chemical may or may not have a harmful effect if it were the only one present, but we know next to nothing about their cumulative biological effects on the brain. An expanded cumulative risk assessment approach is needed, and it should focus on health outcomes, like developmental disabilities, arising from the accumulation of effects of multiple chemicals on the brain. The laws regulating the safety of additives already require that regulators in Europe and the USA consider cumulative effects; so far, they seem to have neglected the mandate. We must move beyond treating chemical exposures as isolated incidents and look at their cumulative biological effects on organs and their role in the onset of chronic diseases. The time has come to overhaul chemical risk assessment. C1 [Maffini, Maricel V.; Neltner, Thomas G.] Nat Resources Def Council, Washington, DC 20005 USA. RP Maffini, MV (reprint author), Nat Resources Def Council, 1152 15th St NW, Washington, DC 20005 USA. EM drmvma@gmail.com FU Pew Charitable Trusts FX This work was supported by a grant from The Pew Charitable Trusts to the Natural Resources Defense Council. CR Barouki R, 2012, ENVIRON HEALTH-GLOB, V11, DOI 10.1186/1476-069X-11-42 Bartlett ES, 2013, EUR J PUBLIC HEALTH, V24, P21 Bellinger DC, 2011, ENV HLTH PERSPECT, V120, P501 Boyle CA, 2011, PEDIATRICS, V127, P1034, DOI 10.1542/peds.2010-2989 European Food Safety Authority Panel on Plant Protection Products and their Residues, 2013, EFSA J, V11, P3293 Grandjean P, 2006, LANCET, V368, P2167, DOI 10.1016/S0140-6736(06)69665-7 Grandjean P, 2014, LANCET NEUROL, V13, P330, DOI 10.1016/S1474-4422(13)70278-3 Hansen FS, 2014, J EPIDEMIOL COMMUNIT, V68, P890 Khoury MJ, 2013, CANCER EPIDEM BIOMAR, V22, P508, DOI 10.1158/1055-9965.EPI-13-0146 Landrigan PJ, 2012, ENVIRON HEALTH PERSP, V120, pA258, DOI 10.1289/ehp.1104285 Maffini MV, 2014, THYROID KIDS BRAINS Maffini MV, 2014, LOSING OUR MINDS ONG Maffini MV, 2013, COMPR REV FOOD SCI F, V12, P439, DOI 10.1111/1541-4337.12020 Maffini MV, 2014, OVERLOADED APPROACHE Muncke J, 2014, J EPIDEMIOL COMMUN H, V68, P592, DOI 10.1136/jech-2013-202593 National Academy of Sciences National Research Council Committee on Improving Risk Analysis Approaches Used in the U.S. EPA, 2009, SCI DEC ADV RISK ASS National Academy of Sciences National Research Council Committee on the Health Risks of Phthalates, 2008, PHTHAL CUM RISK ASS National Center for Advancing Translational Sciences, TOX 21 CENT Neltner TG, 2013, REPROD TOXICOL, V42, P85, DOI 10.1016/j.reprotox.2013.07.023 Perera F, 2011, REPROD TOXICOL, V31, P363, DOI 10.1016/j.reprotox.2010.12.055 Trasande L, 2011, HLTH AFF, V30, P5 U.S. Environmental Protection Agency, 2014, ASS PEST CUM RISK US Environmental Protection Agency Science Advisory Board, 2013, ADV APPR DER MAX CON World Health Organization, 2010, GLOB STAT REP NONC D NR 24 TC 0 Z9 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD MAY PY 2015 VL 69 IS 5 BP 496 EP 499 DI 10.1136/jech-2014-203980 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CF4TR UT WOS:000352545300016 PM 25336676 ER PT J AU Dimitriou, D Leonard, HC Karmiloff-Smith, A Johnson, MH Thomas, MSC AF Dimitriou, D. Leonard, H. C. Karmiloff-Smith, A. Johnson, M. H. Thomas, M. S. C. TI Atypical development of configural face recognition in children with autism, Down syndrome and Williams syndrome SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; configural processing; Down syndrome; face recognition; inversion effect; Williams syndrome ID SPECTRUM DISORDERS; INFORMATION; EYE; DISCRIMINATION; PROSOPAGNOSIA; TRAJECTORIES; INDIVIDUALS; ATTENTION; PATTERNS; IDENTITY AB BackgroundConfigural processing in face recognition is a sensitivity to the spacing between facial features. It has been argued both that its presence represents a high level of expertise in face recognition, and also that it is a developmentally vulnerable process. MethodWe report a cross-syndrome investigation of the development of configural face recognition in school-aged children with autism, Down syndrome and Williams syndrome compared with a typically developing comparison group. Cross-sectional trajectory analyses were used to compare configural and featural face recognition utilising the Jane faces' task. Trajectories were constructed linking featural and configural performance either to chronological age or to different measures of mental age (receptive vocabulary, visuospatial construction), as well as the Benton face recognition task. ResultsAn emergent inversion effect across age for detecting configural but not featural changes in faces was established as the marker of typical development. Children from clinical groups displayed atypical profiles that differed across all groups. ConclusionWe discuss the implications for the nature of face processing within the respective developmental disorders, and how the cross-sectional syndrome comparison informs the constraints that shape the typical development of face recognition. C1 [Dimitriou, D.] Univ London, Inst Educ, Dept Psychol & Human Dev, London WC1N 1AZ, England. [Leonard, H. C.; Karmiloff-Smith, A.; Johnson, M. H.; Thomas, M. S. C.] Univ London, Ctr Brain & Cognit Dev, Birkbeck, London, England. RP Dimitriou, D (reprint author), Inst Educ, Dept Psychol & Human Dev, London WC1H 0AL, England. 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PD MAY PY 2015 VL 59 IS 5 BP 422 EP 438 DI 10.1111/jir.12141 PG 17 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA CF5BI UT WOS:000352569300003 PM 25059077 ER PT J AU Pulido, R AF Pulido, Rafael TI PTEN: A yin-yang master regulator protein in health and disease SO METHODS LA English DT Article DE PTEN; Lipid phosphatase; Protein tyrosine phosphatase; Oncogenesis; Tumor suppression; Diabetes; Neurosurvival; Neuroregeneration ID TUMOR-SUPPRESSOR PTEN; AUTISM SPECTRUM DISORDERS; BANNAYAN-ZONANA-SYNDROME; GROWTH-FACTOR RECEPTOR; TENSIN HOMOLOG PTEN; PHOSPHATASE-ACTIVITY; SIGNALING PATHWAY; INSULIN HYPERSENSITIVITY; CAENORHABDITIS-ELEGANS; TYROSINE-PHOSPHATASE AB The PTEN gene is a tumor suppressor gene frequently mutated in human tumors, which encodes a ubiquitous protein whose major activity is to act as a lipid phosphatase that counteracts the action of the oncogenic PI3K. In addition, PTEN displays protein phosphatase- and catalytically-independent activities. The physiologic control of PTEN function, and its inactivation in cancer and other human diseases, including some neurodevelopmental disorders, is upon the action of multiple regulatory mechanisms. This provides a wide spectrum of potential therapeutic approaches to reconstitute PTEN activity. By contrast, inhibition of PTEN function may be beneficial in a different group of human diseases, such as type 2 diabetes or neuroregeneration-related pathologies. This makes PTEN a functionally dual yin-yang protein with high potential in the clinics. Here, a brief overview on PTEN and its relation with human disease is presented. (C) 2015 Elsevier Inc. All rights reserved. C1 [Pulido, Rafael] BioCruces Hlth Res Inst, Baracaldo 48903, Bizkaia, Spain. [Pulido, Rafael] Ikerbasque, Basque Fdn Sci, E-48011 Bilbao, Spain. RP Pulido, R (reprint author), BioCruces Hlth Res Inst, Pza Cruces S-N, Baracaldo 48903, Bizkaia, Spain. EM rpulido@gmail.com FU Ministerio de Economia y Competitividad (Spain) [SAF2013-48812-R]; Gobierno Vasco, Departamento de Salud (Basque Country, Spain) [2013111011]; BIOEF/EITB maratoia (Basque Country, Spain) [BIO13/CI/001/BC] FX I thank Nick Leslie for comments to the manuscript. Work in R.P. lab is supported in part by Grants SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), 2013111011 from Gobierno Vasco, Departamento de Salud (Basque Country, Spain), and BIO13/CI/001/BC from BIOEF/EITB maratoia (Basque Country, Spain). 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tumor syndrome: Clinical risk assessment and management protocol SO METHODS LA English DT Article DE PTEN hamartoma tumor syndrome; Tumor suppressor; PI3K/AKT signaling; Cancer ID COWDEN-LIKE SYNDROME; GENOTYPE-PHENOTYPE CORRELATIONS; AUTISM SPECTRUM DISORDERS; RILEY-RUVALCABA-SYNDROMES; BANNAYAN-ZONANA-SYNDROME; GERMLINE PTEN; THYROID-CANCER; BREAST-CANCER; DIFFERENTIAL EXPRESSION; PROMOTER MUTATIONS AB The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important phosphatase that counteracts one of the most critical cancer pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathways. Clinically, deregulation of PTEN function resulting in reduced PTEN expression and activity is implicated in human diseases. Cowden syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant tumors. CS-related individual features occur commonly in the general population. Approximately 25% of patients diagnosed with CS have pathogenic germline PTEN mutations, which increase lifetime risks of breast, thyroid, uterine, renal and other cancers. PTEN testing and intensive cancer surveillance allow for early detection and treatment of these cancers for mutation positive patients and their relatives. In this review, we highlight our current knowledge of germline PTEN mutations in relation to human disease. We review current clinical diagnosis and management recommendations for PHTS including recent discoveries in understanding PTEN function regulation and how this can be exploited therapeutically. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ngeow, Joanne; Eng, Charis] Cleveland Clin, Genom Med Inst, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA. [Ngeow, Joanne] Natl Canc Ctr, Div Med Oncol, Singapore 169610, Singapore. [Ngeow, Joanne] Duke NUS Grad Med Sch, Oncol Acad Clin Program, Singapore 169610, Singapore. [Eng, Charis] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA. [Eng, Charis] Case Western Reserve Univ, CASE Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Eng, Charis] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. RP Eng, C (reprint author), Cleveland Clin, Genom Med Inst, 9500 Euclid Ave,NE-50, Cleveland, OH 44106 USA. EM engc@ccf.org RI ahmed, Jamila/E-8653-2015 FU American Cancer Society; Breast Cancer Research Foundation; US Department of Defense Breast Cancer Research Program; Doris Duke Charitable Trust; William Randolph Hearst Foundation; Susan G. Komen for the Cure; Ambrose Monell Foundation; National Cancer Institute; National Institutes of Health; F.M. Kirby Foundation FX We apologize to authors whose works or relevant references were not cited due to word limitations. American Cancer Society, Breast Cancer Research Foundation, US Department of Defense Breast Cancer Research Program, Doris Duke Charitable Trust, William Randolph Hearst Foundation, Susan G. Komen for the Cure, Ambrose Monell Foundation, National Cancer Institute and National Institutes of Health are gratefully acknowledged for funding C.E.'s patient-oriented research over the last 16 years. C.E. is the Sondra J. and Stephen R. Hardis Chair of Cancer Genomic Medicine at the Cleveland Clinic and is an American Cancer Society Clinical Research Professor, generously funded in part, by the F.M. Kirby Foundation. 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TI C-elegans as a model to study PTEN's regulation and function SO METHODS LA English DT Article DE PTEN; Tumor suppressor; DAF-18; C. elegans; Genetics ID TUMOR-SUPPRESSOR PTEN; NEMATODE CAENORHABDITIS-ELEGANS; AUTISM SPECTRUM DISORDERS; DAUER FORMATION; LIFE-SPAN; SIGNALING PATHWAY; AXON REGENERATION; INSULIN-RECEPTOR; DRUG DISCOVERY; CELL-MIGRATION AB PTEN (phosphatase and tensin homolog deleted on chromosome 10) has important roles in tumor suppression, metabolism, and development, yet its regulators, effectors, and functions are not fully understood. DAF-18 is the PTEN ortholog in Caenorhabditis elegans. DAF-18's role is highly conserved to human PTEN, and can be functionally replaced by human PTEN. Thus C. elegans provides a valuable model to study FTEN. This review assesses current and emerging methods to study DAF-18's regulators and functions in C. elegans. We propose genetic modify screens to identify genes that interact with daf-18/PTEN. 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The work of Philip Reiss, Clare Kelly and Huaihou Chen is supported by National Institutes of Health grant 1R01MH095836-01A1. Clare Kelly and F. Xavier Castellanos are supported by National Institutes of Health grant R33MH086952. Xi-Nian Zuo acknowledges the Hundred Talents Program and the Key Research Program (KSZD-EW-TZ-002) of the Chinese Academy of Sciences, and the Major Joint Fund for International Cooperation and Exchange of the National Natural Science Foundation of China (81220108014, XNZ). 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Gestational exposure to a high-fat diet delayed acquisition of a fixed ratio response, and decreased motivation as assessed by progressive ratio. In contrast, offspring of a low-protein diet displayed no deficits in operant learning, but were more prone to assign salience to a cue that predicts reward (sign-tracking) in a Pavlovian-conditioned approach task. In the 5-choice serial reaction time task (5-CSRTT), gestational exposure to a high-fat diet promoted impulsivity, whereas exposure to a low-protein diet led to marked inattention. These dissociable executive function deficits are known to be mediated by the medial prefrontal cortex (PFC), which displays markers of epigenetic dysregulation in neurodevelopmental disorders. Following behavioral characterization, we assayed PFC gene expression using a targeted PCR array and found that both maternal diets increased overall transcription in PFC. Cluster analysis of the relationships between individual transcripts and behavioral outcomes revealed a cluster of primarily epigenetic modulators, whose overexpression was linked to executive function deficits. The overexpression of four genes, DNA methyltransferase 1 (DNMT1), delta-opioid receptor (OPRD1), cannabinoid receptor 1 (CNR1), and catechol-o-methyltransferase (COMT), was strongly associated with overall poor performance. All 5-CSRTT deficits were associated with DNMT1 upregulation, whereas impulsive behavior could be dissociated from inattention by overexpression of OPRD1 or COMT, respectively, as well as a distinct cluster of epigenetic regulators. These data provide molecular support for dissociable domains of executive function. C1 [Grissom, Nicola M.; Herdt, Christopher T.; Desilets, Jeffery; Lidsky-Everson, Jordan; Reyes, Teresa M.] Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Reyes, TM (reprint author), Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Dept Pharmacol, 10-131 Smilow Ctr Translat Res,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM reyestm@mail.med.upenn.edu FU [MH087978]; [MH091372] FX This work was supported by MH087978 and MH091372 to TMR. The authors declare no conflict of interest. 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Autism has also a striking sex-bias, not fully genetically explainable. Objective: Our goal was to explain how and in which predisposing conditions some compounds can impair neurodevelopment, why this occurs in the first years of age, and, primarily, why more in males than females. Methods: We reviewed articles regarding the genetic and environmental etiology of autism and toxins effects on animal models selected from PubMed and databases about autism and toxicology. Discussion: Our hypothesis proposes that in the first year of life, the decreasing of maternal immune protection and child immune-system immaturity create an immune vulnerability to infection diseases that, especially if treated with antibiotics, could facilitate dysbiosis and GI disorders. This condition triggers a vicious circle between immune system impairment and increasing dysbiosis that leads to leaky gut and neurochemical compounds and/or neurotoxic xenobiotics production and absorption. 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Neurosci. PD MAY PY 2015 VL 18 IS 4 BP 145 EP 161 DI 10.1179/1476830513Y.0000000108 PG 17 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA CF9MQ UT WOS:000352889200001 PM 24621061 ER PT J AU Navarro, F Pearson, DA Fatheree, N Mansour, R Hashmi, SS Rhoads, JM AF Navarro, Fernando Pearson, Deborah A. Fatheree, Nicole Mansour, Rosleen Hashmi, S. Shahrukh Rhoads, J. Marc TI Are 'leaky gut' and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders? SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE Autism spectrum disorder (ASD); Diet; Gluten; Dairy; Behavior; Intestinal permeability ID ABNORMAL INTESTINAL PERMEABILITY; CASEIN-FREE DIET; CELIAC-DISEASE; DOUBLE-BLIND; INTERVENTION; RELIABILITY; VALIDITY; DIARRHEA; ALLERGY; AGE AB Objectives: Studies have suggested a link between diet and behavior in children with autism spectrum disorders (ASDs). Parental reports of behavioral changes upon exposure to gluten and/or casein are common in clinical practice. An association between diet type, intestinal permeability (IP) ('leaky gut'), and behavior has been long proposed but not substantiated. We explored this possible association in this trial. Methods: This randomized double-blind, placebo-controlled study explored the effects of gluten and milk on IP and behavior in children with ASDs over a period of 4 weeks. IP assessed by lactulose: mannitol (L/M) sugar permeability test and behavior assessed by the Aberrant Behavior Checklist and Conners Parent Rating were measured. Gastrointestinal symptoms in both groups were also monitored. Results: Neither the L/M ratio nor behavioral scores were different between groups exposed to gluten/dairy or placebo. The changes observed were noted to be small and not clinically significant. Discussion: Our study although underpowered to show small differences does not support an association between dietary gluten/milk, IP, and behavioral changes in subjects with ASD. C1 [Navarro, Fernando; Fatheree, Nicole; Hashmi, S. Shahrukh; Rhoads, J. Marc] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX 77030 USA. [Pearson, Deborah A.; Mansour, Rosleen] Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Navarro, F (reprint author), Univ Texas Houston, Sch Med, Dept Pediat, Sect Gastroenterol Hepatol & Nutr, 6431 Fannin,Room 3-140, Houston, TX 77030 USA. 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TI Hippocampal neuroligin-2 links early-life stress with impaired social recognition and increased aggression in adult mice SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Cell adhesion molecule; Neuroligin-2; Early life stress; Hippocampus; Social behavior; Aggression ID CELL-ADHESION MOLECULES; INHIBITORY SYNAPSES; SYNAPTIC FUNCTION; SCHIZOPHRENIA; NEUREXINS; BEHAVIOR; CHILDHOOD; DISORDER; VIOLENCE; GENE AB Early-life stress is a key risk factor for the development of neuropsychiatric disorders later in life. Neuronal cell adhesion molecules have been strongly implicated in the pathophysiology of psychiatric disorders and in modulating social behaviors associated with these diseases. Neuroligin-2 is a synaptic cell adhesion molecule, located at the postsynaptic membrane of inhibitory GABAergic synapses, and is involved in synaptic stabilization and maturation. Alterations in neuroligin-2 expression have previously been associated with changes in social behavior linked to psychiatric disorders, including schizophrenia and autism. In this study, we show that early-life stress, induced by limited nesting and bedding material, leads to impaired social recognition and increased aggression in adult mice, accompanied by increased expression levels of hippocampal neuroligin-2. Viral overexpression of hippocampal neuroligin-2 in adulthood mimics early-life stress-induced alterations in social behavior and social cognition. Moreover, viral knockdown of neuroligin-2 in the adult hippocampus attenuates the early-life stress-induced behavioral changes. Our results highlight the importance of neuroligin-2 in mediating early-life stress effects on social behavior and social cognition and its promising role as a novel therapeutic target for neuropsychiatric disorders. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Kohl, Christine; Grosse, Jocelyn; Fournier, Celine; Bacq, Alexandre; Sandi, Carmen] Ecole Polytech Fed Lausanne, Sch Life Sci, Brain Mind Inst, Lab Behav Genet, CH-1015 Lausanne, Switzerland. [Kohl, Christine; Wang, Xiao-Dong; Harbich, Daniela; Westerholz, Soeren; Sippel, Claudia; Hausch, Felix; Schmidt, Mathias V.] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, D-80804 Munich, Germany. [Wang, Xiao-Dong] Zhejiang Univ, Sch Med, Zhejiang Prov Key Lab Neurobiol, Dept Neurobiol,Key Lab Med Neurobiol,Minist Hlth, Hangzhou 310058, Zhejiang, Peoples R China. [Li, Ji-Tao] Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China. RP Schmidt, MV (reprint author), Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, Kraepelinstr 2-10, D-80804 Munich, Germany. EM mschmidt@mpipsykl.mpg.de RI ahmed, Jamila/E-8653-2015 FU European Union from the Swiss National Science Foundation [FP7-HEALTH-F2M-2007-201600, 31003AB-135710, 31003A-152614]; Oak Foundation; EPFL FX This work was supported by the European Union integrated project MEMSTICK (FP7-HEALTH-F2M-2007-201600; MemStick) grants from the Swiss National Science Foundation (31003AB-135710, 31003A-152614, and the NCCR Synapsy), Oak Foundation, and intramural funding from the EPFL. 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Cook, Edwin H., Jr. Devlin, Bernie TI A Genome-wide Association Study of Autism Using the Simons Simplex Collection: Does Reducing Phenotypic Heterogeneity in Autism Increase Genetic Homogeneity? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; Genetics; GWAS; Heterogeneity; Phenotype; Power ID SPECTRUM DISORDERS; SUSCEPTIBILITY GENE; INTELLECTUAL DISABILITY; LINKAGE ANALYSES; SEX-DIFFERENCES; RETT-SYNDROME; RISK LOCI; PDD-NOS; SCHIZOPHRENIA; VARIANTS AB BACKGROUND: Phenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD. METHODS: Genome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup. RESULTS: Association analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups. CONCLUSIONS: In genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD. C1 [Chaste, Pauline; Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Chaste, Pauline] FondaMental Fdn, Paris, France. [Chaste, Pauline] Ctr Hosp St Anne, F-75014 Paris, France. [Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Hus, Vanessa] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Murtha, Michael T.; Moreno-De-Luca, Daniel] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT 06510 USA. [Lowe, Jennifer K.; Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Dept Neurol,Neurogenet Program, Los Angeles, CA 90095 USA. [Lowe, Jennifer K.; Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst, Los Angeles, CA 90095 USA. [Martin, Donna M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Yu, Timothy W.] Harvard Univ, Childrens Hosp Boston, Sch Med, Div Genet, Boston, MA 02115 USA. [Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97201 USA. [Grice, Dorothy E.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Ledbetter, David H.; Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA USA. [Mane, Shrikant M.] Yale Ctr Genome Anal, Orange, CT USA. [Martin, Donna M.] Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA. [Martin, Donna M.] Univ Michigan, Med Ctr, Dept Human Genet, Ann Arbor, MI 48109 USA. [Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Ctr Life Sci, Howard Hughes Med Inst, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Childrens Hosp Boston, Ctr Life Sci, Sch Med,Div Genet, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Ctr Life Sci, Neurol & Pediat, Boston, MA 02115 USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol, Nashville, TN 37235 USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Biophys & Psychiat, Nashville, TN 37235 USA. [Beaudet, Arthur L.] Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, White Plains, NY USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. RP Chaste, P (reprint author), Ctr Hosp St Anne, 1 Rue Cabanis, F-75014 Paris, France. 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CA Simons Variation Individuals Proje TI The Cognitive and Behavioral Phenotype of the 16p11.2 Deletion in a Clinically Ascertained Population SO BIOLOGICAL PSYCHIATRY LA English DT Article DE 16p11.2 Deletion; Autism; Autism spectrum disorder; Developmental disability; Genetics; Psychiatric diagnosis ID AUTISM SPECTRUM DISORDERS; RECURRENT REARRANGEMENTS; DIAGNOSTIC INTERVIEW; CHILDREN; ASSOCIATION; LANGUAGE; INDIVIDUALS; RELIABILITY; IMPAIRMENT; MUTATIONS AB BACKGROUND: Deletion of the recurrent similar to 600 kb BP4-BP5 chromosomal region 16p11.2 has been associated with a wide range of neurodevelopmental outcomes. METHODS: To clarify the phenotype of 16p11.2 deletion, we examined the psychiatric and developmental presentation of predominantly clinically referred individuals, with a particular emphasis on broader autism phenotype characteristics in individuals with recurrent similar to 600 kb chromosome 16p11.2 deletions. Using an extensive standardized assessment battery across three clinical sites, 85 individuals with the 16p11.2 deletion and 153 familial control subjects were evaluated for symptom presentation and clinical diagnosis. RESULTS: Individuals with the 16p11.2 deletion presented with a high frequency of psychiatric and developmental disorders (>90%). The most commonly diagnosed conditions were developmental coordination disorder, phonologic processing disorder, expressive and receptive language disorders (71% of individuals >3 years old with a speech and language-related disorder), and autism spectrum disorder. Individuals with the 16p11.2 deletion not meeting diagnostic criteria for autism spectrum disorder had a significantly higher prevalence of autism-related characteristics compared with the familial noncarrier control group. Individuals with the 16p11.2 deletion had a range of intellectual ability, but IQ scores were 26 points lower than noncarrier family members on average. CONCLUSIONS: Clinically referred individuals with the 16p11.2 deletion have high rates of psychiatric and developmental disorders and provide a genetically well-defined group to study the emergence of developmental difficulties, particularly associated with the broader autism phenotype. C1 [Hanson, Ellen; Porche, Ken; Jackson, Frank I.; Snyder, LeeAnne Green; Snow, Anne V.; Campe, Katherine L.; Miller, Fiona K.; Olson, Jennifer] Childrens Hosp Boston, Div Dev Med, Boston, MA 02215 USA. [Hanson, Ellen; Snow, Anne V.