FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ference, J Curtin, S AF Ference, Jennifer Curtin, Suzanne TI Attention to lexical stress and early vocabulary growth in 5-month-olds at risk for autism spectrum disorder SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE Speech perception; Lexical stress; Vocabulary development; Autism spectrum disorder; Infant siblings; Language ID INFANT-DIRECTED SPEECH; WORD SEGMENTATION; PATTERN-DISCRIMINATION; YOUNG INFANTS; LANGUAGE; PERCEPTION; PREFERENCE; PROSODY; CHILDREN; ENGLISH AB Typically developing infants differentiate strong-weak (trochaic) and weak-strong (iambic) stress patterns by 2 months of age. The ability to discriminate rhythmical patterns, such as lexical stress, has been argued to facilitate language development, suggesting that a difficulty in discriminating stress might affect early word learning as reflected in vocabulary size. Children with autism spectrum disorder (ASD) often have difficulty in correctly producing lexical stress, yet little is known about how they perceive it. The current study tested 5-month-old infants with typically developing older siblings (SIBS-TD) and infants with an older sibling diagnosed with ASD (SIBS-A) on their ability to differentiate the trochaic and iambic stress patterns of the word form gaba. SIBS-TD infants showed an increased interest in attention to the trochaic stress pattern, which was also positively correlated with vocabulary comprehension at 12 months of age. In contrast, SIBS-A infants attended equally to these stress patterns, although this was unrelated to later vocabulary size. (C) 2013 Elsevier Inc. All rights reserved. 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. 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Exp. Child Psychol. PD DEC PY 2013 VL 116 IS 4 BP 891 EP 903 DI 10.1016/j.jecp.2013.08.006 PG 13 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 252GJ UT WOS:000326992800008 PM 24077464 ER PT J AU Thaler, NS Allen, DN Sutton, GP Vertinski, M Ringdahl, EN AF Thaler, Nicholas S. Allen, Daniel N. Sutton, Griffin P. Vertinski, Mary Ringdahl, Erik N. TI Differential impairment of social cognition factors in bipolar disorder with and without psychotic features and schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Social cognition; Psychosis; Theory of mind; Emotion processing; Factor analysis ID HIGH-FUNCTIONING AUTISM; EMOTION PERCEPTION; MIND DEFICITS; RECOGNITION; INTELLIGENCE; METAANALYSIS; MARKERS; ADULTS AB While it is well-established that patients with schizophrenia and bipolar disorder exhibit deficits in social cognition, few studies have separately examined bipolar disorder with and without psychotic features. The current study addressed this gap by comparing patients with bipolar disorder with (BD+) and without (BD-) psychotic features, patients with schizophrenia (SZ), and healthy controls (NC) across social cognitive measures. Principal factor analysis on five social cognition tasks extracted a two-factor structure comprised of social/emotional processing and theory of mind. Factor scores were compared among the four groups. Results identified differential patterns of impairment between the BD+ and BD- group on the social/emotional processing factor while all clinical groups performed poorer than controls on the theory of mind factor. This provides evidence that a history of psychosis should be taken into account while evaluating social cognition in patients with bipolar disorder and also raises hypotheses about the relationship between social cognition and psychosis. (C) 2013 Elsevier Ltd. All rights reserved. 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Psychiatr. Res. PD DEC PY 2013 VL 47 IS 12 BP 2004 EP 2010 DI 10.1016/j.jpsychires.2013.09.010 PG 7 WC Psychiatry SC Psychiatry GA 253ST UT WOS:000327110300023 PM 24112946 ER PT J AU Anderson, LC Bolling, DZ Schelinski, S Coffman, MC Pelphrey, KA Kaiser, MD AF Anderson, L. C. Bolling, D. Z. Schelinski, S. Coffman, M. C. Pelphrey, K. A. Kaiser, M. D. TI Sex differences in the development of brain mechanisms for processing biological motion SO NEUROIMAGE LA English DT Article DE Sex differences; Brain development; Biological motion; fMRI; Amygdala ID EMOTIONAL FACIAL EXPRESSIONS; GENDER-DIFFERENCES; AMYGDALA ACTIVATION; SOCIAL-PERCEPTION; NEURAL MECHANISMS; DE-NOVO; AUTISM; ATTENTION; CHILDREN; CEREBELLUM AB Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. (C) 2013 Elsevier Inc. All rights reserved. C1 [Anderson, L. C.; Bolling, D. Z.; Schelinski, S.; Coffman, M. C.; Pelphrey, K. A.; Kaiser, M. 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TI Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders SO PATHOGENS AND DISEASE LA English DT Article DE Alzheimer's disease; multiple sclerosis; schizophrenia; mood disorders ID PROGRAMMED CELL-DEATH; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; BIPOLAR DISORDER; HUMAN-EVOLUTION; NEURODEGENERATIVE DISORDERS; CCR5-DELTA-32 POLYMORPHISM; SYSTEMATIC METAANALYSES; HELICOBACTER-PYLORI; PARKINSONS-DISEASE AB Herpes simplex virus 1 (HSV-1) can promote beta-amyloid deposition and tau phosphorylation, demyelination or cognitive deficits relevant to Alzheimer's disease or multiple sclerosis and to many neuropsychiatric disorders with which it has been implicated. A seroprevalence much higher than disease incidence has called into question any primary causal role. However, as also the case with risk-promoting polymorphisms (also present in control populations), any causal effects are likely to be conditional. During its life cycle, the virus binds to many proteins and modifies the expression of multiple genes creating a host/pathogen interactome involving 1347 host genes. This data set is heavily enriched in the susceptibility genes for multiple sclerosis (P=1.3E-99)>Alzheimer's disease>schizophrenia>Parkinsonism>depression>bipolar disorder>childhood obesity>chronic fatigue>autism>and anorexia (P=0.047) but not attention deficit hyperactivity disorder, a relationship maintained for genome-wide association study data sets in multiple sclerosis and Alzheimer's disease. Overlapping susceptibility gene/interactome data sets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies. In this way, the same pathogen could contribute to multiple diseases in a gene-dependent manner and condition the risk-promoting effects of the genes whose function it disrupts. This article reports the analysis of existing information on the susceptibility genes for psychiatric and neurological disorders and find that they, with the exception of ADHD, are enriched in the gene set of the herpes simplex (HSV-1)/host interactome. This could shed light on their pathogenesis, and introduces an intriguing hypothesis of a potential viral etiology of these diseases. C1 [Carter, Chris J.] PolygenicPathways, Hastings, E Sussex, England. RP Carter, CJ (reprint author), Flat 2,40 Baldslow Rd, Hastings TN34 2EY, E Sussex, England. 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The structural variations observed in this family may contribute to the observed symptoms, but further studies are necessary to investigate the possible involvement of the described variations in the TS etiology. (c) 2013 Wiley Periodicals, Inc. C1 [Melchior, Linea; Bertelsen, Birgitte; Brondum-Nielsen, Karen; Tumer, Zeynep] Copenhagen Univ Hosp, Kennedy Ctr, Rigshosp, DK-2600 Glostrup, Denmark. [Debes, Nanette Mol; Groth, Camilla; Skov, Liselotte] Herlev Univ Hosp, Dept Pediat, Tourette Clin, DK-2730 Herlev, Denmark. [Mikkelsen, Jens D.] Univ Copenhagen Hosp, Neurobiol Res Unit, Rigshosp, DK-2100 Copenhagen, Denmark. RP Tumer, Z (reprint author), Copenhagen Univ Hosp, Kennedy Ctr, Rigshosp, Gl Landevej 7, DK-2600 Glostrup, Denmark. EM zeynep.tumer@regionh.dk FU Lundbeck Foundation [R24-A2419, R24-2419]; Strategic Research Council Cognito FX Grant sponsor: Lundbeck Foundation; Grant numbers: R24-A2419, R24-2419; Grant sponsor: Strategic Research Council Cognito. 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TI Mood Disorders in Individuals With Distal 18q Deletions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE depression; bipolar disorder; Chromosome 18; 18q-; hemideletion; mood disorders; ZADH2; TSHZ1 ID BIPOLAR AFFECTIVE-DISORDER; AUTISM SPECTRUM DISORDERS; CHROMOSOME-18 DNA MARKERS; GENOME-WIDE ASSOCIATION; EARLY-ONSET; TELEPHONE INTERVIEW; SUSCEPTIBILITY LOCI; MAJOR DEPRESSION; LINKAGE ANALYSIS; II DISORDER AB We examined 36 participants at least 4 years old with hemizygous distal deletions of the long arm of Chromosome 18 (18q-) for histories of mood disorders and to characterize these disorders clinically. Since each participant had a different region of 18q hemizygosity, our goal was also to identify their common region of hemizygosity associated with mood disorders; thereby identifying candidate causal genes in that region. Lifetime mood and other psychiatric disorders were determined by semi-structured interviews of patients and parents, supplemented by reviews of medical and psychiatric records, and norm-referenced psychological assessment instruments, for psychiatric symptoms, cognitive problems, and adaptive functioning. Sixteen participants were identified with lifetime mood disorders (ages 12-42 years, 71% female, 14 having had unipolar depression and 2 with bipolar disorders). From the group of 20 who did not meet criteria for a mood disorder; a comparison group of 6 participants were identified who were matched for age range and deletion size. Mood-disordered patients had high rates of anxiety (75%) and externalizing behavior disorders (44%), and significant mean differences from comparison patients (P<0.05), including higher overall and verbal IQs and lower autistic symptoms. A critical region was defined in the mood-disordered group that included a hypothetical gene, C18orf62, and two known genes, ZADH2 and TSHZ1. We conclude that patients having terminal deletions of this critical region of the long arm of Chromosome 18 are highly likely to have mood disorders, which are often comorbid with anxiety and to a lesser extent with externalizing disorders. (c) 2013 Wiley Periodicals, Inc. C1 [Daviss, William B.; O'Donnell, Louise; Pliszka, Steven R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [O'Donnell, Louise; Soileau, Bridgette T.; Heard, Patricia; Carter, Erika; Hale, Daniel E.; Cody, Jannine D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Gelfond, Jonathan A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Cody, Jannine D.] Chromosome 18 Registry & Res Soc, San Antonio, TX USA. RP Cody, JD (reprint author), Chromosome 18 Clin Res Ctr, Dept Pediat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cody@uthscsa.edu FU Chromosome 18 Registry and Research Society; MacDonald family; CHRISTUS Santa Rosa Children's Hospital; Institute for the Integration of Medicine and Science (CTSA) [8UL1TR000149] FX Grant sponsor: Chromosome 18 Registry and Research Society; Grant sponsor: MacDonald family; Grant sponsor: CHRISTUS Santa Rosa Children's Hospital; Grant sponsor: Institute for the Integration of Medicine and Science (CTSA); Grant number: 8UL1TR000149. 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Genet. B PD DEC PY 2013 VL 162 IS 8 BP 879 EP 888 DI 10.1002/ajmg.b.32197 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246AE UT WOS:000326506700011 PM 24006251 ER PT J AU Sasaki, R Uchiyama, H Okamoto, T Fukada, K Ogiuchi, H Ando, T AF Sasaki, Ryo Uchiyama, Hiroto Okamoto, Toshihiro Fukada, Kenji Ogiuchi, Hideki Ando, Tomohiro TI A toothbrush impalement injury of the floor of mouth in autism child SO DENTAL TRAUMATOLOGY LA English DT Article DE autism; floor of mouth; impalement; penetrating injury ID PENETRATING INJURIES; SOFT PALATE; MANAGEMENT; TRAUMA AB - Penetrating injuries in the oral cavity are common in children. However, penetrating injuries with retained foreign bodies are rare. We report a case of a toothbrush impalement injury of the floor of the mouth in a child with autism. A 5-year-old boy with autism presented with an accidentally impaled toothbrush in the oral cavity. He was taken to the operation room and examined under general anesthesia. The handle of the toothbrush was cut off using rib scissors for mask ventilation, and intra-oral intubation was performed. The toothbrush was located approximately 2.5cm into the floor of the mouth. The toothbrush was removed uneventfully. Intravenous antibiotic therapy was instituted during hospitalization, and discharge from the hospital occurred 4days after the operation. C1 [Sasaki, Ryo; Uchiyama, Hiroto; Okamoto, Toshihiro; Fukada, Kenji; Ogiuchi, Hideki; Ando, Tomohiro] Tokyo Womens Med Univ, Sch Med, Dept Oral & Maxillofacial Surg, Shinjuku Ku, Tokyo 1628666, Japan. [Sasaki, Ryo] Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Shinjuku Ku, Tokyo 1628666, Japan. RP Sasaki, R (reprint author), Tokyo Womens Med Univ, Sch Med, Dept Oral & Maxillofacial Surg, Shinjuku Ku, 8-1 Kawada cho, Tokyo 1628666, Japan. EM sasaki@oms.twmu.ac.jp CR Chauhan N, 2006, INT J PEDIATR OTORHI, V70, P1479, DOI 10.1016/j.ijporl.2006.02.002 Hennelly Kara, 2010, Pediatrics, V126, pe1578, DOI 10.1542/peds.2010-1059 KOSAKI H, 1992, J LARYNGOL OTOL, V106, P813, DOI 10.1017/S002221510012095X Randall DA, 2006, OTOLARYNG HEAD NECK, V135, P356, DOI 10.1016/j.otohns.2005.12.003 Raska GM, 2007, J ORAL MAXIL SURG, V65, P1279, DOI 10.1016/j.joms.2006.10.056 Saravanan B, 2010, Indian J Dent Res, V21, P446, DOI 10.4103/0970-9290.70797 Soose RJ, 2006, ARCH OTOLARYNGOL, V132, P446, DOI 10.1001/archotol.132.4.446 Suskind DL, 1997, INT J PEDIATR OTORHI, V39, P41, DOI 10.1016/S0165-5876(96)01460-7 Topazian RG, 2002, ORAL MAXILLOFACIAL I NR 9 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-4469 EI 1600-9657 J9 DENT TRAUMATOL JI Dent. Traumatol. PD DEC PY 2013 VL 29 IS 6 BP 467 EP 468 DI 10.1111/j.1600-9657.2012.01116.x PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 248HL UT WOS:000326688700008 PM 22296118 ER PT J AU Al-Amin, MM Uddin, MMN Rahman, MM Reza, HM Rana, MS AF Al-Amin, Md. Mamun Uddin, Mir Muhammad Nasir Rahman, Md. Mahbubur Reza, Hasan Mahmud Rana, Md. Sohel TI Effect of diclofenac and antidepressants on the inflammatory response in astrocyte cell culture SO INFLAMMOPHARMACOLOGY LA English DT Article DE Astrocyte; Serotonin; Tryptophan; Lipopolysaccharide ID DEPRESSIVE-LIKE BEHAVIOR; INDOLEAMINE 2,3-DIOXYGENASE; INTERFERON-GAMMA; RAT-BRAIN; T-CELLS; EXPRESSION; ALPHA AB Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and neurotransmitter synthesis. It has been reported that cytokine imbalance is involved in the progression of many CNS diseases such as neuropsychiatric disorders (depression, schizophrenia, autism, and bipolar disorder) and neurodegenerative disorders (Parkinson's and Alzheimer's disease). Here, the effects of diclofenac, different antidepressants (sertraline, venlafaxine, and fluvoxamine), and vitamin B-6 (pyridoxine) on IL-10 and tumor necrosis factor-alpha (TNF-alpha) change with and without immune challenges with lipopolysaccharide (LPS) were investigated in in vitro culture of astrocytes from 2-day-old Swiss-Albino mice. Diclofenac and Sertraline significantly (p < 0.05) improves anti-inflammatory cytokine (IL-10) while suppress (p < 0.05) LPS-induced elevated level of pro-inflammatory mediators (TNF-alpha) in astrocyte culture. Pyridoxine was not able to reduce (p > 0.05) TNF-alpha in the astrocyte culture. Antidepressant (sertraline) showed positive effects (increased IL-10 and reduced TNF-alpha level) possibly through the suppression of Th1 lymphocytes and monocytes and stimulation of Th2 lymphocytes and monocytes/macrophages. NSAID (diclofenac) showed positive immune regulation effect possibly through the inhibition of cyclo-oxygenase enzyme. Based on these findings, it may conclude that, diclofenac and antidepressants (sertraline) may positively contribute in the cytokine production in astrocyte cell culture. C1 [Al-Amin, Md. Mamun; Reza, Hasan Mahmud] North South Univ, Dept Pharm, Dhaka 1229, Bangladesh. [Uddin, Mir Muhammad Nasir] Chittagong Univ, Dept Pharm, Chittagong, Bangladesh. [Rahman, Md. Mahbubur] Univ Lubeck, Inst Pharmacol, D-23538 Lubeck, Germany. [Rana, Md. Sohel] Jahangirnagar Univ, Dept Pharm, Dhaka 1342, Bangladesh. RP Al-Amin, MM (reprint author), North South Univ, Dept Pharm, Plot 15,Block B, Dhaka 1229, Bangladesh. 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To this end, the concept of normative sexual development was used as an organising framework. BackgroundSexual health can be seen as a developmental task for all children, adolescents and adults. Core autism features are related with skills central to sexual development and functioning. More insight in sexual development in people with autism is relevant for education, support and interventions by parents and professionals in somatic and mental health care. MethodsA comprehensive search of scientific online databases and reference lists was conducted. Publications based on qualitative and quantitative research, including case studies, were selected. ResultsFifty-five articles and reports were selected and discussed. Information was grouped according to three domains: sexual behaviour, sexual selfhood and sexual socialisation. ConclusionSexual development is a part of life for people with autism of all developmental levels and is generally understudied in this population. Most information was available on behavioural aspects and experiences of socialising agents, such as parents and professionals. Developmental processes and the relation between sexual behaviour, selfhood and socialisation remained unclear. Relevance to clinical practiceNurses working in schools, institutions and general health care support children, adolescents and adults with autism and advice their families, teachers, other educators and caregivers on sexuality issues. They can have an important role in daily assessment and support of this developmental domain by actively enquiring about the different aspects of sexual development and by offering information. Our findings offer an overview on the existing knowledge and support the idea that sexual development is normative for people with autism just as for anybody else. C1 [Dewinter, Jeroen; van Nieuwenhuizen, Chijs] Tilburg Univ, NL-5000 LE Tilburg, Netherlands. [Dewinter, Jeroen; van Nieuwenhuizen, Chijs] GGzE, Ctr Child & Adolescent Psychiat, NL-5600 AX Eindhoven, Netherlands. [Vermeiren, Robert] Curium LUMC, Dept Child & Adolescent Psychiat, Oegstgeest, Netherlands. [Vermeiren, Robert] VU Univ Med Ctr VUMC, Amsterdam, Netherlands. [Vanwesenbeeck, Ine] Univ Utrecht, Utrecht, Netherlands. [Vanwesenbeeck, Ine] Res Rutgers WPF, Utrecht, Netherlands. RP Dewinter, J (reprint author), GGzE, Ctr Child & Adolescent Psychiat, Postbus 909, NL-5600 AX Eindhoven, Netherlands. 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Clin. Nurs. PD DEC PY 2013 VL 22 IS 23-24 SI SI BP 3467 EP 3483 DI 10.1111/jocn.12397 PG 17 WC Nursing SC Nursing GA 247VK UT WOS:000326650400025 PM 24112137 ER PT J AU Singer, JA Blagov, P Berry, M Oost, KM AF Singer, Jefferson A. Blagov, Pavel Berry, Meredith Oost, Kathryn M. TI Self-Defining Memories, Scripts, and the Life Story: Narrative Identity in Personality and Psychotherapy SO JOURNAL OF PERSONALITY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AUTISM SPECTRUM DISORDERS; AUTOBIOGRAPHICAL MEMORY; REDUCED SPECIFICITY; BIPOLAR DISORDER; OLDER-ADULTS; DEPRESSION; ADOLESCENCE; INTEGRATION; EXPERIENCE AB An integrative model of narrative identity builds on a dual memory system that draws on episodic memory and a long-term self to generate autobiographical memories. Autobiographical memories related to critical goals in a lifetime period lead to life-story memories, which in turn become self-defining memories when linked to an individual's enduring concerns. Self-defining memories that share repetitive emotion-outcome sequences yield narrative scripts, abstracted templates that filter cognitive-affective processing. The life story is the individual's overarching narrative that provides unity and purpose over the life course. Healthy narrative identity combines memory specificity with adaptive meaning-making to achieve insight and well-being, as demonstrated through a literature review of personality and clinical research, as well as new findings from our own research program. A clinical case study drawing on this narrative identity model is also presented with implications for treatment and research. C1 [Singer, Jefferson A.; Berry, Meredith] Connecticut Coll, New London, CT 06320 USA. [Blagov, Pavel; Oost, Kathryn M.] Whitman Coll, Walla Walla, WA 99362 USA. RP Singer, JA (reprint author), Connecticut Coll, Dept Psychol, New London, CT 06320 USA. 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PD DEC PY 2013 VL 81 IS 6 BP 569 EP 582 DI 10.1111/jopy.12005 PG 14 WC Psychology, Social SC Psychology GA 245LY UT WOS:000326466400006 PM 22925032 ER PT J AU Barnard-Brak, L Rojahn, J Wei, TL AF Barnard-Brak, Lucy Rojahn, Johannes Wei, Tianlan TI Psychometric Analysis of the Behavior Problems Inventory Using an Item-Response Theory Framework: A Sample of Individuals with Intellectual Disabilities SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE IRT; Behavior problems inventory; Self-injury; Stereotypy; Aggression; Differential item functioning ID AUTISM SPECTRUM DISORDERS; CHALLENGING BEHAVIORS; DEVELOPMENTAL-DISABILITIES; AGGRESSIVE-BEHAVIOR; FACTOR VALIDITY; RATING-SCALE; EM ALGORITHM; SHORT FORM; ADULTS; PREVALENCE AB The current study used an item response theory (IRT) framework to examine the psychometric properties of the long and short forms of the Behavior Problems Inventory (BPI-01 and BPI-S respectively). The BPI measures self-injurious, aggressive/destructive, and stereotyped behaviors as manifested among individuals with intellectual and developmental disabilities. With a sample of 1,122 individuals with intellectual and developmental disabilities, it is the first IRT examination of either form of the BPI. Results reveal acceptable psychometric properties for each form of the BPI as well as minimal differential item functioning according to sex. C1 [Barnard-Brak, Lucy; Wei, Tianlan] Texas Tech Univ, Dept Educ Psychol & Leadership, Lubbock, TX 79409 USA. [Rojahn, Johannes] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. RP Barnard-Brak, L (reprint author), Texas Tech Univ, Dept Educ Psychol & Leadership, POB 41071, Lubbock, TX 79409 USA. 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PD DEC PY 2013 VL 35 IS 4 BP 564 EP 577 DI 10.1007/s10862-013-9356-3 PG 14 WC Psychology, Clinical SC Psychology GA 248WE UT WOS:000326735400014 ER PT J AU Bessa, C Maciel, P Rodrigues, AJ AF Bessa, Carlos Maciel, Patricia Rodrigues, Ana Joao TI Using C-elegans to Decipher the Cellular and Molecular Mechanisms Underlying Neurodevelopmental Disorders SO MOLECULAR NEUROBIOLOGY LA English DT Review DE Neurodevelopment; C. elegans; Autism; Epilepsy; Intellectual disability ID LINKED MENTAL-RETARDATION; NEMATODE CAENORHABDITIS-ELEGANS; GLUTAMIC-ACID DECARBOXYLASE; NICOTINIC ACETYLCHOLINE-RECEPTORS; IDIOPATHIC GENERALIZED EPILEPSY; AUTISM SPECTRUM DISORDER; NEURONAL MIGRATION DEFECTS; SYNDROME CRITICAL REGION-1; POLYCYSTIC KIDNEY-DISEASE; TAU-INDUCED NEUROTOXICITY AB Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism. C1 [Bessa, Carlos; Maciel, Patricia; Rodrigues, Ana Joao] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal. [Bessa, Carlos; Maciel, Patricia; Rodrigues, Ana Joao] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal. RP Rodrigues, AJ (reprint author), ICVS 3Bs PT Govt Associate Lab, Braga, Portugal. EM ajrodrigues@ecsaude.uminho.pt RI Maciel, Patricia/B-5989-2009 OI Maciel, Patricia/0000-0002-0920-6350 FU Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-GMG/112577/2009]; FCT [SFRH/BPD/33611/2009, SFRH/BPD/74452/2010] FX The authors would like to acknowledge Fundacao para a Ciencia e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively. 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Neurobiol. PD DEC PY 2013 VL 48 IS 3 BP 465 EP 489 DI 10.1007/s12035-013-8434-6 PG 25 WC Neurosciences SC Neurosciences & Neurology GA 248PX UT WOS:000326714700007 PM 23494747 ER PT J AU Agazzi, H Tan, R Tan, SY AF Agazzi, Heather Tan, Robin Tan, Sim Yin TI A Case Study of Parent-Child Interaction Therapy for the Treatment of Autism Spectrum Disorder SO CLINICAL CASE STUDIES LA English DT Article DE parent training; PCIT; ASD ID PERVASIVE DEVELOPMENTAL DISORDER; RANDOMIZED CONTROLLED-TRIAL; EARLY INTERVENTION; YOUNG-CHILDREN; PDD-NOS; BEHAVIOR; FAMILIES AB Comorbid disruptive behavior disorders occur in up to 80% of children with Autism Spectrum Disorder (ASD). Children with ASD often present as inattentive, noncompliant, and aggressive, making it difficult for them to engage in learning and social activities across settings. Parents and school staff report spending excessive time managing disruptive behaviors at the expense of engaging these children in meaningful skill development. Identifying effective interventions to decrease disruptive behaviors and increase positive skill development is of critical importance to improving outcomes for children with ASD. This case study presents the effectiveness of Parent-Child Interaction Therapy, an evidence-based intervention for young children with disruptive behavior, for addressing behavioral problems in a 7-year-old boy with ASD. Results suggested improvements in child compliance and decrease in disruptive behaviors. Further, parents increased their use of positive parenting strategies, including giving effective commands all of which serve to improve the parent-child relationship. Treatment implications for working with young children with ASD are discussed. C1 [Agazzi, Heather; Tan, Robin; Tan, Sim Yin] Univ S Florida, Tampa, FL 33612 USA. RP Agazzi, H (reprint author), Univ S Florida, Dept Pediat, 13101 N Bruce B Downs Blvd,CMS 1057, Tampa, FL 33612 USA. EM hcurtiss@health.usf.edu CR Abner J. 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Case Stud. PD DEC PY 2013 VL 12 IS 6 BP 428 EP 442 DI 10.1177/1534650113500067 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9OU UT WOS:000346587800003 ER PT J AU Chiat, S Roy, P AF Chiat, Shula Roy, Penny TI Early Predictors of Language and Social Communication Impairments at Ages 9-11 Years: A Follow-Up Study of Early-Referred Children SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE language disorders; social communication; specific language impairment; syntax; phonology AB Purpose: In this study, the authors aimed to evaluate hypotheses that early sociocognition will predict later social communication and early phonology will predict later morphosyntax in clinically referred preschoolers. Method: Participants were 108 children ages 9- 11 years who had been referred to clinical services with concerns about language at age 2 - 3 years. Predictors at Time 1 ( T1) were measures of sociocognition, word/ nonword repetition, and receptive language. Outcome measures at Time 3 ( T3) included a social communication questionnaire completed by parents and tests of nonword repetition, morphosyntax, and receptive language. Results: Group- and case- level analyses revealed early sociocognition to be the strongest predictor of social communication problems, which by T3 affected almost one third of the sample. At the group level, early phonology, which was a significant problem for the majority of children at T1, was a weak predictor of morphosyntax at T3. However, at the case level the majority of children with poor morphosyntax and nonword repetition at outcome had had very low repetition scores at T1. Conclusions: In early language referrals, it is important to identify and address sociocognitive problems, a considerable risk for later social communication and autism spectrum disorders. The majority of early- referred children had phonological problems, often severe, but these require further investigation to determine their longer term significance for language. C1 [Chiat, Shula; Roy, Penny] City Univ London, London, England. RP Chiat, S (reprint author), City Univ London, London, England. 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Speech Lang. Hear. Res. PD DEC PY 2013 VL 56 IS 6 BP 1824 EP 1836 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA V37NY UT WOS:000209283700010 PM 23926296 ER PT J AU Arciuli, J Stevens, K Trembath, D Simpson, IC AF Arciuli, Joanne Stevens, Kirsten Trembath, David Simpson, Ian Craig TI The Relationship Between Parent Report of Adaptive Behavior and Direct Assessment of Reading Ability in Children With Autism Spectrum Disorder SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism; autism spectrum disorder (ASD); reading; literacy; Vineland Adaptive Behavior Scales-II; parent report AB Purpose: This study was designed to shed light on the profile of reading ability in children with autism spectrum disorder (ASD). A key aim was to examine the relationship between parent report of adaptive behavior and direct assessment of reading ability in these children. Method: The authors investigated children's reading ability using the Wide Range Achievement Test- Fourth Edition ( Wilkinson & Robertson, 2006) and the Neale Analysis of Reading Ability- Third Edition ( Neale, 2007). Parent report data was collected using the Vineland Adaptive Behavior Scales- Second Edition ( Sparrow, Cicchetti, & Balla, 2005). Participants were 21 children with ASD ( 6-11 years) and their primary caregivers. Results: Direct assessment of children's reading ability showed that some children with ASD have difficulty learning to read and exhibit particular weaknesses in comprehension. The results revealed positive relationships between Vineland Adaptive Behavior Scales scores in the Adaptive Communication domain and direct assessment of children's reading ability across 3 measures of reading ( word- level accuracy, passagelevel accuracy, and passage- level comprehension). 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S., 2006, WIDE RANGE ACHIEVEME NR 55 TC 0 Z9 0 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 EI 1558-9102 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2013 VL 56 IS 6 BP 1837 EP 1844 PG 8 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA V37NY UT WOS:000209283700011 PM 23926295 ER PT J AU Angoa-Perez, M Kane, MJ Briggs, DI Francescutti, DM Kuhn, DM AF Angoa-Perez, Mariana Kane, Michael J. Briggs, Denise I. Francescutti, Dina M. Kuhn, Donald M. TI Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 82; compulsive-like behaviors; obsessive-compulsive disorder (OCD); autism spectrum disorders (ASD); marble burying; nestlet shredding; TPH2 KO mice AB Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a significant public health concern, particularly in children. Both of these conditions are highlighted by the repeated expression of meaningless behaviors. Individuals with OCD often show checking, frequent hand washing, and counting. Children with ASDs also engage in repetitive tapping, arm or hand flapping, and rocking. These behaviors can vary widely in intensity and frequency of expression. More intense forms of repetitive behaviors can even result in injury (e.g. excessive grooming, hand washing, and self-stimulation). These behaviors are therefore very disruptive and make normal social discourse difficult. Treatment options for repetitive behaviors in OCD and ASDs are somewhat limited and there is great interest in developing more effective therapies for each condition. Numerous animal models for evaluating compulsive-like behaviors have been developed over the past three decades. Perhaps the animal models with the greatest validity and ease of use are the marble burying test and the nestlet shredding test. Both tests take advantage of the fact that the target behaviors occur spontaneously in mice. In the marble burying test, 20 marbles are arrayed on the surface of clean bedding. The number of marbles buried in a 30 min session is scored by investigators blind to the treatment or status of the subjects. In the nestlet shredding test, a nestlet comprised of pulped cotton fiber is preweighed and placed on top of cage bedding and the amount of the nestlet remaining intact after a 30 min test session is determined. Presently, we describe protocols for and show movie documentation of marble burying and nestlet shredding. Both tests are easily and accurately scored and each is sensitive to small changes in the expression of compulsive-like behaviors that result from genetic manipulations, disease, or head injury. C1 [Angoa-Perez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Kuhn, Donald M.] Wayne State Univ, Sch Med, John D Dingell VA Med Ctr, Res & Dev Serv, Detroit, MI 48202 USA. [Angoa-Perez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Kuhn, Donald M.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA. RP Kuhn, DM (reprint author), Wayne State Univ, Sch Med, John D Dingell VA Med Ctr, Res & Dev Serv, Detroit, MI 48202 USA. EM donald.kuhn@wayne.edu FU Department of Veterans Affairs; National Institutes of Health FX This work was supported by grants from the Department of Veterans Affairs and the National Institutes of Health. 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M., 2008, CURR PROTOC NEUROSCI, V30, P1, DOI [10.1002/0471142301.ns0930s45, DOI 10.1002/0471142301.NS0930S45] NR 21 TC 0 Z9 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD DEC PY 2013 IS 82 DI 10.3791/50978 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36RR UT WOS:000209229000052 ER PT J AU Ross, AS Hunter, SK Groth, MA Ross, RG AF Ross, Anne Spencer Hunter, Sharon Kay Groth, Mark A. Ross, Randal Glenn TI P50 Sensory Gating in Infants SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 82; Child Development; Psychophysiology; Attention Deficit and Disruptive Behavior Disorders; Evoked Potentials; Auditory; auditory evoked potential; sensory gating; infant; attention; electrophysiology; infants; sensory gating; endophenotype; attention; P50 AB Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating. Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is "gated"). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits. Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations. C1 [Ross, Anne Spencer; Hunter, Sharon Kay; Groth, Mark A.; Ross, Randal Glenn] Univ Colorado, Sch Med, Dept Psychiat, Boulder, CO 80309 USA. [Ross, Anne Spencer] Colorado State Univ, Ft Collins, CO 80523 USA. RP Ross, RG (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Boulder, CO 80309 USA. EM randy.ross@ucdenver.edu FU National Institutes of Health (NIH) [MH086383, MH056539, MH015442]; Institute for Children's Mental Disorders FX This work was funded, at least in part, by the National Institutes of Health (NIH grant numbers MH086383, MH056539 and MH015442) and by the Institute for Children's Mental Disorders. 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Vis. Exp. PD DEC PY 2013 IS 82 DI 10.3791/50065 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36RR UT WOS:000209229000001 ER PT J AU Cambridge, P AF Cambridge, Paul TI A rights approach to supporting the sexual fetish of a man with learning disability: method, process and applied learning SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE gender; learning (intellectual) disabilities; male and female sex lives; sexuality ID INTELLECTUAL DISABILITIES; MEN; SERVICE; PEOPLE; ABUSE AB Accessible summary Some men with learning disabilities have a sexual fetish which may present a support challenge for staff or carers. Sexual fetish in people with learning disabilities is often ignored, seen as pathological or associated with risk. It is possible to support sexual fetish in person-centred ways which respect individual rights and informed choice. SummaryThis paper reports on a psycho-educational intervention associated with the sexual fetish of a man with mild learning disability and autism which centred on his use of nappies and baby paraphernalia. It outlines the nature and expression of his sexual fetish and the risks perceived to be associated with it and describes the approach developed to support him, including the aims which underpinned the work and the methods and processes employed. It was found that a person-centred psycho-educational approach from a rights based perspective achieved important changes in his life and self-esteem and helped challenge assumptions about his sexual risk. The paper also reflects on the organisational location of this work and identifies the applied learning for supporting the sexual fetish of people with learning disabilities, of value for informing sex education and sexuality support for people with learning disabilities more widely. C1 Univ Kent, Dept Social Work, Chatham ME4 4AG, Kent, England. RP Cambridge, P (reprint author), Univ Kent, Dept Social Work, Chatham ME4 4AG, Kent, England. 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J. Learn. Disabil. PD DEC PY 2013 VL 41 IS 4 BP 259 EP 265 DI 10.1111/j.1468-3156.2012.00750.x PG 7 WC Education, Special SC Education & Educational Research GA 241QP UT WOS:000326182600003 ER PT J AU James, DM Hall, A Phillipson, J McCrossan, G Falck, C AF James, Deborah Michelle Hall, Alex Phillipson, John McCrossan, Geraldine Falck, Claire TI Creating a person-centred culture within the North East Autism Society: preliminary findings SO BRITISH JOURNAL OF LEARNING DISABILITIES LA English DT Article DE Autism; intervention; person-centred; qualitative methods; video feedback; workforce ID DISCRETE-TRIAL INSTRUCTION; TRAINING STAFF; METAANALYSIS AB Accessible Summary Staff who care for people with autism were shown video of themselves at work. Only good bits of video were shown to staff. Good bits were chosen because the video showed that the staff and the people with autism were enjoying being with each other. We asked four members of staff how watching the good bits of video made them think and feel. In this paper, we report what the staff said. We grouped their ideas into sets. In this paper, we report exactly what the staff said. We found that all staff felt more confident after watching the videos. They could see more ways that the people with autism were communicating with them. They could imagine being better at making relationships with people with autism. We think that finding positive moments of enjoyment using video is a good way to make things work better for staff and for the people with autism. SummaryThis paper provides preliminary findings of the impact of a workforce coaching intervention that used video feedback in a service for children and adults with autism. The proposed mechanism for change in the intervention was the way that video footage was highlighted through editing on the part of the practitioner and the positive coaching conversation that was used to review the video edits. Four participants who had received the intervention were interviewed after the intervention. Thematic analysis of the participants' responses during the narrative style interview was conducted. The results suggest that the participants found the intervention a positive experience that raised their confidence in their work role. They reported heightened awareness of the individual needs of the people they worked with and a new appreciation of the potential for relationship between themselves and the services' users. C1 [James, Deborah Michelle] Northumbria Univ, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. [James, Deborah Michelle; Falck, Claire] Univ Nottingham, NIHR Natl Biomed Res Unit Hearing, Nottingham NG7 2RD, England. [Hall, Alex] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Phillipson, John; McCrossan, Geraldine] North East Autism Soc, Sunderland, Durham, England. RP James, DM (reprint author), Northumbria Univ, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England. 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J. Learn. Disabil. PD DEC PY 2013 VL 41 IS 4 BP 296 EP 303 DI 10.1111/j.1468-3156.2012.00757.x PG 8 WC Education, Special SC Education & Educational Research GA 241QP UT WOS:000326182600008 ER PT J AU Yochim, EC Silva, VT AF Yochim, Emily Chivers Silva, Vesta T. TI Everyday Expertise, Autism, and "Good" Mothering in the Media Discourse of Jenny McCarthy SO COMMUNICATION AND CRITICAL-CULTURAL STUDIES LA English DT Article DE autism; expertise; mothering in the media; ethopolitics; Jenny McCarthy; postfeminism AB We examine Jenny McCarthy's mediated crusade to cure and prevent autism to better understand contemporary discourses about mothering, expertise, and gender. McCarthy distrusts traditional scientific and medical expertise and exalts what have long been seen as feminine modes of knowing such as instinct and experience. Her claims dismiss the medical community as wholly corrupt while reifying women's stereotypical identity as mothers. 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Crit.-Cult. Stud. PD DEC 1 PY 2013 VL 10 IS 4 BP 406 EP 426 DI 10.1080/14791420.2013.841320 PG 21 WC Cultural Studies; Communication SC Cultural Studies; Communication GA 241HG UT WOS:000326156400004 ER PT J AU Ennis, RP Jolivette, K Fredrick, LD Alberto, PA AF Ennis, Robin Parks Jolivette, Kristine Fredrick, Laura D. Alberto, Paul A. TI Using Comparison Peers as an Objective Measure of Social Validity: Recommendations for Researchers SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE behavior; special education; research ID TREATMENT ACCEPTABILITY; CLASSROOM-BEHAVIOR; SCHOOL-STUDENTS; MANAGEMENT; DISABILITIES; EDUCATION; AUTISM C1 [Ennis, Robin Parks; Jolivette, Kristine; Fredrick, Laura D.; Alberto, Paul A.] Georgia State Univ, Atlanta, GA 30302 USA. RP Ennis, RP (reprint author), Georgia State Univ, Dept Educ Psychol & Special Educ, POB 3979, Atlanta, GA 30302 USA. EM rennis1@gsu.edu CR Alberto P. A., 2013, APPL BEHAV ANAL TEAC Boden L., 2012, TEACHING EXCEPTIONAL, V45, P32 Carter SL, 2007, EDUC TRAIN DEV DISAB, V42, P301 Carter SL, 2008, EDUC TRAIN DEV DISAB, V43, P411 Chesley GM, 2012, EDUC LEADERSHIP, V69, P41 Coyle C, 2004, J INTELLECT DEV DIS, V29, P3, DOI 10.1080/08927020410001662642 Crone D. A., 2010, RESPONDING PROBLEM B Eber L, 2002, J EMOT BEHAV DISORD, V10, P171, DOI 10.1177/10634266020100030501 Ennis R. P., 2012, RESIDENTIAL TREATMEN, V29, P79 Fairbanks S, 2007, EXCEPT CHILDREN, V73, P288 Horner RH, 2005, EXCEPT CHILDREN, V71, P165 Jull S, 2011, J POSIT BEHAV INTERV, V13, P17, DOI 10.1177/1098300709358111 Kennedy C, 2005, SINGLE CASE DESIGNS Kern L, 2001, BEHAV DISORDERS, V26, P214 Lane KL, 2006, J EMOT BEHAV DISORD, V14, P108, DOI 10.1177/10634266060140020101 Lane KL, 2012, EDUC TREAT CHILD, V35, P51 Maag J. 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PD DEC PY 2013 VL 28 IS 4 BP 195 EP 201 DI 10.1177/1088357612475078 PG 7 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200001 ER PT J AU Buggey, T Ogle, L AF Buggey, Tom Ogle, Lindsey TI The Use of Self-Modeling to Promote Social Interactions Among Young Children SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; video modeling; social interaction; young children ID AUTISM SPECTRUM DISORDERS; INITIATIONS; PRESCHOOLERS; INTERVENTION; BEHAVIOR; PLAY AB Video self-modeling (VSM) has been used to teach social skills to children with autism older than 4 years of age. Attempts to use VSM with younger children with disabilities have produced less than favorable results; however, it is unclear whether VSM could be used to promote social initiations by typically developing children. Thirty minutes of staged filming, in which the four typically developing participants were prompted to interact with a peer with autism on the playground and inside during center time, was edited into 2.5- to 3-min clips. Each clip took less than 2 hr to edit. Data were collected on frequency of solitary play, initiations, parallel play, and engaged play and were then analyzed in a multiple-baseline-across-participants single-case design. Visual analysis led to the conclusion that VSM did not affect the typically developing children's behavior. Limitations of the study and cautions for using VSM with very young children are discussed. C1 [Buggey, Tom; Ogle, Lindsey] Univ Tennessee, Chattanooga, TN 37402 USA. RP Buggey, T (reprint author), Univ Tennessee, 205 Hunter Hall, Chattanooga, TN 37402 USA. EM tom-buggey@utc.edu CR Akullian J., 2007, EXCEPT CHILDREN, V73, P261 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bandura A, 2001, ANNU REV PSYCHOL, V52, P1, DOI 10.1146/annurev.psych.52.1.1 Bauman ML, 1999, DEV COGN NEUROSCI, P383 Bellini S, 2007, SCHOOL PSYCHOL REV, V36, P80 Bellini S, 2007, REM SPEC EDUC, V28, P153, DOI 10.1177/07419325070280030401 Buggey T., 2005, FOCUS AUTISM OTHER D, V20, P52, DOI DOI 10.1177/10883576050200010501 Buggey T, 2011, FOCUS AUTISM DEV DIS, V26, P25, DOI 10.1177/1088357609344430 Buggey T, 2012, FOCUS AUTISM DEV DIS, V27, P102, DOI 10.1177/1088357612441826 Buggey T, 2009, SEEING IS BELIEVING Clarke E., 1993, SCHOOL PSYCHOL INT, V14, P83, DOI DOI 10.1177/0143034393141006 DiSalvo C., 2002, FOCUS AUTISM OTHER D, V17, P198, DOI DOI 10.1177/10883576020170040201 DOWRICK PW, 1995, J DEV PHYS DISABIL, V7, P25, DOI 10.1007/BF02578712 Ganz J., 2011, TEACHING EXCEPTIONAL, V43, P8 Gelbar NW, 2012, PSYCHOL SCHOOLS, V49, P15, DOI 10.1002/pits.20628 Hine JF, 2006, TOP EARLY CHILD SPEC, V26, P83, DOI 10.1177/02711214060260020301 Kennedy C, 2005, SINGLE CASE DESIGNS Lewis M, 2004, CHILD DEV, V75, P1821, DOI 10.1111/j.1467-8624.2004.00819.x Litras S., 2010, AUTISM RES TREATMENT, DOI 10. 1155/2010/834979 LOVAAS OI, 1987, J CONSULT CLIN PSYCH, V55, P3, DOI 10.1037/0022-006X.55.1.3 Nikopoulos CK, 2003, BEHAV INTERVENT, V18, P87, DOI 10.1002/bin.129 Rosenwasser B, 2001, BEHAV MODIF, V25, P671, DOI 10.1177/0145445501255001 Schreibman L., 2000, J POSIT BEHAV INTERV, V1, P3 Strain P. S., 1996, PSYCHOSOCIAL TREATME, P573, DOI 10.1037/10196-022 Strain Phillip S., 1998, Seminars in Speech and Language, V19, P391, DOI 10.1055/s-2008-1064056 STRAIN PS, 1979, J AUTISM DEV DISORD, V9, P41, DOI 10.1007/BF01531291 Wert BY, 2003, J POSIT BEHAV INTERV, V5, P30, DOI 10.1177/10983007030050010501 Woods JJ, 2003, LANG SPEECH HEAR SER, V34, P180, DOI 10.1044/0161-1461(2003/015) NR 28 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 EI 1538-4829 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD DEC PY 2013 VL 28 IS 4 BP 202 EP 211 DI 10.1177/1088357612464518 PG 10 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200002 ER PT J AU Downs, A Downs, RC AF Downs, Andrew Downs, Robyn Conley TI Training New Instructors to Implement Discrete Trial Teaching Strategies With Children With Autism in a Community-Based Intervention Program SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE training; discrete trial teaching; supervision; preschools ID BEHAVIORAL TREATMENT; SPECTRUM DISORDERS; SKILLS; STUDENTS AB The effects of training and supervision on instructor knowledge and performance of discrete trial teaching (DTT) within three domains (DTT Technical Skills; Work Session Preparation/Conclusion; and Student Engagement/Management) were examined in this study. Eight undergraduate student instructors received an 8-hr training in DTT and support skills accompanied by a pre- and post-test of knowledge. The instructors then taught a variety of skills to six students with autism in a community-based preschool, where instructor competence was tracked and performance feedback provided using the Discrete Trial Teaching Competency Checklist for Instructors. Competence in all three domains improved over time with performance feedback. However, significant variability was observed within and between instructors, and performance in some areas remained below optimal levels even with regular supervision and performance feedback. Implications for training and supervising instructors to implement DTT with children with autism in community-based settings are discussed. C1 [Downs, Andrew] Univ Portland, Portland, OR 97203 USA. [Downs, Robyn Conley] Portland State Univ, Portland, OR 97207 USA. RP Downs, A (reprint author), Univ Portland, Dept Social & Behav Sci, MSC 185,5000 N Willamette Blvd, Portland, OR 97203 USA. EM downs@up.edu CR Arnal L., 2007, DEV DISABILITIES B, V35, P131 BABEL DA, 2008, DEV DISABILITIES B, V36, P67 Belfiore PJ, 2008, FOCUS AUTISM DEV DIS, V23, P95, DOI 10.1177/1088357607311445 Bolton J, 2008, FOCUS AUTISM DEV DIS, V23, P103, DOI 10.1177/1088357608316269 Chasson G. 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C., 2005, FOCUS AUTISM OTHER D, V20, P66, DOI DOI 10.1177/1088357 Stahmer AC, 2007, J AUTISM DEV DISORD, V37, P1344, DOI 10.1007/s10803-006-0284-x Thomson K, 2009, RES AUTISM SPECT DIS, V3, P590, DOI 10.1016/j.rasd.2009.01.003 Weisz JR, 2004, CLIN PSYCHOL-SCI PR, V11, P300, DOI 10.1093/clipsy/bph085 YOUNG JM, 1994, J APPL BEHAV ANAL, V27, P685, DOI 10.1901/jaba.1994.27-685 NR 37 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 EI 1538-4829 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD DEC PY 2013 VL 28 IS 4 BP 212 EP 221 DI 10.1177/1088357612465120 PG 10 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200003 ER PT J AU Fletcher-Watson, S Leekam, SR Findlay, JM AF Fletcher-Watson, Sue Leekam, Susan R. Findlay, John M. TI Social Interest in High-Functioning Adults With Autism Spectrum Disorders SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE high-functioning autism; Asperger syndrome; content analysis; social interest ID ASPERGER-SYNDROME; ANIMATED SHAPES; EYE-MOVEMENTS; MENTAL STATES; ATTENTION; ATTRIBUTION; PERCEPTION; PATTERNS; CHILDREN; INDIVIDUALS AB Autism spectrum disorders (ASD) are principally characterized by impairments in social functioning. Experimental investigation often is conducted using methods measuring social attention, social cognition, and social communication. In this study, we instead measured interest in social information, making a distinction between basic-level person-centered social information such as physical attributes of people (human information) and high-level social information such as hypotheses about mental states, emotion, and relationships (social information). Based on content analysis of verbal descriptions of color images, 31 young adults (4 women), aged 17 to 25 years with ASD, and 35 typically developing young adults (8 women), aged 17 to 31 years, devoted similar proportions of their descriptions to human and social topics. Results are interpreted in the context of current calls for more ecologically valid methodology and in relation to other assessments of social processing in ASD. C1 [Fletcher-Watson, Sue] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. [Leekam, Susan R.] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales. [Findlay, John M.] Univ Durham, Durham DH1 3HP, England. RP Fletcher-Watson, S (reprint author), Inst Educ Community & Soc, Moray House Sch Educ, Holyrood Rd, Edinburgh EH8 8AQ, Midlothian, Scotland. 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Disabil. PD DEC PY 2013 VL 28 IS 4 BP 222 EP 229 DI 10.1177/1088357613480829 PG 8 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200004 ER PT J AU Strid, K Heimann, M Gillberg, C Smith, L Tjus, T AF Strid, Karin Heimann, Mikael Gillberg, Christopher Smith, Lars Tjus, Tomas TI Deferred Imitation and Social Communication in Speaking and Nonspeaking Children With Autism SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; social communication; deferred imitation; joint attention ID EARLY LANGUAGE-ACQUISITION; JOINT ATTENTION; DIAGNOSTIC INTERVIEW; SPECTRUM DISORDER; YOUNG-CHILDREN; DEVELOPMENTAL-CHANGES; 24-MONTH-OLD INFANTS; MEMORY; IMMEDIATE; 14-MONTH-OLD AB Deferred imitation and early social communication skills were compared among speaking and nonspeaking children with autism and children developing typically. Overall, the children with autism showed a lower frequency on measures of deferred imitation and social communication compared with typically developing children. Deferred imitation was observed at a significantly lower level among the speaking and nonspeaking groups of children with autism. However, when comparing the speaking autism group with the typical group, many differences in observed social communication disappeared. These results underscore the importance of considering children's verbal ability in autism research and clinical practice, and indicate that there are specific difficulties in deferred imitation in autism but that the social communication deficits that are observed are greatly influenced by low level of verbal ability. C1 [Strid, Karin; Gillberg, Christopher; Tjus, Tomas] Univ Gothenburg, Gothenburg, Sweden. [Heimann, Mikael] Linkoping Univ, S-58183 Linkoping, Sweden. [Heimann, Mikael] Swedish Inst Disabil Res, Linkoping, Sweden. 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Disabil. PD DEC PY 2013 VL 28 IS 4 BP 230 EP 240 DI 10.1177/1088357612468030 PG 11 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200005 ER PT J AU Hughes, C Bernstein, RT Kaplan, LM Reilly, CM Brigham, NL Cosgriff, JC Boykin, MP AF Hughes, Carolyn Bernstein, Rebekah T. Kaplan, Lauren M. Reilly, Caitlin M. Brigham, Nicolette L. Cosgriff, Joseph C. Boykin, Michaela P. TI Increasing Conversational Interactions Between Verbal High School Students With Autism and Their Peers Without Disabilities SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; high school; communication books; general education peers; conversational interactions ID GENERAL-EDUCATION PEERS; SOCIAL-SKILLS INTERVENTIONS; INTELLECTUAL DISABILITIES; SPECTRUM DISORDERS; ADOLESCENTS; YOUTH; CHILDREN; IMPROVE AB Self-prompted communication books were used in combination with conversational peer orientation to increase conversational interactions of verbal high school students with autism or autistic-like behavior with their peers without disabilities. Previous investigators have used communication books only with students with autism or intellectual disability with limited or no verbal or reading skills. The six high school participants in this study could read and were verbal. We sought to determine whether the communication books would be accepted by peers without disabilities in general education classrooms or whether the books would stigmatize the students with disabilities. Finally, we assessed the effects of having a peer with a learning disability as the teacher of conversational interaction skills. We interpreted our results to conclude that the communication book package was associated with increased conversational interactions for all participants with their general education peers and that communication books were viewed positively by conversational partners. C1 [Hughes, Carolyn; Bernstein, Rebekah T.; Kaplan, Lauren M.; Reilly, Caitlin M.; Brigham, Nicolette L.; Cosgriff, Joseph C.; Boykin, Michaela P.] Vanderbilt Univ, Nashville, TN 37203 USA. RP Hughes, C (reprint author), Vanderbilt Univ, Dept Special Educ, Box 228 Peabody,230 Appleton Pl, Nashville, TN 37203 USA. 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PD DEC PY 2013 VL 28 IS 4 BP 241 EP 254 DI 10.1177/1088357613487019 PG 14 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 245GK UT WOS:000326450200006 ER PT J AU Woolcott, G AF Woolcott, Geoff TI Giftedness and cultural accumulation: an information processing perspective SO HIGH ABILITY STUDIES LA English DT Article DE expertise; giftedness; cultural accumulation; environmental interaction; information processing systems ID EDUCATION; NEUROSCIENCE; MIND; INTELLIGENCE; EVOLUTION; COGNITION; ABILITY; SCIENCE; AUTISM; BRAINS AB There appears to be differing approaches, in modern education, to the identification and development of gifted students, but researchers are beginning to find some cohesiveness through approaches that examine giftedness from within broad views of human cognition and behavior. 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PD DEC 1 PY 2013 VL 24 IS 2 BP 153 EP 170 DI 10.1080/13598139.2013.838897 PG 18 WC Education, Special SC Education & Educational Research GA 248CS UT WOS:000326671900006 ER PT J AU Wang, Y Zhou, WD Yuan, Q Li, XL Meng, QF Zhao, XH Wang, JW AF Wang, Yu Zhou, Weidong Yuan, Qi Li, Xueli Meng, Qingfang Zhao, Xiuhe Wang, Jiwen TI COMPARISON OF ICTAL AND INTERICTAL EEG SIGNALS USING FRACTAL FEATURES SO INTERNATIONAL JOURNAL OF NEURAL SYSTEMS LA English DT Article DE Electroencephalogram (EEG); nonlinear features; blanket dimension; fractal intercept ID FUZZY SYNCHRONIZATION LIKELIHOOD; EPILEPTIC SEIZURE DETECTION; NEURAL NETWORK METHODOLOGY; WAVELET-CHAOS METHODOLOGY; AUTISM SPECTRUM DISORDER; ALZHEIMERS-DISEASE; CORRELATION DIMENSION; NONLINEAR FEATURES; FEATURE-EXTRACTION; CLASSIFICATION AB The feature analysis of epileptic EEG is very significant in diagnosis of epilepsy. This paper introduces two nonlinear features derived from fractal geometry for epileptic EEG analysis. The features of blanket dimension and fractal intercept are extracted to characterize behavior of EEG activities, and then their discriminatory power for ictal and interictal EEGs are compared by means of statistical methods. It is found that there is significant difference of the blanket dimension and fractal intercept between interictal and ictal EEGs, and the difference of the fractal intercept feature between interictal and ictal EEGs is more noticeable than the blanket dimension feature. Furthermore, these two fractal features at multi-scales are combined with support vector machine (SVM) to achieve accuracies of 97.58% for ictal and interictal EEG classification and 97.13% for normal, ictal and interictal EEG classification. C1 [Wang, Yu; Zhou, Weidong; Yuan, Qi; Li, Xueli; Meng, Qingfang] Shandong Univ, Sch Informat Sci & Engn, Jinan 250100, Peoples R China. [Zhao, Xiuhe; Wang, Jiwen] Shandong Univ, Qilu Hosp, Jinan 250100, Peoples R China. RP Zhou, WD (reprint author), Shandong Univ, Sch Informat Sci & Engn, 27 Shanda Rd, Jinan 250100, Peoples R China. EM wdzhou@sdu.edu.cn FU Program of Science and Technology of Suzhou [ZXY2013030]; Independent Innovation Foundation of Shandong University [2012DX008]; National Natural Science Foundation of China [61201428] FX The support of the Program of Science and Technology of Suzhou (No. ZXY2013030), the Independent Innovation Foundation of Shandong University (No. 2012DX008), and the National Natural Science Foundation of China (No. 61201428) is gratefully acknowledged. 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J. Neural Syst. PD DEC PY 2013 VL 23 IS 6 AR 1350028 DI 10.1142/S0129065713500287 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA 245FV UT WOS:000326448400004 PM 24156671 ER PT J AU Guevara-Campos, J Gonzalez-Guevara, L Puig-Alcaraz, C Cauli, O AF Guevara-Campos, Jose Gonzalez-Guevara, Lucia Puig-Alcaraz, Carmen Cauli, Omar TI Autism spectrum disorders associated to a deficiency of the enzymes of the mitochondrial respiratory chain SO METABOLIC BRAIN DISEASE LA English DT Article DE Mitochondrial alteration; Autism; Lactate; Muscular biopsy ID CHILDREN; DISEASES; PREVALENCE; DIAGNOSIS; GENETICS; INFANTS AB Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interest and stereotypies. The etiology is generally multifactorial, including genetic, immunological and/or environmental factors. A group of ASD has been linked to mitochondrial dysfunction with subsequent deficiency in energy production. Patients with ASD and mitochondrial disease often show signs and symptoms uncommon to idiopathic ASD such as cardiac, pancreatic or liver dysfunction, cardiac, growth retardation, fatigability, but in some cases semiology is different. We show two clinical cases of ASD associated to a deficiency of the mitochondrial respiratory chain (complex I+III and IV) with different clinical presentations. In one case, signs and symptoms of mitochondrial disorder were mild and the second diagnosis was attained many years after that of ASD. These findings support the recent growing body of evidence that ASD can be associated with mitochondrial disorder. Children with ASD and abnormal neurologic or systemic findings should be evaluated for mitochondrial disorder. C1 [Guevara-Campos, Jose; Gonzalez-Guevara, Lucia] Univ Oriente, Serv Pediat, Felipe Guevara Rojas Hosp, El Tigre, Anzoategui, Venezuela. [Gonzalez-Guevara, Lucia] Epilepsy & Encephalog Unit, El Tigre, Anzoategui, Venezuela. [Puig-Alcaraz, Carmen] Area 4 Sagunto, Psychiat Unit, Valencia, Spain. [Cauli, Omar] Univ Valencia, Dept Nursing, Valencia 46010, Spain. RP Cauli, O (reprint author), Univ Valencia, Dept Nursing, C Jaume Roig S-N, Valencia 46010, Spain. 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Y. Wong, Denys Chung, Anthony C. Y. Kwok, Natalie Lam, Madeleine K. Y. Yuen, Cheri M. C. Arblaster, Karen Kwan, Aldous C. S. TI Effectiveness of a Workplace Training Programme in Improving Social, Communication and Emotional Skills for Adults with Autism and Intellectual Disability in Hong Kong - A Pilot Study SO OCCUPATIONAL THERAPY INTERNATIONAL LA English DT Article DE workplace training; social and communication skills; adults with autism and intellectual disability ID SPECTRUM DISORDERS; ADOLESCENTS; PEOPLE; OUTCOMES; LIFE AB This pilot study explored the effectiveness of workplace training programme that aimed to enhance the work-related behaviours in individuals with autism and intellectual disabilities. Fourteen participants with autism and mild to moderate intellectual disability (mean age=24.6years) were recruited. The workplace training programme included practices in work context and group educational sessions. A pre-test-post-test design was used with the Work Personality Profile, the Scale of Independent Behaviour Revised and the Observational Emotional Inventory Revised to evaluate the targeted behaviours. Improvement in social and communication skills specific to the workplace was achieved. For emotional control, participants became less confused and had a better self-concept. However, improvement in other general emotional behaviours, such as impulse control, was limited. The results indicated that a structured workplace training programme aimed at improving social, communication and emotional behaviours can be helpful for people with autism and intellectual disability. Further study with a larger sample size and a control group is recommended. The development of specific programme to cater for the emotional control needs at workplace for people with autism is also suggested. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Liu, Karen P. 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Zhang, Heping Luo, Xingguang TI Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence SO PSYCHIATRIC GENETICS LA English DT Article DE alcohol dependence; homolog; male specificity; NLGN4X; synaptogenesis; Y chromosome ID SYNAPSE FORMATION; NEUROLIGINS; AUTISM; NEUREXINS; NLGN4; EXPRESSION; EVOLUTION; REGION AB BackgroundAlcohol dependence is more common among men than among women. Potential explanations for this include the role of genes in sex chromosomes (X and Y). In the present study, we scanned the entire Y chromosome and its homologs on the X chromosome in men to identify male-specific risk genes for alcohol dependence.MethodsTwo thousand nine hundred and twenty-seven individuals in two independent cohorts were analyzed. The European-American male cohort (883 cases with alcohol dependence and 445 controls) served as the discovery cohort and the European-American female cohort (526 cases and 1073 controls) served as a contrast group. All individuals were genotyped on the Illumina Human 1M beadchip. Two thousand two hundred and twenty-four single nucleotide polymorphisms (SNPs) on the Y chromosome or in the homologs on the X chromosome were analyzed. The allele frequencies were compared between cases and controls within each cohort using logistic regression analysis.ResultsWe found that, after experiment-wide correction, two SNPs on the X chromosome were associated significantly with alcohol dependence in European-American men (P=1.0x10(-4) for rs5916144 and P=5.5x10(-5) for rs5961794 at 3 UTR of NLGN4X), but not in the women. A total of 26 SNPs at 3UTR of or within NLGN4X were nominally associated with alcohol dependence in men (5.5x10(-5)P0.05), all of which were not statistically significant in women.ConclusionWe conclude that NLGN4X was a significant male-specific risk gene for alcohol dependence in European-Americans. NLGN4X might harbor a causal variant(s) for alcohol dependence. A defect of synaptogenesis in neuronal circuitry caused by NLGN4X mutations is believed to play a role in alcohol dependence. C1 [Zuo, Lingjun; Krystal, John H.; Luo, Xingguang] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Pan, Xinghua] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Wang, Guilin] Yale Univ, Sch Med, Yale Ctr Genome Anal, Dept Genet, West Haven, CT 06516 USA. [Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Wang, Kesheng] E Tennessee State Univ, Coll Publ Hlth, Dept Biostat & Epidemiol, Johnson City, TN 37614 USA. [Zhang, Xiangyang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Luo, XG (reprint author), Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. EM lingjun.zuo@yale.edu; xingguang.luo@yale.edu FU National Alliance for Research on Schizophrenia and Depression (NARSAD) Award [17616]; ABMRF/The Foundation for Alcohol Research; National Institute on Drug Abuse (NIDA) [K01 DA029643, K24 DA017899, R01 DA016750, K02 DA026990, R01 DA013423]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01 AA016015, R21 AA020319, K24 AA013736, P50 AA012870, U10 AA008401]; Genes, Environment and Health Initiative (GEI) [U01HG004422, U01HG004438]; GENEVA Coordinating Center [U01 HG004446]; National Cancer Institute [P01 CA089392]; NIH [HHSN268200782096C]; Department of Veterans Affairs (the VA Alcohol Research Center); Department of Veterans Affairs (VA National Center for PTSD); Department of Veterans Affairs (Depression REAP) FX The authors thank NIH GWAS Data Repository, the Contributing Investigator(s) (Drs. Bierut, Edenberg, etc.) who contributed the phenotype and genotype data (SAGE and COGA) from his/her original study, and the primary funding organization that supported the contributing study. Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research or at deCODE. Grant sponsor: National Alliance for Research on Schizophrenia and Depression (NARSAD) Award (L.Z.); Grant number: 17616; Grant sponsor: ABMRF/The Foundation for Alcohol Research (L.Z.); Grant sponsor: National Institute on Drug Abuse (NIDA); Grant numbers: K01 DA029643, K24 DA017899, R01 DA016750, K02 DA026990, R01 DA013423; Grant sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Grant numbers: R01 AA016015, R21 AA020319, K24 AA013736, P50 AA012870, U10 AA008401; Grant sponsor: Genes, Environment and Health Initiative (GEI); Grant numbers: U01HG004422, U01HG004438; Grant sponsor: GENEVA Coordinating Center; Grant number: U01 HG004446; Grant sponsor: National Cancer Institute; Grant number: P01 CA089392; Grant sponsor: NIH contract 'High throughput genotyping for studying the genetic contributions to human disease'; Grant number: HHSN268200782096C; Grant sponsor: Department of Veterans Affairs (the VA Alcohol Research Center, the VA National Center for PTSD, and the Depression REAP). 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Genet. PD DEC PY 2013 VL 23 IS 6 BP 233 EP 238 DI 10.1097/YPG.0b013e328364b8c7 PG 6 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 247AB UT WOS:000326583200002 PM 23907288 ER PT J AU Camacho-Garcia, RJ Hervas, A Toma, C Balmana, N Cormand, B Martinez-Mir, A Scholl, FG AF Camacho-Garcia, Rafael J. Hervas, Amaia Toma, Claudio Balmana, Noemi Cormand, Bru Martinez-Mir, Amalia Scholl, Francisco G. TI Rare variants analysis of neurexin-1 beta in autism reveals a novel start codon mutation affecting protein levels at synapses SO PSYCHIATRIC GENETICS LA English DT Article DE autism; mutation; neurexin; neuroligin; NRXN; synapse; translation ID NEUROLIGINS; GENES AB Neurexins are synaptic plasma membrane proteins encoded by three genes (NRXN1, -2, -3) with alternative promoters. Mutations in neurexin genes have been identified in different neurodevelopmental disorders, including autism. Recently, two point mutations altering the translation initiation site of NRXN1 (c.