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bernier, Raphael; Wallace, Arianne Stevens] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Goin-Kochel, Robin P.; Berry, Leandra] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Zhang, Yuan; Chen, Qixuan; D'Angelo, Debra] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Moreno-De-Luca, Andres; Orr, Patrick T.; Evans, David W.; Martin, Christa L.; Ledbetter, David H.] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA USA. [Moreno-De-Luca, Andres; Martin, Christa L.; Ledbetter, David H.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA. [Moreno-De-Luca, Andres] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. [Boomer, K. B.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. [Kanne, Stephen] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO USA. [Sherr, Elliot] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Spiro, John E.] Simons Fdn, New York, NY USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY 10027 USA. RP Hanson, E (reprint author), Childrens Hosp Boston, Div Dev Med, 1295 Boylston St,3rd Floor, Boston, MA 02215 USA. EM ellen.hanson@chil-drens.harvard.edu FU Simons Foundation (Simons Foundation Autism Research Initiative Grant) [198677, 312100]; National Institutes of Health [MH074090] FX This work was supported by two grants from the Simons Foundation (Simons Foundation Autism Research Initiative Grant No. 198677 to EH, RB, RPG-K, and WKC and Simons Foundation Autism Research Initiative Grant No. 312100 to CLM, and DHL) and a grant from the National Institutes of Health (Grant No. MH074090 to DHL and CLM). 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Kenet, Tal TI Altered Development and Multifaceted Band-Specific Abnormalities of Resting State Networks in Autism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; Connectivity; Cortex; Development; MEG activity; Resting state ID FUNCTIONAL CONNECTIVITY MRI; SPACE SEPARATION METHOD; SPECTRUM DISORDERS; DEFAULT-MODE; HUMAN BRAIN; CORTICAL ACTIVITY; MEG MEASUREMENTS; WORKING-MEMORY; FRONTAL-CORTEX; GAMMA AB BACKGROUND: Extensive evidence indicates that cortical connectivity patterns are abnormal in autism spectrum disorders (ASD), showing both overconnectivity and underconnectivity. Since, however, studies to date have focused on either spatial or spectral dimensions, but not both simultaneously, much remains unknown about the nature of these abnormalities. In particular, it remains unknown whether abnormal connectivity patterns in ASD are driven by specific frequency bands, by spatial network properties, or by some combination of these factors. METHODS: Magnetoencephalography recordings (15 ASD, 15 control subjects) mapped back onto cortical space were used to study resting state networks in ASD with both spatial and spectral specificity. The data were quantified using graph theoretic metrics. RESULTS: The two major factors that drove the nature of connectivity abnormalities in ASD were the mediating frequency band and whether the network included frontal nodes. These factors determined whether clustering and integration were increased or decreased in cortical resting state networks in ASD. These measures also correlated with abnormalities in the developmental trajectory of resting state networks in ASD. Lastly, these measures correlated with ASD severity in some frequency bands and spatially specific subnetworks. CONCLUSIONS: Our findings suggest that network abnormalities in ASD are widespread, are more likely in subnetworks that include the frontal lobe, and can be opposite in nature depending on the frequency band. These findings thus elucidate seemingly contradictory prior findings of both overconnectivity and underconnectivity in ASD. C1 [Kitzbichler, Manfred G.; Khan, Sheraz; Ganesan, Santosh; Vangel, Mark G.; Herbert, Martha R.; Haemaelaeinen, Matti S.; Kenet, Tal] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kitzbichler, Manfred G.; Khan, Sheraz; Ganesan, Santosh; Herbert, Martha R.; Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Vangel, Mark G.; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Kenet, T (reprint author), Massachusetts Gen Hosp, 149 Thirteenth St,Room 2275, Charlestown, MA 02129 USA. EM tal@nmr.mgh.harvard.edu FU Nancy Lurie Marks Foundation; Nancy Lurie Marks Family Foundation; Autism Speaks; National Center for Research Resources [P41RR14075]; National Institute for Biomedical Imaging and Bioengineering [5R01EB009048]; Cognitive Rhythms Collaborative: A Discovery Network [NFS 1042134] FX We gratefully acknowledge the financial support from the Nancy Lurie Marks Foundation without which this work would not have been possible. Authors received research funding from the following organizations and funding bodies: The Nancy Lurie Marks Family Foundation (TK, MGK, SK), Autism Speaks (TK), The National Center for Research Resources (P41RR14075, MSH), National Institute for Biomedical Imaging and Bioengineering (5R01EB009048, MSH), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, MSH). MGK is currently affiliated with the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom. 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Rumbaugh, Gavin TI Syngap1 Haploinsufficiency Damages a Postnatal Critical Period of Pyramidal Cell Structural Maturation Linked to Cortical Circuit Assembly SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Development; Epilepsy; Intellectual disability; Mouse model; Synapse; Syngap1 ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; GTPASE-ACTIVATING PROTEIN; INTELLECTUAL DISABILITY; SYNAPTIC PLASTICITY; NEUROPSYCHIATRIC DISORDERS; MENTAL-RETARDATION; NEURONS; CORTEX; SCHIZOPHRENIA AB BACKGROUND: Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders. METHODS: A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development. RESULTS: Syngap1 mutations broadly disrupted a developmentally sensitive period that corresponded to the period of heightened postnatal cortical synaptogenesis. Pathogenic Syngap1 mutations caused a coordinated acceleration of dendrite elongation and spine morphogenesis and pruning of these structures in neonatal cortical pyramidal neurons. These mutations also prevented a form of developmental structural plasticity associated with experience-dependent reorganization of brain circuits. Consistent with these findings, Syngap1 mutant mice displayed an altered pattern of long-distance synaptic inputs into a cortical area important for cognition. Interestingly, the ability to genetically improve the behavioral endophenotype of Syngap1 mice decreased slowly over postnatal development and mapped onto the developmental period of coordinated dendritic insults. CONCLUSIONS: Pathogenic Syngap1 mutations have a profound impact on the dynamics and structural integrity of pyramidal cell postsynaptic structures known to guide the de novo wiring of nascent cortical circuits. These findings support the idea that disrupted critical periods of dendritic growth and spine plasticity may be a common pathologic process in developmental brain disorders. C1 [Aceti, Massimiliano; Creson, Thomas K.; Vaissiere, Thomas; Rojas, Camilo; Huang, Wen-Chin; Page, Damon T.; Miller, Courtney A.; Rumbaugh, Gavin] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA. [Vaissiere, Thomas; Miller, Courtney A.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA. [Wang, Ya-Xian; Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD USA. RP Rumbaugh, G (reprint author), Scripps Florida, 130 Scripps Way, Jupiter, FL 33458 USA. EM grumbaug@scripps.edu FU National Institute for Neurological Disorders and Stroke [R01NS064079]; National Institute for Mental Health [R01MH096847]; National Institute for Drug Abuse [R01 DA034116, R03 DA033499]; National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural Research Program; State of Florida FX This work was supported by grants to GR from The National Institute for Neurological Disorders and Stroke (R01NS064079) andThe National Institute for Mental Health (R01MH096847). CAM was supported by grants from the National Institute for Drug Abuse (R01 DA034116; R03 DA033499). Y-XW and RSP were supported by the National Institute on Deafness and Other Communication Disorders/National Institutes of Health Intramural Research Program. W-CH and DTP were supported by gift funds from Mrs. Nancy Lurie Marks. GR, CAM, and DTP were supported by the State of Florida. 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Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 BP 805 EP 815 DI 10.1016/j.biopsych.2014.08.001 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800007 PM 25444158 ER PT J AU Pinggera, A Lieb, A Benedetti, B Lampert, M Monteleone, S Liedl, KR Tuluc, P Striessnig, J AF Pinggera, Alexandra Lieb, Andreas Benedetti, Bruno Lampert, Michaela Monteleone, Stefania Liedl, Klaus R. Tuluc, Petronel Striessnig, Joerg TI CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Calcium channel blockers; Human genetics; L-type calcium channels; Neuropsychiatric disorders; Whole-exome sequencing ID GATED CA2+ CHANNELS; CONGENITAL DEAFNESS; PACEMAKER ACTIVITY; CA(V)1.3; MICE; SCHIZOPHRENIA; DYSFUNCTION; ELIMINATION; DEPENDENCE; SYNAPSES AB BACKGROUND: Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 alpha(1)-subunits (CACNA1D), the second main LTCC in the brain, as 1 of 62 high risk-conferring mutations in a cohort of patients with autism and intellectual disability. We screened all published genetic information available from whole-exome sequencing studies and identified a second de novo CACNA1D mutation, p.G407R. Both mutations are present only in the probands and not in their unaffected parents or siblings. METHODS: We functionally expressed both mutations in tsA-201 cells to study their functional consequences using whole-cell patch-clamp. RESULTS: The mutations p.A749G and p.G407R caused dramatic changes in channel gating by shifting (similar to 15 mV) the voltage dependence for steady-state activation and inactivation to more negative voltages (p.A749G) or by pronounced slowing of current inactivation during depolarizing stimuli (p.G407R). In both cases, these changes are compatible with a gain-of-function phenotype. CONCLUSIONS: Our data, together with the discovery that Cav1.3 gain-of-function causes primary aldosteronism with seizures, neurologic abnormalities, and intellectual disability, suggest that Cav1.3 gain-of-function mutations confer a major part of the risk for autism in the two probands and may even cause the disease. Our findings have immediate clinical relevance because blockers of LTCCs are available for therapeutic attempts in affected individuals. Patients should also be explored for other symptoms likely resulting from Cav1.3 hyperactivity, in particular, primary aldosteronism. C1 [Pinggera, Alexandra; Lieb, Andreas; Benedetti, Bruno; Lampert, Michaela; Tuluc, Petronel; Striessnig, Joerg] Univ Innsbruck, Ctr Mol Biosci, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. [Monteleone, Stefania; Liedl, Klaus R.] Univ Innsbruck, Ctr Mol Biosci, Inst Gen Inorgan & Theoret Chem, A-6020 Innsbruck, Austria. RP Striessnig, J (reprint author), Univ Innsbruck, Ctr Mol Biosci, Pharmacol & Toxicol, Innrain 80-82, A-6020 Innsbruck, Austria. EM joerg.striessnig@uibk.ac.at RI Liedl, Klaus/F-3099-2015 OI Liedl, Klaus/0000-0002-0985-2299 FU Austrian Science Fund [F44020, W11]; University of Innsbruck FX This work was supported by the Austrian Science Fund Grant Nos. F44020 and W11 and the University of Innsbruck. 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Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 BP 816 EP 822 DI 10.1016/j.biopsych.2014.11.020 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800008 PM 25620733 ER PT J AU Machado, CJ Whitaker, AM Smith, SEP Patterson, PH Bauman, MD AF Machado, Christopher J. Whitaker, Alexander M. Smith, Stephen E. P. Patterson, Paul H. Bauman, Melissa D. TI Maternal Immune Activation in Nonhuman Primates Alters Social Attention in Juvenile Offspring SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Immunology; Macaque; Nonhuman primate; Poly IC; Schizophrenia; Social attention ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; ULTRA-HIGH RISK; FACIAL EXPRESSIONS; PRENATAL STRESS; AMYGDALA DAMAGE; IN-UTERO; NEURODEVELOPMENTAL DISORDERS; IMPAIRED RECOGNITION; 1ST-DEGREE RELATIVES AB BACKGROUND: Sickness during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders. Rodent models have played a critical role in establishing causal relationships and identifying mechanisms of altered brain and behavior development in pups prenatally exposed to maternal immune activation (MIA). We recently developed a novel nonhuman primate model to bridge the gap between human epidemiological studies and rodent models of prenatal immune challenge. Our initial results demonstrated that rhesus monkeys given the viral mimic synthetic double-stranded RNA (polyinosinic: polycytidylic acid stabilized with poly-l-lysine) during pregnancy produce offspring with abnormal repetitive behaviors, altered communication, and atypical social interactions. METHODS: We utilized noninvasive infrared eye tracking to further evaluate social processing capabilities in a subset of the first trimester MIA-exposed offspring (n = 4) and control animals (n = 4) from our previous study. RESULTS: As juveniles, the MIA offspring differed from control animals on several measures of social attention, particularly when viewing macaque faces depicting the fear grimace facial expression. Compared with control animals, MIA offspring had a longer latency before fixating on the eyes, had fewer fixations directed at the eyes, and spent less total time fixating on the eyes of the fear grimace images. CONCLUSIONS: In the rhesus monkey model, exposure to MIA at the end of the first trimester results in abnormal gaze patterns to salient social information. The use of noninvasive eye tracking extends the findings from rodent MIA models to more human-like behaviors resembling those in both autism spectrum disorder and schizophrenia. C1 [Machado, Christopher J.; Whitaker, Alexander M.; Bauman, Melissa D.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. 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Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 BP 823 EP 832 DI 10.1016/j.biopsych.2014.07.035 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800009 PM 25442006 ER PT J AU McKeague, IW Brown, AS Bao, YY Hinkka-Yli-Salomaki, S Huttunen, J Sourander, A AF McKeague, Ian W. Brown, Alan S. Bao, Yuanyuan Hinkka-Yli-Salomaki, Susanna Huttunen, Jukka Sourander, Andre TI Autism with Intellectual Disability Related to Dynamics of Head Circumference Growth during Early Infancy SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; Development; Epidemiology; Growth Velocity; Head Circumference; Trajectories ID EARLY BRAIN OVERGROWTH; AGE 2 YEARS; SPECTRUM DISORDER; 1ST YEAR; ACCELERATED HEAD; BODY GROWTH; CHILDREN; LIFE; ENLARGEMENT; REGRESSION AB BACKGROUND: It is not yet definitively known whether dynamic features of head circumference growth are associated with autism. To address this issue, we carried out a nested matched case-control study using data from national well baby clinics in Finland; autism cases were identified from the Finnish Hospital and Outpatient Discharge Registry. METHODS: A nonparametric Bayesian method was used to construct growth velocity trajectories between birth and 2 years of age in autism cases and matched control subjects (n = 468 in main analyses, 1:1 matched control subjects). Estimates of odds ratios for autism risk in relation to the growth velocities were obtained using conditional logistic regression. RESULTS: Growth velocity of head circumference at 3 months of age, adjusting for gestational age at birth and maternal age, is significantly associated with autism (p = .014); the finding was observed in subjects with comorbid intellectual disability (ID) (p = .025) but not in those without ID (p = .15). Height growth velocity among subjects with autism and without ID is significantly associated with autism at 6 months (p = .007), and weight growth velocity at 18 months without ID (p = .02) and 24 months without ID (p = .042) and with ID (p = .037). CONCLUSIONS: Acceleration in head circumference growth is associated with autism with comorbid ID at 3 months but not subsequently. This association is unrelated to acceleration in height and weight, which are not strongly associated with autism until after 6 months. C1 [McKeague, Ian W.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Brown, Alan S.; Bao, Yuanyuan; Sourander, Andre] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. [Brown, Alan S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Hinkka-Yli-Salomaki, Susanna; Huttunen, Jukka; Sourander, Andre] Univ Turku, Dept Child Psychiat, Fac Med, Turku 20014, Finland. RP Sourander, A (reprint author), Univ Turku, Dept Child Psychiat, Fac Med, Turku 20014, Finland. EM andsou@utu.fi FU National Institutes of Health [R01GM095722-01]; National Institute of Environmental Health Sciences Grant [1R01ES019004]; National Institute of Mental Health [K02MH065422] FX The work was supported by National Institutes of Health Grant R01GM095722-01, National Institute of Environmental Health Sciences Grant 1R01ES019004, and National Institute of Mental Health Grant K02MH065422. The funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. 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Psychiatry PD MAY 1 PY 2015 VL 77 IS 9 BP 833 EP 840 DI 10.1016/j.biopsych.2014.08.008 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CE8LM UT WOS:000352093800010 PM 25444163 ER PT J AU Bradford, EEF Jentzsch, I Gomez, JC AF Bradford, Elisabeth E. F. Jentzsch, Ines Gomez, Juan-Carlos TI From self to social cognition: Theory of Mind mechanisms and their relation to Executive Functioning SO COGNITION LA English DT Article DE Theory of Mind; False belief; Belief attribution; Social cognition ID INDIVIDUAL-DIFFERENCES; PERSPECTIVE-TAKING; INHIBITORY CONTROL; ASPERGER-SYNDROME; FALSE BELIEF; DUAL-TASK; AUTISM; ADULTS; CHILDREN; REPRESENTATION AB 'Theory of Mind' refers to the ability to attribute mental states to oneself and other people (Premack 82 Woodruff, 1978). This study examined the extent to which 'Self' and 'Other' belief-attribution processes within the Theory of Mind (TOM) mechanism could be distinguished behaviourally, and whether these separable components differentially related to Executive Functioning (EF) abilities. A computerized false-belief task, utilizing a matched-design to allow direct comparison of self-oriented vs. other-oriented belief-attribution, was used to assess ToM, and a face-image Stroop task was employed to assess EF, within a population of typically-developed adults. Results revealed significantly longer reaction times when attributing beliefs to other people as opposed to recognizing and attributing beliefs to oneself. Intriguingly, results revealed that 'perspective-shift' requirements (i.e. changing from adoption of the 'self' perspective to the perspective of the 'other', or vice versa) across false-belief trials influenced reaction times. Reaction times were significantly longer when the perspective shift was from self-to-other than from other-to-self. It is suggested that the 'self' forms the stem of understanding the 'other', and is therefore processed regardless of ultimate task demands; in contrast, the 'other' perspective is only processed when explicitly required. We conclude that adopting another person's perspective, even when their belief state is matched to one's own, requires more cognitive effort than recalling and reflecting on self-oriented belief-states. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Bradford, Elisabeth E. F.; Jentzsch, Ines; Gomez, Juan-Carlos] Univ St Andrews, Sch Psychol & Neurosci, St Andrews KY16 9JP, Fife, Scotland. RP Bradford, EEF (reprint author), Univ St Andrews, Sch Psychol & Neurosci, St Andrews KY16 9JP, Fife, Scotland. EM eefb@st-andrews.ac.uk; ij7@st-andrews.ac.uk; jg5@st-andrews.ac.uk RI Jentzsch, Ines/A-1586-2010 FU Economic and Social Research Council [ES/J500136/1] FX This work was supported by the Economic and Social Research Council [grant number ES/J500136/1] in the form of a three-year PhD studentship awarded to Elisabeth Bradford. 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J. Anaesth. PD MAY PY 2015 VL 32 IS 5 BP 298 EP 300 DI 10.1097/EJA.0000000000000148 PG 3 WC Anesthesiology SC Anesthesiology GA CF4AN UT WOS:000352490800002 PM 25840346 ER PT J AU Bai, Z Blackwell, AF Coulouris, G AF Bai, Zhen Blackwell, Alan F. Coulouris, George TI Using Augmented Reality to Elicit Pretend Play for Children with Autism SO IEEE TRANSACTIONS ON VISUALIZATION AND COMPUTER GRAPHICS LA English DT Article DE Augmented Reality; pretend play; children; autism ID SYMBOLIC PLAY; MIND AB Children with autism spectrum condition (ASC) suffer from deficits or developmental delays in symbolic thinking. In particular, they are often found lacking in pretend play during early childhood. Researchers believe that they encounter difficulty in generating and maintaining mental representation of pretense coupled with the immediate reality. We have developed an interactive system that explores the potential of Augmented Reality (AR) technology to visually conceptualize the representation of pretense within an open-ended play environment. Results from an empirical study involving children with ASC aged 4 to 7 demonstrated a significant improvement of pretend play in terms of frequency, duration and relevance using the AR system in comparison to a non computer-assisted situation. We investigated individual differences, skill transfer, system usability and limitations of the proposed AR system. We discuss design guidelines for future AR systems for children with ASC and other pervasive developmental disorders. C1 [Bai, Zhen] Univ Cambridge, Comp Lab, Graph & Interact Grp, Cambridge CB3 0FD, England. [Blackwell, Alan F.] Univ Cambridge, Comp Lab, Interdisciplinary Design, Cambridge CB3 0FD, England. [Coulouris, George] Univ Cambridge, Comp Lab, Cambridge CB3 0FD, England. RP Bai, Z (reprint author), Univ Cambridge, Comp Lab, Graph & Interact Grp, Cambridge CB3 0FD, England. 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PD MAY 1 PY 2015 VL 21 IS 5 BP 598 EP 610 DI 10.1109/TVCG.2014.2385092 PG 13 WC Computer Science, Software Engineering SC Computer Science GA CE9HJ UT WOS:000352154500006 ER PT J AU Ference, J Curtin, S AF Ference, Jennifer Curtin, Suzanne TI The Ability to Map Differentially Stressed Labels to Objects Predicts Language Development at 24 months in 12-month-olds at High Risk for Autism SO INFANCY LA English DT Article ID ENGLISH-LEARNING INFANTS; SPECTRUM DISORDERS; WORD SEGMENTATION; BIRTH-WEIGHT; PATTERN-DISCRIMINATION; SPEECH; CHILDREN; PERCEPTION; PREFERENCES; 5-MONTH-OLDS AB Sensitivity to language-specific stress patterns during infancy facilitates finding, mapping, and recognizing words, and early preferences for the predominate stress pattern of the infant's native language have been argued to facilitate language relevant outcomes (Ference & Curtin, 2013 Journal of Experimental Child Psychology, 116, 891; Weber etal., 2005 Cognitive Brain Research, 25, 180). We examined 12-month-old infant siblings of typically developing children (SIBS-TD) and infant siblings of children diagnosed with autism spectrum disorder (ASD; SIBS-A) on their ability to map differentially stressed labels to objects. We also examined whether success at this task relates to infants' vocabulary size at 12months, and more specifically to SIBS-A's vocabulary at both 12 and 24months. SIBS-TD successfully mapped the word-object pairings, which related to their vocabulary comprehension at 12months. In contrast, SIBS-A as a group did not map the word-object pairings, which was unrelated to vocabulary size at 12months. However, success on this task for SIBS-A predicted expressive language abilities at 24months using the Mullen Scales of Early Learning (MSEL; Mullen, 1995 Mullen Scales of Early Learning. Circle Pines, MN: American Guidance) and the MacArthur-Bates Communicative Development Inventory (MB-CDI; Fenson etal., 1993 MacArthur Communicative Development Inventory: Users Guide and Technical Manual. San Diego, CA: Singular Publishing Company). Our study is the first to demonstrate that 12-month-old SIBS-A who succeed at word mapping using lexical stress are more likely to have stronger expressive language abilities at 24months. C1 [Ference, Jennifer; Curtin, Suzanne] Univ Calgary, Dept Psychol, Calgary, AB T2N 1N4, Canada. RP Curtin, S (reprint author), Univ Calgary, Dept Psychol, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada. EM scurtin@ucalgary.ca FU Alberta Centre for Child, Family, and Community Research (ACCFCR) FX This research was supported by funding from an Alberta Centre for Child, Family, and Community Research (ACCFCR) research grant awarded to Suzanne Curtin. 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Three embedding entropy measurements (approximate entropy, sample entropy, permutation entropy (PermEn)) are used to estimate single channel EEG complexity for 19-channel eyes closed cortical measurements. Mean coherence and mutual information are examined to measure the level of interhemispheric dependency in frequency and statistical domain, respectively for eight distinct electrode pairs placed on the scalp with respect to the international 10-20 electrode placement system. All methods are applied to short EEG segments of 2 s. The classification performance is measured 20 times with different 2-fold cross-validation data for both single channel complexity features (19 features) and interhemispheric dependency features (eight features). The highest classification accuracy of 85 +/- 5.2% is provided by PermEn at prefrontal regions of the brain. Even if the classification success do not provided by other methods as high as PermEn, the clear differences between patients and controls at prefrontal regions can also be obtained by using other methods except coherence. In conclusion, OCD, defined as illness of orbitofronto-striatal structures [Beucke et al., JAMA Psychiatry 70 (2013) 619-629; Cavedini et al., Psychiatry Res. 78 (1998) 21-28; Menzies et al., Neurosci. Biobehav. Rev. 32(3) (2008) 525-549], is caused by functional abnormalities in the pre-frontal regions. Particularly, patients are characterized by lower EEG complexity at both pre-frontal regions and right fronto-temporal locations. Our results are compatible with imaging studies that define OCD as a sub group of anxiety disorders exhibited a decreased complexity (such as anorexia nervosa [Toth et al., Int. J. Psychophysiol. 51(3) (2004) 253-260] and panic disorder [Bob et al., Physiol. Res. 55 (2006) S113-S119]). C1 [Aydin, Serap] Bahcesehir Univ, Dept Biomed Engn, TR-34353 Istanbul, Turkey. [Arica, Nafiz] Bahcesehir Univ, Software Engn Dept, TR-34353 Istanbul, Turkey. [Ergul, Emrah] Kocaeli Univ, Elect & Commun Engn Dept, Kocaeli, Turkey. [Tan, Oguz] Uskudar Univ, Neuropsychiat Hlth Practice & Res Ctr, Istanbul, Turkey. RP Aydin, S (reprint author), Bahcesehir Univ, Dept Biomed Engn, TR-34353 Istanbul, Turkey. 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J. Neural Syst. PD MAY PY 2015 VL 25 IS 3 AR 1550010 DI 10.1142/S0129065715500100 PG 16 WC Computer Science, Artificial Intelligence SC Computer Science GA CF6AZ UT WOS:000352640100005 PM 25804351 ER PT J AU Zhou, ZB Yang, XY Yuan, BL Niu, LJ Zhou, X Huang, WQ Feng, X Zhou, LH AF Zhou, Zhi-Bin Yang, Xiao-Yu Yuan, Bao-Long Niu, Li-Jun Zhou, Xue Huang, Wen-Qi Feng, Xia Zhou, Li-Hua TI Sevoflurane-Induced Down-regulation of Hippocampal Oxytocin and Arginine Vasopressin Impairs Juvenile Social Behavioral Abilities SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Sevoflurane; Oxytocin; Arginine vasopressin; Hippocampus; Social behavior ID AUTISM SPECTRUM DISORDERS; NEUROENDOCRINE BASIS; EARLY EXPOSURE; RECOGNITION; RATS; ANESTHESIA; MICE; EPIGENETICS; AMYGDALA; HUMANS AB Cumulative evidence indicates that early childhood anesthesia can alter a child's future behavioral performance. Animal researchers have found that sevoflurane, the most commonly used anesthetic for children, can produce damage in the neonatal brains of rodents. To further investigate this phenomenon, we focused on the influence of sevoflurane anesthesia on the development of juvenile social behavioral abilities and the pro-social proteins oxytocin (OT) and arginine vasopressin (AVP) in the neonatal hippocampus. A single 6-h sevoflurane exposure for postnatal day 5 mice resulted in decreased OT and AVP messenger RNA (mRNA) and protein levels in the hippocampus. OT and AVP proteins became sparsely distributed in the dorsal hippocampus after the exposure to sevoflurane. Compared with the air-treated group, mice in the sevoflurane-treated group showed signs of impairment in social recognition memory formation and social discrimination ability. Sevoflurane anesthesia reduces OT and AVP activities in the neonatal hippocampus and impairs social recognition memory formation and social discrimination ability in juvenile mice. C1 [Zhou, Zhi-Bin; Yang, Xiao-Yu; Yuan, Bao-Long; Niu, Li-Jun; Zhou, Xue; Huang, Wen-Qi; Feng, Xia] Sun Yat Sen Univ, Dept Anesthesiol, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. [Zhou, Li-Hua] Sun Yat Sen Univ, Zhong Shan Med Coll, Dept Anat, Guangzhou 510275, Guangdong, Peoples R China. RP Feng, X (reprint author), Sun Yat Sen Univ, Dept Anesthesiol, Affiliated Hosp 1, 58 Zhongshan 2nd Rd, Guangzhou 510275, Guangdong, Peoples R China. EM zhouzhibin1986@aliyun.com; wooyoung@163.com; yuanbl6523@163.com; 183513575@qq.com; 550145912@qq.com; huangwenqisysu@163.com; fengxia@mail.sysu.edu.cn; zhoulih@mail.sysu.edu.cn RI ahmed, Jamila/E-8653-2015 FU Guangdong Science and Technology Planning Project [2011B050400024]; Guangzhou International Science and Technology Cooperation Project [2012J5100019] FX This work was supported by Funding from Guangdong Science and Technology Planning Project (No. 2011B050400024) and Guangzhou International Science and Technology Cooperation Project (No. 2012J5100019). The sources of funding had no role in the design and conduct of this project or in the preparation of the manuscript. 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Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. 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RP Zhong, N (reprint author), New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM nanbert.zhong@opwdd.ny.gov RI ahmed, Jamila/E-8653-2015 FU "973" project of the Chinese Ministry of Sciences and technology [2012CB517905]; National Nature Science Foundation [30671157, 81301403]; Shanghai Municipal Department of Science and Technology [2009JC1412600]; New York State Office of Mental Retardation and Developmental Disabilities (NYS OMRDD) FX This work was supported in part by the "973" project (2012CB517905) of the Chinese Ministry of Sciences and technology, National Nature Science Foundation (30671157, 81301403), the Shanghai Municipal Department of Science and Technology (2009JC1412600), and the New York State Office of Mental Retardation and Developmental Disabilities (NYS OMRDD). 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Thus, reliable methods for quantifying cellular variation in this region could greatly benefit researchers interested in addressing the cellular correlates of typical and atypical function associated with these critical cognitive abilities. To facilitate this task, we first present a general set of cytoarchitectonic criteria targeted specifically toward stereological analyses of thick, Nissl-stained sections for the homotypical cortex of the STG, referred to here as BA22/TA. Second, we use the optical fractionator to estimate pyramidal neuron number and the nucleator for pyramidal somal and nuclear volume. We also investigated the influence of age and sex on these parameters, as well as set a typically developing baseline for future comparisons. In 11 typically developing cases aged 4-48 years, the most distinguishing features of BA22/TA were the presence of distinct granular layers, a prominent, jagged layer IIIc, and a distinctly staining VIa. The average number of neurons was 91 +/- 15 million, the volume of pyramidal soma 1,512 mu m(3), and the nuclear volume 348 mu m(3). We found no correlation with age and neuron number. In contrast, pyramidal somal and nuclear volume were both negatively correlated and linearly associated with age in regression analyses. We found no significant sex differences. Overall, the data support the idea that postnatal neuron numbers are relatively stable through development but also suggest that neuronal volume may be subject to important developmental variation. Both measures are critical variables in the study of developmental neuropathology. (C) 2015 Wiley Periodicals, Inc. C1 [Barger, Nicole; Schumann, Cynthia M.] Univ Calif Davis, Dept Psychiat & Behav Sci, MIND Inst, Sacramento, CA 95817 USA. [Sheley, Matthew F.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. 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Comp. Neurol. PD MAY 1 PY 2015 VL 523 IS 7 BP 1054 EP 1072 DI 10.1002/cne.23707 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA CE9CQ UT WOS:000352141600003 PM 25556320 ER PT J AU Severance, EG Prandovszky, E Castiglione, J Yolken, RH AF Severance, Emily G. Prandovszky, Emese Castiglione, James Yolken, Robert H. TI Gastroenterology Issues in Schizophrenia: Why the Gut Matters SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Microbiome; Autoimmunity; Blood-brain barrier; Gluten; Autism; Synapses ID CENTRAL-NERVOUS-SYSTEM; REGULATORY T-CELLS; BARRIER FUNCTION; IMMUNE-RESPONSE; CELIAC-DISEASE; FREE DIET; GASTROINTESTINAL INFLAMMATION; RELAPSED SCHIZOPHRENICS; INTESTINAL MICROBIOTA; HOSPITAL ADMISSIONS AB Genetic and environmental studies implicate immune pathologies in schizophrenia. The body's largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Cuirent studies of antipsychotic-naive patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community, and early reports show that it is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement Clq, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction. C1 [Severance, Emily G.; Prandovszky, Emese; Yolken, Robert H.] Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA. [Castiglione, James] CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. RP Severance, EG (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, 600 N Wolfe St,Blalock 1105, Baltimore, MD 21287 USA. EM eseverance@jhmi.edu; eodonne3@jhmi.edu; jcast1@optonline.net; rhyolken@gmail.com FU NIMH P50 Silvio O. Conte Center at Johns Hopkins [MH-94268]; Stanley Medical Research Institute; Brain & Behavior Research Foundation (NARSAD) FX Emily G. Severance reports that this work was supported by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant no. MH-94268) and by the Stanley Medical Research Institute. Dr. Severance also has received a grant from the Brain & Behavior Research Foundation (NARSAD) and has received support for travel to meetings from the Stanley Medical Research Institute.Emese Prandovszky has received a grant and support for travel to meetings from the Stanley Medical Research Institute. 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Psychiatry Rep. PD MAY PY 2015 VL 17 IS 5 DI 10.1007/s11920-015-0574-0 PG 10 WC Psychiatry SC Psychiatry GA CD9TO UT WOS:000351441500001 ER PT J AU Roffeei, SHM Abdullah, N BasarDepartment, SKR AF Roffeei, Siti Hajar Mohd Abdullah, Noorhidawati BasarDepartment, Siti Khairatul Razifah TI Seeking social support on Facebook for children with Autism Spectrum Disorders (ASDs) SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Social support; Support group; Facebook; Autism; ASD ID ONLINE SUPPORT; COMMUNICATION; SATISFACTION; HEALTH AB Purpose: This study examined the types of social support messages exchanged between parents and/or caregivers of children with Autism Spectrum Disorders (ASDs) who communicate via Facebook (FB); it studies two autism support groups: Autism Malaysia (AM) and Autism Children Club (ACA). Method: A total of 3637 messages including both postings (381) and comments (3256) were gathered from August to November 2013. The study employed a deductive content-analysis approach. The qualitative data were analyzed for social support themes adapted from the Social Support Behavior Code (SSBC). Before collecting the data, email was sent to the FB groups' moderators to gain formal consent from the members. Result: The finding indicated that the highest percentage of messages offered dealt with Informational support (30.7%) followed by Emotional support (27.8%). Network and Esteem support messages were responsible for 20.97% and 20.2%, respectively. Tangible Assistance was the least frequent category (0.4%). A majority of these messages discussed and addressed challenges and difficulties associated with caring and raising ASD children, as well as issues such as children's social lives and self-care routines. Conclusion: Understandings of how FB is used to seek social support could impact supporting and maintaining effective communication among parents and/or caregivers of children with ASDs. This information could also improve approaches used by health professionals in developing, improving and evaluating social support systems for parents/caregivers. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Roffeei, Siti Hajar Mohd; Abdullah, Noorhidawati; BasarDepartment, Siti Khairatul Razifah] Univ Malaya, Fac Comp Sci & Informat Technol, Dept Lib & Informat Sci, Kuala Lumpur 50603, Malaysia. RP Abdullah, N (reprint author), Univ Malaya, Fac Comp Sci & Informat Technol, Dept Lib & Informat Sci, Kuala Lumpur 50603, Malaysia. EM hajaroff@gmail.com; noorhidawati@um.edu.my; razifabasar@yahoo.com FU University of Malaya High Impact Research Grant [UM.C/625/1/HIR/MOHE/FCSIT/16/H-22001-00-B00016] FX This research was partially funded by the University of Malaya High Impact Research Grant (No: UM.C/625/1/HIR/MOHE/FCSIT/16/H-22001-00-B00016). CR Azlina W. 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Among them, small molecule inhibitor of Formin Homology 2 domains (SMIFH2) is often used as a pharmacological Formin blocker. Although SMIFH2 inhibits actin polymerization by Formins and affects the actin cytoskeleton, its cellular mechanism of action and target specificity remain unclear. Here we show that SMIFH2 induces remodelling of actin filaments, microtubules and the Golgi complex as a result of its effects on Formins and p53. We found that SMIFH2 triggers alternated depolymerization-repolymerization cycles of actin and tubulin, increases cell migration, causes scattering of the Golgi complex, and also cytotoxicity at high dose. Moreover, SMIFH2 reduces expression and activity of p53 through a post-transcriptional, proteasome-independent mechanism that influences remodelling of the cytoskeleton. As the action of SMIFH2 may go beyond Formin inhibition, only short-term and low-dose SMIFH2 treatments minimize confounding effects induced by loss of p53 and cytotoxicity. 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Recently, Homberg and Lesch (2011) urged for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR S-allele and argued that the S-allele could be considered adaptive in certain contexts. They postulated that S-allele carriers show hypervigilant behavior in social situations and should thus show increased social conformity. Therefore, we tested whether 5-HTTLPR modulates the neural correlates of real-life social joint action through functional near-infrared spectroscopy (fNIRS). Thirty participants, homozygote for 5-HTTLPR, were measured and analyzed while they were involved in a previously published joint-action paradigm, which reliably leads to an activation of the left parietal cortex. We found that homozygote S-allele carriers showed increased inferior parietal lobe activation, compared to the LL-allele carriers for the contrast "joint action greater solo action". Therefore, our results provide evidence for beneficial effects of the S-allele on the neural correlates of social interactions. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Herrmann, M. J.; Cordes, A.; Reif, A.] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, D-97080 Wurzburg, Germany. [Bogon, J.] Univ Regensburg, Dept Psychol, D-93053 Regensburg, Germany. [Quester, S.] Humboldt Univ, Berlin Sch Mind & Brain, D-10099 Berlin, Germany. [Stenneken, P.] Univ Cologne, Dept Rehabil & Special Educ, D-50931 Cologne, Germany. [Reif, A.] Univ Hosp Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Ehlis, A. -C.] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany. RP Herrmann, MJ (reprint author), Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Fuchsleinstr 15, D-97080 Wurzburg, Germany. 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We used data from a population-based developmental disabilities surveillance program for 8-year-olds in metropolitan Atlanta. From 1991-2010, prevalence estimates of ID and HL were stable with slight increases in VI prevalence. CP prevalence was constant from 1993-2010. The average annual increase in ASD prevalence was 9.3% per year from 1996-2010, with a 269% increase from 4.2 per 1,000 in 1996 to 15.5 per 1,000 in 2010. From 2000-2010, the prevalence of ID without ASD was stable; during the same time, the prevalence of ASD with and without co-occurring ID increased by an average of 6.6% and 9.6% per year, respectively. ASD prevalence increases were found among both males and females, and among nearly all racial/ethnic subgroups and levels of intellectual ability. Average annual prevalence estimates from 1991-2010 underscore the significant community resources needed to provide early intervention and ongoing supports for children with ID (13.0 per 1,000), CP, (3.5 per 1,000), HL (1.4 per 1,000) and VI (1.3 in 1,000), with a growing urgency for children with ASD. C1 [Braun, Kim Van Naarden; Christensen, Deborah; Doernberg, Nancy; Schieve, Laura; Rice, Catherine; Wiggins, Lisa; Schendel, Diana; Yeargin-Allsopp, Marshalyn] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Dev Disabil Branch, Atlanta, GA 30333 USA. RP Braun, KVN (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Dev Disabil Branch, Atlanta, GA 30333 USA. 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Romcy-Pereira, Rodrigo N. TI Interplay of environmental signals and progenitor diversity on fate specification of cortical GABAergic neurons SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE interneuron; cortical development; non-autonomous specification; inhibitory circuit; cell identity ID CAUDAL GANGLIONIC EMINENCE; EMBRYONIC PREOPTIC AREA; RAT FRONTAL-CORTEX; CEREBRAL-CORTEX; INTERNEURON DEVELOPMENT; SONIC HEDGEHOG; CELL FATE; NEURODEVELOPMENTAL DISORDERS; TELENCEPHALIC PROGENITORS; IMMUNOREACTIVE NEURONS AB Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. They play a crucial role regulating inhibitory-excitatory balance in brain circuits, gating sensory perception, and regulating spike timing to brain oscillations during distinct behaviors. Dysfunctions in the establishment of proper inhibitory circuits have been associated to several brain disorders such as autism, epilepsy, and schizophrenia. In the rodent adult cortex, inhibitory neurons are generated during the second gestational week from distinct progenitor lineages located in restricted domains of the ventral telencephalon. However, only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. Here we will discuss some the events involved in the production of cortical GABAergic neuron diversity with focus on the interaction between intrinsically driven genetic programs and environmental signals during development. C1 [Brandao, Juliana A.; Romcy-Pereira, Rodrigo N.] Univ Fed Rio Grande do Norte, Inst Brain, BR-59056450 Natal, RN, Brazil. RP Romcy-Pereira, RN (reprint author), Univ Fed Rio Grande do Norte, Inst Brain, Ave Nascimento Castro 2155, BR-59056450 Natal, RN, Brazil. 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Cell. Neurosci. PD APR 28 PY 2015 VL 9 AR 149 DI 10.3389/fncel.2015.00149 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CI5LS UT WOS:000354798400001 PM 25972784 ER PT J AU Levin, IP Gaeth, GJ Foley-Nicpon, M Yegorova, V Cederberg, C Yan, HY AF Levin, Irwin P. Gaeth, Gary J. Foley-Nicpon, Megan Yegorova, Vitaliya Cederberg, Charles Yan, Haoyang TI Extending decision making competence to special populations: a pilot study of persons on the autism spectrum SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE decision making; persons on the autism spectrum; risk taking; perception of social norms; framing effects ID HIGH-FUNCTIONING AUTISM; INDIVIDUAL-DIFFERENCES; YOUNG-ADULTS; ASPERGERS-DISORDER; EMPATHY QUOTIENT; MIND; EMPLOYMENT; CHILDREN; DEFICITS; DIFFICULTIES AB The area of decision making has much to offer in our effort to understand special populations. This pilot study is an example of just such a project, where we illustrate how traditional decision making tools and tasks can be used to uncover strengths and weaknesses within a growing population of young adults with autism. In this pilot project we extended accounts of autistic behavior such as those derived from "theory of mind" to predict key components of decision making in high-functioning young adults on the autism spectrum. A battery of tests was administered to 15 high-functioning college students with autism spectrum disorder (ASD), focusing on decision making competence (DMC) and other aspects of decision making related to known deficits associated with autism. Data from this group were compared to data from unselected college students receiving the same measures. First, as a test of a key social deficit associated with autism, the target group scored much lower on the Empathy Quotient scale. Traditional elements of decision making competency such as Numeracy and application of decision rules were comparable across groups. However, there were differences in thinking style, with the ASD group showing lesser ability and engagement in intuitive thinking, and they showed lower levels of risk taking. For comparisons within the ASD group, autobiographical reports concerning individual lifestyles and outcomes were used to derive a scale of Social Functioning. The lowest scoring individuals showed the lowest levels of intuitive thinking, the lowest perceived levels of others' endorsement of socially undesirable behaviors, and the lowest ability to discriminate between "good" and "bad" risks. Results are discussed in terms of interventions that might aid high-functioning young adults with ASD in their everyday decision making. C1 [Levin, Irwin P.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Gaeth, Gary J.] Univ Iowa, Dept Mkt, Iowa City, IA 52242 USA. 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Psychol. PD APR 28 PY 2015 VL 6 AR 539 DI 10.3389/fpsyg.2015.00539 PG 10 WC Psychology, Multidisciplinary SC Psychology GA CI1XP UT WOS:000354538700002 PM 25972831 ER PT J AU Lundstrom, S Reichenberg, A Anckarsater, H Lichtenstein, P Gillberg, C AF Lundstrom, Sebastian Reichenberg, Abraham Anckarsater, Henrik Lichtenstein, Paul Gillberg, Christopher TI Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; AFFECTED SIBLING PAIRS; COMORBIDITIES A-TAC; SPECTRUM DISORDERS; TELEPHONE INTERVIEW; PRESCHOOL-CHILDREN; CHILDHOOD AUTISM; EPIDEMIOLOGY; RISK; SUBSTITUTION AB OBJECTIVE To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. DESIGN Population based study. SETTING Child and Adolescent Twin Study and national patient register, Sweden. PARTICIPANTS 19 993 twins (190 with autism spectrum disorder) and all children (n=1 078 975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. MAIN OUTCOME MEASURES Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. RESULTS The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (P<0.001 for linear trend). CONCLUSIONS The prevalence of the autism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder. C1 [Lundstrom, Sebastian; Gillberg, Christopher] Univ Gothenburg, Gillberg Neuropsychiat Ctr, S-41119 Gothenburg, Sweden. [Lundstrom, Sebastian; Anckarsater, Henrik] Univ Gothenburg, Ctr Eth Law & Mental Hlth, S-41119 Gothenburg, Sweden. [Reichenberg, Abraham] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Reichenberg, Abraham] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Lundstrom, S (reprint author), Univ Gothenburg, Gillberg Neuropsychiat Ctr, Kungsgatan 12, S-41119 Gothenburg, Sweden. EM sebastian.lundstrom@gnc.gu.se FU Swedish Council for Working Life under the ALF; Soderstrom-Konigska Foundation; Swedish Research Council (Medicine); Swedish Research Council (SIMSAM) FX The Child and Adolescent Twin Study in Sweden study was supported by the Swedish Council for Working Life, funds under the ALF agreement, the Soderstrom-Konigska Foundation, and the Swedish Research Council (Medicine and SIMSAM). The current study received no specific funding. The funding sources had no involvement in the study design; collection, analysis, and interpretation of the data; or the decision to submit this paper for publication. 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Eng. News PD APR 27 PY 2015 VL 93 IS 17 BP 30 EP 31 PG 2 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA CG8XM UT WOS:000353599000049 ER PT J AU Lopez, AJ Wood, MA AF Lopez, Alberto J. Wood, Marcelo A. TI Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Review DE epigenetics; nucleosome remodeling; autism spectrum disorders (ASD); intellectual disability; BAF53b; rubinstein-taybi syndrome; coffin-sins syndrome; nicolaides-baraitser syndrome ID RUBINSTEIN-TAYBI-SYNDROME; COFFIN-SIRIS SYNDROME; LONG-TERM-MEMORY; HISTONE ACETYLTRANSFERASE ACTIVITY; DE-NOVO MUTATIONS; IFN-BETA ENHANCEOSOME; YEAST HO GENE; SYNAPTIC PLASTICITY; RETT-SYNDROME; MENTAL-RETARDATION AB It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg 1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Sins syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development. C1 [Lopez, Alberto J.; Wood, Marcelo A.] Univ Calif Irvine, Dept Neurobiol & Behav, Ctr Neurobiol Learning & Memory, Irvine, CA 92697 USA. RP Wood, MA (reprint author), Univ Calif Irvine, Dept Neurobiol & Behav, Qureshey Res Lab 301, Irvine, CA 92697 USA. EM mwood@uci.edu FU NIH [DA025922, MH101491, DA036984]; DOE GAANN [P200A120165]; MBRS-IMSD [GM055246] FX We would like to thank Christina R. 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Behav. Neurosci. PD APR 23 PY 2015 VL 9 AR 100 DI 10.3389/fnbeh.2015.00100 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CI2HK UT WOS:000354566500001 PM 25954173 ER PT J AU Kaushik, G Thomas, MA Aho, KA AF Kaushik, Gaurav Thomas, Michael A. Aho, Ken A. TI Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network SO BMC BIOINFORMATICS LA English DT Article ID SPECTRUM DISORDERS; EXPRESSION; EXPOSURE; MODELS; CELLS AB Background: Most cases of idiopathic autism spectrum disorder (ASD) likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a fetus to minute concentrations of pharmaceuticals, such as carbamazepine (CBZ), venlafaxine (VNX) and fluoxetine (FLX). Unmetabolized pharmaceuticals reach drinking water through a variety of routes, including ineffectively treated sewage. Previous studies in our laboratory examined the extent to which gene sets were enriched in minnow brains treated with pharmaceuticals. Here, we tested the hypothesis that genes in fish brains and human cell cultures, significantly enriched by pharmaceuticals, would have distinct characteristics in an ASD-associated protein interaction network. We accomplished this by comparing these groups using 10 network indices. Results: A network of 7212 proteins and 33,461 interactions was generated. We found that network characteristics for enriched gene sets for particular pharmaceuticals were distinct from each other, and were different from non-enriched ASD gene sets. In particular, genes in fish brains, enriched by CBZ and VNX 1) had higher network importance than that in the overall network, and those enriched by FLX, and 2) were distinct from FLX and non-enriched ASD genes in multivariate network space. Similarly, genes in human cell cultures enriched by pharmaceutical mixtures (at environmental concentrations) and valproate (at clinical dosages) had similar network signatures, and had greater network importance than genes in the overall ASD network. Conclusions: The results indicate that important gene sets in the ASD network are particularly susceptible to perturbation by pharmaceuticals at environmental concentrations. C1 [Kaushik, Gaurav; Thomas, Michael A.; Aho, Ken A.] Idaho State Univ, Dept Biol Sci, Pocatello, ID 83209 USA. RP Aho, KA (reprint author), Idaho State Univ, Dept Biol Sci, Stop 8007,921 S 8th Ave, Pocatello, ID 83209 USA. EM ahoken@isu.edu FU INBRE Program, NIH (National Center for Research Resources) [P20 RR016454]; University Research Council (URC) of Idaho State University; INBRE Program, NIH Grant (national Institute of General Medical Sciences) [P20 GM103408] FX The authors thank Dr. Pete Hallock for providing the guidance for using Cytoscape software for our study. Dr. Luobin Yang also assisted in carrying out gene set enrichment analyses. We also thank Dr. Terry Bowyer for providing his guidance in writing; Cheng Han Chung for reviewing this manuscript. The project described was supported by the INBRE Program, NIH Grant Nos. P20 RR016454 (National Center for Research Resources) and P20 GM103408 (national Institute of General Medical Sciences), and the University Research Council (URC) of Idaho State University. 