-3G>T and c.3G>T) have been described in patients with autism and mental retardation. In this study, we analyzed the NRXN1 gene in a sample of 153 patients with autism. We report the identification of a novel mutation, c.3G>A (p.Met1), affecting the translation initiation site. Expression analysis showed that the c.3G>A mutation switches the translation start site of NRXN1 to an in-frame downstream methionine and decreases synaptic levels of the mutant protein in cultured neurons. These data reinforce a role for synaptic defects of NRXN1 in neurodevelopmental disorders. C1 [Camacho-Garcia, Rafael J.; Martinez-Mir, Amalia; Scholl, Francisco G.] Virgen Rocio Univ Hosp, CSIC, Seville Biomed Res Inst IBiS, Seville, Spain. [Scholl, Francisco G.] Univ Seville, Dept Physiol & Med Biophys, Seville, Spain. [Hervas, Amaia; Balmana, Noemi] Mutua Terrassa Univ Hosp, Child & Adolescent Mental Hlth Unit, Terrassa, Spain. [Toma, Claudio; Cormand, Bru] Univ Barcelona, Fac Biol, Dept Genet, E-08007 Barcelona, Spain. [Toma, Claudio; Cormand, Bru] Univ Barcelona, Biomed Network Res Ctr Rare Dis CIBERER, E-08007 Barcelona, Spain. [Cormand, Bru] Univ Barcelona, Inst Biomed IBUB, E-08007 Barcelona, Spain. RP Scholl, FG (reprint author), Campus Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Avda,Manuel Siurot S-N, Seville 41013, Spain. EM fgs@us.es RI Toma, Claudio/L-7853-2014 OI Toma, Claudio/0000-0003-3901-7507 FU Instituto de Salud Carlos III, Spain (ISCIII-FIS) [PI111058]; Ministerio de Economia y Competitividad, Spain [PIM2010ERN-0070, SAF2012-33484]; Fundacio La Marato de TV3 [092010]; Fundacion Alicia Koplowitz; Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR, Generalitat de Catalunya [2009SGR00971]; Instituto de Salud Carlos III [FI08/00730]; European Union [PIEF-GA-2009-254930] FX This study was supported by grants from Instituto de Salud Carlos III, Spain (ISCIII-FIS; PI111058), Ministerio de Economia y Competitividad, Spain (PIM2010ERN-0070, SAF2012-33484), Fundacio La Marato de TV3 (092010), Fundacion Alicia Koplowitz and Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR, Generalitat de Catalunya (2009SGR00971). R.J.C.-G. was a recipient of a fellowship from Instituto de Salud Carlos III (FI08/00730) and C. T. was supported by the European Union (Marie Curie, PIEF-GA-2009-254930). 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TI Public School-Based Interventions for Adolescents and Young Adults With an Autism Spectrum Disorder: A Meta-Analysis SO REVIEW OF EDUCATIONAL RESEARCH LA English DT Article DE autism spectrum disorder; meta-analysis; intervention; public schools; adolescents ID SOCIAL-SKILLS INTERVENTIONS; PERSONAL DIGITAL ASSISTANT; SINGLE-SUBJECT RESEARCH; OF-THE-LITERATURE; SPECIAL-EDUCATION; MODELING INTERVENTIONS; COMMUNITY SETTINGS; ASPERGER-SYNDROME; STUDENTS; VIDEO AB This article reviews research on the effectiveness of four categories of intervention when implemented in public schools with adolescents and young adults diagnosed with an autism spectrum disorder. The study's inclusionary criteria include a setting of public schools, participants aged between 12 and 22 years, and the investigation of an antecedent-, consequence-, self-management-, or video-based intervention strategy to influence skills or behaviors in students. A total of 34 studies met these criteria. The procedures of the What Works Clearinghouse Standards for Single-Case Designs and Evidence are used to evaluate whether sufficient high-quality research in using antecedent-, consequence-, self-management-, and video-based strategies exists to consider these evidence-based practices. Intervention effectiveness is estimated using PAND scores and phi coefficients. The results suggest that sufficient research exists to consider antecedent-, video-, and consequence-based interventions evidence-based practices for adolescents and young adults in public schools. The need for more applied research with adolescents and young adults is highlighted. C1 [de Bruin, Catriona L.; Deppeler, Joanne M.] Monash Univ, Fac Educ, Melbourne, Vic 3004, Australia. [Moore, Dennis W.] Monash Univ, Melbourne, Vic 3004, Australia. [Diamond, Neil T.] Monash Univ, Dept Econometr & Business Stat, Melbourne, Vic 3004, Australia. 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Educ. Res. PD DEC PY 2013 VL 83 IS 4 BP 521 EP 550 DI 10.3102/0034654313498621 PG 30 WC Education & Educational Research SC Education & Educational Research GA 242KM UT WOS:000326239900002 ER PT J AU Sowden, H Clegg, J Perkins, M AF Sowden, Hannah Clegg, Judy Perkins, Michael TI The development of co-speech gesture in the communication of children with autism spectrum disorders SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE ASD; autism; autism spectrum disorder; children; development; gesture; speech; audio-visual integration; supplementary gesture ID EARLY LANGUAGE-DEVELOPMENT; YOUNG-CHILDREN; 2-WORD SPEECH; TRANSITION; COMPREHENSION; INTEGRATION; PROFILES; WORDS AB Co-speech gestures have a close semantic relationship to speech in adult conversation. In typically developing children co-speech gestures which give additional information to speech facilitate the emergence of multi-word speech. A difficulty with integrating audio-visual information is known to exist for individuals with Autism Spectrum Disorder (ASD), which may affect development of the speech-gesture system. A longitudinal observational study was conducted with four children with ASD, aged 2;4 to 3;5 years. Participants were video-recorded for 20 min every 2 weeks during their attendance on an intervention programme. Recording continued for up to 8 months, thus affording a rich analysis of gestural practices from pre-verbal to multi-word speech across the group. All participants combined gesture with either speech or vocalisations. Co-speech gestures providing additional information to speech were observed to be either absent or rare. Findings suggest that children with ASD do not make use of the facilitating communicative effects of gesture in the same way as typically developing children. C1 [Sowden, Hannah] Univ Leeds, Sch Modern Languages & Cultures, Leeds LS2 9JT, W Yorkshire, England. [Clegg, Judy; Perkins, Michael] Univ Sheffield, Sheffield, S Yorkshire, England. RP Sowden, H (reprint author), Univ Leeds, Sch Modern Languages & Cultures, Leeds LS2 9JT, W Yorkshire, England. 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Linguist. Phon. PD DEC PY 2013 VL 27 IS 12 BP 922 EP 939 DI 10.3109/02699206.2013.818715 PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 240TD UT WOS:000326119000006 PM 23944149 ER PT J AU Huang, SF Oi, M AF Huang, Su-Fen Oi, Manabu TI Responses to Wh-, Yes/No-, A-not-A, and choice questions in Taiwanese children with high-functioning autism spectrum disorder SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE A-not-A questions; choice questions; high-functioning autism spectrum disorder; Taiwanese; Wh-questions; Yes/No questions ID JAPANESE CHILDREN; ASPERGER-SYNDROME; DOWN-SYNDROME; ASKING; COMPREHENSION; DIFFICULTIES; IMPAIRMENTS; DISABILITY; ADEQUACY; SPEECH AB The present study investigated the hypothesis that children with high-functioning autism spectrum disorder (HFASD) have a greater difficulty in responding to Wh- than Yes/No questions across languages. Conversations between Taiwanese children and their mothers were investigated and the children's response adequacy to maternal questions in a semi-structured setting were examined. Twelve Taiwanese children with HFASD, ranging in age from 7.1 to 14.9 years old, were compared with 12 typically developing (TD) children matched on age, sex, IQ and mean length of utterance in syllable (MLUs). Compared to TD children, HFASD children produced more inadequate or inappropriate responses to Wh-and Yes/No questions than to A-not-A and Choice questions. Taiwanese HFASD children share a greater difficulty in responding to maternal Wh-questions with their Japanese counterparts and do not show a relative ease in responding to Yes/No questions, while A-not-A and Choice questions were easier to respond to for the Taiwanese children. C1 [Huang, Su-Fen] Natl Taitung Univ, Dept Early Childhood Educ, Taitung, Taiwan. [Oi, Manabu] Kanazawa Univ, United Grad Sch Child Dev, Kanazawa, Ishikawa 9208640, Japan. RP Oi, M (reprint author), Kanazawa Univ, United Grad Sch Child Dev, B-B43,13-1 Takaramachi, Kanazawa, Ishikawa 9208640, Japan. EM oimanabu@ed.kanazawa-u.ac.jp FU Japan Society for Promotion of Science [18330202] FX The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of this article. This research was supported by a Grant-in-Aid for Scientific Research (No. 18330202) from the Japan Society for Promotion of Science. CR Ambridge B, 2006, J CHILD LANG, V33, P519, DOI 10.1017/S0305000906007513 Bishop DVM, 2000, DEV PSYCHOPATHOL, V12, P177, DOI 10.1017/S0954579400002042 Chao R. 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Linguist. Phon. PD DEC PY 2013 VL 27 IS 12 BP 969 EP 985 DI 10.3109/02699206.2013.835446 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 240TD UT WOS:000326119000009 PM 24093161 ER PT J AU Shaughnessy, N AF Shaughnessy, Nicola TI Imagining Otherwise: Autism, Neuroaesthetics and Contemporary Performance SO INTERDISCIPLINARY SCIENCE REVIEWS LA English DT Article DE drama; autism; neuroaesthetics; performance AB Perspectives on the phenomenology of the autistic experience are presented with particular reference to the imagination in autism and what may be conceptualized as 'neurodivergent aesthetics'. Drawing upon a research project that explored the potential of drama as an 'intervention' in autism, an attempt is made to de-mythologize the condition by challenging stereotypes and by suggesting that the multimodalities of performance offer an appropriate space for 'encounters' with autistic states of being while also questioning the dualisms which distinguish between the aesthetic and non-aesthetic. C1 Univ Kent, Canterbury CT2 7NZ, Kent, England. RP Shaughnessy, N (reprint author), Univ Kent, Canterbury CT2 7NZ, Kent, England. 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Sci. Rev. PD DEC PY 2013 VL 38 IS 4 BP 321 EP 334 DI 10.1179/0308018813Z.00000000062 PG 14 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA 239JK UT WOS:000326018700005 ER PT J AU Baeza-Velasco, C Michelon, C Rattaz, C Pernon, E Baghdadli, A AF Baeza-Velasco, Carolina Michelon, Cecile Rattaz, Cecile Pernon, Eric Baghdadli, Amaria TI Separation of Parents Raising Children with Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Autism; Separation; Timing of separation; Sociodemographic variables; Cohort ID FAMILIES; DISABILITIES; ADJUSTMENT; DIVORCE; MOTHERS; HEALTH; RISK AB We examined the occurrence and timing of separation of parents raising children with Autism Spectrum Disorders followed over a 10-year period (n = 119). We also compared the clinical characteristics of children and sociodemographic variables between parents who remained as a couple versus parents who separated. The results showed that after 10 years of follow-up 74.8 % of the couples remained together (n = 89), representing a separation rate of 25.2 %. This rate remained stable over the study period. There was no significant difference in any of the clinical and sociodemographic variables between comparison groups. Our results suggest that raising a child with autism does not often lead to the dissolution of the parents' relationship, as is commonly believed. The occurrence of parental separation in children with Autism Spectrum Disorders does not appear to vary according to their stage of life (childhood or adolescence). Lastly, the clinical profile of children and sociodemographic variables do not seem to influence the relationship status of parents. 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Tincani, Matt Dodge, Jessica Gilroy, Shawn Hickey, Anna Hantula, Donald TI Evaluating Picture Exchange and the iPad (TM) as a Speech Generating Device to Teach Communication to Young Children with Autism SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Review DE Autism; Mand; Picture exchange; Speech generating device; Voice output communication aid; Augmentative and alternative communication ID DEVELOPMENTAL-DISABILITIES; FUNCTIONAL COMMUNICATION; GRAPHIC SYMBOLS; PECS; STUDENTS; VOCA AB The purpose of the study was to compare picture exchange (PE) and an iPad (TM) -based speech generating device (SGD) in teaching mands to five preschool boys diagnosed with autism. Participants' preferences for each device were assessed following training. Three participants met mastery criterion for mands using the SGD more quickly, while two participants met mastery criterion for mands using PE more readily. However, the overall rate of independent manding across training and maintenance was higher for four participants using the SGD. Four participants demonstrated a clear preference for the SGD device and one for PE. Results are consistent with previous research showing that acquisition of alternative communication modalities varies across children with autism, and supports the use of assessment to determine modality preference. C1 [Lorah, Elizabeth R.; Tincani, Matt; Dodge, Jessica; Gilroy, Shawn; Hickey, Anna; Hantula, Donald] Temple Univ, Philadelphia, PA 19122 USA. RP Lorah, ER (reprint author), Temple Univ, Philadelphia, PA 19122 USA. EM erlorah@temple.edu CR Beck AR, 2008, EDUC TRAIN DEV DISAB, V43, P198 Bock SJ, 2005, EDUC TRAIN DEV DISAB, V40, P264 Bondy A, 2001, BEHAV MODIF, V25, P725, DOI 10.1177/0145445501255004 Charlop-Christy MH, 2002, J APPL BEHAV ANAL, V35, P213, DOI 10.1901/jaba.2002.35-213 Cooper J. 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PD DEC PY 2013 VL 25 IS 6 BP 637 EP 649 DI 10.1007/s10882-013-9337-1 PG 13 WC Rehabilitation SC Rehabilitation GA 240NY UT WOS:000326105000005 ER PT J AU Gilmore, L Campbell, M Shochet, I Roberts, C AF Gilmore, Linda Campbell, Marilyn Shochet, Ian Roberts, Clare TI RESILIENCY PROFILES OF CHILDREN WITH INTELLECTUAL DISABILITY AND THEIR TYPICALLY DEVELOPING PEERS SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID MENTAL-HEALTH; SELF-CONCEPT; ADOLESCENTS; MOTIVATION; PEOPLE; PARTICIPATION; INTERVENTIONS; CONSTRUCT; DISORDER; AUTISM AB Intellectual disability (ID) is associated with a range of risk factors that make children more vulnerable to adverse developmental outcomes, including mental health problems. Nevertheless, some children with ID do much better than others, presumably because of the presence of protective factors that increase their resilience. The current study compared resiliency profiles of children with ID (n = 115; mean age, 11.9 years) and their typically developing peers (n = 106; mean age, 11.8 years) using the Resiliency Scales for Children and Adolescents and the Healthy Kids Resilience Assessment. In many respects, children with ID and their typically developing peers reported similar levels of the protective factors that are associated with resilience. However, the children with ID reported higher levels of emotional sensitivity and lower tolerance, as well as fewer future goals. Compared with typically developing children, those with ID reported more support at school and less support within their communities. These findings have important implications for interventions that aim to promote positive developmental outcomes and to prevent the adverse sequelae that have been associated with low intelligence. C1 [Gilmore, Linda; Campbell, Marilyn; Shochet, Ian] Queensland Univ Technol, Kelvin Grove, Qld 4059, Australia. [Roberts, Clare] Curtin Univ, Perth, WA, Australia. RP Gilmore, L (reprint author), Queensland Univ Technol, Sch Learning & Profess Studies, Victoria Pk Rd, Kelvin Grove, Qld 4059, Australia. EM l.gilmore@qut.edu.au CR Australian Bureau of Statistics, 2006, SOC IND AR SEIFA Brown B. B., 2009, HDB ADOLESCENT PSYCH, V2, P74, DOI DOI 10.1002/9780470479193 Bukowski WM, 2007, MERRILL PALMER QUART, V53, P507, DOI 10.1353/mpq.2007.0014 Caselman T. 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Schools PD DEC PY 2013 VL 50 IS 10 BP 1032 EP 1043 DI 10.1002/pits.21728 PG 12 WC Psychology, Educational SC Psychology GA 240BD UT WOS:000326068800006 ER PT J AU Sudarov, A AF Sudarov, Anamaria TI Defining the Role of Cerebellar Purkinje Cells in Autism Spectrum Disorders SO CEREBELLUM LA English DT Article DE ASD; Tsc1; Purkinje cells; Behavior; Synapses ID TUBEROUS SCLEROSIS COMPLEX; MOUSE MODEL; TSC1; SURVIVAL AB Understanding the contribution of cerebellar dysfunction to complex neurological diseases such as autism spectrum disorders (ASD) is an ongoing topic of investigation. In a recent paper, Tsai et al. (Nature 488:647-651, 2012) used a powerful combination of conditional mouse genetics, electrophysiology, behavioral tests, and pharmacological manipulations to address the role of Tuberous sclerosis complex 1 (Tsc1) in Purkinje cells and cerebellar function. The authors make the staggering discovery that morphological and electrophysiological defects in Purkinje cells are linked to system-wide ASD-like behavioral deficits. In this journal club, I discuss the major findings of this paper and critically assess the implications of this seminal work. C1 Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY 10065 USA. RP Sudarov, A (reprint author), Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY 10065 USA. 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The purpose of this research is to see the effects of video modelling practice over the mental retarded students, when they meet people. In this research, teaching the social skills to the students with mental retardations were evaluated with the effectiveness of teaching with video modelling, model of multiple probe design between subjects from research models of single subject design. In this research four students, whose ages ranged from ten to eleven attending a special education class at a primary school in Ankara and who had intellectual disabilities were participated. The peers group consisted of 3 girls and 2 boys who studied at the same elementary school with the target students (all of them were 11 years old and continue their studied at 5th grade class). Research findings showed that using the video modelling in teaching students with intellectual disabilities help them to acquire the skill of greeting people and after gaining those skills they continued to use the skills and have shown that they continue to use in different situation and to different people. After the interviews done with the mothers and the teachers of the students about the results of teaching the skill of "greeting when meet people" through video modelling, it was seen that they were satisfied with these skills to have been taught to the students. They also expressed that the students had more interaction with their friends around them in much earlier time. C1 [Avcioglu, Hasan] Cyprus Int Univ, Nicosia, Northern Cyprus, Cyprus. RP Avcioglu, H (reprint author), Cyprus Int Univ, Fac Educ, Dept Mentally Handicapped Teaching, Nicosia, Northern Cyprus, Cyprus. EM hasana@ciu.edu.tr CR Akmanoglu N, 2008, THESIS ANADOLU U Allison S. 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R., 1991, SOCIAL SKILLS SCH CO Scattone D, 2008, J AUTISM DEV DISORD, V38, P395, DOI 10.1007/s10803-007-0392-2 Schreibman L., 2000, J POSIT BEHAV INTERV, V2, P3, DOI 10.1177/109830070000200102 Sherer M, 2001, BEHAV MODIF, V25, P140, DOI 10.1177/0145445501251008 Tekin-Iftar E, 2001, OZEL EGITIMDE YANLIS, V3 Thorkildsen R, 1985, AM ANN DEAF, V140, P295 Westwood P., 1993, COMMONSENSE METHODS Wilson A. R. S, 2002, PRIMARY ED, V8, P17 NR 57 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 J9 KURAM UYGUL EGIT BIL JI Kuram Uygulamada Egit. Bilim. PD WIN PY 2013 VL 13 IS 1 BP 466 EP 477 PG 12 WC Education & Educational Research SC Education & Educational Research GA 094LO UT WOS:000315264600023 ER PT J AU Ergul, C Baydik, B Demir, S AF Ergul, Cevriye Baydik, Berrin Demir, Seyda TI Opinions of In-Service and Pre-Service Special Education Teachers on the Competencies of the Undergraduate Special Education Programs SO KURAM VE UYGULAMADA EGITIM BILIMLERI LA English DT Article DE Undergraduate Special Education Programs; Field Competencies; Special Education Teachers; Pre-Service Teachers; Special Education Teaching Certificate AB The purpose of this study was to examine the opinions of in-service and pre-service special education teachers on the undergraduate special education programs, field competencies, and their own professional competence. Participants' suggestions for improving undergraduate special education programs and in-service training programs including topics they need for their own professional development were also obtained. The study designed as a survey model included 107 special education teachers and 160 seniors in the undergraduate special education programs of 4 different universities. The data were gathered using an information form and the Special Education Teacher Program Field Competencies Scale which were developed by the researchers. Results showed that the teachers who graduated from an undergraduate special education program perceived themselves and their teaching education more sufficient than both subject matter teachers and teachers with a special education teaching certificate. Teaching academic skills, classroom management, teaching speech, and language skills and autism were the topics on which the majority of participants found themselves inadequate and requested in-service training. Extending the duration of the practicum, spreading it over the whole duration of the program, and making the courses more field-oriented were the most frequently suggested changes by the participants to be made in the undergraduate special education programs. Based on the results of the study, implications for practice were discussed. C1 [Ergul, Cevriye] Ankara Univ, TR-06590 Ankara, Turkey. [Baydik, Berrin; Demir, Seyda] Ankara Univ, Fac Educ Sci, Dept Special Educ, TR-06590 Ankara, Turkey. RP Ergul, C (reprint author), Ankara Univ, Fac Educ Sci, Dept Special Educ, TR-06590 Ankara, Turkey. EM cergul@ankara.edu.tr CR Balci A., 2005, ACIKLAMALI EGITIM YO Bettencourt L. 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PD WIN PY 2013 VL 13 IS 1 BP 518 EP 522 PG 5 WC Education & Educational Research SC Education & Educational Research GA 094LO UT WOS:000315264600025 ER PT J AU Odluyurt, S AF Odluyurt, Serhat TI A Comparison of the Effects of Direct Modeling and Video Modeling Provided by Peers to Students with Autism who are Attending in Rural Play Teaching in an Inclusive Setting SO KURAM VE UYGULAMADA EGITIM BILIMLERI LA English DT Article DE Children with Autism; Video Modeling Education; Modeling Education; Single Subject Designs ID DEVELOPMENTAL-DISABILITIES; IN-VIVO; CHILDREN; PRESCHOOLERS; BEHAVIOR AB In the present research, the peers of children with autism at primary school level and in an inclusive environment were taught using direct modeling and video modeling education processes, and it was observed whether or not they could effectively and efficiently teach how to play games to their friends with autism. This study used adapted alternating treatments design from single subject designs. The research included 21 students from the first and second grades of primary education, 18 of whom participated as peer tutors with normal development, and 3 of whom participated as peer tutees with autism. The dependent variable of the research was the game learning skills determined through interviews with teachers for each sample. The independent variables were the implementation of direct modeling education and video modeling education by peers. The effectuality results of the study indicated that the participants played these games at 83-100% accuracy level and generalized it to different environments. In addition, the participants were observed to have the rules of games at 83-100% level one and three weeks after the completion of the implementation. Comparing the efficiency of the two education implementations, no significant difference was observed between direct modeling and video modeling education implementations in terms of the efficiency variable. The social validity findings of the research indicated the positive expressions of peer tutors regarding the study. C1 [Odluyurt, Serhat] Anadolu Eylul Univ, Eskisehir, Turkey. RP Odluyurt, S (reprint author), Anadolu Univ, Res Inst Handicapped, Eskisehir, Turkey. 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Harding, Jay W. Morgan, Theresa A. Berg, Wendy K. Schieltz, Kelly M. Lee, John F. Padilla, Yaniz C. TI AN EVALUATION OF RESURGENCE DURING FUNCTIONAL COMMUNICATION TRAINING SO PSYCHOLOGICAL RECORD LA English DT Article DE functional communication training; resurgence; negative reinforcement ID DIFFERENTIAL REINFORCEMENT; ALTERNATIVE BEHAVIOR; STIMULUS-CONTROL; EXTINCTION; HISTORY; VARIABILITY; RESISTANCE; AUTISM; MODEL; RATS AB Three children who displayed destructive behavior maintained by negative reinforcement received functional communication training (FCT). During FCT, the children were required to complete a demand and then to mand (touch a card attached to a microswitch, sign, or vocalize) to receive brief play breaks. Prior to and 1 to 3 times following the initiation of FCT, extinction probes were conducted to evaluate the resurgence of destructive behavior when the microswitch without the mand card was present or the microswitch and the mand card were absent to determine if different patterns,of resurgence occurred when the microswitch was present or absent and, for 2 of the children, if changes in resurgence occurred at different points in treatment. Results showed that FCT led to relatively rapid reductions in destructive behavior. During all extinction sessions, resurgence of destructive behavior occurred with only minimal differences across the switch/no card and no-switch conditions. C1 [Wacker, David P.; Harding, Jay W.; Morgan, Theresa A.; Berg, Wendy K.; Schieltz, Kelly M.; Lee, John F.; Padilla, Yaniz C.] Univ Iowa, Iowa City, IA 52242 USA. RP Wacker, DP (reprint author), Ctr Disabil & Dev, 100 Hawkins Dr,Room 251, Iowa City, IA 52242 USA. 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P., 2004, MAINTENANCE EFFECTS Wacker DP, 2011, J EXP ANAL BEHAV, V96, P261, DOI 10.1901/jeab.2011.96-261 Wilson KG, 1996, J EXP ANAL BEHAV, V66, P267, DOI 10.1901/jeab.1996.66-267 NR 37 TC 4 Z9 4 PU PSYCHOLOGICAL RECORD PI CARBONDALE PA SOUTHERN ILLINOIS UNIV, REHABILITATION INSTITUTE, CARBONDALE, IL 62901-4609 USA SN 0033-2933 J9 PSYCHOL REC JI Psychol. Rec. PD WIN PY 2013 VL 63 IS 1 BP 3 EP 20 PG 18 WC Psychology, Multidisciplinary SC Psychology GA 087BC UT WOS:000314735200001 ER PT J AU Odom, SL Cox, AW Brock, ME AF Odom, Samuel L. Cox, Ann W. Brock, Matthew E. CA Natl Professional Dev Ctr ASD TI Implementation Science, Professional Development, and Autism Spectrum Disorders SO EXCEPTIONAL CHILDREN LA English DT Article AB The increased prevalence of autism spectrum disorders (ASD) has intensified the need for high-quality special education services designed for children and youth with ASD and their families. Implementation science provides guidance for moving innovation, such as utilizing evidence-based practices for students with ASD, into regular practice in schools. The National Professional Development Center on ASD (NPDC) incorporated the principles of implementation science, the scientific knowledge about evidence-based practices, and the measurement of program quality into an intervention approach for students with ASD. This article presents the NPDC model as an example of using implementation science to build systems of professional development that increase the quality of services and promote teachers' use of evidence-based practices. C1 [Odom, Samuel L.; Cox, Ann W.] Univ N Carolina, FPG Child Dev Inst, Chapel Hill, NC 27514 USA. [Brock, Matthew E.] Vanderbilt Univ, Nashville, TN USA. Univ Wisconsin, Waisman Ctr, Madison, WI 53706 USA. [Natl Professional Dev Ctr ASD] Univ Calif Davis, Sch Med, MIND Inst, Davis, CA USA. RP Odom, SL (reprint author), Univ N Carolina, FPG Child Dev Inst, CB 8180,105 Smith Level Rd, Chapel Hill, NC 27514 USA. EM slodom@unc.edu CR Odom S, 2012, BEHAV MODIF, V36, P270, DOI 10.1177/0145445512444595 Odom S. L., 2010, HDB YOUTH PREVENTION, P413 Ruble L., 2012, J AUTISM DEV DISORDE Schlosser R. W., 2008, EVIDENCE BASED COMMU, V2, P61, DOI DOI 10.1016/J.JCOMDIS.2003.09.003 Shuster S. K., 1984, J EARLY INTERVENTION, V8, P26, DOI [10.1177/105381518400800104, DOI 10.1177/105381518400800104] U.S. Department of Education Data Accountability Center, 2006, TABL 1 8 CHILDR ST B Volkmar FR, 2004, J CHILD PSYCHOL PSYC, V45, P135, DOI 10.1046/j.0021-9630.2003.00317.x Yell M., 2003, FOCUS AUTISM OTHER D, V18, P182, DOI DOI 10.1177/10883576030180030601 Yell M. Y., 2005, FOCUS AUTISM OTHER D, V20, P130, DOI 10.1177/10883576050200030101 Zahner G., 1987, HDB AUTISM PERVASIVE, P199 Zirkel P., 2002, FOCUS AUTISM OTHER D, V17, P84, DOI 10.1177/10883576020170020301 NR 11 TC 10 Z9 10 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 0014-4029 J9 EXCEPT CHILDREN JI Except. Child. PD WIN PY 2013 VL 79 IS 2 SI SI BP 233 EP 251 PG 19 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 066LB UT WOS:000313221200008 ER PT J AU Ewing, L Leach, K Pellicano, E Jeffery, L Rhodes, G AF Ewing, Louise Leach, Katie Pellicano, Elizabeth Jeffery, Linda Rhodes, Gillian TI Reduced Face Aftereffects in Autism Are Not Due to Poor Attention SO PLOS ONE LA English DT Article ID SPECTRUM DISORDERS; FACIAL IDENTITY; VISUAL-ADAPTATION; SOCIAL-STIMULI; RECOGNITION; CHILDREN; MECHANISMS; INSIGHTS; MIND AB This study aimed to determine why face identity aftereffects are diminished in children with autism, relative to typical children. To address the possibility that reduced face aftereffects might reflect reduced attention to adapting stimuli, we investigated the consequence of controlling attention to adapting faces during a face identity aftereffect task in children with autism and typical children. We also included a size-change between adaptation and test stimuli to determine whether the reduced aftereffects reflect atypical adaptation to low-or higher-level stimulus properties. Results indicated that when attention was controlled and directed towards adapting stimuli, face identity aftereffects in children with autism were significantly reduced relative to typical children. This finding challenges the notion that atypicalities in the quality and/or quantity of children's attention during adaptation might account for group differences previously observed in this paradigm. Additionally, evidence of diminished face identity aftereffects despite a stimulus size change supports an adaptive processing atypicality in autism that extends beyond low-level, retinotopically coded stimulus properties. These findings support the notion that diminished face aftereffects in autism reflect atypicalities in adaptive norm-based coding, which could also contribute to face processing difficulties in this group. C1 [Ewing, Louise; Leach, Katie; Pellicano, Elizabeth; Jeffery, Linda; Rhodes, Gillian] Univ Western Australia, Sch Psychol, Australian Res Council, Ctr Excellence Cognit & Its Disorders, Perth, WA 6009, Australia. [Pellicano, Elizabeth] Univ London, Inst Educ, Ctr Res Autism & Educ, London WC1N 1AZ, England. RP Ewing, L (reprint author), Univ Western Australia, Sch Psychol, Australian Res Council, Ctr Excellence Cognit & Its Disorders, Perth, WA 6009, Australia. EM louise.ewing@uwa.edu.au RI Ewing, Louise/H-9158-2014 FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; Australian Research Council Professorial Fellowship [DP0877379]; Australian Research Council [DP0770923]; University of Western Australia; Australian Federation of University Women; Clothworkers' Foundation; Pears Foundation FX This work was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (project number CE110001021) and an Australian Research Council Professorial Fellowship to G. R (project number DP0877379). It was also supported by an Australian Research Council Discovery Grant (DP0770923) to LJ and GR, and awards to L. E. from the University of Western Australia and the Australian Federation of University Women. Research at the Centre for Research in Autism and Education (CRAE) is supported by The Clothworkers' Foundation and Pears Foundation (E.P.). 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 NOV 28 PY 2013 VL 7 AR 801 DI 10.3389/fnhum.2013.00801 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 266PW UT WOS:000328037200001 PM 24348360 ER PT J AU Padmanabhan, A Lynn, A Foran, W Luna, B O'Hearn, K AF Padmanabhan, Aarthi Lynn, Andrew Foran, William Luna, Beatriz O'Hearn, Kirsten TI Age related changes in striatal resting state functional connectivity in autism SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; fMRI; resting state; functional connectivity; striatum; development ID POSITRON-EMISSION-TOMOGRAPHY; SPECTRUM DISORDERS; MAGNETIC-RESONANCE; EXECUTIVE FUNCTION; SENTENCE COMPREHENSION; CEREBELLAR FUNCTION; SYMPTOM SEVERITY; WORKING-MEMORY; SOCIAL BRAIN; MOTOR TASK AB Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD) and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity, with resting state fMRI from late childhood to early adulthood (8-36 years), using a seed based functional connectivity method with the striatal regions. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to typically developed (TD) participants. In addition, ASD participants showed aberrant age-related connectivity with anterior aspects of cerebellum, and posterior temporal regions (e. g., fusiform gyrus, inferior and superior temporal gyri). In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, a typical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which may also help clarify discrepant findings in the literature. C1 [Padmanabhan, Aarthi; Lynn, Andrew; Foran, William; Luna, Beatriz; O'Hearn, Kirsten] Univ Pittsburgh, Dept Psychiat, Lab Neurocognit Dev, Pittsburgh, PA 15206 USA. RP Padmanabhan, A (reprint author), Univ Pittsburgh, Dept Psychiat, Lab Neurocognit Dev, 121 Meyran Ave,Loeffler Bldg 108, Pittsburgh, PA 15206 USA. EM padmanabhana@upmc.edu FU NIMH from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [5 R01 MH067924]; NIH from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [HD055748]; NIMH [K01 MH081191]; NICHD ACE [HD055648]; NICHD CPEA [HD35469] FX This work was completed at the University of Pittsburgh and supported by NIMH 5 R01 MH067924 (PI Luna), NIH HD055748 (PI Minshew) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and NIMH K01 MH081191 (PI O'Hearn). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Recruitment was supported by NICHD ACE grant HD055648 and CPEA grant HD35469. We thank the participants, their families, Jennifer Fedor, and the staff at the Autism Center for Excellence for their generous help. 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TI RGMa Regulates Cortical Interneuron Migration and Differentiation SO PLOS ONE LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; MEDIAL GANGLIONIC EMINENCE; CENTRAL-NERVOUS-SYSTEM; NEURAL-TUBE CLOSURE; SPINAL-CORD-INJURY; GABAERGIC INTERNEURONS; AXON GUIDANCE; RECEPTOR NEOGENIN; CEREBRAL-CORTEX; CELL-MIGRATION AB The etiology of neuropsychiatric disorders, including schizophrenia and autism, has been linked to a failure to establish the intricate neural network comprising excitatory pyramidal and inhibitory interneurons during neocortex development. A large proportion of cortical inhibitory interneurons originate in the medial ganglionic eminence (MGE) of the ventral telencephalon and then migrate through the ventral subventricular zone, across the corticostriatal junction, into the embryonic cortex. Successful navigation of newborn interneurons through the complex environment of the ventral telencephalon is governed by spatiotemporally restricted deployment of both chemorepulsive and chemoattractive guidance cues which work in concert to create a migratory corridor. Despite the expanding list of interneuron guidance cues, cues responsible for preventing interneurons from re-entering the ventricular zone of the ganglionic eminences have not been well characterized. Here we provide evidence that the chemorepulsive axon guidance cue, RGMa (Repulsive Guidance Molecule a), may fulfill this function. The ventricular zone restricted expression of RGMa in the ganglionic eminences and the presence of its receptor, Neogenin, in the ventricular zone and on newborn and maturing MGE-derived interneurons implicates RGMa-Neogenin interactions in interneuron differentiation and migration. Using an in vitro approach, we show that RGMa promotes interneuron differentiation by potentiating neurite outgrowth. In addition, using in vitro explant and migration assays, we provide evidence that RGMa is a repulsive guidance cue for newborn interneurons migrating out of the ganglionic eminence ventricular zone. Intriguingly, the alternative Neogenin ligand, Netrin-1, had no effect on migration. However, we observed complete abrogation of RGMa-induced chemorepulsion when newborn interneurons were simultaneously exposed to RGMa and Netrin-1 gradients, suggesting a novel mechanism for the tight regulation of RGMa-guided interneuron migration. We propose that during peak neurogenesis, repulsive RGMa-Neogenin interactions drive interneurons into the migratory corridor and prevent re-entry into the ventricular zone of the ganglionic eminences. C1 [O'Leary, Conor; Cole, Stacey J.; Langford, Michael; Hewage, Jayani; White, Amanda; Cooper, Helen M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. RP Cooper, HM (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. EM h.cooper@uq.edu.au FU National Health and Medical Research Council of Australia Project Grant [569638]; Australian Government Australian Postgraduate Award; Queensland State Government Smart Futures Fellowship FX i) National Health and Medical Research Council of Australia Project Grant (569638). ii) Australian Government Australian Postgraduate Award iii) Queensland State Government Smart Futures Fellowship The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Learning, but Normal Working and Spatial Reference Memory SO PLOS ONE LA English DT Article ID ACTIVATED POTASSIUM CHANNELS; ACOUSTIC STARTLE RESPONSE; CA2+-ACTIVATED K+ CHANNELS; TRANSMITTER RELEASE; SPONTANEOUS-ALTERNATION; PYRAMIDAL NEURONS; NERVE-TERMINALS; RAT-BRAIN; CALCIUM; SCHIZOPHRENIA AB Genetic variations in the large-conductance, voltage-and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming a-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection. C1 [Typlt, Marei; Mirkowski, Magdalena; Azzopardi, Erin; Schmid, Susanne] Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, London, ON, Canada. [Ruettiger, Lukas] Univ Tubingen, Hearing Res Ctr, Tubingen, Germany. [Ruth, Peter] Univ Tubingen, Inst Pharm, Tubingen, Germany. RP Schmid, S (reprint author), Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, London, ON, Canada. EM Susanne.Schmid@schulich.uwo.ca RI Schmid, Susanne/J-3201-2012 OI Schmid, Susanne/0000-0001-5366-8061 FU Canadian Institute for Health Research (CIHR) MOP [114870]; Deutsche Forschungsgemeinschaft (DFG) FX Canadian Institute for Health Research (CIHR) MOP#114870 to S. Schmid Deutsche Forschungsgemeinschaft (DFG) scholarship to M.Typlt Ontario Ministry of Training, Colleges and Universities scholarship to E. Azzopardi. 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Ebeling, Hanna Moilanen, Irma Tervonen, Osmo Kiviniemi, Vesa J. TI Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; resting state; fMRI; ICA; default mode; motion ID INDEPENDENT COMPONENT ANALYSIS; AUTISM SPECTRUM DISORDERS; FUNCTIONAL CONNECTIVITY MRI; SCHOOL-AGE-CHILDREN; ASPERGER-SYNDROME; POSTEROMEDIAL CORTEX; EPISODIC MEMORY; SUBJECT MOTION; BRAIN ACTIVITY; HEAD MOTION AB In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered. C1 [Starck, Tuomo; Nikkinen, Juha; Remes, Jukka; Tervonen, Osmo; Kiviniemi, Vesa J.] Oulu Univ Hosp, Dept Diagnost Radiol, Oulu 90029, Oys, Finland. [Starck, Tuomo; Tervonen, Osmo; Kiviniemi, Vesa J.] Oulu Univ, Dept Diagnost Radiol, Oulu, Finland. [Rahko, Jukka; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma] Oulu Univ Hosp, Inst Clin Med, Dept Child Psychiat, Oulu 90029, Oys, Finland. [Rahko, Jukka; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma] Oulu Univ, Oulu, Finland. [Remes, Jukka] Oulu Univ, Elect & Informat Engn Dept, Oulu, Finland. [Jansson-Verkasalo, Eira] Univ Turku, Dept Behav Sci & Philosophy, Turku, Finland. [Pauls, David L.] Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. RP Starck, T (reprint author), Oulu Univ Hosp, Dept Diagnost Radiol, POB 50, Oulu 90029, Oys, Finland. EM tuomo.starck@ppshp.fi RI Remes, Jukka/E-4217-2015 OI Remes, Jukka/0000-0003-1685-8346 FU Alma and K. A. Snellman Foundation, Oulu, Finland; Child Psychiatric Research Foundation, Finland; Emil Aaltonen Foundation, Finland; Rinnekoti Research Foundation, Espoo, Finland; Sigrid Juselius Foundation, Finland; Thule Institute, Oulu, Finland; Finnish Academy Grant [117111]; Finnish Medical Foundation grants; Graduate School of Circumpolar Wellbeing Health and Adaptation; National Alliance for Autism Research FX We wish to thank the adolescents and their families for participating. This study received financial support from the Alma and K. A. Snellman Foundation, Oulu, Finland, the Child Psychiatric Research Foundation, Finland, the Emil Aaltonen Foundation, Finland, the Rinnekoti Research Foundation, Espoo, Finland, the Sigrid Juselius Foundation, Finland and the Thule Institute, Oulu, Finland. This study was funded by Finnish Academy Grant # 117111 and Finnish Medical Foundation grants. The Graduate School of Circumpolar Wellbeing Health and Adaptation is acknowledged for its support. We would also like to thank the National Alliance for Autism Research for financial support granted to Prof David Pauls. 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Hum. Neurosci. PD NOV 22 PY 2013 VL 7 AR 802 DI 10.3389/fnhum.2013.00802 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 266PZ UT WOS:000328037500001 PM 24319422 ER PT J AU Kruger, S Sokolov, AN Enck, P Krageloh-Mann, I Pavlova, MA AF Krueger, Samuel Sokolov, Alexander N. Enck, Paul Kraegeloh-Mann, Ingeborg Pavlova, Marina A. TI Emotion through Locomotion: Gender Impact SO PLOS ONE LA English DT Article ID POINT-LIGHT DISPLAYS; BIOLOGICAL MOTION; SEX-DIFFERENCES; BRAIN; PERCEPTION; EPIDEMIOLOGY; JUDGMENTS; AUTISM; CUES; RECOGNITION AB Body language reading is of significance for daily life social cognition and successful social interaction, and constitutes a core component of social competence. Yet it is unclear whether our ability for body language reading is gender specific. In the present work, female and male observers had to visually recognize emotions through point-light human locomotion performed by female and male actors with different emotional expressions. For subtle emotional expressions only, males surpass females in recognition accuracy and readiness to respond to happy walking portrayed by female actors, whereas females exhibit a tendency to be better in recognition of hostile angry locomotion expressed by male actors. In contrast to widespread beliefs about female superiority in social cognition, the findings suggest that gender effects in recognition of emotions from human locomotion are modulated by emotional content of actions and opposite actor gender. In a nutshell, the study makes a further step in elucidation of gender impact on body language reading and on neurodevelopmental and psychiatric deficits in visual social cognition. C1 [Krueger, Samuel; Kraegeloh-Mann, Ingeborg; Pavlova, Marina A.] Univ Tubingen, Sch Med, Dept Pediat Neurol & Dev Med, Childrens Hosp, Tubingen, Germany. [Sokolov, Alexander N.; Enck, Paul] Univ Tubingen, Sch Med, Dept Psychosomat Med & Psychotherapy, Tubingen, Germany. [Sokolov, Alexander N.] Univ Tubingen, Sch Med, Ctr Pediat Clin Studies, Tubingen, Germany. [Kraegeloh-Mann, Ingeborg] Univ Tubingen, Werner Reichardt Ctr Integrat Neurosci, Tubingen, Germany. [Pavlova, Marina A.] Univ Tubingen, Inst Womens Hlth Baden Wurttemberg, Tubingen, Germany. RP Pavlova, MA (reprint author), Univ Tubingen, Sch Med, Dept Pediat Neurol & Dev Med, Childrens Hosp, Tubingen, Germany. EM marina.pavlova@uni-tuebingen.de FU Else Kroner Fresenius Foundation [P2010_92, P2013_127]; Werner Reichardt Center for Integrative Neuroscience, CIN [2009-24]; Deutsche Forschungsgemeinschaft (DFG); Reinhold Beitlich Foundation; Heidehof Foundation; Berthold Leibinger Foundation; [EXC 307] FX This work was supported by the Else Kroner Fresenius Foundation (Grants P2010_92 and P2013_127), the Werner Reichardt Center for Integrative Neuroscience, CIN (pool project 2009-24), EXC 307 funded by Deutsche Forschungsgemeinschaft (DFG), the Reinhold Beitlich Foundation, the Heidehof Foundation, and the Berthold Leibinger Foundation to MAP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge support toward open access publishing by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Eberhard Karls University of Tubingen. 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Bekkering, Harold TI Action Recognition Depends on Observer's Level of Action Control and Social Personality Traits SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDERS; MIRROR NEURON SYSTEM; UNDERSTANDING ACTION; AUTOMATIC IMITATION; FUNCTIONING AUTISM; JOINT ACTION; TOOL-USE; MIND; INTENTIONS; BRAIN AB Humans recognize both the movement (physical) goals and action (conceptual) goals of individuals with whom they are interacting. Here, we assessed whether spontaneous recognition of others' goals depends on whether the observers control their own behavior at the movement or action level. We also examined the relationship between individual differences in empathy and ASD-like traits, and the processing of other individual's movement and action goals that are known to be encoded in the "mirroring" and "mentalizing" brain networks. In order to address these questions, we used a computer-based card paradigm that made it possible to independently manipulate movement and action congruency of observed and executed actions. In separate blocks, participants were instructed to select either the right or left card (movement-control condition) or the higher or lower card (action-control condition), while we manipulated action-and movement-congruency of both actors' goals. An action-congruency effect was present in all conditions and the size of this effect was significantly correlated with self-reported empathy and ASD-like traits. In contrast, movement-congruency effects were only present in the movement-control block and were strongly dependent on action-congruency. These results illustrate that spontaneous recognition of others' behavior depends on the control scheme that is currently adopted by the observer. The findings suggest that deficits in action recognition are related to abnormal synthesis of perceived movements and prior conceptual knowledge that are associated with activations in the "mirroring" and "mentalizing" cortical networks. C1 [Ondobaka, Sasha; de lange, Floris P.; Bekkering, Harold] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Newman-Norlund, Roger D.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. RP Ondobaka, S (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. EM s.ondobaka@donders.ru.nl RI de Lange, Floris/D-2860-2009 OI de Lange, Floris/0000-0002-6730-1452 FU NWO Top grant [NWO: 407-11-040] FX The present study was supported by the NWO Top grant (NWO: 407-11-040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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M. Clem, R. L. Huganir, R. L. TI The Human Language-Associated Gene SRPX2 Regulates Synapse Formation and Vocalization in Mice SO SCIENCE LA English DT Article ID ACTIVITY-DEPENDENT REGULATION; ULTRASONIC VOCALIZATION; HIKARU-GENKI; SPEECH; FOXP2; DISORDERS; PROTEIN; AUTISM; DIFFERENTIATION; DROSOPHILA AB Synapse formation in the developing brain depends on the coordinated activity of synaptogenic proteins, some of which have been implicated in a number of neurodevelopmental disorders. Here, we show that the sushi repeat-containing protein X-linked 2 (SRPX2) gene encodes a protein that promotes synaptogenesis in the cerebral cortex. In humans, SRPX2 is an epilepsy- and language-associated gene that is a target of the foxhead box protein P2 (FoxP2) transcription factor. We also show that FoxP2 modulates synapse formation through regulating SRPX2 levels and that SRPX2 reduction impairs development of ultrasonic vocalization in mice. Our results suggest FoxP2 modulates the development of neural circuits through regulating synaptogenesis and that SRPX2 is a synaptogenic factor that plays a role in the pathogenesis of language disorders. C1 [Sia, G. M.; Huganir, R. L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Sia, G. M.; Huganir, R. L.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Clem, R. L.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA. RP Huganir, RL (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, 725 North Wolfe St, Baltimore, MD 21205 USA. EM rhuganir@jhmi.edu FU National Institutes of Health [P50MH084020, NS050274]; Millipore FX We thank M. Pletnikov and J. Yocum of the Behavioral Core Facility and M. Pucak of the Multiphoton/Electrophysiology Core Facility. We also thank H. Vega, S. Yang, N. O'Sullivan, and X. Wang for technical assistance. This study was supported by National Institutes of Health grant P50MH084020 to R.L.H. and grant NS050274 to the Multiphoton Core Facility. Under a licensing agreement between Millipore and the Johns Hopkins University, R.L.H. is entitled to a share of royalties received by the University on sales of products described in this article. R.L.H. is a paid consultant to Millipore. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict-of-interest policies. 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Brown, Keith N. Shi, Song-Hai TI Production and organization of neocortical interneurons SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE neocortex; inhibition; interneurons; neurogenesis; migration; organization ID MEDIAL GANGLIONIC EMINENCE; CORTICAL GABAERGIC INTERNEURONS; GROWTH FACTOR/SCATTER FACTOR; PROJECTION NEURON SUBTYPES; DEVELOPING CEREBRAL-CORTEX; MAMMALIAN BASAL FOREBRAIN; ADHESION MOLECULE TAG-1; FATE MAPPING REVEALS; INHIBITORY INTERNEURONS; SOMATOSENSORY CORTEX AB Inhibitory GABA (gamma-aminobutyric acid)-ergic interneurons are a vital component of the neocortex responsible for shaping its output through a variety of inhibitions. Consisting of many flavors, interneuron subtypes are predominantly defined by their morphological, physiological, and neurochemical properties that help to determine their functional role within the neocortex. During development, these cells are born in the subpallium where they then tangentially migrate over long distances before being radially positioned to their final location in the cortical laminae. As development progresses into adolescence, these cells mature and form chemical and electrical connections with both glutamatergic excitatory neurons and other interneurons ultimately establishing the cortical network. The production, migration, and organization of these cells are determined by vast array of extrinsic and intrinsic factors that work in concert in order to assemble a proper functioning cortical inhibitory network. Failure of these cells to undergo these processes results in abnormal positioning and cortical function. In humans, this can bring about several neurological disorders including schizophrenia, epilepsy, and autism spectrum disorders. In this article, we will review previous literature that has revealed the framework for interneuron neurogenesis and migratory behavior as well as discuss recent findings that aim to elucidate the spatial and functional organization of interneurons within the neocortex. C1 [Sultan, Khadeejah T.; Brown, Keith N.; Shi, Song-Hai] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10075 USA. [Sultan, Khadeejah T.; Brown, Keith N.; Shi, Song-Hai] Weill Cornell Med Coll, Grad Program Neurosci, New York, NY USA. RP Shi, SH (reprint author), Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10075 USA. EM shis@mskcc.org FU National Institute of Health [R01DA024681, P01NS048120]; McKnight Foundation FX We apologize to the authors whose work we could not cite owing to space limitations, and thank the anonymous reviewers whose insightful comments significantly improved the paper. Our research is supported by grants from the National Institute of Health (R01DA024681 and P01NS048120) and the McKnight Foundation. 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Cell. Neurosci. PD NOV 21 PY 2013 VL 7 DI 10.3389/fncel.2013.00221 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 264BI UT WOS:000327851500001 PM 24312011 ER PT J AU Wondolowski, J Dickman, D AF Wondolowski, Joyce Dickman, Dion TI Emerging links between homeostatic synaptic plasticity and neurological disease SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE synaptic plasticity; homeostasis; neurological disease; retrograde signaling; presynaptic plasticity ID FAMILIAL HEMIPLEGIC MIGRAINE; SCHIZOPHRENIA SUSCEPTIBILITY GENE; AUTISM SPECTRUM DISORDER; FRAGILE-X-SYNDROME; PRESYNAPTIC FUNCTION DRIVEN; TUBEROUS SCLEROSIS COMPLEX; MENTAL-RETARDATION PROTEIN; GTPASE-ACTIVATING PROTEIN; TYROSINE KINASE MUSK; RETINOIC ACID AB Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control. Recent work from an array of diverse systems and approaches has revealed exciting new links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric diseases. These include autism spectrum disorders, intellectual disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular mechanisms through which defective homeostatic signaling may lead to disease pathogenesis remain unclear, rapid progress is likely to be made in the coming years using a powerful combination of genetic, imaging, electrophysiological, and next generation sequencing approaches. Importantly, understanding homeostatic synaptic plasticity at a cellular and molecular level may lead to developments in new therapeutic innovations to treat these diseases. In this review we will examine recent studies that demonstrate homeostatic control of postsynaptic protein translation, retrograde signaling, and presynaptic function that may contribute to the etiology of complex neurological and psychiatric diseases. C1 [Wondolowski, Joyce; Dickman, Dion] Univ So Calif, Dept Biol, Los Angeles, CA 90089 USA. RP Dickman, D (reprint author), Univ So Calif, Dept Biol, 3641 Watt Way, Los Angeles, CA 90089 USA. EM dickman@usc.edu FU Ellison Medical Foundation; National Institute of Mental Health [MH092351] FX This work was supported by an award from the Ellison Medical Foundation and a grant from the National Institute of Mental Health (MH092351) to Dion Dickman. 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Cell. Neurosci. PD NOV 21 PY 2013 VL 7 AR 223 DI 10.3389/fncel.2013.00223 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 264BI UT WOS:000327851500003 PM 24312013 ER PT J AU Kramvis, I Mansvelder, HD Loos, M Meredith, R AF Kramvis, Ioannis Mansvelder, Huibert D. Loos, Maarten Meredith, Rhiannon TI Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE Fragile X; attention; hyperactivity; 5-choice serial reaction time task; learning; perseveration; MPEP; prefrontal cortex ID AUTISM SPECTRUM DISORDERS; MGLUR5 ANTAGONIST MPEP; REACTION-TIME-TASK; PREFRONTAL CORTEX; MENTAL-RETARDATION; BEHAVIORAL FLEXIBILITY; REPETITIVE BEHAVIOR; YOUNG MALES; MICE; FMR1 AB Attentional deficits and executive function impairments are common to many neurodevelopmental disorders of intellectual disability and autism, including Fragile X syndrome (FXS). In the knockout mouse model for FXS, significant changes in synaptic plasticity and connectivity are found in the prefrontal cortex (PFC)-a prominent region for attentional processing and executive control. Given these alterations in PFC synaptic function, we tested whether adult Fragile X knockout mice exhibited corresponding impairments in inhibitory control, perseveration, and sustained attention. Furthermore, we investigated individual performance during attentional rule acquisition. Using the 5-choice serial reaction time task, our results show no impairments in inhibitory control and sustained attention. Fragile X knockout mice exhibited enhanced levels of correct and incorrect responding, as well as perseveration of responding during initial phases of rule acquisition, that normalized with training. For both knockout and wild type mice, pharmacological attenuation of metabotropic glutamate receptor 5 signaling did not affect response accuracy but reduced impulsive responses and increased omission errors. Upon rule reversal, Fragile X knockout mice made more correct and incorrect responses, similar to the initial phases of rule acquisition. Analogous to heightened activity upon novel rule acquisition, Fragile X knockout mice were transiently hyperactive in both a novel open field (OF) arena and novel home cage. Hyperactivity ceased with familiarization to the environment. Fragile X knockout mice. We therefore provide evidence for subtle but significant differences in the processing of novel stimuli in the mouse model for the FXS. C1 [Kramvis, Ioannis; Mansvelder, Huibert D.; Meredith, Rhiannon] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Integrat Neurophysiol, NL-1081 HV Amsterdam, Netherlands. [Kramvis, Ioannis; Loos, Maarten] Sylics Synaptol BV, Amsterdam, Netherlands. [Loos, Maarten] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, NL-1081 HV Amsterdam, Netherlands. RP Meredith, R (reprint author), Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Integrat Neurophysiol, De Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM r.m.meredith@vu.nl RI Loos, Maarten/A-2768-2012; Meredith, Rhiannon/A-4657-2010 OI Loos, Maarten/0000-0003-1629-2928; FU Nederlandse Organisatie voor Wetenschappelijke Onderzoek (NWO) [917.10.372]; European Commission [FP7-People_ITN-2008-238055]; Agentschap NL (NeuroBasic PharmaPhenomics Consortium, LSH) [FES0908] FX These experiments were supported by the Nederlandse Organisatie voor Wetenschappelijke Onderzoek (NWO #917.10.372 to Rhiannon Meredith) and by the European Commission Seventh Framework Programme grant agreement FP7-People_ITN-2008-238055 ("Brain Train" project; Ioannis Kramvis, Rhiannon Meredith). 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Behav. Neurosci. PD NOV 21 PY 2013 VL 7 AR 172 DI 10.3389/fnbeh.2013.00172 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 263BY UT WOS:000327782800001 PM 24312033 ER PT J AU Zehendner, CM Wedler, HE Luhmann, HJ AF Zehendner, Christoph M. Wedler, Hannah E. Luhmann, Heiko J. TI A Novel In Vitro Model to Study Pericytes in the Neurovascular Unit of the Developing Cortex SO PLOS ONE LA English DT Article ID BLOOD-BRAIN-BARRIER; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SYSTEMIC INFLAMMATION; NEURONAL APOPTOSIS; CEREBRAL-CORTEX; WHITE-MATTER; INJURY; CNS; SCHIZOPHRENIA; EXPRESSION AB Cortical function is impaired in various disorders of the central nervous system including Alzheimer's disease, autism and schizophrenia. Some of these disorders are speculated to be associated with insults in early brain development. Pericytes have been shown to regulate neurovascular integrity in development, health and disease. Hence, precisely controlled mechanisms must have evolved in evolution to operate pericyte proliferation, repair and cell fate within the neurovascular unit (NVU). It is well established that pericyte deficiency leads to NVU injury resulting in cognitive decline and neuroinflammation in cortical layers. However, little is known about the role of pericytes in pathophysiological processes of the developing cortex. Here we introduce an in vitro model that enables to precisely study pericytes in the immature cortex and show that moderate inflammation and hypoxia result in caspase-3 mediated pericyte loss. Using heterozygous EYFP-NG2 mouse mutants we performed live imaging of pericytes for several days in vitro. In addition we show that pericytes maintain their capacity to proliferate which may allow cell-based therapies like reprogramming of pericytes into induced neuronal cells in the presented approach. C1 [Zehendner, Christoph M.; Wedler, Hannah E.; Luhmann, Heiko J.] Johannes Gutenberg Univ Mainz, Inst Physiol & Pathophysiol, Univ Med Ctr, Mainz, Germany. RP Zehendner, CM (reprint author), Johannes Gutenberg Univ Mainz, Inst Physiol & Pathophysiol, Univ Med Ctr, Saarstr 21, Mainz, Germany. EM Zehendner@uni-mainz.de FU University Medical Center of the Johannes Gutenberg-University of Mainz; DFG FX CMZ was supported by a Stage 1 grant of the University Medical Center of the Johannes Gutenberg-University of Mainz. This work was supported by DFG grants to HJL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Jeremy Sanders, Stephan J. Li, Mingfeng Dong, Shan Tebbenkamp, Andrew T. Muhle, Rebecca A. Reilly, Steven K. Lin, Leon Fertuzinhos, Sofia Miller, Jeremy A. Murtha, Michael T. Bichsel, Candace Niu, Wei Cotney, Justin Ercan-Sencicek, A. Gulhan Gockley, Jake Gupta, Abha R. Han, Wenqi He, Xin Hoffman, Ellen J. Klei, Lambertus Lei, Jing Liu, Wenzhong Liu, Li Lu, Cong Xu, Xuming Zhu, Ying Mane, Shrikant M. Lein, Ed S. Wei, Liping Noonan, James P. Roeder, Kathryn Devlin, Bernie Sestan, Nenad State, Matthew W. TI Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism SO CELL LA English DT Article ID SPECTRUM DISORDERS; NOVO MUTATIONS; GENES; RISK; CNVS AB Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to contribute to a common phenotype, we have attempted to identify time periods, brain regions, and cell types in which these genes converge. We have constructed coexpression networks based on the hcASD "seed'' genes, leveraging a rich expression data set encompassing multiple human brain regions across human development and into adulthood. By assessing enrichment of an independent set of probable ASD (pASD) genes, derived from the same sequencing studies, we demonstrate a key point of convergence in midfetal layer 5/6 cortical projection neurons. This approach informs when, where, and in what cell types mutations in these specific genes may be productively studied to clarify ASD pathophysiology. C1 [Willsey, A. Jeremy; Sanders, Stephan J.; Dong, Shan; Muhle, Rebecca A.; Reilly, Steven K.; Niu, Wei; Cotney, Justin; Gockley, Jake; Liu, Wenzhong; Noonan, James P.; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Willsey, A. Jeremy; Sanders, Stephan J.; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Li, Mingfeng; Tebbenkamp, Andrew T.; Fertuzinhos, Sofia; Bichsel, Candace; Han, Wenqi; Xu, Xuming; Zhu, Ying; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Li, Mingfeng; Tebbenkamp, Andrew T.; Muhle, Rebecca A.; Fertuzinhos, Sofia; Bichsel, Candace; Niu, Wei; Han, Wenqi; Xu, Xuming; Zhu, Ying; Noonan, James P.; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. [Dong, Shan; Wei, Liping] Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. [Muhle, Rebecca A.; Niu, Wei; Ercan-Sencicek, A. Gulhan; Gupta, Abha R.; Hoffman, Ellen J.; State, Matthew W.] Yale Univ, Sch Med, Child Study Ctr, New Haven, CT 06510 USA. [Lin, Leon] Yale Univ, Dept Computat Biol & Bioinformat, New Haven, CT 06511 USA. [Miller, Jeremy A.; Lein, Ed S.] Allen Inst Brain Sci, Seattle, WA 98103 USA. [Murtha, Michael T.; Ercan-Sencicek, A. Gulhan; Hoffman, Ellen J.; State, Matthew W.] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT 06510 USA. [Gupta, Abha R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [He, Xin; Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Lei, Jing; Liu, Li; Lu, Cong; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Mane, Shrikant M.] Yale Univ, Sch Med, Yale Ctr Genom Anal, New Haven, CT 06417 USA. [Wei, Liping] Natl Inst Biol Sci, Beijing 102206, Peoples R China. [State, Matthew W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. RP Devlin, B (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. EM devlinbj@upmc.edu; nenad.sestan@yale.edu; matthew.state@ucsf.edu RI Liu, Li/G-1897-2015 FU Overlook International Foundation; Simons Foundation; Kavli Foundation; National Institute of Mental Health [RC2 MH089956, U01 MH081896, R37 MH057881]; Foster-Davis Foundation Inc. (NARSAD DI); Howard Hughes Medical Institute; Canadian Institutes of Health Research FX We are grateful to the families participating in the Simons Foundation Autism Research Initiative (SFARI) Simplex Collection (SSC). This work was supported by a gift from the Overlook International Foundation (to M. W. S., N. S., B. D., K. R., and J. N.), as well as grants from the Simons Foundation (to M. W. S., N. S., K. R., and J. N.), the Kavli Foundation (to N. S.), the National Institute of Mental Health (RC2 MH089956 to M. W. S., U01 MH081896 to N. S., and R37 MH057881 to B. D. and K. R.), the Foster-Davis Foundation Inc. (NARSAD DI to N. S.), the Howard Hughes Medical Institute (International Student Research Fellowship to both S. J. S. and W. H.), and the Canadian Institutes of Health Research (Doctoral Foreign Study Award to A. J. W.). We would like to thank the SSC principal investigators (A. L. Beaudet, R. Bernier, J. Constantino, E. H. Cook, Jr, E. Fombonne, D. Geschwind, D. E. Grice, A. Klin, D. H. Ledbetter, C. Lord, C. L. Martin, D. M. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. W. State, W. Stone, J. S. Sutcliffe, C. A. Walsh, and E. Wijsman) and the coordinators and staff at the SSC clinical sites; the SFARI staff, in particular M. Benedetti; the Rutgers University Cell and DNA repository for accessing biomaterials; the Yale Center of Genomic Analysis, in particular J. Overton, S. Umlauf, I. Tikhonova, and A. Lopez, for generating sequencing data; T. Brooks-Boone, N. Wright-Davis, and M. Wojciechowski for their help in administering the project at Yale; and H. Rankin for unwavering support. 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Luo, Rui Zhang, Alice Won, Hyejung Lowe, Jennifer K. Chandran, Vijayendran Horvath, Steve Geschwind, Daniel H. TI Integrative Functional Genomic Analyses Implicate Specific Molecular Pathways and Circuits in Autism SO CELL LA English DT Article ID DE-NOVO MUTATIONS; COMMON GENETIC-VARIANTS; SPECTRUM DISORDERS; INTELLECTUAL DISABILITY; TRANSCRIPTIONAL REGULATION; NEURAL DEVELOPMENT; BRAIN-DEVELOPMENT; MESSENGER-RNAS; CHROMATIN; NETWORK AB Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: (1) do these genetic loci converge on specific biological processes, and (2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto coexpression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortical laminae. 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[Luo, Rui; Horvath, Steve; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Luo, Rui; Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Ctr Autism Treatment & Res, Los Angeles, CA 90095 USA. [Chandran, Vijayendran; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA. EM dhg@ucla.edu FU Simons Foundation Autism Research Initiative; Autism Genetic Resource Exchange; Brain Span consortium; Allen Brain Institute; NIMH Training; NRSA Fellowship [T32MH073526, F30MH099886]; NIMH [5R37MH060233, 5R01MH094714]; Autism Center for Excellence network grant [9R01MH100027]; Simons Foundation [SFARI 206744]; Medical Scientist Training Program at UCLA; NINDS Informatics Center for Neurogenetics and Neurogenomics [P30NS062691] FX We thank the Simons Foundation Autism Research Initiative (http://www.sfari.org) and the Autism Genetic Resource Exchange (http://www.agre.org) and all families involved for making this work possible. We gratefully acknowledge data resources from the Brain Span consortium and the Allen Brain Institute http://www.brain-map.org). This work was supported by a NIMH Training and NRSA Fellowship (T32MH073526 and F30MH099886, N.N.P.), NIMH grants (5R37MH060233 and 5R01MH094714, D. H. G.), an Autism Center for Excellence network grant (9R01MH100027), the Simons Foundation (SFARI 206744, D. H. G.), and the Medical Scientist Training Program at UCLA. We thank the NINDS Informatics Center for Neurogenetics and Neurogenomics (funded by grant P30NS062691) at UCLA for computing resources, and we specifically thank Yeongshnn Ong and Giovanni Coppola for making the interactive network available. We thank Jason Chen, Michael Gandal, and Jason Stein for critically reading the manuscript, as well as Willsey et al. (2013) for sharing their findings prior to publication. 