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However, emotion recognition (ER) studies have focused mostly on recognition of the six 'basic' emotions, usually using still pictures of faces. Methods: This study describes a new battery of tasks for testing recognition of nine complex emotions and mental states from video clips of faces and from voice recordings taken from the Mindreading DVD. This battery (the Cambridge Mindreading Face-Voice Battery for Children or CAM-C) was given to 30 high-functioning children with ASC, aged 8 to 11, and to 25 matched controls. Results: The ASC group scored significantly lower than controls on complex ER from faces and voices. In particular, participants with ASC had difficulty with six out of nine complex emotions. Age was positively correlated with all task scores, and verbal IQ was correlated with scores in the voice task. CAM-C scores were negatively correlated with parent-reported level of autism spectrum symptoms. Conclusions: Children with ASC show deficits in recognition of complex emotions and mental states from both facial and vocal expressions. The CAM-C may be a useful test for endophenotypic studies of ASC and is one of the first to use dynamic stimuli as an assay to reveal the ER profile in ASC. It complements the adult version of the CAM Face-Voice Battery, thus providing opportunities for developmental assessment of social cognition in autism. C1 [Golan, Ofer; Sinai-Gavrilov, Yana] Bar Ilan Univ, Dept Psychol, IL-5290002 Ramat Gan, Israel. [Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 2AH, England. [Baron-Cohen, Simon] Fulbourn Hosp, CLASS Clin, Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge CB21 5EF, England. RP Golan, O (reprint author), Bar Ilan Univ, Dept Psychol, IL-5290002 Ramat Gan, Israel. EM ofer.golan@biu.ac.il FU Wingate Foundation; Corob Charitable Trust; B'nai B'rith Scholarships; Shirley Foundation; Medical Research Council (MRC) UK; Wellcome Trust; Autism Research Trust FX OG was supported by the Wingate Foundation, the Corob Charitable Trust and B'nai B'rith Scholarships. SBC was supported by the Shirley Foundation, the Medical Research Council (MRC) UK, the Wellcome Trust and the Autism Research Trust. This study was conducted in association with the NIHR CLAHRC-EoE, EU ASC-Inclusion, and EU-AIMS. We would like to thank the Wirral Autistic Society, Umbrella Autism Cambridgeshire, the Hertfordshire Autistic Resource Centre, Brookside Family Consultation Clinic, Mayfield Primary School and Kings Hedges Primary School for their help with recruiting participants. We are grateful to Jacqueline Hill, Chris Ashwin, Sally Wheelwright, Yael Golan, Sarah Johnson and Emma Chapman for their help, and to Bhisma Chakrabarti for valuable discussions. 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Autism PD APR 23 PY 2015 VL 6 AR 22 DI 10.1186/s13229-015-0018-z PG 9 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA CG9EK UT WOS:000353617400001 PM 25932320 ER PT J AU Chen, J Lin, MY Hrabovsky, A Pedrosa, E Dean, J Jain, S Zheng, DY Lachman, HM AF Chen, Jian Lin, Mingyan Hrabovsky, Anastasia Pedrosa, Erika Dean, Jason Jain, Swati Zheng, Deyou Lachman, Herbert M. TI ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin SO PLOS ONE LA English DT Article ID MATERNAL IMMUNE ACTIVATION; GENOME-WIDE ASSOCIATION; AUTISM SPECTRUM DISORDER; HISTOCOMPATIBILITY COMPLEX LOCUS; RISK GENE NEUREGULIN-1; ALPHA-B-CRYSTALLIN; BIPOLAR DISORDER; PRENATAL INFECTION; CANDIDATE GENES; NEURODEVELOPMENTAL PATHWAYS AB ZNF804A (Zinc Finger Protein 804A) has been identified as a candidate gene for schizophrenia (SZ), autism spectrum disorders (ASD), and bipolar disorder (BD) in replicated genome wide association studies (GWAS) and by copy number variation (CNV) analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD) approach to reduce its expression in neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs). KD was accomplished by RNA interference (RNAi) using lentiviral particles containing shRNAs that target ZNF804A mRNA. Stable transduced NPC lines were generated after puromycin selection. A control cell line expressing a random (scrambled) shRNA was also generated. Neuronal differentiation was induced, RNA was harvested after 14 days and transcriptome analysis was carried out using RNA-seq. 1815 genes were found to be differentially expressed at a nominally significant level (p<0.05); 809 decreased in expression in the KD samples, while 1106 increased. Of these, 370 achieved genome wide significance (FDR<0.05); 125 were lower in the KD samples, 245 were higher. Pathway analysis showed that genes involved in interferon-signaling were enriched among those that were down-regulated in the KD samples. Correspondingly, ZNF804A KD was found to affect interferon-alpha 2 (IFNA2)-mediated gene expression. The findings suggest that ZNF804A may affect a differentiating neuron's response to inflammatory cytokines, which is consistent with models of SZ and ASD that support a role for infectious disease, and/or autoimmunity in a subgroup of patients. C1 [Chen, Jian; Hrabovsky, Anastasia; Pedrosa, Erika; Dean, Jason; Jain, Swati; Lachman, Herbert M.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. [Lin, Mingyan; Zheng, Deyou; Lachman, Herbert M.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Zheng, Deyou; Lachman, Herbert M.] Albert Einstein Coll Med, Dominick Purpura Dept Neurosci, Bronx, NY 10467 USA. [Zheng, Deyou] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Lachman, Herbert M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Zheng, DY (reprint author), Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. EM Deyou.Zheng@einstein.yu.edu; Herb.Lachman@einstein.yu.edu FU National Institute of Mental Health [MH073164, MH097893, MH099427, MH087840] FX This work was supported by the National Institute of Mental Health (MH073164, MH097893, MH099427, and MH087840). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2. The interactions were confirmed by co-immunoprecipitation and colocalization analyses of proteins expressed in human embryonic kidney cells, mouse neuronal cells, and rat primary neuronal cells. Furthermore, we show KIRREL3 colocalization with the marker for the Golgi apparatus and synaptic vesicles. Previously, we have shown that KIRREL3 interacts with the X-linked intellectual disability associated synaptic scaffolding protein CASK through its cytoplasmic domain. In addition, we found a genomic deletion encompassing MAP1B in one patient with intellectual disability, microcephaly and seizures and deletions encompassing MYO16 in two unrelated patients with intellectual disability, autism and microcephaly. MAP1B has been previously implicated in synaptogenesis and is involved in the development of the actin-based membrane skeleton. MYO16 is expressed in hippocampal neurons and also indirectly affects actin cytoskeleton through its interaction with WAVE1 complex. We speculate KIRREL3 interacting proteins are potential candidates for intellectual disability and autism spectrum disorder. Moreover, our findings provide further insight into understanding the molecular mechanisms underlying the physiological action of KIRREL3 and its role in neurodevelopment. C1 [Liu, Ying F.; Sowell, Sarah M.; Luo, Yue; Chaubey, Alka; Srivastava, Anand K.] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. [Srivastava, Anand K.] Clemson Univ, Dept Genet & Biochem, Clemson, SC USA. [Cameron, Richard S.] Georgia Regents Univ, Dept Med, Augusta, GA USA. [Kim, Hyung-Goo] Georgia Regents Univ, Dept OB GYN, Inst Mol Med & Genet, Augusta, GA USA. 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Simon, Jeremy M. Philpot, Benjamin D. TI Gene Length Matters in Neurons SO NEURON LA English DT Editorial Material ID AUTISM SPECTRUM DISORDER; LONG GENES; MOUSE; MUTATIONS AB A recent study by Gabel et al. (2015) found that Mecp2, the gene mutated in Rett syndrome, represses long (> 100 kb) genes associated with neuronal physiology and connectivity by binding to methylated CA sites in DNA. This study adds to a growing body of literature implicating gene length and transcriptional mechanisms in neurodevelopmental and neurodegenerative disorders. C1 [Zylka, Mark J.; Simon, Jeremy M.; Philpot, Benjamin D.] Univ N Carolina, Carolina Inst Dev Disabil, UNC Neurosci Ctr, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. RP Zylka, MJ (reprint author), Univ N Carolina, Carolina Inst Dev Disabil, UNC Neurosci Ctr, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. 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Pierce, Karen Eyler, Lisa T. Barnes, Cindy Carter Ahrens-Barbeau, Clelia Solso, Stephanie Campbell, Kathleen Courchesne, Eric TI Different Functional Neural Substrates for Good and Poor Language Outcome in Autism SO NEURON LA English DT Article ID FOLLOW-UP; SPECTRUM DISORDER; ASPERGER-SYNDROME; BEHAVIORAL TREATMENT; NEUROIMAGING DATA; TEMPORAL CORTEX; CHILDREN; SPEECH; ORGANIZATION; TRAJECTORIES AB Autism (ASD) is vastly heterogeneous, particularly in early language development. While ASD language trajectories in the first years of life are highly unstable, by early childhood these trajectories stabilize and are predictive of longer-term outcome. Early neural substrates that predict/precede such outcomes are largely unknown, but could have considerable translational and clinical impact. Pre-diagnosis fMRI response to speech in ASD toddlers with relatively good language outcome was highly similar to non-ASD comparison groups and robustly recruited language-sensitive superior temporal cortices. In contrast, language-sensitive superior temporal cortices were hypoactive in ASD toddlers with poor language outcome. Brain-behavioral relationships were atypically reversed in ASD, and a multimodal combination of pre-diagnostic clinical behavioral measures and speech-related fMRI response showed the most promise as an ASD prognosis classifier. Thus, before ASD diagnoses and outcome become clinically clear, distinct functional neuroimaging phenotypes are already present that can shed insight on an ASD toddler's later outcome. C1 [Lombardo, Michael V.] Univ Cyprus, Dept Psychol, CY-1678 Nicosia, Cyprus. [Lombardo, Michael V.] Univ Cyprus, Ctr Appl Neurosci, CY-1678 Nicosia, Cyprus. [Lombardo, Michael V.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Eyler, Lisa T.; Barnes, Cindy Carter; Ahrens-Barbeau, Clelia; Solso, Stephanie; Campbell, Kathleen; Courchesne, Eric] Univ Calif San Diego, Dept Neurosci, Autism Ctr Excellence, La Jolla, CA 92093 USA. [Eyler, Lisa T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92161 USA. [Eyler, Lisa T.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 22, San Diego, CA 92161 USA. RP Lombardo, MV (reprint author), Univ Cyprus, Dept Psychol, 1 Panepistimiou Ave, CY-1678 Nicosia, Cyprus. EM mvlombardo@gmail.com; ecourchesne@ucsd.edu FU NIMH Autism Center of Excellence [P50-MH081755]; NIMH [R01-MH080134, R01-MH036840]; NFAR; Jesus College, Cambridge; British Academy FX This work was supported by NIMH Autism Center of Excellence grant P50-MH081755 (E.C.), NIMH R01-MH080134 (K.P.), NFAR grant (K.P.), NIMH R01-MH036840 (E.C.), and fellowships from Jesus College, Cambridge and the British Academy (M.V.L.). We thank Richard Znamirowski, Maisi Mayo, and Julia Young for help with data collection and Stuart Spendlove and Melanie Weinfeld for assistance with clinical characterization of subjects. 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Nowhere is this more evident than in the classed moralities of motherhood with the harshest criticisms aimed at the 'chav' poor and working-class families and their children whose lifestyles and moral respectability may be called into question for causing or even fabricating particular disabilities in the first place. Alongside these characterisations of parental deficits and immorality associated with working-class and poor parents, connections between 'invisible' disability, poverty and poor parenting continue. C1 Univ Sheffield, Dept Sociol Studies, Sheffield, S Yorkshire, England. RP Heeney, J (reprint author), Univ Sheffield, Dept Sociol Studies, Sheffield, S Yorkshire, England. 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Soc. PD APR 21 PY 2015 VL 30 IS 4 BP 650 EP 653 DI 10.1080/09687599.2015.1026745 PG 4 WC Rehabilitation; Social Sciences, Interdisciplinary SC Rehabilitation; Social Sciences - Other Topics GA CI9VM UT WOS:000355118200012 ER PT J AU Potrzeba, ER Fein, D Naigles, L AF Potrzeba, Emily R. Fein, Deborah Naigles, Letitia TI Investigating the shape bias in typically developing children and children with autism spectrum disorders SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE shape bias; autism; word learning; intermodal preferential looking; developmental disorders ID PREFERENTIAL LOOKING PARADIGM; LANGUAGE-ACQUISITION; YOUNG-CHILDREN; COMPREHENSION; ATTENTION; RELIANCE; ACCOUNT; OBJECTS; WORDS AB Young typically developing (TD) children have been observed to utilize word learning strategies such as the noun bias and shape bias; these improve their efficiency in acquiring and categorizing novel terms. Children using the shape bias extend object labels to new objects of the same shape; thus, the shape bias prompts the categorization of object words based on the global characteristic of shape over local, discrete details. Individuals with autism spectrum disorders (ASDs) frequently attend to minor details of objects rather than their global structure. Therefore, children with ASD may not use shape bias to acquire new words. Previous research with children with ASD has provided evidence that they parallel TD children in showing a noun bias, but not a shape bias (Tek et al., 2008). However, this sample was small and individual and item differences were not investigated in depth. In an extension of Tek et al. (2008) with twice the sample size and a wider developmental timespan, we tested 32 children with ASD and 35 TD children in a longitudinal study across 20 months using the intermodal preferential looking paradigm. Children saw five triads of novel objects (target, shapematch, color-match) in both NoName and Name trials; those who looked longer at the shape-match during the Name trials than the NoName trials demonstrated a shape bias. The TD group showed a significant shape bias at all visits, beginning at 20 months of age while the language-matched ASD group did not show a significant shape bias at any visit. Within the ASD group, though, some children did show a shape bias; these children had larger vocabularies concurrently and longitudinally. Degree of shape bias elicitation varied by item, but did not seem related to perceptual complexity. We conclude that shape does not appear to be an organizing factor for word learning by children with ASD. C1 [Potrzeba, Emily R.; Fein, Deborah; Naigles, Letitia] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Potrzeba, Emily R.] Univ N Carolina, Dept Allied Hlth Sci, Chapel Hill, NC 27599 USA. RP Potrzeba, ER (reprint author), Univ N Carolina, Dept Allied Hlth Sci, Chapel Hill, NC 27599 USA. EM emily_potrzeba@med.unc.edu FU National Institute on Deafness and Other Communication Disorders grant [R01 DC007428]; UCONN Summer Undergraduate Research Fund FX This research was funded by a grant from the National Institute on Deafness and Other Communication Disorders grant to LN (Grant number: R01 DC007428) and by a UCONN Summer Undergraduate Research Fund fellowship to EP. We extend our gratitude to Dr. Saime Tek for helping to launch this line of research, to Rose Jaffery, Janina Piotroski, and Andrea Tovar for assistance in data collection, and to the undergraduates of the UConn Child Language Lab for their expert coding. We appreciate the helpful feedback we received from attendants of IMFAR 2014 in Atlanta. Finally, we also thank the children and families who participated in the study. 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Preece, Kathryn A. de Wit, Bianca Glenn, Katharine Fieder, Nora Thie, Johnson McArthur, Genevieve TI Validation of the Emotiv EPOC EEG system for research quality auditory event-related potentials in children SO PEERJ LA English DT Article DE EEG; ERP; Emotiv EPOC; Validation; Mismatchnegativity; MMN; Intraclass correlation; Methods; Auditory odd-ball; Children ID MISMATCH NEGATIVITY MMN; LANGUAGE IMPAIRMENT; EVOKED-POTENTIALS; MATURATION; ADOLESCENCE; ERP; AUTISM AB Background. Previous work has demonstrated that a commercial gaming electroencephalography (EEG) system, Emotiv EPOC, can be adjusted to provide valid auditory event-related potentials (ERPs) in adults that are comparable to ERPs recorded by a research-grade EEG system, Neuroscan. The aim of the current study was to determine if the same was true for children. Method. An adapted Emotiv EPOC system and Neuroscan system were used to make simultaneous EEG recordings in nineteen 6-to 12-year-old children under "passive" and "active" listening conditions. In the passive condition, children were instructed to watch a silent DVD and ignore 566 standard (1,000 Hz) and 100 deviant (1,200 Hz) tones. In the active condition, they listened to the same stimuli, and were asked to count the number of `high' (i.e., deviant) tones. Results. Intraclass correlations (ICCs) indicated that the ERP morphology recorded with the two systems was very similar for the P1, N1, P2, N2, and P3 ERP peaks (r =.82 to.95) in both passive and active conditions, and less so, though still strong, for mismatch negativity ERP component (MMN; r =.67 to.74). There were few differences between peak amplitude and latency estimates for the two systems. Conclusions. An adapted EPOC EEG system can be used to index children's late auditory ERP peaks (i.e., P1, N1, P2, N2, P3) and theirMMNERP component. C1 [Badcock, Nicholas A.; Preece, Kathryn A.; de Wit, Bianca; Fieder, Nora; McArthur, Genevieve] Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, N Ryde, NSW, Australia. [Badcock, Nicholas A.; Preece, Kathryn A.; de Wit, Bianca; Fieder, Nora; McArthur, Genevieve] Macquarie Univ, Dept Cognit Sci, N Ryde, NSW, Australia. [Glenn, Katharine] MultiLit, Macquarie Pk, NSW, Australia. [Thie, Johnson] Univ Sydney, Sch Elect & Informat Engn, Sydney, NSW 2006, Australia. RP Badcock, NA (reprint author), Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, N Ryde, NSW, Australia. EM nicholas.badcock@mq.edu.au FU ARC Centre of Excellence Grant [CE110001021]; NHMRC equipment grant FX This research was supported by an ARC Centre of Excellence Grant [CE110001021] and an NHMRC equipment grant. 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 study aimed to evaluate difficulties in daily functioning of children and adolescents with pervasive developmental disorder (PDD) using the QCD. Results were compared with those for a community sample. Methods A case-control design was used. The cases comprised elementary school students (182 males, 51 females) and junior high school students (100 males, 39 females) with PDD, whereas a community sample of elementary school students (568 males, 579 females) and junior high school students (180 males, 183 females) was enrolled as controls. Their behavior was assessed using the QCD, the Tokyo Autistic Behavior Scale (TABS), the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI) for elementary and junior high school students, respectively. Effects of gender and diagnosis on the QCD scores were analyzed. Correlation coefficients between QCD and TABS, ADHD-RS, and ODBI scores were analyzed. Results The QCD scores for the children with PDD were significantly lower compared with those from the community sample (P < 0.001). Significantly strong correlations were observed in more areas of the ADHD-RS and ODBI scores compared with the TABS scores. Conclusions Children with PDD experienced greater difficulties in completing basic daily activities; moreover, their QCD scores revealed stronger associations with their ADHD-RS and ODBI scores in comparison with their TABS scores. The difficulties of PDD, ADHD and OBDI symptoms combined in children makes it necessary to assess all diagnoses before any therapy for PDD is initiated in order to be able to evaluate its results properly. C1 [Sasaki, Yoshinori; Usami, Masahide; Iwadare, Yoshitaka; Watanabe, Kyota; Ushijima, Hirokage; Tanaka, Tetsuya; Harada, Maiko; Tanaka, Hiromi] Kohnodai Hosp, Natl Ctr Global Hlth & Med, Dept Child & Adolescent Psychiat, Chiba, Japan. [Sasayama, Daimei; Sugiyama, Nobuhiro] Shinshu Univ, Dept Psychiat, Matsumoto, Nagano 390, Japan. [Okada, Takashi] Nagoya Univ, Grad Sch Med, Dept Child & Adolescent Psychiat, Nagoya, Aichi 4648601, Japan. [Kodaira, Masaki; Saito, Kazuhiko] Aiiku Hosp, Aiiku Maternal & Child Hlth Ctr, Imperial Gift Fdn, Dept Child & Adolescent Mental Hlth, Tokyo, Japan. [Sawa, Tetsuji] Kitasato Univ, Grad Sch Med Sci, Dept Dev Psychiat, Tokyo, Japan. RP Sasaki, Y (reprint author), Kohnodai Hosp, Natl Ctr Global Hlth & Med, Dept Child & Adolescent Psychiat, Chiba, Japan. EM lalala.ponyo@gmail.com RI Sugiyama, Nobuhiro/C-6388-2008; Usami, Masahide/G-1404-2015 OI Usami, Masahide/0000-0002-1145-9971 CR Achenbach T. 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TI Promising Forecast for Autism Spectrum Disorders SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MEASLES; MUMPS C1 [King, Bryan H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98145 USA. [King, Bryan H.] Seattle Childrens Hosp, Seattle, WA 98145 USA. RP King, BH (reprint author), Univ Washington, Seattle Childrens Autism Ctr, POB 5371-M1-1, Seattle, WA 98145 USA. 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Am. Med. Assoc. PD APR 21 PY 2015 VL 313 IS 15 BP 1518 EP 1519 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CG3SA UT WOS:000353198700014 PM 25898047 ER PT J AU Bearss, K Johnson, C Smith, T Lecavalier, L Swiezy, N Aman, M McAdam, DB Butter, E Stillitano, C Minshawi, N Sukhodolsky, DG Mruzek, DW Turner, K Neal, T Hallett, V Mulick, JA Green, B Handen, B Deng, YH Dziura, J Scahill, L AF Bearss, Karen Johnson, Cynthia Smith, Tristram Lecavalier, Luc Swiezy, Naomi Aman, Michael McAdam, David B. Butter, Eric Stillitano, Charmaine Minshawi, Noha Sukhodolsky, Denis G. Mruzek, Daniel W. Turner, Kylan Neal, Tiffany Hallett, Victoria Mulick, James A. Green, Bryson Handen, Benjamin Deng, Yanhong Dziura, James Scahill, Lawrence TI Effect of Parent Training vs Parent Education on Behavioral Problems in Children With Autism Spectrum Disorder A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; YOUNG-CHILDREN; PROGRAM; INTERVENTION; RISPERIDONE; CHECKLIST; STRESS; IMPACT AB IMPORTANCE Disruptive behavior is common in children with autism spectrum disorder. Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale randomized trials. OBJECTIVE To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior. DESIGN, SETTING, AND PARTICIPANTS This 24-week randomized trial compared parent training (n = 89) to parent education (n = 91) at 6 centers (Emory University, Indiana University, Ohio State University, University of Pittsburgh, University of Rochester, Yale University). We screened 267 children; 180 children (aged 3-7 years) with autism spectrum disorder and disruptive behaviors were randomly assigned (86% white, 88% male) between September 2010 and February 2014. INTERVENTIONS Parent training (11 core, 2 optional sessions; 2 telephone boosters; 2 home visits) provided specific strategies to manage disruptive behavior. Parent education (12 core sessions, 1 home visit) provided information about autism but no behavior management strategies. MAIN OUTCOMES AND MEASURES Parents rated disruptive behavior and noncompliance on co-primary outcomes: the Aberrant Behavior Checklist-Irritability subscale (range, 0-45) and the Home Situations Questionnaire-Autism Spectrum Disorder (range, 0-9). On both measures, higher scores indicate greater severity and a 25% reduction indicates clinical improvement. A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression (range, 1-7), a secondary outcome, with a positive response less than 3. RESULTS At week 24, the Aberrant Behavior Checklist-Irritability subscale declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for parent education (23.9 to 16.3) (treatment effect, -3.9; 95% CI, -6.2 to -1.7; P < .001, standardized effect size = 0.62). The Home Situations Questionnaire-Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared with 34.2% in parent education (3.8 to 2.5) (treatment effect, -0.7; 95% CI, -1.1 to -0.3; P < .001, standardized effect size = 0.45). Neither measure met the prespecified minimal clinically important difference. The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5% for parent training vs 39.6% for parent education (P < .001). CONCLUSIONS AND RELEVANCE For children with autism spectrum disorder, a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes, although the clinical significance of the improvement is unclear. The rate of positive response judged by a blinded clinician was greater for parent training vs parent education. C1 [Bearss, Karen; Green, Bryson; Scahill, Lawrence] Childrens Healthcare Atlanta, Marcus Autism Ctr, Dept Pediat, Atlanta, GA 30329 USA. [Bearss, Karen; Green, Bryson; Scahill, Lawrence] Emory Univ, Atlanta, GA 30329 USA. [Johnson, Cynthia; Stillitano, Charmaine] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. [Smith, Tristram; McAdam, David B.; Mruzek, Daniel W.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Lecavalier, Luc; Aman, Michael] Ohio State Univ, Nisonger Ctr, UCEDD, Dept Psychol, Columbus, OH 43210 USA. [Lecavalier, Luc; Aman, Michael] Ohio State Univ, Nisonger Ctr, UCEDD, Dept Psychiat, Columbus, OH 43210 USA. [Swiezy, Naomi; Minshawi, Noha; Neal, Tiffany] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. [Butter, Eric; Mulick, James A.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Butter, Eric; Mulick, James A.] Natl Childrens Hosp, Columbus, OH USA. [Sukhodolsky, Denis G.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Turner, Kylan] Arizona State Univ, Mary Lou Fulton Teachers Coll, Div Educ Leadership & Innovat, Tempe, AZ USA. [Hallett, Victoria] Kings Coll London, Dept Psychol, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Handen, Benjamin] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Deng, Yanhong] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Dziura, James] Yale Univ, Dept Emergency Med, New Haven, CT USA. RP Scahill, L (reprint author), Childrens Healthcare Atlanta, Marcus Autism Ctr, 1920 Briarcliff NE, Atlanta, GA 30329 USA. EM lawrence.scahill@emory.edu FU National Institute of Mental Health [MH081148, MH080965, MH081105, MH081221, MH080906]; University of Rochester from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1 TR000042]; National Center for Research Resources (NCRR), a component of the NIH [UL1 RR024139, 5KL2RR024138]; NIH Roadmap for Medical Research; Public Health Service grant from the CTSA program of the NIH NCRR at Emory University School of Medicine [UL1 RR025008]; Marcus Foundation; Joseph B. Whitehead Foundation; Children's Healthcare of Atlanta Foundation; Cox Foundation; [MH079130] FX This work was funded by the National Institute of Mental Health by grants to Yale University/Emory University (MH081148; principal investigator: Dr Scahill), the University of Pittsburgh (MH080965; principal investigator: Dr Johnson), Ohio State University (MH081105; principal investigator: Dr Lecavalier), Indiana University (MH081221; principal investigator: Dr Swiezy), and the University of Rochester (MH080906; principal investigator: Dr Smith). The project described in this publication also was supported by MH079130 (principal investigator: Dr Sukhodolsky); a University of Rochester Clinical and Translational Scholar Award (CTSA) (UL1 TR000042) from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); a CTSA (UL1 RR024139) and grant from the National Center for Research Resources (NCRR) (5KL2RR024138), a component of the NIH; and the NIH Roadmap for Medical Research. This work was supported in part by a Public Health Service grant (UL1 RR025008) from the CTSA program of the NIH NCRR at Emory University School of Medicine and also supported by the Marcus Foundation, Joseph B. Whitehead Foundation, Children's Healthcare of Atlanta Foundation, and Cox Foundation. 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Am. Med. Assoc. PD APR 21 PY 2015 VL 313 IS 15 BP 1524 EP 1533 DI 10.1001/jama.2015.3150 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CG3SA UT WOS:000353198700017 PM 25898050 ER PT J AU Jain, A Marshall, J Buikema, A Bancroft, T Kelly, JP Newschaffer, CJ AF Jain, Anjali Marshall, Jaclyn Buikema, Ami Bancroft, Tim Kelly, Jonathan P. Newschaffer, Craig J. TI Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SPECTRUM DISORDERS; SAFETY CONCERNS; MEASLES; RECURRENCE; MUMPS; RISK AB IMPORTANCE Despite research showing no link between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine causes autism persist, leading to lower vaccination levels. Parents who already have a child with ASD may be especially wary of vaccinations. OBJECTIVE To report ASD occurrence by MMR vaccine status in a large sample of US children who have older siblings with and without ASD. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study using an administrative claims database associated with a large commercial health plan. Participants included children continuously enrolled in the health plan from birth to at least 5 years of age during 2001-2012 who also had an older sibling continuously enrolled for at least 6 months between 1997 and 2012. EXPOSURES MMR vaccine receipt (0, 1, 2 doses) between birth and 5 years of age. MAIN OUTCOMES AND MEASURES ASD status defined as 2 claims with a diagnosis code in any position for autistic disorder or other specified pervasive developmental disorder (PDD) including Asperger syndrome, or unspecified PDD (International Classification of Diseases, Ninth Revision, Clinical Modification 299.0x, 299.8x, 299.9x). RESULTS Of 95 727 children with older siblings, 994 (1.04%) were diagnosed with ASD and 1929 (2.01%) had an older sibling with ASD. Of those with older siblings with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings (P < .001). MMR vaccination rates (>= 1 dose) were 84%(n = 78 564) at age 2 years and 92%(n = 86 063) at age 5 years for children with unaffected older siblings, vs 73%(n = 1409) at age 2 years and 86%(n = 1660) at age 5 years for children with affected siblings. MMR vaccine receipt was not associated with an increased risk of ASD at any age. For children with older siblings with ASD, at age 2, the adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was 0.76 (95% CI, 0.49-1.18; P = .22), and at age 5, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052). For children whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1 dose was 0.91 (95% CI, 0.67-1.20; P = .50) and at age 5, the RR of ASD for 2 doses was 1.12 (95% CI, 0.78-1.59; P = .55). CONCLUSIONS AND RELEVANCE In this large sample of privately insured children with older siblings, receipt of the MMR vaccine was not associated with increased risk of ASD, regardless of whether older siblings had ASD. These findings indicate no harmful association between MMR vaccine receipt and ASD even among children already at higher risk for ASD. C1 [Jain, Anjali; Marshall, Jaclyn; Kelly, Jonathan P.] Lewin Grp, Falls Church, VA 22042 USA. [Buikema, Ami; Bancroft, Tim] Optum, Eden Prairie, MN USA. [Newschaffer, Craig J.] Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. RP Jain, A (reprint author), Lewin Grp, 3130 Fairview Pk Dr,Ste SOO, Falls Church, VA 22042 USA. EM anjali.jain@lewin.com FU National Institute of Mental Health, National Institutes of Health; US Department of Health and Human Services [HHSN-271-2010-00033-C] FX This project was funded by the National Institute of Mental Health, National Institutes of Health, and the US Department of Health and Human Services under contract HHSN-271-2010-00033-C. 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Am. Med. Assoc. PD APR 21 PY 2015 VL 313 IS 15 BP 1534 EP 1540 DI 10.1001/jama.2015.3077 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CG3SA UT WOS:000353198700018 PM 25898051 ER PT J AU Segel, R Ben-Pazi, H Zeligson, S Fatal-Valevski, A Aran, A Gross-Tsur, V Schneebaum-Sender, N Shmueli, D Lev, D Perlberg, S Blumkin, L Deutsch, L Levy-Lahad, E AF Segel, Reeval Ben-Pazi, Hilla Zeligson, Sharon Fatal-Valevski, Aviva Aran, Adi Gross-Tsur, Varda Schneebaum-Sender, Nira Shmueli, Dorit Lev, Dorit Perlberg, Shira Blumkin, Luba Deutsch, Lisa Levy-Lahad, Ephrat TI Copy number variations in cryptogenic cerebral palsy SO NEUROLOGY LA English DT Article ID FUNCTION CLASSIFICATION-SYSTEM; AUTISM SPECTRUM DISORDERS; CHROMOSOMAL MICROARRAY; GENE; INDIVIDUALS; DISABILITY; EPILEPSY; CHILDREN; FEATURES; DELETION AB Objective:To determine the prevalence and characteristics of copy number variations (CNVs) in children with cerebral palsy (CP) of unknown etiology, comprising approximately 20% of the CP population.Methods:Fifty-two participants (age 10.5 7.8 years; Gross Motor Function Classification System scale 2.8 1.3) with nonprogressive pyramidal and/or extrapyramidal signs since infancy and no identified etiology were enrolled. Individuals with evidence of acquired causes were excluded. Participants underwent neurologic and clinical genetic examinations before the genomic testing. Chromosomal microarray analysis to detect CNVs was performed using the Affymetrix platform. CNVs identified were classified as pathogenic, likely pathogenic, likely benign, or benign. Only pathogenic and likely pathogenic CNVs were defined as clinically significant.Results:Thirty-nine CNVs were found in 25 of 52 participants (48%). Sixteen participants (31%) had clinically significant CNVs: 10 pathogenic and 6 likely pathogenic, of which 7 were not previously associated with motor disability. Nine participants had likely benign CNVs. Clinically significant CNVs were more frequently de novo (12/16; p < 0.001) including in 5 of 8 individuals who had a first- or second-degree relative with a major neurologic disorder. Dysmorphic features and nonmotor comorbidities were more prevalent in individuals with clinically significant CNVs (p < 0.05 for both).Conclusion:CNVs, most frequently de novo, are common in individuals with cryptogenic CP. We recommend CNV testing in individuals with CP of unknown etiology. C1 [Segel, Reeval; Zeligson, Sharon; Perlberg, Shira; Levy-Lahad, Ephrat] Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel. [Ben-Pazi, Hilla; Aran, Adi; Gross-Tsur, Varda] Shaare Zedek Med Ctr, Neuropediat Unit, Jerusalem, Israel. [Fatal-Valevski, Aviva; Schneebaum-Sender, Nira] Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Pediat Neurol Unit, IL-64239 Tel Aviv, Israel. [Shmueli, Dorit] Clalit, Jerusalem Child Dev Ctr, Jerusalem, Israel. [Lev, Dorit; Blumkin, Luba] Wolfson Med Ctr, Metab Neurogenet Clin, Holon, Israel. [Deutsch, Lisa] Biostat Consulting, BioStats, Haifa, Israel. RP Segel, R (reprint author), Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel. EM reevals@szmc.org.il FU MOF Joint Israel Ministry of Health [3-6185]; Hebrew University; Shaare Zedek Medical Center FX Supported by grants: MOF Joint Israel Ministry of Health grant (3-6185), and the joint research fund of The Hebrew University and Shaare Zedek Medical Center. 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Schmahl, Christian Demanuele, Charmaine Tost, Heike Kirsch, Peter Meyer-Lindenberg, Andreas TI Information flow between interacting human brains: Identification, validation, and relationship to social expertise SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fMRI; hyperscanning; joint attention ID INDEPENDENT COMPONENT ANALYSIS; RIGHT TEMPOROPARIETAL JUNCTION; JOINT ATTENTION; NETWORK SIZE; FMRI DATA; COGNITION; METAANALYSIS; COMMUNICATION; ACTIVATION; AUTISM AB Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. C1 [Bilek, Edda; Schaefer, Axel; Akdeniz, Ceren; Demanuele, Charmaine; Tost, Heike; Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-68159 Mannheim, Germany. [Ruf, Matthias] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Neuroimaging, D-68159 Mannheim, Germany. [Schmahl, Christian] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychosomat Med & Psychotherapy, D-68159 Mannheim, Germany. [Kirsch, Peter] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Clin Psychol, D-68159 Mannheim, Germany. [Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Meyer-Lindenberg, A (reprint author), Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-68159 Mannheim, Germany. EM a.meyer-lindenberg@zi-mannheim.de FU German Research Foundation (DFG) [SFB 636]; European Community [HEALTH-F2-2010-241909]; DFG (Clinical Research Unit 256) [ME 1591/4-1]; German Federal Ministry of Education and Research [BMBF 01GQ1102] FX The authors thank Dr. Emanuel Schwarz for his valuable comments on the analysis and manuscript. E.B. is a PhD grant awardee of the SFB 636 International Graduate Program in Translational Neuroscience funded by the German Research Foundation (DFG). A.M.-L. gratefully acknowledges grant support by European Community's Seventh Framework Programme under Grant HEALTH-F2-2010-241909 (Project EU-GEI). A.M.-L., P.K., and C.S. gratefully acknowledge grant support by DFG (Clinical Research Unit 256, ME 1591/4-1). H.T. gratefully acknowledges grant support by the German Federal Ministry of Education and Research (BMBF 01GQ1102). 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PD APR 21 PY 2015 VL 112 IS 16 BP 5207 EP 5212 DI 10.1073/pnas.1421831112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CG4FJ UT WOS:000353239100088 PM 25848050 ER PT J AU Koeda, M Watanabe, A Tsuda, K Matsumoto, M Ikeda, Y Kim, W Tateno, A Naing, BT Karibe, H Shimada, T Suzuki, H Matsuura, M Okubo, Y AF Koeda, Michihiko Watanabe, Atsushi Tsuda, Kumiko Matsumoto, Miwako Ikeda, Yumiko Kim, Woochan Tateno, Amane Naing, Banyar Than Karibe, Hiroyuki Shimada, Takashi Suzuki, Hidenori Matsuura, Masato Okubo, Yoshiro TI Interaction effect between handedness and CNTNAP2 polymorphism (rs7794745 genotype) on voice-specific frontotemporal activity in healthy individuals: an fMRI study SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE CNTNAP2; fMRI; voice; handedness; SNPs; autism; schizophrenia ID AUTISM SPECTRUM DISORDER; LANGUAGE-RELATED REGIONS; CHINESE HAN POPULATION; HUMAN AUDITORY-CORTEX; FUNCTIONAL MRI; HUMAN BRAIN; CEREBRAL LATERALITY; GENETIC-VARIATION; SCHIZOPHRENIA; ASSOCIATION AB Recent neuroimaging studies have demonstrated that Contactin-associated protein-like2 (CNTNAP2) polymorphisms affect left-hemispheric function of language processing in healthy individuals, but no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception. Further, although recent reports suggest that determination of handedness is influenced by genetic effect, the interaction effect between handedness and CNTNAP2 polymorphisms for brain activity in human voice perception and language processing has not been revealed. We aimed to investigate the interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain function for human voice perception and language processing in healthy individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non-right-handed) was examined while they were passively listening to reverse sentences (rSEN), identifiable non-vocal sounds (SND), and sentences (SEN). Full factorial design analysis was calculated by using three factors: (1) rs7794745 (A/A or A/T), (2) rs2710102 [G/G or A carrier (A/G and A/A)], and (3) voice-specific response (rSEN or SND). The main effect of rs7794745 (A/A or A/T) was significantly revealed at the right middle frontal gyrus (MFG) and bilateral superior temporal gyrus (STG). This result suggests that rs7794745 genotype affects voice-specific brain function. Furthermore, interaction effect was significantly observed among MFG-STG activations by human voice perception, rs7794745 (A/A or A/T), and handedness. These results suggest that CNTNAP2 polymorphisms could be one of the important factors in the neural development related to vocal communication and language processing in both right-handed and non-right-handed healthy individuals. C1 [Koeda, Michihiko; Kim, Woochan; Tateno, Amane; Okubo, Yoshiro] Nippon Med Sch, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138603, Japan. [Watanabe, Atsushi; Naing, Banyar Than] Nippon Med Coll Hosp, Div Personalized Genet Med, Tokyo, Japan. [Watanabe, Atsushi; Naing, Banyar Than; Shimada, Takashi] Nippon Med Sch, Grad Sch Med, Dept Biochem & Mol Biol, Tokyo 1138603, Japan. [Tsuda, Kumiko; Matsumoto, Miwako; Matsuura, Masato] Tokyo Med & Dent Univ, Dept Biofunct Informat, Tokyo, Japan. [Ikeda, Yumiko; Karibe, Hiroyuki] Nippon Dent Univ Tokyo, Dept Pediat Dent, Tokyo, Japan. [Suzuki, Hidenori] Nippon Med Sch, Grad Sch Med, Dept Pharmacol, Tokyo 1138603, Japan. RP Koeda, M (reprint author), Nippon Med Sch, Grad Sch Med, Dept Neuropsychiat, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138603, Japan. EM mkoeda@nms.ac.jp FU Health and Labor Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health from Japanese Ministry of Health, Labor and Welfare [H23-seishin-ippan-002] FX We gratefully acknowledge the staff of Yaesu Clinic, Nippon Medical School Hospital; Section of Biofunctional Informatics, Tokyo Medical and Dental University; and Voice Neurocognition Laboratory, University of Glasgow. This work was supported by a Health and Labor Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H23-seishin-ippan-002) from the Japanese Ministry of Health, Labor and Welfare. 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Behav. Neurosci. PD APR 20 PY 2015 VL 9 AR 87 DI 10.3389/fnbeh.2015.00087 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CI2GX UT WOS:000354565000001 PM 25941478 ER PT J AU Grier, MD Carson, RP Lagrange, AH AF Grier, Mark D. Carson, Robert P. Lagrange, Andre Hollis TI Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells SO PLOS ONE LA English DT Article ID UBIQUITIN LIGASE; WHITE-MATTER; AUTISM; REVEALS; NEURONS; GENE AB Angelman Syndrome (AS) is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development. C1 [Grier, Mark D.; Carson, Robert P.; Lagrange, Andre Hollis] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37232 USA. [Carson, Robert P.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Lagrange, Andre Hollis] Tennessee Valley Vet Adm, Dept Neurol, Nashville, TN 37212 USA. RP Lagrange, AH (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37232 USA. EM Andre.H.Lagrange@vanderbilt.edu FU Vanderbilt Kennedy Center [VA 1I01BX001189]; National Institute of Neurological Disorders and Stroke; NIH [5K08NS050484] FX This research was supported by a Hobbs Discovery Grant from the Vanderbilt Kennedy Center and VA 1I01BX001189 to AHL and the National Institute of Neurological Disorders and Stroke; NIH (5K08NS050484) to RPC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Assidi, Mourad Abu-Elmagd, Muhammad Turki, Rola F. TI Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring SO REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY LA English DT Review DE Paternal age; Infertility; Semen parameters; Reproduction; Genetics; Sperm DNA damage; Telomere length; Aneuploidy; Epigenetics; Offspring; Assisted reproductive techniques ID DE-NOVO MUTATIONS; CHROMATIN-STRUCTURE ASSAY; LEUKOCYTE TELOMERE LENGTH; IN-VITRO FERTILIZATION; LOW-BIRTH-WEIGHT; FOLLICLE-STIMULATING-HORMONE; EJACULATED HUMAN SPERMATOZOA; AUTISM SPECTRUM DISORDERS; POPULATION-BASED COHORT; DNA-DAMAGE AB Over the last decade, there has been a significant increase in average paternal age when the first child is conceived, either due to increased life expectancy, widespread use of contraception, late marriages and other factors. While the effect of maternal ageing on fertilization and reproduction is well known and several studies have shown that women over 35 years have a higher risk of infertility, pregnancy complications, spontaneous abortion, congenital anomalies, and perinatal complications. The effect of paternal age on semen quality and reproductive function is controversial for several reasons. First, there is no universal definition for advanced paternal ageing. Secondly, the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease. Our exhaustive literature review has demonstrated negative effects on sperm quality and testicular functions with increasing paternal age. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny. It is thereby essential to educate the infertile couples on the disturbing links between increased paternal age and rising disorders in their offspring, to better counsel them during their reproductive years. C1 [Sharma, Rakesh; Agarwal, Ashok; Rohra, Vikram K.] Cleveland Clin, Ctr Reprod Med, Cleveland, OH 44106 USA. [Assidi, Mourad; Abu-Elmagd, Muhammad] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21413, Saudi Arabia. [Assidi, Mourad; Abu-Elmagd, Muhammad; Turki, Rola F.] King Abdulaziz Univ, KACST Technol Innovat Ctr Personalized Med, Jeddah 21413, Saudi Arabia. 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Biol. Endocrinol. PD APR 19 PY 2015 VL 13 AR 35 DI 10.1186/s12958-015-0028-x PG 20 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA CI6IP UT WOS:000354862700001 PM 25928123 ER PT J AU Ma, L Piirainen, S Kulesskaya, N Rauvala, H Tian, L AF Ma, Li Piirainen, Sami Kulesskaya, Natalia Rauvala, Heikki Tian, Li TI Association of brain immune genes with social behavior of inbred mouse strains SO Journal of Neuroinflammation LA English DT Article DE Social deficit; Inbred mouse strains; Immune genes; Behaviors; Brain morphology ID GENOME-WIDE ASSOCIATION; DBA/2 MICE; SCHIZOPHRENIA; ACTIVATION; MICROGLIA; SYSTEM; AUTISM; EXPRESSION; ANXIETY; CNS AB Background: Social deficit is one of the core symptoms of neuropsychiatric diseases, in which immune genes play an important role. Although a few immune genes have been shown to regulate social and emotional behaviors, how immune gene network(s) may jointly regulate sociability has not been investigated so far. Methods: To decipher the potential immune-mediated mechanisms underlying social behavior, we first studied the brain microarray data of eight inbred mouse strains with known variations in social behavior and retrieved the differentially expressed immune genes. We then made a protein-protein interaction analysis of them to find the major networks and explored the potential association of these genes with the behavior and brain morphology in the mouse phenome database. To validate the expression and function of the candidate immune genes, we selected the C57BL/6 J and DBA/2 J strains among the eight inbred strains, compared their social behaviors in resident-intruder and 3-chambered social tests and the mRNA levels of these genes, and analyzed the correlations of these genes with the social behaviors. Results: A group of immune genes were differentially expressed in the brains of these mouse strains. The representative C57BL/6 J and DBA/2 J strains displayed significant differences in social behaviors, DBA/2 J mice being less active in social dominance and social interaction than C57BL/6 J mice. The mRNA levels of H2-d1 in the prefrontal cortex, hippocampus, and hypothalamus and C1qb in the hippocampus of the DBA/2 J strain were significantly down-regulated as compared to those in the C57BL/6 J strain. In contrast, Polr3b in the hippocampus and Tnfsf13b in the prefrontal cortex of the DBA/2 J strain were up-regulated. Furthermore, C1qb, Cx3cl1, H2-d1, H2-k1, Polr3b, and Tnfsf13b were predicted to be associated with various behavioral and brain morphological features across the eight inbred strains. Importantly, the C1qb mRNA level was confirmed to be significantly correlated with the sociability in DBA/2 J but not in C57BL/6 J mice. Conclusions: Our study provided evidence on the association of immune gene network(s) with the brain development and behavior in animals and revealed neurobiological functions of novel brain immune genes that may contribute to social deficiency in animal models of neuropsychiatric disorders. C1 [Ma, Li; Piirainen, Sami; Kulesskaya, Natalia; Rauvala, Heikki; Tian, Li] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. [Tian, Li] Beijing Huilongguan Hosp, Psychiat Res Ctr, Beijing 100096, Changping, Peoples R China. RP Tian, L (reprint author), Univ Helsinki, Ctr Neurosci, Viikinkaari 4, FIN-00014 Helsinki, Finland. EM li.tian@helsinki.fi FU Academy of Finland [1273108]; National Natural Science Foundation of China [81461130016]; European Commission [602919]; Integrative Life Science graduate program of the University of Helsinki; Ida Montinin foundation; TEKES, Finland FX This study is supported by the Academy of Finland Project No. 1273108, National Natural Science Foundation of China Project No. 81461130016, and European Commission FP7/Cooperation sub-programme/HEALTH-2013-Innovation Grant No. 602919 to LT. LM is supported by the Integrative Life Science graduate program of the University of Helsinki, Ida Montinin foundation, and Academy of Finland. SP is supported by the Academy of Finland. NK and HR are supported by TEKES, Finland. 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Genetic linkage or environmental factors were proposed as sources for pathogenesis of autism. BTBR T+tf/J (BTBR) mice were reported as an appropriate animal model for autism investigation because of their similarities in behavioral abnormalities with human autistic subjects. The aim of this study was to evaluate expression levels of proteins involved with brain development at fetal stage of BTBR mice. FVB/NJ mice were used as a control strain because of their social behaviors. Level of fetal brain immunoglobulin (Ig) G deposit was also evaluated. Fetal brains were obtained at d 18 of gestational period. Thirty-one and 27 fetuses were obtained from 3 pregnant BTBR and FVB dams, respectively. The level of glial fibrillary acidic protein expression was significantly lower in fetal brains of BTBR than FVB/NJ mice. Expression of brain-derived neurotrophic factor and myelin basic protein was significantly more upregulated in BTBR than in FVB/NJ mice. 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[Elkayam, Elad; Joshua-Tor, Leemor] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA. [Jaber, Nadia; Zong, Wei-Xing] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Marks, Michael S.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Marks, Michael S.] Childrens Hosp Philadelphia, Lab Med, Philadelphia, PA 19104 USA. [Marks, Michael S.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Marks, Michael S.] Univ Penn, Lab Med & Physiol, Philadelphia, PA 19104 USA. RP Trotman, LC (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. 