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Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259AU UT WOS:000327500600007 PM 24267887 ER PT J AU Magrelli, S Jermann, P Noris, B Ansermet, F Hentsch, F Nadel, J Billard, A AF Magrelli, Silvia Jermann, Patrick Noris, Basilio Ansermet, Francois Hentsch, Francois Nadel, Jacqueline Billard, Aude TI Social orienting of children with autism to facial expressions and speech: a study with a wearable eye-tracker in naturalistic settings SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE autism spectrum conditions; eye-tracking; social orienting; overt attention; facial expressions of emotion; speech ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; ASPERGER-SYNDROME; HOME VIDEOTAPES; REVISED VERSION; DIAGNOSTIC INTERVIEW; EMOTION-RECOGNITION; ATTENTION SHIFTS; BASIC EMOTIONS; NORMAL ADULTS AB This study investigates attention orienting to social stimuli in children with Autism Spectrum Conditions (ASC) during dyadic social interactions taking place in real-life settings. We study the effect of social cues that differ in complexity and distinguish between social cues produced by facial expressions of emotion and those produced during speech. We record the children's gazes using a head-mounted eye-tracking device and report on a detailed and quantitative analysis of the motion of the gaze in response to the social cues. The study encompasses a group of children with ASC from 2 to 11-years old (n = 14) and a group of typically developing (TD) children (n = 17) between 3 and 6-years old. While the two groups orient overtly to facial expressions, children with ASC do so to a lesser extent. Children with ASC differ importantly from TD children in the way they respond to speech cues, displaying little overt shifting of attention to speaking faces. When children with ASC orient to facial expressions, they show reaction times and first fixation lengths similar to those presented by TD children. 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RP Magrelli, S (reprint author), Ecole Polytech Fed Lausanne, Learning Algorithms & Syst Lab, EPFL STI LASA I2S, Stn 9, CH-1015 Lausanne, Switzerland. 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Psychol. PD NOV 20 PY 2013 VL 4 AR 840 DI 10.3389/fpsyg.2013.00840 PG 16 WC Psychology, Multidisciplinary SC Psychology GA AB1VV UT WOS:000331582900001 PM 24312064 ER PT J AU Hopkins, WD Russell, J McIntyre, J Leavens, DA AF Hopkins, William D. Russell, Jamie McIntyre, Joe Leavens, David A. TI Are Chimpanzees Really So Poor at Understanding Imperative Pointing? Some New Data and an Alternative View of Canine and Ape Social Cognition SO PLOS ONE LA English DT Article ID PAN-TROGLODYTES; INTENTIONAL COMMUNICATION; PONGO-PYGMAEUS; CUES; COMPREHENSION; INFERENCES; AUTISM; FOLLOW; GAZE AB There is considerable interest in comparative research on different species' abilities to respond to human communicative cues such as gaze and pointing. It has been reported that some canines perform significantly better than monkeys and apes on tasks requiring the comprehension of either declarative or imperative pointing and these differences have been attributed to domestication in dogs. Here we tested a sample of chimpanzees on a task requiring comprehension of an imperative request and show that, though there are considerable individual differences, the performance by the apes rival those reported in pet dogs. We suggest that small differences in methodology can have a pronounced influence on performance on these types of tasks. We further suggest that basic differences in subject sampling, subject recruitment and rearing experiences have resulted in a skewed representation of canine abilities compared to those of monkeys and apes. C1 [Hopkins, William D.; Russell, Jamie] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. [Hopkins, William D.; Russell, Jamie] Georgia State Univ, Language Res Ctr, Atlanta, GA 30303 USA. [Hopkins, William D.; Russell, Jamie; McIntyre, Joe] Yerkes Natl Primate Res Ctr, Div Dev & Cognit Neurosci, Atlanta, GA USA. [Leavens, David A.] Univ Sussex, Dept Psychol, Brighton, E Sussex, England. RP Hopkins, WD (reprint author), Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. EM whopkins4@gsu.edu RI Leavens, David/B-2750-2014 FU NIH [MH-92923, NS-42867, NS-73134, HD-60563]; National Center for Research Resources [P51RR165]; Office of Research Infrastructure Programs/OD [P51OD11132] FX This research was supported by NIH grants MH-92923, NS-42867, NS-73134 and HD-60563 to WDH and National Center for Research Resources P51RR165 to YNPRC, which is currently supported by the Office of Research Infrastructure Programs/OD P51OD11132). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Shitamichi, Kiyomi Munesue, Toshio Tsubokawa, Tsunehisa Higashida, Haruhiro Minabe, Yoshio TI The Brain's Response to the Human Voice Depends on the Incidence of Autistic Traits in the General Population SO PLOS ONE LA English DT Article ID LINGUISTIC PITCH PATTERNS; EVENT-RELATED POTENTIALS; ASPERGER-SYNDROME; MISMATCH NEGATIVITY; SPECTRUM DISORDERS; AUDITORY-CORTEX; STEM RESPONSE; SPEECH; ATTENTION; CHILDREN AB Optimal brain sensitivity to the fundamental frequency (F0) contour changes in the human voice is important for understanding a speaker's intonation, and consequently, the speaker's attitude. However, whether sensitivity in the brain's response to a human voice F0 contour change varies with an interaction between an individual's traits (i.e., autistic traits) and a human voice element (i.e., presence or absence of communicative action such as calling) has not been investigated. In the present study, we investigated the neural processes involved in the perception of F0 contour changes in the Japanese monosyllables "ne" and "nu." "Ne" is an interjection that means "hi" or "hey" in English; pronunciation of "ne" with a high falling F0 contour is used when the speaker wants to attract a listener's attention (i.e., social intonation). Meanwhile, the Japanese concrete noun "nu" has no communicative meaning. We applied an adaptive spatial filtering method to the neuromagnetic time course recorded by whole-head magnetoencephalography (MEG) and estimated the spatiotemporal frequency dynamics of event-related cerebral oscillatory changes in beta band during the oddball paradigm. During the perception of the F0 contour change when "ne" was presented, there was event-related de-synchronization (ERD) in the right temporal lobe. In contrast, during the perception of the F0 contour change when "nu" was presented, ERD occurred in the left temporal lobe and in the bilateral occipital lobes. ERD that occurred during the social stimulus "ne" in the right hemisphere was significantly correlated with a greater number of autistic traits measured according to the Autism Spectrum Quotient (AQ), suggesting that the differences in human voice processing are associated with higher autistic traits, even in non-clinical subjects. C1 [Yoshimura, Yuko; Kikuchi, Mitsuru; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa, Japan. [Ueno, Sanae; Shitamichi, Kiyomi; Minabe, Yoshio] Kanazawa Univ, Grad Sch Med Sci, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa, Japan. [Okumura, Eiichi] Yokogawa Elect Corp, Dept MEG, Tokyo, Japan. [Remijn, Gerard B.] Kyushu Univ, Int Educ Ctr, Fukuoka 812, Japan. [Tsubokawa, Tsunehisa] Kanazawa Univ, Grad Sch Med Sci, Dept Anesthesiol, Kanazawa, Ishikawa, Japan. RP Kikuchi, M (reprint author), Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa, Japan. EM mitsuru@zc4.so-net.ne.jp FU Hokuriku Innovation Cluster for Health Science (MEXT Program for Fostering Regional Innovation); MEXT, Japan; [24000012] FX This study was supported by Grant-in-Aid for Specially Promoted (Research Number 24000012), the Hokuriku Innovation Cluster for Health Science (MEXT Program for Fostering Regional Innovation), and the Strategic Research Program for Brain Sciences from MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Dewey, Colleen M. Reimers, Jeremy M. Widman, Allie J. Gupta, Natasha Liu, Shunan Jaramillo, Thomas C. Bangash, Muhammad Xiao, Bo Worley, Paul F. Powell, Craig M. TI Loss of Predominant Shank3 Isoforms Results in Hippocampus-Dependent Impairments in Behavior and Synaptic Transmission SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AUTISM SPECTRUM DISORDERS; 22Q13.3 DELETION SYNDROME; POSTSYNAPTIC DENSITY PROTEINS; MICE LACKING; MUTANT MICE; MUTATIONS; GENE; CHILDREN; RECEPTOR; FAMILY AB The Shank3 gene encodes a scaffolding protein that anchors multiple elements of the postsynaptic density at the synapse. Previous attempts to delete the Shank3 gene have not resulted in a complete loss of the predominant naturally occurring Shank3 isoforms. We have now characterized a homozygous Shank3 mutation in mice that deletes exon 21, including the Homer binding domain. In the homozygous state, deletion of exon 21 results in loss of the major naturally occurring Shank3 protein bands detected by C-terminal and N-terminal antibodies, allowing us to more definitively examine the role of Shank3 in synaptic function and behavior. This loss of Shank3 leads to an increased localization of mGluR5 to both synaptosome and postsynaptic density-enriched fractions in the hippocampus. These mice exhibit a decrease in NMDA/AMPA excitatory postsynaptic current ratio in area CA1 of the hippocampus, reduced long-term potentiation in area CA1, and deficits in hippocampus-dependent spatial learning and memory. In addition, these mice also exhibit motor-coordination deficits, hypersensitivity to heat, novelty avoidance, altered locomotor response to novelty, and minimal social abnormalities. These data suggest that Shank3 isoforms are required for normal synaptic transmission/plasticity in the hippocampus, as well as hippocampus-dependent spatial learning and memory. C1 [Kouser, Mehreen; Speed, Haley E.; Dewey, Colleen M.; Reimers, Jeremy M.; Widman, Allie J.; Gupta, Natasha; Liu, Shunan; Jaramillo, Thomas C.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Bangash, Muhammad; Xiao, Bo; Worley, Paul F.] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. RP Powell, CM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. EM craig.powell@utsouthwestern.edu FU National Institute of Child Health and Human Development [R01HD069560, R01HD069560-0251]; National Institute of Mental Health [R01MH093697, P50MH084020]; National Institute of Neurological Disorders and Stroke [R01NS070301]; National Institute on Drug Abuse [T32DA007290]; Autism Speaks; Autism Science Foundation Postdoctoral Fellowship; Autism Speaks Dennis Weatherstone Predoctoral Fellowship; BRAINS for Autism; Hartwell Foundation; National 973 Basic Research Program of China [20009CB941400] FX This work was funded by National Institute of Child Health and Human Development Grants R01HD069560 (C. M. P.) and R01HD069560-0251 Diversity Supplement (T.C.J.), National Institute of Mental Health Grants R01MH093697 (C. M. P.) and P50MH084020 (P. F. W.), National Institute of Neurological Disorders and Stroke Grant R01NS070301 (P. F. W.), National Institute on Drug Abuse Grant T32DA007290 (J.M.R.), Autism Speaks (C. M. 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While basic electrophysiological response parameters were normal, there were specific and striking abnormalities in how. individual facial features drove neuronal response. Compared to control patients, a population of neurons in the two ASD patients responded significantly more to the mouth, but less to the eyes. Moreover, we found a second class of face-responsive neurons for which responses to faces appeared normal. The findings confirm the amygdala's pivotal role in abnormal face processing by people with ASD at the cellular level and suggest that dysfunction may be traced to a specific subpopulation of neurons with altered selectivity for the features of faces. 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. [Adolphs, Ralph] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Rutishauser, Ueli; Tudusciuc, Oana; Wang, Shuo; Adolphs, Ralph] CALTECH, Pasadena, CA 91125 USA. [Ross, Ian B.] Huntington Mem Hosp, Pasadena, CA 91105 USA. RP Rutishauser, U (reprint author), Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. EM rutishauseru@csmc.edu RI Rutishauser, Ueli/E-5721-2011 FU Simons Foundation; Gordon and Betty Moore Foundation; Max Planck Society; Cedars-Sinai Medical Center; Autism Speaks; Conte Center from the National Institute of Mental Health FX We thank all patients and their families for their help in conducting the studies; Lynn Paul, Daniel Kennedy, and Christina Corsello for performing ADOS; Christopher Heller for neurosurgical implantation in some of our subjects; Linda Philpott for neuropsychological assessment; and William Sutherling and the staff of the Huntington Memorial Hospital for their support with the studies. We also thank Erin Schuman for advice and providing some of the electrophysiology equipment, and Frederic Gosselin, Michael Spezio, Julien Dubois, and Jeffrey Wertheimer for discussion. This research was made possible by funding from the Simons Foundation (to R.A.), the Gordon and Betty Moore Foundation (to R.A.), the Max Planck Society (to U.R.), the Cedars-Sinai Medical Center (to U.R. and A.M.), a fellowship from Autism Speaks (to O.T.), and a Conte Center from the National Institute of Mental Health (to R.A.). 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RP Feng, L (reprint author), Natl Univ Singapore, NUHS Tower Block,1 E Kent Ridge Rd, Singapore 119228, Singapore. EM pcmfl@nus.edu.sg CR American Psychiatric Association, 2013, DIAGN STAT MAN MENT Cedars MI, 2013, JAMA-J AM MED ASSOC, V310, P42, DOI 10.1001/jama.2013.7223 Sandin S, 2013, JAMA-J AM MED ASSOC, V310, P75, DOI 10.1001/jama.2013.7222 Suren P, 2013, JAMA-J AM MED ASSOC, V309, P570, DOI 10.1001/jama.2012.155925 NR 4 TC 0 Z9 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 2013 VL 310 IS 19 BP 2100 EP 2101 DI 10.1001/jama.2013.278595 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 253OQ UT WOS:000327098900030 PM 24240941 ER PT J AU Sandin, S Hultman, C Reichenberg, A AF Sandin, Sven Hultman, Christina Reichenberg, Abraham TI Autism in Children Born After In Vitro Fertilization Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Sandin, Sven; Reichenberg, Abraham] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Hultman, Christina] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Sandin, S (reprint author), Kings Coll London, Inst Psychiat, De Crespigny Pk, London SE5 8AF, England. EM sven.sandin@kl.ac.uk CR Hultman CM, 2011, MOL PSYCHIATR, V16, P1203, DOI 10.1038/mp.2010.121 McPartland JC, 2012, J AM ACAD CHILD PSY, V51, P368, DOI 10.1016/j.jaac.2012.01.007 NR 2 TC 0 Z9 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 20 PY 2013 VL 310 IS 19 BP 2101 EP 2101 DI 10.1001/jama.2013.278610 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 253OQ UT WOS:000327098900031 PM 24240943 ER PT J AU Baron-Cohen, S Johnson, D Asher, J Wheelwright, S Fisher, SE Gregersen, PK Allison, C AF Baron-Cohen, Simon Johnson, Donielle Asher, Julian Wheelwright, Sally Fisher, Simon E. Gregersen, Peter K. Allison, Carrie TI Is synaesthesia more common in autism? SO MOLECULAR AUTISM LA English DT Article ID GRAPHEME-COLOR SYNESTHESIA; FUNCTIONING AUTISM; ASPERGER-SYNDROME; SAVANT MEMORY; CONNECTIVITY; PREVALENCE; ACTIVATION; EXPERIENCE; PATTERNS; HEARING AB Background: Synaesthesia is a neurodevelopmental condition in which a sensation in one modality triggers a perception in a second modality. Autism (shorthand for Autism Spectrum Conditions) is a neurodevelopmental condition involving social-communication disability alongside resistance to change and unusually narrow interests or activities. Whilst on the surface they appear distinct, they have been suggested to share common atypical neural connectivity. Methods: In the present study, we carried out the first prevalence study of synaesthesia in autism to formally test whether these conditions are independent. After exclusions, 164 adults with autism and 97 controls completed a synaesthesia questionnaire, Autism Spectrum Quotient, and Test of Genuineness-Revised (ToG-R) online. Results: The rate of synaesthesia in adults with autism was 18.9% (31 out of 164), almost three times greater than in controls (7.22%, 7 out of 97, P <0.05). ToG-R proved unsuitable for synaesthetes with autism. Conclusions: The significant increase in synaesthesia prevalence in autism suggests that the two conditions may share some common underlying mechanisms. Future research is needed to develop more feasible validation methods of synaesthesia in autism. C1 [Baron-Cohen, Simon; Johnson, Donielle; Asher, Julian; Wheelwright, Sally; Allison, Carrie] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. [Fisher, Simon E.] Max Planck Inst Psycholinguist, NL-6500 AH Nijmegen, Netherlands. [Fisher, Simon E.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Gregersen, Peter K.] North Shore LIJ, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY 11030 USA. RP Johnson, D (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. EM doniellenjohnson@gmail.com RI Fisher, Simon/E-9130-2012 OI Fisher, Simon/0000-0002-3132-1996 FU Gates Foundation; MRC UK; Max Planck Society FX This work was submitted in part fulfilment of the degree of Master of Philosophy by DJ. It was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough. DJ was funded by the Gates Foundation. SBC and SW were funded by the MRC UK. SEF was funded by the Max Planck Society. 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However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. Results: The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. Conclusions: The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. 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EM beeisinger@wisc.edu FU United States National Institutes of Health [R01 MH 085642]; National Science Foundation [IOS-0921706] FX This work was primarily funded by United States National Institutes of Health Grant R01 MH 085642 to S. G. Additional support was provided by the National Science Foundation Grant IOS-0921706 to S. G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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To investigate whether call repertoires and call rates are different when the male is interacting with a female and after the removal of the female, we designed a novel male-female social interaction test in which vocalizations were recorded across three phases. During phase 1, the male subject freely interacts with an unfamiliar estrus female mouse in a clean cage for 5 min. During phase 2, the female is removed while the male remains in the cage for 3 min. During phase 3, the same female is returned to the cage to rejoin the male subject mouse for 3 min. C57BL/6J (B6), FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant (FVB), and BTBR T+ tf/J (BTBR) male subject mice were tested in this paradigm. All three strains emitted USVs during their initial interaction with the female partner. When the female was reintroduced in phase 3, numbers of USVs were similar to the initial introductory phase 1. Strain comparisons indicated fewer calls in pairs of BTBR males and stimulus females than in pairs of B6 males and stimulus females and pairs of FVB males and stimulus females. In the absence of the female, all FVB males vocalized, while only one third of B6 males and one third of BTBR males vocalized. In all three strains, changes in call category repertoires were detected after the female was removed. Call categories reverted to the phase 1 pattern when the female was returned in phase 3. Present findings indicate that males of commonly used inbred strains emit USVs when a partner female leaves the testing arena, suggesting that removing a salient social stimulus may be a unique approach to elicit USVs from mice. Our three-phase paradigm may also be useful for studying attention to social cues, and qualitative differences in vocalizations when a social partner is present vs. suddenly absent. C1 [Yang, Mu; Crawley, Jacqueline N.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sch Med, Sacramento, CA 95817 USA. [Yang, Mu; Loureiro, Darren; Kalikhman, David; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Univ Calif Davis, Dept Psychiat & Behav Sci, Sch Med, Room 1001,Res 2 Bldg 96,4625 2nd Ave, Sacramento, CA 95817 USA. EM mu.yang@ucdmc.ucdavis.edu FU National Institute of Mental Health Intramural Research Program; MIND Institute FX This work was supported by the National Institute of Mental Health Intramural Research Program. The experiments were conducted at National Institutes of Health. A significant portion of data analysis was done in our current laboratory at University of California, Davis, with support from the MIND Institute. 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We present rSeqDiff, an efficient algorithm for the detection of differential expression and differential splicing of genes from RNA-Seq experiments across multiple conditions. Unlike existing approaches which detect differential expression of transcripts, our approach considers three cases for each gene: 1) no differential expression, 2) differential expression without differential splicing and 3) differential splicing. We specify statistical models characterizing each of these three cases and use hierarchical likelihood ratio test for model selection. Simulation studies show that our approach achieves good power for detecting differentially expressed or differentially spliced genes. Comparisons with competing methods on two real RNA-Seq datasets demonstrate that our approach provides accurate estimates of isoform abundances and biological meaningful rankings of differentially spliced genes. The proposed approach is implemented as an R package named rSeqDiff. C1 [Shi, Yang; Jiang, Hui] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Jiang, Hui] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. RP Jiang, H (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. EM jianghui@umich.edu FU Rackham Centennial Summer Research Fellowship; Summer Internship Funds of Certificate in Public Health Genetics (CPHG) Program at University of Michigan; NIH [5U54CA163059-02]; GAPPS Grant from the Bill & Melinda Gates Foundation FX YS was supported by the Rackham Centennial Summer Research Fellowship and Summer Internship Funds of Certificate in Public Health Genetics (CPHG) Program at University of Michigan. HJ's research was supported in part by an NIH grant 5U54CA163059-02 and a GAPPS Grant from the Bill & Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Kolk, Sharon M. Schubert, Dirk TI Editorial perspective of the Research Topic "Deciphering serotonin's role in neurodevelopment" SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Editorial Material DE serotonin; neurodevelopment; placental serotonin; sensory system; prefrontal cortex; raphe nuclei; cortical integrity; autism C1 [Homberg, Judith R.; Schubert, Dirk] Radboud Univ Nijmegen, Ctr Med, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Kolk, Sharon M.] Radboud Univ Nijmegen, Dept Mol Anim Physiol, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Homberg, JR (reprint author), Radboud Univ Nijmegen, Ctr Med, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. EM j.homberg@cns.umcn.nl RI Homberg, Judith/D-2473-2010; Kolk, Sharon/A-9055-2011; Schubert, Dirk/B-4339-2011 OI Kolk, Sharon/0000-0003-2116-5456; Schubert, Dirk/0000-0002-1202-4363 CR Engel M, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00076 Kinast K, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00072 Miceli S, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00088 Olivier JDA, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00073 Smidt MP, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00200 Velasquez JC, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00047 Vitalis T, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00093 Weikum WM, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00180 Witteveen JS, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00143 Zhang JL, 2013, FRONT CELL NEUROSCI, V7, DOI 10.3389/fncel.2013.00067 NR 10 TC 2 Z9 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD NOV 18 PY 2013 VL 7 AR 212 DI 10.3389/fncel.2013.00212 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 264AH UT WOS:000327848800002 PM 24302896 ER PT J AU Liyanage, VRB Zachariah, RM Rastegar, M AF Liyanage, Vichithra R. B. Zachariah, Robby M. Rastegar, Mojgan TI Decitabine alters the expression of Mecp2 isoforms via dynamic DNA methylation at the Mecp2 regulatory elements in neural stem cells SO MOLECULAR AUTISM LA English DT Article DE Epigenetics; Mecp2e1; Mecp2e2; Decitabine/5-aza-2'-deoxycytidine; DNA methylation; Autism ID RETT-SYNDROME; CANCER-CELLS; MILD OVEREXPRESSION; GENE-EXPRESSION; MOUSE MODEL; IN-VITRO; NEURONS; MICE; PROMOTER; 5-AZA-2'-DEOXYCYTIDINE AB Background: Aberrant MeCP2 expression in brain is associated with neurodevelopmental disorders including autism. In the brain of stressed mouse and autistic human patients, reduced MeCP2 expression is correlated with Mecp2/MECP2 promoter hypermethylation. Altered expression of MeCP2 isoforms (MeCP2E1 and MeCP2E2) is associated with neurological disorders, highlighting the importance of proper regulation of both isoforms. While known regulatory elements (REs) within the MECP2/Mecp2 promoter and intron 1 are involved in MECP2/Mecp2 regulation, Mecp2 isoform-specific regulatory mechanisms are unknown. We hypothesized that DNA methylation at these REs may impact the expression of Mecp2 isoforms. Methods: We used a previously characterized in vitro differentiating neural stem cell (NSC) system to investigate the interplay between Mecp2 isoform-specific expression and DNA methylation at the Mecp2 REs. We studied altered expression of Mecp2 isoforms, affected by global DNA demethylation and remethylation, induced by exposure and withdrawal of decitabine (5-Aza-2'-deoxycytidine). Further, we performed correlation analysis between DNA methylation at the Mecp2 REs and the expression of Mecp2 isoforms after decitabine exposure and withdrawal. Results: At different stages of NSC differentiation, Mecp2 isoforms showed reciprocal expression patterns associated with minor, but significant changes in DNA methylation at the Mecp2 REs. Decitabine treatment induced Mecp2e1/MeCP2E1 (but not Mecp2e2) expression at day (D) 2, associated with DNA demethylation at the Mecp2 REs. In contrast, decitabine withdrawal downregulated both Mecp2 isoforms to different extents at D8, without affecting DNA methylation at the Mecp2 REs. NSC cell fate commitment was minimally affected by decitabine under tested conditions. Expression of both isoforms negatively correlated with methylation at specific regions of the Mecp2 promoter, both at D2 and D8. The correlation between intron 1 methylation and Mecp2e1 (but not Mecp2e2) varied depending on the stage of NSC differentiation (D2: negative; D8: positive). Conclusions: Our results show the correlation between the expression of Mecp2 isoforms and DNA methylation in differentiating NSC, providing insights on the potential role of DNA methylation at the Mecp2 REs in Mecp2 isoform-specific expression. The ability of decitabine to induce Mecp2e1/MeCP2E1, but not Mecp2e2 suggests differential sensitivity of Mecp2 isoforms to decitabine and is important for future drug therapies for autism. C1 [Liyanage, Vichithra R. B.; Zachariah, Robby M.; Rastegar, Mojgan] Univ Manitoba, Regenerat Med Program, Dept Biochem & Med Genet, Fac Med, Winnipeg, MB R3E 0J9, Canada. RP Rastegar, M (reprint author), Univ Manitoba, Regenerat Med Program, Dept Biochem & Med Genet, Fac Med, Rm 627,Basic Med Sci Bldg,745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada. EM rastegar@cc.umanitoba.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) [3724052009]; Scottish Rite Charitable Foundation of Canada (SRCFC) [10110] FX We thank Mr Carl Olson in the Rastegar laboratory for neurosphere sectioning. This work was supported by funds from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant 3724052009), and Scottish Rite Charitable Foundation of Canada (SRCFC, Grant 10110). VRBL and RMZ are recipients of MHRC-MICH studentship awards. The NESTIN monoclonal antibody developed by Susan Hockfield was obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242. 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The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a core clinical disability. Methods: Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA constructs. Whole genome expression analysis was conducted for each of the knockdown cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing an anti-luciferase shRNA. Gene set enrichment and a causal reasoning engine was employed to identify pathway level perturbations generated by the transcript knockdown. 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Autism PD NOV 15 PY 2013 VL 4 AR 45 DI 10.1186/2040-2392-4-45 PG 17 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 291OC UT WOS:000329837000001 PM 24238429 ER PT J AU Moldrich, RX Leanage, G She, D Dolan-Evans, E Nelson, M Reza, N Reutens, DC AF Moldrich, Randal X. Leanage, Gayeshika She, David Dolan-Evans, Elliot Nelson, Michael Reza, Nargis Reutens, David C. TI Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Sodium valproate; Autism; Trichostatin A; Histone deacetylase; Sociability; Histone acetylation ID VALPROIC ACID; ANTIEPILEPTIC DRUGS; SODIUM VALPROATE; ANIMAL-MODEL; PRENATAL EXPOSURE; MOOD STABILIZER; RAT PUPS; AUTISM; MOUSE; ANTICONVULSANT AB Exposure to sodium valproate (VPA) in utero increases the risk of language impairment and a diagnosis of autism spectrum disorder (ASD). Mice exposed to VPA while in utero have also shown postnatal social deficits. Inhibition of histone deacetylase (HDAC) is one of VPA's many biological effects. The main objective of this study was to test the hypothesis that HDAC inhibition causes these behavioral outcomes following prenatal VPA exposure in mice. We exposed embryonic mice to VPA, the HDAC inhibitor trichostatin A (TSA), or vehicle controls. TSA (1 mg/kg) inhibited HDAC in embryonic tissue at a level comparable to 600 mg/kg VPA, resulting in significant increases in histone H3 and H4 acetylation, and histone H3 lysine 4 tri-methylation. Postnatally, decreases in ultrasonic vocalization, olfactory motivation and sociability were observed in TSA and VPA-exposed pups. Treated mice exhibited elevated digging and grooming suggestive of mild restrictive and repetitive behaviors. Olfactory social preference, social novelty and habituation were normal. Together, these data indicate that embryonic HDAC inhibition alone can cause abnormal social behaviors in mice. This result serves as a molecular understanding of infant outcomes following mild VPA exposure in utero. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved. C1 [Moldrich, Randal X.; Leanage, Gayeshika; She, David; Dolan-Evans, Elliot; Nelson, Michael; Reza, Nargis; Reutens, David C.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia. RP Moldrich, RX (reprint author), Univ Queensland, Ctr Adv Imaging, Bldg 57,Res Rd, Brisbane, Qld 4072, Australia. EM r.moldrich@uq.edu.au FU University of Queensland FX The study was funded by The University of Queensland. The authors wish to thank Drs. Tom Burne and Gilyana Borlikova for technical assistance and advice with the behavior experiments. 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Additional novel findings that will facilitate the future clinical interpretation of smaller CNVs in schizophrenia include: (i) a greater proportion of individuals with two or more rare exonic CNVs 10 kb in size (1.5-fold increase, P 0.0109) in schizophrenia; (ii) the systematic discovery of new candidate genes for schizophrenia; and, (iii) functional gene enrichment mapping highlighting a differential impact in schizophrenia of rare exonic deletions involving diverse functions, including neurodevelopmental and synaptic processes (4.7-fold increase, P 0.0060). These findings suggest consideration of a potential role for clinical microarray testing in schizophrenia, as is now the suggested standard of care for related developmental disorders like autism. C1 [Costain, Gregory; Russell, Kathryn; Lowther, Chelsea; Yuen, Tracy; Chow, Eva W. C.; Bassett, Anne S.] Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON M5S 2S1, Canada. [Lionel, Anath C.; Merico, Daniele; Marshall, Christian R.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom & Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada. [Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5G 1L7, Canada. [Forsythe, Pamela] Horizon Hlth, St John, NB E2L 4L4, Canada. [Forsythe, Pamela] Dalhousie Univ, St John, NB E2L 4L4, Canada. [Husted, Janice] Univ Waterloo, Hlth Studies, Waterloo, ON N2L 3G1, Canada. [Stavropoulos, Dimitri J.] Hosp Sick Children, Dept Pediat Lab Med, Cytogenet Lab, Toronto, ON M5G 1X8, Canada. [Stavropoulos, Dimitri J.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Speevak, Marsha] Credit Valley Hosp, Dept Genet, Mississauga, ON L5M 2N1, Canada. [Chow, Eva W. C.; Bassett, Anne S.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. RP Bassett, AS (reprint author), 33 Russell St,Room 1100, Toronto, ON M5S 2S1, Canada. EM anne.bassett@utoronto.ca RI Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU Canadian Institutes of Health Research (CIHR) [MOP-89066, MOP-111238]; University of Toronto McLaughlin Centre; NeuroDevNet; Genome Canada; Ontario Genomics Institute; CIHR; Canadian Institute for Advanced Research; Canada Foundation for Innovation; government of Ontario; Autism Speaks; Hospital for Sick Children Foundation; CIHR Vanier Canada Graduate Scholarship; NeuroDevNet doctoral fellowship FX This work was supported by the Canadian Institutes of Health Research (CIHR) (MOP-89066 to A. S. B., MOP-111238 to A. S. B.). A. S. B. holds the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders and the Dalglish Chair in 22q11.2 Deletion Syndrome. A. C. L. holds a NeuroDevNet doctoral fellowship. G. C. holds a CIHR Vanier Canada Graduate Scholarship. S. W. S. is supported by grants from the University of Toronto McLaughlin Centre, NeuroDevNet, Genome Canada and the Ontario Genomics Institute, the CIHR, the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, the government of Ontario, Autism Speaks, and The Hospital for Sick Children Foundation. S. W. S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. 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Mol. Genet. PD NOV 15 PY 2013 VL 22 IS 22 BP 4485 EP 4501 DI 10.1093/hmg/ddt297 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 248EA UT WOS:000326675300004 PM 23813976 ER PT J AU Mennes, M Biswal, BB Castellanos, FX Milham, MP AF Mennes, Maarten Biswal, Bharat B. Castellanos, F. Xavier Milham, Michael P. TI Making data sharing work: The FCP/INDI experience SO NEUROIMAGE LA English DT Article DE Open-access; Open science; fMRI; R-fMRI; Database; Informatics; Neuroinformatics ID DEMENTED OLDER-ADULTS; OPEN ACCESS SERIES; MRI DATA; FUNCTIONAL CONNECTIVITY; DISCOVERY SCIENCE; BRAIN-FUNCTION; NEUROSCIENCE; AUTISM; REPLICATION; CHALLENGES AB Over a decade ago, the fMRI Data Center (fMRIDC) pioneered open-access data sharing in the task-based functional neuroimaging community. Well ahead of its time, the fMRIDC effort encountered logistical, sociocultural and funding barriers that impeded the field-wise instantiation of open-access data sharing. In 2009, ambitions for open-access data sharing were revived in the resting state functional MRI community in the form of two grassroots initiatives: the 1000 Functional Connectomes Project (FCP) and its successor, the International Neuroimaging Datasharing Initiative (INDI). Beyond providing open access to thousands of clinical and non-clinical imaging datasets, the FCP and INDI have demonstrated the feasibility of large-scale data aggregation for hypothesis generation and testing. Yet, the success of the FCP and INDI should not be confused with widespread embracement of open-access data sharing. Reminiscent of the challenges faced by fMRIDC, key controversies persist and include participant privacy, the role of informatics, and the logistical and cultural challenges of establishing an open science ethos. We discuss the FCP and INDI in the context of these challenges, highlighting the promise of current initiatives and suggesting solutions for possible pitfalls. (C) 2012 Elsevier Inc. All rights reserved. C1 [Mennes, Maarten] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Biswal, Bharat B.] Univ Med & Dent New Jersey, Dept Radiol, Newark, NJ 07103 USA. [Mennes, Maarten; Castellanos, F. Xavier] NYU Child Study Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA. [Biswal, Bharat B.; Castellanos, F. Xavier; Milham, Michael P.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Milham, Michael P.] Child Mind Inst, Ctr Dev Brain, New York, NY 10022 USA. RP Milham, MP (reprint author), Child Mind Inst, Ctr Dev Brain, 445 Pk Ave, New York, NY 10022 USA. EM Michael.milham@childmind.org RI Mennes, Maarten/C-9924-2011; Milham, Michael/K-9501-2014 OI Mennes, Maarten/0000-0002-7279-3439; FU Joseph P. Healy and the Stavros Niarchos Foundation; NIMH [R03 MH096321, R01MH094639, R01MH083246]; Leon Levy Foundation; Stavros Niarchos Foundation; NIH Blueprint for Neurosciences Research FX Current financial support for the INDI team is provided by gifts from Joseph P. Healy and the Stavros Niarchos Foundation, and an endowment provided to the NYU Child Study Center by Phyllis Green and Randolph Cowen. Additional current support includes NIMH awards to MPM (R03 MH096321, R01MH094639) and FXC (R01MH083246). Past support to MPM was provided by the Leon Levy Foundation and to FXC by the Stavros Niarchos Foundation. NITRC is funded by an NIH Blueprint for Neurosciences Research (neuroscienceblueprintnih.gov) contract to TCG, Inc. 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Hum. Neurosci. PD NOV 14 PY 2013 VL 7 AR 785 DI 10.3389/fnhum.2013.00785 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 265GI UT WOS:000327937800001 PM 24294201 ER PT J AU Shcheglovitov, A Shcheglovitova, O Yazawa, M Portmann, T Shu, R Sebastiano, V Krawisz, A Froehlich, W Bernstein, JA Hallmayer, JF Dolmetsch, RE AF Shcheglovitov, Aleksandr Shcheglovitova, Olesya Yazawa, Masayuki Portmann, Thomas Shu, Rui Sebastiano, Vittorio Krawisz, Anna Froehlich, Wendy Bernstein, Jonathan A. Hallmayer, Joachim F. Dolmetsch, Ricardo E. TI SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients SO NATURE LA English DT Article ID SCAFFOLDING PROTEIN SHANK3; AUTISM SPECTRUM DISORDERS; PLURIPOTENT STEM-CELLS; CORTICAL-NEURONS; HUMAN FIBROBLASTS; MUTANT MICE; MUTATIONS; DYSFUNCTION; GENERATION; CONVERSION AB Phelan-McDermid syndrome (PMDS) is a complex neurodevelopmental disorder characterized by global developmental delay, severely impaired speech, intellectual disability, and an increased risk of autism spectrum disorders (ASDs)(1). PMDS is caused by heterozygous deletions of chromosome 22q13.3. Among the genes in the deleted region is SHANK3, which encodes a protein in the postsynaptic density (PSD)(2,3). Rare mutations in SHANK3 have been associated with idiopathic ASDs(4-7), non-syndromic intellectual disability(8), and schizophrenia(9). Although SHANK3 is considered to be the most likely candidate gene for the neurological abnormalities in PMDS patients(10), the cellular and molecular phenotypes associated with this syndrome in human neurons are unknown. We generated induced pluripotent stem (iPS) cells from individuals with PMDS and autism and used them to produce functional neurons. We show that PMDS neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission. Excitatory synaptic transmission in PMDS neurons can be corrected by restoring SHANK3 expression or by treating neurons with insulin-like growth factor 1 (IGF1). IGF1 treatment promotes formation of mature excitatory synapses that lack SHANK3 but contain PSD95 and N-methyl-D-aspartate (NMDA) receptors with fast deactivation kinetics. Our findings provide direct evidence for a disruption in the ratio of cellular excitation and inhibition in PMDS neurons, and point to a molecular pathway that can be recruited to restore it. C1 [Shcheglovitov, Aleksandr; Shcheglovitova, Olesya; Yazawa, Masayuki; Portmann, Thomas; Shu, Rui; Krawisz, Anna] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. [Sebastiano, Vittorio] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Sebastiano, Vittorio] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Froehlich, Wendy; Bernstein, Jonathan A.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Froehlich, Wendy; Hallmayer, Joachim F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Dolmetsch, Ricardo E.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Dolmetsch, RE (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM Ricardo.dolmetsch@novartis.com FU National Institutes of Health (NIH) [NS069375]; California Institute for Regenerative Medicine CIRM; Autism Science Foundation; Phelan-McDermid Syndrome Foundation; Swiss National Science Foundation; Japan Society for the Promotion of Research Abroad; American Heart Association; National Institute of Mental Health (NIMH) [R33MH087898]; NIH [5DP1OD3889]; CIRM [RT2-01906]; Simons Foundation; JDH; Flora foundation FX We are grateful to participants and their families for their support; M. Adam for assistance with recruitment; to X. Jia, A. Cherry, C. Bangs, P. Jones, and J. Williams for assistance with tissue culture; P. Liao for help with multiplex ligation-dependent probe amplification (MLPA); M. Fabian for astrocyte preparations; H.N. Nguyen for consultations on the neural differentiation protocol and spectral karyotyping (SKY); V. Vu and G. Lin for help with data analysis; T. Sudhof, T. Boeckers, A. Grabruker, C. Garner and C. Sala for antibodies; R. Xavier for SHANK3 complementary DNA; R. Reijo-Pera and members of the Dolmetsch laboratory for commenting on the manuscript; E. Nigh for editing the manuscript. We also thank the Stanford Neuroscience Microscopy Service (supported by National Institutes of Health (NIH) NS069375). Support for this study came from the California Institute for Regenerative Medicine CIRM, the Autism Science Foundation and the Phelan-McDermid Syndrome Foundation (to A. S.), the Swiss National Science Foundation (to T. P.), the Japan Society for the Promotion of Research Abroad and American Heart Association (to M.Y.), the National Institute of Mental Health (NIMH) grant R33MH087898 (to J. F. H.); NIH Pioneer Award (5DP1OD3889), CIRM (grant RT2-01906) and Simons Foundation (to R. E. D.). We are also grateful for funding from the JDH research fund, N. Juaw, B. and F. Horowitz, M. McCafferey, B. and J. Packard, P. Kwan and K. Wang, and the Flora foundation. 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Surprisingly, however, there is a paucity of work directly investigating the reward value of faces for individuals with autism and the evidence for diminished face rewards in this population remains equivocal. In the current study, we measured how hard children with autism would work to view faces, using an effortful key-press sequence, and whether they were sensitive to the differential reward value of attractive and unattractive faces. Contrary to expectations, cognitively able children with autism did not differ from typically developing children of similar age and ability in their willingness to work to view faces. Moreover, the effort expended was strongly positively correlated with facial attractiveness ratings in both groups of children. There was also no evidence of atypical reward values for other, less social categories (cars and inverted faces) in the children with autism. These results speak against the possibility that face recognition difficulties in autism are explained by atypical reward value of faces. C1 [Ewing, Louise; Pellicano, Elizabeth; Rhodes, Gillian] Univ Western Australia, Sch Psychol, Ctr Excellence Cognit & its Disorders, Australian Res Council, Perth, WA 6009, Australia. [Pellicano, Elizabeth] Univ London, Inst Educ, Ctr Res Autism & Educ, London WC1N 1AZ, England. RP Ewing, L (reprint author), Univ Western Australia, Sch Psychol, Ctr Excellence Cognit & its Disorders, Australian Res Council, Perth, WA 6009, Australia. EM louise.ewing@uwa.edu.au RI Ewing, Louise/H-9158-2014 FU Australian Research Council Centre of Excellence in Cognition and its Disorders [CE110001021]; Australian Research Council Professorial Fellowship [DP0877379]; University of Western Australia; Australian Federation of University Women; Clothworkers' Foundation; Pears Foundation FX This work was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (project number CE110001021) and an Australian Research Council Professorial Fellowship to G.R (project number DP0877379). It was also supported by awards to L.E. from the University of Western Australia and the Australian Federation of University Women. Research at the Centre for Research in Autism and Education (CRAE) is supported by The Clothworkers' Foundation and Pears Foundation (E.P.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Litterman, Nadia Ikeuchi, Yoshiho de la Torre-Ubieta, Luis Bennett, Eric J. Zhang, Chi Harper, J. Wade Bonni, Azad TI A Novel Hap1-Tsc1 Interaction Regulates Neuronal mTORC1 Signaling and Morphogenesis in the Brain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; TSC1-TSC2 COMPLEX; POLARITY; IDENTIFICATION; PROTEIN; GENE; TSC1; EXPRESSION; HAMARTIN; PATHWAY AB Tuberous sclerosis complex (TSC) is a leading genetic cause of autism. The TSC proteins Tsc1 and Tsc2 control the mTORC1 signaling pathway in diverse cells, but how the mTORC1 pathway is specifically regulated in neurons remains to be elucidated. Here, using an interaction proteomics approach in neural cells including neurons, we uncover the brain-enriched protein huntingtin-associated protein 1 (Hap1) as a novel functional partner of Tsc1. Knockdown of Hap1 promotes specification of supernumerary axons in primary hippocampal neurons and profoundly impairs the positioning of pyramidal neurons in the mouse hippocampus in vivo. The Hap1 knockdown-induced phenotypes in primary neurons and in vivo recapitulate the phenotypes induced by Tsc1 knockdown. We also find that Hap1 knockdown in hippocampal neurons induces the downregulation of Tsc1 and stimulates the activity of mTORC1, as reflected by phosphorylation of the ribosomal protein S6. Inhibition of mTORC1 activity suppresses the Hap1 knockdown-induced polarity phenotype in hippocampal neurons. Collectively, these findings define a novel link between Hap1 and Tsc1 that regulates neuronal mTORC1 signaling and neuronal morphogenesis, with implications for our understanding of developmental disorders of cognition. C1 [Mejia, Luis A.; Litterman, Nadia; Ikeuchi, Yoshiho; de la Torre-Ubieta, Luis; Zhang, Chi; Bonni, Azad] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Mejia, Luis A.; Litterman, Nadia; de la Torre-Ubieta, Luis; Bonni, Azad] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Ikeuchi, Yoshiho; Bonni, Azad] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Bennett, Eric J.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Bonni, A (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. EM bonni@wustl.edu RI ikeuchi, yoshiho/C-1713-2014 OI ikeuchi, yoshiho/0000-0002-2829-3840 FU National Institutes of Health [NS041021]; Harvard-Roche; F31 National Research Service Award fellowship [NS068037] FX This work was supported by National Institutes of Health Grant NS041021 to A.B., a Harvard-Roche grant to A.B., and F31 National Research Service Award fellowship NS068037 to L.A.M. We thank Mathew E. Sowa and John R. Lydeard for expert help with MS and A.B. laboratory members for helpful discussions. 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Behav. Neurosci. PD NOV 13 PY 2013 VL 7 AR 157 DI 10.3389/fnbeh.2013.00157 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 250SW UT WOS:000326875700001 PM 24312026 ER PT J AU Lockwood, PL Bird, G Bridge, M Viding, E AF Lockwood, Patricia L. Bird, Geoffrey Bridge, Madeleine Viding, Essi TI Dissecting empathy: high levels of psychopathic and autistic traits are characterized by difficulties in different social information processing domains SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE psychopathy; autism spectrum disorder; alexithymia; empathy; affective resonance; cognitive perspective-taking ID ASPERGER-SYNDROME; FUNCTIONING AUTISM; GENERAL-POPULATION; ANIMATED SHAPES; MENTAL STATES; ALEXITHYMIA; BRAIN; MIND; RESPONSIVENESS; CHILDREN AB Individuals with psychopathy or autism spectrum disorder (ASD) can behave in ways that suggest lack of empathy towards others. However many different cognitive and affective processes may lead to unempathic behavior and the social processing profiles of individuals with high psychopathic vs. ASD traits are likely different Whilst psychopathy appears characterized by problems with resonating with others' emotions, ASD appears characterized by problems with cognitive perspective-taking. In addition, alexithymia has previously been associated with both disorders, but the contribution of alexithymia needs further exploration. In a community sample (N = 110) we show for the first time that although affective resonance and cognitive perspective-taking are related, high psychopathic traits relate to problems with resonating with others' emotions, but not cognitive perspective taking. Conversely, high ASD traits relate to problems with cognitive perspective-taking but not resonating with others' emotions. Alexithymia was associated with problems with affective resonance independently of psychopathic traits, suggesting that different component processes (reduced tendency to feel what others feel and reduced ability to identify and describe feelings) comprise affective resonance. Alexithymia was not associated with the reduced cognitive perspective-taking in high ASD traits. Our data suggest that (1) elevated psychopathic and ASD traits are characterized by difficulties in different social information processing domains and (2) reduced affective resonance in individuals with elevated psychopathic traits and the reduced cognitive perspective taking in individuals with elevated ASD traits are not explained by co-occurring alexithymia. (3) Alexithymia is independently associated with reduced affective resonance. Consequently, our data point to different component processes within the construct of empathy that are suggestive of partially separable cognitive and neural systems. C1 [Lockwood, Patricia L.; Bridge, Madeleine; Viding, Essi] UCL, Div Psychol & Language Sci, London WC1H 0AP, England. [Bird, Geoffrey] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC1H 0AP, England. [Bird, Geoffrey] UCL, Inst Cognit Neurosci, London WC1H 0AP, England. RP Lockwood, PL (reprint author), UCL, Div Psychol & Language Sci, 26 Bedford Way, London WC1H 0AP, England. EM p.lockwood@ucl.ac.uk FU Medical Research Council; Baily Thomas Charitable Fund [3089/1] FX This work was supported by a Doctoral Training Account studentship from the Medical Research Council awarded to Patricia L Lockwood. Essi Viding is a Royal Society Wolfson Research Merit Award holder. Geoffrey Bird was supported by a grant from the Baily Thomas Charitable Fund (3089/1). Geoffrey Bird completed the paper while a Senior Fellow at the Netherlands Institute for Advanced. Study in the Humanities and Social Sciences. 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PD NOV 13 PY 2013 VL 7 DI 10.3389/fnhum.2013.00760 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 250SS UT WOS:000326875300001 ER PT J AU Richard, AE Lajiness-O'Neill, RR Bowyer, SM AF Richard, Annette E. Lajiness-O'Neill, Renee R. Bowyer, Susan M. TI Impaired prefrontal gamma band synchrony in autism spectrum disorders during gaze cueing SO NEUROREPORT LA English DT Article DE autism spectrum disorder; eye gaze; gamma band synchrony; magnetoencephalography ID EYE GAZE; CHILDREN; BRAIN; PERCEPTION; OSCILLATIONS; INDIVIDUALS; DEFICITS AB Orienting to eye gaze is a vital social skill that is absent or developmentally delayed in autism spectrum disorders (ASD). Neural synchrony in the gamma frequency band is believed to be involved in perceptual and cognitive functions such as eye-gaze processing, and has been found to be abnormal in ASD. The current study used magnetoencephalography to measure neural synchrony in the gamma frequency band in neurotypicals (n=8) and individuals with ASD (n=10) while performing a directional eye-gaze processing task. Results support impaired generation of neural synchrony in the gamma frequency band during eye-gaze processing in ASD. Impaired gamma oscillatory activity in the prefrontal cortex may be associated with impairments in social cognitive functions such as eye-gaze processing in ASD. C1 [Richard, Annette E.; Lajiness-O'Neill, Renee R.; Bowyer, Susan M.] Eastern Michigan Univ, Dept Psychol, Ypsilanti, MI 48197 USA. RP Richard, AE (reprint author), Eastern Michigan Univ, Dept Psychol, Mark Jefferson Sci Complex, Ypsilanti, MI 48197 USA. 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Experimental and self-report evidence reveals similarities between AN and autism spectrum condition (ASC) populations in socio-emotional and cognitive domains; this includes difficulties with empathy, set-shifting and global processing. Focusing on these similarities may lead to better tailored interventions for both conditions. Methods: A cross-sectional independent-groups design was employed. Participants with AN (n = 66) and typical controls (n = 66) completed self-report questionnaires including the Short (10-Item) Version Autism Spectrum Quotient (AQ-10) questionnaire (the first time this has been implemented in this population), the Eating Disorder Examination Questionnaire, the Hospital Anxiety and Depression Scale and the Work and Social Adjustment Scale. Group differences and the relationship between autistic traits and other questionnaire measures were investigated. Results: The AN group had a significantly higher AQ-10 total score and a greater proportion scored above the clinical cut-off than the control group. Seven out of ten AQ-10 items significantly discriminated between groups. In the AN group, levels of autistic traits correlated with a greater self-reported anxiety and depression and a lower ability to maintain close relationships; however, eating disorder symptoms were not associated with autistic traits. Conclusions: Women with anorexia possess a greater number of autistic traits than typical women. AQ-10 items that discriminated between groups related to 'bigger picture' (global) thinking, inflexibility of thinking and problems with social interactions, suggesting that autistic traits may exacerbate factors that maintain the eating disorder rather than cause the eating disorder directly. Using screening instruments may improve understanding of patients' problems, leading to better tailoring of intervention. We conclude that further investigation of autistic traits in AN could inform new intervention approaches based on joint working between ASC and eating disorder services. C1 [Tchanturia, Kate; Smith, Emma] Inst Psychiat, Kings Coll London, London SE5 8AF, England. [Tchanturia, Kate; Smith, Emma; Kern, Nikola; Treasure, Janet] South London & Maudsley NHS Trust, Psychol Med Clin Acad Grp, London, England. [Tchanturia, Kate; Weineck, Felicitas; Fidanboylu, Eliz; Treasure, Janet] Inst Psychiat, Kings Coll London, Mental Hlth Studies Programme, London SE5 8AF, England. [Cohen, Simon Baron] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. [Cohen, Simon Baron] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England. RP Tchanturia, K (reprint author), Inst Psychiat, Kings Coll London, De Crespigny Pk, London SE5 8AF, England. EM Kate.Tchanturia@kcl.ac.uk FU Medical Research Council; NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust; Autism Research Trust; Swiss Anorexia Foundation; Mental Health Studies Programme of King's College London FX The authors would like to thank the Swiss Anorexia Foundation and the Mental Health Studies Programme of King's College London for financial support of this study. SBC was supported by the Medical Research Council, the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust, and the Autism Research Trust during the period of this work. The authors would also like to thank Dr Daniel Stahl and Nick Lao-Kaim for their guidance and expertise regarding the statistical analysis. 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Autism PD NOV 12 PY 2013 VL 4 AR 44 DI 10.1186/2040-2392-4-44 PG 8 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 291NP UT WOS:000329835700001 PM 24220604 ER PT J AU Gheldof, N Witwicki, RM Migliavacca, E Leleu, M Didelot, G Harewood, L Rougemont, J Reymond, A AF Gheldof, Nele Witwicki, Robert M. Migliavacca, Eugenia Leleu, Marion Didelot, Gerard Harewood, Louise Rougemont, Jacques Reymond, Alexandre TI Structural Variation-Associated Expression Changes Are Paralleled by Chromatin Architecture Modifications SO PLOS ONE LA English DT Article ID COPY NUMBER VARIATION; WILLIAMS-BEUREN-SYNDROME; HUMAN GENOME; GENE-EXPRESSION; HISTONE MODIFICATIONS; MOUSE GENOME; HI-C; CHROMOSOME; LANDSCAPE; CELLS AB Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. 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GEO Series accession number: GSE33784, GSE33867. C1 [Gheldof, Nele; Witwicki, Robert M.; Migliavacca, Eugenia; Didelot, Gerard; Harewood, Louise; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Gen, Lausanne, Switzerland. [Migliavacca, Eugenia; Leleu, Marion; Rougemont, Jacques] SIB, Lausanne, Switzerland. [Leleu, Marion; Rougemont, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland. RP Gheldof, N (reprint author), Nestle Inst Hlth Sci, Lausanne, Switzerland. EM nele.gheldof@rd.nestle.com; alexandre.reymond@unil.ch FU European Commission anEUploidy Integrated Project [037627]; Swiss National Science Foundation; SNSF Sinergia grant; doctoral school of the Faculty of Biology and Medicine, University of Lausanne FX This work was supported by the European Commission anEUploidy Integrated Project (grant 037627), the Swiss National Science Foundation and a SNSF Sinergia grant to AR. RMW was supported by a fellowship from the doctoral school of the Faculty of Biology and Medicine, University of Lausanne. NG is a grantee of the Marie Heim Vogtlin and the Pro-Women programs of the SNSF and the Faculty of Biology and Medicine, University of Lausanne, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Alberts, I. Li, X. TI BRAIN IL-6 AND AUTISM SO NEUROSCIENCE LA English DT Review DE autism; brain; Interleukin-6; neuroimmune response; behavior ID CEREBELLAR GRANULE NEURONS; DENDRITIC SPINE DENSITY; SPECTRUM DISORDERS; INDUCED NEUROTOXICITY; SYNAPTIC PLASTICITY; INTERLEUKIN-6 IL-6; IMMUNE ACTIVATION; GENE-EXPRESSION; CHILDREN; SCHIZOPHRENIA AB Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and non-verbal communication, and repetitive behavior and restricted interests. Emerging evidence suggests that aberrant neuroimmune responses may contribute to phenotypic deficits and could be appropriate targets for pharmacologic intervention. Interleukin (IL)-6, one of the most important neuroimmune factors, has been shown to be involved in physiological brain development and in several neurological disorders. For instance, findings from postmortem and animal studies suggest that brain IL-6 is an important mediator of autism-like behaviors. In this review, a possible pathological mechanism behind autism is proposed, which suggests that IL-6 elevation in the brain, caused by the activated glia and/or maternal immune activation, could be an important inflammatory cytokine response involved in the mediation of autism-like behaviors through impairments of neuroanatomical structures and neuronal plasticity. Further studies to investigate whether IL-6 could be used for therapeutic interventions in autism would be of great significance. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Wei, H.] Shanxi Med Univ, Cent Lab, Shanxi Prov Peoples Hosp, Taiyuan 030012, Peoples R China. [Alberts, I.] CUNY, Dept Nat Sci, LaGuardia CC, New York, NY 11101 USA. [Li, X.] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA. 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Corbett, Blythe A. TI Examining associations between anxiety and cortisol in high functioning male children with autism SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Anxiety; Stress; Cortisol; Self-report ID COMPLEX DEVELOPMENTAL DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SPECTRUM DISORDERS; SOCIAL STRESS; CONTROLLED-TRIAL; PSYCHIATRIC-SYMPTOMS; INFORMANT AGREEMENT; PSYCHOSOCIAL STRESS; SALIVARY CORTISOL; CIRCADIAN-RHYTHMS AB Background: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal. Methods: Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol). Results: Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism. Conclusions: Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances. C1 [Simon, David M.; Corbett, Blythe A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37203 USA. [Simon, David M.; Corbett, Blythe A.] Vanderbilt Kennedy Ctr, Nashville, TN USA. RP Corbett, BA (reprint author), Vanderbilt Univ, Dept Psychiat, 230 Appleton Way, Nashville, TN 37203 USA. EM blythe.corbett@vanderbilt.edu FU National Institute of Health [R01 MH085717] FX This work was supported in part by National Institute of Health R01 MH085717 awarded to BAC. 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Neurodev. Disord. PD NOV 11 PY 2013 VL 5 AR 32 DI 10.1186/1866-1955-5-32 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 281SS UT WOS:000329121900001 PM 24216056 ER PT J AU Horwitz, B Hwang, C Alstott, J AF Horwitz, Barry Hwang, Chuhern Alstott, Jeff TI Interpreting the effects of altered brain anatomical connectivity on fMRI functional connectivity: a role for computational neural modeling SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE neural modeling; fMRI; functional connectivity; brain disorders; huma nbrain ID HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; WORKING-MEMORY; NEURONAL DYNAMICS; NETWORK ANALYSIS; VISUAL PATHWAYS; STATE; SCHIZOPHRENIA; SYSTEMS; AUTISM AB Recently, there have been a large number of studies using resting state fMRI to characterize abnormal brain connectivity in patients with a variety of neurological, psychiatric, and developmental disorders. However, interpreting what the differences in resting state fMRI functional connectivity (rsfMRI-FC) actually reflect in terms of the underlying neural pathology has proved to be elusive because of the complexity of brain anatomical connectivity. The same is the case for task-based fMRI studies. In the last few years, several groups have used large-scale neural modeling to help provide some insight into the relationship between brain anatomical connectivity and the corresponding patterns of fMRI-FC. In this paper we review several efforts at using large-scale neural modeling to investigate the relationship between structural connectivity and functional/effective connectivity to determine how alterations in structural connectivity are manifested in altered patterns of functional/effective connectivity. Because the alterations made in the anatomical connectivity between specific brain regions in the model are known in detail, one can use the results of these simulations to determine the corresponding alterations in rsfMRI-FC. Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification. Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights. Note that increases in rsfMRI-FC in patients have been interpreted in some cases as resulting from neural plasticity. These results suggest that this interpretation can be mistaken. The relevance of these simulation findings to the use of functional/effective fMRI connectivity as biomarkers for brain disorders is also discussed C1 [Horwitz, Barry; Hwang, Chuhern] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. [Hwang, Chuhern] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Hwang, Chuhern] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Alstott, Jeff] NIMH, Sect Crit Brain Dynam, NIH, Bethesda, MD 20892 USA. [Alstott, Jeff] Univ Cambridge, Brain Mapping Unit, Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, 10 Ctr Dr,Room 5D39,MSC 1402, Bethesda, MD 20892 USA. EM horwitzb@nidcd.nih.gov FU ntramural Research Programs of the National Institute on Deafness; Other Communication Disorders, the National Institute of Mental Health; National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Institute on Deafness and Other Communication Disorders, the National Institute of Mental Health, and the National Institute of Biomedical Imaging and Bioengineering, all part of the National Institutes of Health. The simulations performed for this paper utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. 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Hum. Neurosci. PD NOV 11 PY 2013 VL 7 AR 649 DI 10.3389/fnhum.2013.00649 PG 11 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 248TU UT WOS:000326727600001 PM 24273500 ER PT J AU Lehnhardt, FG Gawronski, A Pfeiffer, K Kockler, H Schilbach, L Vogeley, K AF Lehnhardt, Fritz-Georg Gawronski, Astrid Pfeiffer, Kathleen Kockler, Hanna Schilbach, Leonhard Vogeley, Kai TI The Investigation and Differential Diagnosis of Asperger Syndrome in Adults SO DEUTSCHES ARZTEBLATT INTERNATIONAL LA English DT Review ID AUTISM SPECTRUM DISORDERS; FUNCTIONING AUTISM; EPIDEMIOLOGY; QUOTIENT; OVERLAP; AQ AB Background: As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD-impaired social interaction and communication, bizarre interests-are now commonly recognized as being typical of autism, not only in children, but in adults as well. More often than before, general practitioners, neurologists, and psychiatrists find themselves being asked whether a patient is suffering from previously unrecognized Asperger syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic evaluation of AS in adulthood. Methods: We selectively searched the Medline database for pertinent literature, paying special attention to diagnostic manuals and to the guideline of the United Kingdom's National Institute for Health and Care Excellence (NICE). Results: Centrally important aspects of the diagnosis of AS include an assessment of the patient's ability to assume the emotional perspectives of others, non-verbal modes of expression, repetitive behavior patterns, and childhood social behavioral history. The autism quotient (AQ) is now established as a simple but nonspecific screening test. Up to 70% of all affected adults have comorbid disturbances, most often depression and anxiety disorders. The differential diagnosis includes personality disorders, anxiety disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The diagnostic assessment should proceed in stepwise fashion, starting from simple screening in primary care and then moving on to evaluation of the suspected diagnosis by a mental health care specialist, followed by extensive further investigation in an outpatient clinic specifically devoted to patients with autism spectrum disorders. Conclusion: The diagnostic assessment of autism in adults requires knowledge of the core and accompanying manifestations of autism and of their differential diagnoses. More research is needed for the development of further screening tests and the precise determination of diagnosis rates, differential diagnoses, and comorbidities. C1 [Lehnhardt, Fritz-Georg; Gawronski, Astrid; Pfeiffer, Kathleen; Kockler, Hanna; Schilbach, Leonhard; Vogeley, Kai] Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany. [Vogeley, Kai] Forschungszentrum Julich, Inst Cognit Neurosci, Inst Neurosci & Med INM 3, D-52425 Julich, Germany. RP Lehnhardt, FG (reprint author), Uniklin Koln, Klin & Poliklin Psychiat & Psychotherapie, Kerpener Str 62, D-50937 Cologne, Germany. EM Fritz-Georg.Lehnhardt@uk-koeln.de RI Vogeley, K/E-4860-2012 OI Vogeley, K/0000-0002-5891-5831 FU Volkswagen Foundation FX Dr. Schilbach received financial support from the Volkswagen Foundation for an interdisciplinary research project on social cognition. 