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Cell PD APR 16 PY 2015 VL 58 IS 2 BP 255 EP 268 DI 10.1016/j.molcel.2015.03.011 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CG4AR UT WOS:000353222900008 PM 25866245 ER PT J AU Esposito, G Setoh, P Yoshida, S Kuroda, KO AF Esposito, Gianluca Setoh, Peipei Yoshida, Sachine Kuroda, Kumi O. TI The calming effect of maternal carrying in different mammalian species SO FRONTIERS IN PSYCHOLOGY LA English DT Review DE maternal carrying; mother-infant interaction; mother-child relations; mother-infant bonding; transport response; attachment ID TRANSPORT RESPONSE; RAT PUPS; AUTISM; MOTHER; DIAGNOSIS; CONTACT; HUMANS; GAIT; MICE AB Attachment theory postulates that mothers and their infants possess some basic physiological mechanisms that favor their dyadic interaction and bonding. Many studies have focused on the maternal physiological mechanisms that promote attachment (e.g., mothers' automatic responses to infant faces and/or cries), and relatively less have examined infant physiology. Thus, the physiological mechanisms regulating infant bonding behaviors remain largely undefined. This review elucidates some of the neurobiological mechanisms governing social bonding and cooperation in humans by focusing on maternal carrying and its beneficial effect on mother infant interaction in mammalian species (e.g., in humans, big cats, and rodents). These studies show that infants have a specific calming response to maternal carrying. A human infant carried by his/her walking mother exhibits a rapid heart rate decrease, and immediately stops voluntary movement and crying compared to when he/she is held in a sitting position. Furthermore, strikingly similar responses were identified in mouse rodents, who exhibit immobility, diminished ultra-sonic vocalizations and heart rate. In general, the studies described in the current review demonstrate the calming effect of maternal carrying to be comprised of a complex set of behavioral and physiological components, each of which has a specific postnatal time window and is orchestrated in a well-matched manner with the maturation of the infants. Such reactions could have been evolutionarily adaptive in mammalian mother infant interactions. The findings have implications for parenting practices in developmentally normal populations. In addition, we propose that infants' physiological response may be useful in clinical assessments as we discuss possible implications on early screening for child psychopathology (e.g., autism spectrum disorders and perinatal brain disorders). C1 [Esposito, Gianluca] Univ Trento, Dept Psychol & Cognit Sci, Affiliat Behav & Physiol Lab, I-38068 Rovereto, Italy. [Esposito, Gianluca; Setoh, Peipei] Nanyang Technol Univ, Div Psychol, Singapore 639798, Singapore. [Yoshida, Sachine] Toho Univ, Fac Med, Tokyo, Japan. [Yoshida, Sachine] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Saitama, Japan. [Kuroda, Kumi O.] RIKEN Brain Sci Inst, Unit Affiliat Social Behav Unit, Saitama, Japan. RP Esposito, G (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Affiliat Behav & Physiol Lab, Corso Bettini 31, I-38068 Rovereto, Italy. EM gianluca.esposito@unitn.it FU Japan Society for the Promotion of Science [24730563, 2402747]; FP7 PEOPLE-Marie Curie Career Integration [PCIG14-GA-2013-630166]; Intramural Research Program of the Humanities and Social Sciences School, Nanyang Technological University FX This research was supported by the Grant-in-aid for Scientific Research from Japan Society for the Promotion of Science (Projects #24730563 and #2402747), FP7 PEOPLE-Marie Curie Career Integration Grants (PCIG14-GA-2013-630166), and the Intramural Research Program of the Humanities and Social Sciences School, Nanyang Technological University. 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PD APR 16 PY 2015 VL 6 AR 445 DI 10.3389/fpsyg.2015.00445 PG 6 WC Psychology, Multidisciplinary SC Psychology GA CG0JS UT WOS:000352953400001 PM 25932017 ER PT J AU Codina-Sola, M Rodriguez-Santiago, B Homs, A Santoyo, J Rigau, M Aznar-Lain, G del Campo, M Gener, B Gabau, E Botella, MP Gutierrez-Arumi, A Antinolo, G Perez-Jurado, LA Cusco, I AF Codina-Sola, Marta Rodriguez-Santiago, Benjamin Homs, Aida Santoyo, Javier Rigau, Maria Aznar-Lain, Gemma del Campo, Miguel Gener, Blanca Gabau, Elisabeth Pilar Botella, Maria Gutierrez-Arumi, Armand Antinolo, Guillermo Alberto Perez-Jurado, Luis Cusco, Ivon TI Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders SO MOLECULAR AUTISM LA English DT Article DE ASD; Whole-exome sequencing; CNV; SNV ID DE-NOVO MUTATIONS; GAIN-OF-FUNCTION; INTELLECTUAL DISABILITY; DIFFERENTIAL EXPRESSION; MENTAL-RETARDATION; MISSENSE MUTATIONS; IMPRINTED GENES; IDENTIFICATION; GENETICS; VARIANTS AB Background: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. Methods: We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. Results: We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. Conclusions: Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression. C1 [Codina-Sola, Marta; Homs, Aida; Rigau, Maria; del Campo, Miguel; Gutierrez-Arumi, Armand; Alberto Perez-Jurado, Luis; Cusco, Ivon] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona 08003, Spain. [Codina-Sola, Marta; Homs, Aida; Gutierrez-Arumi, Armand; Alberto Perez-Jurado, Luis; Cusco, Ivon] Hosp del Mar, Res Inst IMIM, Barcelona 08003, Spain. [Codina-Sola, Marta; Homs, Aida; del Campo, Miguel; Gutierrez-Arumi, Armand; Antinolo, Guillermo; Alberto Perez-Jurado, Luis; Cusco, Ivon] Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Madrid 28029, Spain. [Rodriguez-Santiago, Benjamin] Quantitat Genom Med Labs qGenom, Barcelona 08003, Spain. [Santoyo, Javier; Antinolo, Guillermo] Genom & Bioinformat Platform Andalusia, Med Genome Project, Seville 41092, Spain. [Aznar-Lain, Gemma] Hosp del Mar, Pediat Neurol, Barcelona 08003, Spain. [del Campo, Miguel] Hosp Valle De Hebron, Serv Genet, Barcelona 08015, Spain. [Gener, Blanca] Hosp Univ Cruces, BioCruces Hlth Res Inst, Genet Serv, Baracaldo 48093, Bizkaia, Spain. [Gabau, Elisabeth] Corp Sanitaria Parc Tauli, Serv Pediat, Sabadell 08208, Spain. [Pilar Botella, Maria] Hosp Txagorritxu, Pediat Neurol, Vitoria 01009, Spain. [Antinolo, Guillermo] Univ Seville, CSIC, Univ Hosp Virgen del Rocio, Inst Biomed Seville IBIS,Dept Genet Reprod & Feta, Seville 41013, Spain. RP Perez-Jurado, LA (reprint author), Univ Pompeu Fabra, Dept Expt & Hlth Sci, C Doctor Aiguader 88,422, Barcelona 08003, Spain. EM luis.perez@upf.edu; ivon.cusco@upf.edu FU Spanish Ministry of Health - FEDER [FIS PI1002512, PI1302481, PI1300823]; Fundacion Alicia Koplowitz; Generalitat de Catalunya [2014SGR1468]; 'Subprograma de actuaciones Cientificas y Tecnologicas en Parques Cientificos y Tecnologicos' (ACTEPARQ); 'Programa Nacional de Proyectos de investigacion Aplicada', I + D + i; FEDER FX We would like to thank the patients and their families for their support. This work was funded by grants from the Spanish Ministry of Health (FIS PI1002512, PI1302481, and PI1300823 cofunded by FEDER), Fundacion Alicia Koplowitz and Generalitat de Catalunya (2014SGR1468). The 'Medical Genome Project' is a joint initiative of the Consejeria de Salud de la Junta de Andalucia and Roche, supported by the 'Programa Nacional de Proyectos de investigacion Aplicada', I + D + i 2008, 'Subprograma de actuaciones Cientificas y Tecnologicas en Parques Cientificos y Tecnologicos' (ACTEPARQ 2009) and FEDER. The CIBER de Enfermedades Raras is an initiative of the ISCIII. CDTI FEDER-Innterconecta EXP00052887/ITC-20111037. 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TI Thimerosal: Clinical, epidemiologic and biochemical studies SO CLINICA CHIMICA ACTA LA English DT Review DE Thimerosal; Ethylmercury; Humans; Neurodevelopment ID HEPATITIS-B VACCINATION; NEURODEVELOPMENTAL DISORDERS; CONTAINING VACCINES; NEUROPSYCHOLOGICAL OUTCOMES; AUTISTIC DISORDERS; MERCURY LEVELS; UNITED-STATES; US CHILDREN; CELL-DEATH; EXPOSURE AB Introduction: Thimerosal (or Thiomersal) is a trade name for an organomercurial compound (sodium ethylmercury (Hg) thiosalicylate) that is 49.55% Hg by weight, which rapidly decomposes in aqueous saline solutions into ethyl-Hg hydroxide and ethyl-Hg chloride. Developed in 1927, it has been and is still being used as a preservative in some cosmetics, topical pharmaceuticals, and biological drug products, including vaccines. Concerns have been voiced about its use because it is toxic to human cells. Although it is banned in several countries, it continues to be added to some vaccines in the United States and many vaccines in the developing world. Discussion: This critical review focuses on the clinical, epidemiological, and biochemical studies of adverse effects from Thimerosal in developing humans. This review will include research that examines fetal, infant, and childhood death; birth defects; neurodevelopmental testing deficits in children; and neurodevelopmental disorders (attention deficit/hyperactivity disorder, autism spectrum disorder, tic disorder, and specific developmental delays). The review will also look at the research that examined the outcomes of acute accidental ethyl-Hg poisoning in humans. The studies that examine the underlying biochemical insights into the neuronal cellular damage will also be explored. Conclusion: The culmination of the research that examines the effects of Thimerosal in humans indicates that it is a poison at minute levels with a plethora of deleterious consequences, even at the levels currently administered in vaccines. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Geier, David A.; Kern, Janet K.; Geier, Mark R.] Inst Chron Illnesses Inc, Silver Spring, MD 20905 USA. [King, Paul G.; Sykes, Lisa K.] CoMeD Inc, Silver Spring, MD 20905 USA. [Hooker, Brian S.] Simpson Univ, Dept Biol, Redding, CA 96001 USA. [Dorea, Jose G.] Univ Brasilia, Hlth Sci, BR-70919970 Brasilia, DF, Brazil. RP Kern, JK (reprint author), 14 Redgate Ct, Silver Spring, MD 20905 USA. 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Chim. Acta PD APR 15 PY 2015 VL 444 BP 212 EP 220 DI 10.1016/j.cca.2015.02.030 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CG1BH UT WOS:000353007500038 PM 25708367 ER PT J AU Pedrotti, S Giudice, J Dagnino-Acosta, A Knoblauch, M Singh, RK Hanna, A Mo, QX Hicks, J Hamilton, S Cooper, TA AF Pedrotti, Simona Giudice, Jimena Dagnino-Acosta, Adan Knoblauch, Mark Singh, Ravi K. Hanna, Amy Mo, Qianxing Hicks, John Hamilton, Susan Cooper, Thomas A. TI The RNA-binding protein Rbfox1 regulates splicing required for skeletal muscle structure and function SO HUMAN MOLECULAR GENETICS LA English DT Article ID SARCOPLASMIC-RETICULUM; IN-VIVO; SATELLITE CELLS; GENOME-WIDE; HITS-CLIP; EXPRESSION; BRAIN; AUTISM; MOUSE; GENE AB The Rbfox family of RNA-binding proteins is highly conserved with established roles in alternative splicing (AS) regulation. High-throughput studies aimed at understanding transcriptome remodeling have revealed skeletal muscle as displaying one of the largest number of AS events. This finding is consistent with requirements for tissue-specific protein isoforms needed to sustain muscle-specific functions. Rbfox1 is abundant in vertebrate brain, heart and skeletal muscle. Genome-wide genetic approaches have linked the Rbfox1 gene to autism, and a brain-specific knockout mouse revealed a critical role for this splicing regulator in neuronal function. Moreover, a Caenorhabditis elegans Rbfox1 homolog regulates muscle-specific splicing. To determine the role of Rbfox1 in muscle function, we developed a conditional knockout mouse model to specifically delete Rbfox1 in adult tissue. We show that Rbfox1 is required for muscle function but a >70% loss of Rbfox1 in satellite cells does not disrupt muscle regeneration. Deep sequencing identified aberrant splicing of multiple genes including those encoding myofibrillar and cytoskeletal proteins, and proteins that regulate calcium handling. Ultrastructure analysis of Rbfox1(-/-) muscle by electron microscopy revealed abundant tubular aggregates. Immunostaining showed mislocalization of the sarcoplasmic reticulum proteins Serca1 and Ryr1 in a pattern indicative of colocalization with the tubular aggregates. Consistent with mislocalization of Serca1 and Ryr1, calcium handling was drastically altered in Rbfox1(-/-) muscle. Moreover, muscle function was significantly impaired in Rbfox1(-/-) muscle as indicated by decreased force generation. These results demonstrate that Rbfox1 regulates a network of AS events required to maintain multiple aspects of muscle physiology. C1 [Pedrotti, Simona; Giudice, Jimena; Singh, Ravi K.; Hicks, John; Cooper, Thomas A.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Cooper, Thomas A.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Dagnino-Acosta, Adan; Knoblauch, Mark; Hanna, Amy; Hamilton, Susan; Cooper, Thomas A.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Mo, Qianxing] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Mo, Qianxing] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hicks, John] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Hicks, John] Texas Childrens Hosp, Houston, TX 77030 USA. RP Cooper, TA (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza,Room 268B, Houston, TX 77030 USA. EM tcooper@bcm.edu FU NIH [R01HL045565, R01AR060733, R01AR045653, T32 HL007676]; Muscular Dystrophy Association; BCM: Genomic and RNA Profiling Core; Integrated Microscopy Core [HD007495, DK56338, CA125123]; Baculovirus/Monoclonal Antibody Facility [P30 CA125123]; [R01AR053349]; [R01AR041802] FX This project is funded by the NIH R01HL045565, R01AR060733 and R01AR045653 (T.A.C.) and the Muscular Dystrophy Association (T.A.C.); R01AR053349, R01AR041802 and NIH T32 HL007676 to S.H. This project was supported by three cores at BCM: Genomic and RNA Profiling Core (Lisa D. White), Integrated Microscopy Core (HD007495, DK56338 and CA125123) (Michael Mancini), and Baculovirus/Monoclonal Antibody Facility (P30 CA125123). 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PD APR 15 PY 2015 VL 24 IS 8 BP 2360 EP 2374 DI 10.1093/hmg/ddv003 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1WM UT WOS:000353066200021 PM 25575511 ER PT J AU Shimamoto, C Ohnishi, T Maekawa, M Watanabe, A Ohba, H Arai, R Iwayama, Y Hisano, Y Toyota, T Toyoshima, M Suzuki, K Shirayama, Y Nakamura, K Mori, N Owada, Y Kobayashi, T Yoshikawa, T AF Shimamoto, Chie Ohnishi, Tetsuo Maekawa, Motoko Watanabe, Akiko Ohba, Hisako Arai, Ryoichi Iwayama, Yoshimi Hisano, Yasuko Toyota, Tomoko Toyoshima, Manabu Suzuki, Katsuaki Shirayama, Yukihiko Nakamura, Kazuhiko Mori, Norio Owada, Yuji Kobayashi, Tetsuyuki Yoshikawa, Takeo TI Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies (vol 23, pg 6495, 2014) SO HUMAN MOLECULAR GENETICS LA English DT Correction CR Shimamoto Chie, 2014, Hum Mol Genet, V23, P6495, DOI 10.1093/hmg/ddu369 NR 1 TC 0 Z9 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2015 VL 24 IS 8 BP 2409 EP 2409 DI 10.1093/hmg/ddv011 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CG1WM UT WOS:000353066200025 PM 25655139 ER PT J AU Gilani, SZ Tan, DW Russell-Smith, SN Maybery, MT Mian, A Eastwood, PR Shafait, F Goonewardene, M Whitehouse, AJO AF Gilani, Syed Zulqarnain Tan, Diana Weiting Russell-Smith, Suzanna N. Maybery, Murray T. Mian, Ajmal Eastwood, Peter R. Shafait, Faisal Goonewardene, Mithran Whitehouse, Andrew J. O. TI Sexually dimorphic facial features vary according to level of autistic-like traits in the general population SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Autism spectrum disorder; Hypermasculinisation; Gender defiant disorder; Facial features; Masculinity; Femininity; Raine study ID MALE BRAIN THEORY; PERVASIVE DEVELOPMENTAL DISORDERS; FETAL TESTOSTERONE; SPECTRUM QUOTIENT; DIGIT RATIO; MORPHOLOGY; ADULTS; FACE; ADOLESCENCE; DIFFERENCE AB Background: In a recent study, Bejerot et al. observed that several physical features (including faces) of individuals with an autism spectrum disorder (ASD) were more androgynous than those of their typically developed counterparts, suggesting that ASD may be understood as a 'gender defiant' disorder. These findings are difficult to reconcile with the hypermasculinisation account, which proposes that ASD may be an exaggerated form of cognitive and biological masculinity. The current study extended these data by first identifying six facial features that best distinguished males and females from the general population and then examining these features in typically developing groups selected for high and low levels of autistic-like traits. Methods: In study 1, three-dimensional (3D) facial images were collected from 208 young adult males and females recruited from the general population. Twenty-three facial distances were measured from these images and a gender classification and scoring algorithm was employed to identify a set of six facial features that most effectively distinguished male from female faces. In study 2, measurements of these six features were compared for groups of young adults selected for high (n = 46) or low (n = 66) levels of autistic-like traits. Results: For each sex, four of the six sexually dimorphic facial distances significantly differentiated participants with high levels of autistic-like traits from those with low trait levels. All four features were less masculinised for high-trait males compared to low-trait males. Three of four features were less feminised for high-trait females compared to low-trait females. One feature was, however, not consistent with the general pattern of findings and was more feminised among females who reported more autistic-like traits. Based on the four significantly different facial distances for each sex, discriminant function analysis correctly classified 89.7% of the males and 88.9% of the females into their respective high-and low-trait groups. Conclusions: The current data provide support for Bejerot et al.'s androgyny account since males and females with high levels of autistic-like traits generally showed less sex-typical facial features than individuals with low levels of autistic-like traits. C1 [Gilani, Syed Zulqarnain; Mian, Ajmal; Shafait, Faisal] Univ Western Australia, Sch Comp Sci & Software Engn, Perth, WA 6009, Australia. [Tan, Diana Weiting; Russell-Smith, Suzanna N.; Maybery, Murray T.; Whitehouse, Andrew J. O.] Univ Western Australia, Sch Psychol, Neurocognit Dev Unit, Perth, WA 6009, Australia. [Eastwood, Peter R.] Univ Western Australia, Sch Anat Physiol & Human Biol, Perth, WA 6009, Australia. [Goonewardene, Mithran] Univ Western Australia, Oral Hlth Ctr Western Australia, Sch Dent, Perth, WA 6009, Australia. [Tan, Diana Weiting; Whitehouse, Andrew J. O.] Univ Western Australia, Telethon Kids Inst, Perth, WA 6008, Australia. RP Tan, DW (reprint author), Univ Western Australia, Sch Psychol, Neurocognit Dev Unit, 35 Stirling Highway, Perth, WA 6009, Australia. EM diana.tan@research.uwa.edu.au FU University of Western Australia (UWA); Curtin University; UWA Faculty of Medicine, Dentistry and Health Sciences; Raine Medical Research Foundation; Telethon Kids Institute; Women's and Infants Research Foundation; National Health and Medical Research Council (NHMRC) [1021105, 1021858, 1044840]; NHMRC [APP1003424, 1004065, 513704]; UWA Faculty of Engineering, Computing and Mathematics; International Postgraduate Research Scholarships in Australia; Australian Research Council (ARC) [DP120104713, DP110102399, LP 110201008] FX Core Management of the Raine Study is 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 Kids Institute, and the Women's and Infants Research Foundation. The authors acknowledge National Health and Medical Research Council (NHMRC) project grants (#1021105, #1021858, #1044840) towards funding this data collection. The writing of this article was also supported by an NHMRC project grant (#APP1003424) and the UWA Faculty of Engineering, Computing and Mathematics. SZG and DWT are supported by International Postgraduate Research Scholarships in Australia. SRS is partly supported by an Australian Research Council (ARC) Discovery grant (DP120104713). AM (DP110102399) and FS (LP 110201008) are supported by ARC. AJOW is funded by a Career Development Fellowship from the NHMRC (#1004065). PRE is supported by a NHMRC Senior Research Fellowship (#513704). The authors are extremely grateful to the UWA participants, Raine Study participants and to the Raine Study team for cohort management and data collection. 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PD APR 15 PY 2015 VL 7 AR 14 DI 10.1186/s11689-015-9109-6 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CG3OX UT WOS:000353190600001 PM 25901187 ER PT J AU Skogan, AH Zeiner, P Egeland, J Urnes, AG Reichborn-Kjennerud, T Aase, H AF Skogan, Annette Holth Zeiner, Pal Egeland, Jens Urnes, Anne-Grethe Reichborn-Kjennerud, Ted Aase, Heidi TI Parent ratings of executive function in young preschool children with symptoms of attention-deficit/-hyperactivity disorder SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE ADHD; Executive function; Preschool; BRIEF-P; Inhibition; Working memory ID AUTISM SPECTRUM DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; INDIVIDUAL-DIFFERENCES; EMOTION REGULATION; ADHD; PERFORMANCE; ANXIETY; VALIDITY; INVENTORY; ADOLESCENTS AB Background: Recent research has demonstrated that deficits in basic, self-regulatory processes, or executive function (EF), may be related to symptoms of attention-deficit/hyperactivity disorder (ADHD) already during the preschool period. As the majority of studies investigating these relations in young children have been based primarily on clinically administered tests, it is not clear how early symptoms of ADHD may be related to observations of EF in an everyday context. The preschool version of the Behavior Rating Inventory of Executive Function (BRIEF-P) was developed to provide information about EF through observable, behavioral manifestations of self-regulation, and is the most commonly used rating scale for EF assessment in children. Methods: Relations between symptoms of ADHD reported in the Preschool Age Psychiatric Assessment interview (PAPA), and EF as measured by the BRIEF-P (parent form), were investigated in a large, nonreferred sample of preschool children (37-47 months, n = 1134) recruited from the Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of Public Health. The inventory's discriminative ability was examined in a subsample consisting of children who met the diagnostic criteria for either ADHD, oppositional defiant disorder (ODD) or anxiety disorder, and typically developing controls (n = 308). The four groups were also compared with regard to patterns of EF difficulties reported in the BRIEF-P. Results: Of the five BRIEF-P subscales, Inhibit and Working Memory were the two most closely related to ADHD symptoms, together explaining 38.5% of the variance in PAPA symptom ratings. Based on their scores on the Inhibit and Working Memory subscales (combined), 86.4% of the children in the ADHD and TD groups were correctly classified. ADHD symptoms were associated with more severe difficulties across EF domains, and a different EF profile in comparison to children with other symptoms (anxiety, ODD) and to typically developing controls. Conclusions: Early symptoms of ADHD were linked to parent-reported difficulties primarily within inhibition and working memory, suggesting that deficiencies within these two EF domains characterize early forms of ADHD. Our findings support the clinical utility of the BRIEF-P as a measure of EF in young preschool children with symptoms of ADHD. C1 [Skogan, Annette Holth; Zeiner, Pal] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway. [Egeland, Jens] Univ Oslo, Inst Psychol, N-0317 Oslo, Norway. [Egeland, Jens] Vestfold Hosp Trust, Tonsberg, Norway. [Urnes, Anne-Grethe] Eastern & Southern Norway RBUP, Reg Ctr Child & Adolescent Mental Hlth, N-0405 Oslo, Norway. [Reichborn-Kjennerud, Ted; Aase, Heidi] Norwegian Inst Publ Hlth, Div Mental Hlth, N-0403 Oslo, Norway. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Clin Med, N-0317 Oslo, Norway. RP Skogan, AH (reprint author), Oslo Univ Hosp, Div Mental Hlth & Addict, Pb 4959,Nydalen 0424, N-0424 Oslo, Norway. EM annette.holth.skogan@ous-hf.no FU Norwegian South Eastern Health Region [2010081]; Norwegian Ministry of Health; Norwegian Health Directorate; South-Eastern Health Region; G&PJ Sorensen Fund for Scientific Research; Norwegian Resource Centre for ADHD; Ministry of Education and Research; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1, NO1-ES-75558]; Norwegian Research Council/FUGE [151918/S10] FX The present study was supported by a grant from the Norwegian South Eastern Health Region, grant no. 2010081. The ADHD study, from which the present data were drawn, was supported by funds and grants from the Norwegian Ministry of Health, the Norwegian Health Directorate, the South-Eastern Health Region, G&PJ Sorensen Fund for Scientific Research, and from the Norwegian Resource Centre for ADHD, Tourette syndrome and Narcolepsy. MoBa is supported by the Norwegian Ministry of Health, the Ministry of Education and Research, NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1, contract no NO1-ES-75558), and the Norwegian Research Council/FUGE (grant no. 151918/S10). We are grateful to the children and their parents for their efforts in taking part in the study, and to the staff of the ADHD study. The authors also wish to thank Peter Isquith PhD for his valuable input during the preparation of this paper. 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Brain Funct. PD APR 15 PY 2015 VL 11 AR 16 DI 10.1186/s12993-015-0060-1 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CG1HE UT WOS:000353022900001 PM 25889243 ER PT J AU Yan, CL Zhang, J Hou, Y AF Yan, Chun-Lin Zhang, Ji Hou, Yong TI Decreased plasma levels of lipoxin A4 in children with autism spectrum disorders SO NEUROREPORT LA English DT Article DE autism spectrum disorders; Chinese; lipoxin A4 ID NEUROTROPHIC FACTOR; CHINESE CHILDREN; LIPID MEDIATORS; INFLAMMATION; A(4); RESOLUTION; PHASE; ACID AB The aim of this study was to evaluate the plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation in Chinese children with autism spectrum disorders (ASD). From January 2013 to June 2014, a total of 150 children (75 confirmed ASD cases and 75 their age-matched and sex-matched control cases) participated in this study after consent was obtained from their parents. Clinical information was collected. Plasma levels of LXA4 were measured at baseline. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean plasma levels of LXA4 were significantly lower in autistic children compared with the normal children (P< 0.0001). There was a significant negative relationship between circulating LXA4 levels and severity of autism evaluated by Childhood Autism Rating Scale scores (P= 0.006) after adjustment for the possible covariates. On the basis of the receiver operating characteristic curve, the optimal cutoff value of plasma LXA4 levels as an indicator for an auxiliary diagnosis of ASD was projected to be 81.5 pg/ml, which yielded a sensitivity of 90.7% and a specificity of 76.0%, with the area under the curve at 0.911 (95% confidence interval, 0.867-0.955). These results suggested that autistic children had lower plasma LXA4 levels, suggesting an increased susceptibility to recurring inflammation in these samples. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Yan, Chun-Lin] Hebei North Univ, Basic Med Coll, Zhangjiakou, Hebei Province, Peoples R China. [Zhang, Ji; Hou, Yong] Hebei North Univ, Dept Pharmacol, Zhangjiakou, Hebei Province, Peoples R China. RP Yan, CL (reprint author), 10 Zuanshi South Rd, Zhangjiakou 075000, Hebei Province, Peoples R China. 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A. Lucas, D. Kleven, G. A. TI An ecologically relevant guinea pig model of fetal behavior SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Prenatal behavior; Fetal movement; Interlimb coordination; Restraint stress; Cortisol ID CAVIA-PORCELLUS; PRENATAL STRESS; ANIMAL-MODELS; INFANT RATS; FETUS; EMERGENCE; MOVEMENTS; RESPONSES; CORTISOL; SLEEP AB The laboratory guinea pig, Cavia porcellus, shares with humans many similarities during pregnancy and prenatal development, including precocial offspring and social dependence. These similarities suggest the guinea pig as a promising model of fetal behavioral development as well. Using innovative methods of behavioral acclimation, fetal offspring of female IAF hairless guinea pigs time mated to NIH multicolored Hartley males were observed longitudinally without restraint using noninvasive ultrasound at weekly intervals across the 10 week gestation. To ensure that the ultrasound procedure did not cause significant stress, salivary cortisol was collected both before and after each observation. Measures of fetal spontaneous movement and behavioral state were quantified from video recordings from week 3 through the last week before birth. Results from prenatal quantification of Interlimb Movement Synchrony and state organization reveal guinea pig fetal development to be strikingly similar to that previously reported for other rodents and preterm human infants. Salivary cortisol readings taken before and after sonography did not differ at any observation time point. These results suggest this model holds translational promise for studying the prenatal mechanisms of neurobehavioral development, including those that may result from adverse events. Because the guinea pig is a highly social mammal with a wide range of socially oriented vocalizations, this model may also have utility for studying the prenatal origins and trajectories of developmental disabilities with social-emotional components, such as autism. (C) 2015 Elsevier B.V. All rights reserved. C1 [Bellinger, S. A.; Lucas, D.; Kleven, G. A.] Wright State Univ, Dept Psychol, Dayton, OH 45435 USA. [Bellinger, S. A.; Lucas, D.] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA. RP Kleven, GA (reprint author), Wright State Univ, Dept Psychol, 3640 Colonel Glenn Hwy, Dayton, OH 45435 USA. EM gale.kleven@wright.edu FU [NR010798]; [GM086257] FX The authors thank Ryan Rakoczy, Chris Fitch, Jessica Lane, Neena Zwier, and Angela Compton, for help with animal handling. Special thanks to Emily Dudley, D.V.M. for her veterinary expertise, and to the Wright State University Laboratory of Animal Resource technicians for the care of our guinea pigs. S. A. Bellinger is now affiliated with the Department of Psychology at Florida Atlantic University, Boca Raton, FL. This research was supported by grants NR010798 to GAK and GM086257 to SAB and DL. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research, the National Heart Lung and Blood Institute, or the National Institutes of Health. Portions of this work were previously presented at the annual meeting of the International Society for Developmental Psychobiology (New Orleans, LA, 2012), and in 2013 at the annual meeting of the Society for Neuroscience (San Diego, CA). 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Brain Res. PD APR 15 PY 2015 VL 283 BP 175 EP 183 DI 10.1016/j.bbr.2015.01.047 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CE6UF UT WOS:000351973000022 PM 25655512 ER PT J AU Olivier, JDA Akerud, H Poromaa, IS AF Olivier, Jocelien D. A. Akerud, Helena Poromaa, Inger Sundstrom TI Antenatal depression and antidepressants during pregnancy: Unraveling the complex interactions for the offspring SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Antenatal depressro; Antidepressants; SSRI; Pregnancy; Neurodevelopment; Epigenetics ID SEROTONIN REUPTAKE INHIBITORS; EXPOSED IN-UTERO; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; CORTICOTROPIN-RELEASING HORMONE; CORTICOSTEROID-BINDING GLOBULIN; MATERNAL PSYCHOLOGICAL DISTRESS; NATIONAL-COMORBIDITY-SURVEY; AUTISM SPECTRUM DISORDERS; PROMOTER GENOTYPE SLC6A4; INFANT TEMPERAMENT AB During pregnancy the risk for a woman to develop a depressive episode is as high as 20%. Antenatal depression is not harmless for the developing child as several changes, including neurodevelopmental alterations, have been reported. Sometimes it is unavoidable to treat a pregnant mother with antidepressants, especially when she is suicidal. Currently, selective serotonin reuptake inhibitors (SSRls) are the pharmacological choice of antidepressant treatment. SSRIs do not cause gross teratogenic alterations and are generally considered safe for use in pregnancy. However, although SSRls may relieve the maternal symptoms, they definitively cross the placenta partially influencing the neurodevelopment of the fetus. In this review an overview is given of the effects on the offspring of maternal antenatal depression and the putative neurodevelopmental effects of SSRI treatment during pregnancy. Although we primarily focus on human data, some animal data are discussed to describe possible mechanisms on how SSRls are affecting underlying biological mechanisms associated with depression. In summary, maternal depression may have long-lasting effects on the offspring, whereas prenatal SSRI exposure also increases the risk for long-lasting effects. It remains to be determined whether the effects found after SSRI treatment in pregnant women are only due to the SSRI exposure or if the underlying depression is also contributing to these effects. The possibility of epigenetic alterations as one of the underlying mechanisms that is altered by SSRI exposure is discussed. However much more research in this area is needed to explain the exact role of epigenetic mechanisms in SSRI exposure during pregnancy. (C) 2014 Elsevier BA/. All rights reserved, C1 [Olivier, Jocelien D. A.; Akerud, Helena; Poromaa, Inger Sundstrom] Uppsala Univ, Dept Womens & Childrens Hlth, SE-75185 Uppsala, Sweden. [Olivier, Jocelien D. A.] Karolinska Inst, Ctr Gender Med, Stockholm, Sweden. [Olivier, Jocelien D. A.] Univ Groningen, Dept Behav Physiol, Ctr Behav & Neurosci, Groningen, Netherlands. RP Olivier, JDA (reprint author), Uppsala Univ, Dept Womens & Childrens Hlth, SE-75185 Uppsala, Sweden. EM jocelien.olivier@kbh.uu.se FU Swedish Research Council [K2014-54X-20642-07-4]; Marianne and Marcus Wallenberg Foundation [2010:0031]; KI fonder research [2013fobi37758]; Soderstrom-Konigska [SLS-303881]; Svenska Lakaresallskapet [SLS-384001] FX This work was supported by grants from the Swedish Research Council, (Grant No. K2014-54X-20642-07-4) the Marianne and Marcus Wallenberg Foundation (2010:0031), KI fonder research (2013fobi37758), Soderstrom-Konigska (SLS-303881) and Svenska Lakaresallskapet (SLS-384001). 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J. Pharmacol. PD APR 15 PY 2015 VL 753 BP 257 EP 262 DI 10.1016/j.ejphar.2014.07.049 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CE6ND UT WOS:000351953200024 PM 25094036 ER PT J AU Micucci, JA Sperry, ED Martin, DM AF Micucci, Joseph A. Sperry, Ethan D. Martin, Donna M. TI Chromodomain Helicase DNA-Binding Proteins in Stem Cells and Human Developmental Diseases SO STEM CELLS AND DEVELOPMENT LA English DT Review ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; HUMAN CHARGE SYNDROME; EPILEPTIC ENCEPHALOPATHIES; INTELLECTUAL DISABILITY; CHROMATIN-STRUCTURE; TUMOR-SUPPRESSOR; PROSTATE-CANCER; GENE-EXPRESSION; DAMAGE RESPONSE AB Dynamic regulation of gene expression is vital for proper cellular development and maintenance of differentiated states. Over the past 20 years, chromatin remodeling and epigenetic modifications of histones have emerged as key controllers of rapid reversible changes in gene expression. Mutations in genes encoding enzymes that modify chromatin have also been identified in a variety of human neurodevelopmental disorders, ranging from isolated intellectual disability and autism spectrum disorder to multiple congenital anomaly conditions that affect major organ systems and cause severe morbidity and mortality. In this study, we review recent evidence that chromodomain helicase DNA-binding (CHD) proteins regulate stem cell proliferation, fate, and differentiation in a wide variety of tissues and organs. We also highlight known roles of CHD proteins in human developmental diseases and present current unanswered questions about the pleiotropic effects of CHD protein complexes, their genetic targets, nucleosome sliding functions, and enzymatic effects in cells and tissues. C1 [Micucci, Joseph A.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Sperry, Ethan D.; Martin, Donna M.] Univ Michigan, Sch Med, Med Scientist Training Program, Ann Arbor, MI USA. [Sperry, Ethan D.; Martin, Donna M.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA. [Martin, Donna M.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA. RP Martin, DM (reprint author), 3520A MSRBI,1150 West Med Ctr Dr,SPC 5652, Ann Arbor, MI 48109 USA. EM donnamm@umich.edu FU NIH Hearing, Balance, and Chemical Senses Training Grant [T32-DC000011]; NRSA [F31-DC013227]; University of Michigan Medical Scientist Training Program [NIH T32-GM007863]; NIH [R01-DC009410]; University of Michigan Donita B. Sullivan, MD Research Professorship Funds; [T32-HL007439] FX J.A.M. was supported by the NIH Hearing, Balance, and Chemical Senses Training Grant (T32-DC000011) and an Individual NRSA (F31-DC013227) and is currently supported by T32-HL007439. E.D.S. is a fellow of the University of Michigan Medical Scientist Training Program (NIH T32-GM007863) and is supported by T32-DC000011. D.M.M. is supported by NIH R01-DC009410 and the University of Michigan Donita B. Sullivan, MD Research Professorship Funds. 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TI Convergent Differential Regulation of SLIT-ROBO Axon Guidance Genes in the Brains of Vocal Learners SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE songbird; parrot; hummingbird; neural connectivity; axon guidance; vocal learning ID MELOPSITTACUS-UNDULATUS; CONTROL PATHWAYS; NEURAL PATHWAYS; ZEBRA FINCHES; BIRDS; ORGANIZATION; LANGUAGE; COMMUNICATION; BUDGERIGARS; FOREBRAIN AB Only a few distantly related mammals and birds have the trait of complex vocal learning, which is the ability to imitate novel sounds. This ability is critical for speech acquisition and production in humans, and is attributed to specialized forebrain vocal control circuits that have several unique connections relative to adjacent brain circuits. As a result, it has been hypothesized that there could exist convergent changes in genes involved in neural connectivity of vocal learning circuits. In support of this hypothesis, expanding on our related study (Pfenning et al. [2014] Science 346: 1256846), here we show that the forebrain part of this circuit that makes a relatively rare direct connection to brainstem vocal motor neurons in independent lineages of vocal learning birds (songbird, parrot, and hummingbird) has specialized regulation of axon guidance genes from the SLIT-ROBO molecular pathway. The SLIT1 ligand was differentially downregulated in the motor song output nucleus that makes the direct projection, whereas its receptor ROBO1 was developmentally upregulated during critical periods for vocal learning. Vocal nonlearning bird species and male mice, which have much more limited vocal plasticity and associated circuits, did not show comparable specialized regulation of SLIT-ROBO genes in their nonvocal motor cortical regions. These findings are consistent with SLIT and ROBO gene dysfunctions associated with autism, dyslexia, and speech sound language disorders and suggest that convergent evolution of vocal learning was associated with convergent changes in the SLIT-ROBO axon guidance pathway. J. Comp. Neurol. 523:892-906, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Wang, Rui; Chen, Chun-Chun; Hara, Erina; Rivas, Miriam V.; Roulhac, Petra L.; Howard, Jason T.; Chakraborty, Mukta; Jarvis, Erich D.] Duke Univ, Med Ctr, Dept Neurobiol, Howard Hughes Med Inst, Durham, NC 27710 USA. [Wang, Rui] Duke Univ, Inst Genome Sci & Policy, Computat Biol & Bioinformat Program, Durham, NC 27710 USA. [Wang, Rui] Beijing Prosperous Biopharm, Beijing 100085, Peoples R China. [Rivas, Miriam V.] Vet Affairs Med Ctr, Res Serv, Durham, NC 27710 USA. [Audet, Jean-Nicolas] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. RP Jarvis, ED (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Howard Hughes Med Inst, Durham, NC 27710 USA. EM jarvis@neuro.duke.edu RI Audet, Jean-Nicolas/P-2535-2014; Jarvis, Erich/A-2319-2008 OI Audet, Jean-Nicolas/0000-0002-0511-183X; Jarvis, Erich/0000-0001-8931-5049 FU National Institutes of Health; Howard Hughes Medical Institute FX Grant sponsor: National Institutes of Health (Director's Pioneer Award); Grant sponsor: the Howard Hughes Medical Institute (to E.D.J.). 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Dufour, Nicholas Hurlemann, Rene Saxe, Rebecca Adolphs, Ralph TI Amygdala lesions do not compromise the cortical network for false-belief reasoning SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE theory-of-mind; amygdala; lesions; false-belief; fMRI ID MONKEYS MACACA-MULATTA; SOCIAL COGNITION; TEMPOROPARIETAL JUNCTION; INDIVIDUAL-DIFFERENCES; FUNCTIONAL AMYGDALA; PREFRONTAL CORTEX; FRONTAL-CORTEX; MIND; DAMAGE; AUTISM AB The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. 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Getahun, Darios TI Association of Maternal Diabetes With Autism in Offspring SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SPECTRUM DISORDERS; ETHNIC DISPARITIES; GLUCOSE-TOLERANCE; CHILDHOOD AUTISM; OXIDATIVE STRESS; RISK-FACTORS; MELLITUS; PREGNANCY; OBESITY; METAANALYSIS AB IMPORTANCE Information about the association of maternal diabetes and autism spectrum disorders (ASDs) in offspring is limited, with no report on the importance of timing of exposure during gestation. OBJECTIVE To assess ASD risk associated with intrauterine exposure to preexisting type 2 diabetes and gestational diabetes mellitus (GDM) by gestational age at GDM diagnosis. DESIGN, SETTING, AND PATIENTS Retrospective longitudinal cohort study including 322 323 singleton children born in 1995-2009 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC health plan membership, death due to any cause, or December 31, 2012. Relative risks of ASD were estimated by hazard ratios (HRs) using Cox regression models adjusted for birth year. EXPOSURES Maternal preexisting type 2 diabetes (n = 6496), GDM diagnosed at 26 weeks' gestation or earlier (n = 7456) or after 26 weeks' gestation (n = 17 579), or no diabetes (n = 290 792) during the index pregnancy. MAIN OUTCOMES AND MEASURES Clinical diagnosis of ASD in offspring. RESULTS During follow-up, 3388 children were diagnosed as having ASD (115 exposed to preexisting type 2 diabetes, 130 exposed to GDM at <= 26 weeks, 180 exposed to GDM at >26 weeks, and 2963 unexposed). Unadjusted annual ASD incidences were 3.26, 3.02, 1.77, and 1.77 per 1000 among children of mothers with preexisting type 2 diabetes, GDM diagnosed at 26 weeks or earlier, GDM diagnosed after 26 weeks, and no diabetes, respectively. The birth year-adjusted HRs were 1.59(95% Cl, 1.29-1.95) for preexisting type 2 diabetes, 1.63(95% Cl, 1.35-1.97) for GDM diagnosed at 26 weeks or earlier, and 0.98 (95% Cl, 0.84-1.15) for GDM diagnosed after 26 weeks relative to no exposure. After adjustment for maternal age, parity, education, household income, race/ethnicity, history of comorbidity, and sex of the child, maternal preexisting type 2 diabetes was not significantly associated with risk of ASD in offspring (HR, 1.21; 95% Cl, 0.97-1.52), but GDM diagnosed at 26 weeks or earlier remained so (HR, 1.42; 95% Cl, 1.15-1.74). Antidiabetic medication exposure was not independently associated with ASD risk. Adjustment for a mother or older sibling with ASD in the full cohort and for maternal smoking, prepregnancy body mass index, and gestational weight gain in the subset with available data (n = 68 512) did not affect the results. CONCLUSIONS AND RELEVANCE In this large, multiethnic clinical cohort of singleton children born at 28 to 44 weeks' gestation, exposure to maternal GDM diagnosed by 26 weeks' gestation was associated with risk of ASD in offspring. C1 [Xiang, Anny H.; Wang, Xinhui; Martinez, Maya P.; Coleman, Karen J.; Getahun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Walthall, Johanna C.] Kaiser Permanente So Calif, Dept Psychiat, Pasadena, CA 91101 USA. [Curry, Edward S.] Kaiser Permanente So Calif, Dept Pediat, Pasadena, CA 91101 USA. [Page, Kathleen; Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol & Diabet, Los Angeles, CA 90033 USA. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. 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We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome. C1 [Martinez de Paz, Alexia; Vicente Sanchez-Mut, Jose; Samitier-Marti, Mireia; Petazzi, Paolo; Saez, Mauricio; Szczesna, Karolina; Huertas, Dori; Esteller, Manel; Ausio, Juan] Bellvitge Biomed Res Inst IDIBELL, PEBC, Barcelona, Catalonia, Spain. [Esteller, Manel] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Catalonia, Spain. [Esteller, Manel] ICREA, Barcelona, Catalonia, Spain. [Ausio, Juan] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. RP Esteller, M (reprint author), Bellvitge Biomed Res Inst IDIBELL, PEBC, Barcelona, Catalonia, Spain. EM emesteller@idibell.cat; jausio@uvic.ca FU European Community [PITN-GA2009-238242]; European Research Council [268626]; E-RARE EuroRETT network (Carlos III Health Institute) [PI071327]; Foundation Lejeune; MINECO [SAF2011 22803]; Catalan Association of Rett Syndrome; Health and Science Department of the Catalan Government (Generalitat de Catalunya); Canadian Institutes of Health Research (CIHR) [MOP-97878]; Catalan Institution for Research and Advanced Studies FX Funding was provided by the European Community's Seven Framework Programme (FP7/2007-2013) under grant agreement no PITN-GA2009-238242 DISCHROM project and by the European Research Council under grant agreement no. 268626 EPINORC project, E-RARE EuroRETT network (Carlos III Health Institute Project no PI071327), the Foundation Lejeune, MINECO Project no SAF2011 22803, the Catalan Association of Rett Syndrome, and the Health and Science Department of the Catalan Government (Generalitat de Catalunya) (M.E.). Canadian Institutes of Health Research (CIHR) [MOP-97878] grant (J.A.). M.E. is supported as a Catalan Institution for Research and Advanced Studies Research Professor. 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The verbal difficulties of children with SLI have been largely documented, and a growing number of studies suggest that these children may also have difficulties in processing non-verbal complex auditory stimuli (Corriveau et al., 2007: Brandt et al., 2012). In a recent study, we reported that a large proportion of children with SLI present deficits in music perception (Planchou et al., under revision). Little is known, however, about the singing abilities of children with SLI. In order to investigate whether or not the impairments in expressive language extend to the musical domain, we assessed singing abilities in eight children with SLI and 15 children with Typical Language Development (TLD) matched for age and non-verbal intelligence. To this aim, we designed a ludic activity consisting of two singing tasks: a pitch-matching and a melodic reproduction task. In the pitch-matching task, the children were requested to sing single notes. In the melodic reproduction task, children were asked to sing short melodies that were either familiar (FAM-SONG and FAM-TUNE conditions) or unfamiliar (UNFAM-TUNE condition). The analysis showed that children with SLI were impaired in the pitch-matching task, with a mean pitch error of 250 cents (mean pitch error for children with TLD: 154 cents). In the melodic reproduction task, we asked 30 healthy adults to rate the quality of the sung productions of the children on a continuous rating scale. The results revealed that singing of children with SLI received lower mean ratings than the children with TLD. Our findings thus indicate that children with SLI showed impairments in musical production and are discussed in light of a general auditory-motor dysfunction in children with SLI. C1 [Clement, Sylvain; Planchou, Clement; Samson, Severine] Univ Lille, UFR Psychol, Lab PSITEC, Neuropsychol Auditory Cognit Act Team, F-59653 Villeneuve Dascq, France. [Planchou, Clement; Motte, Jacques] Amer Mem Hosp, Pole Femme Mere Enfant, Neurol Pediat, Reims, France. [Beland, Renee] Univ Montreal, Ecole Orthophonie & Audiol, Montreal, PQ, Canada. [Samson, Severine] Grp Hosp Pitie Salpetriere, Unite Epilepsie, F-75634 Paris, France. RP Clement, S (reprint author), Univ Lille, UFR Psychol, BP60149,6 Rue Barreau, F-59653 Villeneuve Dascq, France. EM sylvain.clement@univ-lille3.fr FU Institut Universitaire de France; [ANR-09-BLAN-0310-02] FX The authors are grateful to the children who gave their time ensuring the study feasibility. This study has received funding from the French Ministry (ANR-09-BLAN-0310-02), and the Institut Universitaire de France to SS. 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Psychol. PD APR 13 PY 2015 VL 6 AR 420 DI 10.3389/fpsyg.2015.00420 PG 11 WC Psychology, Multidisciplinary SC Psychology GA CF8MT UT WOS:000352815800001 PM 25918508 ER PT J AU Zhang, R Huang, M Cao, ZJ Qi, JY Qiu, ZL Chiang, LY AF Zhang, Ran Huang, Min Cao, Zhijuan Qi, Jieyu Qiu, Zilong Chiang, Li-Yang TI MeCP2 plays an analgesic role in pain transmission through regulating CREB/miR-132 pathway SO Molecular Pain LA English DT Article DE MeCP2; Acute pain; SNI model; Spinal cord; p-CREB/miR-132 ID CPG-BINDING PROTEIN-2; PERIPHERAL-NERVE INJURY; RETT-SYNDROME; TRANSCRIPTIONAL REPRESSOR; MOLECULAR-MECHANISMS; DUPLICATION SYNDROME; NEURAL PLASTICITY; INDUCED MICRORNA; INFLAMMATION; SENSITIVITY AB Background: The Methyl CpG binding protein 2 gene (MeCP2 gene) encodes a critical transcriptional repressor and is widely expressed in mammalian neurons. MeCP2 plays a critical role in neuronal differentiation, neural development, and synaptic plasticity. Mutations and duplications of the human MECP2 gene lead to severe neurodevelopmental disorders, such as Rett syndrome and autism. In this study we investigate the role of MeCP2 in the spinal cord and found that MeCP2 plays an important role as an analgesic mediator in pain circuitry. Findings: Experiments using MeCP2 transgenic mice showed that overexpression of MeCP2 weakens both acute mechanical pain and thermal pain, suggesting an analgesic role of MeCP2 in acute pain transduction. We found that through p-CREB/miR-132 signaling cascade is involved in MeCP2-mediated pain transduction. We also examined the role of MeCP2 in chronic pain formation using spared nerve injury (SNI) model. Strikingly, we found that development of neuropathic pain attenuates in MeCP2 transgenic mice comparing to wild type (WT) mice. Conclusions: Our study shows that MeCP2 plays an analgesic role in both acute pain transduction and chronic pain formation through regulating CREB-miR-132 pathway. This work provides a potential therapeutic target for neural pathologic pain, and also sheds new lights on the abnormal sensory mechanisms associated with autism spectrum orders. C1 [Zhang, Ran; Cao, Zhijuan; Qi, Jieyu; Chiang, Li-Yang] Southeast Univ, Inst Life Sci, Key Lab Dev Genes & Human Dis, Minist Educ, Nanjing, Jiangsu, Peoples R China. [Qiu, Zilong] Chinese Acad Sci, Inst Neurosci, Key Lab Primate Neurobiol, Shanghai, Peoples R China. [Huang, Min] Scripps Res Inst, Kellogg Sch Sci & Technol, La Jolla, CA 92037 USA. RP Qiu, ZL (reprint author), Chinese Acad Sci, Inst Neurosci, Key Lab Primate Neurobiol, Shanghai, Peoples R China. EM zqiu@ion.ac.cn; liyang.chiang@gmail.com FU Southeast University's 985 grant; 973 Program [2011CBA00400]; Strategic Priority Research Program of the Chinese Academy of Science [XDB02050400] FX We thank members of the Chiang and Qiu laboratories for advice and comments on the manuscript. This work was supported by Southeast University's 985 grant (L.Y.C), the 973 Program (2011CBA00400) and Strategic Priority Research Program of the Chinese Academy of Science, Grant No. XDB02050400 to Z.Q.. 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RP Pisula, E (reprint author), Univ Warsaw, Fac Psychol, Warsaw, Poland. EM ewa.pisula@psych.uw.edu.pl FU Polish National Science Centre [N N106 352940]; Warsaw University FX The study was supported by a grant from the Polish National Science Centre (N N106 352940) and by the Warsaw University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Rivas, Fernando Rojas-Martinez, Augusto TI Clinical and molecular delineation of duplication 9p24.3q21.11 in a patient with psychotic behavior SO GENE LA English DT Article DE 9p duplication syndrome; Psychosis; Autism ID COPY NUMBER VARIATION; TRISOMY 9P; CHROMOSOME; SPECTRUM; DELETION; GLYCINE; ORIGIN; AUTISM; REGION; GIRL AB This article describes a 19-year-old female with mild facial dysmorphism, asociality, decreased school performance, and psychotic behavior in whom the karyotype showed an extra-chromosomal marker characterized as 9p24.3-9q21.11 duplication by array-CGH. The 69 Mbp duplicated segment in this patient includes the critical 9p duplication syndrome region, the GLDC and C90RF72 genes associated with psychotic behavior and other conduct disorders, and a potential locus for autism. (C) 2015 Elsevier B.V. All rights reserved. C1 [Martinez-Jacobo, Lizeth; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto] Univ Autonoma Nuevo Leon, Fac Med, Dept Bioquim &Med Mol, Monterrey 64460, Mexico. [Ortiz-Lopez, Rocio; Santuario-Facio, Sandra K.; Rojas-Martinez, Augusto] Univ Autonoma Nuevo Leon, Unidad Genom, Ctr Invest & Desarrollo Ciencias Salud, Monterrey 64460, Mexico. [Rizo-Mendez, Alfredo; Garcia-Molina, Viridiana] Hosp Civil Guadalajara, Serv Psiquiatria, Guadalajara, Mexico. [Rivas, Fernando] Hosp Gen Occidente Seguro Social, Secretaria Salud Jalisco, Guadalajara, Mexico. RP Rojas-Martinez, A (reprint author), Univ Autonoma Nuevo Leon, Fac Med, Colonia Mitras Ctr, Carlos Canseco S-N, Monterrey 64460, Mexico. EM arojasmtz@gmail.com RI ROJAS MARTINEZ, AUGUSTO/D-1710-2011 OI ROJAS MARTINEZ, AUGUSTO/0000-0003-3765-6778 FU CONACYT (Mexico) FX We would like to thank the patient's mother for their cooperation along this study. Lizeth Martinez-Jacobo is supported by a CONACYT (Mexico) scholarship. 