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Arztebl. Int. PD NOV 8 PY 2013 VL 110 IS 45 BP 755 EP 763 DI 10.3238/arztebl.2013.0755 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 258SD UT WOS:000327478100001 PM 24290364 ER PT J AU Stoccoro, A Karlsson, HL Coppede, F Migliore, L AF Stoccoro, Andrea Karlsson, Hanna L. Coppede, Fabio Migliore, Lucia TI Epigenetic effects of nano-sized materials SO TOXICOLOGY LA English DT Article DE Epigenetics; Nano-sized materials; Nanoparticles; DNA methylation; Histone modifications; MicroRNA ID DNA METHYLATION PATTERNS; CERIUM OXIDE NANOPARTICLES; MATTER AIR-POLLUTION; OXIDATIVE STRESS; PARTICULATE MATTER; GENE-EXPRESSION; HIGH-THROUGHPUT; GOLD NANOPARTICLES; CPG ISLANDS; ENVIRONMENTAL-FACTORS AB The term epigenetics includes several phenomena such as DNA methylation, histone tail modifications, and microRNA mediated mechanisms, which are able to mold the chromatin structure and/or gene expression levels, without altering the primary DNA sequence. Environmental agents can exert epigenetic properties and there is increasing evidence of epigenetic deregulation of gene expression in several human diseases, including cancer, cardiovascular diseases, autism spectrum disorders, autoimmune diseases, and neurodegeneration, among others. Given the widespread use and dispersion in the environment of nano-sized materials, this article summarizes the studies performed so far to evaluate their potential epigenetic properties. Those studies highlight the ability of certain nano-sized compounds to induce an impaired expression of genes involved in DNA methylation kactions leading to global DNA methylation changes, as well as changes of gene specific methylation of tumor suppressor genes, inflammatory genes, and DNA repair genes, all potentially involved in cancer development. Moreover, some nano-sized compounds are able to induce changes in the acetylation and methylation of histone tails, as well as microRNA deregulated expression. We also provided a detailed description of currently available methodologies to evaluate epigenetic modifications. Standard protocols are currently available to evaluate cytotoxic and genotoxic effects of nano-sized materials. By contrast, there are at present no available standard protocols to evaluate the epigenetic potential of any given compound. The currently available methodologies offer different, but often complementary information to characterize potential epigenetic changes induced by exposure to nano-sized compounds. Given the widespread use and dispersion in the environment of nano-sized materials, at present and foreseeable in the near future, and in light of the indication of potential epigenetic properties here reviewed, more attention should be paid to unravel the consequences of such effects in future studies. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Stoccoro, Andrea; Migliore, Lucia] Univ Pisa, Med Genet Lab, Dept Translat Res & New Technol Med & Surg, I-56126 Pisa, Italy. [Karlsson, Hanna L.] Karolinska Inst, Inst Environm Med, Div Mol Toxicol, S-10401 Stockholm, Sweden. [Coppede, Fabio] Pisa Univ Hosp AOUP, Dept Lab Med, Pisa, Italy. RP Migliore, L (reprint author), Univ Pisa, Div Med Genet, Dept Translat Res & New Technol Med & Surg, Via S Giuseppe 22, I-56126 Pisa, Italy. EM l.migliore@geog.unipi.it FU FP7 project NanoRetox [CP-FP 214478-2]; FP7 project SANOWORK [280716]; Swedish Council for Working Life and Social Research (FAS) FX This study was financially supported by the FP7 projects No CP-FP 214478-2, NanoRetox and No 280716, SANOWORK and the Swedish Council for Working Life and Social Research (FAS). 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The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives. C1 [Buard, Isabelle; Kronberg, Eugene; Rojas, Donald C.] Univ Colorado Denver, Dept Psychiat, UCD Magnetoencephalog Lab, Aurora, CO 80045 USA. [Rogers, Sally J.] UC Davis MIND Inst, Sacramento, CA USA. [Hepburn, Susan] Univ Colorado JFK Partners, Aurora, CO USA. RP Rojas, DC (reprint author), Univ Colorado Denver, Dept Psychiat, Magnetoencephalog Lab, Anschutz Med Campus,13001 East 17th Pl F546, Aurora, CO 80045 USA. EM don.rojas@ucdenver.edu FU NIH [RO1 MH082820]; Cure Autism FX This work was funded by NIH RO1 MH082820 and Cure Autism Now (currently Autism Speaks). The authors of the manuscript declare that they have no conflict of interest to report regarding this manuscript. 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Hum. Neurosci. PD NOV 8 PY 2013 VL 7 AR 742 DI 10.3389/fnhum.2013.00742 PG 11 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 248EJ UT WOS:000326676200001 PM 24265611 ER PT J AU Moseley, RL Mohr, B Lombardo, MV Baron-Cohen, S Hauk, O Pulvermuller, F AF Moseley, Rachel L. Mohr, Bettina Lombardo, Michael V. Baron-Cohen, Simon Hauk, Olaf Pulvermueller, Friedemann TI Brain and behavioral correlates of action semantic deficits in autism SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE Autism; semantics; motor systems; action ID HIGH-FUNCTIONING AUTISM; MIRROR-NEURON SYSTEM; LONG-TERM-MEMORY; WORD FORM AREA; MOTOR SYSTEM; SPECTRUM DISORDERS; VISUAL-CORTEX; LANGUAGE; SELF; CHILDREN AB Action-perception circuits containing neurons in the motor system have been proposed as the building blocks of higher cognition; accordingly, motor dysfunction should entail cognitive deficits. Autism spectrum conditions (ASC) are marked by motor impairments but the implications of such motor dysfunction for higher cognition remain unclear. We here used word reading and semantic judgment tasks to investigate action-related motor cognition and its corresponding fMRI brain activation in high-functioning adults with ASC. These participants exhibited hypoactivity of motor cortex in language processing relative to typically developing controls. Crucially, we also found a deficit in semantic processing of action-related words, which, intriguingly, significantly correlated with this underactivation of motor cortex to these items. Furthermore, the word-induced hypoactivity in the motor system also predicted the severity of ASC as expressed by the number of autistic symptoms measured by the Autism-Spectrum Quotient (Baron-Cohen et al., 2001). These significant correlations between word-induced activation of the motor system and a newly discovered semantic deficit in a condition known to be characterized by motor impairments, along with the correlation of such activation with general autistic traits, confirm critical predictions of causal theories linking cognitive and semantic deficits in ASC, in part, to dysfunctional action-perception circuits and resultant reduction of motor system activation. C1 [Moseley, Rachel L.; Hauk, Olaf; Pulvermueller, Friedemann] MRC, Cognit & Brain Sci Unit, Cambridge CB2 7EF, England. [Mohr, Bettina] Charite, Dept Psychiat, D-13353 Berlin, Germany. [Lombardo, Michael V.; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. [Pulvermueller, Friedemann] Free Univ Berlin, Dept Philosophy & Humanities, Brain Language Lab, Berlin, Germany. RP Moseley, RL (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England. EM rachel.moseley@cantab.net FU Medical Research Council [MC_US_A060_0034, U1055.04.003.00001.01]; Freie Universitat Berlin; Deutsche Forschungsgemeinschaft (Excellence Cluster Languages of Emotion); Engineering and Physical Sciences Research Council (UK) (BABEL grant) FX The authors would like to thank the following: Clare Cook, Yury Shtyrov, and Francesca Carota for help and input at various stages of theoretical discussion and imaging analysis; Amanda Ludlow for early help with ASC participant recruitment; and staff at the ARC, particularly Bonnie Aeyeung and Carrie Allison, who assisted with participant recruitment. This work was supported by the Medical Research Council (MC_US_A060_0034, U1055.04.003.00001.01 to Friedemann Pulvermuller), the Freie Universitat Berlin (startup grant to Friedemann Pulvermuller), the Deutsche Forschungsgemeinschaft (Excellence Cluster Languages of Emotion), and the Engineering and Physical Sciences Research Council (UK) (BABEL grant). CR Bak T. 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We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anisotropy (FA) and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism. C1 [Schaer, Marie] Stanford Univ, Sch Med, Stanford Cognit & Syst Neurosci Lab, Palo Alto, CA 94304 USA. [Schaer, Marie; Ottet, Marie-Christine; Scariati, Elisa; Franchini, Martina; Eliez, Stephan; Glaser, Bronwyn] Univ Geneva, Sch Med, Dept Psychiat, Off Medicopedagog, CH-1211 Geneva, Switzerland. [Dukes, Daniel] Univ Neuchatel, Ctr Cognit Sci, CH-2000 Neuchatel, Switzerland. [Dukes, Daniel] Univ Geneva, Swiss Ctr Affect Sci, Geneva, Switzerland. [Eliez, Stephan] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. RP Schaer, M (reprint author), Stanford Univ, Sch Med, Stanford Cognit & Syst Neurosci Lab, 1070 Arastradero Rd,Suite 220, Palo Alto, CA 94304 USA. EM marie.schaer@unige.ch FU Eagle Foundation; FHMS ("Fondation Handicap Mentaland Societe"); Fondation Dora; Fondation 1796; Center of Biomedical Imaging; National Center of Competence in Research (NCCR)" SYNAPSY-The Synaptic Bases of Mental Diseases"; Swiss National Science Foundation; Swiss National Foundation of Science [145760] FX We would like to thank the children, adolescents and families who participated in this study. The families were recruited as a part of a remediation study supported by the Eagle Foundation, the FHMS ("Fondation Handicap Mentaland Societe"), the Fondation Dora and the Fondation 1796. Further support for MRI acquisition was provided by the Center of Biomedical Imaging. 5 MS was supported by a grant from the National Center of Competence in Research (NCCR)" SYNAPSY-The Synaptic Bases of Mental Diseases" financed by the Swiss National Science Foundation, and then by a fellowship from the Swiss National Foundation of Science (#145760). The authors would like to extend a special thank you to Hilary Woodde Wilde and Sonia Martinez for their help with patients' assessment. 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Hum. Neurosci. PD NOV 8 PY 2013 VL 7 DI 10.3389/fnhum.2013.00750 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 248EL UT WOS:000326676400001 PM 24265612 ER PT J AU Dodell-Feder, D Lincoln, SH Coulson, JP Hooker, CI AF Dodell-Feder, David Lincoln, Sarah Hope Coulson, Joseph P. Hooker, Christine I. TI Using Fiction to Assess Mental State Understanding: A New Task for Assessing Theory of Mind in Adults SO PLOS ONE LA English DT Article ID HIGH-FUNCTIONING AUTISM; VENTROMEDIAL PREFRONTAL CORTEX; COGNITIVE ENHANCEMENT THERAPY; 1ST EPISODE PSYCHOSIS; SOCIAL-COGNITION; ASPERGER-SYNDROME; MORAL JUDGMENT; FALSE-BELIEF; INDIVIDUAL-DIFFERENCES; 1ST-EPISODE PSYCHOSIS AB Social functioning depends on the ability to attribute and reason about the mental states of others - an ability known as theory of mind (ToM). Research in this field is limited by the use of tasks in which ceiling effects are ubiquitous, rendering them insensitive to individual differences in ToM ability and instances of subtle ToM impairment. Here, we present data from a new ToM task - the Short Story Task (SST) - intended to improve upon many aspects of existing ToM measures. More specifically, the SST was designed to: (a) assess the full range of individual differences in ToM ability without suffering from ceiling effects; (b) incorporate a range of mental states of differing complexity, including epistemic states, affective states, and intentions to be inferred from a first-and second-order level; (c) use ToM stimuli representative of real-world social interactions; (d) require participants to utilize social context when making mental state inferences; (e) exhibit adequate psychometric properties; and (f) be quick and easy to administer and score. In the task, participants read a short story and were asked questions that assessed explicit mental state reasoning, spontaneous mental state inference, and comprehension of the non-mental aspects of the story. Responses were scored according to a rubric that assigned greater points for accurate mental state attributions that included multiple characters' mental states. Results demonstrate that the SST is sensitive to variation in ToM ability, can be accurately scored by multiple raters, and exhibits concurrent validity with other social cognitive tasks. The results support the effectiveness of this new measure of ToM in the study of social cognition. The findings are also consistent with studies demonstrating significant relationships among narrative transportation, ToM, and the reading of fiction. Together, the data indicate that reading fiction may be an avenue for improving ToM ability. C1 [Dodell-Feder, David; Lincoln, Sarah Hope; Hooker, Christine I.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Dodell-Feder, D (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM feder@fas.harvard.edu FU Harvard University FX This work was supported by Harvard University research funds to Christine I. Hooker and David Dodell-Feder. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets ("single-hit etiology") or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets ("multiple-hit etiology"). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches. C1 [Steinberg, Julia; Webber, Caleb] Univ Oxford, MRC, Dept Physiol Anat & Genet, Funct Genom Unit, Oxford OX1 3QX, England. [Steinberg, Julia] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Webber, C (reprint author), Univ Oxford, MRC, Dept Physiol Anat & Genet, Funct Genom Unit, Oxford OX1 3QX, England. EM caleb.webber@dpag.ox.ac.uk FU Wellcome Trust [093941/Z/10/Z, 090532/Z/09/Z]; Medical Research Council; European Union [241995]; National Institute of Mental Health [1U24MH081810] FX We thank the anonymous reviewers for their comments and suggestions. This work was supported by the Wellcome Trust (grants 093941/Z/10/Z to J.S. and 090532/Z/09/Z to the Wellcome Trust Centre for Human Genetics), Medical Research Council (funding to C.W), and the European Union's Seventh Framework Programme project GENCODYS (grant 241995 to C.W.). We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (principal investigator). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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J. Hum. Genet. PD NOV 7 PY 2013 VL 93 IS 5 BP 825 EP 839 DI 10.1016/j.ajhg.2013.09.013 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 252HU UT WOS:000326996600004 PM 24207117 ER PT J AU Suls, A Jaehn, JA Kecskes, A Weber, Y Weckhuysen, S Craiu, DC Siekierska, A Djemie, T Afrikanova, T Gormley, P von Spiczak, S Kluger, G Iliescu, CM Talvik, T Talvik, I Meral, C Caglayan, HS Giraldez, BG Serratosa, J Lemke, JR Hoffman-Zacharska, D Szczepanik, E Barisic, N Komarek, V Hjalgrim, H Moller, RS Linnankivi, T Dimova, P Striano, P Zara, F Marini, C Guerrini, R Depienne, C Baulac, S Kuhlenbaumer, G Crawford, AD Lehesjoki, AE de Witte, PAM Palotie, A Lerche, H Esguerra, CV De Jonghe, P Helbig, I AF Suls, Arvid Jaehn, Johanna A. Kecskes, Angela Weber, Yvonne Weckhuysen, Sarah Craiu, Dana C. Siekierska, Aleksandra Djemie, Tania Afrikanova, Tatiana Gormley, Padhraig von Spiczak, Sarah Kluger, Gerhard Iliescu, Catrinel M. Talvik, Tiina Talvik, Inga Meral, Cihan Caglayan, Hande S. Giraldez, Beatriz G. Serratosa, Jose Lemke, Johannes R. Hoffman-Zacharska, Dorota Szczepanik, Elzbieta Barisic, Nina Komarek, Vladimir Hjalgrim, Helle Moller, Rikke S. Linnankivi, Tarja Dimova, Petia Striano, Pasquale Zara, Federico Marini, Carla Guerrini, Renzo Depienne, Christel Baulac, Stephanie Kuhlenbaeumer, Gregor Crawford, Alexander D. Lehesjoki, Anna-Elina de Witte, Peter A. M. Palotie, Aarno Lerche, Holger Esguerra, Camila V. De Jonghe, Peter Helbig, Ingo CA EuroEPINOMICS RES Consortium TI De Novo Loss-of-Function Mutations in CHD2 Cause a Fever-Sensitive Myoclonic Epileptic Encephalopathy Sharing Features with Dravet Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; DNA-BINDING PROTEIN-2; GENE; PHENOTYPE; DELETION; DISEASE; MEMBER; RATES; SCN1A AB Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore the functional relevance of CHD2 haploinsufficiency in an in vivo model system, we knocked down chd2 in zebrafish by using targeted morpholino antisense oligomers. chd2-knockdown larvae exhibited altered locomotor activity, and the epileptic nature of this seizure-like behavior was confirmed by field-potential recordings that revealed epileptiform discharges similar to seizures in affected persons. Both altered locomotor activity and epileptiform discharges were absent in appropriate control larvae. Our study provides evidence that de novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures. C1 [Suls, Arvid; Weckhuysen, Sarah; Djemie, Tania; De Jonghe, Peter] VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium. [Suls, Arvid; Weckhuysen, Sarah; Djemie, Tania; De Jonghe, Peter] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2610 Antwerp, Belgium. [Jaehn, Johanna A.; von Spiczak, Sarah; Helbig, Ingo] Univ Kiel, Univ Med Ctr Schleswig Holstein, D-24105 Kiel, Germany. [Kecskes, Angela; Siekierska, Aleksandra; Afrikanova, Tatiana; Crawford, Alexander D.; de Witte, Peter A. M.; Esguerra, Camila V.] Univ Louvain, Dept Pharmaceut & Pharmacol Sci, Lab Mol Biodiscovery, B-3000 Louvain, Belgium. [Weber, Yvonne; Lerche, Holger] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, D-72076 Tubingen, Germany. [Craiu, Dana C.; Iliescu, Catrinel M.] Carol Davila Univ Med, Dept Neurol, Pediat Neurol Clin 2, Bucharest 050474, Romania. [Craiu, Dana C.; Iliescu, Catrinel M.] Carol Davila Univ Med, Dept Pediat Neurol, Bucharest 050474, Romania. [Craiu, Dana C.; Iliescu, Catrinel M.] Carol Davila Univ Med, Dept Psychiat, Bucharest 050474, Romania. [Craiu, Dana C.; Iliescu, Catrinel M.] Carol Davila Univ Med, Dept Neurosurg, Bucharest 050474, Romania. [Craiu, Dana C.; Iliescu, Catrinel M.] Prof Doctor Alexandru Obregia Clin Hosp, Pediat Neurol Clin, Bucharest 041914, Romania. [Gormley, Padhraig; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. [Kluger, Gerhard] Schon Klin Vogtareuth, Tagesklin Neuropadiatrie, Epilepsiezentrum Kinder & Jugendliche, D-83569 Vogtareuth, Germany. [Talvik, Tiina; Talvik, Inga] Univ Tartu, Dept Pediat, EE-51014 Tartu, Estonia. [Talvik, Tiina; Talvik, Inga] Tartu Univ Hosp, Dept Neurol & Neurorehabil, Childrens Clin, EE-50406 Tartu, Estonia. [Meral, Cihan] GATA Haydarpasa Teaching Hosp, Dept Pediat Neurol, TR-34668 Istanbul, Turkey. [Caglayan, Hande S.] Bogazici Univ, Dept Mol Biol & Genet, TR-34342 Istanbul, Turkey. [Giraldez, Beatriz G.; Serratosa, Jose] Hosp Univ Fdn Jimenez Diaz, Epilepsy Unit, Madrid 28040, Spain. [Giraldez, Beatriz G.; Serratosa, Jose] Ctr Invest Biomed Red Enfermedades Raras, Madrid 28040, Spain. [Lemke, Johannes R.] Univ Childrens Hosp, Inselspital, Div Human Genet, CH-3010 Bern, Switzerland. [Hoffman-Zacharska, Dorota] Inst Mother & Child Hlth, Dept Med Genet, PL-01211 Warsaw, Poland. [Szczepanik, Elzbieta] Inst Mother & Child Hlth, Clin Neurol Child & Adolescents, PL-01211 Warsaw, Poland. [Barisic, Nina] Univ Zagreb, Sch Med, Univ Hosp Ctr Zagreb, Dept Paediat, Zagreb 10000, Croatia. [Komarek, Vladimir] Univ Hosp Motol, Child Neurol Dept, Prague 15006, Czech Republic. [Hjalgrim, Helle; Moller, Rikke S.] Danish Epilepsy Ctr, DK-4293 Dianalund, Denmark. [Hjalgrim, Helle] Univ Southern Denmark, Inst Reg Hlth Res, DK-5230 Odense, Denmark. [Linnankivi, Tarja] Univ Helsinki, Childrens Hosp, Helsinki 00029, Finland. [Linnankivi, Tarja] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland. [Dimova, Petia] St Naum Univ Hosp Neurol & Psychiat, Clin Child Neurol, Sofia 1113, Bulgaria. [Striano, Pasquale] Univ Genoa, Dept Neurosci, Pediat Neurol & Muscular Dis Unit, I-16147 Genoa, Italy. [Striano, Pasquale] Univ Genoa, Dept Rehabil, I-16147 Genoa, Italy. [Striano, Pasquale] Univ Genoa, Dept Ophthalmol, I-16147 Genoa, Italy. [Striano, Pasquale] Univ Genoa, Dept Genet, I-16147 Genoa, Italy. [Striano, Pasquale] Univ Genoa, Dept Maternal & Child Hlth, I-16147 Genoa, Italy. [Striano, Pasquale] Gaslini Inst, I-16147 Genoa, Italy. [Zara, Federico] Gaslini Inst, Dept Neurosci, Neurogenet Lab, Pediat Neurol & Muscular Dis Unit, I-16147 Genoa, Italy. [Marini, Carla; Guerrini, Renzo] Univ Florence, Meyer Childrens Hosp, Pediat Neurol Unit, I-50132 Florence, Italy. [Marini, Carla; Guerrini, Renzo] Univ Florence, Meyer Childrens Hosp, Pediat Neurol Labs, I-50132 Florence, Italy. [Depienne, Christel; Baulac, Stephanie] Hop La Pitie Salpetriere, Ctr Rech, INSERM, Inst Cerveau & Moelle Epiniere,U975, F-75013 Paris, France. [Depienne, Christel; Baulac, Stephanie] Hop La Pitie Salpetriere, Ctr Rech, CNRS 7225, Inst Cerveau & Moelle Epiniere, F-75013 Paris, France. [Baulac, Stephanie] Univ Paris 06, UMR S 975, F-75013 Paris, France. [Depienne, Christel] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Unite Fonct Neurogenet Mol & Cellulaire, F-75013 Paris, France. [Kuhlenbaeumer, Gregor] Univ Kiel, Inst Expt Med, Dept Neurol, D-24105 Kiel, Germany. [Crawford, Alexander D.] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg. [Lehesjoki, Anna-Elina] Folkhalsan Inst Genet, Helsinki 00290, Finland. [Lehesjoki, Anna-Elina] Univ Helsinki, Res Programs Unit, FIN-00290 Helsinki, Finland. [Lehesjoki, Anna-Elina] Univ Helsinki, Ctr Neurosci, FIN-00290 Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland. [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA 02142 USA. RP De Jonghe, P (reprint author), VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium. EM peter.dejonghe@molgen.vib-ua.be RI Esguerra, Camila/D-7657-2014 OI Esguerra, Camila/0000-0001-7891-1427 FU European Science Foundation; state budget of Romania; Scientific and Technological Research Council of Turkey; National Science Centre Poland [800/N-ESF-EuroEPINOMICS/10/2011/0]; MH CZ-DRO, University Hospital Motol, Prague [00064203]; "Investissements d'avenir" [ANR-10-IAIHU-06]; Academy of Finland [141549, 251704]; Folkhalsan Research Foundation; Wellcome Trust [WT089062, 098051]; Academy of Finland Center of Excellence in Complex Disease Genetics grants [213506, 129680]; European Community [HEALTH-F4-2007-201413]; Synaptic Systems grant [242167]; Sigrid Juselius Foundation; European Commission [261123]; Federal Ministry of Education and Research [NGENplus/EMINet 01GS08123, IonNeurONet 01GM1105A]; German Research Foundation (DFG) [Le1030/11-1]; German Society for Epileptology; Fund for Scientific Research Flanders (FWO); Flemish government Methusalem excellence grant; University of Antwerp FX We thank the probands and their families for their cooperation. The research was supported by the EUROCORES program EuroEPINOMICS of the European Science Foundation; funds from the state budget of Romania, managed by the Executive Agency for Higher Education, Research, Development, and Innovation Funding for Project 6-EUROC; the Scientific and Technological Research Council of Turkey; National Science Centre Poland funding for project 800/N-ESF-EuroEPINOMICS/10/2011/0; MH CZ-DRO, University Hospital Motol, Prague (00064203); "Investissements d'avenir" ANR-10-IAIHU-06; the Academy of Finland (grant 141549) and Folkhalsan Research Foundation; Wellcome Trust grants WT089062 and 098051; Academy of Finland grant 251704; Academy of Finland Center of Excellence in Complex Disease Genetics grants 213506 and 129680; the European Community's Seventh Framework Programme (FP7/2007-2013) ENGAGE Consortium (grant HEALTH-F4-2007-201413); Synaptic Systems grant 242167; the Sigrid Juselius Foundation; European Commission FP7 project 261123 (gEUVADIS); Federal Ministry of Education and Research NGENplus/EMINet 01GS08123; IonNeurONet 01GM1105A; German Research Foundation (DFG) Le1030/11-1; the German Society for Epileptology; the Fund for Scientific Research Flanders (FWO); the Flemish government Methusalem excellence grant; and the University of Antwerp. We thank the VIB Genetic Service Facility and the institute of Clinical Molecular Biology in Kiel for providing Sanger sequencing, supported in part by DFG Cluster of Excellence "Inflammation at Interfaces" and "Future Ocean." We thank technicians S. Greve, S. Arndt, and T. Henke for technical support. G.K. is a member of the DFG-funded Cluster of Excellence "Inflammation at Interfaces." A.S. is a FWO postdoctoral fellow. T.D. and A.K. are Institute of Science and Technology PhD fellows. 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TI SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties SO NATURE LA English DT Article ID AUTISM SPECTRUM DISORDER; SCAFFOLDING PROTEIN SHANK3; 22Q13.3 DELETION SYNDROME; BIPOLAR DISORDER; PSYCHIATRIC-DISORDERS; POSTSYNAPTIC DENSITY; GENE; MUTATIONS; DYSFUNCTION; PROFILIN AB Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function. However, SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit manic-like behaviour and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype, we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate, but not lithium, rescues the manic-like behaviour of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile. C1 [Han, Kihoon; Schaaf, Christian P.; Lu, Hui; Kang, Hyojin; Cheung, Sau Wai; Yu, Peng; Breman, Amy M.; Patel, Ankita; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Han, Kihoon; Lu, Hui; Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. [Han, Kihoon; Holder, J. Lloyd, Jr.; Schaaf, Christian P.; Lu, Hui; Chen, Hongmei; Kang, Hyojin; Tang, Jianrong; Wu, Zhenyu; Hao, Shuang; Yu, Peng; Sun, Hao; Lu, Hui-Chen; Zoghbi, Huda Y.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Holder, J. Lloyd, Jr.; Chen, Hongmei; Tang, Jianrong; Wu, Zhenyu; Hao, Shuang; Sun, Hao; Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Holder, J. Lloyd, Jr.] Baylor Coll Med, Div Neurol & Dev Neurosci, Houston, TX 77030 USA. [Chen, Hongmei; Sun, Hao; Lu, Hui-Chen] Texas Childrens Hosp, Cain Fdn Labs, Houston, TX 77030 USA. [Cheung, Sau Wai; Breman, Amy M.; Patel, Ankita] Baylor Coll Med, Med Genet Labs, Houston, TX 77030 USA. [Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. [Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. RP Zoghbi, HY (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM hzoghbi@bcm.edu FU Howard Hughes Medical Institute; National Institutes of Health (NIH) ARRA grant [1R01NS070302]; Baylor Intellectual and Developmental Disabilities Research Center [P30HD024064]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP110784]; Thrasher Research Fund; NIH [2T32NS043124]; Ting Tsung and Wei Fong Chao Foundation; Joan and Stanford Alexander family; Doris Duke Clinical Scientist Development Award FX We are indebted to the patients and families who participated in this study; to J. W. Belmont and N. Miller for contributing patients to this study; G. Feng for sharing Shank3B mice; G. Schuster for injection of Shank3 BAC; and C. Spencer for behavioural assays training. This project was supported by The Howard Hughes Medical Institute (H.Y.Z.), National Institutes of Health (NIH) ARRA grant (1R01NS070302) (H.Y.Z.), the Baylor Intellectual and Developmental Disabilities Research Center (P30HD024064) confocal, electrophysiology and mouse neurobehavioral cores, and the Cancer Prevention and Research Institute of Texas (CPRIT) RP110784. J. L. H. was supported by an Early Career Award from the Thrasher Research Fund, NIH 2T32NS043124 and the Ting Tsung and Wei Fong Chao Foundation; C. P. S. was supported by the Joan and Stanford Alexander family, the Ting Tsung and Wei Fong Chao Foundation and the Doris Duke Clinical Scientist Development Award. 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TI Developmental changes in expression of inhibitory neuronal proteins in the Fragile X Syndrome mouse basolateral amygdala SO BRAIN RESEARCH LA English DT Article DE Fragile X Syndrome; Basolateral amygdala; Development; GABA(A) receptor; Inhibitory synapse; Autism ID MENTAL-RETARDATION PROTEIN; FMR1 KNOCKOUT MOUSE; GABA(A) RECEPTOR SUBTYPES; MESSENGER-RNA; GABAERGIC SYNAPSES; DENDRITIC SPINES; YOUNG MALES; FEAR MEMORY; OUT MICE; IN-VIVO AB In humans, Fragile X Syndrome (FXS) is characterized by enhanced fear, hyperactivity, social anxiety, and, in a subset of individuals, autism. Many of the emotional and social deficits point to defects in the amygdala. We have previously shown defects in inhibitory neuron drive onto excitatory projection neurons in the basolateral amygdala (BLA) of juvenile Fmr1(-/y) knockout (KO) mice. Using pharmacological approaches, we have also previously revealed dynamic functional deficits in alpha 1, alpha 2, and alpha 3 subunit-containing GABA(A) receptors (GABA(A)Rs alpha 1, alpha 2, and alpha 3) during early postnatal development. In this study, we sought to determine whether these defects in GABA(A)R function are accompanied by changes in protein expression of GABA(A)Rs alpha 1, alpha 2, and alpha 3 and the post-synaptic GABA(A)R-clustering protein gephyrin. Interestingly, we found that while the expression of these proteins did not significantly differ between wildtype (WT) and KO mice at each time point, the timing of developmental expression of GABA(A)R alpha 1, alpha 2, and gephyrin was altered. Collectively, these data reveal novel defects in inhibitory synapse protein expression during critical periods of early postnatal development that could contribute to observed inhibitory neurotransmission deficits in the KO mouse BLA. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kratovac, Sebila; Corbin, Joshua G.] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. [Kratovac, Sebila] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Corbin, JG (reprint author), Childrens Natl Med Ctr, Ctr Neurosci Res, 111 Michigan Ave, Washington, DC 20010 USA. EM jcorbin@cnmcresearch.org FU FRAXA; Autism Speaks; NSF FX This research was supported by FRAXA and Autism Speaks grants to J.G.C., and an NSF Graduate Research Fellowship to S.K. We also thank Luis Olmos-Serrano for technical support. 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PD NOV 6 PY 2013 VL 1537 BP 69 EP 78 DI 10.1016/j.brainres.2013.08.052 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 264XV UT WOS:000327915200008 PM 24008143 ER PT J AU Roberts, TPL Lanza, MR Dell, J Qasmieh, S Hines, K Blaskey, L Zarnow, DM Levy, SE Edgar, JC Berman, JI AF Roberts, Timothy P. L. Lanza, Matthew R. Dell, John Qasmieh, Saba Hines, Katherine Blaskey, Lisa Zarnow, Deborah M. Levy, Susan E. Edgar, J. Christopher Berman, Jeffrey I. TI Maturational differences in thalamocortical white matter microstructure and auditory evoked response latencies in autism spectrum disorders SO BRAIN RESEARCH LA English DT Article DE Magnetoencephalography; Autism spectrum disorder; Auditory evoked response; Fractional anisotropy; White matter; M50 ID LANGUAGE IMPAIRMENT; DIFFUSION; CHILDREN; BRAIN; ADOLESCENCE; ANISOTROPY; SYSTEM; FIELDS AB White matter diffusion anisotropy in the acoustic radiations was characterized as a function of development in autistic and typically developing children. Auditory-evoked neuromagnetic fields were also recorded from the same individuals and the latency of the left and right middle latency superior temporal gyrus auditory similar to 50 ms response (M50)(1) was measured. Group differences in structural and functional auditory measures were examined, as were group differences in associations between white matter pathways, M50 latency, and age. Acoustic radiation white matter fractional anisotropy did not differ between groups. Individuals with autism displayed a significant M50 latency delay. Only in typically developing controls, white matter fractional anisotropy increased with age and increased white matter anisotropy was associated with earlier M50 responses. M50 latency, however, decreased with age in both groups. Present findings thus indicate that although there is loss of a relationship between white matter structure and auditory cortex function in autism spectrum disorders, and although there are delayed auditory responses in individuals with autism than compared with age-matched controls, M50 latency nevertheless decreases as a function of age in autism, parallel to the observation in typically developing controls (although with an overall latency delay). To understand auditory latency delays in autism and changes in auditory responses as a function of age in controls and autism, studies examining white matter as well as other factors that influence auditory latency, such as synaptic transmission, are of interest. (C) 2013 Published by Elsevier B.V. C1 [Roberts, Timothy P. L.; Lanza, Matthew R.; Dell, John; Qasmieh, Saba; Hines, Katherine; Blaskey, Lisa; Zarnow, Deborah M.; Edgar, J. Christopher; Berman, Jeffrey I.] Childrens Hosp Philadelphia, Lurie Family Fdn, MEG Imaging Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Blaskey, Lisa; Levy, Susan E.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Roberts, TPL (reprint author), Childrens Hosp Philadelphia, Lurie Family Fdn, MEG Imaging Ctr, Dept Radiol, Wood Bldg,Suite 2115,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM robertstim@email.chop.edu FU NIH [R01DC008871, P30-HD026979, K01-MH 096091]; Nancy Lurie Marks Family Foundation; Pennsylvania Department of Health FX This study was supported in part by the NIH Grants R01DC008871 (T.R.), P30-HD026979, K01-MH 096091 (J.B.) and a grant from the Nancy Lurie Marks Family Foundation. This research has been funded, in part, by a grant from the Pennsylvania Department of Health. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Dr. Roberts gratefully acknowledges the Oberkircher Family for the Oberkircher Family Chair in Pediatric Radiology at the Children's Hospital of Philadelphia. 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RP Timimi, S (reprint author), Lincolnshire Partnership NHS Fdn Trust, Sleaford NG34 8GG, England. EM stimimi@talk21.com CR Currie J, 19105 NBER Government of Western Australia Department of Health, 2010, RAINE ADHD STUD LONG Kendall T, 2008, BRIT MED J, V337, DOI 10.1136/bmj.a1239 McClure I, 2013, BMJ-BRIT MED J, V347, DOI 10.1136/bmj.f6216 Santosh PJ, 2005, CLIN NEUROSCI RES, V5, P307, DOI 10.1016/j.cnr.2005.09.010 Swanson JM, 2007, J AM ACAD CHILD PSY, V46, P1003, DOI 10.1097/CHI.0b013e3180686d63 NR 6 TC 2 Z9 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD NOV 6 PY 2013 VL 347 AR f6622 DI 10.1136/bmj.f6622 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 250XO UT WOS:000326890300010 PM 24196507 ER PT J AU Zuko, A Kleijer, KTE Oguro-Ando, A Kas, MJH van Daalen, E van der Zwaag, B Burbach, JPH AF Zuko, Amila Kleijer, Kristel T. E. Oguro-Ando, Asami Kas, Martien J. H. van Daalen, Emma van der Zwaag, Bert Burbach, J. Peter H. TI Contactins in the neurobiology of autism SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Review DE Autism spectrum disorder; Contactins Neurobiology Behavior; Cell adhesion molecules; Dendrites; Synapse ID RECOGNITION MOLECULE NB-3; FRAGILE-X-SYNDROME; COPY NUMBER VARIATION; CELL-ADHESION; NEURODEVELOPMENTAL DISORDERS; MYELINATED AXONS; IMMUNOGLOBULIN SUPERFAMILY; CHROMOSOMAL LOCALIZATION; SPECTRUM DISORDERS; NEURITE OUTGROWTH AB Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen on neuronal plasticity has stimulated us to investigate gene defects in autism and the consequences for brain development. The central process in the pathogenesis of autism is local dendritic mRNA translation which is dependent on axodendritic communication. Hence, most autism related gene products (i) are part of the protein synthesis machinery itself, (ii) are components of the mTOR signal transduction pathway, or (iii) shape synaptic activity and plasticity. Accordingly, prototype drugs have been recognized that interfere with these pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs) harbours at least three members that have genetically been implicated in autism: CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and neurobiological data underpinning their role in normal and abnormal development of brain systems, and the consequences for behavior. Although data on each of these CNTNs are far from complete, we tentatively conclude that these three contactins play roles in brain development in a critical phase of establishing brain systems and their plasticity. They modulate neuronal activities, such as neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal branching of axons in forming neural circuits. Current research on these CNTNs concentrate on the neurobiological mechanism of their developmental functions. A future task will be to establish if proposed pharmacological strategies to counteract ASD-relaLed symptomes can also be applied to reversal of phenotypes caused by genetic defects in these CNTN genes. (C) 2013 Elsevier B.V. All tights reserved. C1 [Zuko, Amila; Kleijer, Kristel T. E.; Oguro-Ando, Asami; Kas, Martien J. H.; Burbach, J. Peter H.] UMC Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurosci & Pharmacol, NL-3584 CG Utrecht, Netherlands. [van Daalen, Emma] UMC Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands. [van der Zwaag, Bert] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CG Utrecht, Netherlands. RP Burbach, JPH (reprint author), UMC Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Str 4-205,POB 85060, NL-3508 AB Utrecht, Netherlands. EM j.p.h.burbach@umcutrecht.nl FU EU-AIMS (European Autism Interventions); Innovative Medicines Initiative joint Undertaking [115300]; European Union from the European Federation of Pharmaceutical Industries [P7/2007-2013]; Canon foundation research fellowship in Europe; Dutch Brain Foundation [F2008(1)-08, 2011(1)-10] FX Authors of this review were supported by EU-AIMS (European Autism Interventions), which receives support from the Innovative Medicines Initiative joint Undertaking under Grant agreement no. 115300, the resources of which are composed of financial contributions from the European Union's Seventh Framework Programme Grant (P7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations Companies in-kind contributions, and from Autism Speaks, resulting in a total of (sic)29.6 million (K.T.E.K., M.J.H.K., and J.P.H.B.), by a Canon foundation research fellowship in Europe (A.O.A.), by a Fellowship from the Dutch Brain Foundation no. F2008(1)-08 (B.V.D.Z.), and a project Grant from the Dutch Brain Foundation no. 2011(1)-10 (E.V.D.). 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PD NOV 5 PY 2013 VL 719 IS 1-3 BP 63 EP 74 DI 10.1016/j.ejphar.2013.07.016 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258VQ UT WOS:000327487200009 PM 23872404 ER PT J AU Verpelli, C Montani, C Vicidomini, C Heise, C Sala, C AF Verpelli, Chiara Montani, Caterina Vicidomini, Cinzia Heise, Christopher Sala, Carlo TI Mutations of the synapse genes and intellectual disability syndromes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Review DE Intellectual disability; Brain synapses; Dendritic spine; Autism ID LINKED MENTAL-RETARDATION; AUTISM SPECTRUM DISORDER; ACCESSORY PROTEIN-LIKE; 22Q13.3 DELETION SYNDROME; DEPENDENT REGULATION; DENDRITIC SPINES; MESSENGER-RNA; SHANK3; IL1RAPL1; OLIGOPHRENIN-1 AB Intellectual disability syndromes have been found associated to numerous mutated genes that code for proteins functionally involved in synapse formation, the regulation of dendritic spine morphology, the regulation of the synaptic cytoskeleton or the synthesis and degradation of specific synapse proteins. These studies have strongly demonstrated that even mild alterations in synapse morphology and function give rise to mild or severe alteration in intellectual abilities. Interestingly, pharmacological agents that are able to counteract these morphological and functional synaptic anomalies can also improve the symptoms of some of these conditions. This review is summarizing recent discoveries on the functions of some of the genes responsible for intellectual disability syndromes connected with synapse dysfunctions. (C) 2013 Elsevier B.V. All rights reserved. C1 [Verpelli, Chiara; Montani, Caterina; Vicidomini, Cinzia; Heise, Christopher; Sala, Carlo] Univ Milan, CNR Inst Neurosci, I-20129 Milan, Italy. [Verpelli, Chiara; Montani, Caterina; Vicidomini, Cinzia; Heise, Christopher; Sala, Carlo] Univ Milan, Dept Med Biotechnol & Translat Med, I-20129 Milan, Italy. [Sala, Carlo] Neurol Inst Fdn Carlo Besta, I-20133 Milan, Italy. RP Sala, C (reprint author), Univ Milan, CNR Inst Neurosci, Via Vanvitelli 32, I-20129 Milan, Italy. EM c.sala@in.cnr.it RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 FU Telethon - Italy [GGP11095]; Fondazione CARIPLO; Italian Institute of technology; Seed Grant; Ministry of Health in the frame of ERA-NET NEURON; Marie Curie Actions 7 Framework Programme: SyMBad Marie Curie (Synapse: from molecules to brain diseases) International Research and Training program FX Funding This work was supported by Grants Telethon - Italy (Grant no. GGP11095), Fondazione CARIPLO, Italian Institute of technology, Seed Grant and Ministry of Health in the frame of ERA-NET NEURON. C.H. is supported by Marie Curie Actions 7 Framework Programme: SyMBad Marie Curie (Synapse: from molecules to brain diseases) International Research and Training program 2002-2007. 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J. Pharmacol. PD NOV 5 PY 2013 VL 719 IS 1-3 BP 112 EP 116 DI 10.1016/j.ejphar.2013.07.023 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258VQ UT WOS:000327487200013 PM 23872408 ER PT J AU Garcia-Junco-Clemente, P Chow, DK Tring, E Lazaro, MT Trachtenberg, JT Golshani, P AF Garcia-Junco-Clemente, Pablo Chow, David K. Tring, Elaine Lazaro, Maria T. Trachtenberg, Joshua T. Golshani, Peyman TI Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gain; visual cortex; SK; mTOR; sensory processing ID PRIMARY VISUAL-CORTEX; TUMOR-SUPPRESSOR GENE; DE-NOVO MUTATIONS; SPECTRUM DISORDERS; SYNAPTIC-TRANSMISSION; DENDRITIC SPINES; SK CHANNELS; IN-VIVO; EXCITABILITY; MOUSE AB De novo phosphatase and tensin homolog on chromosome ten (PTEN) mutations are a cause of sporadic autism. How single-copy loss of PTEN alters neural function is not understood. Here we report that Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels. The resultant augmentation of this conductance increases the amplitude of the afterspike hyperpolarization, causing a decrease in intrinsic excitability. In vivo, this change in intrinsic excitability reduces evoked firing rates of cortical pyramidal neurons but does not alter receptive field tuning. The decreased in vivo firing rate is not associated with deficits in the dendritic integration of synaptic input or with changes in dendritic complexity. These findings identify calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism and provide potential molecular therapeutic targets. C1 [Garcia-Junco-Clemente, Pablo; Chow, David K.; Tring, Elaine; Trachtenberg, Joshua T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Lazaro, Maria T.; Golshani, Peyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Golshani, P (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. EM pgolshani@mednet.ucla.edu FU National Institutes of Health [NS-056210, MH-101198, MH082935]; Spanish Ministry of Education, Culture and Sport [EX2009-0750] FX We thank Dr. Sandra Kuhlman for her help and advice during the analysis of the data. We also thank Dr. Mathias Groszer, Dr. Tom Otis, Dr. Dario Ringach, and Dr. Larry Zipursky for their critical discussions of the data. This work was supported by National Institutes of Health K08 Grant NS-056210 and NIH R01 Grant MH-101198 (to P. G.) and NIH R01 Grant MH082935 (to J.T.T. and P. G.). P.G.-J.-C. was supported by postdoctoral Fellowship EX2009-0750 from the Spanish Ministry of Education, Culture and Sport. 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The present study was undertaken to compare the effect of orally administered PA with that of clindamycin-induced PA-microbial producers in inducing persistent biochemical autistic features in hamsters. The neuroprotective potency of carnosine and carnitine supplements against PA toxicity was also investigated. Methods: The following groups were studied. 1. Control group, which received phosphate buffered saline orally, 2. Propionic acid treated group which were given PA at a dose of 250 mg/kg body weight/day for 3 days orally, 3. Clindamycin treated group which received a single dose of the antibiotic orogastrically at a dose of 30 mg/kg on the day of the experiment, 4. Carnosine-treated group which were given carnosine at a dose of 10 mg/kg body weight/day orally for one week, 5. Carnitine treated group given 50 mg/kg body weight/day carnitine orally daily for one week. Group 6. Carnosine followed by PA, Group 7. Carnitine followed by PA. Dopamine, adrenaline and noradrenaline, serotonin and Gamma amino-butyric acid (GABA) were measured in the cortex and medulla of the nine studied groups. Results: PA administration caused significant decrease in the neurotransmitters in the brains of treated hamsters while clindamycin caused a significant decrease only in dopamine in hamster brains (cortex and medulla) and GABA in the cerebral cortex of the treated hamsters. Administration of carnosine and carnitine which are known antioxidants caused no significant changes in the levels of neurotransmitters when administered alone to hamsters. However when administered with PA both carnosine and carnitine restored the altered neurotransmitters to near normal levels. Conclusion: Carnosine and carnitine may be used as supplements to protect against PA neurotoxicity. C1 [El-Ansary, Afaf; Siddiqi, Nikhat J.] King Saud Univ, Dept Biochem, Coll Sci, Riyadh 11495, Saudi Arabia. [Shaker, Ghada] Zagazig Univ, Dept Microbiol & Immunol, Coll Pharm, Zagazig, Egypt. [Al-Ayadhi, Laila Y.] King Saud Univ, Dept Physiol, Fac Med, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila Y.] Autism Res & Treatment Unit, Riyadh, Saudi Arabia. [El-Ansary, Afaf; Al-Ayadhi, Laila Y.] King Saud Univ, Shaik AL Amodi Autism Res Chair, Riyadh 11495, Saudi Arabia. [El-Ansary, Afaf] Natl Res Ctr, Therapuet Chem Dept, Dokki, Guiza, Egypt. RP El-Ansary, A (reprint author), King Saud Univ, Dept Biochem, Coll Sci, POB 22452, Riyadh 11495, Saudi Arabia. EM elansary@ksu.edu.sa FU Research Center of the Center for Female Scientific and Medical Colleges in King Saud University FX This research project was supported by a grant from the Research Center of the Center for Female Scientific and Medical Colleges in King Saud University. 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M. TI Platelets of mice heterozygous for neurobeachin, a candidate gene for autism spectrum disorder, display protein changes related to aberrant protein kinase A activity SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; AKAP; Calpain; Candidate gene; Neurobeachin; Platelets; Serotonin; Talin-1 ID COPY NUMBER VARIANTS; WISTAR FURTH RAT; MOLECULAR-MECHANISMS; INTEGRIN ACTIVATION; BEACH FAMILY; SEROTONIN; CALPAIN; ACTIN; SITE; PHOSPHORYLATION AB Background: Neurobeachin (NBEA) has been identified as a candidate gene for autism spectrum disorders (ASD) in several unrelated patients with alterations in the NBEA gene. The exact function of NBEA, a multidomain scaffolding protein, is currently unknown. It contains an A-kinase anchoring protein (AKAP) domain which binds the regulatory subunit of protein kinase A (PKA) thereby confining its activity to specific subcellular regions. NBEA has been implicated in post-Golgi membrane trafficking and in regulated secretion. The mechanism of regulated secretion is largely conserved between neurons and platelets, and the morphology of platelet dense granules was found to be abnormal in several ASD patients, including one with NBEA haploinsufficiency. Platelet dense granules are secreted upon vascular injury when platelets are exposed to for instance collagen. Dense granules contain serotonin, ATP and ADP, which are necessary for platelet plug formation and vascular contraction. Methods: To further investigate possible roles for NBEA in secretion or dense granule morphology, platelets from Nbea(+/-) mice were analyzed morphometrically, functionally and biochemically. A differential proteomics and peptidomics screen was performed between Nbea(+/-) and Nbea(+/+) mice, in which altered Talin-1 cleavage was further investigated and validated in brain samples. Finally, the phosphorylation pattern of PKA substrates was analyzed. Results: Platelet dense granules of Nbea(+/-) mice had a reduced surface area and abnormal dense-core halo, but normal serotonin-content. Nbea haploinsufficiency did not affect platelet aggregation and ATP secretion after collagen stimulation, although the platelet shape change was more pronounced. Furthermore, peptidomics revealed that Nbea(+/-) platelets contain significantly reduced levels of several actin-interacting peptides. Decreased levels were detected of the actin-binding head and rod domain of Talin-1, which are cleavage products of Calpain-2. This is most likely due to increased PKA-mediated phosphorylation of Calpain-2, which renders the enzyme less active. Analysis of other PKA substrates revealed both increased and reduced phosphorylation. Conclusion: Our results show the pleiotropic effects of alterations in PKA activity due to Nbea haploinsufficiency, highlighting the important function of the AKAP domain in Nbea in regulating and confining PKA activity. Furthermore, these results suggest a role for Nbea in remodeling the actin cytoskeleton of platelets. C1 [Nuytens, Kim; Tuand, Krizia; Boonen, Kurt; Creemers, John W. M.] Katholieke Univ Leuven, Dept Human Genet, Biochem Neuroendocrinol Lab, B-3000 Louvain, Belgium. [Nuytens, Kim; Tuand, Krizia; Freson, Kathleen; Creemers, John W. M.] Katholieke Univ Leuven, Leuven Autism Res Consortium LAuRes, B-3000 Louvain, Belgium. [Di Michele, Michela; Freson, Kathleen] Katholieke Univ Leuven, Ctr Mol & Vasc Biol, Dept Cardiovasc Sci, B-3000 Louvain, Belgium. [Waelkens, Etienne] Katholieke Univ Leuven, Lab Prot Phosphorylat & Prote, Dept Cellular & Mol Med, B-3000 Louvain, Belgium. RP Creemers, JWM (reprint author), Katholieke Univ Leuven, Dept Human Genet, Biochem Neuroendocrinol Lab, B-3000 Louvain, Belgium. EM John.Creemers@med.kuleuven.be RI Tuand, Krizia/E-1657-2015 OI Tuand, Krizia/0000-0003-2670-5415 FU agentschap voor Innovatie door Wetenschap en Technologie Vlaanderen (IWT-Vlaanderen); Fund for Scientific Research (FWO-Vlaanderen) [G.0490.10 N, G.0743.09]; steunfonds Marguerite-Marie Delacroix, KU Leuven [IDO/08/013, GOA/2009/13, GOA/12/24]; Interuniversity Attraction Poles Programme - Belgian Federal Science Policy [P7/13] FX We would like to thank Sandra Meulemans and Chantal Thys for the technical assistance, and the EM-facility of the Center of Human Genetics, VIB KU Leuven for the use of their appliances. This work was supported by the agentschap voor Innovatie door Wetenschap en Technologie Vlaanderen (IWT-Vlaanderen), the Fund for Scientific Research (FWO-Vlaanderen) (grants G.0490.10 N and G.0743.09) steunfonds Marguerite-Marie Delacroix, KU Leuven (IDO/08/013; GOA/2009/13; GOA/12/24), and a grant of the Interuniversity Attraction Poles Programme (P7/13) - Belgian Federal Science Policy). The funding sources were not involved in the design, collection, analysis or interpretation of the data; in writing the manuscript; or in the decision to submit the manuscript for publication. 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Autism PD NOV 4 PY 2013 VL 4 AR 43 DI 10.1186/2040-2392-4-43 PG 13 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254ZB UT WOS:000327207700002 PM 24188528 ER PT J AU Wang, L Christophersen, CT Sorich, MJ Gerber, JP Angley, MT Conlon, MA AF Wang, Lv Christophersen, Claus T. Sorich, Michael J. Gerber, Jacobus P. Angley, Manya T. Conlon, Michael A. TI Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder; Gut; Feces; Microbiota; Sutterella ID SP NOV.; CAMPYLOBACTER; PREVALENCE; MUCIN AB Background: A recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies taken from children with autism spectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease (Ruminococcus gnavus and Ruminococcus torques) are also altered in the stool of these children. Findings: We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder. Conclusions: We show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool. C1 [Wang, Lv; Sorich, Michael J.; Gerber, Jacobus P.; Angley, Manya T.] Univ S Australia, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia. 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Carson, Rori Woods-Groves, Suzanne Mendenhall, Janis Scheidecker, Bethany TI UI REACH: A Postsecondary Program Serving Students with Autism and Intellectual Disabilities SO EDUCATION AND TREATMENT OF CHILDREN LA English DT Article ID TRANSITION-AGE STUDENTS; DEVELOPMENTAL-DISABILITIES; SPECTRUM DISORDERS; COLLEGE; EDUCATION; SCHOOL; EXPERIENCES; TEACHERS; OUTCOMES; CHILDREN AB Across the United States postsecondary education (PSE) options for young adults with autism and intellectual disabilities (ID) are emerging as a result of parent-professional advocacy group actions and legislation such as the Higher Education Opportunity Act of 2008 (HEOA). In this article the University of Iowa Realizing Educational and Career Hopes (UI REACH) Program, a thriving, well-integrated two year certificate program is described. We discuss the UI REACH model-its mission, student-centered and program goals, and strategies employed to ensure quality, sustainability, and continuous improvement. The student population, curriculum, staffing needs, and day-to-day operating issues are described. The experiences and perceptions of 14 students with autism spectrum disorder (ASD) suggest that the program facilitates a positive campus living-learning experience for these students. Challenges and recommendations for institutions of higher education considering developing, or in the early stages of developing, similar programs are presented. C1 [Hendrickson, Jo M.; Carson, Rori; Woods-Groves, Suzanne; Mendenhall, Janis; Scheidecker, Bethany] Univ Iowa, Iowa City, IA 52242 USA. RP Hendrickson, JM (reprint author), Univ Iowa, REACH Program, Lindquist Ctr 229, Iowa City, IA 52242 USA. EM jo-hendrickson@uiowa.edu CR Adreon D, 2007, INTERV SCH CLIN, V42, P271, DOI 10.1177/10534512070420050201 Allen R. K., 2012, 3 STAGES ORG DEV PRE Benz MR, 2000, EXCEPT CHILDREN, V66, P509 Clark G. 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R., 1997, PROGRAM EVALUATION A Zafft C, 2004, EDUC TRAIN DEV DISAB, V39, P45 Zager D, 2010, FOCUS AUTISM DEV DIS, V25, P151, DOI 10.1177/1088357610371331 NR 48 TC 0 Z9 0 PU WEST VIRGINIA UNIV PRESS PI MORGANTOWN PA COMMUNICATIONS BLDG PATTESON DR, PO BOX 6295, MORGANTOWN, WV 26506-6295 USA SN 0748-8491 EI 1934-8924 J9 EDUC TREAT CHILD JI Educ. Treat. Child. PD NOV PY 2013 VL 36 IS 4 BP 169 EP 194 PG 26 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA AP0JK UT WOS:000341747400009 ER PT J AU Roesler, CP Flax, J MacRoy-Higgins, M Fermano, Z Morgan-Byrne, J Benasich, AA AF Roesler, Cynthia P. Flax, Judy MacRoy-Higgins, Michelle Fermano, Zena Morgan-Byrne, Julie Benasich, April A. TI Sensory Desensitization Training for Successful Net Application and EEG/ERP Acquisition in Difficult to Test Children SO COMMUNICATION DISORDERS QUARTERLY LA English DT Article DE ASD; EEG/ERPs; sensory desensitization; behavior modification; tactile reactivity; nonverbal ID AUTISM SPECTRUM DISORDERS; YOUNG-CHILDREN; DEVELOPMENTAL DELAY; TYPICAL DEVELOPMENT; SENSITIVITY; PATTERNS AB This study examined the effectiveness of sensory desensitization training for 12 nonverbal children with autism to facilitate participation in an electrophysiological study assessing linguistic processing. Sensory desensitization was achieved for 10 of the 12 children and thus allowed collection of usable data in a passive linguistic paradigm. Application of such desensitization methods may be useful as a precursor to other assessment protocols for individuals who are difficult to test. C1 [Roesler, Cynthia P.; Flax, Judy; Fermano, Zena; Morgan-Byrne, Julie; Benasich, April A.] Rutgers State Univ, Newark, NJ 07102 USA. [MacRoy-Higgins, Michelle] CUNY Hunter Coll, New York, NY 10021 USA. RP Roesler, CP (reprint author), Rutgers State Univ, Ctr Mol & Behav Neurosci, 197 Univ Ave, Newark, NJ 07102 USA. EM croesler@andromeda.rutgers.edu CR Baker AEZ, 2008, J AUTISM DEV DISORD, V38, P867, DOI 10.1007/s10803-007-0459-0 Baranek GT, 2007, AM J MENT RETARD, V112, P233, DOI 10.1352/0895-8017(2007)112[233:HSPIYC]2.0.CO;2 Blakemore SJ, 2006, BRAIN COGNITION, V61, P5, DOI 10.1016/j.bandc.2005.12.013 Dawson G, 2002, CHILD DEV, V73, P700, DOI 10.1111/1467-8624.00433 Gray C., 1994, NEW SOCIAL STORY BOO Karkhaneh M, 2010, AUTISM, V14, P641, DOI 10.1177/1362361310373057 Liss M, 2008, PERS INDIV DIFFER, V45, P255, DOI 10.1016/j.paid.2008.04.009 McIntosh D. N., 1999, SENSORY PROFILE EXAM, P59 Russo N, 2009, J AUTISM DEV DISORD, V39, P1185, DOI 10.1007/s10803-009-0737-0 Schmidt GL, 2009, NEUROREPORT, V20, P1037, DOI 10.1097/WNR.0b013e32832e0ca7 Schoen SA, 2008, AM J OCCUP THER, V62, P393 Tager-Flusberg H., 2005, HDB AUTISM PERVASIVE, V1, P335 Tomchek SD, 2007, AM J OCCUP THER, V61, P190 Wiggins LD, 2009, J AUTISM DEV DISORD, V39, P1087, DOI 10.1007/s10803-009-0711-x Yu Y. H., 2012, P 36 ANN BOST U C LA, V2, P686 NR 15 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1525-7401 EI 1538-4837 J9 COMMUN DISORD Q JI Comm. Disord. Q. PD NOV PY 2013 VL 35 IS 1 BP 14 EP 20 DI 10.1177/1525740113489167 PG 7 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA AL7SJ UT WOS:000339335100003 ER PT J AU Paloscia, C Baglioni, V Alessandrelli, R Rosa, C Guerini, R Aceti, F Pasini, A AF Paloscia, Claudio Baglioni, Valentina Alessandrelli, Riccardo Rosa, Caterina Guerini, Rossella Aceti, Franca Pasini, Augusto TI Executive function deficits in ADHD and Asperger syndrome SO RIVISTA DI PSICHIATRIA LA Italian DT Article DE Asperger syndrome; ADHA; working memory; inhibition response; cognitive flexibility; children ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM DIAGNOSTIC INTERVIEW; WORKING-MEMORY; HYPERACTIVITY DISORDER; CHILDREN; PERFORMANCE; SPECTRUM; PSYCHOPATHOLOGY; RELIABILITY; DYSFUNCTION AB Background. The aim of this study is to evaluate the executive functioning of children with attention deficit hyperactivity disorder combined subtype (ADHD-C) and Asperger syndrome (AS) compared to a control group. Methods. A sample of 79 children (28 ADHD-C; 24 AS; 27 subjects with typical development) was tested on a wide range of tasks related to major domains of executive functioning: inhibition response (prepotent and interference), visual working memory, planning and cognitive flexibility. Results. Patients with AS showed deficits on visual working memory and cognitive flexibility. ADHD-C children were impaired on inhibition control (prepotent response) but also showed deficits on working memory and cognitive flexibility. The only executive functioning measure that differentiated ADHD from AS was inhibition of prepotent response and a more high deficit in cognitive flexibility and working memory in AS compared to ADHD-C. Conclusions. This study confirms recent evidence about the identification of specific executive profiles in these disorders. Other studies are warranted to evaluate the presence and specifity of a dysexecutive syndrome in ADHD and AS in a larger sample with girls. 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Psichiatr. PD NOV-DEC PY 2013 VL 48 IS 6 BP 441 EP 447 PG 7 WC Psychiatry SC Psychiatry GA AL4XB UT WOS:000339137000004 PM 24441520 ER PT J AU Erden, MS AF Erden, Mustafa Suphi TI Emotional Postures for the Humanoid-Robot Nao SO INTERNATIONAL JOURNAL OF SOCIAL ROBOTICS LA English DT Article DE Emotion; Posture; Humanoid-robot; Social interaction ID STATIC BODY POSTURES; ATTRIBUTING EMOTION; MOVEMENT; CHILDREN; AUTISM; INTERVENTION; EXPRESSION AB This paper presents the development of emotional postures for the humanoid robot Nao. The approach is based on adaptation of the postures that are developed for a virtual human body model to the case of the physical robot Nao. In the paper the association between the joints of the human body model and the joints of the Nao robot are described and the transformation of postures is explained. The non-correspondence between the joints of the actual physical robot and the joints of the human body model was a major challenge in this work. Moreover, the implementation of the postures into the robot was constrained by the physical structure and the artificial mass distribution. Postures for the three emotions of anger, sadness, and happiness are studied. Thirty two postures are generated for each emotion. Among them the best five postures for each emotion are selected based on the votes of twenty five external observers. The distribution of the votes indicates that many of the implemented postures do not convey the intended emotions. The emotional content of the selected best five postures are tested by the votes of forty observers. The intended emotions received the highest recognition rate for each group of these selected postures. This study can be considered to be the last step of a general process for developing emotional postures for robots. This process starts with qualitative descriptions of human postures, continues with encoding those descriptions in quantitative terms, and ends with adaptation of the quantitative values to a specific robot. The present study demonstrates the last step of this process. C1 Ecole Polytech Fed Lausanne, Learning Agorithms & Syst Lab, Lausanne, Switzerland. RP Erden, MS (reprint author), Ecole Polytech Fed Lausanne, Learning Agorithms & Syst Lab, Lausanne, Switzerland. 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TI Behavior genetics: Past, present, future SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; EQUAL ENVIRONMENTS ASSUMPTION; DISCORDANT MONOZYGOTIC TWINS; CALLOUS-UNEMOTIONAL TRAITS; SEROTONIN TRANSPORTER GENE; AUTISM SPECTRUM DISORDERS; MESSENGER-RNA EXPRESSION; COMMON SNPS EXPLAIN; HIGH-FAT DIET; DE-NOVO AB The disciplines of developmental psychopathology and behavior genetics are concerned with many of the same questions about the etiology and course of normal and abnormal behavior and about the factors that promote typical development despite the presence of risk. The goal of this paper is to summarize how research in behavior genetics has shed light on questions that are central to developmental psychopathology. We briefly review the origins of behavior genetics, summarize the findings that have been gleaned from several decades of quantitative and molecular genetics research, and describe future directions for research that will delineate gene function as well as pathways from genes to brain to behavior. The importance of environmental contributions, at both genetic and epigenetic levels, will be discussed. We conclude that behavior genetics has made significant contributions to developmental psychopathology by documenting the interplay among risk and protective factors at multiple levels of the organism, by clarifying the causal status of risk exposures, and by identifying factors that account for change and stability in psychopathology. As the tools to identify gene function become increasingly sophisticated, and as behavioral geneticists become increasingly interdisciplinary in their scope, the field is poised to make ever greater contributions to our understanding of typical and atypical development. C1 [Jaffee, Sara R.; Price, Thomas S.; Reyes, Teresa M.] Univ Penn, Philadelphia, PA 19104 USA. [Jaffee, Sara R.] Kings Coll London, London WC2R 2LS, England. RP Jaffee, SR (reprint author), Univ Penn, Dept Psychol, 3720 Walnut St, Philadelphia, PA 19104 USA. 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Psychopathol. PD NOV PY 2013 VL 25 IS 4 SI SI BP 1225 EP 1242 DI 10.1017/S0954579413000588 PN 2 PG 18 WC Psychology, Developmental SC Psychology GA AC2YP UT WOS:000332382500004 PM 24342837 ER PT J AU Plomin, R Simpson, MA AF Plomin, Robert Simpson, Michael A. TI The future of genomics for developmentalists SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID COPY-NUMBER VARIANTS; AUTISM SPECTRUM DISORDERS; GENERAL COGNITIVE-ABILITY; WIDE ASSOCIATION; COMMON DISEASES; STRUCTURAL VARIATION; DNA METHYLATION; PSYCHIATRIC-DISORDERS; LEARNING-ABILITIES; CHILD-DEVELOPMENT AB The momentum of genomic science will carry it far into the future and into the heart of research on typical and atypical behavioral development. The purpose of this paper is to focus on a few implications and applications of these advances for understanding behavioral development. Quantitative genetics is genomic and will chart the course for molecular genomic research now that these two worlds of genetics are merging in the search for many genes of small effect. Although current attempts to identify specific genes have had limited success, known as the missing heritability problem, whole-genome sequencing will improve this situation by identifying all DNA sequence variations, including rare variants. Because the heritability of complex traits is caused by many DNA variants of small effect in the population, polygenic scores that are composites of hundreds or thousands of DNA variants will be used by developmentalists to predict children's genetic risk and resilience. The most far-reaching advance will be the widespread availability of whole-genome sequence for children, which means that developmentalists would no longer need to obtain DNA or to genotype children in order to use genomic information in research or in the clinic. 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TI A translational neuroscience framework for the development of socioemotional functioning in health and psychopathology SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID AUTISM SPECTRUM DISORDERS; SEROTONIN TRANSPORTER GENE; GENOME-WIDE ASSOCIATION; GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; MEDIAL PREFRONTAL CORTEX; EMOTIONAL FACIAL EXPRESSIONS; PROMOTER REGION POLYMORPHISM; BIAS MODIFICATION TREATMENT; BRAINS DEFAULT NETWORK AB The development of socioemotional functioning is a complex process that occurs over a protracted time period and requires coordinating affective, cognitive, and social faculties. At many points in development, the trajectory of socioemotional development can be deleteriously altered due to a combination of environmental insults and individual vulnerabilities. The result can be psychopathology. However, researchers are just beginning to understand the neural and genetic mechanisms involved in the development of healthy and disordered socioemotional functioning. We propose a translational developmental neuroscience framework to understand the transactional process that results in socioemotional functioning in both healthy and disordered populations. We then apply this framework to healthy socioemotional development, pediatric anxiety, pediatric depression, and autism spectrum disorder, selectively reviewing current literature in light of the framework. Finally, we examine ways that the framework can help to frame future directions of research on socioemotional development and translational implications for intervention. C1 [Wiggins, Jillian Lee; Monk, Christopher S.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Wiggins, JL (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bldg 15K,MSC-2670, Bethesda, MD 20892 USA. 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PD NOV PY 2013 VL 25 IS 4 SI SI BP 1293 EP 1309 DI 10.1017/S095457941300062X PN 2 PG 17 WC Psychology, Developmental SC Psychology GA AC2YP UT WOS:000332382500008 PM 24342841 ER PT J AU Dawson, G Bernier, R AF Dawson, Geraldine Bernier, Raphael TI A quarter century of progress on the early detection and treatment of autism spectrum disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID INTENSIVE BEHAVIORAL INTERVENTION; PERVASIVE DEVELOPMENTAL DISORDERS; DE-NOVO MUTATIONS; YOUNG-CHILDREN; JOINT ATTENTION; FOLLOW-UP; COMMUNICATION DEVELOPMENT; ENVIRONMENTAL ENRICHMENT; NONVERBAL-COMMUNICATION; LANGUAGE-DEVELOPMENT AB The last 25 years have witnessed tremendous changes in our ability to detect autism very early in life and provide interventions that can significantly influence children's outcomes. It was once questioned whether autism could be recognized before children had developed language and symbolic play skills; now changes in early behaviors, as well as structural brain changes, have been documented in infants 6-12 months of age who later develop autism. Advances in brain imaging and genetics offer the possibility of detecting autism before the syndrome is fully manifest, thereby reducing or preventing symptoms from developing. Whereas the primary mode of behavioral intervention a few decades ago relied on operant conditioning, recent approaches integrate the methods of applied behavioral analysis within a developmental, relationship-focused intervention model that are implemented by both parents and clinicians. These interventions have been found to have positive effects on children's developmental trajectory, as measured by both behavioral and neurophysiological assessments. Future approaches will likely combine both behavioral and pharmacological treatments for children who have less robust responses to behavioral interventions. There has been a paradigm shift in the way that autism is viewed, evolving from a lifelong condition with a very poor prognosis to one in which significant gains and neuroplasticity is expected, especially when the condition is detected early and appropriate interventions are provided. The grand challenge for the future is to bridge the tremendous gap between research and the implementation of evidence-based practices in the broader community, both in the United States and worldwide. Significant disparities in access to appropriate health care for children with autism exist that urgently require advocacy and more resources. C1 [Dawson, Geraldine] Duke Univ, Durham, NC 27701 USA. [Bernier, Raphael] Univ Washington, Seattle, WA 98195 USA. 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Psychopathol. PD NOV PY 2013 VL 25 IS 4 SI SI BP 1455 EP 1472 DI 10.1017/S0954579413000710 PN 2 PG 18 WC Psychology, Developmental SC Psychology GA AC2YP UT WOS:000332382500017 PM 24342850 ER PT J AU Beauchaine, TP McNulty, T AF Beauchaine, Theodore P. McNulty, Tiffany TI Comorbidities and continuities as ontogenic processes: Toward a developmental spectrum model of externalizing psychopathology SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; ONSET CONDUCT PROBLEMS; CALLOUS-UNEMOTIONAL TRAITS; PRENATAL COCAINE EXPOSURE; STRIATAL DOPAMINE RELEASE; BRAIN-STIMULATION REWARD; RESEARCH DOMAIN CRITERIA; SUBSTANCE USE DISORDERS AB Research on child and adolescent mental health problems has burgeoned since the inaugural issue of Development and Psychopathology was published in 1989. In the quarter century since, static models of psychopathology have been abandoned in favor of transactional models, following the agenda set by editor Dante Cicchetti and other proponents of the discipline. The transactional approach, which has been applied to autism, depression, self-injury, and delinquency, (a) specifies vulnerabilities and risk factors across multiple levels of analysis spanning genes to cultures, (b) identifies multifinal and equifinal pathways to psychopathology, and (c) transcends traditional disciplinary boundaries. However, as noted by Rutter and Sroufe (2000), specific mechanisms of continuity, discontinuity, and comorbidity of psychopathology must be identified if we wish to understand etiology fully. In this article, we present a model of early-onset externalizing behavior in which comorbidities and continuities are viewed as ontogenic processes: products of complex longitudinal transactions between interdependent individual-level vulnerabilities (e.g., genetic, epigenetic, allostatic) and equally interdependent contextual risk factors (e.g., coercive parenting, deviant peer group affiliations, neighborhood criminality). Through interactions across levels of analysis, some individuals traverse along the externalizing spectrum, beginning with heritable trait impulsivity in preschool and ending in antisociality in adulthood. In describing our model, we note that (a) the approach outlined in the DSM to subtyping externalizing disorders continues to obscure developmental pathways to antisociality, (b) molecular genetics studies will likely not identify meaningful subtypes of externalizing disorder, and (c) ontogenic trait approaches to psychopathology are much more likely to advance the discipline in upcoming years. C1 [Beauchaine, Theodore P.; McNulty, Tiffany] Ohio State Univ, Columbus, OH 43210 USA. RP Beauchaine, TP (reprint author), Ohio State Univ, Dept Psychol, 225 Psychol Bldg,1835 Neil Ave, Columbus, OH 43210 USA. 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TI Olfaction in autism SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 21st Annual Meeting of the Israel-Society-for-Neuroscience / 1st Binational Australian-Israeli Meeting on Neuroscience CY DEC 15-15, 2012 CL Eilat, ISRAEL SP Israel Soc Neuroscience C1 [Eisen, A.; Heller, I; Plotkin, A.; Weissbrod, A.; Sobel, N.] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Zachor, D.] Asaf Harofeh Med Ctr, Autism Ctr, Zerifin, Israel. NR 0 TC 0 Z9 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2013 VL 51 SU 1 BP S34 EP S34 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AC9DF UT WOS:000332833800081 ER PT J AU Braddick, O Atkinson, J AF Braddick, Oliver Atkinson, Janette TI Visual control of manual actions: brain mechanisms in typical development and developmental disorders SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Review ID DORSAL-STREAM VULNERABILITY; COORDINATION DISORDER; WILLIAMS-SYNDROME; MOTION COHERENCE; DEPTH-PERCEPTION; CHILDREN; INFANTS; INFORMATION; ATTENTION; COGNITION AB Some key stages in the development of manual actions have been discussed in this supplement based on the idea of the dorsal cortical stream as the pathway for translating visual information into action control. We argue that visual information, transmitted through specialized visuomotor dorsal-stream modules, is required in the control of manual actions for selecting and attending to the target object of the action, translating visual spatial information into motor programmes and planning a coordinated sequence of actions so as to reach an optimal end-state. In typical development, we illustrate dorsal-stream processing through results on the use of stereoscopic information to guide infants' reaches, and changes in target selection and detailed kinematics of reaches depending on age, object size, and reaching in darkness (when dorsal-stream information rapidly decays). We hypothesize 'dorsal-stream vulnerability' as a widespread feature of neurodevelopmental disorders, such as autism, Williams syndrome, and children born very preterm. Such deficits, identified as abnormal visuomanual actions, are seen in bimanual coordination, visual guidance of action in the 'postbox' task, and failures in motor planning for end-state comfort. We discuss the possible application of these approaches to a wider range of disorders including developmental coordination disorder. C1 [Braddick, Oliver] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Atkinson, Janette] UCL, Dept Dev Sci, Visual Dev Unit, London, England. RP Braddick, O (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM oliver.braddick@psy.ox.ac.uk FU Medical Research Council [G0601007, G7908507]; Medical Research Council; Economic and Social Research Council; Oxford University Clarendon Fund FX We thank members of the Visual Development Unit, University College London and Oxford, who contributed to work reviewed here, in particular Shirley Anker, Erin Babinsky, Dee Birtles, Kate Breckinridge, Bruce Hood, John King, Chris Newman, and John Wattam-Bell. Research reviewed here was supported by Medical Research Council programme grants G0601007 and G7908507, and by studentship funding from the Medical Research Council, the Economic and Social Research Council, and Oxford University Clarendon Fund. 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RP Yu, RR (reprint author), Zhejiang Univ Technol, Sch Educ Sci & Technol, Hangzhou 310032, Zhejiang, Peoples R China. EM libin0571@zju.edu.cn; qfy@zjut.edu.cn FU Ministry of Education of Humanities and Social Science Project [10YJCXLX053]; Zhejiang Provincial Natural Science Foundation of China [LQ12H09005]; Fundamental "Zhijiang Qingnian" Research of Zhejiang Provincial Philosophy and Social Science Foundation of China [11ZJQN065YB]; Zhejiang Provincial Ministry of education of Humanities and Social Science Project [Y201018729]; Major Program of the National Social Science Foundation of China [12ZD229]; National Science & Technology Pillar Program [2012BAI34B02, 2012BAI34B03] FX This work was supported by The Ministry of Education of Humanities and Social Science Project (10YJCXLX053), Zhejiang Provincial Natural Science Foundation of China (LQ12H09005), the Fundamental "Zhijiang Qingnian" Research of Zhejiang Provincial Philosophy and Social Science Foundation of China (11ZJQN065YB), Zhejiang Provincial Ministry of education of Humanities and Social Science Project (Y201018729); Project supported by the Major Program of the National Social Science Foundation of China (12&ZD229), Projects in the National Science & Technology Pillar Program d(2012BAI34B02, 2012BAI34B03). 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We administer the Social Responsiveness Scale (SRS), a measure of autistic traits that examines reciprocal social behavior, to the parents of 117 adolescents (61 CHR individuals, 20 age-matched adolescents with a psychotic disorder [AOP], and 36 healthy controls) participating in a longitudinal study of psychosis risk. AOP and CHR individuals have significantly elevated SRS scores relative to healthy controls, indicating more severe social deficits. Mean scores for AOP and CHR youths are typical of scores obtained in individuals with high functioning autism (Constantino & Gruber, 2005). SRS scores are significantly associated with concurrent real-world social functioning in both clinical groups. Finally, baseline SRS scores significantly predict social functioning at follow-up (an average of 7.2 months later) in CHR individuals, over and above baseline social functioning measures (p < .009). 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In this review, we summarize the results of a metallomics study in which scalp hair concentrations of 26 trace elements were examined for 1,967 autistic children (1,553 males and 414 females aged 0-15 years-old), and discuss recent advances in our understanding of epigenetic roles of infantile mineral imbalances in the pathogenesis of autism. In the 1,967 subjects, 584 (29.7%) and 347 (17.6%) were found deficient in zinc and magnesium, respectively, and the incidence rate of zinc deficiency was estimated at 43.5% in male and 52.5% in female infantile subjects aged 0-3 years-old. In contrast, 339 (17.2%), 168 (8.5%) and 94 (4.8%) individuals were found to suffer from high burdens of aluminum, cadmium and lead, respectively, and 2.8% or less from mercury and arsenic. High toxic metal burdens were more frequently observed in the infants aged 0-3 years-old, whose incidence rates were 20.6%, 12.1%, 7.5%, 3.2% and 2.3% for aluminum, cadmium, lead, arsenic and mercury, respectively. These findings suggest that infantile zinc-and magnesium-deficiency and/or toxic metal burdens may be critical and induce epigenetic alterations in the genes and genetic regulation mechanisms of neurodevelopment in the autistic children, and demonstrate that a time factor "infantile window" is also critical for neurodevelopment and probably for therapy. Thus, early metallomics analysis may lead to early screening/estimation and treatment/prevention for the autistic neurodevelopment disorders. C1 [Yasuda, Hiroshi; Tsutsui, Toyoharu] La Belle Vie Res Lab, Chuo Ku, Tokyo 1030006, Japan. RP Yasuda, H (reprint author), La Belle Vie Res Lab, Chuo Ku, 8-4 Nihonbashi Tomizawacho, Tokyo 1030006, Japan. 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J. Environ. Res. Public Health PD NOV PY 2013 VL 10 IS 11 BP 6027 EP 6043 DI 10.3390/ijerph10116027 PG 17 WC Environmental Sciences SC Environmental Sciences & Ecology GA 301GM UT WOS:000330520800042 PM 24284360 ER PT J AU Hartley, SL Schaidle, EM Burnson, CF AF Hartley, Sigan L. Schaidle, Emily M. Burnson, Cynthia F. TI Parental Attributions for the Behavior Problems of Children and Adolescents With Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism; behavior problems; attribution; parents; parenting stress ID SOCIAL COGNITION; MOTHERS; EMOTION; FATHERS; SAMPLES; STRESS; ADULTS AB Objective: The authors examined parental attributions for child behavior problems in 63 married couples of children and adolescents (aged 3-20 years) with autism spectrum disorders (ASDs). Both child-referent attributions (i.e., beliefs about causes related to the child or adolescent) and parent-referent attributions (i.e., beliefs about causes related to the parent) were examined along the dimensions of locus, stability, and controllability. Parent and child/adolescent factors related to parental attributions were identified, and the associations between parental attributions and parenting burden were explored. Method: Mothers and fathers independently completed self-reported measures of parental attributions, parenting burden, and child behavior problems. Couples jointly reported on their son or daughter's severity of autism symptoms, intellectual disability status, age, and gender. Results: Parents tended to attribute the behavior problems of their child/adolescent with an ASD to characteristics that were not only internal to and stable in the child/adolescent but also controllable by the child/adolescent. Mothers were more likely to attribute their son or daughter's behavior problems to characteristics that were less internal to and less stable in the child/adolescent with an ASD than were fathers. In addition, parents with a higher level of symptoms of the broader autism phenotype, parents of younger children, and parents of children/adolescents with intellectual disability, a higher severity of autism symptoms, and a higher severity of overall behavior problems were more likely to attribute their son or daughter's behavior problems to characteristics that were more internal to and stable in the child/adolescent and factors that were less controllable by the child/adolescent. Parental attributions were related to parents' level of parenting burden. Implications: Findings have implications for designing appropriate interventions and services for families of children and adolescents with ASDs. C1 [Hartley, Sigan L.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. 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Dev. Behav. Pediatr. PD NOV-DEC PY 2013 VL 34 IS 9 BP 651 EP 660 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 298YB UT WOS:000330359500003 PM 24217029 ER PT J AU Danial, JT Wood, JJ AF Danial, John T. Wood, Jeffrey J. TI Cognitive Behavioral Therapy for Children With Autism: Review and Considerations for Future Research SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Review DE cognitive behavior therapy; autism treatment; anxiety; disruptive behavior; social functioning ID RANDOMIZED CONTROLLED-TRIAL; HIGH-FUNCTIONING CHILDREN; SPECTRUM DISORDERS; ASPERGER-SYNDROME; ANXIETY DISORDERS; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; CHILDHOOD ANXIETY; SOCIAL-SKILLS; YOUNG-PEOPLE AB Objective: Cognitive behavioral therapy (CBT) is now commonly used for high-functioning children with an autism spectrum disorder. 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TI Parental Influence on a Child's Autistic Traits SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE autistic behaviors; parent behavior; parent assessment ID FAMILY AB CASE: Robbie is a 4-year-old boy whose parents are concerned about his speech, social skills, and repetitive behaviors. He has poor articulation; at time, he is difficult to understand. On the other hand, he has a fair vocabulary, and he has good intent to communicate. He is generally able to communicate his needs and wants. He likes to tell his parents about his day. When he begins the day at preschool, Robbie initially stands by himself and watches. He slowly warms up and eventually participates in activities. He engages in parallel play or follows other children. He knows names of children at preschool, and he is well liked. He is affectionate with his parents. When Robbie is excited, he wiggles his fingers, flaps his arms, and grimaces. He can be quite rigid; for example, he gets very distressed when his mother sets his cup down on his right side instead of his left. However, in general, Robbie has a sunny personality. He likes to watch children's television shows. He pretends plays with action figures. Robbie is an only child who lives with both parents. His mother works full-time, and his father is in home with Robbie during the day. When examined in the office, Robbie had a bright affect, good eye contact, and social referencing. He demonstrated good communicative intent, but poor articulation and some jargoning. He frequently wiggled his fingers and flapped his hands with excitement. Robbie had a borderline score on the Autism Diagnostic Observation Schedule. During the visit, the pediatrician noted that Robbie's father was rather quiet and rarely responded to questions. When he did respond, he had a monotone quality to his voice. He maintained either a flat or nervous affect throughout the visit. He made limited eye contact, and occasionally he stared excessively. C1 [Phelps, Randall; Nickel, Robert; Eisert, Debi] Oregon Hlth & Sci Univ, Dept Pediat, Inst Dev Disabil, Portland, OR 97201 USA. [Stein, Martin T.] Univ Calif San Diego, Div Gen Acad Pediat Child Dev & Community Hlth, San Diego, CA 92103 USA. RP Phelps, R (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, Inst Dev Disabil, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA. CR BOLTON P, 1994, J CHILD PSYCHOL PSYC, V35, P877, DOI 10.1111/j.1469-7610.1994.tb02300.x FOLSTEIN S, 1977, J CHILD PSYCHOL PSYC, V18, P297, DOI 10.1111/j.1469-7610.1977.tb00443.x Schor EL, 2003, PEDIATRICS, V111, P1541 NR 3 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD NOV-DEC PY 2013 VL 34 IS 9 BP 730 EP 732 PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 298YB UT WOS:000330359500011 PM 24217028 ER PT J AU Visser, E Zwiers, MP Kan, CC Hoekstra, L van Opstal, J Buitelaar, JK AF Visser, Eelke Zwiers, Marcel P. Kan, Cornelis C. Hoekstra, Liesbeth van Opstal, John Buitelaar, Jan K. TI Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID FUNCTIONAL CONNECTIVITY MRI; DORSAL COCHLEAR NUCLEUS; AUDITORY BRAIN-STEM; SUPERIOR OLIVE; ACOUSTIC STRIAE; SPATIAL HEARING; HEAD MOTION; CHILDREN; RESPONSES; ADULTS AB Background: Autism spectrum disorders (ASDs) are associated with auditory hyper-or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. Methods: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). Results: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. Limitations: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. Conclusion: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs. C1 [Visser, Eelke; Zwiers, Marcel P.; Buitelaar, Jan K.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 EN Nijmegen, Netherlands. [Visser, Eelke; Zwiers, Marcel P.; Hoekstra, Liesbeth; Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 EN Nijmegen, Netherlands. [Kan, Cornelis C.; Hoekstra, Liesbeth] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 EN Nijmegen, Netherlands. [van Opstal, John] Radboud Univ Nijmegen, Dept Biophys, NL-6525 EN Nijmegen, Netherlands. [van Opstal, John] Ctr Neurosci, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [Hoekstra, Liesbeth; Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. RP Visser, E (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Kapittelweg 29, NL-6525 EN Nijmegen, Netherlands. EM eelke.visser@donders.ru.nl RI Zwiers, Marcel/D-2968-2009 OI Zwiers, Marcel/0000-0001-5483-2935 FU University Medical Centre, Radboud University FX C. Kan is on the ADHD Advisory Board at Eli Lilly and has received royalties for 2 Dutch books on autism. J.K. Buitelaar declares an internal grant from the University Medical Centre, Radboud University. No other competing interests declared. 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NR 55 TC 2 Z9 2 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 EI 1488-2434 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD NOV PY 2013 VL 38 IS 6 BP 398 EP 406 DI 10.1503/jpn.120177 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 301IM UT WOS:000330526000007 PM 24148845 ER PT J AU Kim, P Arizpe, J Rosen, BH Razdan, V Haring, CT Jenkins, SE Deveney, CM Brotman, MA Blair, JR Pine, DS Baker, CI Leibenluft, E AF Kim, Pilyoung Arizpe, Joseph Rosen, Brooke H. Razdan, Varun Haring, Catherine T. Jenkins, Sarah E. Deveney, Christen M. Brotman, Melissa A. Blair, James R. Pine, Daniel S. Baker, Chris I. Leibenluft, Ellen TI Impaired fixation to eyes during facial emotion labelling in children with bipolar disorder or severe mood dysregulation SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID VISUAL SCAN PATHS; AMYGDALA ACTIVATION; NEURAL CIRCUITRY; FACE RECOGNITION; RATING-SCALE; SCHIZOPHRENIA; EXPRESSIONS; GAZE; PERCEPTION; AUTISM AB Background: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces. Methods: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions. Results: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls. Limitations: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns. Conclusion: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study. C1 [Kim, Pilyoung; Rosen, Brooke H.; Razdan, Varun; Haring, Catherine T.; Jenkins, Sarah E.; Deveney, Christen M.; Brotman, Melissa A.; Blair, James R.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kim, Pilyoung] Univ Denver, Dept Psychol, Denver, CO 80208 USA. [Arizpe, Joseph; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kim, P (reprint author), Univ Denver, Dept Psychol, 2155 South Race St, Denver, CO 80208 USA. EM pilyoung.kim@du.edu RI Brotman, Melissa/H-7409-2013; Arizpe, Joseph/N-1399-2014 OI Arizpe, Joseph/0000-0001-8958-7757 FU Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health FX Funding for this study was provided exclusively by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health. We thank the staff of the Emotion and Development Branch at NIMH and the children and families for their participation. 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Psychiatry Neurosci. PD NOV PY 2013 VL 38 IS 6 BP 407 EP 416 DI 10.1503/jpn.120232 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 301IM UT WOS:000330526000008 PM 23906351 ER PT J AU Moskowitz, LJ Mulder, E Walsh, CE McLaughlin, DM Zarcone, JR Proudfit, GH Carr, EG AF Moskowitz, Lauren J. Mulder, Emile Walsh, Caitlin E. McLaughlin, Darlene Magito Zarcone, Jennifer R. Proudfit, Greg Hajcak Carr, Edward G. TI A Multimethod Assessment of Anxiety and Problem Behavior in Children With Autism Spectrum Disorders and Intellectual Disability SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE anxiety; problem behavior; autism; multimethod ID PERVASIVE DEVELOPMENTAL DISORDERS; HEART-RATE-VARIABILITY; FRAGILE-X-SYNDROME; CHALLENGING BEHAVIORS; YOUNG-CHILDREN; SETTING EVENT; INTERVENTION; PHOBIAS; INDIVIDUALS; ASSOCIATION AB Despite the increased risk for anxiety disorders in children with autism spectrum disorders (ASD), there is a lack of research on the assessment and treatment of anxiety in this population, particularly for those with an intellectual disability (ID). The present study evaluated a multimethod strategy for the assessment of anxiety and problem behavior in three children with ASD and ID. Anxiety was operationally defined using: (1) behavioral data from anxious behaviors, (2) affective/contextual data from parent-report and observer ratings of overall anxiety, and (3) physiological data (heart rate [HR] and respiratory sinus arrhythmia [RSA]). A functional assessment of problem behavior during high-and low-anxiety conditions was conducted. Higher levels of problem behavior and HR and lower RSA were found in the high-anxiety than in the low-anxiety conditions. C1 [Moskowitz, Lauren J.] NYU Langone Med Ctr, NYU Child Study Ctr, New York, NY 10016 USA. [Mulder, Emile; Walsh, Caitlin E.; Proudfit, Greg Hajcak; Carr, Edward G.] SUNY Stony Brook, Stony Brook, NY USA. [McLaughlin, Darlene Magito] Posit Behav Support Consulting & Psychol Resource, Centerport, NY USA. [Zarcone, Jennifer R.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Moskowitz, LJ (reprint author), NYU Langone Med Ctr, NYU Child Study Ctr, New York, NY 10016 USA. 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However, few studies have examined this association in young children with FXS. The authors examined whether patterns of arousal and behavior during an experimental stranger approach paradigm differ between a cross-sectional sample of 21 young children with FXS and 19 controls (1258 months old). Groups did not differ in mean levels of behavioral fear. Unlike the control group, however, the FXS group demonstrated increased facial fear at older ages, as well as age-dependent changes in associations between heart activity and distress vocalizations. These findings may inform theoretical models of anxiety etiology in FXS and early detection efforts. C1 [Tonnsen, Bridgette L.; Shinkareva, Svetlana V.; Deal, Sara C.; Roberts, Jane E.] Univ S Carolina, Columbia, SC 29201 USA. [Hatton, Deborah D.] Vanderbilt Univ, Nashville, TN USA. RP Roberts, JE (reprint author), Univ S Carolina, 1512 Pendleton St, Columbia, SC 29201 USA. 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J. Intellect. Dev. Disabil. PD NOV PY 2013 VL 118 IS 6 BP 447 EP 459 DI 10.1352/1944-7558-118.6.447 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 296LC UT WOS:000330185500006 PM 24432858 ER PT J AU Klusek, J Martin, GE Losh, M AF Klusek, Jessica Martin, Gary E. Losh, Molly TI Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links With Pragmatic Language SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; ASD; fragile X syndrome; arousal; vagal tone; heart rate; pragmatic language; social communication; endophenotype ID DIAGNOSTIC-OBSERVATION-SCHEDULE; CHILD-DIRECTED SPEECH; SPECTRUM DISORDERS; YOUNG-CHILDREN; DOWN-SYNDROME; VAGAL TONE; CONVERSATIONAL CHARACTERISTICS; DEVELOPMENTAL DISORDER; POLYVAGAL PERSPECTIVE; REVISED ALGORITHMS AB This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 27 with typical development (TD), aged 4-15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did not differ from boys with ASD. Dampened vagal tone predicted pragmatic impairment in ASD, and associations emerged between cardiac activity and receptive/expressive vocabulary across groups. Findings support autonomic dysfunction as a mechanism underlying pragmatic impairment in ASD and suggest that biophysiological profiles are shared in ASD and FXS, which has implications for understanding the role of fragile X mental retardation-1 (FMR1, the FXS gene) in the pathophysiology of ASD. C1 [Klusek, Jessica] Frank Porter Graham Child Dev Inst, Chapel Hill, NC USA. [Martin, Gary E.] Univ N Carolina, Chapel Hill, NC USA. [Losh, Molly] Northwestern Univ, Evanston, IL 60208 USA. RP Losh, M (reprint author), Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, 2240 Campus Dr, Evanston, IL 60208 USA. 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PD NOV PY 2013 VL 118 IS 6 BP 475 EP 495 DI 10.1352/1944.7558-118.6.475 PG 21 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 296LC UT WOS:000330185500008 PM 24432860 ER PT J AU Mohammadi, MR Yadegari, N Hassanzadeh, E Farokhnia, M Yekehtaz, H Mirshafiee, O Akhondzadeh, S AF Mohammadi, Mohammad-Reza Yadegari, Nourrollah Hassanzadeh, Elmira Farokhnia, Mehdi Yekehtaz, Habibeh Mirshafiee, Omid Akhondzadeh, Shahin TI Double-Blind, Placebo-Controlled Trial of Risperidone Plus Amantadine in Children With Autism: A 10-Week Randomized Study SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE amantadine; autism; glutamate; randomized controlled trial; risperidone ID SPECTRUM DISORDERS; ABERRANT BEHAVIOR; MEMANTINE; SYMPTOMS; THERAPY; SCHIZOPHRENIA; DYSFUNCTION; MICROGLIA; MECHANISM; DISEASE AB Objective: This study aimed to investigate the effect of adding amantadine to risperidone for treatment of autism. Methods: Forty outpatients aged 4 to 12 years, who were diagnosed with autism spectrum disorders based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, were assigned to this double-blind clinical trial. The subjects were divided randomly into 2 groups. One group received risperidone plus amantadine, and the other group received risperidone plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and the dose of amantadine was 100 or 150 mg/d for patients less than 30 kg or more than 30 kg, respectively. The patients were assessed using the Aberrant Behavioral Checklist-Community (ABC-C) and adverse effects checklist as well as clinical global impression-improvement (CGI-I) at 2 checkpoints of 5-week intervals after the baseline. Informed consent was obtained from the parents of each participant. Results: Among ABC-C subscales, Hyperactivity and Irritability showed significantly greater reduction in the amantadine group than the placebo group. There was no significant difference in adverse effects between the 2 groups. The CGI-I scores show significant improvement in the amantadine group compared to the placebo group. Conclusions: The present study suggests that amantadine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. C1 [Mohammadi, Mohammad-Reza; Yadegari, Nourrollah; Hassanzadeh, Elmira; Farokhnia, Mehdi; Yekehtaz, Habibeh; Mirshafiee, Omid; Akhondzadeh, Shahin] Univ Tehran Med Sci, Roozbeh Hosp, Psychiat Res Ctr, Tehran 13337, Iran. RP Akhondzadeh, S (reprint author), Univ Tehran Med Sci, Roozbeh Psychiat Hosp, Psychiat Res Ctr, South Kargar St, Tehran 13337, Iran. EM s.akhond@neda.net FU Tehran University of Medical Sciences [10797] FX No conflict of interest exists for any of the authors associated with the manuscript and there was no source of extra-institutional commercial funding. This study was supported by a grant from Tehran University of Medical Sciences to Prof Shahin Akhondzadeh (Grant 10797). The funding organization had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript and the decision to submit the paper for publication. 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Neuropharmacol. PD NOV-DEC PY 2013 VL 36 IS 6 BP 179 EP 184 DI 10.1097/WNF.0b013e3182a9339d PG 6 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 299BK UT WOS:000330369400001 PM 24201232 ER PT J AU Caravagna, C Soliz, J Seaborn, T AF Caravagna, Celine Soliz, Jorge Seaborn, Tommy TI Brain-derived neurotrophic factor interacts with astrocytes and neurons to control respiration SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE astrocyte; brain-derived neurotrophic factor; brainstem; rhythmogenesis; TrkB ID PRE-BOTZINGER COMPLEX; CENTRAL-NERVOUS-SYSTEM; CENTRAL HYPOVENTILATION SYNDROME; KOLLIKER-FUSE NUCLEUS; RETT-SYNDROME; MOUSE MODEL; PREBOTZINGER COMPLEX; GROWTH-FACTOR; IN-VITRO; SYNAPTIC-TRANSMISSION AB Respiratory rhythm is generated and modulated in the brainstem. Neuronal involvement in respiratory control and rhythmogenesis is now clearly established. However, glial cells have also been shown to modulate the activity of brainstem respiratory groups. Although the potential involvement of other glial cell type(s) cannot be excluded, astrocytes are clearly involved in this modulation. In parallel, brain-derived neurotrophic factor (BDNF) also modulates respiratory rhythm. The currently available data on the respective roles of astrocytes and BDNF in respiratory control and rhythmogenesis lead us to hypothesize that there is BDNF-mediated control of the communication between neurons and astrocytes in the maintenance of a proper neuronal network capable of generating a stable respiratory rhythm. According to this hypothesis, progression of Rett syndrome, an autism spectrum disease with disordered breathing, can be stabilized in mouse models by re-expressing the normal gene pattern in astrocytes or microglia, as well as by stimulating the BDNF signaling pathway. These results illustrate how the signaling mechanisms by which glia exerts its effects in brainstem respiratory groups is of great interest for pathologies associated with neurological respiratory disorders. C1 [Caravagna, Celine; Soliz, Jorge; Seaborn, Tommy] Univ Laval, Dept Pediat, Ctr Rech, Hop St Francois Assise,Ctr Hosp Univ CHU Quebec, Quebec City, PQ, Canada. RP Seaborn, T (reprint author), Univ Laval, Dept Pediat, Ctr Rech, Hop St Francois Assise,Ctr Hosp Univ CHU Quebec, 10 Rue Espinay,Room D0-742, Quebec City, PQ, Canada. EM Tommy.Seaborn@crchuq.ulaval.ca FU Respiratory Health Network of the Quebec Health Research Funds (FRQS); Foundation of Stars for Children's Health Research; Molly Towell Foundation; Faculty of Medicine of Laval University FX The authors thank Drs Aida Bairam and Vincent Joseph for their helpful comments, as well as Dr Richard Kinkead for his thoughtful reading of the manuscript and Miss NagaPraveena Uppari for partial revision of the English. Celine Caravagna is a PhD student supported by the Faculty of Medicine of Laval University. This work was supported by the Respiratory Health Network of the Quebec Health Research Funds (FRQS) (Dr Tommy Seaborn), and by the Foundation of Stars for Children's Health Research and the Molly Towell Foundation (Dr Jorge Soliz). The authors have no actual or potential conflicts of interest to declare. 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J. Neurosci. PD NOV PY 2013 VL 38 IS 9 BP 3261 EP 3269 DI 10.1111/ejn.12320 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 295FF UT WOS:000330101300001 PM 23930598 ER PT J AU Pardoe, HR Abbott, DF Jackson, GD AF Pardoe, Heath R. Abbott, David F. Jackson, Graeme D. CA Alzheimer's Dis Neuroimaging Initi TI Sample Size Estimates for Well-Powered Cross-Sectional Cortical Thickness Studies SO HUMAN BRAIN MAPPING LA English DT Article DE MRI; neuroimaging; study design; power analysis; morphometry; cortical thickness ID CEREBRAL-CORTEX; CHILDREN; DISEASE; MRI; AUTISM AB Introduction: Cortical thickness mapping is a widely used method for the analysis of neuroanatomical differences between subject groups. We applied power analysis methods over a range of image processing parameters to derive a model that allows researchers to calculate the number of subjects required to ensure a well-powered cross-sectional cortical thickness study. Methods: 0.9-mm isotropic T-1-weighted 3D MPRAGE MRI scans from 98 controls (53 females, age 29.1 +/- 9.7 years) were processed using Freesurfer 5.0. Power analyses were carried out using vertex-wise variance estimates from the coregistered cortical thickness maps, systematically varying processing parameters. A genetic programming approach was used to derive a model describing the relationship between sample size and processing parameters. The model was validated on four Alzheimer's Disease Neuroimaging Initiative control datasets (mean 126.5 subjects/site, age 76.6 +/- 5.0 years). Results: Approximately 50 subjects per group are required to detect a 0.25-mm thickness difference; less than 10 subjects per group are required for differences of 1 mm (two-sided test, 10 mm smoothing, = 0.05). Sample size estimates were heterogeneous over the cortical surface. The model yielded sample size predictions within 2-6% of that determined experimentally using independent data from four other datasets. Fitting parameters of the model to data from each site reduced the estimation error to less than 2%. Conclusions: The derived model provides a simple tool for researchers to calculate how many subjects should be included in a well-powered cortical thickness analysis. Hum Brain Mapp 34:3000-3009, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Pardoe, Heath R.; Abbott, David F.; Jackson, Graeme D.] Austin Hosp, Melbourne Brain Ctr, Florey Neurosci Inst, Brain Res Inst, Heidelberg, Vic 3084, Australia. [Pardoe, Heath R.; Abbott, David F.; Jackson, Graeme D.] Univ Melbourne, Dept Med, Melbourne, Vic 3010, Australia. [Jackson, Graeme D.] Univ Melbourne, Dept Radiol, Melbourne, Vic 3010, Australia. RP Jackson, GD (reprint author), Austin Hosp, Melbourne Brain Ctr, Florey Neurosci Inst, Brain Res Inst, 245 Burgundy St, Heidelberg, Vic 3084, Australia. EM BRI@brain.org.au RI Abbott, David/E-5412-2010; Jackson, Graeme/A-9064-2013 OI Abbott, David/0000-0002-7259-8238; FU National Institutes of Health [NIH-NINDS R37-31146]; Victorian Life Sciences Computation Initiative (VLSCI; Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government) [VR0056]; Victorian Government's Operational Infrastructure Support Program; Scobie nd McKinnon Trust; NHMRC program [628952]; Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health) [U01 AG024904] FX Contract grant sponsor: National Institutes of Health; contract grant number: NIH-NINDS R37-31146; Contract grant sponsor: Victorian Life Sciences Computation Initiative (VLSCI; Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government); Contract grant number: VR0056; Contract grant sponsor: Victorian Government's Operational Infrastructure Support Program; Contract grant sponsor: Scobie nd McKinnon Trust; Contract grant sponsor: NHMRC program; Contract grant number: 628952; Contract grant sponsor: Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health); Contract grant number: U01 AG024904. 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Abbeduto, Leonard TI Language Comprehension Profiles of Young Adolescents With Fragile X Syndrome SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE adolescents; developmental disorders; language; syntax ID WITHIN-SYNDROME DIFFERENCES; DOWN-SYNDROME; EXPRESSIVE LANGUAGE; RECEPTIVE LANGUAGE; WORKING-MEMORY; BOYS; CHILDREN; AUTISM; ADULTS; SKILLS AB Purpose: In this study, the authors sought to characterize the language phenotype of fragile X syndrome (FXS), focusing on the extent of impairment in receptive syntax, within-syndrome variability in those impairments in relation to gender, and the syndrome specificity of those impairments. Method: The Test for Reception of Grammar, Version 2 (Bishop, 2003), was used to examine the overall receptive syntactic skills of adolescents with FXS (n = 35; 30 males, 5 females), adolescents with Down syndrome (DS; n = 28; 18 males, 10 females), and younger typically developing (TD) children (n = 23; 14 males, 9 females) matched on nonverbal cognition. Performance on specific grammatical constructions and error types was examined for a subset of matched participants. Results: Participants with FXS had overall receptive syntax scores that were lower than those of the TD participants but higher than those of the participants with DS; however, there was no difference in performance between the FXS and DS groups when females were excluded. 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PD NOV-DEC PY 2013 VL 13 IS 6 BP 291 EP + PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 293NO UT WOS:000329979100012 PM 24348132 ER PT J AU Arnold, LE AF Arnold, L. Eugene TI Placebo Response and the Company It Keeps SO JAMA PEDIATRICS LA English DT Editorial Material ID CHILDREN; RISPERIDONE; AUTISM C1 Ohio State Univ, Dept Psychiat, Sunbury, OH 43074 USA. RP Arnold, LE (reprint author), Ohio State Univ, Dept Psychiat, 479 S Galena Rd, Sunbury, OH 43074 USA. EM l.arnold@osumc.edu CR [Anonymous], 2002, N ENGL J MED, V347, P314 Arnold LE, 2010, J CHILD ADOL PSYCHOP, V20, P83, DOI 10.1089/cap.2009.0022 King BH, 2009, ARCH GEN PSYCHIAT, V66, P583, DOI 10.1001/archgenpsychiatry.2009.30 King BH, 2013, JAMA PEDIATR, V167, P1045, DOI 10.1001/jamapediatrics.2013.2698 SAHAKIAN BJ, 1977, MED HYPOTHESES, V3, P154, DOI 10.1016/0306-9877(77)90065-2 NR 5 TC 0 Z9 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD NOV PY 2013 VL 167 IS 11 BP 1000 EP 1001 DI 10.1001/jamapediatrics.2013.2704 PG 2 WC Pediatrics SC Pediatrics GA 291PX UT WOS:000329842300008 PM 24061596 ER PT J AU King, BH Dukes, K Donnelly, CL Sikich, L McCracken, JT Scahill, L Hollander, E Bregman, JD Anagnostou, E Robinson, F Sullivan, L Hirtz, D AF King, Bryan H. Dukes, Kimberly Donnelly, Craig L. Sikich, Linmarie McCracken, James T. Scahill, Lawrence Hollander, Eric Bregman, Joel D. Anagnostou, Evdokia Robinson, Fay Sullivan, Lisa Hirtz, Deborah TI Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders A Multisite Randomized Clinical Trial SO JAMA PEDIATRICS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; DOUBLE-BLIND; REPETITIVE BEHAVIOR; ABERRANT BEHAVIOR; SECRETIN; RISPERIDONE; IRRITABILITY; METAANALYSIS; HYPERACTIVITY; ARIPIPRAZOLE AB IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression-Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children's Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelveweeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopramwas 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression-Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale-Revised, and the Children's Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. C1 [King, Bryan H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [King, Bryan H.] Seattle Childrens Hosp, Dept Psychiat & Behav Med, Seattle, WA 98105 USA. [Dukes, Kimberly; Robinson, Fay] DM STAT Inc, Malden, MA USA. [Donnelly, Craig L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Sikich, Linmarie] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [McCracken, James T.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Scahill, Lawrence] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Hollander, Eric] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Bregman, Joel D.] Ctr Autism, Philadelphia, PA USA. [Anagnostou, Evdokia] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada. [Sullivan, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. RP King, BH (reprint author), Seattle Childrens Hosp, Dept Psychiat & Behav Med, 4800 Sand Point Way NE, Seattle, WA 98105 USA. EM bhking@uw.edu FU National Institute of Mental Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Environmental Health Sciences via STAART Center contract Boston University/Dartmouth [U54-MH066398]; National Institute of Environmental Health Sciences via STAART Center contract DM-STAT, Inc [U01-HD045023]; National Institute of Environmental Health Sciences via STAART Center contract Mount Sinai [U54-MH066673]; National Institute of Environmental Health Sciences via STAART Center contract UCLA [U54-MH068172]; National Institute of Environmental Health Sciences via STAART Center contract University of North Carolina [U54-MH066418]; National Institute of Environmental Health Sciences via STAART Center contract Yale University [U54-MH066494] FX This work was funded by the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, and the National Institute of Environmental Health Sciences via the following STAART Center contracts: Boston University/Dartmouth (U54-MH066398), Helen Tager-Flusberg, principal investigator (PI); DM-STAT, Inc (U01-HD045023), Kimberly Dukes, PI; Mount Sinai (U54-MH066673), Eric Hollander, PI; UCLA (U54-MH068172), Marian Sigman, PI; University of North Carolina (U54-MH066418), Joseph Piven, PI; and Yale University (U54-MH066494), Fred Volkmar, PI. 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TI Towards improved animal models for evaluating social cognition and its disruption in schizophrenia: The CNTRICS initiative SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Sociability; Social recognition; Emotion; Negative symptoms; Affective behaviour; Psychosis; Antipsychotic; Oxytocin; Gaze; Eye-tracking; Mouse; Rat; Non-human primate ID AUTISM SPECTRUM DISORDERS; VOLES MICROTUS-OCHROGASTER; DOPAMINE D-3 RECEPTORS; TEMPORAL VISUAL AREA; INTRANASAL OXYTOCIN; NOVELTY DISCRIMINATION; PARTNER PREFERENCE; RHESUS-MONKEYS; MOUSE MODELS; EYE-TRACKING AB Social cognition refers to processes used to monitor and interpret social signals from others, to decipher their state of mind, emotional status and intentions, and select appropriate social behaviour. Social cognition is sophisticated in humans, being embedded with verbal language and enacted in a complex cultural environment. Its disruption characterises the entire course of schizophrenia and is correlated with poor functional outcome. Further, deficits in social cognition are related to impairment in other cognitive domains, positive symptoms (paranoia and delusions) and negative symptoms (social withdrawal and reduced motivation). In light of the significance and inadequate management of social cognition deficits, there is a need for translatable experimental procedures for their study, and identification of effective pharmacotherapy. No single paradigm captures the multi-dimensional nature of social cognition, and procedures for assessing ability to infer mental states are not well-developed for experimental therapeutic settings. Accordingly, a recent CNTRICS meeting prioritised procedures for measuring a specific construct: "acquisition and recognition of affective (emotional) states", coupled to individual recognition. Two complementary paradigms for refinement were identified: social recognition/preference in rodents, and visual tracking of social scenes in non-human primates (NHPs). Social recognition is disrupted in genetic, developmental or pharmacological disease models for schizophrenia, and performance in both procedures is improved by the neuropeptide oxytocin. The present article surveys a broad range of procedures for studying social cognition in rodents and NHPs, discusses advantages and drawbacks, and focuses on development of social recognition/preference and gaze-following paradigms for improved study of social cognition deficits in schizophrenia and their potential treatment. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Millan, Mark J.] IDR Servier, Unit Res & Discovery Neurosci, F-78290 Croissy Sur Seine, France. [Bales, Karen L.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. RP Millan, MJ (reprint author), IDR Servier, Unit Res & Discovery Neurosci, 125 Chemin Ronde, F-78290 Croissy Sur Seine, France. 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Biobehav. Rev. PD NOV PY 2013 VL 37 IS 9 BP 2166 EP 2180 DI 10.1016/j.neubiorev.2013.09.012 PN B PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 292EC UT WOS:000329884000008 PM 24090822 ER PT J AU Rustan, OG Folsom, TD Yousefi, MK Fatemi, SH AF Rustan, Oyvind G. Folsom, Timothy D. Yousefi, Mahtab K. Fatemi, S. Hossein TI Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling SO MOLECULAR AUTISM LA English DT Letter DE mGluR5; FMRP; Cerebellar vermis; Superior frontal cortex; Phosphorylation of FMRP ID TRANSLATION; POSTMORTEM; FMRP AB Lohith et al. (Mol Autism 4: 15, 2013) recently identified increased metabotropic glutamate receptor 5 (mGluR5) expression in the frontal cortex (FC) of subjects with fragile X syndrome. These results are consistent with postmortem findings in cerebellar vermis and FC of subjects with autism (Fatemi and Folsom, Mol Autism 2: 6, 2011; Fatemi et al. Anat Rec 294: 1635-1645, 2011), suggesting that increased mGluR5 signaling is common to multiple autism spectrum disorders. Increased mGluR5 signaling may be associated with reduced phosphorylation of fragile X mental retardation protein (FMRP), which could result in the inactivation of this protein. In the current study, we report on reduced expression of phosphorylated FMRP in cerebellar vermis of adults and children with autism and in FC of adults with autism. C1 [Rustan, Oyvind G.; Folsom, Timothy D.; Yousefi, Mahtab K.; Fatemi, S. Hossein] Univ Minnesota, Sch Med, Div Neurosci Res, Dept Psychiat, Minneapolis, MN 55455 USA. [Fatemi, S. Hossein] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA. [Fatemi, S. Hossein] Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. 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Autism PD NOV 1 PY 2013 VL 4 AR 41 DI 10.1186/2040-2392-4-41 PG 3 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 291NL UT WOS:000329835300001 PM 24180586 ER PT J AU Friedman, SH Dani, N Rushton, E Broadie, K AF Friedman, Samuel H. Dani, Neil Rushton, Emma Broadie, Kendal TI Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila SO DISEASE MODELS & MECHANISMS LA English DT Article ID METABOTROPIC GLUTAMATE-RECEPTOR; HEPARAN-SULFATE PROTEOGLYCANS; WINGLESS MORPHOGEN GRADIENT; ANAPLASTIC LYMPHOMA KINASE; DALLY-LIKE PROTEIN; NEUROMUSCULAR-JUNCTION; MESSENGER-RNA; NERVOUS-SYSTEM; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX AB Fragile X syndrome (FXS), the most common inherited determinant of intellectual disability and autism spectrum disorders, is caused by loss of the fragile X mental retardation 1 (FMR1) gene product (FMRP), an mRNA-binding translational repressor. A number of conserved FMRP targets have been identified in the well-characterized Drosophila FXS disease model, but FMRP is highly pleiotropic in function and the full spectrum of FMRP targets has yet to be revealed. In this study, screens for upregulated neural proteins in Drosophila fmr1 (dfmr1) null mutants reveal strong elevation of two synaptic heparan sulfate proteoglycans (HSPGs): GPI-anchored glypican Dally-like protein (Dip) and transmembrane Syndecan (Sdc). Our recent work has shown that Dlp and Sdc act as co-receptors regulating extracellular ligands upstream of intracellular signal transduction in multiple trans-synaptic pathways that drive synaptogenesis. Consistently, dfmr1 null synapses exhibit altered WNT signaling, with changes in both Wingless (Wg) ligand abundance and downstream Frizzled-2 (Fz2) receptor C-terminal nuclear import. Similarly, a parallel anterograde signaling ligand, Jelly belly (Jeb), and downstream ERK phosphorylation (dpERK) are depressed at dfmr1 null synapses. In contrast, the retrograde BMP ligand Glass bottom boat (Gbb) and downstream signaling via phosphorylation of the transcription factor MAD (pMAD) seem not to be affected. To determine whether HSPG upregulation is causative for synaptogenic defects, HSPGs were genetically reduced to control levels in the dfmr1 null background. HSPG correction restored both (1) Wg and Jeb trans-synaptic signaling, and (2) synaptic architecture and transmission strength back to wild-type levels. Taken together, these data suggest that FMRP negatively regulates HSPG co-receptors controlling trans-synaptic signaling during synaptogenesis, and that loss of this regulation causes synaptic structure and function defects characterizing the FXS disease state. C1 [Friedman, Samuel H.; Dani, Neil; Rushton, Emma; Broadie, Kendal] Vanderbilt Univ, Dept Biol Sci, Kennedy Ctr Res Human Dev, Nashville, TN 37212 USA. RP Broadie, K (reprint author), Vanderbilt Univ, Dept Biol Sci, Kennedy Ctr Res Human Dev, Nashville, TN 37212 USA. EM kendal.broadie@vanderbilt.edu FU FRAXA Research Foundation; National Institutes of Health [MH084989, MH096832] FX This work was supported by research grants to K.B. from the FRAXA Research Foundation and National Institutes of Health (MH084989 and MH096832). 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Model. Mech. PD NOV PY 2013 VL 6 IS 6 BP 1400 EP 1413 DI 10.1242/dmm.012229 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 283VL UT WOS:000329275000011 PM 24046358 ER PT J AU Wachtel, LE Schuldt, S Ghaziuddin, N Shorter, E AF Wachtel, L. E. Schuldt, S. Ghaziuddin, N. Shorter, E. TI The potential role of electroconvulsive therapy in the 'Iron Triangle' of pediatric catatonia, autism, and psychosis SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Letter ID ECT C1 [Wachtel, L. E.] Kennedy Krieger Inst, Neurobehav Unit, Baltimore, MD USA. [Wachtel, L. E.] Johns Hopkins Univ, Sch Med, Dept Child & Adolescent Psychiat, Baltimore, MD USA. [Schuldt, S.; Ghaziuddin, N.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Shorter, E.] Univ Toronto, Fac Med, Hist Med Program, Toronto, ON, Canada. RP Wachtel, LE (reprint author), Kennedy Krieger Inst, Neurobehav Unit, Baltimore, MD USA. 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PD NOV PY 2013 VL 128 IS 5 BP 408 EP 409 DI 10.1111/acps.12158 PG 2 WC Psychiatry SC Psychiatry GA 282UE UT WOS:000329198300011 PM 23773168 ER PT J AU Han, JC Thurm, A Williams, CG Joseph, LA Zein, WM Brooks, BP Butman, JA Brady, SM Fuhr, SR Hicks, MD Huey, AE Hanish, AE Danley, KM Raygada, MJ Rennert, OM Martinowich, K Sharp, SJ Tsao, JW Swedo, SE AF Han, Joan C. Thurm, Audrey Williams, Christine Golden Joseph, Lisa A. Zein, Wadih M. Brooks, Brian P. Butman, John A. Brady, Sheila M. Fuhr, Shannon R. Hicks, Melanie D. Huey, Amanda E. Hanish, Alyson E. Danley, Kristen M. Raygada, Margarita J. Rennert, Owen M. Martinowich, Keri Sharp, Stephen J. Tsao, Jack W. Swedo, Susan E. TI Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome SO CORTEX LA English DT Article DE Brain-derived neurotrophic factor; WAGR syndrome; 11p Deletion; IQ; Autism ID MESSENGER-RNA EXPRESSION; INTELLECTUAL DISABILITY; WAGR SYNDROME; MENTAL-RETARDATION; VISUAL IMPAIRMENT; CHRONIC DISEASES; AUTISM; CHILDREN; SPECTRUM; ADOLESCENTS AB In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/-). We hypothesized that BDNF+/- would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high-resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), reduced cognitive functioning (p = .04), higher levels of reported historical (p = .02) and current (p = .02) social impairment, and higher percentage meeting cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive Behaviour Compose score that was 14-points lower and a mean intelligence quotient (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development. Published by Elsevier Ltd. C1 [Han, Joan C.; Fuhr, Shannon R.; Hicks, Melanie D.; Huey, Amanda E.; Hanish, Alyson E.; Danley, Kristen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Metab & Neuroendocrinol, NIH, Bethesda, MD USA. [Han, Joan C.; Brady, Sheila M.] NICHD, Program Dev Endocrinol & Genet, Sect Growth & Obes, NIH, Bethesda, MD 20892 USA. [Thurm, Audrey; Williams, Christine Golden; Joseph, Lisa A.; Swedo, Susan E.] NIH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. [Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Hanish, Alyson E.] NINR, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Raygada, Margarita J.; Rennert, Owen M.] NICHD, Sect Clin & Dev Genom, NIH, Bethesda, MD 20892 USA. [Martinowich, Keri] Lieber Inst Brain Dev, Baltimore, MD USA. [Sharp, Stephen J.; Tsao, Jack W.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Han, JC (reprint author), NICHD, Unit Metab & Neuroendocrinol, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM hanjo@mail.nih.gov FU Intramural Research Programs of the Eunice Kennedy Shriller National Institute of Child Health and Human Development [ZIAHD008898, Z1AHD00641]; National Institute of Mental Health of the National Institutes of Health (NIH) [ZIAMH002868]; NIH Bench-to-Bedside Program FX This study was funded by the Intramural Research Programs of the Eunice Kennedy Shriller National Institute of Child Health and Human Development (ZIAHD008898 and Z1AHD00641) and the National Institute of Mental Health (ZIAMH002868) of the National Institutes of Health (NIH), and by the NIH Bench-to-Bedside Program. We thank the members of International WAGR Syndrome Association for assistance in identifying families who were willing to participate in this study. We thank Jack Yanovski and Daniel Weinberger for helpful discussions. We thank Margaret Pekar, Miriya Tune, Mark Lee, Matthew Tsang, Tanvee Singh, Emily Yin, Jamila Grossman, and Rachel Kim for assistance with psychological testing and administrative support. Disclaimer: the opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense. 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McIntosh, Daniel N. TI The response is more than reflection: Mirror neurons function within social contexts SO CORTEX LA English DT Editorial Material ID EMOTIONAL FACIAL EXPRESSIONS; BODY PERCEPTION; MIMICRY; AUTISM C1 [Reed, Catherine L.] Claremont Mckenna Coll, Claremont, CA 91711 USA. [Reed, Catherine L.; McIntosh, Daniel N.] Univ Denver, Denver, CO 80208 USA. RP Reed, CL (reprint author), Claremont Mckenna Coll, Dept Psychol, Claremont, CA 91711 USA. 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M. Damsteegt, Ruth Trezza, Viviana Voorn, Pieter Vanderschuren, Louk J. M. J. TI Functional integrity of the habenula is necessary for social play behaviour in rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE adolescence; c-fos; habenula; social behaviour; social isolation ID VENTRAL TEGMENTAL AREA; MEDIAL PREFRONTAL CORTEX; IN-SITU HYBRIDIZATION; LATERAL HABENULA; ADOLESCENT RATS; JUVENILE RATS; MESSENGER-RNA; ELECTRICAL-STIMULATION; RATTUS-NORVEGICUS; FOS EXPRESSION AB During post-weaning development, a marked increase in peer-peer interactions is observed in mammals, including humans, which is signified by the abundance of social play behaviour. Social play is highly rewarding, and known to be modulated through monoaminergic neurotransmission. Recently, the habenula has received widespread attention because of its role in the regulation of monoaminergic neurotransmission as well as in a variety of emotional and cognitive functions. Therefore, in the present study, we investigated the involvement of the habenula in social play behaviour. Using the neuronal activity maker c-fos, we showed that the habenula was activated after 24h of social isolation in adolescent rats, and that a subsequent social play interaction reduced c-fos activity in the medial part of the lateral habenula. This suggested that habenula activity modulated the aversive properties of social isolation, which was alleviated by the positive effects of social play. Furthermore, after functional inactivation of the habenula, using a mixture of the GABA receptor agonists baclofen and muscimol, social play behaviour was markedly reduced, whereby responsiveness to play solicitation was more sensitive to habenula inactivation than play solicitation itself. Together, our data indicate an important role for the habenula in the processing of positive (i.e. social play behaviour) and negative (i.e. social isolation) social information in adolescent rats. Altered habenula function might therefore be related to the social impairments in childhood and adolescent psychiatric disorders such as autism, attention deficit/hyperactivity disorder and early-onset schizophrenia. C1 [van Kerkhof, Linda W. M.; Damsteegt, Ruth; Trezza, Viviana; Vanderschuren, Louk J. M. J.] Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Trezza, Viviana] Univ Roma Tre, Dept Sci, Sect Biomed Sci & Technol, Rome, Italy. [Voorn, Pieter] Vrije Univ Amsterdam, Dept Anat & Neurosci, Med Ctr, Amsterdam, Netherlands. [Vanderschuren, Louk J. M. J.] Univ Utrecht, Fac Vet Med, Dept Anim Sci & Soc, Div Behav Neurosci, NL-3584 CM Utrecht, Netherlands. RP Vanderschuren, LJMJ (reprint author), Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. EM l.j.m.j.vanderschuren@uu.nl FU National Institute on Drug Abuse [R01 DA022628]; Netherlands Organization for Scientific Research (NWO) Veni [91611052]; Marie Curie Career Reintegration [PCIG09-GA-2011-293589] FX This work was supported by the National Institute on Drug Abuse (grant R01 DA022628 to L.J.M.J.V.), Netherlands Organization for Scientific Research (NWO) Veni (grant 91611052 to V. T.) and Marie Curie Career Reintegration (grant PCIG09-GA-2011-293589 to V. T.). The authors have no conflict of interest to disclose. 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J. Neurosci. PD NOV PY 2013 VL 38 IS 10 BP 3465 EP 3475 DI 10.1111/ejn.12353 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 253AM UT WOS:000327054000008 PM 24103016 ER PT J AU Battaglia, A Doccini, V Bernardini, L Novelli, A Loddo, S Capalbo, A Filippi, T Carey, JC AF Battaglia, Agatino Doccini, Viola Bernardini, Laura Novelli, Antonio Loddo, Sara Capalbo, Anna Filippi, Tiziana Carey, John C. TI Confirmation of chromosomal microarray as a firsttier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features. SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE Chromosomal microarray (CMA); Array-CGH; Developmental delay; Intellectual disability; Neurodevelopmental disorders; Autism spectrum disorders; Dysmorphic features ID IDIOPATHIC MENTAL-RETARDATION; COMPARATIVE GENOMIC HYBRIDIZATION; CONGENITAL-ANOMALIES; ETIOLOGIC YIELD; SINGLE-GENE; CHILD; STANDARDS; COMPLEX; RAS; SON AB Background and objectives: Submicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients. Patients and methods: We studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases. Results: 91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID. Conclusions: Our study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting. (C) 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Battaglia, Agatino; Doccini, Viola; Filippi, Tiziana] Stella Maris Clin Res Inst Child & Adolescent Neu, I-56128 Pisa, Italy. [Bernardini, Laura; Novelli, Antonio; Loddo, Sara; Capalbo, Anna] Casa Sollievo Sofferenza Hosp, IRCCS, Mendel Lab, San Giovanni Rotondo, FG, Italy. [Carey, John C.] Univ Utah, Hlth Sci Ctr, Dept Pediat, Div Med Genet, Salt Lake City, UT USA. RP Battaglia, A (reprint author), Stella Maris Clin Res Inst Child & Adolescent Neu, Via Giacinti 2, I-56128 Pisa, Italy. EM agatino.battaglia@inpe.unipi.it FU Italian Ministry of Health FX This study was supported by grants from the Italian Ministry of Health to AB and LB. 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PD NOV PY 2013 VL 17 IS 6 BP 589 EP 599 DI 10.1016/j.ejpn.2013.04.010 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 277GM UT WOS:000328807000010 PM 23711909 ER PT J AU Olsson, I Danielsson, S Hedstrom, A Nordborg, C Viggedal, G Uvebrant, P Rydenhag, B AF Olsson, Ingrid Danielsson, Susanna Hedstrom, Anders Nordborg, Claes Viggedal, Gerd Uvebrant, Paul Rydenhag, Bertil TI Epilepsy surgery in children with accompanying impairments SO EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY LA English DT Article DE Epilepsy surgery; Children; Learning disability; Cerebral palsy ID DRUG-RESISTANT EPILEPSY; CORTICAL DYSPLASIA; SURGICAL-TREATMENT; POPULATION; CHILDHOOD; OUTCOMES; PSYCHOPATHOLOGY; DISORDERS; SEIZURES; AUTISM AB The aim of this study was to assess seizure outcome 2 years after epilepsy surgery in a consecutive series of paediatric patients, with special focus on children with learning disabilities and other neuroimpairments in addition to the epilepsy. Outcome 2 years after surgery was assessed in 110 of 125 children operated upon for drug resistant epilepsy in Gothenburg 1987-2006. More than half of the children had learning disabilities, 43% motor impairments and 30% a neuropsychiatric diagnosis. Fifty-six per cent of those with an IQ < 70 became seizure-free or had a >75% reduction in seizure frequency, and two thirds if the operation was a resection. The corresponding figure in those with more than 100 seizures per month was 15 out of 31, and another seven had a 50-75% reduction in seizure frequency. The message is that learning disability, motor impairment and psychiatric morbidity should not be contraindications for paediatric epilepsy surgery. More than half of the children with learning disabilities had a worthwhile seizure outcome, with even better results after resective surgery. Children with drug resistant epilepsy and additional severe neurological impairments should have the benefit of referral to a tertiary centre for evaluation for epilepsy surgery. (C) 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. C1 [Olsson, Ingrid; Viggedal, Gerd; Uvebrant, Paul] Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden. [Danielsson, Susanna] Cty Hosp Ryhov, Jonkoping, Sweden. [Hedstrom, Anders; Rydenhag, Bertil] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Nordborg, Claes] Gothenburg Univ, Sahlgrenska Acad, Dept Pathol, S-41124 Gothenburg, Sweden. RP Olsson, I (reprint author), Queen Silvia Childrens Hosp, Dept Paediat, S-41685 Gothenburg, Sweden. EM ingrid.b.olsson@vgregion.se FU Margarethahem Foundation; Sahlgrenska Academy at Gothenburg University through the ALF agreement FX The authors wish to thank epilepsy nurse and coordinator Birgitta Olovson for the contribution of data. The work was funded by The Margarethahem Foundation and the Sahlgrenska Academy at Gothenburg University through the ALF agreement. 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J. Paediatr. Neurol. PD NOV PY 2013 VL 17 IS 6 BP 645 EP 650 DI 10.1016/j.ejpn.2013.06.004 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 277GM UT WOS:000328807000018 PM 23948291 ER PT J AU Dinwiddie, DL Bracken, JM Bass, JA Christenson, K Soden, SE Saunders, CJ Miller, NA Singh, V Zwick, DL Roberts, CC Dalal, J Kingsmore, SF AF Dinwiddie, Darrell L. Bracken, Julia M. Bass, Julie A. Christenson, Kathy Soden, Sarah E. Saunders, Carol J. Miller, Neil A. Singh, Vivekanand Zwick, David L. Roberts, Charles C. Dalal, Jignesh Kingsmore, Stephen F. TI Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing SO GENOMICS LA English DT Article DE Inflammatory bowel disease; Crohn's disease; IL10RA; IL10; Hematopoietic stem cell transplantation; Colitis; Exome sequencing ID DE-NOVO MUTATIONS; GENETIC-VARIATION; DISORDERS; RECEPTOR; STANDARDS; VARIANTS; DATABASE; AUTISM AB Pediatric-onset inflammatory bowel disease (IBD) is known to be associated with severe disease, poor response to therapy, and increased morbidity and mortality. We conducted exome sequencing of two brothers from a non-consanguineous relationship who presented before the age of one with severe infantile-onset IBD, failure to thrive, skin rash, and perirectal abscesses refractory to medical management. We examined the variants discovered in all known IBD-associated and primary immunodeficiency genes in both siblings. The siblings were identified to harbor compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys). Upon molecular diagnosis, the proband underwent successful hematopoietic stem cell transplantation and demonstrated marked clinical improvement of all IBD-associated clinical symptoms. Exome sequencing can be an effective tool to aid in the molecular diagnosis of pediatric-onset IBD. We provide additional evidence of the safety and benefit of HSCT for patients with IBD due to mutations in the IL10RA gene. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dinwiddie, Darrell L.; Soden, Sarah E.; Saunders, Carol J.; Miller, Neil A.; Kingsmore, Stephen F.] Childrens Mercy Hosp, Ctr Pediat Genom Med, Kansas City, MO 64108 USA. [Dinwiddie, Darrell L.; Bracken, Julia M.; Bass, Julie A.; Christenson, Kathy; Soden, Sarah E.; Saunders, Carol J.; Miller, Neil A.; Roberts, Charles C.; Dalal, Jignesh; Kingsmore, Stephen F.] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Dinwiddie, Darrell L.; Saunders, Carol J.; Singh, Vivekanand; Zwick, David L.; Kingsmore, Stephen F.] Childrens Mercy Hosp, Dept Pathol, Kansas City, MO 64108 USA. [Dinwiddie, Darrell L.; Bracken, Julia M.; Bass, Julie A.; Soden, Sarah E.; Saunders, Carol J.; Singh, Vivekanand; Zwick, David L.; Roberts, Charles C.; Dalal, Jignesh; Kingsmore, Stephen F.] Univ Missouri, Sch Med, Kansas City, MO 64110 USA. [Dalal, Jignesh] Childrens Mercy Hosp, Div Hematol Oncol, Kansas City, MO 64108 USA. [Bracken, Julia M.; Bass, Julie A.; Christenson, Kathy; Roberts, Charles C.] Childrens Mercy Hosp, Div Pediat Gastroenterol, Kansas City, MO 64108 USA. [Dinwiddie, Darrell L.] Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. [Dinwiddie, Darrell L.] Univ New Mexico, Clin Translat Sci Ctr, Albuquerque, NM 87131 USA. RP Dinwiddie, DL (reprint author), 1 Univ New Mexico, MSC08 4635, Albuquerque, NM 87131 USA. EM dldinwiddie@salud.unm.edu; jmbracken@cmh.edu; jabass@cmh.edu; kchristenson@cmh.edu; ssoden@cmh.edu; csaunders@cmh.edu; nmiller@cmh.edu; vsingh@cmh.edu; dzwick@cmh.edu; croberts@cmh.edu; jddalal@cmh.edu; sfkingsmore@cmh.edu FU Marion Merrell Dow Foundation; Patton Trust; WT Kemper Foundation; Children's Mercy Hospital FX This work was funded by the Marion Merrell Dow Foundation, the Patton Trust, the WT Kemper Foundation and Children's Mercy Hospital. 