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Michael Adolphs, Ralph Kennedy, Daniel P. TI Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE autism spectrum disorder; default mode network; heterogeneity; machine learning; naturalistic; social comprehension ID SPECTRUM DISORDERS; FUNCTIONAL CONNECTIVITY; COGNITIVE NEUROSCIENCE; NATURAL SCENES; CHILDREN; NETWORK; ADULTS; MIND; ORGANIZATION; VARIABILITY AB Autism spectrum disorder (ASD) features profound social deficits but neuroimaging studies have failed to find any consistent neural signature. Here we connect these two facts by showing that idiosyncratic patterns of brain activation are associated with social comprehension deficits. Human participants with ASD (N = 17) and controls (N = 20) freely watched a television situation comedy (sitcom) depicting seminaturalistic social interactions ("The Office", NBC Universal) in the scanner. Intersubject correlations in the pattern of evoked brain activation were reduced in the ASD group-but this effect was driven entirely by five ASD subjects whose idiosyncratic responses were also internally unreliable. The idiosyncrasy of these five ASD subjects was not explained by detailed neuropsychological profile, eye movements, or data quality; however, they were specifically impaired in understanding the social motivations of characters in the sitcom. Brain activation patterns in the remaining ASD subjects were indistinguishable from those of control subjects using multiple multivariate approaches. Our findings link neurofunctional abnormalities evoked by seminaturalistic stimuli with a specific impairment in social comprehension, and highlight the need to conceive of ASD as a heterogeneous classification. C1 [Byrge, Lisa; Kennedy, Daniel P.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Dubois, Julien; Tyszka, J. Michael; Adolphs, Ralph] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA. RP Byrge, L (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 East 10th St, Bloomington, IN 47405 USA. EM lbyrge@indiana.edu; jcrdubois@gmail.com FU National Institutes of Health [K99MH094409 / R00MH094409]; NARSAD from Brain and Behavior Research Foundation; Simons Foundation [SFARI-07-01]; National Institutes of Mental Health Conte Center [P50MH094258]; National Science Foundation Graduate Research Fellowship FX This work was supported by the National Institutes of Health Grant K99MH094409 / R00MH094409 (D.P.K.), NARSAD Young Investigator Award from the Brain and Behavior Research Foundation (D.P.K.), Simons Foundation SFARI-07-01 (R.A.), National Institutes of Mental Health Conte Center P50MH094258 (R.A.), and a National Science Foundation Graduate Research Fellowship (L.B.). We thank Lynn K. Paul for assistance with clinical diagnoses, Catherine Holcomb and Tim Armstrong for assistance with scheduling and testing of participants, and Haley Gedek and Susannah Burkholder for assistance in scoring the comprehension task. 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Neurosci. PD APR 8 PY 2015 VL 35 IS 14 BP 5837 EP 5850 DI 10.1523/JNEUROSCI.5182-14.2015 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CG1SS UT WOS:000353054900031 PM 25855192 ER PT J AU Foulkes, L Bird, G Gokcen, E McCrory, E Viding, E AF Foulkes, Lucy Bird, Geoffrey Gokcen, Elif McCrory, Eamon Viding, Essi TI Common and Distinct Impacts of Autistic Traits and Alexithymia on Social Reward SO PLOS ONE LA English DT Article ID SPECTRUM DISORDERS; FACIAL EXPRESSIONS; CHILDREN; ADOLESCENTS; DEPRESSION; INDIVIDUALS; RECOGNITION; IMPAIRMENTS; LONELINESS; FRIENDSHIP AB According to the social motivation hypothesis of autism, individuals with high levels of autistic traits experience reduced levels of reward from social interactions. However, empirical evidence to date has been mixed, with some studies reporting lower levels of social reward in individuals with Autism Spectrum Disorder (ASD), and others finding no difference when compared to typically developing controls. Alexithymia, a subclinical condition associated with the reduced ability to identify and describe one's own emotions, has been found to account for other affective difficulties observed inconsistently in individuals with ASD. The current study used a nonclinical sample (N = 472) to explore the associations between autistic traits and the value of six types of social reward, as measured by the Social Reward Questionnaire. In addition, we measured alexithymia to assess if this accounted for associations between autistic traits and social reward. There were three main findings. Firstly, higher levels of autistic traits were associated with significantly less enjoyment of admiration and sociability, and adding alexithymia to these models did not account for any additional variance. Secondly, both autistic traits and alexithymia were uniquely associated with reduced levels of enjoyment of prosocial interactions and sexual relationships. Thirdly, autistic traits were associated with higher levels of enjoyment of passivity and negative social potency, but these associations were no longer significant once alexithymia was taken into account, suggesting that co-occurring alexithymia accounted for these apparent associations. Overall, the current findings provide a novel and more nuanced picture of the relationship between autistic traits and social reward. C1 [Foulkes, Lucy; Gokcen, Elif; McCrory, Eamon; Viding, Essi] UCL, Dept Clin Educ & Hlth Psychol, London, England. [Bird, Geoffrey] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, London, England. [Bird, Geoffrey] UCL, Inst Cognit Neurosci, London, England. RP Foulkes, L (reprint author), UCL, Dept Clin Educ & Hlth Psychol, London, England. EM l.foulkes.11@ucl.ac.uk FU UK Medical Research Council [MR/J500422/1] FX This work was supported by a Four-Year PhD studentship in Mental Health from the UK Medical Research Council (MR/J500422/1) awarded to LF. 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 study examined the role of social context on viewing behaviour of participants whilst they watched a dynamic social scene, under three different conditions. In two social groups, participants believed they were watching a live webcam of other participants. The socially-engaged group believed they would later complete a group task with the people in the video, whilst the non-engaged group believed they would not meet the people in the scene. In a third condition, participants simply free-viewed the same video with the knowledge that it was pre-recorded, with no suggestion of a later interaction. Results demonstrated that the social context in which the stimulus was viewed significantly influenced viewing behaviour. Specifically, participants in the social conditions allocated less visual attention towards the heads of the actors in the scene and followed their gaze less than those in the free-viewing group. These findings suggest that by underestimating the impact of social context in social attention, researchers risk coming to inaccurate conclusions about how we attend to others in the real world. C1 [Gregory, Nicola Jean; Bate, Sarah] Bournemouth Univ, Fac Sci & Technol, Psychol Res Ctr, Poole BH12 5BB, Dorset, England. [Gregory, Nicola Jean; Lopez, Beatriz; Graham, Gemma; Marshman, Paul; Kargas, Niko] Univ Portsmouth, Dept Psychol, Portsmouth, Hants, England. RP Gregory, NJ (reprint author), Bournemouth Univ, Fac Sci & Technol, Psychol Res Ctr, Poole BH12 5BB, Dorset, England. EM ngregory@bournemouth.ac.uk FU Bournemouth University Fusion Investment Fund Staff Networking and Mobility Award; Department of Psychology, University of Portsmouth FX NG and SB were supported by a Bournemouth University Fusion Investment Fund Staff Networking and Mobility Award. BL and NG were supported by a research grant from the Department of Psychology, University of Portsmouth. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders. C1 [Kalinowska, Magdalena; Castillo, Catherine; Francesconi, Anna] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, New York, NY 10461 USA. RP Francesconi, A (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, New York, NY 10461 USA. EM anna.francesconi@einstein.yu.edu FU Autism Speaks [7287]; NIH [MH082870] FX This study was supported by a grant from Autism Speaks (grant # 7287), www.autismspeaks.org; and NIH grant MH082870 to A.F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Dissanayake, Cheryl Barbaro, Josephine TI Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012 SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Article AB Objectives: To investigate the frequency and age at diagnosis of autism spectrum disorder (ASD) in children aged under 7 years living in Australia. Design and participants: Analysis of de-identified data on 15074 children aged under 7 years registered with the Helping Children with Autism Package (HCWAP; a program that provides funding for access to early intervention and support services throughout Australia) between 1 July 2010 and 30 June 2012. Main outcome measures: Age at diagnosis of ASD as confirmed by a paediatrician, psychiatrist and/or multidisciplinary team assessment. Results: The average age at diagnosis of ASD in children registered with the HCWAP is currently 49 months, with the most frequently reported age being 71 months. Differences were evident in age at diagnosis across states, with children in Western Australia and New South Wales being diagnosed at a younger age. Across Australia, 0.74% of the population of children aged under 7 years are currently diagnosed with ASD and registered with the HCWAP. A higher proportion of children were registered with the HCWAP in Victoria compared with other states. There was no difference in age at diagnosis between Indigenous and non-Indigenous Australians, but children from a culturally and linguistically diverse background were diagnosed 5 months earlier than other children. Conclusions: There may be a substantial gap between the age at which a reliable and accurate diagnosis of ASD is possible and the average age that children are currently diagnosed. The frequency of ASD diagnoses In Australia has increased substantially from previously published estimates. C1 [Bent, Catherine A.; Dissanayake, Cheryl; Barbaro, Josephine] La Trobe Univ, Melbourne, Vic, Australia. RP Bent, CA (reprint author), La Trobe Univ, Melbourne, Vic, Australia. EM c.dissanayake@latrobe.edu.au FU La Trobe University FX Catherine Bent is supported by a La Trobe University Postgraduate Research Scholarship. NR 0 TC 0 Z9 0 PU AUSTRALASIAN MED PUBL CO LTD PI PYRMONT PA LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD APR 6 PY 2015 VL 202 IS 6 BP 317 EP 320 DI 10.5694/mja14.00328 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CG6UO UT WOS:000353438100027 PM 25832158 ER PT J AU Gecz, J Corbett, M AF Gecz, Jozef Corbett, Mark TI Developmental disorders: deciphering exomes on a grand scale SO LANCET LA English DT Editorial Material ID DE-NOVO MUTATIONS; INTELLECTUAL DISABILITY; INCIDENTAL FINDINGS; DISEASE; AUTISM C1 [Gecz, Jozef] Univ Adelaide, Womens & Childrens Hosp, Sch Paediat & Reprod Hlth, Adelaide, SA 5006, Australia. Univ Adelaide, Womens & Childrens Hosp, Robinson Res Inst, Adelaide, SA 5006, Australia. RP Gecz, J (reprint author), Univ Adelaide, Womens & Childrens Hosp, Sch Paediat & Reprod Hlth, Adelaide, SA 5006, Australia. 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M. Dilalla, L. F. TI Psychological and Genetic Contributions to The Development of Social Cognition in Children with and without Autism Spectrum Disorder SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD APR 3 PY 2015 VL 29 IS 3 MA 126S BP 370 EP 371 PG 2 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI6KL UT WOS:000354867800127 ER PT J AU Jashar, DT Brennan, L Robins, D Barton, M Fein, D AF Jashar, D. T. Brennan, L. Robins, D. Barton, M. Fein, D. TI Diagnostic Stability in Toddlers Who Lose An Autism Diagnosis in DSM-5 SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD APR 3 PY 2015 VL 29 IS 3 MA 127S BP 371 EP 371 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI6KL UT WOS:000354867800128 ER PT J AU Zoltowski, A Heinrich, K Ktiri, M Badaly, D Hodges, E AF Zoltowski, A. Heinrich, K. Ktiri, M. Badaly, D. Hodges, E. TI Social Cognition Measures and Their Relationship to Ratings of Social Problems in Autism Spectrum Disorder SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD APR 3 PY 2015 VL 29 IS 3 MA 128S BP 371 EP 372 PG 2 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI6KL UT WOS:000354867800129 ER PT J AU Ludwig, NN Abrams, DN Fein, D Adamson, LB Robins, DL AF Ludwig, N. N. Abrams, D. N. Fein, D. Adamson, L. B. Robins, D. L. TI The Utility of Early Autism Spectrum Disorder (ASD) Screening Tools in Predicting The Presence of ASD Symptoms and Symptom Severity SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD APR 3 PY 2015 VL 29 IS 3 MA 129S BP 372 EP 372 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA CI6KL UT WOS:000354867800130 ER PT J AU Simpson, K Keen, D Lamb, J AF Simpson, Kate Keen, Deb Lamb, Janeen TI Teaching receptive labelling to children with autism spectrum disorder: A comparative study using infant-directed song and infant-directed speech SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE autism spectrum disorder; communication; music; children; intervention ID PRESCHOOL-CHILDREN; COMMUNICATIVE DEVELOPMENT; PHYSIOLOGICAL-RESPONSES; AUDITORY PREFERENCES; INTONATION CONTOURS; WORD RECOGNITION; YOUNG-CHILDREN; LANGUAGE; MUSIC; MOTHERESE AB Background There is a growing body of literature investigating the efficacy of music interventions for children with autism spectrum disorder (ASD); however, little empirical research has been conducted into the use of musical elements to facilitate language learning. Methods This crossover-design study compared the responses of 22 children with ASD (M age = 5.88 years) to sung and spoken instructions embedded into a computer-based communication intervention designed to teach receptive labelling. Results There was no significant difference between the sung and spoken conditions. Following both conditions, there was a significant increase in receptive labelling skills; skills were generalised and were maintained at follow-up. A difference in group performance was found. Conclusion Further research is required to investigate child characteristics that may impact on children's performance using this approach. C1 [Simpson, Kate; Lamb, Janeen] Australian Catholic Univ, Fac Educ & Arts, Brisbane, Qld, Australia. [Simpson, Kate; Keen, Deb] Griffith Univ, Sch Educ & Profess Studies, Brisbane, Qld 4122, Australia. RP Simpson, K (reprint author), Griffith Univ, Sch Educ & Profess Studies, Brisbane, Qld 4122, Australia. 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Hao, Grace Zou, Xiaobing Li, Ling Shao, Zhi Yao, Meiling Xu, Xiu Ke, Xiaoyan Wu, Lijie Zhou, Jiaxiu Jiang, Zhimei TI Differentiating low- and high-functioning children with autism spectrum disorder, children with intellectual disability, and typically developing children in a Chinese population SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE intellectual disability; Chinese; behaviours; lower and higher functioning; autism spectrum disorder; assessment; domains ID MENTAL-RETARDATION; UNITED-STATES; PREVALENCE; LANGUAGE; NETWORK; PROFILE AB Background There is a dearth of research or inconsistency in findings of behaviours among children with autism spectrum disorder (ASD) and children with intellectual disability (ID) as well as children who are typically developing (TD). This study compared 7 behavioural domains of 96 behaviours among Chinese children. Method There were 803 children, including 426 children with low-functioning ASD (LFASD), 193 children with high-functioning ASD (HFASD), 128 children with ID, and 56 TD children. Ages ranged from 36 to 84 months. Each individual was administered the Chinese Autism Diagnostic Scale by a group of Chinese professionals. Results All 7 domains were found to be more impaired for the children with ASD than the other groups. Three domains contained the most distinctive behaviours: Play behaviours, Social-Interactive behaviours, and Receptive Language behaviours. The Expressive Language domain was different for the LFASD group versus the group with ID. Conclusion Children with ASD differed from children without ASD by several specific behaviours. These behaviours also differentiated performances by the children with HFASD and LFASD. C1 [Layton, Thomas L.] T&T Commun Serv Inc, Durham, NC 27713 USA. [Hao, Grace] N Carolina Cent Univ, Dept Allied Hlth Profess, Durham, NC USA. 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Intellect. Dev. Dis. PD APR 3 PY 2015 VL 40 IS 2 BP 137 EP 146 DI 10.3109/13668250.2015.1022514 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CH3TM UT WOS:000353953200004 ER PT J AU Hidalgo, NJ McIntyre, LL McWhirter, EH AF Hidalgo, Nina Jamilette McIntyre, Laura Lee McWhirter, Ellen Hawley TI Sociodemographic differences in parental satisfaction with an autism spectrum disorder diagnosis SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE diagnosis; parent satisfaction; autism spectrum disorder; maternal education; ASD; family income ID SOCIOECONOMIC-STATUS; CHILDREN; HEALTH; RISK; INTERVENTION; EPIDEMIOLOGY; SERVICES; STRESS; RACE; SES AB Background The diagnostic process for autism spectrum disorder (ASD) can be difficult for families. Growing evidence suggests that the diagnostic process may vary as a function of sociodemographic factors, such as socioeconomic status. The purpose of this study was to extend findings related to families' experiences obtaining a diagnosis and accessing services for their young child with ASD. Method A mixed methods approach was used in this study, in which 46 families with children with ASD participated. A chi-square analysis compared ratings of parental satisfaction with the diagnostic process and current services between sociodemographic groups, and this was supplemented by thematic analysis of relevant open-ended questions. Results Results indicated that satisfaction ratings varied significantly by maternal education and family income levels. Ratings of satisfaction with the child's paediatrician also differed by family income. Major themes from the open-ended questions are discussed. Conclusions Results support assessing satisfaction and barriers in families seeking healthcare and school-based services to facilitate access to services. C1 [Hidalgo, Nina Jamilette; McWhirter, Ellen Hawley] Univ Oregon, Dept Counseling Psychol & Human Serv, Eugene, OR 97403 USA. [McIntyre, Laura Lee] Univ Oregon, Dept Special Educ & Clin Sci, Eugene, OR 97403 USA. RP McIntyre, LL (reprint author), 5208 Univ Oregon, Dept Special Educ & Clin Sci, Eugene, OR 97403 USA. EM llmcinty@uoregon.edu FU Fairway Foundation; National Institutes of Health [R01 HD059838] FX This research was funded in part by a grant from the Fairway Foundation and the National Institutes of Health (R01 HD059838) awarded to the second author. 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C., 2001, STAT PLAIN ENGLISH Woods JJ, 2003, LANG SPEECH HEAR SER, V34, P180, DOI 10.1044/0161-1461(2003/015) NR 26 TC 0 Z9 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1366-8250 EI 1469-9532 J9 J INTELLECT DEV DIS JI J. Intellect. Dev. Dis. PD APR 3 PY 2015 VL 40 IS 2 BP 147 EP 155 DI 10.3109/13668250.2014.994171 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CH3TM UT WOS:000353953200005 ER PT J AU Derguy, C Michel, G M'bailara, K Roux, S Bouvard, M AF Derguy, Cyrielle Michel, Gregory M'bailara, Katia Roux, Solenne Bouvard, Manuel TI Assessing needs in parents of children with autism spectrum disorder: A crucial preliminary step to target relevant issues for support programs SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE parent support; autism spectrum disorder (ASD); parenting needs; therapeutic education ID DEVELOPMENTAL-DISABILITIES; PRESCHOOL-CHILDREN; FAMILIES; STRESS; EXPERIENCES; BEHAVIORS; INFANTS; MOTHERS; QUALITY; HEALTH AB Background Raising a child with an autism spectrum disorder (ASD) implies significant stress levels and changes in family functioning. Most studies deal with parental difficulties, whereas those focusing on parental self-reported support needs related to ASD are fewer, especially in France. Our objective was to explore in a French sample the needs of parents of children with ASD so as to provide recommendations for support. Method Parents were interviewed (N = 162, including 84 controls), and content analysis was performed from parental responses. Results Six dimensions of need emerged: material, information, guidance, daily management, relational support, and emotional support. Needs priorities were different for parents with a child with ASD involving the transmission of knowledge and skills as well as emotional and relational support. Conclusions This study highlights the need to develop support programs focused on the needs of the parents that reflect educational, behavioural, and psychological dimensions. C1 [Derguy, Cyrielle; Michel, Gregory; M'bailara, Katia; Roux, Solenne] Univ Bordeaux, Dept Psychol Hlth & Qual Life, F-33076 Bordeaux, France. [Derguy, Cyrielle; Bouvard, Manuel] Charles Perrens Hosp, Expert Autism Ctr, Bordeaux, France. [Bouvard, Manuel] Univ Bordeaux, Aquitaine Inst Cognit & Integrat Neurosci INCIA, F-33076 Bordeaux, France. RP Derguy, C (reprint author), Univ Bordeaux, Dept Psychol Hlth & Qual Life, EA 4139, 3Ter Pl Victoire, F-33076 Bordeaux, France. EM cyrielle.derguy@u-bordeaux.fr FU Orange Foundation, Paris, France FX This study received financial support from the Orange Foundation, Paris, France. The Orange Foundation has not imposed any restrictions on free access to or publication of the research data. There are no conflicts of interest for any of the authors. CR Ahmadi A, 2011, PROCD SOC BEHV, V15, DOI 10.1016/j.sbspro.2011.03.094 Albanese A. 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Intellect. Dev. Dis. PD APR 3 PY 2015 VL 40 IS 2 BP 156 EP 166 DI 10.3109/13668250.2015.1023707 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CH3TM UT WOS:000353953200006 ER PT J AU Dix, L Fallows, R Murphy, G AF Dix, Leigh Fallows, Rachael Murphy, Glynis TI Effectiveness of the ADEC as a Level 2 screening test for young children with suspected autism spectrum disorders in a clinical setting SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE early detection; ADEC; autism; screening ID EARLY-CHILDHOOD ADEC; 2-YEAR-OLDS STAT; TODDLERS; TOOL; INTERVENTION; MANAGEMENT; INFANTS; RISK AB Background The Autism Detection in Early Childhood (ADEC) is a clinician-administered, Level 2 screening tool. A retrospective file audit was used to investigate its clinical effectiveness. Method Toddlers referred to an Australian child development service between 2008 and 2010 (N = 53, M age = 32.2 months) were screened with the ADEC. Their medical records were reviewed in 2013 when their mean age was 74.5 months, and the original ADEC screening results were compared with later diagnostic outcomes. Results The ADEC had good sensitivity (87.5%) and moderate specificity (62%). Three behaviours predicted autism spectrum disorders (ASDs): response to name, gaze switching, and gaze monitoring (p <= .001). Conclusions The ADEC shows promise as a screening tool that can discriminate between young children with ASDs and those who have specific communication disorders or developmental delays that persist into middle childhood but who do not meet the criteria for ASDs. C1 [Dix, Leigh; Fallows, Rachael] WA Hlth, Child & Adolescent Community Hlth, Perth, WA, Australia. [Murphy, Glynis] Univ Kent, Tizard Ctr, Canterbury, Kent, England. 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Intellect. Dev. Dis. PD APR 3 PY 2015 VL 40 IS 2 BP 179 EP 188 DI 10.3109/13668250.2015.1014323 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA CH3TM UT WOS:000353953200008 ER PT J AU Jung, S Sainato, DM AF Jung, Sunhwa Sainato, Diane M. TI Teaching games to young children with autism spectrum disorder using special interests and video modelling SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE autism spectrum disorder; social skills; video modelling; social engagement; play skills; restricted interests ID POWER CARD STRATEGY; OF-THE-LITERATURE; PRETEND PLAY; SOCIODRAMATIC PLAY; SOCIAL PLAY; SKILLS; PRESCHOOLERS; DISABILITIES; BEHAVIORS; INTERVENTION AB Background Children with autism spectrum disorder (ASD) may exhibit delayed play skills or repetitive play and have difficulty engaging in spontaneous play with peers. Method A multiple-probe design across participants was used to investigate the effectiveness of a video modelling intervention and the use of children's special interests on their engagement with games and with peers for kindergarten children with ASD. Results Results indicated that all three children with ASD demonstrated increased engagement with the games and social engagement with their peers. Inappropriate behaviour decreased with the intervention. The effects were maintained during the follow-up and generalised to a novel game. Social validity data indicated that the study was meaningful and the intervention was feasible and effective. Conclusion Future research should focus on designing play skills interventions that serve to motivate both children with ASD and their typically developing peers in order to promote more spontaneous and interactive play among them. C1 [Jung, Sunhwa] Otterbein Univ, Dept Educ, Westerville, OH 43081 USA. 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