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E., 2012, J GENOMES EXOMES, V1, P15 Stenson Peter D, 2009, Hum Genomics, V4, P69 Worthey EA, 2011, GENET MED, V13, P255, DOI 10.1097/GIM.0b013e3182088158 Wu TD, 2010, BIOINFORMATICS, V26, P873, DOI 10.1093/bioinformatics/btq057 NR 35 TC 6 Z9 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV-DEC PY 2013 VL 102 IS 5-6 BP 442 EP 447 DI 10.1016/j.ygeno.2013.08.008 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 278UE UT WOS:000328914500002 PM 24001973 ER PT J AU Hall, SS Jiang, HD Reiss, AL Greicius, MD AF Hall, Scott S. Jiang, Heidi Reiss, Allan L. Greicius, Michael D. TI Identifying Large-Scale Brain Networks in Fragile X Syndrome SO JAMA PSYCHIATRY LA English DT Article ID MENTAL-RETARDATION PROTEIN; DEFAULT-MODE NETWORK; IDIOPATHIC AUTISM; INSULAR CORTEX; BEHAVIOR; FMRI; IDENTIFICATION; LOCALIZATION; CONNECTIVITY; MORPHOMETRY AB IMPORTANCE Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS. OBJECTIVE To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10-23 years) included 17 males and females with FXS and 16 males and females serving as controls. MAIN OUTCOMES AND MEASURES Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression. RESULTS Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS. CONCLUSIONS AND RELEVANCE Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that insula integrity and connectivity may be compromised in FXS. This method could prove useful in establishing an imaging biomarker for FXS. C1 [Hall, Scott S.; Reiss, Allan L.] Stanford Univ, Ctr Interdisciplinary Brain Sci Res, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Jiang, Heidi; Greicius, Michael D.] Stanford Univ, Funct Imaging Neuropsychiat Disorders Lab, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA. [Reiss, Allan L.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. [Reiss, Allan L.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Reiss, Allan L.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. RP Hall, SS (reprint author), Stanford Univ, Ctr Interdisciplinary Brain Sci Res, Dept Psychiat & Behav Sci, Room 1365,401 Quarry Rd, Stanford, CA 94305 USA. EM hallss@stanford.edu FU National Institutes of Health [K08MH081998, MH064708, NS073498] FX This study was funded by grants K08MH081998 (Dr Hall), MH064708 (Dr Reiss), and NS073498 (Dr Greicius) from the National Institutes of Health. 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Class, Quetzal A. Rickert, Martin E. Larsson, Henrik Langstrom, Niklas Lichtenstein, Paul TI Preterm Birth and Mortality and Morbidity A Population-Based Quasi-experimental Study SO JAMA PSYCHIATRY LA English DT Article ID SWEDISH NATIONAL COHORT; MATERNAL SMOKING; RISK-FACTORS; GESTATIONAL-AGE; SOCIOECONOMIC ACHIEVEMENTS; PSYCHIATRIC-DISORDER; BEHAVIORAL OUTCOMES; BIPOLAR DISORDER; INDIVIDUALS BORN; YOUNG ADULTHOOD AB IMPORTANCE Preterm birth is associated with increased mortality and morbidity. However, previous studies have been unable to rigorously examine whether confounding factors cause these associations rather than the harmful effects of being born preterm. OBJECTIVE To estimate the extent to which the associations between early gestational age and offspring mortality and morbidity are the result of confounding factors by using a quasi-experimental design, the sibling-comparison approach, and by controlling for statistical covariates that varied within families. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study, combining Swedish registries to identify all individuals born in Sweden from 1973 to 2008 (3 300 708 offspring of 1 736 735 mothers) and link them with multiple outcomes. MAIN OUTCOMES AND MEASURES Offspring mortality (during infancy and throughout young adulthood) and psychiatric (psychotic or bipolar disorder, autism, attention-deficit/hyperactivity disorder, suicide attempts, substance use, and criminality), academic (failing grades and educational attainment), and social (partnering, parenthood, low income, and social welfare benefits) outcomes through 2009. RESULTS In the population, there was a dose-response relationship between early gestation and the outcome measures. For example, extreme preterm birth (23-27 weeks of gestation) was associated with infant mortality (odds ratio, 288.1; 95% CI, 271.7-305.5), autism (hazard ratio [HR], 3.2; 95% CI, 2.6-4.0), low educational attainment (HR, 1.7; 1.5-2.0), and social welfare benefits (HR, 1.3; 1.2-1.5) compared with offspring born at term. The associations between early gestation and mortality and psychiatric morbidity generally were robust when comparing differentially exposed siblings and controlling for statistical covariates, whereas the associations with academic and some social problems were greatly or completely attenuated in the fixed-effects models. CONCLUSIONS AND RELEVANCE The mechanisms responsible for the associations between preterm birth and mortality and morbidity are outcome-specific. Associations between preterm birth and mortality and psychiatric morbidity are largely independent of shared familial confounds and measured covariates, consistent with a causal inference. However, some associations, particularly predicting suicide attempt, educational attainment, and social welfare benefits, are the result of confounding factors. The findings emphasize the importance of both reducing preterm birth and providing wraparound services to all siblings in families with an offspring born preterm. C1 [D'Onofrio, Brian M.; Class, Quetzal A.; Rickert, Martin E.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Larsson, Henrik; Langstrom, Niklas; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP D'Onofrio, BM (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA. EM bmdonofr@indiana.edu FU National Institute of Child Health and Human Development [HD061817]; National Institute of Mental Health [MH094011]; Swedish Research Council (Medicine); Swedish Prison and Probation Services FX The study was supported by grant HD061817 from the National Institute of Child Health and Human Development, grant MH094011 from the National Institute of Mental Health), the Swedish Research Council (Medicine), and the Swedish Prison and Probation Services. CR Academy of Medical Sciences Working Group, 2007, IDENTIFYING THE ENVI Allison P. 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Williams, David M. Raber, Jacob Peel, Anna Bowler, Dermot M. TI Spatial Navigation Impairments Among Intellectually High-Functioning Adults With Autism Spectrum Disorder: Exploring Relations With Theory of Mind, Episodic Memory, and Episodic Future Thinking SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE autism spectrum disorder; episodic memory; episodic future thinking; spatial navigation; theory of mind ID ASPERGER-SYNDROME; SEX-DIFFERENCES; ANIMATED SHAPES; COGNITIVE MAPS; MENTAL STATES; KNOWLEDGE; BRAIN; CHILDREN; ABILITY; HUMANS AB Research suggests that spatial navigation relies on the same neural network as episodic memory, episodic future thinking, and theory of mind (ToM). Such findings have stimulated theories (e. g., the scene construction and self-projection hypotheses) concerning possible common underlying cognitive capacities. Consistent with such theories, autism spectrum disorder (ASD) is characterized by concurrent impairments in episodic memory, episodic future thinking, and ToM. However, it is currently unclear whether spatial navigation is also impaired. Hence, ASD provides a test case for the scene construction and self-projection theories. The study of spatial navigation in ASD also provides a test of the extreme male brain theory of ASD, which predicts intact or superior navigation (purportedly a systemizing skill) performance among individuals with ASD. Thus, the aim of the current study was to establish whether spatial navigation in ASD is impaired, intact, or superior. Twenty-seven intellectually high-functioning adults with ASD and 28 sex-, age-, and IQ-matched neurotypical comparison adults completed the memory island virtual navigation task. Tests of episodic memory, episodic future thinking, and ToM were also completed. Participants with ASD showed significantly diminished performance on the memory island task, and performance was positively related to ToM and episodic memory, but not episodic future thinking. These results suggest that (contra the extreme male brain theory) individuals with ASD have impaired survey-based navigation skills-that is, difficulties generating cognitive maps of the environment-and adds weight to the idea that scene construction/self-projection are impaired in ASD. The theoretical and clinical implications of these results are discussed. C1 [Lind, Sophie E.; Williams, David M.; Peel, Anna] Univ Durham, Dept Psychol, Durham DH1 3HP, England. [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Bowler, Dermot M.] City Univ London, Dept Psychol, London EC1R 0JD, England. RP Lind, SE (reprint author), City Univ London, Dept Psychol, Whiskin St, London EC1R 0JD, England. 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Abnorm. Psychol. PD NOV PY 2013 VL 122 IS 4 BP 1189 EP 1199 DI 10.1037/a0034819 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 280PU UT WOS:000329044000025 PM 24364620 ER PT J AU Rhodes, G Jeffery, L Taylor, L Ewing, L AF Rhodes, Gillian Jeffery, Linda Taylor, Libby Ewing, Louise TI Autistic traits are linked to reduced adaptive coding of face identity and selectively poorer face recognition in men but not women SO NEUROPSYCHOLOGIA LA English DT Article DE Autistic traits; Broader autism phenotype; Face recognition; Face identity aftereffects; Individual differences ID SPECTRUM QUOTIENT AQ; MEMORY TEST; INDIVIDUAL-DIFFERENCES; ENDOPHENOTYPE CONCEPT; CHILDREN; PHENOTYPE; ABILITY; POPULATION; ADAPTATION; PERCEPTION AB Our ability to discriminate and recognize thousands of faces despite their similarity as visual patterns relies on adaptive, norm-based, coding mechanisms that are continuously updated by experience. Reduced adaptive coding of face identity has been proposed as a neurocognitive endophenotype for autism, because it is found in autism and in relatives of individuals with autism. Autistic traits can also extend continuously into the general population, raising the possibility that reduced adaptive coding of face identity may be more generally associated with autistic traits. In the present study, we investigated whether adaptive coding of face identity decreases as autistic traits increase in an undergraduate population. Adaptive coding was measured using face identity aftereffects, and autistic traits were measured using the Autism-Spectrum Quotient (AQ) and its subscales. We also measured face and car recognition ability to determine whether autistic traits are selectively related to face recognition difficulties. We found that men who scored higher on levels of autistic traits related to social interaction had reduced adaptive coding of face identity. This result is consistent with the idea that atypical adaptive face-coding mechanisms are an endophenotype for autism. Autistic traits were also linked with face-selective recognition difficulties in men. However, there were some unexpected sex differences. In women, autistic traits were linked positively, rather than negatively, with adaptive coding of identity, and were unrelated to face-selective recognition difficulties. These sex differences indicate that autistic traits can have different neurocognitive correlates in men and women and raise the intriguing possibility that endophenotypes of autism can differ in males and females. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Rhodes, Gillian; Jeffery, Linda; Taylor, Libby; Ewing, Louise] Univ Western Australia, Sch Psychol, ARC Ctr Excellence Cognit & Its Disorders, Crawley, WA 6009, Australia. RP Rhodes, G (reprint author), Univ Western Australia, Sch Psychol, ARC Ctr Excellence Cognit & Its Disorders, 35 Stirling Highway, Crawley, WA 6009, Australia. EM gillian.rhodes@uwa.edu.au RI Ewing, Louise/H-9158-2014 FU Australian Research Council Centre of Excellence [CE110001021]; ARC Professorial Fellowship [DP0877379]; ARC Discovery Outstanding Researcher Award [DP130102300] FX This research was supported by the Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021), an ARC Professorial Fellowship to Rhodes (DP0877379) and an ARC Discovery Outstanding Researcher Award to Rhodes (DP130102300). We thank Mayu Nishimura and Daphne Maurer for co-creating the Robbers Game used in the Identity Aftereffects task and Ainsley Read for assistance with testing. Ethical approval was granted by the Human Research Ethics Committee of the University of Western Australia. 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TI Fragile X Syndrome: From Protein Function to Therapy SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Review DE fragile X syndrome; FMR1; FMRP; intellectual disability; treatment; review; Fmr1 KO mouse; protein function ID MENTAL-RETARDATION PROTEIN; LONG-TERM DEPRESSION; FMR1 KNOCKOUT MICE; MESSENGER-RNA LOCALIZATION; PRIMARY SOMATOSENSORY CORTEX; MOUSE MODEL; SYNAPTIC PLASTICITY; GABA(A) RECEPTOR; DENDRITIC SPINES; BINDING PROTEIN AB Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. 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A PD NOV PY 2013 VL 161 IS 11 SI SI BP 2809 EP 2821 DI 10.1002/ajmg.a.36241 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 267ZP UT WOS:000328137500018 PM 24115651 ER PT J AU De Wolf, V Brison, N Devriendt, K Peeters, H AF De Wolf, Veerle Brison, Nathalie Devriendt, Koenraad Peeters, Hilde TI Genetic Counseling for Susceptibility Loci and Neurodevelopmental Disorders: The del15q11.2 as an Example SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Review DE genetic counseling; del15q11; 2; neurodevelopmental disorders; susceptibility locus ID HEREDITARY SPASTIC PARAPLEGIA; PRADER-WILLI-SYNDROME; COPY-NUMBER VARIANTS; DE-NOVO MUTATIONS; VARIABLE EXPRESSIVITY; MENTAL-RETARDATION; NIPA1 GENE; RECURRENT MICRODELETIONS; INTELLECTUAL DISABILITY; DEVELOPMENTAL DELAY AB In recent years, several recurrent copy number variations (CNVs) that confer risk of neurodevelopmental disorders have been identified (e.g., del and dup 16p11.2, del15q13.3, del and dup 1q21.1, del16p13.3, del15q11.2). They are often inherited from an unaffected parent and lack phenotypic specificity. Although there is growing evidence from association studies to consider them as susceptibility CNVs, their clinical utility is debated. Yet the clinician is frequently challenged to deal with these counseling situations without guidelines or consensus. In this report, counseling issues and research opportunities are discussed, with the recurrent 15q11.2 BP1-BP2 (including CYFIP1, NIPA1, NIPA2, TUBGCP5) as an example. Several clinical reports have been published describing patients with del15q11.2 featuring intellectual disability, developmental delay, neurological problems, autism spectrum disorder (ASD), attention problems, speech delay, and dysmorphism. The del15q11.2 was found to be significantly associated with intellectual disability, schizophrenia, epilepsy, and ASD. In this report we discuss how patient-specific and family-specific information may alter the interpretation of del15q11.2 as a contributing factor to the disorder in practical counseling situations. In addition, an association study for ASD in a Belgian Flemish cohort and an overview of reported association studies, clinical reports and genomics data for del15q11.2 are presented. (c) 2013 Wiley Periodicals, Inc. C1 [De Wolf, Veerle; Brison, Nathalie; Devriendt, Koenraad; Peeters, Hilde] Katholieke Univ Leuven, Ctr Human Genet, Univ Hosp Leuven, Louvain, Belgium. RP Peeters, H (reprint author), Univ Louvain, Ctr Human Genet, Herestr 49, B-3000 Louvain, Belgium. EM hilde.peeters@med.kuleuven.be FU Concerted Research Actions KULeuven [GOA/12/015]; Foundation "Marguerite-Marie Delacroix"; Scientific Research-Flanders FWO Belgium; Clinical Research Foundation of UZ Leuven [IWT-O&O-100629-Cartagenia]; Belgian government Interuniversitary Attraction Poles programme; Foundation Jerome Lejeune FX Grant sponsors: Concerted Research Actions KULeuven (GOA/12/015); Foundation "Marguerite-Marie Delacroix"; Foundation Jerome Lejeune; Scientific Research-Flanders FWO Belgium; Clinical Research Foundation of UZ Leuven. IWT-O&O-100629-Cartagenia; Belgian government Interuniversitary Attraction Poles programme. 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J. Med. Genet. A PD NOV PY 2013 VL 161 IS 11 SI SI BP 2846 EP 2854 DI 10.1002/ajmg.a.36209 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 267ZP UT WOS:000328137500021 PM 24123946 ER PT J AU Roman, GC Ghassabian, A Bongers-Schokking, JJ Jaddoe, VWV Hofman, A de Rijke, YB Verhulst, FC Tiemeier, H AF Roman, Gustavo C. Ghassabian, Akhgar Bongers-Schokking, Jacoba J. Jaddoe, Vincent W. V. Hofman, Albert de Rijke, Yolanda B. Verhulst, Frank C. Tiemeier, Henning TI Association of Gestational Maternal Hypothyroxinemia and Increased Autism Risk SO ANNALS OF NEUROLOGY LA English DT Article ID FETAL-BRAIN DEVELOPMENT; GENERATION-R; THYROID-FUNCTION; EARLY-PREGNANCY; NEUROPSYCHOLOGICAL DEVELOPMENT; COMPREHENSIVE METAANALYSIS; BEHAVIORAL-PROBLEMS; SPECTRUM DISORDER; CHILDREN; REELIN AB ObjectiveTransient gestational hypothyroxinemia in rodents induces cortical neuronal migration brain lesions resembling those of autism. We investigated the association between maternal hypothyroxinemia (gestational weeks 6-18) and autistic symptoms in children. MethodsThe mother-and-child cohort of the Generation R Study (Rotterdam, the Netherlands) began prenatal enrollment between 2002 and 2006. At a mean gestational age of 13.4 weeks (standard deviation = 1.9, range = 5.9-17.9), maternal thyroid function tests (serum thyrotropin [TSH], free thyroxine [fT(4)], and thyroid peroxidase [TPO] antibodies) were assessed in 5,100 women. We defined severe maternal hypothyroxinemia as fT(4) < 5th percentile with normal TSH. Six years later, parents reported behavioral and emotional symptoms in 4,039 children (79%) using the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist and/or the Social Responsiveness Scale (SRS). We defined a probable autistic child by a PDP score > 98th percentile and SRS score in the top 5% of the sample (n = 81, 2.0%). ResultsSevere maternal hypothyroxinemia (n = 136) was associated with an almost 4-fold increase in the odds of having a probable autistic child (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 1.83-8.20, p < 0.001). Using PDP scores, children of mothers with severe hypothyroxinemia had higher scores of autistic symptoms by age 6 years (adjusted B = 0.23, 95% CI = 0.03-0.37); SRS results were similar. No risk was found for children of TPO-antibody-positive mothers (n = 308). InterpretationWe found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring. Findings are concordant with epidemiological, biological, and experimental data on autism. Although these findings cannot establish causality, they open the possibility of preventive interventions. Ann Neurol 2013;74:733-742 C1 [Roman, Gustavo C.] Methodist Neurol Inst, Houston, TX 77030 USA. [Roman, Gustavo C.] Weill Cornell Med Coll, Dept Neurol, New York, NY USA. [Ghassabian, Akhgar; Jaddoe, Vincent W. V.; Hofman, Albert] Generat R Study Grp, Rotterdam, Netherlands. [Ghassabian, Akhgar; Verhulst, Frank C.; Tiemeier, Henning] Erasmus Univ, Dept Child & Adolescent Psychiat, Med Ctr, Rotterdam, Netherlands. [Bongers-Schokking, Jacoba J.; Jaddoe, Vincent W. V.; Hofman, Albert; Tiemeier, Henning] Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands. [Bongers-Schokking, Jacoba J.] Erasmus Univ, Dept Endocrinol, Med Ctr, Rotterdam, Netherlands. [Jaddoe, Vincent W. V.] Erasmus Univ, Dept Pediat, Med Ctr, Rotterdam, Netherlands. [de Rijke, Yolanda B.] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands. [de Rijke, Yolanda B.] Erasmus Univ, Dept Clin Chem, Med Ctr, Rotterdam, Netherlands. [Tiemeier, Henning] Erasmus Univ, Dept Psychiat, Med Ctr, Rotterdam, Netherlands. RP Roman, GC (reprint author), Methodist Neurol Inst, 6560 Fannin St,Suite 802, Houston, TX 77030 USA. EM GCRoman@tmhs.org FU Nancy Lurie Marks Family Foundation, Wellesley, Massachusetts; European Community [212652]; Erasmus University Trust Fund; Janivo Foundation; Merck-Serono; Dutch Research Council; Ministry of Family Affairs (the Netherlands) FX The work of G.C.R. is supported by a grant from the Nancy Lurie Marks Family Foundation, Wellesley, Massachusetts. The work of H.T. and A.G. was supported by a research grant from the European Community's 7th Framework Program (FP7/2008-2013) under grant agreement 212652 (Nutrimenthe project, "The Effect of Diet on the Mental Performance of Children"). Measurements of thyroid parameters have been made possible by Ortho Clinical Diagnostics, Jan Dekker/Ludgardine Bouwman Foundation, Fa. Merck, and Foundation Zeist. Funding was also received from the Erasmus University Trust Fund, Janivo Foundation, Merck-Serono, Dutch Research Council, and Ministry of Family Affairs (the Netherlands). 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Neurol. PD NOV PY 2013 VL 74 IS 5 BP 733 EP 742 DI 10.1002/ana.23976 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 273NX UT WOS:000328543200013 PM 23943579 ER PT J AU Johnson, RA Barrett, MS Sisti, DA AF Johnson, Rebecca A. Barrett, Marna S. Sisti, Dominic A. TI The Ethical Boundaries of Patient and Advocate Influence on DSM-5 SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE Diagnostic and Statistical Manual of Mental Disorders; ethics; mental disorders; patient advocacy; social stigma ID PSYCHOSIS RISK SYNDROME; MENTAL-ILLNESS; DIAGNOSTIC-CRITERIA; DECISION-MAKING; UNITED-STATES; HEALTH; DISORDER; HEBEPHILIA; POLICY; CLASSIFICATION AB This article discusses the relationship between disease-advocacy groups and the revision process for the Diagnostic and Statistical Manual of Mental Disorders. We discuss three examples in which patient-advocacy groups engaged with the DSM-5 revision process: Autism Speaks' worries about the contraction of the autism diagnostic category, the National Alliance on Mental Illness's support for the inclusion of psychosis risk syndrome, and B4U-ACT's critique of the expansion of pedophilia. After a descriptive examination of the cases, we address two prescriptive questions. First, what is the ethical basis for patient and advocate influence on DSM diagnoses? Second, how should the American Psychiatric Association proceed when this influence comes into conflict with other goals of the revision process? We argue that the social effects of, and values embedded in, psychiatric classification, combined with patient and advocates' experiential knowledge about those aspects of diagnosis, ethically justify advocate influence in relation to those particular matters. However, this advocate influence ought to have limits, which we briefly explore. Our discussion has implications for discussions of disease categories as loci for social movements, for analyses of the expanding range of processes and institutions that advocacy groups target, and for broader questions regarding the aims of the DSM revision process. C1 [Johnson, Rebecca A.] Univ Penn, Perelman Sch Med, Dept Bioeth, NIH, Philadelphia, PA 19104 USA. [Johnson, Rebecca A.; Sisti, Dominic A.] Univ Penn, Perelman Sch Med, Scattergood Program Appl Eth Behav Healthcare, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Barrett, Marna S.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Johnson, RA (reprint author), 10 Ctr Dr,Rm 1C118, Bethesda, MD 20892 USA. 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We set two goals: first, to assess the effectiveness based on the score the participants obtained from the Revised Clinical Scale for the Evaluation of Autistic Behavior (ECA-R) after a series of dance/movement and music therapeutic procedures on adults with severe autism; second, to contrast the differences in effectiveness in concrete areas defined by subscales of the ECA-R, especially in its defined 2 factors and 12 functions. An overall of 36 one-hour sessions were carried out during 17 weeks on a sample of 8 participants with severe autism (approximately 2 sessions per week). During the treatment 8 measurements were taken (1 every 3 weeks) from this sample and from a control sample, which was also comprised of 8 subjects who were equally monitored at the same care center by two independent psychologists. Our experimental study seems to suggest that combined dance/movement and music therapy could be effective if used regularly for the improvement of autistic symptoms in adults diagnosed with severe autism. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mateos-Moreno, Daniel; Atencia-Dona, Lidia] Univ Malaga, E-29071 Malaga, Spain. RP Mateos-Moreno, D (reprint author), Univ Malaga, Fac Psicol & Ciencias Educ, Campus Teatinos S-N, E-29071 Malaga, Spain. EM danielmm@uma.es CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Asociacion Espanola de Danza Movimiento Terapia, 2001, QUE DMT Barthelemy C., 2003, ECHELLE EVALUATION C BARTHELEMY C, 1990, Brain Dysfunction, V3, P271 Barthelemy C, 1997, J AUTISM DEV DISORD, V27, P139, DOI 10.1023/A:1025887723360 Boso M, 2007, J ALTERN COMPLEM MED, V13, P709, DOI 10.1089/acm.2006.6334 Brown S, 2004, NEUROREPORT, V15, P2033, DOI 10.1097/00001756-200409150-00008 Capello P., 2008, VIDA DANZA ARTE CIEN Clair A. 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PD NOV PY 2013 VL 40 IS 5 BP 465 EP 472 DI 10.1016/j.aip.2013.09.004 PG 8 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 270JO UT WOS:000328314900003 ER PT J AU Mesman, J Emmen, RAG AF Mesman, Judi Emmen, Rosanneke A. G. TI Mary Ainsworth's legacy: a systematic review of observational instruments measuring parental sensitivity SO ATTACHMENT & HUMAN DEVELOPMENT LA English DT Review DE maternal sensitivity; observation; instruments; positive affect; review ID INFANT-MOTHER ATTACHMENT; RANDOMIZED CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDER; MATERNAL SENSITIVITY; EMOTIONAL AVAILABILITY; DIFFERENTIAL SUSCEPTIBILITY; COGNITIVE-DEVELOPMENT; CHILDRENS DEVELOPMENT; ENVIRONMENTAL-FACTORS; POSTNATAL DEPRESSION AB Since Mary Ainsworth's formulation of the Sensitivity-Insensitivity to Infant Signals and Communications observational scale, new instruments have been developed to observe parental sensitivity. In this paper, we provide an overview of eight commonly used observational instruments to measure parental sensitivity. Their similarities and differences in comparison to the original Ainsworth sensitivity construct and its applications will be discussed. Consistent with the search criteria, each of the instruments clearly includes the key elements of Ainsworth's definition of sensitivity. Notable deviations from the original scale are the use of composite scales rather than a single global scale and the related inclusion of new elements, and specifically the inclusion of positive affect as an indicator of sensitivity. Further, most of the instruments have a wider scope than Ainsworth's sensitivity scale in terms of target age groups and the assessment of sensitivity in fathers. We discuss the interpretation of the sensitivity construct depending on variations in how the construct is defined in different observational instruments, and advances in the application of the construct. 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Hum. Dev. PD NOV 1 PY 2013 VL 15 IS 5-6 SI SI BP 485 EP 506 DI 10.1080/14616734.2013.820900 PG 22 WC Psychology, Developmental SC Psychology GA 268SC UT WOS:000328189800004 PM 24299131 ER PT J AU Edvardson, S Ashikov, A Jalas, C Sturiale, L Shaag, A Fedick, A Treff, NR Garozzo, D Gerardy-Schahn, R Elpeleg, O AF Edvardson, Simon Ashikov, Angel Jalas, Chaim Sturiale, Luisa Shaag, Avraham Fedick, Anastasia Treff, Nathan R. Garozzo, Domenico Gerardy-Schahn, Rita Elpeleg, Orly TI Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and arthrogryposis SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Neurology ID NUCLEOTIDE-SUGAR TRANSPORTER; UDP-N-ACETYLGLUCOSAMINE; COMPLEX VERTEBRAL MALFORMATION; MOLECULAR-CLONING; GENE; GOLGI; EXPRESSION; IDENTIFICATION; SPECIFICITY; DISEASES AB Background The heritability of autism spectrum disorder is currently estimated at 55%. Identification of the molecular basis of patients with syndromic autism extends our understanding of the pathogenesis of autism in general. The objective of this study was to find the gene mutated in eight patients from a large kindred, who suffered from autism spectrum disorder, arthrogryposis and epilepsy. Methods and results By linkage analysis and exome sequencing, we identified deleterious mutations in SLC35A3 in these patients. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar was significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms. Conclusions Spontaneous mutation in SLC35A3 has been discovered in cattle worldwide, recapitulating the human phenotype with arthrogryposis and additional skeletal defects known as Complex Vertebral Malformation syndrome. The skeletal anomalies in the mutant cattle and in our patients, and perhaps even the neurological symptoms are likely the consequence of the lack of high-branched N-glycans and the concomitant abundance of lower-branched glycoforms at the cell surface. This pattern has previously been associated with growth arrest and induction of differentiation. With this study, we add SLC35A3 to the gene list of autism spectrum disorders, and underscore the crucial importance of UDP-GlcNAc in the regulation of the N-glycan branching pathway in the Golgi apparatus. C1 [Edvardson, Simon; Shaag, Avraham; Elpeleg, Orly] Hadassah Hebrew Univ, Med Ctr, Dept Genet Res, Jerusalem, Israel. [Ashikov, Angel; Gerardy-Schahn, Rita] Hannover Med Sch, Inst Cellular Chem, D-30625 Hannover, Germany. [Jalas, Chaim] Bonei Olam Ctr Rare Jewish Genet Disorders, Brooklyn, NY USA. [Sturiale, Luisa; Garozzo, Domenico] CNR, Inst Chem & Technol Polymers, Sect Catania, I-00185 Rome, Italy. [Fedick, Anastasia; Treff, Nathan R.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet, Piscataway, NJ 08854 USA. [Treff, Nathan R.] Reprod Med Associates New Jersey, Morristown, NJ USA. RP Elpeleg, O (reprint author), Hebrew Univ Jerusalem, Med Ctr, Monique & Jacques Roboh Dept Genet Res, IL-91120 Jerusalem, Israel. EM Gerardy-Schahn.Rita@mh-hannover.de; Elpeleg@Hadassah.org.il RI Garozzo, Domenico/I-8839-2014 OI Garozzo, Domenico/0000-0002-9087-9818 FU Bonei Olam organization FX We are grateful to Professor Jorgen S Agerholm for the contribution of figure 2G. This work was supported in part by Rabbi S Bochner of the Bonei Olam organization and impact oriented funding (LOM) to the Institute of Cellular Chemistry at Hannover Medical School. 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Med. Genet. PD NOV PY 2013 VL 50 IS 11 BP 733 EP 739 DI 10.1136/jmedgenet-2013-101753 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 268AY UT WOS:000328141400003 PM 24031089 ER PT J AU Capo-Chichi, JM Tcherkezian, J Hamdan, FF Decarie, JC Dobrzeniecka, S Patry, L Nadon, MA Mucha, BE Major, P Shevell, M Bencheikh, BOA Joober, R Samuels, ME Rouleau, GA Roux, PP Michaud, JL AF Capo-Chichi, Jose-Mario Tcherkezian, Joseph Hamdan, Fadi F. Decarie, Jean Claude Dobrzeniecka, Sylvia Patry, Lysanne Nadon, Marc-Antoine Mucha, Bettina E. Major, Philippe Shevell, Michael Bencheikh, Bouchra Ouled Amar Joober, Ridha Samuels, Mark E. Rouleau, Guy A. Roux, Philippe P. Michaud, Jacques L. TI Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Clinical genetics; Molecular genetics ID TUBEROUS SCLEROSIS COMPLEX; MUTATIONS; DISORDERS; GERMLINE; RHEB; GENE AB Background Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), a disorder characterised by the development of hamartomas or benign tumours in various organs as well as the variable presence of epilepsy, intellectual disability (ID) and autism. TSC1, TSC2 and the recently described protein TBC1D7 form a complex that inhibits mTORC1 signalling and limits cell growth. Although it has been proposed that mutations in TBC1D7 might also cause TSC, loss of its function has not yet been documented in humans. Methods and Results We used homozygosity mapping and exome sequencing to study a consanguineous family with ID and megalencephaly but without any specific features of TSC. We identified only one rare coding variant, c.538delT:p.Y180fsX1 in TBC1D7, in the regions of homozygosity shared by the affected siblings. We show that this mutation abolishes TBC1D7 expression and is associated with increased mTORC1 signalling in cells of the affected individuals. Conclusions Our study suggests that disruption of TBC1D7 causes ID but without the other typical features found in TSC. Although megalencephaly is not commonly observed in TSC, it has been associated with mTORC1 activation. Our observation thus reinforces the relationship between this pathway and the development of megalencephaly. C1 [Capo-Chichi, Jose-Mario; Hamdan, Fadi F.; Patry, Lysanne; Nadon, Marc-Antoine; Mucha, Bettina E.; Major, Philippe; Samuels, Mark E.; Michaud, Jacques L.] Ctr Hosp Univ CHU St Justine Res Ctr, Montreal, PQ H3T 1C5, Canada. [Tcherkezian, Joseph; Roux, Philippe P.] Univ Montreal, IRIC, Montreal, PQ, Canada. [Decarie, Jean Claude] CHU St Justine, Dept Med Imaging, Montreal, PQ, Canada. [Dobrzeniecka, Sylvia; Bencheikh, Bouchra Ouled Amar] CHUM Res Ctr, Montreal, PQ, Canada. [Shevell, Michael] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Shevell, Michael] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. [Bencheikh, Bouchra Ouled Amar; Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Joober, Ridha] McGill Univ, Douglas Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada. [Roux, Philippe P.] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ, Canada. RP Michaud, JL (reprint author), Ctr Hosp Univ CHU St Justine Res Ctr, 3175 Cote St Catherine, Montreal, PQ H3T 1C5, Canada. EM jacques.michaud@recherche-ste-justine.qc.ca FU March of Dimes [12-FY10-236]; Canadian Institutes for Health Research [MOP123408] FX This work was supported by March of Dimes (grant no. 12-FY10-236 to MS and JLM) and the Canadian Institutes for Health Research (grant no. MOP123408 to PPR). 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Med. Genet. PD NOV PY 2013 VL 50 IS 11 BP 740 EP 744 DI 10.1136/jmedgenet-2013-101680 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 268AY UT WOS:000328141400004 PM 23687350 ER PT J AU Zeyer, A Cetin-Dindar, A Zain, ANM Jurisevic, M Devetak, I Odermatt, F AF Zeyer, Albert Cetin-Dindar, Ayla Zain, Ahmad Nurulazam Md Jurisevic, Mojca Devetak, Iztok Odermatt, Freia TI Systemizing: A Cross-Cultural Constant for Motivation to Learn Science SO JOURNAL OF RESEARCH IN SCIENCE TEACHING LA English DT Article DE motivation; gender; attitudes; cognitive science; international education ID SELF-EFFICACY BELIEFS; STRUCTURAL EQUATION MODELS; HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; NONSCIENCE MAJORS; ASPERGER-SYNDROME; MEASUREMENT INVARIANCE; GENDER-DIFFERENCES; EMPATHY QUOTIENT; SCHOOL-STUDENTS AB The present study is based on the empathizing-systemizing (E-S) theory of cognitive science. It was hypothesized that the influence of students' gender on their motivation to learn science is often overestimated in the research literature and that cognitive style is more important formotivation than students' gender. By using structural equation modeling, and based on previous research, a precise causal model was formulated to test this hypothesis. Then, using multiple group confirmatory analysis, the model was tested in a cross-cultural context that included four countries-Malaysia, Slovenia, Switzerland, andTurkey-and 1,188 upper secondary students. Datawere collected using standard questionnaires on cognitive style andmotivation to learn science. The results showed fullmediation of systemizing-the second dimension of the E-S theory-between gender andmotivation. That is, gender had no direct impact on motivation, but systemizing explained 27% of thevariation in students'motivation scores. The indirect impact of genderwas significant but very low; it explained 1.5% of the variance, in favor of boys. Empathizing-the first dimension of the E-S theory-had noimpact on students' motivation scores. This causalmodel proved to be similar (invariant) in all four cultures. The results suggest that considering students' cognitive style, instead of or in addition to their gender, could lead to a better understanding of students' motivation to learn science. Science teaching methods that support both cognitive styles-systemizing and empathizing-could enhance students' learning of science. (C) 2013Wiley Periodicals, Inc. J Res SciTeach 50: 1047-1067, 2013 C1 [Zeyer, Albert; Odermatt, Freia] Univ Zurich, Inst Educ, CH-8006 Zurich, Switzerland. [Cetin-Dindar, Ayla] Middle E Tech Univ, Fac Educ, TR-06531 Ankara, Turkey. [Zain, Ahmad Nurulazam Md] Univ Sains Malaysia, Sch Educ Studies, George Town, Malaysia. 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Pascual-Pascual, S. I. Viano, J. Gutierrez-Molina, M. Velazquez-Fragua, R. Quinones Tapia, D. Morales Bastos, C. TI Significance of tuber size for complications of tuberous sclerosis complex SO NEUROLOGIA LA Spanish DT Article DE Tuberous sclerosis complex; Tubers; Seizures in tuberous sclerosis complex; Autism in tuberous sclerosis complex; Mental retardation in tuberous sclerosis complex; Magnetic resonance imaging in tuberous sclerosis complex ID GIANT-CELL ASTROCYTOMAS; CORTICAL TUBERS; EPILEPSY SURGERY; INFANTILE SPASMS; CHILDREN; FOCI; MR; POPULATION; IMPAIRMENT; SEVERITY AB Introduction: Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. Objective: The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. Material and methods: We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. Results: Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. Conclusions: Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous. (C) 2012 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved. C1 [Pascual-Castroviejo, I.; Pascual-Pascual, S. I.; Velazquez-Fragua, R.] Hosp Univ La Paz, Serv Neurol, Madrid, Spain. [Hernandez-Moneo, J. L.] Hosp Gen Toledo, Serv Neurocirugia, Toledo, Spain. [Viano, J.; Quinones Tapia, D.] Hosp Rosario, Unidad Imagen, Madrid, Spain. [Gutierrez-Molina, M.; Morales Bastos, C.] Hosp Univ La Paz, Secc Neuropatol, Madrid, Spain. RP Pascual-Castroviejo, I (reprint author), Hosp Univ La Paz, Serv Neurol, Madrid, Spain. 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Selvakumar, Balakrishnan Weil, Zachary M. Snyder, Solomon H. Nelson, Randy J. TI Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE nNOS; p47phox; Schizophrenia; Hippocampus; Autism ID LONG-TERM POTENTIATION; PROTEIN S-NITROSYLATION; HIPPOCAMPAL AREA CA1; KNOCK-OUT MICE; INBRED STRAINS; PREPULSE INHIBITION; SYNAPTIC PLASTICITY; AGGRESSIVE-BEHAVIOR; NUCLEUS-ACCUMBENS; OXIDATIVE STRESS AB Both nitric oxide (NO) and reactive oxygen species (ROS) generated by nNOS and NADPH oxidase (NOX), respectively, in the brain have been implicated in an array of behaviors ranging from learning and memory to social interactions. Although recent work has elucidated how these separate redox pathways regulate neural function and behavior, the interaction of these two pathways in the regulation of neural function and behavior remains unspecified. Toward this end, the p47phox subunit of NOX, and nNOS were deleted to generate double knockout mice that were used to characterize the behavioral outcomes of concurrent impairment of the NO and ROS pathways in the brain. Mice were tested in a battery of behavioral tasks to evaluate learning and memory, as well as social, affective, and cognitive behaviors. p47phox deletion did not affect depressive-like behavior, whereas nNOS deletion abolished it. Both p47phox and nNOS deletion singly reduced anxiety-like behavior, increased general locomotor activity, impaired spatial learning and memory, and impaired preference for social novelty. Deletion of both genes concurrently had synergistic effects to elevate locomotor activity, impair spatial learning and memory, and disrupt prepulse inhibition of acoustic startle. Although preference for social novelty was impaired in single knockouts, double knockout mice displayed elevated levels of preference for social novelty above that of wild type littermates. These data demonstrate that, depending upon modality, deletion of p47phox and nNOS genes have dissimilar, similar, or additive effects. The current findings provide evidence that the NOX and nNOS redox signaling cascades interact in the brain to affect both cognitive function and social behavior. (C) 2013 Elsevier B.V. All rights reserved. C1 [Walton, James C.; Weil, Zachary M.; Nelson, Randy J.] Ohio State Univ, Wexner Med Ctr, Dept Neurosci, Columbus, OH 43210 USA. [Selvakumar, Balakrishnan; Snyder, Solomon H.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. RP Walton, JC (reprint author), Dept Neurosci, 636 Biomed Res Tower,460W,12th Ave, Columbus, OH 43210 USA. EM walton.315@osu.edu RI Walton, James/F-7435-2010; Weil, Zachary/A-2439-2008; Weil, Zachary/B-5003-2008 OI Walton, James/0000-0002-3049-1029; Weil, Zachary/0000-0003-3758-1809 FU NIH [MH18501]; NINDS [P30 NS045758] FX We thank Shan Chen and Erika Sulecki from the Nelson lab for technical assistance. We also thank Masoumeh Saleh from the Snyder lab for technical assistance with maintaining mice. This research was supported by NIH grant MH18501 to SHS, and NINDS grant P30 NS045758 to OSU Neuroscience Center. 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Brain Res. PD NOV 1 PY 2013 VL 256 BP 320 EP 327 DI 10.1016/j.bbr.2013.08.003 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 267JO UT WOS:000328094100040 PM 23948215 ER PT J AU Sacrey, LAR Bryson, SE Zwaigenbaum, L AF Sacrey, Lori-Ann R. Bryson, Susan E. Zwaigenbaum, Lonnie TI Prospective examination of visual attention during play in infants at high-risk for autism spectrum disorder: A longitudinal study from 6 to 36 months of age SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Disengage; Engage; Reaching; Infant sibling; Autism spectrum disorder; Visual attention ID PERVASIVE DEVELOPMENTAL DISORDERS; EYE-HAND COORDINATION; YOUNG-CHILDREN; HOME VIDEOTAPES; DEFICITS; DISENGAGEMENT; RECOGNITION; SACCADES; COMMUNICATION; MOVEMENTS AB Regulation of visual attention is essential to learning about one's environment. Children with autism spectrum disorder (ASD) exhibit impairments in regulating their visual attention, but little is known about how such impairments develop over time. This prospective longitudinal study is the first to describe the development of components of visual attention, including engaging, sustaining, and disengaging attention, in infants at high-risk of developing ASD (each with an older sibling with ASD). Non-sibling controls and high-risk infant siblings were filmed at 6, 9, 12, 15, 18, 24, and 36 months of age as they engaged in play with small, easily graspable toys. Duration of time spent looking at toy targets before moving the hand toward the target and the duration of time spent looking at the target after grasp were measured. At 36 months of age, an independent, gold standard diagnostic assessment for ASD was conducted for all participants. As predicted, infant siblings subsequently diagnosed with ASD were distinguished by prolonged latency to disengage ('sticky attention') by 12 months of age, and continued to show this characteristic at 15, 18, and 24 months of age. The results are discussed in relation to how the development of visual attention may impact later cognitive outcomes of children diagnosed with ASD. (C) 2013 Elsevier B.V. All rights reserved. C1 [Sacrey, Lori-Ann R.; Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. [Bryson, Susan E.] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. [Bryson, Susan E.] Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. [Bryson, Susan E.] IWK Hlth Ctr, Halifax, NS, Canada. [Zwaigenbaum, Lonnie] Glenrose Rehabil Hosp, Edmonton, AB T5G 0B7, Canada. RP Sacrey, LAR (reprint author), Glenrose Rehabil Hosp, Autism Res Ctr E209, 10230-111 Ave, Edmonton, AB T5G 0B7, Canada. EM sacrey@ualberta.ca FU CIHR; Autism Speaks Canada; Stollery Children's Hospital Foundation Chair in Autism Research; Alberta Innovates-Health Solutions Scholar Award; Craig Chair in Autism Research; Dalhousie Medical Research Foundation; CIHR Autism Research Training Program Postdoctoral Fellowship award FX The authors would like to thank Ellen Robertson for her assistance in the collection and blinding of infant tapes. This research is supported by CIHR and Autism Speaks Canada. LZ is supported by the Stollery Children's Hospital Foundation Chair in Autism Research and an Alberta Innovates-Health Solutions Scholar Award. SEB is supported by the Craig Chair in Autism Research and the Dalhousie Medical Research Foundation. LRS is supported by a CIHR Autism Research Training Program Postdoctoral Fellowship award. 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Brain Res. PD NOV 1 PY 2013 VL 256 BP 441 EP 450 DI 10.1016/j.bbr.2013.08.028 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 267JO UT WOS:000328094100054 PM 24004846 ER PT J AU Ey, E Torquet, N Le Sourd, AM Leblond, CS Boeckers, TM Faure, P Bourgeron, T AF Ey, Elodie Torquet, Nicolas Le Sourd, Anne-Marie Leblond, Claire S. Boeckers, Tobias M. Faure, Philippe Bourgeron, Thomas TI The Autism ProSAP1/Shank2 mouse model displays quantitative and structural abnormalities in ultrasonic vocalisations SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism spectrum disorder; Mouse model; ProSAP1/Shank2; Synaptic protein; Ultrasonic vocalization; Peak frequency ID SPECTRUM DISORDER; MUTANT MICE; FEMALE MICE; SHANK3; BEHAVIORS; MUTATIONS; AGE; DYSFUNCTION; DEFECTS; SONGS AB Mouse ultrasonic vocalisations have been often used as a paradigm to extrapolate vocal communication defects observed in patients with autism spectrum disorders (ASD). The role of these vocalisations as well as their development, structure and informational content, however, remain largely unknown. In the present study, we characterised in depth the emission of pup and adult ultrasonic vocalisations of wild-type mice and their ProSAP1/Shank2(-/-) littermates lacking a synaptic scaffold protein mutated in ASD. We hypothesised that the vocal behaviour of ProSAP1/Shank2(-/-) mice not only differs from the vocal behaviour of their wild-type littermates in a quantitative way, but also presents more qualitative abnormalities in temporal organisation and acoustic structure. We first quantified the rate of emission of ultrasonic vocalisations, and analysed the organisation of vocalisations sequences using Markov models. We subsequently measured duration and peak frequency characteristics of each ultrasonic vocalisation, to characterise their acoustic structure. In wild-type mice, we found a high level of organisation in sequences of ultrasonic vocalisations, suggesting a communicative function in this complex system. Very limited significant sex-related variations were detected in their usage and acoustic structure, even in adult mice. In adult ProSAP1/Shank2(-/-) mice, we found abnormalities in the call usage and the structure of ultrasonic vocalisations. Both ProSAP1/Shank2(-/-) male and female mice uttered less vocalisations with a different call distribution and at lower peak frequency in comparison with wild-type littermates. This study provides a comprehensive framework to characterise abnormalities of ultrasonic vocalisations in mice and confirms that ProSAP1/Shank2(-/-) mice represent a relevant model to study communication defects. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved. C1 [Ey, Elodie; Torquet, Nicolas; Le Sourd, Anne-Marie; Leblond, Claire S.; Bourgeron, Thomas] Inst Pasteur, F-75015 Paris, France. [Ey, Elodie; Torquet, Nicolas; Le Sourd, Anne-Marie; Leblond, Claire S.; Bourgeron, Thomas] Inst Pasteur, CNRS URA Genes Synapses & Cognit 2182, F-75015 Paris, France. [Ey, Elodie; Torquet, Nicolas; Le Sourd, Anne-Marie; Leblond, Claire S.; Bourgeron, Thomas] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Boeckers, Tobias M.] Univ Ulm, Inst Anat & Cell Biol, D-89069 Ulm, Germany. [Faure, Philippe] Univ Paris 06, CNRS, UMR 7102, Paris, France. [Faure, Philippe; Bourgeron, Thomas] Lab Excellence Biol Psychiat Labex BIOPSY, Paris, France. RP Ey, E (reprint author), Inst Pasteur, 25 Rue Docteur Roux, F-75015 Paris, France. EM elodie.ey@pasteur.fr FU Fondation de France; ANR FLEXNEURIM [ANRO9BLANO34003, ANR08-MNPS-037-01-SynGen]; Neuron-ERANET (EUHF-AUTISM); Fondation Orange; Fondation FondaMentale; Fondation Bettencourt-Schueller; Innovative Medicines Initiative Joint Undertaking [115300]; European Union FX This work was supported by the Fondation de France; by the ANR FLEXNEURIM [ANRO9BLANO34003]; by the ANR [ANR08-MNPS-037-01-SynGen]; by Neuron-ERANET (EUHF-AUTISM); by the Fondation Orange; by the Fondation FondaMentale; by the Fondation Bettencourt-Schueller. The research leading to these results has also received 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) and EFPIA companies' in kind contribution. 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Using functional connectivity MRI and graph theory, we found that local functional connectivity was atypically increased in adolescents with ASD in temporo-occipital regions bilaterally. Posterior overconnectivity was found to be associated with higher ASD symptom severity, whereas an ASD subsample with low severity showed frontal underconnectivity. The findings suggest links between symptomatology and local connectivity, which vary within the autism spectrum. C1 [Keown, Christopher Lee; Nair, Aarti; Peterson, Nick; Mulvey, Mark Edward; Mueller, Ralph-Axel] San Diego State Univ, Brain Dev Imaging Lab, Dept Psychol, San Diego, CA 92120 USA. [Keown, Christopher Lee; Mulvey, Mark Edward] San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92182 USA. [Shih, Patricia] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Nair, Aarti; Mueller, Ralph-Axel] San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. [Nair, Aarti; Mueller, Ralph-Axel] Univ Calif San Diego, San Diego, CA 92182 USA. [Peterson, Nick] San Diego State Univ, Dept Math & Stat, San Diego, CA 92182 USA. RP Muller, RA (reprint author), San Diego State Univ, Brain Dev Imaging Lab, Dept Psychol, San Diego, CA 92120 USA. EM rmueller@mail.sdsu.edu FU National Institutes of Health [R01-MH081023]; Autism Speaks (Dennis Weatherstone Predoctoral Fellowship) [7850]; NIH [T32-MH020068] FX This study was supported by the National Institutes of Health (R01-MH081023) with additional funding from Autism Speaks (Dennis Weatherstone Predoctoral Fellowship 7850 to A.N.) and NIH T32-MH020068 (to P.S.). Special thanks to the participants and their families. 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Khouzam, Amirah Phillips, Jennifer Gaillard, William D. Kenworthy, Lauren E. Yerys, Benjamin E. Vaidya, Chandan J. Menon, Vinod TI Brain Hyperconnectivity in Children with Autism and its Links to Social Deficits SO CELL REPORTS LA English DT Article ID STATE FUNCTIONAL MRI; LOW-FREQUENCY FLUCTUATION; SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; PREFRONTAL CORTEX; NEURAL SYSTEMS; CONNECTIVITY; NETWORK; ORGANIZATION; UNDERCONNECTIVITY AB Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism. C1 [Supekar, Kaustubh; Uddin, Lucina Q.; Khouzam, Amirah; Phillips, Jennifer; Menon, Vinod] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA. [Gaillard, William D.; Kenworthy, Lauren E.; Yerys, Benjamin E.; Vaidya, Chandan J.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA. [Yerys, Benjamin E.] Grad Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19146 USA. [Vaidya, Chandan J.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Menon, Vinod] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94304 USA. [Menon, Vinod] Stanford Univ, Sch Med, Program Neurosci, Stanford, CA 94304 USA. [Menon, Vinod] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94304 USA. RP Supekar, K (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA. EM ksupekar@stanford.edu; menon@stanford.edu FU Singer Foundation; Isadore and Bertha Gudelsky Foundation; Stanford Institute for Neuro-Innovation & Translational Neurosciences; Children's National Medical Center; National Institutes of Health [HD047520, HD059205, DC0111095, MH084164, MH084961, K01MH092288, K23MH086111, P30HD40677] FX This research was supported by grants from the Singer Foundation, the Isadore and Bertha Gudelsky Foundation, Stanford Institute for Neuro-Innovation & Translational Neurosciences, Children's National Medical Center, and the National Institutes of Health (grants HD047520, HD059205, DC0111095, MH084164, MH084961, K01MH092288, K23MH086111, and P30HD40677). We would like to thank Brian Koser and Dan Hall for their valuable assistance in obtaining data from the National Database of Autism Research. We greatly appreciate the contributions of the participants, without whom this work would not be possible. 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C. TI Extracellular Mitochondrial ATP, Suramin, and Autism? (vol 35, pg 1454, 2013) SO CLINICAL THERAPEUTICS LA English DT Correction CR Theoharides TC, 2013, CLIN THER, V35, P1454, DOI 10.1016/j.clinthera.2013.07.419 NR 1 TC 0 Z9 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2013 VL 35 IS 11 BP 1863 EP 1863 DI 10.1016/j.clinthera.2013.10.003 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267LF UT WOS:000328098500022 ER PT J AU Gentile, I Zappulo, E Coppola, N Bonavolta, R Portella, G Cernia, DS Riccio, MP Settimi, A Pascotto, A Borgia, G Bravaccio, C AF Gentile, Ivan Zappulo, Emanuela Coppola, Nicola Bonavolta, Raffaele Portella, Giuseppe Cernia, Daniela Spalletti Riccio, Maria Pia Settimi, Alessandro Pascotto, Antonio Borgia, Guglielmo Bravaccio, Carmela TI Prevalence of HHV-6 and HHV-8 Antibodies in Patients with Autism Spectrum Disorders SO IN VIVO LA English DT Article DE Autism spectrum disorder; HHV-6; HHV-8 ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; HERPES-SIMPLEX ENCEPHALITIS; EPSTEIN-BARR-VIRUS; HUMAN HERPESVIRUS-6; MULTIPLE-SCLEROSIS; VIRAL-INFECTIONS; DEVELOPMENTAL REGRESSION; ANTIVIRAL DEFENSE; INFANTILE-AUTISM; EXANTHEM-SUBITUM AB Background/Aim: The etiology of autism spectrum disorders (ASD) still eludes investigators. Several viral infections have been associated with ASD etiopathogenesis but few studies have ever focused on the role of HHV-6 and HHV-8, two members of the herpesviridae family. The aim of the present study was to evaluate seropositivity rate and levels of antibodies to HHV6 and HHV-8 in children with ASD compared to controls. Patients and Methods: We measured and compared seropositivity rate and levels of antibodies to HHV-6 and HHV-8 in 30 children with ASD (14 with autistic disorder and 16 with non-autistic disorder ASD) and in 28 healthy controls of the same age. Results: Seropositivity rate and levels of the two antibodies were similar in cases and controls. Seropositivity rate and levels of antibodies were not correlated with disease severity in children with ASD. Conclusion: Levels and seropositivity rate of antibodies to HHV-6 and HHV-8 do not differ between children with ASD and controls. 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Thompson, Paul M. TI Mapping connectivity in the developing brain SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Development; Brain connectivity; DTI; HARDI; rs-fMRI; Autism; ADHD; Fragile X; 22q11.2 DS; Turner syndrome; Williams syndrome ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; STATE FUNCTIONAL CONNECTIVITY; WHITE-MATTER DEVELOPMENT; HUMAN CEREBRAL-CORTEX; FRAGILE-X-SYNDROME; 22Q11.2 DELETION SYNDROME; DEFAULT MODE NETWORK; DIFFUSION-TENSOR; SEX-DIFFERENCES AB Recently, there has been a wealth of research into structural and functional brain connectivity, and how they change over development. While we are far from a complete understanding, these studies have yielded important insights into human brain development. There is an ever growing variety of methods for assessing connectivity, each with its own advantages. Here we review research on the development of structural and/or functional brain connectivity in both typically developing subjects and subjects with neurodevelopmental disorders. Space limitations preclude an exhaustive review of brain connectivity across all developmental disorders, so we review a representative selection of recent findings on brain connectivity in autism, Fragile X, 22q11.2 deletion syndrome. Williams syndrome; Turner syndrome, and ADHD. Major strides have been made in understanding the developmental trajectory of the human connectome, offering insight into characteristic features of brain development and biological processes involved in developmental brain disorders. We also discuss some common themes, including hemispheric specialization - or asymmetry - and sex differences. We conclude by discussing some promising future directions in connectomics, including the merger of imaging and genetics, and a deeper investigation of the relationships between structural and functional connectivity. (C) 2013 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Dennis, Emily L.; Thompson, Paul M.] Univ Calif Los Angeles, Imaging Genet Ctr, Lab Neuro Imaging, Sch Med, Los Angeles, CA 90095 USA. RP Dennis, EL (reprint author), Univ Calif Los Angeles, Imaging Genet Ctr, Lab Neuro Imaging, Sch Med, 635 Charles Young Dr South,Suite 225, Los Angeles, CA 90095 USA. EM eldennis@ucla.edu FU NIH Training Grant in Neurobehavioral Genetics [T32MH073526-06]; National Institute of Child Health and Human Development [R01 HD050735]; National Health and Medical Research Council Australia [NHMRC 486682, 1009064]; NIH R01 [EB008432, EB008281, EB007813, P41 RR013642] FX ED was funded, in part, by an NIH Training Grant in Neurobehavioral Genetics (T32MH073526-06). Our work on brain connectivity reported here is supported in part by the National Institute of Child Health and Human Development (R01 HD050735), and the National Health and Medical Research Council (NHMRC 486682, 1009064), Australia. Additional support for algorithm development was provided by NIH R01 grants EB008432, EB008281, EB007813 and P41 RR013642. 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J. Dev. Neurosci. PD NOV PY 2013 VL 31 IS 7 SI SI BP 525 EP 542 DI 10.1016/j.ijdevneu.2013.05.007 PG 18 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 269JG UT WOS:000328237000009 PM 23722009 ER PT J AU Feliciano, DM Lin, TV Hartman, NW Bartley, CM Kubera, C Hsieh, L Lafourcade, C O'Keefe, RA Bordey, A AF Feliciano, David M. Lin, Tiffany V. Hartman, Nathaniel W. Bartley, Christopher M. Kubera, Cathryn Hsieh, Lawrence Lafourcade, Carlos O'Keefe, Rachel A. Bordey, Angelique TI A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Tuberous sclerosis complex; Tuber; Mental retardation; Neurogenesis; mTOR; Epilepsy; Autism; SEGA; Seizures; FMRP; Spine; Dendrite; Migration; Differentiation; Stem cell; Progenitor cell ID GIANT-CELL ASTROCYTOMA; LONG-TERM DEPRESSION; IMPAIRED SYNAPTIC PLASTICITY; RAPAMYCIN SIGNALING PATHWAY; FOCAL CORTICAL DYSPLASIA; GAP-RELATED DOMAIN; MAMMALIAN TARGET; CEREBRAL-LESIONS; MOUSE MODEL; ADULT NEUROGENESIS AB Tuberous sclerosis complex (TSC) is an autosomal dominant monogenetic disorder that is characterized by the formation of benign tumors in several organs as well as brain malformations and neuronal defects. TSC is caused by inactivating mutations in one of two genes, TSC1 and TSC2, resulting in increased activity of the mammalian Target of Rapamycin (mTOR). Here, we explore the cytoarchitectural and functional CNS aberrations that may account for the neurological presentations of TSC, notably seizures, hydrocephalus, and cognitive and psychological impairments. In particular, recent mouse models of brain lesions are presented with an emphasis on using electroporation to allow the generation of discrete lesions resulting from loss of heterozygosity during perinatal development. Cortical lesions are thought to contribute to epileptogenesis and worsening of cognitive defects. However, it has recently been suggested that being born with a mutant allele without loss of heterozygosity and associated cortical lesions is sufficient to generate cognitive and neuropsychiatric problems. We will thus discuss the function of mTOR hyperactivity on neuronal circuit formation and the potential consequences of being born heterozygous on neuronal function and the biochemistry of synaptic plasticity, the cellular substrate of learning and memory. Ultimately, a major goal of TSC research is to identify the cellular and molecular mechanisms downstream of mTOR underlying the neurological manifestations observed in TSC patients and identify novel therapeutic targets to prevent the formation of brain lesions and restore neuronal function. (C) 2013 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Feliciano, David M.; Lin, Tiffany V.; Hartman, Nathaniel W.; Bartley, Christopher M.; Kubera, Cathryn; Hsieh, Lawrence; Lafourcade, Carlos; O'Keefe, Rachel A.; Bordey, Angelique] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. [Feliciano, David M.; Lin, Tiffany V.; Hartman, Nathaniel W.; Kubera, Cathryn; Hsieh, Lawrence; Lafourcade, Carlos; O'Keefe, Rachel A.; Bordey, Angelique] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. [Bartley, Christopher M.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. RP Bordey, A (reprint author), Yale Univ, Sch Med, 333 Cedar St,FMB 422, New Haven, CT 06520 USA. EM angelique.bordey@yale.edu FU Department of Defense grant (Idea development award) [W81XWH-10-1-0041]; McKnight Disorder award, a CT stem Cell grant; National Institute of Health [NRSA 10668225]; NIH [MSTP TG T32GM07205] FX This work was supported by a Department of Defense grant (Idea development award, W81XWH-10-1-0041), a McKnight Disorder award, a CT stem Cell grant (A.B.), a National Institute of Health NRSA 10668225 (D.M.F) and NIH MSTP TG T32GM07205 (C.M.B.). 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J. Dev. Neurosci. PD NOV PY 2013 VL 31 IS 7 SI SI BP 667 EP 678 DI 10.1016/j.ijdevneu.2013.02.008 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 269JG UT WOS:000328237000025 PM 23485365 ER PT J AU Saban, F Arikan, D AF Saban, Fatma Arikan, Duygu TI The self-esteem and anxiety of children with and without mentally retarded siblings SO JOURNAL OF RESEARCH IN MEDICAL SCIENCES LA English DT Article DE Mental retardation; self-esteem; sibling; trait anxiety ID DEVELOPMENTAL-DISABILITIES; BEHAVIORAL-ADJUSTMENT; ADOLESCENT SIBLINGS; DISABLED-CHILDREN; AUTISM; RETARDATION; COMPETENCE AB Background: The study was carried out with the aim of determining the factors affecting and to evaluate anxiety situations and self-esteem of children with and without mentally retarded siblings. Materials and Methods: The sampling included 227 healthy children: 108 of them have mental retarded sibling and 119 of them do not have mental retarded sibling. The context of this study consisted of 15-18 year of age healthy children with mentally retarded siblings and 15-18 year of aged healthy children having at least one sibling between the dates February 15st and June 26st 2010. Personal Information Form, Rosenberg Self-Esteem Scale and Trait Anxiety Scale were used. Results: It was found out that trait anxiety of 17-18 aged of children with mental retarded sibling (47.04 +/- 7.3) was higher than that of the children without mental retarded siblings (44.05 +/- 11.23) (P < 0.05). It was observed that self-esteem of children with mentally retarded sibling was not affected from the handicap of their siblings (P > 0.05). Trait anxiety score averages of children with mentally retarded sibling and experience some difficulties due to his or her siblings's handicap (47.00 +/- 7.76) were found higher than those of those of the children without any problem with the environment (42.61 +/- 7.48) (P < 0.05). Conclusion: Although the average score of trait anxiety and self-esteem in both groups were not significant different, score of trait anxiety for children with mentally disabled siblings was higher in comparison. It was concluded that anxiety of children with and without mentally retarded siblings increased as self-esteem of these children decreased. C1 [Saban, Fatma; Arikan, Duygu] Ataturk Univ, Dept Child Hlth Nursing, Fac Hlth Sci, TR-25240 Erzurum, Turkey. RP Arikan, D (reprint author), Ataturk Univ, Dept Child Hlth Nursing, Fac Hlth Sci, TR-25240 Erzurum, Turkey. 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Hardy, John Ryten, Mina CA North Amer Brain Expression TI Widespread sex differences in gene expression and splicing in the adult human brain SO NATURE COMMUNICATIONS LA English DT Article ID X-CHROMOSOME; PARKINSONS-DISEASE; GENDER-DIFFERENCES; SEQUENCE; AUTISM; GENOTYPE; TRANSCRIPTOME; INFLAMMATION; METAANALYSIS; NEUROSCIENCE AB There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures. C1 [Trabzuni, Daniah; Imran, Sabaena; Hardy, John; Ryten, Mina] UCL Inst Neurol, Dept Mol Neurosci, Reta Lilla Weston Labs, London WC1N 3BG, England. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Ramasamy, Adaikalavan; Weale, Michael E.; Ryten, Mina] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England. [Walker, Robert; Smith, Colin] Univ Edinburgh, Dept Neuropathol, MRC Sudden Death Brain Bank Project, Edinburgh EH8 9AG, Midlothian, Scotland. RP Ryten, M (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Reta Lilla Weston Labs, Queen Sq, London WC1N 3BG, England. EM mina.ryten@ucl.ac.uk RI Trabzuni, Daniah/C-4034-2012; Hardy, John/C-2451-2009; Weale, Michael/F-2587-2010; Ramasamy, Adaikalavan/G-2632-2010 OI Trabzuni, Daniah/0000-0003-4826-9570; Weale, Michael/0000-0003-4593-1186; Ramasamy, Adaikalavan/0000-0002-7598-2892 FU MRC through the MRC Sudden Death Brain Bank [G0802462]; King Faisal Specialist Hospital and Research Centre, Saudi Arabia; Intramural Research Program of the National Institute on Aging, National Institutes of Health, part of the US Department of Health and Human Services [ZIA AG000932-04]; National Institute of Neurological Disorders and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; Michael J. Fox Foundation for Parkinson's Research; National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust; National Institute for Health Research (NIHR) Biomedical Research Centre at King's College London FX This work was supported by the MRC through the MRC Sudden Death Brain Bank (C.S.), a Project Grant (to J.H. and M.E.W.) and Training Fellowship (G0802462 to M.R.). D.T. was supported by the King Faisal Specialist Hospital and Research Centre, Saudi Arabia. The work performed by the North American Brain Expression Consortium was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, part of the US Department of Health and Human Services; project number ZIA AG000932-04. We are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human biospecimens. The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. Computing facilities used at King's College London were partially supported by National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. 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TI Altered Cytokine and BDNF Levels in Autism Spectrum Disorder SO NEUROTOXICITY RESEARCH LA English DT Article DE Autism; Immune system; Cytokines; Handicap; Immunoexcitotoxicity ID POSSIBLE CENTRAL MECHANISM; ELEVATED SERUM-LEVELS; NEUROTROPHIC FACTOR; INCREASED FREQUENCY; BRAIN INFLAMMATION; ALZHEIMERS-DISEASE; NEURON NUMBER; CHILDREN; STRESS; PROTEIN AB The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age-and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder. C1 [Ricci, S.; Massoni, F.; Onofri, E.; Troili, G. M.] Univ Roma La Sapienza, Dept Anat Histol Legal Med & Orthopaed, I-00161 Rome, Italy. [Businaro, R.; Pontecorvi, V.; Morelli, M.] Sapienza Univ, Dept Medicosurg Sci & Biotechnol, I-04100 Latina, Italy. [Ippoliti, F.] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. [Lo Vasco, V. R.] Univ Roma La Sapienza, Dept Organi Senso, I-00161 Rome, Italy. [Ricciardi, M. Rapp; Archer, T.] Univ Gothenburg, Dept Psychol, S-40530 Gothenburg, Sweden. [Ricciardi, M. Rapp; Archer, T.] Linnea Univ, Dept Psychol Educ & Sports Sci, Kalmar, Sweden. RP Ricci, S (reprint author), Univ Roma La Sapienza, Dept Anat Histol Legal Med & Orthopaed, Viale Regina Elena 336, I-00161 Rome, Italy. EM serafino.ricci@uniroma1.it RI Lo Vasco, Vincenza Rita/F-9290-2010 FU REGIONE BASILICATA, ASP (Azienda Sanitaria Provinciale) Potenza, Italy-General Director Dott. Mario Marra; Center for Diet- Related diseases "G. Gioia", CHIAROMONTE Hospital FX Research funded by REGIONE BASILICATA, ASP (Azienda Sanitaria Provinciale) Potenza, Italy-General Director Dott. Mario Marra; Center for Diet- Related diseases "G. Gioia", CHIAROMONTE Hospital (PZ), ASP Potenza, Italy-Director Dott.ssa Rosa Trabace-Head of laboratory Dott.ssa Nicolina La Sala-Psychologist/ Psychotherapist Dott.ssa Maria Tosti; ASP (Azienda Sanitaria Provinciale) Ospedale Chiaromonte/Lagonegro, Potenza, Italy-Pediatrician Dott. Rocco Orofino, MD-Childish Neuropsychiatrist Dott. Vincenzo D'Onofrio, MD-Administrative Manager Dott. Giacomo Chiarelli; ASP (Azienda Sanitaria Provinciale) Matera, Italy Hospital "Madonna delle Grazie" Department of Children and Adolescent Neuropsychiatry-Director U.O.C. Dott. Carlo Calzone, MD-Neuropsychiatrist Dott. Caterina Lattarulo, MD; Stella Maris Mediterraneo Foundation, ASP Potenza, Italy; Dr. Lars Goran Wallgren provided excellent technical assistance. 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PD NOV PY 2013 VL 24 IS 4 BP 491 EP 501 DI 10.1007/s12640-013-9393-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 268CJ UT WOS:000328145300004 PM 23604965 ER PT J AU Zettergren, A Jonsson, L Johansson, D Melke, J Lundstrom, S Anckarsater, H Lichtenstein, P Westberg, L AF Zettergren, Anna Jonsson, Lina Johansson, Daniel Melke, Jonas Lundstrom, Sebastian Anckarsater, Henrik Lichtenstein, Paul Westberg, Lars TI Associations between polymorphisms in sex steroid related genes and autistic-like traits SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Autism spectrum disorders; Autistic-like traits; Sex steroids; Gene; Association; 5-alpha-reductase; Estrogen receptor; Testosterone ID BREAST-CANCER RISK; RECEPTOR-ALPHA GENE; POLYCYSTIC-OVARY-SYNDROME; HORMONE-BINDING GLOBULIN; SPECTRUM DISORDERS; PROSTATE-CANCER; 5-ALPHA-REDUCTASE TYPE-1; NEUROPSYCHIATRIC DISORDERS; TELEPHONE INTERVIEW; ALCOHOL DEPENDENCE AB Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n = 1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3'-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Zettergren, Anna; Jonsson, Lina; Johansson, Daniel; Melke, Jonas; Westberg, Lars] Univ Gothenburg, Inst Neurosci & Physiol, Dept Pharmacol, SE-40530 Gothenburg, Sweden. [Lundstrom, Sebastian; Anckarsater, Henrik] Univ Gothenburg, Ctr Eth Law & Mental Hlth CELAM, Inst Neurosci & Physiol, SE-40530 Gothenburg, Sweden. [Lundstrom, Sebastian] Univ Gothenburg, Gillberg Neuropsychiat Ctr, Inst Neurosci & Physiol, SE-40530 Gothenburg, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Zettergren, A (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Pharmacol, POB 431, SE-40530 Gothenburg, Sweden. EM anna.zettergren@pharm.gu.se FU Swedish Research Council; Swedish Research Council for Working Life and Social Research; Swedish Brain Foundation; Svenska Sallskapet for Medicinsk Forskning (SSMF); Fredrik and Ingrid Thurings stiftelse; Ake Wibergs stiftelse; Ahlen-stiftelsen; Jeanssons-stiftelsen; Mangus Bergvalls stiftelse; Soderstrom-Konigska stiftelsen; Marta Lundqvists stiftelse; Novo Nordisk Foundation FX Funding for the study was provided by grants from the Swedish Research Council, Swedish Research Council for Working Life and Social Research, Swedish Brain Foundation, Svenska Sallskapet for Medicinsk Forskning (SSMF), Fredrik and Ingrid Thurings stiftelse, Ake Wibergs stiftelse, Ahlen-stiftelsen, Jeanssons-stiftelsen, Mangus Bergvalls stiftelse, Soderstrom-Konigska stiftelsen, Marta Lundqvists stiftelse and the Novo Nordisk Foundation. 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Norlin, Chuck Gillespie, R. J. Weissman, Mark McGrath, Jane TI The National Improvement Partnership Network: State-Based Partnerships That Improve Primary Care Quality SO ACADEMIC PEDIATRICS LA English DT Article DE maternal and child health; preventive services; quality improvement ID PREVENTIVE SERVICES; HEALTH-CARE; CHILDREN; CHILDHOOD; OBESITY; EDUCATION; DELIVERY; CENTERS AB Improvement partnerships (IPs) are a model for collaboration among public and private organizations that share interests in improving child health and the quality of health care delivered to children. Their partners typically include state public health and Medicaid agencies, the local chapter of the American Academy of Pediatrics, and an academic health care organization or children's hospital. Most IPs also engage other partners, including a variety of public, private, and professional organizations and individuals. IPs lead and support measurement-based, systems-focused quality improvement (QI) efforts that primarily target primary care practices that care for children. Their projects are most often conducted as learning collaboratives that involve a team from each of 8 to 15 participating practices over 9 to 12 months. The improvement teams typically include a clinician, office manager, clinical staff (nurses or medical assistants), and, for some projects, a parent; the IPs provide the staff and local infrastructure. The projects target clinical topics, chosen because of their importance to public health, local clinicians, and funding agencies, including asthma, attention-deficit/hyperactivity disorder, autism, developmental screening, obesity, mental health, medical home implementation, and several others. Over the past 13 years, 19 states have developed (and 5 are exploring developing) IPs. These organizations share similar aims and methods but differ substantially in leadership, structure, funding, and longevity. Their projects generally engage pediatric and family medicine practices ranging from solo private practices to community health centers to large corporate practices. The practices learn about the project topic and about QI, develop specific improvement strategies and aims that align with the project aims, perform iterative measures to evaluate and guide their improvements, and implement systems and processes to support and sustain those improvements. Since 2008, IPs have offered credit toward Part 4 of Maintenance of Certification for participants in some of their projects. To date, IPs have focused on achieving improvements in care delivery through individual projects. Rigorous measurement and evaluation of their efforts and impact will be essential to understanding, spreading, and sustaining state/regional child health care QI programs. We describe the origins, evolution to date, and hopes for the future of these partnerships and the National Improvement Partnership Network (NIPN), which was established to support existing and nurture new IPs. C1 [Shaw, Judith S.] Univ Vermont, Coll Med, Dept Pediat, Vermont Child Hlth Improvement Program, Burlington, VT 05405 USA. [Norlin, Chuck] Univ Utah, Hlth Sci Ctr, Dept Pediat, Utah Pediat Partnership Improve Healthcare Qual, Salt Lake City, UT USA. [Gillespie, R. J.] Oregon Hlth & Sci Univ, Dept Pediat, Oregon Pediat Improvement Partnership, Portland, OR 97201 USA. [Weissman, Mark] Childrens Natl Med Ctr, Childrens Natl Hlth Network, DC Partnership Improve Childrens Healthcare Qual, Div Gen Pediat & Community Hlth, Washington, DC 20010 USA. [McGrath, Jane] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Envis New Mexico, Albuquerque, NM 87131 USA. RP Shaw, JS (reprint author), Univ Vermont, Coll Med, Dept Pediat, Vermont Child Hlth Improvement Program, N329 Courtyard Given,89 Beaumont Ave, Burlington, VT 05405 USA. EM judith.shaw@uvm.edu FU US Department of Health and Human Services, Centers for Medicare & Medicaid Services [CFDA 93.767] FX This document was developed, in part, under grant CFDA 93.767 from the US Department of Health and Human Services, Centers for Medicare & Medicaid Services. However, these contents do not necessarily represent the policy of the US Department of Health and Human Services, and you should not assume endorsement by the Federal Government. 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Pediatr. PD NOV-DEC PY 2013 VL 13 IS 6 SU S BP S84 EP S94 PG 11 WC Pediatrics SC Pediatrics GA 261TY UT WOS:000327688700017 PM 24268091 ER PT J AU Ajzenman, HF Standeven, JW Shurtleff, TL AF Ajzenman, Heather F. Standeven, John W. Shurtleff, Tim L. TI Effect of Hippotherapy on Motor Control, Adaptive Behaviors, and Participation in Children With Autism Spectrum Disorder: A Pilot Study SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE activities of daily living; adaptation, psychological; autistic disorder; equine-assisted therapy; motor skills; postural balance ID SENSORY PROCESSING DISORDERS; YOUNG-CHILDREN; IMPAIRMENT AB OBJECTIVE. The purpose of this investigation was to determine whether hippotherapy increased function and participation in children with autism spectrum disorder (ASD). We hypothesized improvements in motor control, which might increase adaptive behaviors and participation in daily activities. METHOD. Six children with ASD ages 5-12 participated in 12 weekly 45-min hippotherapy sessions. Measures pre- and post-hippotherapy included the Vineland Adaptive Behavior Scales-II and the Child Activity Card Sort. Motor control was measured preintervention and postintervention using a video motion capture system and force plates. RESULTS. Postural sway significantly decreased postintervention. Significant increases were observed in overall adaptive behaviors (receptive communication and coping) and in participation in self-care, low-demand leisure, and social interactions. CONCLUSION. These results suggest that hippotherapy has a positive influence on children with ASD and can be a useful treatment tool for this population. C1 [Ajzenman, Heather F.] Childrens Therapy Associates, Hillsborough, NC USA. [Standeven, John W.] Washington Univ, Sch Med, Human Performance Lab, Program Occupat Therapy, St Louis, MO 63108 USA. 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PD NOV-DEC PY 2013 VL 67 IS 6 BP 653 EP 663 DI 10.5014/ajot.2013.008383 PG 11 WC Rehabilitation SC Rehabilitation GA 260FB UT WOS:000327579300005 PM 24195899 ER PT J AU Classen, S Monahan, M Wang, YN AF Classen, Sherrilene Monahan, Miriam Wang, Yanning TI Driving Characteristics of Teens With Attention Deficit Hyperactivity and Autism Spectrum Disorder SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE attention deficit disorder with hyperactivity; automobile driving; child development disorders, pervasive; cognition; psychomotor performance ID SPECIAL-EDUCATION SERVICES; FIELD-OF-VIEW; DEFICIT/HYPERACTIVITY DISORDER; UNITED-STATES; OLDER-ADULTS; CHILDREN; PERFORMANCE; ADHD; ADOLESCENTS; PERCEPTION AB Vehicle crashes are a leading cause of death among teens. Teens with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or both (ADHD ASD) may have a greater crash risk. We examined the between-groups demographic, clinical, and predriving performance differences of 22 teens with ADHD ASD (mean age = 15.05, standard deviation [SD] = 0.95) and 22 healthy control (HC) teens (mean age = 14.32, SD = 0.72). Compared with HC teens, the teens with ADHD ASD performed more poorly on right-eye visual acuity, selective attention, visual motor integration, cognition, and motor performance and made more errors on the driving simulator pertaining to visual scanning, speed regulation, lane maintenance, adjustment to stimuli, and total number of driving errors. Teens with ADHD ASD, compared with HC teens, may have more predriving deficits and as such require the skills of a certified driving rehabilitation specialist to assess readiness to drive. C1 [Classen, Sherrilene] Univ Western Ontario, Elborn Coll, Sch Occupat Therapy, London, ON N6A 5B9, Canada. 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N., 2003, MMWR-MORBID MORTAL W, V54, P842 Visual Awareness Inc., 2002, UFOV US GUID VERS 6 Wechsler D., 2004, WECHSLER INTELLIGENC NR 38 TC 1 Z9 1 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 NOV-DEC PY 2013 VL 67 IS 6 BP 664 EP 673 DI 10.5014/ajot.2013.008821 PG 10 WC Rehabilitation SC Rehabilitation GA 260FB UT WOS:000327579300006 PM 24195900 ER PT J AU Yonkman, J Lawler, B Laity, J O'Neil, J Bull, M AF Yonkman, Janell Lawler, Bryanna Laity, Judith O'Neil, Joseph Bull, Marilyn TI Safely Transporting Children With Autism Spectrum Disorder: Evaluation and Intervention SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE child development disorders, pervasive; child restraint systems; motor vehicles; safety; transportation AB OBJECTIVE. The purpose of this study was to investigate transportation practices of caregivers who transport children diagnosed with autism spectrum disorders (ASD). METHOD. We reviewed documented transportation evaluations of children with ASD. The evaluations were conducted by pediatric occupational therapists at an outpatient center of a large children's hospital. RESULTS. A review of 82 charts of patients diagnosed with ASD revealed that 74% of children with ASD were escaping their child safety restraint. More than 20% of parents reported that their child demonstrated aggressive or self-injurious behavior during travel, affecting not only their own safety but also that of others in the vehicle, including the driver. CONCLUSION.. Escaping from a child restraint can be a life-threatening problem among children with ASD. Parents, caregivers, and health care professionals should be aware of services available from trained therapists, certified child passenger safety technicians, or both to maximize safety during personal travel in the family vehicle. C1 [Yonkman, Janell; Lawler, Bryanna; Laity, Judith; O'Neil, Joseph; Bull, Marilyn] Indiana Univ Hlth, Riley Hosp Children, Natl Ctr Safe Transportat Children Special Health, Indianapolis, IN 46202 USA. RP Yonkman, J (reprint author), Indiana Univ Hlth, Riley Hosp Children, Natl Ctr Safe Transportat Children Special Health, 1120 South Dr,Fesler Hall 207, Indianapolis, IN 46202 USA. EM jyonkman@iuhealth.org CR Centers for Disease Control and Prevention, 2012, MMWR-MORBID MORTAL W, V60, P1 Falkmer T., 2004, SCANDINAVIAN J OCCUP, V11, P90, DOI 10.1080/11038120410020575 National Center for Injury Prevention and Control, 2010, WEB BAS INJ STAT QUE National Center for Injury Prevention and Control, 2011, CHILD PASS SAF FACT National Highway Traffic Safety Administration, 2004, 809671 DOT HS NAT HI National Highway Traffic Safety Administration, 2007, 810731 DOT HS NAT HI Weber K., 2000, UMTRI RES REV, V31, P311 NR 7 TC 1 Z9 1 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 NOV-DEC PY 2013 VL 67 IS 6 BP 711 EP 716 DI 10.5014/ajot.2013.008250 PG 6 WC Rehabilitation SC Rehabilitation GA 260FB UT WOS:000327579300011 PM 24195905 ER PT J AU Senechal, C Larivee, S Thermidor, G AF Senechal, Carole Larivee, Serge Thermidor, Ghitza TI Parents as co-therapists: A winning solution for treating autistic children SO ANNALES MEDICO-PSYCHOLOGIQUES LA French DT Article DE Autism; Early intervention; Parental involvement ID EARLY INTERVENTION; YOUNG-CHILDREN; SPECTRUM DISORDER; COMMUNICATION; KNOWLEDGE; BEHAVIOR; BELIEFS; PROGRAM; MOTHERS; FAMILY AB Objectives. - This article aims to report on the effects of an intervention program carried out in a clinical context and destined to parents of autistic children. The program was part of a diagnostic evaluation process and sought to provide parents with essential support as soon as their child was diagnosed. It was also designed to increase their knowledge of autism's particular characteristics. Method. - Each of the fourteen families participating in this research had a child aged between two and six years old who had been diagnosed with autism. They were assessed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule Generic (ADOS-G) by a team from Riviere-des-Prairies Hospital, in the Montreal area, specialized in Pervasive Developmental Disorder. The specification identified for this study was a quasi-experimental protocol with a pre- and post-test and a non-equivalent control group. The first eight families registered with the clinic were part of the experimental group; the other six formed the control group. The experimental group was composed of six boys and two girls whose average age was 48 months (span: 34-72). The implemented program contained two intervention targets: communication and the child's learning. Five individual sessions of approximately 90 minutes each were provided to each family. A psycho-educator directed activities chosen according to the developmental level of each child. Because one of the objectives of the program was to help parents intervene with their child, they were involved in the intervention each in turn, either by observing or by practising those intervention techniques identified for their child. In order to measure the change in parental practices, the Maternal Behavior Rating Scale was used. This observation table is composed of 12 items assessed with a Likert-type five-point scale, one meaning very low, and five meaning very elevated, evaluating four scales of parental educational practices designed to improve children's development: the parent's response (three items), the parent's animation (five items), the parent's support with the task (two items) and his or her authority (two items). The program's impact with the child was assessed with the Child Behavior Rating Scale, an observation table comprised of two scales recognized as preconditions to children's development: attention (four items) and initiation (two items). These items were assessed by two observers with a Likert-type five-point scale, one meaning very low and five meaning very elevated. Inter-rater coefficients varied between 0.88 and 0.93. Results. Variance analyses undertaken from the results obtained with the Maternal Behavior Rating Scales and the Child Behavior Rating Scales before and after the intervention showed that both groups improved but that this improvement did not vary significantly from one group to the other. Conclusions. Four elements may help explain the absence of significant results. Firstly, all children except one were recipients of other services during the intervention. Secondly, with regards to the objective of helping parents better understand their child's diagnostic, five 90-minute individual sessions appeared to be sufficient, but obviously that was not the case. Thirdly, there were difficulties with the recruitment and the sample's non-homogeneity. Fourthly, over and above their good psychometric qualities, the two instruments used were not sufficiently attuned to more subtle changes. Finally, we must insist on the importance, especially in human and social sciences, of publishing results considered as negative in as much as those results form an integral part of the scientific process. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [Senechal, Carole] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Larivee, Serge; Thermidor, Ghitza] Univ Montreal, Ecole Psychoeduc, Montreal, PQ H3C 3J7, Canada. RP Senechal, C (reprint author), Univ Ottawa, Pavillon Lamoureux,145 Jean Jacques Lussier, Ottawa, ON K1N 6N5, Canada. 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PD NOV PY 2013 VL 171 IS 9 BP 603 EP 609 DI 10.1016/j.amp.2012.11.013 PG 7 WC Pharmacology & Pharmacy; Psychiatry; Psychology; Psychology, Multidisciplinary SC Pharmacology & Pharmacy; Psychiatry; Psychology GA 260FF UT WOS:000327579700002 ER PT J AU Velloso, RD Duarte, CP Schwartzman, JS AF Velloso, Renata de Lima Duarte, Cintia Perez Schwartzman, Jose Salomao TI Evaluation of the theory of mind in autism spectrum disorders with the Strange Stories test SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Article DE child developmental disorders; pervasive; autism; theory of mind ID ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; PERFORMANCE; REPLICATION; ADULTS; TASKS AB Objective: To evaluate the theory of mind in autism spectrum disorders (ASD) and control individuals by applying the Strange Stories test that was translated and adapted to the Portuguese language. Method: Twenty-eight children with ASD and 56 controls who were all mate and aged between 6 and 12 years participated in the study. Results: There were significant differences between the median scores of the groups for each of the 12 stories of the test and for the sum total of all the median scores. The median scores for all stories were significantly greater in the control group than those in the experimental group (children with ASD). In addition, the protocol had excellent internal consistency. Conclusion: The theory of mind skills assessed with the Strange Stories test indicated alterations in children with ASD compared with children in the control group. C1 [Velloso, Renata de Lima; Duarte, Cintia Perez] Univ Presbiteriana Mackenzie, Sao Paulo, Brazil. [Schwartzman, Jose Salomao] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Schwartzman, Jose Salomao] Univ Presbiteriana Mackenzie, Programs Posgrad Disturbios Desenvolvimento, Sao Paulo, Brazil. RP Velloso, RD (reprint author), Rua Piaui 181, BR-01241001 Sao Paulo, Brazil. EM relimavelloso@yahoo.com.br CR APA American Psychiatric Association, 2002, DIAGN STAT MAN MENT BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Baron-Cohen S, 1995, MINDBLINDNESS Brent E, 2004, AUTISM, V8, P283, DOI 10.1177/1362361304045217 Frith U., 1996, AUTISM ASPERGERS SYN HAPPE FGE, 1994, J AUTISM DEV DISORD, V24, P129, DOI 10.1007/BF02172093 HAPPE FGE, 1993, COGNITION, V48, P101, DOI 10.1016/0010-0277(93)90026-R Happe FGE, 1993, AUTISM INTRO PSYCHOL Hermelin B, 1985, COMMUNICATION PROBLE, P283 Jolliffe T, 1999, J AUTISM DEV DISORD, V29, P395, DOI 10.1023/A:1023082928366 Kaland N, 2008, J AUTISM DEV DISORD, V38, P1112, DOI 10.1007/s10803-007-0496-8 Kaland N, 2005, EUR CHILD ADOLES PSY, V14, P73, DOI 10.1007/s00787-005-0434-2 Kaland N, 2002, J CHILD PSYCHOL PSYC, V43, P517, DOI 10.1111/1469-7610.00042 Loth E, 2011, J AUTISM DEV DISORD, V41, P945, DOI 10.1007/s10803-010-1124-6 Milosky LM, 1996, PROCESSOS DISTURBIOS O'Hare AE, 2009, J AUTISM DEV DISORD, V39, P916, DOI 10.1007/s10803-009-0699-2 Rutter M, 2005, J AUTISM DEV DISORD, V35, P241, DOI 10.1007/s10803-005-2003-4 Sattler J, 1992, ASSESSMENT CHILDRE S Sperber D., 1986, RELEVANCE COMMUNICAT Wechsler D, 2002, WECHSLER INTELLIGENC, V3rd WING L, 1979, J AUTISM DEV DISORD, V9, P11, DOI 10.1007/BF01531288 World Health Organisation, 2000, INT CLASS DIS ICD 10 NR 22 TC 0 Z9 0 PU ASSOC ARQUIVOS NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X EI 1678-4227 J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD NOV PY 2013 VL 71 IS 11 BP 871 EP 876 DI 10.1590/0004-282X20130171 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263SH UT WOS:000327827800010 ER PT J AU Ponde, MP Rousseau, C Carlos, MAC AF Ponde, Milena Pereira Rousseau, Cecile Costa Carlos, Marco Antonio TI Pervasive developmental disorder in the children of immigrant parents: comparison of different assessment instruments SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Article DE autism spectrum disorder; diagnosis ID AUTISM SPECTRUM DISORDERS; OBSERVATION-SCHEDULE ADOS; CHILDHOOD AUTISM; RATING-SCALE; BEHAVIOR; DIAGNOSIS AB The objective of this study was to describe how the Childhood Autism Rating Scale (CARS) behaves in relation to the Autism Diagnostic Observation Schedule (ADDS) and to clinical diagnosis based on the criteria defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) for children of immigrant parents. Forty-nine children of parents who had immigrated to Canada were evaluated. In this sample, the ADOS and the DSM-IV showed complete agreement. Using the standard cut-off point of 30, the CARS showed high specificity and poor sensitivity. The study proposes a cut-off point for the CARS that would include pervasive developmental disorder not otherwise specified (PDD-NOS). Reducing the cut-off point to 20/21 increased the specificity of the instrument for this group of children without significantly reducing its sensitivity. C1 [Ponde, Milena Pereira; Costa Carlos, Marco Antonio] Bahiana Sch Med & Publ Hlth, Interdisciplinary Lab Autism Res LABIRINTO, Salvador, BA, Brazil. [Rousseau, Cecile] McGill Univ, Div Social & Cultural Psychiat, TRIT, Montreal, PQ, Canada. RP Ponde, MP (reprint author), Av Dom Joao 6 275, BR-40290000 Salvador, BA, Brazil. EM milenaponde@bahiana.edu.br FU Bahia State Research Foundation (FAPESB) [0086/2009] FX This study formed part of a postdoctoral thesis by the first author and was financially supported by the Bahia State Research Foundation (FAPESB), Grant No 0086/2009. CR American Psychiatric Association (APA), 2012, DSM 5 PROP CRIT AUT APA, 2000, DSM 4 TR DIAGN STAT Bolte S, 2004, Z KINDER JUG-PSYCH, V32, P45, DOI 10.1024/1422-4917.32.1.45 Chlebowski C, 2010, J AUTISM DEV DISORD, V40, P787, DOI 10.1007/s10803-009-0926-x Gotham K, 2009, J AUTISM DEV DISORD, V39, P693, DOI 10.1007/s10803-008-0674-3 Gotham K, 2008, J AM ACAD CHILD PSY, V47, P642, DOI 10.1097/CHI.0b013e31816bffb7 Kleinman JM, 2008, J AUTISM DEV DISORD, V38, P606, DOI 10.1007/s10803-007-0427-8 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Lord C., 2006, AUTISM DIAGNOSTIC OB Minshew NJ, 2007, ARCH NEUROL-CHICAGO, V64, P945, DOI 10.1001/archneur.64.7.945 Novaes CM, 2008, ARQ NEURO-PSIQUIAT, V66, P646, DOI 10.1590/S0004-282X2008000500008 Papanikolaou K, 2009, J AUTISM DEV DISORD, V39, P414, DOI 10.1007/s10803-008-0639-6 Ponde MP, 2010, ARQ NEURO-PSIQUIAT, V68, P103, DOI 10.1590/S0004-282X2010000100022 Rellini E, 2004, J AUTISM DEV DISORD, V34, P703, DOI 10.1007/s10803-004-5290-2 Rousseau C, 2008, EUR CHILD ADOLES PSY, V17, P264, DOI 10.1007/s00787-007-0640-1 Schopler E., 1988, CHILDHOOD AUTISM RAT SHAFFER D, 1983, ARCH GEN PSYCHIAT, V40, P1228 Tachimori H, 2003, PSYCHIAT CLIN NEUROS, V57, P113, DOI 10.1046/j.1440-1819.2003.01087.x Volkmar F, 2005, ANNU REV PSYCHOL, V56, P315, DOI 10.1146/annurev.psych.56.091103.070159 NR 19 TC 0 Z9 0 PU ASSOC ARQUIVOS NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X EI 1678-4227 J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD NOV PY 2013 VL 71 IS 11 BP 877 EP 882 DI 10.1590/0004-282X20130091 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263SH UT WOS:000327827800011 PM 24394875 ER PT J AU Wolstenholme, JT Goldsby, JA Rissman, EF AF Wolstenholme, Jennifer T. Goldsby, Jessica A. Rissman, Emilie F. TI Transgenerational effects of prenatal bisphenol A on social recognition SO HORMONES AND BEHAVIOR LA English DT Article DE Endocrine disrupting chemicals; Social recognition; Transgenerational inheritance; Attention deficit hyperactivity disorder; Autism; Epigenetics ID ENDOCRINE-DISRUPTING CHEMICALS; ESTROGEN-RECEPTOR-ALPHA; PERINATAL EXPOSURE; GESTATIONAL EXPOSURE; AGGRESSIVE-BEHAVIOR; MATERNAL-BEHAVIOR; AUTISTIC TRAITS; GENE-EXPRESSION; SEX-DIFFERENCES; WATER MAZE AB Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture polycarbonate plastics. It is found in plastic bottles, canned food linings, thermal receipts and other commonly used items. Over 93% of people have detectable BPA levels in their urine. Epidemiological studies report correlations between BPA levels during pregnancy and activity, anxiety, and depression in children. We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. First (F1) and third (F3) generation juveniles were tested for social recognition and in the open field. Adult F3 mice were tested for olfactory discrimination. In both generations, BPA exposed juvenile mice displayed higher levels of investigation than controls in a social recognition task. In F3 EPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. These results demonstrate that BPA exposure during gestation has long lasting, transgenerational effects on social recognition and activity in mice. These findings show that BPA exposure has transgenerational actions on behavior and have implications for human neurodevelopmental behavioral disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wolstenholme, Jennifer T.; Goldsby, Jessica A.; Rissman, Emilie F.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Rissman, EF (reprint author), Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. EM Rissman@virginia.edu FU NIH [R01 MH057759]; [F32 ES019404] FX This work is supported by NIH R01 MH057759 (EFR). JTW is supported by F32 ES019404. 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Behav. PD NOV PY 2013 VL 64 IS 5 BP 833 EP 839 DI 10.1016/j.yhbeh.2013.09.007 PG 7 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 261TO UT WOS:000327687700010 PM 24100195 ER PT J AU Field, T Ezell, S Nadel, J Grace, A Allender, S Siddalingappa, V AF Field, Tiffany Ezell, Shauna Nadel, Jacqueline Grace, Ava Allender, Susan Siddalingappa, Vijaya TI Reciprocal Imitation Following Adult Imitation by Children with Autism SO INFANT AND CHILD DEVELOPMENT LA English DT Article DE imitation; social attention; children with autism ID LANGUAGE AB This study examined the effects of adult imitation and adult playfulness on the imitation, social attention and initiation of new behaviours by non-verbal preschoolers with autism. Videotapes taken from a previous study were recoded for the adult's imitation and playful behaviour and the children's imitation, social attention (looking at the adult's actions) and initiation of new behaviours. In the original study, twenty non-verbal, 4- to 6-year-old children with autism were randomly assigned to an imitation or a contingent responsivity group. Both groups of children engaged in an intervention phase (during which the adult imitated the children or contingently responded to them) and a subsequent spontaneous play phase (during which the adult interacted spontaneously with the children). ANOVA for the current study revealed that the imitation group children versus the contingent responsivity group children spent a greater percent time showing social attention and initiating new behaviours during the intervention phase and showing social attention and imitating the adult's behaviours during the subsequent spontaneous play phase. A correlation analysis yielded significant correlations between the percent time the adult imitated the child during the intervention phase and the percent time the child showed social attention during the same intervention phase and imitating the adult during the subsequent spontaneous play phase. Adult imitation and playfulness during the spontaneous play phase were also correlated with the children's social attention during that phase. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Field, Tiffany] Univ Miami, Sch Med, Dept Pediat, Miami, FL 33152 USA. [Field, Tiffany; Ezell, Shauna; Grace, Ava; Allender, Susan; Siddalingappa, Vijaya] Univ Miami, Fielding Grad Univ, Sch Med, Miami, FL USA. [Nadel, Jacqueline] Hop La Pitie Salpetriere, Ctr Emot, CNRS, USR 3246, Paris, France. RP Field, T (reprint author), Univ Miami, Sch Med, Dept Pediat, Miami, FL 33152 USA. EM tfield@med.miami.edu CR Cardon TA, 2011, J AUTISM DEV DISORD, V41, P654, DOI 10.1007/s10803-010-1086-8 Field T., 2008, EARLY CHILD DEV CARE, V178, P1 Field T, 2001, AUTISM, V5, P317, DOI 10.1177/1362361301005003008 Heimann M, 2006, INFANT CHILD DEV, V15, P297, DOI 10.1002/icd.463 Ingersoll B, 2006, J AUTISM DEV DISORD, V36, P487, DOI 10.1007/s10803-006-0089-y Ingersoll B, 2012, J AUTISM DEV DISORD, V42, P1768, DOI 10.1007/s10803-011-1423-6 Katagiri M, 2010, RES AUTISM SPECT DIS, V4, P474, DOI 10.1016/j.rasd.2009.11.004 Nadel J., 2008, EARLY CHILD DEV CARE, V178, P461, DOI 10.1080/03004430600801699 Nadel J., 2006, IMITATION SOCIAL MIN, P118 Vanvuchelen M, 2011, RES DEV DISABIL, V32, P148, DOI 10.1016/j.ridd.2010.09.010 NR 10 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-7219 J9 INFANT CHILD DEV JI Infant Child Dev. PD NOV PY 2013 VL 22 IS 6 BP 642 EP 648 DI 10.1002/icd.1812 PG 7 WC Psychology, Developmental SC Psychology GA 264ST UT WOS:000327901500006 ER PT J AU Tajeran, M Baghbani, F Hassanzadeh-Nazarabadi, M AF Tajeran, Massoumeh Baghbani, Fatemeh Hassanzadeh-Nazarabadi, Mohammad TI A Case of Autism with Ring Chromosome 14 SO IRANIAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE Autistic disorder; Ring chromosome 14; Cytogenetic analysis ID SPECTRUM DISORDERS; MUTATIONS; DELETIONS; GENETICS; LOCUS; ETIOLOGY; EPILEPSY; SHANK3; GENES AB Background: Autism is a complex neuropsychiatric disorder that manifests in early childhood. Although the etiology is unknown yet but, new hypothesis focused on identifying the key genes related to autism may elucidate its etiology. The main objective of the present study was to verify the value of karyotyping in autistic children and identifying association between chromosome abnormalities and autism. Methods: We examined the peripheral blood lymphocytes cell culture for cytogenetic alterations by GTG-banding technique. The investigation was carried out on 50 autistic patients referred by Pediatric neurologist to Cytogenetic Laboratory in Khorasan-e-razavi Province, Iran. Results: Using GTG-banding technique, the chromosome analysis of patients identified an unbalanced male karyotype with a r (14) in all 50 metaphases were examined. Conclusion: Since structural abnormalities may have a critical role in the etiology of autism, according to the region where is affected and number of related genes, therefore an outcome with wide spectrum of clinical manifestations could be expected. Furthermore by considering of recent study, the results indicated that there is an association between chromosome 14 with brain development and neurological disorders, but, in conclusion, it could not be suggested that in order to postulate cytogenetic testing in idiopathic autism patients, specifically screening for chromosome 14 which might has diagnostic value. C1 [Tajeran, Massoumeh; Baghbani, Fatemeh; Hassanzadeh-Nazarabadi, Mohammad] Mashhad Univ Med Sci, Dept Med Genet, Sch Med, Mashhad, Iran. RP Hassanzadeh-Nazarabadi, M (reprint author), Mashhad Univ Med Sci, Dept Med Genet, Sch Med, Mashhad, Iran. 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Public Health PD NOV PY 2013 VL 42 IS 11 BP 1316 EP 1320 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 262NX UT WOS:000327743500015 ER PT J AU Jaarsma, P Welin, S AF Jaarsma, Pier Welin, Stellan TI Human capabilities, mild autism, deafness and the morality of embryo selection SO MEDICINE HEALTH CARE AND PHILOSOPHY LA English DT Article DE Autism; Reproduction; Genetic selection; Ethics; Human capabilities; Procreative beneficence; Quality of life ID ASPERGERS; CHICKENS; BLIND AB A preimplantation genetic test to discriminate between severe and mild autism spectrum disorder might be developed in the foreseeable future. Recently, the philosophers Julian Savulescu and Guy Kahane claimed that there are strong reasons for prospective parents to make use of such a test to prevent the birth of children who are disposed to autism or Asperger's disorder. In this paper we will criticize this claim. We will discuss the morality of selection for mild autism in embryo selection in a hypothetical in vitro fertilization (IVF) situation where preimplantation genetic diagnosis is performed and compare this with a similar selection for congenital deafness. To do this we first discuss relevant human differences. We then introduce the principle of human capabilities (PC) and compare this principle with the principle of procreative beneficence (PB) introduced by Savulescu and Kahane. We apply the two principles to selection for mild autism and selection for congenital deafness. We argue that PC allows for the selection for mild autism but rules out selection for congenital deafness. PB will not give clear answers; the ruling of PB depends to a large extent on expected social, cultural and political developments. We will argue that PC is preferable to PB. We will discuss arguments for the value of mild autism for individuals who have this condition and argue that they are able to lead a life with human dignity provided autism-friendly social circumstances are present. Neither PC nor PB yields strong reasons for prospective parents to seek to prevent the birth of children who are disposed to mild autism spectrum disorder. C1 [Jaarsma, Pier; Welin, Stellan] Linkoping Univ, IMH, Div Hlth & Soc, SE-58183 Linkoping, Sweden. RP Jaarsma, P (reprint author), Linkoping Univ, IMH, Div Hlth & Soc, SE-58183 Linkoping, Sweden. EM pier.jaarsma@liu.se CR ALI A, 1985, POULTRY SCI, V64, P789 Allred S, 2009, DISABIL SOC, V24, P343, DOI 10.1080/09687590902789511 Barashkov N. A., 2011, J HUM GENET, V56, P631 Barnbaum Deborah R, 2008, ETHICS AUTISM THEM N Baron- Cohen S., 2002, FOCUS AUTISM OTHER D, V17, P186, DOI 10.1177/10883576020170030801 Baron-Cohen S, 2001, J AUTISM DEV DISORD, V31, P5, DOI 10.1023/A:1005653411471 Baron-Cohen S., 2002, TRENDS COGN SCI, V6, P253 Baron-Cohen S., 2011, SCI EVIL Baron-Cohen S, 2011, PLOS BIOL, V9, DOI 10.1371/journal.pbio.1001081 Baron-Cohen S, 2007, HUM NATURE-INT BIOS, V18, P125, DOI 10.1007/s12110-007-9014-0 Baron-Cohen S., 2010, AUTISM TALENT Bruhwiler C, 2011, LEARN INSTR, V21, P95, DOI 10.1016/j.learninstruc.2009.11.004 Campbell D. B., 2010, FOCUS, V8, P339 Casanova MF, 2010, BRAIN PATHOL, V20, P451, DOI 10.1111/j.1750-3639.2009.00319.x Clarke J, 2008, SOC WORK HEALTH CARE, V46, P85, DOI 10.1300/J010v46n03_05 Collins S, 2011, APPL ANIM BEHAV SCI, V133, P60, DOI 10.1016/j.applanim.2011.04.013 Davis DS, 1997, HASTINGS CENT REP, V27, P7, DOI 10.2307/3527620 Fitzgerald M., 2004, AUTISM CREATIVITY IS Fung CHM, 2009, PERS INDIV DIFFER, V46, P775, DOI 10.1016/j.paid.2009.01.019 Garcia-Falgueras A, 2010, ENDOCRIN DEV, V17, P22, DOI 10.1159/000262525 Glover J., 2006, CHOOSING CHILDREN GE Grandin Temple, 2006, THINKING PICTURES MY, Vrev Greenspan P., 2004, THINKING FEELING CON Habermas Jurgen, 2003, FUTURE HUMAN NATURE Hacking I, 2009, PHILOS T R SOC B, V364, P1467, DOI 10.1098/rstb.2008.0329 Happe F., 2010, AUTISM TALENT Jaarsma P, 2012, HEALTH CARE ANAL, V20, P20, DOI 10.1007/s10728-011-0169-9 Kruijver FPM, 2000, J CLIN ENDOCR METAB, V85, P2034, DOI 10.1210/jc.85.5.2034 Lajos S., 2011, J BEHAV THER EXP PSY, V42, P38 Luders E, 2009, NEUROIMAGE, V46, P904, DOI 10.1016/j.neuroimage.2009.03.048 Nussbaum M., 2011, CREATING CAPABILITIE Nussbaum M., 2004, THINKING FEELING CON Nussbaum Martha, 2006, FRONTIERS JUSTICE DI Rutter M, 2010, MONOGR SOC RES CHILD, V75, P1, DOI 10.1111/j.1540-5834.2010.00548.x Sacks O. W., 1989, SEEING VOICES JOURNE Savulescu J, 2009, BIOETHICS, V23, P274, DOI 10.1111/j.1467-8519.2008.00687.x Williams Emily L, 2010, Bol Asoc Med P R, V102, P17 NR 37 TC 0 Z9 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-7423 EI 1572-8633 J9 MED HEALTH CARE PHIL JI Med. Health Care Philos. PD NOV PY 2013 VL 16 IS 4 BP 817 EP 824 DI 10.1007/s11019-013-9464-6 PG 8 WC Ethics; History & Philosophy Of Science SC Social Sciences - Other Topics; History & Philosophy of Science GA 253ZE UT WOS:000327128500021 PM 23334404 ER PT J AU Frye, RE Rose, S Slattery, J Wynne, R Tippett, M Melynk, S James, SJ AF Frye, Richard E. Rose, Shannon Slattery, John Wynne, Rebecca Tippett, Marie Melynk, Stephan James, S. Jill TI Mitochondrial dysfunction in immune cells derived from children with autism spectrum disorder (ASD): A unique metabolic endophenotype of children with ASD SO MITOCHONDRION LA English DT Meeting Abstract C1 [Frye, Richard E.; Rose, Shannon; Slattery, John; Wynne, Rebecca; Tippett, Marie; Melynk, Stephan; James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2013 VL 13 IS 6 MA 37 BP 910 EP 910 DI 10.1016/j.mito.2013.07.034 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 255ZY UT WOS:000327280500074 ER PT J AU Coskun, PE Nemantinejad, Z Schwarts, PH Brick, DJ Busciglio, J AF Coskun, Pinar E. Nemantinejad, Zahra Schwarts, Phillip H. Brick, David J. Busciglio, Jorge TI Mitochondrial dysfunction in autism fibroblasts SO MITOCHONDRION LA English DT Meeting Abstract C1 [Coskun, Pinar E.; Nemantinejad, Zahra; Busciglio, Jorge] Univ Calif Irvine, Dept Neurobiol & Behav, iMIND, Irvine, CA 92697 USA. [Coskun, Pinar E.; Busciglio, Jorge] Univ Calif Irvine, CNLM, Irvine, CA 92697 USA. [Schwarts, Phillip H.; Brick, David J.] Childrens Hosp Orange Cty Res Inst CHOC, Neurosci Labs, Ctr Neurosci, Orange, CA 92868 USA. [Schwarts, Phillip H.; Brick, David J.] Childrens Hosp Orange Cty Res Inst CHOC, Neurosci Labs, Ctr Translat Res, Orange, CA 92868 USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2013 VL 13 IS 6 MA 108 BP 937 EP 938 DI 10.1016/j.mito.2013.07.100 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 255ZY UT WOS:000327280500140 ER PT J AU Moraes, CT Anderson, V Mohan, C AF Moraes, Carlos T. Anderson, Vernon Mohan, Charles TI Translational research in primary mitochondrial diseases: Challenges and opportunities SO MITOCHONDRION LA English DT Article DE Workshop; Mitochondrial diseases; Animal models; NIH AB On March 8-9, 2012, the NIH intramural and extramural research communities as well as representatives from industries and foundations with a common interest in primary mitochondrial diseases met in Bethesda to identify the major barriers to the development of better treatment for mitochondrial diseases. Besides the importance to the patient population, it has become clear in the last decade that advances in understanding and treating primary mitochondrial diseases will impact research into a large number of degenerative conditions known to have a significant mitochondrial dysfunction component in their pathogenic mechanisms (secondary mitochondrial diseases) that affect millions of people, including Alzheimer's disease, Parkinson's disease, diabetes, ALS, autism spectrum disorders, and many others. We would like to make this discussion available to the scientific community, as it provides a framework on how patient advocacy groups, individual academic units, pharmaceutical companies, and the NIH can interact to address problems related to mitochondrial diseases. The main goals of this workshop were as follows: (1) to share information related to primary mitochondrial disease among the NIH Intramural and Extramural Research Program Investigators, (2) to develop and/or enhance systems to facilitate future collaboration and sharing of information, (3) to survey obstacles, needs and priorities of primary mitochondrial diseases research, and (4) to develop mechanisms to enhance translation of basic science discoveries to diagnostics and therapeutics. C1 [Moraes, Carlos T.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Anderson, Vernon] NIGMS, Div Pharmacol Physiol & Biol Chem, Bethesda, MD USA. [Mohan, Charles] United Mitochondrial Dis Fdn, Pittsburgh, PA USA. RP Moraes, CT (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. EM cmoraes@med.miami.edu FU UMDF/NIH FX A UMDF/NIH sponsored workshop to identify barriers to treatments to mitochondrial diseases. NR 0 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD NOV PY 2013 VL 13 IS 6 BP 945 EP 952 DI 10.1016/j.mito.2013.08.002 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 255ZY UT WOS:000327280500155 PM 23962609 ER PT J AU Ozcaliskan, S Dimitrova, N AF Ozcaliskan, Seyda Dimitrova, Nevena TI How Gesture Input Provides a Helping Hand to Language Development SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Gesture production; gesture input; language development; gesture-speech combination ID JOINT ATTENTION; YOUNG-CHILDREN; DOWNS-SYNDROME; MOTHERS SPEECH; INFANTS; COMMUNICATION; COMPREHENSION; VOCABULARY; WORDS; AUTISM AB Children use gesture to refer to objects before they produce labels for these objects and gesture-speech combinations to convey semantic relations between objects before conveying sentences in speecha trajectory that remains largely intact across children with different developmental profiles. Can the developmental changes that we observe in children be traced back to the gestural input that children receive from their parents? A review of previous work shows that parents provide models for their children for the types of gestures and gesture-speech combinations to produce, and do so by modifying their gestures to meet the communicative needs of their children. More importantly, the gestures that parents produce, in addition to providing models, help children learn labels for referents and semantic relations between these referents and even predict the extent of children's vocabularies several years later. The existing research thus highlights the important role parental gestures play in shaping children's language learning trajectory. C1 [Ozcaliskan, Seyda; Dimitrova, Nevena] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. RP Ozcaliskan, S (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. 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PD NOV PY 2013 VL 34 IS 4 BP 227 EP 236 DI 10.1055/s-0033-1353447 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 260XR UT WOS:000327628400003 PM 24297615 ER PT J AU Naigles, LR AF Naigles, Letitia R. TI Input and Language Development in Children with Autism SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Language; maternal effects; autism ID PARENT VERBAL RESPONSIVENESS; TYPICAL DEVELOPMENT; SPECTRUM DISORDERS; JOINT ATTENTION; YOUNG-CHILDREN; DOWN-SYNDROME; SPEECH; GROWTH; COMMUNICATION AB The social deficits associated with autism spectrum disorders (ASD) have been implicated in the language delays and deficits of children with ASD. Consequently, the extent to which children with ASD utilize their language-related interactions and input in the same ways as typically developing children is only just beginning to be investigated. The current article summarizes the role of input for typically developing children learning language, and then reviews in some detail recent studies demonstrating influential effects of maternal responsivity (e.g., following in on children's focus of attention) and aspects of maternal speech (e.g., word frequency, word diversity, structural complexity) on the language production and comprehension of young children with ASD. Maternal responsivity appears to play a particularly influential role with children who are minimally verbal whereas the content and structure of maternal speech facilitate language in children who are already verbal. C1 Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. RP Naigles, LR (reprint author), Univ Connecticut, Dept Psychol, 406 Babbidge Rd U-20, Storrs, CT 06269 USA. EM Letitia.naigles@uconn.edu FU National Institutes of Health (NIH-DCD) [R01 DC07428]; National Alliance for Autism Research FX The research described in this article was supported by the National Institutes of Health (NIH-DCD, R01 DC07428) and the National Alliance for Autism Research. I am happy to acknowledge my collaborators Deborah Fein, Lauren Swensen Meade, and Anthony Goodwin. Gratitude goes to our parent and child participants, and to Rose Jaffery, Janina Piotroski, and the many undergraduate students of the UConn Child Language Laboratory for their assistance in data collection, coding, and analysis. I would also like to thank James Dixon, Inge-Marie Eigsti, James Green, Andrea McDuffie, and Manuela Wagner for their helpful suggestions and commentary on this research. This chapter was written while the author was on sabbatical leave; she thanks the University of Connecticut for providing the leave and the MIND Institute at UC Davis for providing such a stimulating place to spend the sabbatical. 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Long-term maintenance of treatment effects is an important issue after behavior change has taken place and is the goal of most programs. Areas discussed include factors affecting the study of maintenance, techniques for programming it, and analyzing and evaluating strategies for promoting it. This article presents a number of long-term follow-ups of programs designed to treat the addictive behaviors of typical adults (Foxx, 1982; Foxx, Brown, & Katz, 1981) and to teach social skills (Foxx & Faw, 1992) and language (Foxx & Faw, 1990) to individuals with intellectual disabilities and autism as well as to decrease their severe maladaptive behaviors (Foxx, 1990; Foxx & Livesay, 1984). In the process, various factors that appeared to contribute to long-term maintenance are identified. The article concludes with some recommendations regarding the study of maintenance. C1 [Foxx, Richard M.] Penn State Harrisburg, Middletown, PA 17057 USA. 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TI A temporally sustained implicit theory of mind deficit in autism spectrum disorders SO COGNITION LA English DT Article DE Implicit theory of mind; Social cognition; Autism spectrum disorders; Eye-movements ID HIGH-FUNCTIONING AUTISM; NORMAL SEX-DIFFERENCES; ASPERGER-SYNDROME; FALSE-BELIEF; MENTAL STATES; ADULTS; ATTENTION; QUOTIENT; INFANTS; OTHERS AB Eye movements during false-belief tasks can reveal an individual's capacity to implicitly monitor others' mental states (theory of mind - TOM). It has been suggested, based on the results of a single-trial-experiment, that this ability is impaired in those with a high-functioning autism spectrum disorder (ASD), despite neurotypical-like performance on explicit ToM measures. However, given there are known attention differences and visual hypersensitivities in ASD it is important to establish whether such impairments are evident over time. In addition, investigating implicit ToM using a repeated trial approach allows an assessment of whether learning processes can reduce the ASD impairment in this ability, as is the case with explicit ToM. Here we investigated the temporal profile of implicit ToM in individuals with ASD and a control group. Despite similar performance on explicit ToM measures, ASD-diagnosed individuals showed no evidence of implicit false-belief tracking even over a one-hour period and many trials, whereas control participants did. These findings demonstrate that the systems involved in implicit and explicit ToM are distinct and hint that impaired implicit false-belief tracking may play an important role in ASD. Further, they indicate that learning processes do not alleviate this impairment across the presentation of multiple trials. (C) 2013 Elsevier B.V. All rights reserved. C1 [Schneider, Dana; Slaughter, Virginia P.; Dux, Paul E.] Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia. 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However, recent data suggest that the immune response of the offspring is also affected by events during the gestational period. Here, we evaluated the impact of prenatal immune activation on the innate and adaptive immune responses of adult offspring. Pregnant Swiss mice received saline or lipopolysaccharide (LPS) on gestational day 17. In adulthood, male offspring were analyzed using 2 experimental techniques: in vitro analysis of cytokine production and immune cell activity and development of the delayed-type hypersensitivity (DTH) responses of ovalbumin-sensitized mice. We analyzed Th1/Th2/Th17 cytokine production in vitro, neutrophil and dendritic cell function, and the DTH response. Offspring from LPS-treated dams displayed increased cell-mediated immunity as indicated by increased IL-12 production by cultured antigen-presenting cells and an enhanced DTH response as well as impaired production of the regulatory cytokine IL-10. This study provides new insights regarding the influence of immune activation during late gestation on the immunological homeostasis of offspring, particularly on Th1 immunity. (C) 2013 Elsevier B.V. All rights reserved. C1 [Zager, Adriano; Pinheiro, Milena Lobao; Ferraz-de-Paula, Viviane; Ribeiro, Alison; Palermo-Neto, Joao] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Neuroimmunomodulat Res Grp, BR-05508270 Sao Paulo, Brazil. RP Zager, A (reprint author), Univ Sao Paulo, Sch Vet Med, Dept Pathol, Av Prof Dr Orlando Marques de Paiva 87,Cidade Uni, BR-05508270 Sao Paulo, Brazil. EM adrianozager@hotmail.com FU CNPq; FAPESP [09/51886-3, 09/51998-6] FX This work was supported by grants from the CNPq and FAPESP (Thematic Awards #09/51886-3 to JPN, #09/51998-6 to AZ). 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Immunopharmacol. PD NOV PY 2013 VL 17 IS 3 SI SI BP 633 EP 637 DI 10.1016/j.intimp.2013.08.007 PG 5 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 255ZU UT WOS:000327280100021 PM 23994465 ER PT J AU Pilarski, R Burt, R Kohlman, W Pho, L Shannon, KM Swisher, E AF Pilarski, Robert Burt, Randall Kohlman, Wendy Pho, Lana Shannon, Kristen M. Swisher, Elizabeth TI Cowden Syndrome and the PTEN Hamartoma Tumor Syndrome: Systematic Review and Revised Diagnostic Criteria SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RILEY-RUVALCABA-SYNDROME; AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; CORE-NEEDLE-BIOPSY; GENOTYPE-PHENOTYPE CORRELATIONS; LIFETIME CANCER-RISKS; GERMLINE PTEN; MULTIPLE HAMARTOMA; BREAST-CANCER; GASTROINTESTINAL POLYPOSIS AB Background PTEN hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Diagnostic criteria for Cowden syndrome, the principal PTEN-related disorder, were first established in 1996 before the identification of the PTEN gene and the ability to molecularly confirm a clinical diagnosis. These consortium criteria were based on clinical experience and case reports in the existing literature, with their inherent selection biases. Although it was initially reported that approximately 80% of patients with Cowden syndrome had an identifiable germline PTEN mutation, more recent work has shown these diagnostic criteria to be far less specific. In addition, increasing evidence has documented the association of a broader spectrum of clinical features with PTEN mutations. Our goal was to develop revised, evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN-related clinical syndromes. Methods We performed a systematic search and review of the medical literature related to clinical features reported in individuals with a PTEN mutation and/or a related clinical diagnosis. Results We found no sufficient evidence to support inclusion of benign breast disease, uterine fibroids, or genitourinary malformations as diagnostic criteria. There was evidence to include autism spectrum disorders, colon cancer, esophageal glycogenic acanthosis, penile macules, renal cell carcinoma, testicular lipomatosis, and vascular anomalies. Conclusions We propose revised, evidence-based criteria covering the spectrum of PTEN-related clinical disorders. Additional research on clinical features associated with PTEN mutations is warranted. C1 [Pilarski, Robert] Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43240 USA. [Pilarski, Robert] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43240 USA. [Burt, Randall; Kohlman, Wendy; Pho, Lana] Huntsman Canc Inst, Salt Lake City, UT USA. [Burt, Randall; Kohlman, Wendy] Univ Utah, Sch Med, Salt Lake City, UT USA. [Pho, Lana] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Shannon, Kristen M.] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Assessment, Boston, MA USA. [Swisher, Elizabeth] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. RP Pilarski, R (reprint author), Ohio State Univ, Clin Canc Genet Program, 2001 Polaris Pkwy, Columbus, OH 43240 USA. 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Natl. Cancer Inst. PD NOV PY 2013 VL 105 IS 21 BP 1607 EP 1616 DI 10.1093/jnci/djt277 PG 11 WC Oncology SC Oncology GA 251ZL UT WOS:000326973900007 PM 24136893 ER PT J AU Kral, TVE Eriksen, WT Souders, MC Pinto-Martin, JA AF Kral, Tanja V. E. Eriksen, Whitney T. Souders, Margaret C. Pinto-Martin, Jennifer A. TI Eating Behaviors, Diet Quality, and Gastrointestinal Symptoms in Children With Autism Spectrum Disorders: A Brief Review SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Review DE Children; Autism spectrum disorders; Eating behaviors; Dietary intake; Gastrointestinal health ID TYPICALLY DEVELOPING-CHILDREN; INTESTINAL BARRIER; FOOD SELECTIVITY; YOUNG-CHILDREN; PREVALENCE; ACCEPTANCE; SUPPLEMENT; PATTERNS; GLIADIN AB Children with autism spectrum disorders (ASD) and their caregivers face unique challenges in the children's daily eating routines and food intake patterns. The aim of this brief review is to describe eating behaviors of children with ASD, including increased food neophobia and food selectivity, and review findings on children's diet quality, and gastrointestinal (GI) symptoms. Advancing knowledge about the interrelationships between these nutrition-related domains in children with ASD is expected to have important implications for clinical nursing practice and caregiver care. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kral, Tanja V. E.; Eriksen, Whitney T.; Souders, Margaret C.; Pinto-Martin, Jennifer A.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Kral, Tanja V. E.; Pinto-Martin, Jennifer A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kral, TVE (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. EM tkral@nursing.upenn.edu FU Hillman Scholars Program in Nursing Innovation FX We acknowledge funding support from the Hillman Scholars Program in Nursing Innovation. 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Pediatr. Nurs. PD NOV-DEC PY 2013 VL 28 IS 6 BP 548 EP 556 DI 10.1016/j.pedn.2013.01.008 PG 9 WC Nursing; Pediatrics SC Nursing; Pediatrics GA 251NX UT WOS:000326937600016 PM 23531467 ER PT J AU Giarelli, E Ruttenberg, J Segal, A AF Giarelli, Ellen Ruttenberg, Jean Segal, Andrea TI Bridges and Barriers to Successful Transitioning as Perceived by Adolescents and Young Adults With Asperger Syndrome SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES LA English DT Article DE Asperger syndrome; Autism spectrum disorder; Transition to community; Adolescents ID AUTISM SPECTRUM DISORDERS; CHILDREN; BEHAVIOR; SCHOOL AB In this thematic content analysis we examined the expectations, and perceived facilitators of (referred to as bridges) and barriers to transition to community as reported by adolescents and young adults with Asperger syndrome. Participants were adolescents/young adults, ages 18-23 years were from the East Coast of the United States. Seventy percent of adolescents hoped for employment (n = 10). Thirty percent desired to find a partner and raise a family. Perceived barriers were: self-assessed behavioral problems, self-assessed associated features, other personal factors, and institutional factors. Bridges to facilitate transition were: accommodations in the community, cognitive abilities, personal qualities/strengths, and mentor's qualities. (C) 2013 Elsevier Inc. All rights reserved. C1 [Giarelli, Ellen] Drexel Univ, Coll Nursing & Hlth Profess, Philadelphia, PA 19104 USA. [Ruttenberg, Jean] Ctr Autism, Philadelphia, PA USA. [Segal, Andrea] Drexel Univ, Sch Arts & Sci, Philadelphia, PA 19104 USA. RP Giarelli, E (reprint author), Drexel Univ, Coll Nursing & Hlth Profess, Philadelphia, PA 19104 USA. EM eg446@drexel.edu FU Philadelphia Health Care Trust FX The project was funded by a grant from the Philadelphia Health Care Trust. 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PD NOV-DEC PY 2013 VL 28 IS 6 BP 563 EP 574 DI 10.1016/j.pedn.2012.12.010 PG 12 WC Nursing; Pediatrics SC Nursing; Pediatrics GA 251NX UT WOS:000326937600018 PM 23541737 ER PT J AU Bohm, HV Stewart, MG Healy, AM AF Bohm, H. V. Stewart, M. G. Healy, A. M. TI On the Autistic Spectrum Disorder concordance rates of twins and non-twin siblings SO MEDICAL HYPOTHESES LA English DT Article AB Using the Interactive Autism Network Research Database, the Autistic Spectrum Disorder concordance rates for twins and non-twin siblings were calculated. For males, females and both genders together, the concordance rate for dizygotic twins is approximately twice that of non-twin siblings. We also determined that the concordance rate for non-twin siblings decreases as the interval between pregnancies increases. Our results appear to indicate that the uterine environment may contribute to autism concordance rates. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Bohm, H. V.; Stewart, M. 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USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2013 VL 31 IS 4 BP 951 EP + DI 10.1016/j.ncl.2013.04.009 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 261QP UT WOS:000327680000005 PM 24176418 ER PT J AU Rodrigues, JL Goncalves, N Costa, S Soares, F AF Rodrigues, Jose L. Goncalves, Nuno Costa, Sandra Soares, Filomena TI Stereotyped movement recognition in children with ASD SO SENSORS AND ACTUATORS A-PHYSICAL LA English DT Article; Proceedings Paper CT 26th European Conference on Solid-State Transducers (Eurosensors) CY SEP 09-12, 2012 CL Krakow, POLAND HO Wroclaw Univ Technol, Fac Microsystem Elect & Photon DE Accelerometer sensor; Stereotyped motor movements; Gesture recognition AB Autism Spectrum Disorders (ASD) manifest in different behaviors, being one of them body rocking, mouthing, and complex hand and finger movements [1]. The traditional methods for recording the number of occurrences and duration of stereotypes are inadequate and time consuming. Therefore, it was used a commercial system with accelerometers sensors that records the movement of wrist. The collected data is sent through a wireless network to the computer, where an application was developed to distinguish the movement made by the children as a stereotyped gesture, hand flapping movement, from a normal gesture. The system was previously tested in laboratory environment and during the intervention sessions. Statistical methods were used to characterize the signal acquired from a previously expressed stereotype recorded from a child with ASD. The parameters that were analyzed are: Root Mean Square (RMS), Standard Variation, Peaks and Valleys. At the end, the proposed methodology facilitates to identify behavioral patterns special relevant when studying interaction skills in children with ASD. (C) 2013 Published by Elsevier B.V. C1 [Rodrigues, Jose L.; Goncalves, Nuno; Costa, Sandra; Soares, Filomena] Univ Minho, R&D Ctr Algoritmi, P-4800058 Guimaraes, Portugal. RP Soares, F (reprint author), Univ Minho, R&D Ctr Algoritmi, Campus Azurem, P-4800058 Guimaraes, Portugal. EM filomena.soares@algoritmi.uminho.pt CR Albinali F., RECOGNIZING STEREOTY Baek J, 2004, LECT NOTES ARTIF INT, V3215, P610 Costa S., 2009, EMBC 2009 ENG MED BI Costa S., 2011, ROMAN 2011 20 IEEE I Costa S., 2010, EMBC 2010 ENG MED BI Goodwin MS, 2011, J AUTISM DEV DISORD, V41, P770, DOI 10.1007/s10803-010-1102-z Silva S., 2012, 2 PORT M BIOENG PORT NR 7 TC 0 Z9 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0924-4247 J9 SENSOR ACTUAT A-PHYS JI Sens. Actuator A-Phys. PD NOV 1 PY 2013 VL 202 SI SI BP 162 EP 169 DI 10.1016/j.sna.2013.04.019 PG 8 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 252KO UT WOS:000327003800025 ER PT J AU Schreck, KA Russell, M Vargas, LA AF Schreck, Kimberly A. Russell, Melissa Vargas, Luis A. TI AUTISM TREATMENTS IN PRINT: MEDIA'S COVERAGE OF SCIENTIFICALLY SUPPORTED AND ALTERNATIVE TREATMENTS SO BEHAVIORAL INTERVENTIONS LA English DT Article ID SPECTRUM DISORDERS; CHILDREN; COMPLEMENTARY; PARENTS; MEDICINE AB Professionals, celebrities, and media frequently suggest to parents the possible treatment options for their children with autism. Some treatment recommendations advocate for scientifically supported treatments whereas others suggest novel, untested interventions, or potentially ineffective or harmful treatments. The current study examined the print media's coverage of applied behavior analysis (ABA) and non-scientifically supported autism treatments. Over the last 10years, print media have increasingly published articles referring to autism treatments with little scientific support and a decreased coverage of ABA. Print media's positive statements about non-scientifically supported treatments also increased over the last decade, whereas positive statements about ABA decreased. ABA received two times as many positive comments as negative; however, non-scientifically supported treatments as a group received four times as many positive comments as negative. These results could contribute to parents' decisions to implement treatments for their children with autism. To contribute to future positive perception of ABA, we provided suggestions for the dissemination of information to increase positive reporting of ABA in print media. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Schreck, Kimberly A.; Russell, Melissa; Vargas, Luis A.] Penn State Harrisburg, Middletown, PA 17057 USA. RP Schreck, KA (reprint author), Penn State Harrisburg, 777 West Harrisburg Pike, Middletown, PA 17057 USA. 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PD NOV PY 2013 VL 28 IS 4 BP 299 EP 321 DI 10.1002/bin.1370 PG 23 WC Psychology, Clinical SC Psychology GA 254ZA UT WOS:000327207600003 ER PT J AU Lequia, J Machalicek, W Lyons, G AF Lequia, Jenna Machalicek, Wendy Lyons, Gregory TI PARENT EDUCATION INTERVENTION RESULTS IN DECREASED CHALLENGING BEHAVIOR AND IMPROVED TASK ENGAGEMENT FOR STUDENTS WITH DISABILITIES DURING ACADEMIC TASKS SO BEHAVIORAL INTERVENTIONS LA English DT Article ID AUTISM SPECTRUM DISORDERS; STRUCTURED DESCRIPTIVE ASSESSMENT; SCHOOL INVOLVEMENT; CONTROLLED-TRIAL; YOUNG-CHILDREN; HOMEWORK; ADHD; ACHIEVEMENT; TODDLERS; STRESS AB Children with developmental disabilities and attention deficit hyperactivity disorder often engage in challenging behavior when presented with academic demands. Parents of school-age children with such diagnoses are commonly asked to assist their child with academic tasks but may struggle to do so as a result of challenging behavior. This study evaluated the effects of a parent education intervention on the challenging behaviors and task engagement of three school-age children with disabilities during academic activities. Parent education consisted of (i) weekly didactic instruction; (ii) modeling; (iii) role-play; and (iv) in vivo coaching and performance feedback. Using a non-concurrent multiple baseline across participants with embedded individual multi-element design, this study demonstrates that a parent education intervention results in decreases in challenging behavior and increases in task engagement. These results suggest that parent education focused on addressing challenging behavior during one-to-one instruction may facilitate completion of academic tasks. Implications for practice and suggestions for future research are discussed. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Lequia, Jenna; Lyons, Gregory] Univ Wisconsin, Madison, WI 53706 USA. [Machalicek, Wendy] Univ Oregon, Eugene, OR 97403 USA. 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Alessandri, Michael TI DIFFERENTIAL RESPONSE PATTERNS TO THE CONTROL CONDITION BETWEEN TWO PROCEDURES TO ASSESS SOCIAL REINFORCERS FOR CHILDREN WITH AUTISM SO BEHAVIORAL INTERVENTIONS LA English DT Article ID PREFERENCE; DISABILITIES AB Historically, reinforcer assessment procedures focus primarily on identifying nonsocial reinforcers (e.g., tangibles and edibles). Far less empirical attention has been allocated to the systematic identification of social consequences that function as reinforcers. This discrepancy is problematic given that social consequences are commonly incorporated into behavioral treatment programs without systematic evaluation of their efficacy. In this study, two methodologies (a single operant and a concurrent choice) were used to assess social reinforcers for children with autism. Results highlighted differences in response allocation to the control condition between procedures. 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PD NOV PY 2013 VL 28 IS 4 BP 353 EP 361 DI 10.1002/bin.1372 PG 9 WC Psychology, Clinical SC Psychology GA 254ZA UT WOS:000327207600006 ER PT J AU Lado, FA Rubboli, G Capovilla, P Avanzini, G Moshe, SL AF Lado, Fred A. Rubboli, Guido Capovilla, Pippo Avanzini, Giuliano Moshe, Solomon L. TI Pathophysiology of epileptic encephalopathies SO EPILEPSIA LA English DT Article DE Epileptic encephalopathy; Epilepsy; Mental retardation; Cognitive impairment; Interneuron; Genetics; Subcortical nuclei; Synapse; Synaptic plasticity; Animal models ID INFANTILE SPASMS; INTERNEURON DISTRIBUTION; CORTICAL DYSPLASIA; MOUSE MODEL; SEIZURES; CNTNAP2; AUTISM; SLEEP; CLASSIFICATION; SUSCEPTIBILITY AB The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype. C1 [Lado, Fred A.] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Bronx, NY 10467 USA. [Lado, Fred A.; Moshe, Solomon L.] Montefiore Med Ctr, Bronx, NY 10461 USA. [Rubboli, Guido] Epilepsihosp, Danish Epilepsy Ctr, Dianalund, Denmark. [Rubboli, Guido] Bellaria Hosp, Dept Neurosci, Neurol Unit, Bologna, Italy. [Capovilla, Pippo] Carlo Poma Hosp, Epilepsy Ctr, Dept Child Neuropsychiat, Mantua, Italy. [Avanzini, Giuliano] IRCCS Fdn, Neurol Inst, Dept Neurophysiol, Milan, Italy. [Moshe, Solomon L.] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA. [Moshe, Solomon L.] Albert Einstein Coll Med, Montefiore Einstein Epilepsy Management Ctr, Dept Pediat, Lab Dev Epilepsy, Bronx, NY 10467 USA. RP Lado, FA (reprint author), Montefiore Med Ctr, EEG Lab, 111 E 210 St, Bronx, NY 10461 USA. 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Oerlemans, Anoek M. de Ruiter, Saskia W. van Aken, Marcel A. G. Buitelaar, Jan K. Rommelse, Nanda N. J. TI Are parental autism spectrum disorder and/or attention-deficit/Hyperactivity disorder symptoms related to parenting styles in families with ASD ( plus ADHD) affected children? SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Autism spectrum disorder; Attention-deficit/hyperactivity disorder; Parental symptoms; Parenting styles ID DEFICIT HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; GENERAL-POPULATION; BEHAVIOR PROBLEMS; QUOTIENT AQ; SELF-REPORT; ADULTS; PERSONALITY; VALIDITY; TRAITS AB An understudied and sensitive topic nowadays is that even subthreshold symptoms of autism spectrum disorder (ASD) and attention-deficit/Hyperactivity disorder (ADHD) in parents may relate to their parenting styles. The aim of this study was to explore the influence of (the combined) effect of child diagnosis (ASD or ASD + ADHD affected/unaffected children) and parental ASD and/or ADHD on parenting styles. Ninety-six families were recruited with one child with a clinical ASD (+ADHD) diagnosis, and one unaffected sibling. Parental ASD and ADHD symptoms were assessed using self-report. The Parenting Styles Dimensions Questionnaire (PSDQ) self- and spouse-report were used to measure the authoritative, authoritarian, and permissive parenting styles. Fathers and mothers scored significantly higher than the norm data of the PSDQ on the permissive style regarding affected children, and lower on the authoritative and authoritarian parenting style for affected and unaffected children. Self- and spouse-report correlated modestly too strongly. Higher levels of paternal (not maternal) ADHD symptoms were suboptimally related to the three parenting styles. Further, two parent-child pathology interaction effects were found, indicating that fathers with high ADHD symptoms and mothers with high ASD symptoms reported to use a more permissive parenting style only towards their unaffected child. The results highlight the negative effects of paternal ADHD symptoms on parenting styles within families with ASD (+ADHD) affected offspring and the higher permissiveness towards unaffected offspring specifically when paternal ADHD and/or maternal ASD symptoms are high. Parenting training in these families may be beneficial for the well-being of all family members. C1 [van Steijn, Daphne J.; Oerlemans, Anoek M.; Buitelaar, Jan K.; Rommelse, Nanda N. J.] Karakter Child & Adolescent Psychiat Univ Ctr, NL-6525 GC Nijmegen, Netherlands. [Oerlemans, Anoek M.; de Ruiter, Saskia W.; Rommelse, Nanda N. J.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [van Aken, Marcel A. G.] Univ Utrecht, Dept Dev Psychol, Utrecht, Netherlands. [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP van Steijn, DJ (reprint author), Karakter Child & Adolescent Psychiat Univ Ctr, Reinier Postlaan 12, NL-6525 GC Nijmegen, Netherlands. EM d.vansteijn@karakter.com RI Rommelse, Nanda/D-4872-2009 OI Rommelse, Nanda/0000-0002-1711-0359 FU Netherlands Organisation for Scientific Research (NWO) [91610024] FX We would like to thank parents, teachers, and children for participating in this project. This study was partly funded by a grant assigned to Dr. N. Rommelse by the Netherlands Organisation for Scientific Research (NWO grant # 91610024). 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Child Adolesc. Psych. PD NOV PY 2013 VL 22 IS 11 BP 671 EP 681 DI 10.1007/s00787-013-0408-8 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 253GC UT WOS:000327070800003 PM 23564208 ER PT J AU South, ST Lee, C Lamb, AN Higgins, AW Kearney, HM AF South, Sarah T. Lee, Charles Lamb, Allen N. Higgins, Anne W. Kearney, Hutton M. CA Amer Coll Med Genetics Genomics TI ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013 SO GENETICS IN MEDICINE LA English DT Article DE constitutional; guidelines; microarray; postnatal; prenatal; standards ID COPY NUMBER VARIANTS; MEDICAL GENETICS; AMERICAN-COLLEGE; RESOURCES; ABNORMALITIES; PLATFORMS; DATABASE AB Microarray methodologies, including array comparative genomic hybridization and single-nucleotide polymorphism detecting arrays, are accepted as an appropriate first-tier test for the evaluation of imbalances associated with intellectual disability, autism, and multiple congenital anomalies. This technology also has applicability in prenatal specimens. To assist clinical laboratories in validation of microarray methodologies for constitutional applications, the American College of Medical Genetics and Genomics has produced the following revised professional standards and guidelines. C1 [South, Sarah T.; Lamb, Allen N.] ARUP Labs, Salt Lake City, UT USA. [South, Sarah T.; Lamb, Allen N.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Lee, Charles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Higgins, Anne W.] UMass Mem Med Ctr, Dept Pathol, Worcester, MA USA. [Higgins, Anne W.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kearney, Hutton M.] Mission Hlth, Fullerton Genet Ctr, Asheville, NC USA. RP South, ST (reprint author), ARUP Labs, Salt Lake City, UT USA. 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Little empirical evidence is available involving social cognitive functioning in patients with chronic pain conditions. We investigated the ability of patients with CRPS to recognize the mental/emotional states of other people. Forty-three patients with CRPS and 30 healthy controls performed the Reading Mind in the Eyes Test, which consists of photos in which human eyes express various emotional and mental states. Neuropsychological tests, including the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time test, were administered to evaluate other cognitive functions. Patients with CRPS were significantly less accurate at recognizing emotional states in other persons, but not on other cognitive tests, compared with control subjects. We found a significant association between the deficit in social-emotion recognition and the affective dimension of pain, whereas this deficit was not related to the sensory dimension of pain. 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Pain PD NOV PY 2013 VL 14 IS 11 BP 1304 EP 1309 DI 10.1016/j.jpain.2013.05.008 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252YD UT WOS:000327047900004 PM 23876283 ER PT J AU Zaslav, AL Marino, MA Jurgens, CY Mercado, T AF Zaslav, Ann-Leslie Marino, Marie Ann Jurgens, Corrine Y. Mercado, Theresa TI Cytogenetic Evaluation: A Primer for Pediatric Nurse Practitioners SO JOURNAL OF PEDIATRIC HEALTH CARE LA English DT Article DE Cytogenetics; karyotyping; FISH; CGH; chromosomal microarrays ID HUMAN CHROMOSOMES; HUMAN GENOME; COPY NUMBER; MICROARRAY; HYBRIDIZATION; STATEMENT; GENETICS AB Patients with genetic disorders require specific types of cytogenetic testing for accurate diagnosis and prognosis followed by prompt treatment. This primer will serve as a guide for pediatric nurse practitioners on the use of various cytogenetic testing for the diagnosis of genetic disorders. Knowledge of the latest cytogenetic technologies will facilitate diagnosis and counseling related to genetic abnormalities such as inherited disorders, mental retardation, developmental delay, and autism. This reference will enable pediatric nurse practitioners to help identify patients with various inherited genetic disorders and provide subsequent monitoring and treatment. C1 [Zaslav, Ann-Leslie; Mercado, Theresa] SUNY Stony Brook, Med Ctr, Dept Pathol, Cytogenet Lab, Stony Brook, NY 11794 USA. [Marino, Marie Ann; Jurgens, Corrine Y.] SUNY Stony Brook, Sch Nursing, Stony Brook, NY 11794 USA. RP Jurgens, CY (reprint author), SUNY Stony Brook, Sch Nursing, HSC L2-246, Stony Brook, NY 11794 USA. EM corrine.jurgens@stonybrook.edu CR CASPERSS.T, 1970, EXP CELL RES, V60, P315, DOI 10.1016/0014-4827(70)90523-9 Cummings M. R., 2009, HUMAN HEREDITY PRINC Gardner RJM, 2012, CHROMOSOME ABNORMALI Gersen S. L., 1999, PRINCIPLES CLIN CYTO Graham Jr JM, 2007, SMITHS RECOGNIZABLE, V3 Hsu T. 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Health Care PD NOV-DEC PY 2013 VL 27 IS 6 BP 426 EP 433 DI 10.1016/j.pedhc.2012.04.006 PG 8 WC Health Policy & Services; Nursing; Pediatrics SC Health Care Sciences & Services; Nursing; Pediatrics GA 253PQ UT WOS:000327102000005 PM 22595375 ER PT J AU Zhan, QT Pan, PP Xu, XR Lou, HY Lou, YY Jin, F AF Zhan, Qi-tao Pan, Pei-pei Xu, Xiang-rong Lou, Hang-ying Lou, Yi-yun Jin, Fan TI An overview of studies on psychological well-being in children born following assisted reproductive technologies SO JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B LA English DT Review DE Assisted reproductive technologies; Psychological well-being; Behavior problems; Parent-child relationship ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; BECKWITH-WIEDEMANN-SYNDROME; QUALITY-OF-LIFE; SPONTANEOUSLY CONCEIVED CHILDREN; PSYCHOMOTOR DEVELOPMENT; COGNITIVE-DEVELOPMENT; SINGLETON CHILDREN; MOTOR DEVELOPMENT; PARENT AB Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review. C1 [Zhan, Qi-tao; Pan, Pei-pei; Xu, Xiang-rong; Lou, Hang-ying; Lou, Yi-yun; Jin, Fan] Zhejiang Univ, Sch Med, Womens Hosp, Dept Reprod Endocrinol, Hangzhou 310006, Zhejiang, Peoples R China. RP Jin, F (reprint author), Zhejiang Univ, Sch Med, Womens Hosp, Dept Reprod Endocrinol, Hangzhou 310006, Zhejiang, Peoples R China. 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Zhejiang Univ.-SCI. B PD NOV PY 2013 VL 14 IS 11 BP 947 EP 960 DI 10.1631/jzus.B1300101 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 251NK UT WOS:000326936000001 PM 24190441 ER PT J AU Eckstein, M Hurlemann, R AF Eckstein, M. Hurlemann, R. TI Oxytocin. Evidence for a therapeutic potential of the social neuromodulator SO NERVENARZT LA German DT Article DE Mental disorders; Oxytocin; Social cognition; Treatment; Human studies ID RANDOMIZED-CONTROLLED-TRIAL; AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; ANXIETY DISORDER; HUMANS; STRESS; FACES; SCHIZOPHRENIA; PERCEPTION; RESPONSES AB Only few substances have achieved such a great prominence in recent years as the hypothalamic neuropeptide oxytocin, which is also widely known as the love hormone. Oxytocin is a potent neuromodulator which can improve social cognitive functions including empathy, trust, cooperation and social learning. However, oxytocin can also promote negative social behavior and increase poor memory and feelings of fear in social situations. Positive data from initial clinical trials give rise to the hope that oxytocin will prove to be a substance which is suitable for targeted treatment of poor social-cognitive behavior in neuropsychiatric diseases. This review article summarizes the most important recent preclinical and clinical human studies and discusses the findings presented with respect to current concepts of personal and contextual influences. C1 [Eckstein, M.; Hurlemann, R.] Klin & Poliklin Psychiat & Psychotherapi, Abt Med Psychol & Soziol, D-53105 Bonn, Germany. RP Hurlemann, R (reprint author), Klin & Poliklin Psychiat & Psychotherapi, Abt Med Psychol & Soziol, Sigmund Freud Str 25, D-53105 Bonn, Germany. 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Plaisted-Grant, Kate TI Executive Functions Are Employed to Process Episodic and Relational Memories in Children With Autism Spectrum Disorders SO NEUROPSYCHOLOGY LA English DT Article DE autism spectrum disorder; relational memory; hippocampus; posterior parietal cortex; executive functions ID FREE-RECALL; AUTOBIOGRAPHICAL MEMORY; ASPERGERS-SYNDROME; TEMPORAL-LOBE; PARIETAL LOBE; COGNITIVE DEFICIT; RETRIEVAL; ADULTS; ITEM; DISCRIMINATION AB Objective: Long-term memory functioning in autism spectrum disorders (ASDs) is marked by a characteristic pattern of impairments and strengths. Individuals with ASD show impairment in memory tasks that require the processing of relational and contextual information, but spared performance on tasks requiring more item-based, acontextual processing. Two experiments investigated the cognitive mechanisms underlying this memory profile. Method: A sample of 14 children with a diagnosis of high-functioning ASD (age: M = 12.2 years), and a matched control group of 14 typically developing (TD) children (age: M = 12.1 years), participated in a range of behavioral memory tasks in which we measured both relational and item-based memory abilities. They also completed a battery of executive function measures. Results: The ASD group showed specific deficits in relational memory, but spared or superior performance in item-based memory, across all tasks. Importantly, for ASD children, executive ability was significantly correlated with relational memory but not with item-based memory. No such relationship was present in the control group. This suggests that children with ASD atypically employed effortful, executive strategies to retrieve relational (but not item-specific) information, whereas TD children appeared to use more automatic processes. Conclusions: The relational memory impairment in ASD may result from a specific impairment in automatic associative retrieval processes with an increased reliance on effortful and strategic retrieval processes. Our findings allow specific neural predictions to be made regarding the interactive functioning of the hippocampus, prefrontal cortex, and posterior parietal cortex in ASD as a neural network supporting relational memory processing. C1 [Maister, Lara; Plaisted-Grant, Kate] Univ Cambridge, Dept Expt Psychol, Cambridge Lab Res Autism, Cambridge CB2 3EB, England. [Simons, Jon S.] Univ Cambridge, Dept Expt Psychol, Memory Lab, Cambridge CB2 3EB, England. RP Maister, L (reprint author), Univ London, Dept Psychol, Royal Holloway, Egham Hill, Egham TW20 0EX, Surrey, England. 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METHODS: This retrospective observational study used administrative medical and pharmacy claims data linked with health plan enrollment and sociodemographic information from 2001 to 2009. Children with ASD were identified by using a validated ASD case algorithm. Psychotropic polypharmacy was defined as concurrent medication fills across >= 2 classes for at least 30 days. Multinomial logistic regression was used to model 5 categories of psychotropic use and multiclass polypharmacy. RESULTS: Among 33 565 children with ASD, 64% had a filled prescription for at least 1 psychotropic medication, 35% had evidence of psychotropic polypharmacy (>= 2 classes), and 15% used medications from >= 3 classes concurrently. Among children with polypharmacy, the median length of polypharmacy was 346 days. Older children, those who had a psychiatrist visit, and those with evidence of co-occurring conditions (seizures, attention-deficit disorders, anxiety, bipolar disorder, or depression) had higher odds of psychotropic use and/or polypharmacy. CONCLUSIONS: Despite minimal evidence of the effectiveness or appropriateness of multidrug treatment of ASD, psychotropic medications are commonly used, singly and in combination, for ASD and its co-occurring conditions. Our results indicate the need to develop standards of care around the prescription of psychotropic medications to children with ASD. C1 [Spencer, Donna; Kulakodlu, Mahesh] OptumInsight, Life Sci, Eden Prairie, MN USA. [Marshall, Jaclyn; Post, Brady; Dennen, Taylor; Jain, Anjali] Lewin Grp, Falls Church, VA 22042 USA. [Newschaffer, Craig] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Azocar, Francisca] OptumHlth Behav Solut, San Francisco, CA USA. RP Jain, A (reprint author), Lewin Grp, 3130 Fairview Pk Dr,Suite 600, Falls Church, VA 22042 USA. EM anjali.jain@lewin.com FU National Institute of Mental Health (NIMH), National Institutes of Health, Department of Health and Human Services [HHSN-271-2010-00033-C]; National Institutes of Health (NIH) FX Sponsored by the National Institute of Mental Health (NIMH), National Institutes of Health, Department of Health and Human Services (HHSN-271-2010-00033-C). The NIMH was given a copy of the final draft of the manuscript, but the content of the manuscript is solely the responsibility of the authors and does not necessarily represent the views of the NIMH, the National Institutes of Health, or the federal government. Funded by the National Institutes of Health (NIH). 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Bakian, Amanda V. Viskochil, Joseph Clark, Erin A. S. Botts, Elizabeth L. Smith, Ken R. Pimentel, Richard McMahon, William M. Coon, Hilary TI Maternal Prenatal Weight Gain and Autism Spectrum Disorders SO PEDIATRICS LA English DT Article DE autism; prenatal; weight gain; risk factors; epidemiology ID BREAST-CANCER; PREGNANCY; BIRTH; RISK; SEX; HEPATOBLASTOMA; INDIVIDUALS; PREVALENCE; ESTROGENS; STEROIDS AB BACKGROUND: The rising population of individuals identified with an autism spectrum disorder (ASD) calls for further investigation of its underlying etiology. A disturbance in the fetal steroid hormone environment may be a mechanism in which environmental and genetic risk factors interact. The mother, fetus, and placenta collectively create the fetal steroid environment. Prepregnancy BMI and pregnancy weight gain have served as markers for fetal steroid hormone exposure in other disease states. This study's objective is to determine whether prepregnancy BMI and pregnancy weight gain are associated with increased ASD risk across study designs and cohorts while controlling for important confounding variables. METHODS: A population-based Utah ASD cohort (n = 128) was ascertained in a 3-county surveillance area and gender-and age-matched to 10 920 control subjects. A second, research-based ASD cohort of Utah children (n = 288) and their unaffected siblings (n = 493) were ascertained through participation in an ASD genetics study. Prenatal variables were obtained from birth certificate records. RESULTS: ASD risk was significantly associated with pregnancy weight gain (adjusted odds ratio = 1.10, 95% confidence interval: 1.03 to 1.17; adjusted odds ratio = 1.17, 95% confidence interval: 1.01 to 1.35 for each 5 pounds of weight gained), but not prepregnancy BMI, in population and research-based cohorts, respectively. When analyses were restricted to ASD cases with normal IQ, these associations remained significant. CONCLUSIONS: ASD risk associated with a modest yet consistent increase in pregnancy weight gain suggests that pregnancy weight gain may serve as an important marker for autism's underlying gestational etiology. This justifies an investigation into phenomena that link pregnancy weight gain and ASD independent of prepregnancy BMI. C1 [Bilder, Deborah A.; Bakian, Amanda V.; Viskochil, Joseph; Botts, Elizabeth L.; McMahon, William M.; Coon, Hilary] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Clark, Erin A. S.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Smith, Ken R.; Pimentel, Richard] Univ Utah, Dept Populat Sci, Salt Lake City, UT USA. RP Bilder, DA (reprint author), Utah Autism Res Program, 650 Komas Dr,Suite 206, Salt Lake City, UT 84108 USA. EM deborah.bilder@hsc.utah.edu FU Centers for Disease Control and Prevention [CCU822365]; National Institute of Mental Health [R01 MH069359, R01 MH094400]; National Institute on Aging [R01 AG022095]; National Institutes of Health (NIH) FX Partially funded by the Centers for Disease Control and Prevention under Cooperative Agreement CCU822365 to establish Population-Based Surveillance of Autism Spectrum Disorders, the Utah Registry of Autism and Developmental Disabilities, the National Institute of Mental Health grants R01 MH069359 and R01 MH094400, National Institute on Aging grant R01 AG022095, and Autism Speaks. Funded by the National Institutes of Health (NIH). 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Bloch, Michael H. Panza, Kaitlyn E. Reichow, Brian TI Cognitive-Behavioral Therapy for Anxiety in Children With High-Functioning Autism: A Meta-analysis SO PEDIATRICS LA English DT Review DE autism spectrum disorder; cognitive-behavior therapy; anxiety; children; adolescents; randomized controlled trial; meta-analysis ID PERVASIVE DEVELOPMENTAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; SPECTRUM DISORDERS; OPEN-LABEL; PSYCHIATRIC-DISORDERS; REPETITIVE BEHAVIOR; ASPERGER-SYNDROME; CLINICAL-TRIAL; ADOLESCENTS; SYMPTOMS AB BACKGROUND: Anxiety is a common and impairing problem in children and adolescents with autism spectrum disorder (ASD). There is emerging evidence that cognitive-behavioral therapy (CBT) could reduce anxiety in children with high-functioning ASD. OBJECTIVE: To systematically review the evidence of using CBT to treat anxiety in children and adolescents with ASD. Methods for this review were registered with PROSPERO (CRD42012002722). METHODS: We included randomized controlled trials published in English in peer-reviewed journals comparing CBT with another treatment, no treatment control, or waitlist control. Two authors independently screened 396 records obtained from database searches and hand searched relevant journals. Two authors independently extracted and reconciled all data used in analyses from study reports. RESULTS: Eight studies involving 469 participants (252 treatment, 217 comparison) met our inclusion criteria and were included in meta-analyses. Overall effect sizes for clinician-and parent-rated outcome measures of anxiety across all studies were d = 1.19 and d = 1.21, respectively. Five studies that included child self-report yielded an average d = 0.68 across self-reported anxiety. CONCLUSIONS: Parent ratings and clinician ratings of anxiety are sensitive to detecting treatment change with CBT for anxiety relative to waitlist and treatment-as-usual control conditions in children with high-functioning ASD. Clinical studies are needed to evaluate CBT for anxiety against attention control conditions in samples of children with ASD that are well characterized with regard to ASD diagnosis and co-occurring anxiety symptoms. C1 [Sukhodolsky, Denis G.; Bloch, Michael H.; Panza, Kaitlyn E.; Reichow, Brian] Yale Univ, Yale Child Study Ctr, New Haven, CT USA. RP Sukhodolsky, DG (reprint author), Yale Child Study Ctr, 230 South Frontage Rd, New Haven, CT 06520 USA. EM denis.sukhodolsky@yale.edu FU National Institutes of Health (NIH); [K01 MH079130]; [K23MH091240] FX Supported in part by grants K01 MH079130 (Dr Sukhodolsky) and K23MH091240 (Dr Bloch). Funded by the National Institutes of Health (NIH). 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J., 2008, CHILD ANXIETY DISORD Wood JJ, 2009, J CHILD PSYCHOL PSYC, V50, P224, DOI 10.1111/j.1469-7610.2008.01948.x Wood JJ, 2005, BEHAV INTERVENTION A NR 77 TC 4 Z9 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2013 VL 132 IS 5 BP E1341 EP E1350 DI 10.1542/peds.2013-1193 PG 10 WC Pediatrics SC Pediatrics GA 245PE UT WOS:000326475000027 PM 24167175 ER PT J AU Jarmolowska, B Teodorowicz, M Fiedorowicz, E Sienkiewicz-Szlapka, E Matysiewicz, M Kostyra, E AF Jarmolowska, Beata Teodorowicz, Malgorzata Fiedorowicz, Ewa Sienkiewicz-Szlapka, Edyta Matysiewicz, Michal Kostyra, Elzbieta TI Glucose and calcium ions may modulate the efficiency of bovine beta-casomorphin-7 permeability through a monolayer of Caco-2 cells SO PEPTIDES LA English DT Article DE beta-Casomorphin-7; Caco-2 cells monolayer; Food allergy; Infant formula; Permeability coefficient ID BETA-CASOMORPHIN; OPIOID-PEPTIDES; TIGHT JUNCTIONS; ENDOTHELIAL PERMEABILITY; INTESTINAL PERMEABILITY; GENE-EXPRESSION; TRANSPORT; MILK; ABSORPTION; IV AB Milk and dairy products provide a lot of valuable nutritive elements. They are also sources of biologically active peptides, including beta-casomorphins that manifest the properties of morphine. An activity of DPPIV seems to be most crucial factor decreasing the efficiency of the beta-casomorphin-7 (BCM7) transport. The increase of BCM7 concentration in blood may intensify symptoms of apparent life threatening events (ALTE), autism, schizophrenia, and allergy. This study aimed at identifying the influence of several selected substances on a transport efficiency of bovine BCM7 through an intestinal monolayer in a Caco-2 cell model system. Applying the ELISA method, the permeability coefficient of BCM7 through the Caco-2 monolayer was calculated. TEER values were used to evaluate the integrity of Caco-2 cell monolayers. An increase of glucose and Ca2+ concentrations in the culture medium was accompanied by an increase of the BCM7 transport efficiency. The lowest permeability coefficients of BCM7 were observed for the membranes with high electrical resistances. The transport was enhanced in the presence of milk infant formulas, whereas no changes were observed when using mu-opioid receptor antagonist (casoxin-6). The results may be useful in understanding the pathogenesis of inflammation and food allergy in infants. (C) 2013 Elsevier Inc. All rights reserved. C1 [Jarmolowska, Beata; Fiedorowicz, Ewa; Sienkiewicz-Szlapka, Edyta; Matysiewicz, Michal; Kostyra, Elzbieta] Univ Warmia & Mazury, Fac Biol & Biotechnol, Dept Biochem, PL-10719 Olsztyn, Poland. [Teodorowicz, Malgorzata] Univ Wageningen & Res Ctr, Cell Biol & Immunol Grp, NL-6708 WD Wageningen, Netherlands. RP Kostyra, E (reprint author), Univ Warmia & Mazury, Fac Biol & Biotechnol, Dept Biochem, Ul Oczapowskiego 1A, PL-10719 Olsztyn, Poland. EM elzbieta.kostyra@uwm.edu.pl FU [NN 312 3153 37] FX The authors would like to thank all their collaborators who participated in the research presented in this study. This scientific research has been financed from the resources designed for science in 2009-2012 as Research Project No. NN 312 3153 37. 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Bernstein, Alec Rojahn, Johannes Schroeder, Stephen R. TI The progression of severe behavior disorder in young children with intellectual and developmental disabilities SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Intellectual disability; Developmental disability; Autism spectrum disorder; Down syndrome; Challenging behaviors; Behavior disorders; Self-injury; Stereotypy; Aggression; Structural equation modeling ID SELF-INJURIOUS-BEHAVIOR; CHALLENGING BEHAVIORS; PROBLEMS-INVENTORY; ADULTS; SPECTRUM; PEOPLE; TODDLERS; VALIDITY; INFANT AB Behavior disorders, such as self-injurious, stereotypic, and aggressive behavior are common among individuals with intellectual or developmental disabilities. While we have learned much about those behaviors over the past few decades, longitudinal research that looks at developmental trajectory has been rare. This study was designed to examine the trajectory of these three forms of severe behavior disorders over a one year time period. The behaviors were measured on two dimensions: frequency of occurrence and severity. Participants were 160 infants and toddlers at risk for developmental delays in Lima, Peru. Using structural equation modeling, we found that the frequency of self-injury and stereotypic behavior and the severity of aggressive behavior remained stable over the 12-month period. Uni-directional structural models fit the data best for self-injurious and aggressive behavior (with frequency being a leading indicator of future severity of sel-injury and severity being a leading indicator of future frequency for aggression). For stereotypic behavior, a cross-lagged autoregressive model fit the data best, with both dimensions of frequency and severity involved as leading indicators of each other. These models did not vary significantly across diagnostic groups, suggesting that toddlers exhibiting behavior disorders may be assisted with interventions that target the specific frequencies or severities of behaviors, regardless of diagnostic category. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Medeiros, Kristen; Curby, Timothy W.; Bernstein, Alec; Rojahn, Johannes] George Mason Univ, Fairfax, VA 22030 USA. [Schroeder, Stephen R.] Univ Kansas, Lawrence, KS 66045 USA. RP Rojahn, J (reprint author), George Mason Univ, 10340 Democracy Lane,Suite 202,MSN 2C6, Fairfax, VA 22030 USA. EM kmedeiro@gmu.edu; tcurby@gmu.edu; abernst2@gmu.edu; jrojahn@gmu.edu; schroeder@ku.edu CR Achenbach T., 2000, HDB DEV PSYCHOPATHOL, P41 Albers CA, 2007, J PSYCHOEDUC ASSESS, V25, P180, DOI 10.1177/0734282906297199 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bayley N, 2006, BAYLEY SCALES INFANT, V3rd Bodfish J.W., 1999, REPETITIVE BEHAV SCA Bollen Kenneth A., 1989, STRUCTURAL EQUATIONS Borkowski J. 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PD NOV PY 2013 VL 34 IS 11 BP 3639 EP 3647 DI 10.1016/j.ridd.2013.08.002 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900002 PM 24012587 ER PT J AU Mazzone, L Postorino, V De Peppo, L Fatta, L Lucarelli, V Reale, L Giovagnoli, G Vicari, S AF Mazzone, Luigi Postorino, Valentina De Peppo, Lavinia Fatta, Laura Lucarelli, Valeria Reale, Laura Giovagnoli, Giulia Vicari, Stefano TI Mood symptoms in children and adolescents with autism spectrum disorders SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorders; Depressive symptoms; Mood symptoms; Global functioning; Comorbidity ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; MANIA RATING-SCALE; ASPERGER-SYNDROME; DEPRESSIVE SYMPTOMS; ANXIETY SYMPTOMS; ITALIAN CHILDREN; ADULTS; COMORBIDITY; VERSION AB Asperger Syndrome (AS) and High Functioning Autism (HFA) are psychiatric conditions belonging to the Autistic Spectrum Disorders (ASDs), characterized by social dysfunction and focused interest, in the absence of mental retardation. Previous reports suggest that AS/HFA may be associated with important psychiatric comorbidities. Among the psychiatric internalizing disorders, depression and anxiety are probably the most common disorders. The aim of this study is to evaluate the prevalence of mood disorders and identifying peculiar clinical features in subjects suffering from AS and HFA. 30 male patients with AS/HFA, 30 male patients affected by Major Depression (MD) and 35 male Typically Developing (TD) comparison were assessed with the CDI and the CDRS-R. Participants' parents were invited to complete the CBCL and the P-YMRS. Moreover, the CGAS was rated by the clinicians. The evaluation of depressive symptoms showed that AS/HFA group reported higher depressive symptoms, as showed by CDI total, CBCL internalizing and CDRS-R total, compared to the TD group. No significant difference of depressive symptoms was found between the AS/HFA and the MD group, with the exception of CDRS-R total score. Moreover, linear regression analysis in the AS/HFA group between CGAS and depressive symptoms revealed that a higher level of depressive symptoms increased the risk of poorer global functioning. These results suggest that the depressive symptoms in AS/HFA patients may be associated with poorer global functioning, with a consequent impairment in their psychological profile and social adjustment, and should alert clinicians to the importance of assessing mood disorders in order to choose the appropriate treatment. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mazzone, Luigi; Postorino, Valentina; De Peppo, Lavinia; Fatta, Laura; Lucarelli, Valeria; Giovagnoli, Giulia; Vicari, Stefano] IRCCS Childrens Hosp Bambino Gesu, Dept Neurosci, Child Neuropsychiat Unit, I-00165 Rome, Italy. [Reale, Laura] Univ Catania, Dept Pediat, Div Child Neurol & Psychiat, I-95124 Catania, Italy. 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Dev. Disabil. PD NOV PY 2013 VL 34 IS 11 BP 3699 EP 3708 DI 10.1016/j.ridd.2013.07.034 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900010 PM 24029798 ER PT J AU Lai, DC Tseng, YC Guo, HR AF Lai, Der-Chung Tseng, Yen-Cheng Guo, How-Ran TI Trends in the prevalence of childhood disability: Analysis of data from the national disability registry of Taiwan, 2000-2011 SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorders; Childhood disability; Intellectual disability; Prevalence; Taiwan ID PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDERS; LOW-BIRTH-WEIGHT; INTELLECTUAL DISABILITY; GEOGRAPHIC DIFFERENCES; CHILDREN ANALYSIS; MENTAL-RETARDATION; INCOME COUNTRIES; EPIDEMIOLOGY; GENDER AB Childhood disability is not uncommon, but data at the national level are limited, especially those on the changes in the prevalence over time. On the basis of the Disabled Welfare Act, Taiwan began to certify disabled residents and provide various services in 1980. All the cases receiving services are registered, and the registry provides a rare opportunity for studying childhood disability at the national level. Using the data from 2000 to 2011, we calculated the age-specific prevalence of all disability combined and assessed the changes over time. We also calculated the prevalence rate and the proportion in all disabilities combined for each disability category and assessed the trends. As certification before 3 years old is generally discouraged by the government, we limited analyses to children between 3 and 17 years old. We found that the registered cases ranged from 49,242 to 61,717 from 2000 to 2011 and that intellectual disability (ID), had been the leading category all through the years. The proportion of autism spectrum disorders (ASD) had been increasing rapidly and become the third leading disability in 2011. The prevalence of all disabilities combined increased constantly from 9.98/1000 to 15.41/1000 (p < 0.01), and increases were generally observed every year in all age groups (p < 0.01). The increase could largely be attributable to the increases in ID and ASD, while the increasing trends were also significant in "multiple disabilities," "speech or language impairment," and "other disabilities listed by the Department of Health" (p < 0.01 for all the five categories). An increase with age in the prevalence of all disabilities combined could be observed all through the years (p < 0.01 in all calendar years). We concluded that the prevalence of childhood disability has been increasing in Taiwan, with ID contributing the most cases and ASD as an emerging problem. However, the increase of prevalence cannot be attributed entirely to the increase in the occurrence of cases, and an increase in the proportion of cases registered was an more important factor, which may be in turn attributable to a better service of the related agencies, lower discrimination against the patients, higher awareness of the disorder, and more willingness of the guardians to register. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lai, Der-Chung] Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Phys Med & Rehabil, Chiayi, Taiwan. [Lai, Der-Chung] Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management, Tainan, Taiwan. [Tseng, Yen-Cheng] Chang Jung Christian Univ, Dept Business Adm, Tainan, Taiwan. [Tseng, Yen-Cheng] Chang Jung Christian Univ, Language Educ Ctr, Tainan, Taiwan. [Guo, How-Ran] Natl Cheng Kung Univ, Dept Environm & Occupat Hlth, Tainan 70428, Taiwan. [Guo, How-Ran] Natl Cheng Kung Univ Hosp, Dept Occupat & Environm Med, Tainan 70428, Taiwan. RP Guo, HR (reprint author), Natl Cheng Kung Univ, Dept Environm & Occupat Hlth, 138 Sheng Li Rd, Tainan 70428, Taiwan. 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Dev. Disabil. PD NOV PY 2013 VL 34 IS 11 BP 3766 EP 3772 DI 10.1016/j.ridd.2013.08.001 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900017 PM 24021391 ER PT J AU Somogyi, E Kiraly, I Gergely, G Nadel, J AF Somogyi, Eszter Kiraly, Ildiko Gergely, Gyoergy Nadel, Jacqueline TI Understanding goals and intentions in low-functioning autism SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Understanding goals; Intentionality; Deferred imitation ID SPECTRUM DISORDERS; YOUNG-CHILDREN; MENTAL STATES; IMITATION; INFANTS; LANGUAGE; OTHERS; COMMUNICATION; IMPAIRMENT; PREDICTORS AB We investigated ability to understand goals and attribute intentions in the context of two imitation studies in low-functioning, nonverbal children with autism (L-F CWA), a population that is rarely targeted by research in the domain. Down syndrome children (DSC) and typically developing children (TDC) were recruited to form matched comparison groups. In the two sets of simple action demonstrations only contextual indicators of the model's intentions were manipulated. In the Head touch experiment the model activated a button on a toy by pushing it with the forehead, whereas in the Hidden box experiment the model used a ball with a magnet to lift a box out of its container. Both actions were unusual and non-affordant with regards to the objects involved, none of the children in the baseline condition produced them. L-F CWA imitated the experimenter exactly, regardless of the model's intention. TDC showed appreciation of the model's intention by imitating her actions selectively. DSC reproduced only the intentional action as often as they imitated the experimenter exactly. It is concluded that L-F CWA attributed goals to the observed model, but did not show an appreciation of the model's intentions even in these simplified, nonverbal contexts. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Somogyi, Eszter] Eotvos Lorand Univ, Dept Cognit Psychol, H-1064 Budapest, Hungary. [Kiraly, Ildiko; Gergely, Gyoergy] Cent European Univ, Dept Cognit Sci, Cognit Dev Ctr, H-1051 Budapest, Hungary. [Nadel, Jacqueline] Hop La Pitie Salpetriere, Ctr Emot, UMR 7593, F-75013 Paris, France. RP Somogyi, E (reprint author), Eotvos Lorand Univ, Dept Cognit Psychol, Izabella U 46, H-1064 Budapest, Hungary. 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Dev. Disabil. PD NOV PY 2013 VL 34 IS 11 BP 3822 EP 3832 DI 10.1016/j.ridd.2013.07.039 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900023 PM 24021392 ER PT J AU Bicer, AH Alsaffar, AA AF Bicer, Ayse Humeyra Alsaffar, Ayten Aylin TI Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD) SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; BMI-for-age; Dietary intake; Feeding problems; Turkey ID TYPICALLY DEVELOPING-CHILDREN; FOOD SELECTIVITY; REPETITIVE BEHAVIORS; DIAGNOSTIC INTERVIEW; EATING BEHAVIORS; YOUNG-CHILDREN; ASSOCIATION; ACCEPTANCE; CHILDHOOD; PATTERNS AB The body mass index of 164 children (aged 4-18 years) attending four autism rehabilitation centers in Istanbul, Turkey, was determined and assessed using the BMI-for-age percentile charts by the World Health Organization (WHO). The mean intake of energy and nutrients of 115 children were calculated using three-day food records. The feeding assessment surveys filled in by the parents/caregivers indicated that the major feeding problem among children was food selectivity. The majority of the children were overweight or obese (58.5%). A total of 11% of children were found to be severely thin and thin. The calcium, zinc, vitamin B6 and folate intake of the majority of children were inadequate. The salt consumption in all age groups and cholesterol intake in normal, overweight and obese children were high. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Bicer, Ayse Humeyra] Yeditepe Univ, Dept Nutr & Dietet, Istanbul, Turkey. [Alsaffar, Ayten Aylin] Ozyegin Univ, Sch Appl Sci, TR-34794 Istanbul, Turkey. RP Alsaffar, AA (reprint author), Ozyegin Univ, Sch Appl Sci, Nisantepe Mah Orman Sok 13, TR-34794 Istanbul, Turkey. 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Dev. Disabil. PD NOV PY 2013 VL 34 IS 11 BP 3978 EP 3987 DI 10.1016/j.ridd.2013.08.024 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900037 PM 24029808 ER PT J AU Straccia, C Tasse, MJ Ghisletta, P Barisnikov, K AF Straccia, Claudio Tasse, Marc J. Ghisletta, Paolo Barisnikov, Koviljka TI The French version of the Reiss Screen for Maladaptive Behavior: Factor structure, point prevalence and associated factors SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE RSMB; Intellectual disability; Psychopathology; Mental illness; Adults; Age; Gender; Down syndrome ID MENTAL ILL-HEALTH; INTELLECTUAL DISABILITIES; DOWN-SYNDROME; PSYCHIATRIC-DISORDERS; GENDER-DIFFERENCES; ADULTS; EPIDEMIOLOGY; ILLNESS; PEOPLE; SCALE AB The main aims of the present study were to examine the factor structure and the internal consistency of the factors in the French version of the Reiss Screen of Maladaptive Behavior in a French-speaking European sample. The prevalence of psychopathology and the influence of associated factors were also examined. The Reiss Screen was administered to 467 adults (age range: 18-73) with intellectual disability living in the French-speaking regions of Switzerland and Belgium. A confirmatory factor analysis was performed to replicate the original factor structure. Internal consistency was examined by using Cronbach's alpha. Analyses of variance were computed to study the influence of gender, age and Down syndrome etiology. The original factor structure of the Reiss Screen was replicated. The overall rate of psychopathology in the sample was 37%. No linear relationship between age and psychopathology was found. However, adults aged less than 26 years had lower scores than older adults on several psychopathological domains. Males had higher scores than females on the Autism and the Avoidant Disorder subscales. Participants with Down syndrome had lower scores on all domains, with the exception of the Autism subscale. The results of this study suggest that the French version of the Reiss Screen can be a useful tool to detect psychopathology in adults with intellectual disability. (C) 2013 Elsevier Ltd. All rights reserved. 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PD NOV PY 2013 VL 34 IS 11 BP 4052 EP 4061 DI 10.1016/j.ridd.2013.08.034 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900045 PM 24042171 ER PT J AU Werner, S Shulman, C AF Werner, Shirli Shulman, Cory TI Subjective well-being among family caregivers of individuals with developmental disabilities: The role of affiliate stigma and psychosocial moderating variables SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Stigma; Developmental disabilities; Caregiving; Subjective well-being ID QUALITY-OF-LIFE; MENTAL-ILLNESS; INTELLECTUAL DISABILITY; STUDENTS ATTITUDES; CONJOINT-ANALYSIS; CHILDREN; PARENTS; AUTISM; EXPERIENCES; PEOPLE AB Studies have shown that stigmatization is linked to lower quality of life; however, only scant research has examined the association between family caregivers' internalization of stigma (affiliate stigma) and their subjective quality of life (subjective well-being, SWB). Furthermore, studies have rarely examined this association via comparison between caregivers of individuals with different developmental disabilities in addition to examining the influence of psychosocial protective factors. These were the aims of the current study. Family caregivers (N = 176) of individuals with autism spectrum disorders (ASD), intellectual disabilities (ID), and physical disabilities (PD) completed a self-report structured questionnaire including scales measuring SWB, affiliate stigma, burden, positive meaning in caregiving, social support and self-esteem. Results showed that SWB of family caregivers was below the average normative level and especially low for caregivers of individuals with ASD. The strongest predictors of SWB were caregivers' self-esteem, social support, positive meaning in caregiving, and affiliate stigma. Furthermore, an interaction was found between affiliate stigma and diagnosis, showing that among caregivers of individuals with ASD, greater levels of stigma were associated with lower ratings of SWB, whereas such an association was not found among caregivers of individuals with ID or PD. Findings from this study point to the importance of supporting caregivers across the life-span in order to decrease stigma, improve social support and self-esteem and improve SWB. Further, findings point to the need to respond differentially to the various developmental disabilities. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Werner, Shirli; Shulman, Cory] Hebrew Univ Jerusalem, Paul Baerwald Sch Social Work & Social Welf, IL-91905 Jerusalem, Israel. RP Werner, S (reprint author), Hebrew Univ Jerusalem, Paul Baerwald Sch Social Work & Social Welf, IL-91905 Jerusalem, Israel. 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A., 1998, SOCIAL SUPPORT Wong DW, 2004, REHABIL COUNS BULL, V47, P194, DOI 10.1177/00343552040470040101 World Health Organization, 2001, ICF INT CLASS FUNCT Yoong A, 2012, J INTELL DISABIL RES, V56, P609, DOI 10.1111/j.1365-2788.2011.01501.x NR 57 TC 2 Z9 2 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 NOV PY 2013 VL 34 IS 11 BP 4103 EP 4114 DI 10.1016/j.ridd.2013.08.029 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900049 PM 24055712 ER PT J AU Jansen, R Ceulemans, E Grauwels, J Maljaars, J Zink, I Steyaert, J Noens, I AF Jansen, Rianne Ceulemans, Eva Grauwels, Jolien Maljaars, Jarymke Zink, Inge Steyaert, Jean Noens, Ilse TI Young children with language difficulties: A dimensional approach to subgrouping SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Language difficulties; Early diagnosis; Cluster analysis; Intentional communication; Symbol understanding ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; LOW-FUNCTIONING CHILDREN; SYMBOLIC PLAY; JOINT ATTENTION; BEHAVIORAL DIFFICULTIES; IMPAIRED CHILDREN; ADOS SCORES; FOLLOW-UP; COMMUNICATION AB A dimensional approach was used to create bottom-up constructed subgroups that captured the behavioral heterogeneity in 36 Dutch-speaking children with language difficulties. Four subgroups were delineated based upon differences in cognitive ability, symbol understanding, joint attention and autism spectrum disorder related characteristics. Children with a different developmental disorder were found within a single cluster. Therefore, the results of this study suggest that bottom-up constructed subgroups might capture the heterogeneous behavioral profiles of young children with developmental difficulties in a more meaningful way. Furthermore, joint attention and symbol understanding seem important skills to assess in young children presenting with language difficulties. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jansen, Rianne; Maljaars, Jarymke; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Louvain, Belgium. [Jansen, Rianne; Maljaars, Jarymke; Steyaert, Jean; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res LAuRes, Louvain, Belgium. [Ceulemans, Eva; Grauwels, Jolien] Katholieke Univ Leuven, Methodol Educ Sci Res Unit, Louvain, Belgium. [Zink, Inge] Katholieke Univ Leuven, Dept Neurosci, ExpORL, Louvain, Belgium. [Zink, Inge] UZ Leuven, Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium. [Steyaert, Jean] Katholieke Univ Leuven, Dept Neurosci Child & Adolescent Psychiat, Louvain, Belgium. [Steyaert, Jean] Univ Maastricht, Dept Clin Genet, Maastricht, Netherlands. RP Jansen, R (reprint author), Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Louvain, Belgium. 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Tureck, Kimberly TI ADHD symptom prevalence and risk factors in a sample of toddlers with ASD or who are at risk for developmental delay SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE ADHD; Toddlers; Autism; Early intervention; Child development; Developmental trajectory; Developmental delay ID AUTISM SPECTRUM DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; COMORBID PSYCHOPATHOLOGY; EXECUTIVE FUNCTIONS; YOUNG-CHILDREN; BEHAVIORS; DIAGNOSIS; BOYS AB Individuals with attention deficit/hyperactivity disorder (ADHD) experience difficulties with inattention, hyperactivity, and impulsivity which significantly interfere with their daily functioning. Symptoms of the disorder occur in children, but the developmental trajectory of ADHD symptoms is not known. The present study examines the prevalence of ADHD symptomology in a sample of 2956 children who were determined to be at risk for developmental delay. 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TI Health related quality of life in parents of six to eight year old children with Down syndrome SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Down syndrome; Parents; Health related quality of life; Predictors; Cross-sectional study; Social support; Leisure ID DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITY; BEHAVIORAL-PROBLEMS; SWEDISH PARENTS; SOCIAL SUPPORT; MENTAL-HEALTH; STRESS; MOTHERS; AUTISM; CARE AB Raising a child with Down syndrome (DS) has been found to be associated with lowered health related quality of life (HRQoL) in the domains cognitive functioning, social functioning, daily activities and vitality. We aimed to explore which socio-demographics, child functioning and psychosocial variables were related to these HRQoL domains in parents of children with DS. Parents of 98 children with DS completed the TNO-AZL adult quality of life questionnaire (TAAQOL) and a questionnaire assessing socio-demographic, child functioning and psychosocial predictors. Using multiple linear regression analyses for each category of predictors, we selected relevant predictors for the final models. The final multiple linear regression models revealed that cognitive functioning was best predicted by the sleep of the child (beta = .29, p < .01) and by the parent having given up a hobby (beta = -.29, p < .01), social functioning by the quality of the partner relation (beta = .34, p < .001), daily activities by the parent having to care for an ill friend or family member (beta = -.31, p < .01), and vitality by the parent having enough personal time (beta. = .32, p < .01). Overall, psychosocial variables rather than socio-demographics or child functioning showed most consistent and powerful relations to the HRQoL domains of cognitive functioning, social functioning, daily activities and vitality. These psychosocial variables mainly related to social support and time pressure. Systematic screening of parents to detect problems timely, and interventions targeting the supportive network and the demands in time are recommended. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Marchal, Jan Pieter; Maurice-Stam, Heleen; Hatzmann, Janneke; Grootenhuis, Martha A.] Emma Childrens Hosp, Acad Med Ctr, Psychosocial Dept, NL-1100 DD Amsterdam, Netherlands. [van Trotsenburg, A. S. Paul] Emma Childrens Hosp, Acad Med Ctr, Dept Endocrinol, NL-1100 DD Amsterdam, Netherlands. RP Grootenhuis, MA (reprint author), Emma Childrens Hosp, Acad Med Ctr, Psychosocial Dept, A3-241,Post Box 22660, NL-1100 DD Amsterdam, Netherlands. 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Dev. Disabil. PD NOV PY 2013 VL 34 IS 11 BP 4239 EP 4247 DI 10.1016/j.ridd.2013.09.011 PG 9 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 251BD UT WOS:000326901900064 PM 24083990 ER PT J AU Chen, YN Wang, J Zhang, J Li, SJ He, L Shao, DD Du, HY AF Chen, Yan-Ni Wang, Jue Zhang, Jie Li, Su-Jiao He, Li Shao, Dong-Dong Du, Hui-Ying TI Effect of thimerosal on the neurodevelopment of premature rats SO WORLD JOURNAL OF PEDIATRICS LA English DT Article DE dopamine D4 receptor; neurodevelopment; serotonin 2A receptor; thimerosal ID EXPOSURE; VACCINES; INFANTS; NEURONS; BRAIN AB Background: This study was undertaken to determine the effect of thimerosal on the neurodevelopment of premature rats. Methods: Thimerosal was injected into premature SD rats at a dose of 32.8, 65.6, 98.4 or 131.2 mu g/kg on postnatal day 1. Expression of dopamine D4 receptor (DRD4) and serotonin 2A receptor (5-HT2AR), apoptosis in the prefrontal cortex on post-injection day 49, and learning and memory function were studied and compared with those in a control group injected with saline. Results: Expression of DRD4 and 5-HT2AR and learning function decreased, and apoptosis increased significantly in the 131.2 mu g/kg group (P<0.001). Memory function was significantly impaired by 65.6 (P<0.05), 98.4 and 131.2 mu g/kg (P<0.001). Conclusions: The negative adverse consequences on neurodevelopment observed in the present study are consistent with previous studies; this study raised serious concerns about adverse neurodevelopmental disorder such as autism in humans following the ongoing worldwide routine administration of thimerosal-containing vaccines to infants. C1 [Chen, Yan-Ni; Wang, Jue; Li, Su-Jiao] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ, Xian 710049, Peoples R China. [Chen, Yan-Ni; Wang, Jue; Li, Su-Jiao] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Biomed Engn, Xian 710049, Peoples R China. [Chen, Yan-Ni; Zhang, Jie; He, Li; Shao, Dong-Dong; Du, Hui-Ying] Xi An Jiao Tong Univ, Xian Childrens Hosp, Coll Med, Xian 710002, Peoples R China. RP Wang, J (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ, Xian 710049, Peoples R China. EM Juewang1@126.com FU Natural Science Foundation of Shannxi Province, China [2009JM4030] FX Project supported by the Natural Science Foundation of Shannxi Province, China (Grant No. 2009JM4030). 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Method: A population-based sample of 1886 twins aged 9 and 12, enriched for childhood mental health problems, was recruited from the Child and Adolescent Twin Study in Sweden (CATSS). Parents were interviewed over the telephone using the Autism-Tics, AD/HD and other Comorbidities (A-TAC) inventory, and in a second step they rated their children according to the Junior Temperament and Character Inventory (JTCI). Results: ADHD was strongly correlated with novelty seeking, while ASD was correlated positively with harm avoidance and negatively with reward dependence. The strongest associations between personality traits and neurodevelopmental disorders were negative correlations between the character dimensions of self-directedness and cooperativeness and ADHD and ASD alike. Cross-twin cross-trait correlations between ADHD, ASD, and personality dimensions in monozygotic twins were more than double those in dizygotic twins, indicating a strong genetic effect behind the phenotypic covariation between neurodevelopmental disorders and personality. Conclusions: Neurodevelopmental disorders are linked specifically to particular temperament profiles and generally to hampered development of the self-governing strategies referred to as "character." Poor self-agency and cooperation may be core functional outcomes in the separation of children with handicapping conditions from those with traits only reminiscent of neurodevelopmental disorders. The associations between neurodevelopmental disorders and personality are at least partly due to genetic effects influencing both conditions. As a consequence, personality must be broadly considered in neuropsychiatry, just as neuropsychiatric disorders and their genetic, neurodevelopmental, and cognitive susceptibilities have to be in personality research and clinical treatment. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kerekes, Nora; Brandstrom, Sven; Lundstrom, Sebastian; Nilsson, Thomas; Anckarsater, Henrik] Univ Gothenburg, Ctr Eth Law & Mental Hlth CELAM, S-43141 Molndal, Sweden. [Rastam, Maria] Lund Univ, Inst Clin Sci, S-22100 Lund, Sweden. [Kerekes, Nora; Lundstrom, Sebastian] Swedish Prison & Probat Serv, R&D Unit, Gothenburg, Sweden. [Lundstrom, Sebastian] Univ Gothenburg, Inst Neurosci & Physiol, Gillberg Neuropsychiat Ctr, S-43141 Molndal, Sweden. RP Kerekes, N (reprint author), Univ Gothenburg, CELAM, Wallinsgatan 8, S-43141 Molndal, Sweden. 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Psychiat. PD NOV PY 2013 VL 54 IS 8 BP 1140 EP 1147 DI 10.1016/j.comppsych.2013.05.009 PG 8 WC Psychiatry SC Psychiatry GA 248OA UT WOS:000326709600002 PM 23790516 ER PT J AU Wu, Z Pan, JT Su, YJ Gros-Louis, J AF Wu, Zhen Pan, Jingtong Su, Yanjie Gros-Louis, Julie TI How joint attention relates to cooperation in 1- and 2-year-olds SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article DE cooperation; ESCS; joint action; joint attention; toddlers ID PRESCHOOL-CHILDREN; SOCIAL COMPETENCE; INFANT; AUTISM; LANGUAGE; POINT; COMMUNICATION; TEMPERAMENT; INTENTIONS; SYSTEM AB Joint attention has been suggested to contribute to children's development of cooperation; however, few empirical studies have directly tested this hypothesis. Children aged 1 and 2 years participated in two joint action activities to assess their cooperation with an adult partner, who stopped participating at a specific moment during the tasks. Children's joint attention skills were measured by the Early Social Communication Scales (ESCS). Results showed that children's responding to joint attention ability contributed to their successful cooperation in an activity that required parallel roles, whereas initiating joint attention ability contributed to their successful cooperation in an activity that required complementary roles. These results suggest a complex relationship between joint attention and cooperative abilities when considering RJA and IJA separately. C1 [Wu, Zhen; Pan, Jingtong; Su, Yanjie] Peking Univ, Beijing 100871, Peoples R China. [Wu, Zhen; Gros-Louis, Julie] Univ Iowa, Iowa City, IA 52242 USA. [Pan, Jingtong] Tufts Univ, Medford, MA 02155 USA. RP Su, YJ (reprint author), Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. 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J. Behav. Dev. PD NOV PY 2013 VL 37 IS 6 BP 542 EP 548 DI 10.1177/0165025413505264 PG 7 WC Psychology, Developmental SC Psychology GA 246KS UT WOS:000326537400008 ER PT J AU Giusti-Rodriguez, P Sullivan, PF AF Giusti-Rodriguez, Paola Sullivan, Patrick F. TI The genomics of schizophrenia: update and implications SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID RARE CHROMOSOMAL DELETIONS; AUTISM SPECTRUM DISORDERS; GATED CALCIUM-CHANNELS; COPY NUMBER VARIANT; DE-NOVO MUTATIONS; PSYCHIATRIC-DISORDERS; WIDE ASSOCIATION; BIPOLAR DISORDER; COMMON VARIANTS; TRANSCRIPTOMIC ANALYSIS AB Schizophrenia is strongly familial yet rarely (if ever) exhibits classical Mendelian inheritance patterns. The advent of large-scale genotyping and sequencing projects has yielded large data sets with higher statistical power in an effort to uncover new associations with schizophrenia. Here, we review the challenges in dissecting the genetics of schizophrenia and provide an update of the current understanding of the underlying genomics. We discuss the breadth of susceptibility alleles, including those that may occur with low frequency and high disease risk, such as the 22q11.2 hemideletion, as well as alleles that may occur with greater frequency but convey a lower risk of schizophrenia, such as variants in genes encoding subunits of the voltage-gated L-type calcium channel. Finally, we provide an overview of the clinical implications for the diagnosis and treatment of schizophrenia based on progress in understanding the underlying genetic basis. C1 [Giusti-Rodriguez, Paola; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Ctr Psychiat Genom, Chapel Hill, NC 27599 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu FU NIH [U01 MH094421, P50 HG006582] FX We thank our colleagues worldwide (particularly in the Psychiatric Genomics Consortium), the tens of thousands of people who participated in the primary studies, and Thomas Lehner of the NIMH for his support. This work was supported by NIH grants U01 MH094421 and P50 HG006582. 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TI Prenatal Corticosteroids Modify Glutamatergic and GABAergic Synapse Genomic Fabric: Insights from a Novel Animal Model of Infantile Spasms SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE glucocorticoids; cortisol; corticosterone; ACTH; steroids; neuroactive steroids; GABA ID CORTICOTROPIN-RELEASING HORMONE; REPEATED ANTENATAL CORTICOSTEROIDS; CONGENITAL ADRENAL-HYPERPLASIA; CEREBRAL GLUCOSE-UTILIZATION; AUTISM SPECTRUM DISORDERS; CRYPTOGENIC WEST SYNDROME; GROWTH-FACTOR-I; TERM-FOLLOW-UP; GLUCOCORTICOID-RECEPTOR; BRAIN TRANSCRIPTOME AB Prenatal exposure to corticosteroids has long-term postnatal somatic and neurodevelopmental consequences. Animal studies indicate that corticosteroid exposure-associated alterations in the nervous system include hypothalamic function. Infants with infantile spasms, a devastating epileptic syndrome of infancy with characteristic spastic seizures, chaotic irregular waves on interictal electroencephalogram (hypsarhythmia) and mental deterioration, have decreased concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in cerebrospinal fluid, strongly suggesting hypothalamic dysfunction. We have exploited this feature to develop a model of human infantile spasms by using repeated prenatal exposure to betamethasone and a postnatal trigger of developmentally relevant spasms with NMDA. The spasms triggered in prenatally primed rats are more severe compared to prenatally saline-injected ones and respond to ACTH, a treatment of choice for infantile spasms in humans. Using autoradiography and immunohistochemistry, we have identified a link between the spasms in our model and the hypothalamus, especially the arcuate nucleus. Transcriptomic analysis of the arcuate nucleus after prenatal priming with betamethasone but before trigger of spasms indicates that prenatal betamethasone exposure down-regulates genes encoding several important proteins participating in glutamatergic and GABAergic transmission. Interestingly, there were significant sex-specific alterations after prenatal betamethasone in synapse-related gene expression but no such sex differences were found in prenatally saline-injected controls. A pairwise relevance analysis revealed that, although the synapse gene expression in controls was independent of sex, these genes form topologically distinct gene fabrics in males and females and these fabrics are altered by betamethasone in a sex-specific manner. These findings may explain the sex differences with respect to both normal behaviour and the occurrence and severity of infantile spasms. Changes in transcript expression and their coordination may contribute to a molecular substrate of permanent neurodevelopmental changes (including infantile spasms) found after prenatal exposure to corticosteroids. C1 [Iacobas, D. A.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Iacobas, S.; Chachua, T.; Goletiani, C.; Sidyelyeva, G.; Veliskova, J.; Velisek, L.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. [Veliskova, J.] New York Med Coll, Dept Obstet & Gynecol, Valhalla, NY 10595 USA. [Veliskova, J.; Velisek, L.] New York Med Coll, Dept Neurol, Valhalla, NY 10595 USA. [Velisek, L.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. RP Velisek, L (reprint author), New York Med Coll, Dept Cell Biol & Anat, BSB-A20,40 Sunshine Cottage Rd, Valhalla, NY 10595 USA. EM libor_velisek@nymc.edu FU NINDS/NIH [NS072966, NS056093]; Citizens United for Research in Epilepsy (CURE) Infantile Spasms Research Initiative FX Supported by grants NS072966 and NS056093 from NINDS/NIH, and by the Citizens United for Research in Epilepsy (CURE) Infantile Spasms Research Initiative. 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Neuroendocrinol. PD NOV PY 2013 VL 25 IS 11 BP 964 EP 979 DI 10.1111/jne.12061 PG 16 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 246DJ UT WOS:000326517100002 PM 23763471 ER PT J AU Kigar, SL Auger, AP AF Kigar, S. L. Auger, A. P. TI Epigenetic Mechanisms may Underlie the Aetiology of Sex Differences in Mental Health Risk and Resilience SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE epigenetics; juvenile; play behaviour; sexual differentiation; methylation; steroid hormones; amygdala ID CONGENITAL ADRENAL-HYPERPLASIA; ESTROGEN-RECEPTOR-ALPHA; JUVENILE SOCIAL PLAY; AUTISM SPECTRUM DISORDERS; DNA METHYLTRANSFERASE 3A; CENTRAL-NERVOUS-SYSTEM; MATERNAL-BEHAVIOR; ANOREXIA-NERVOSA; MOUSE-BRAIN; RAT-BRAIN AB In this review, we propose that experiential and hormonal influences on biological sex during development may produce differences in the epigenome, and that these differences play an important role in gating risk or resilience to a number of neurological and psychiatric disorders. One intriguing hypothesis is that the framework belying sex differences in the brain creates differences in methylation and demethylation patterns, and these in turn confer risk and resilience to mental health disorders. 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Neuroendocrinol. PD NOV PY 2013 VL 25 IS 11 BP 1141 EP 1150 DI 10.1111/jne.12074 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 246DJ UT WOS:000326517100018 PM 23841484 ER PT J AU Kothari, R Skuse, D Wakefield, J Micali, N AF Kothari, Radha Skuse, David Wakefield, Justin Micali, Nadia TI Gender Differences in the Relationship Between Social Communication and Emotion Recognition SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism spectrum disorder (ASD); Avon Longitudinal Study of Parents and Children (ALSPAC); emotion recognition; gender; social communication ID AUTISM SPECTRUM DISORDERS; GENERAL-POPULATION; TRAITS; CHILDREN; IMPAIRMENT; DEFICITS; PARENTS AB Objective: To investigate the association between autistic traits and emotion recognition in a large community sample of children using facial and social motion cues, additionally stratifying by gender. Method: A general population sample of 3,666 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were assessed on their ability to correctly recognize emotions using the faces subtest of the Diagnostic Analysis of Non-Verbal Accuracy, and the Emotional Triangles Task, a novel test assessing recognition of emotion from social motion cues. Children with autistic-like social communication difficulties, as assessed by the Social Communication Disorders Checklist, were compared with children without such difficulties. Results: Autistic-like social communication difficulties were associated with poorer recognition of emotion from social motion cues in both genders, but were associated with poorer facial emotion recognition in boys only (odds ratio = 1.9, 95% CI = 1.4, 2.6, p = .0001). This finding must be considered in light of lower power to detect differences in girls. Conclusions: In this community sample of children, greater deficits in social communication skills are associated with poorer discrimination of emotions, implying there may be an underlying continuum of liability to the association between these characteristics. As a similar degree of association was observed in both genders on a novel test of social motion cues, the relatively good performance of girls on the more familiar task of facial emotion discrimination may be due to compensatory mechanisms. Our study might indicate the existence of a cognitive process by which girls with underlying autistic traits can compensate for their covert deficits in emotion recognition, although this would require further investigation. C1 [Kothari, Radha; Skuse, David; Wakefield, Justin; Micali, Nadia] UCL, London WC1N 1EH, England. RP Kothari, R (reprint author), UCL, 30 Guilford St, London WC1N 1EH, England. EM Radha.kothari.10@ucl.ac.uk RI Micali, nadia/E-6829-2010 OI Micali, nadia/0000-0001-5571-2273 FU National Institute of Health Research (NIHR) clinician scientist award [DHCS/08/08/012]; Wellchild project grant; Wellcome Trust [092731] FX This research was funded by a National Institute of Health Research (NIHR) clinician scientist award (DHCS/08/08/012) to Dr. Micali and by a Wellchild project grant.The authors are extremely grateful to all of the families who took part in this study, the midwives for their help in recruiting them, and the whole Avon Longitudinal Study of Parents and Children (ALSPAC) team. The UK Medical Research Council and the Wellcome Trust (grant 092731) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, and Drs. Kothari, Skuse, Wakefield, and Micah will serve as guarantors for the contents The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service (NHS), NIHR, or the Department of Health. 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Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2013 VL 52 IS 11 BP 1148 EP 1157 DI 10.1016/j.jaac.2013.08.006 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 245RF UT WOS:000326480800006 PM 24157389 ER PT J AU Green, SA Rudie, JD Colich, NL Wood, JJ Shirinyan, D Hernandez, L Tottenham, N Dapretto, M Bookheimer, SY AF Green, Shulamite A. Rudie, Jeffrey D. Colich, Natalie L. Wood, Jeffrey J. Shirinyan, David Hernandez, Leanna Tottenham, Nim Dapretto, Mirella Bookheimer, Susan Y. TI Overreactive Brain Responses to Sensory Stimuli in Youth With Autism Spectrum Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE amygdala; anxiety; autism spectrum disorders; functional magnetic resonance imaging (fMRI); sensory over-responsivity ID OVER-RESPONSIVITY; ANXIETY DISORDERS; YOUNG-CHILDREN; AMYGDALA; ADOLESCENTS; FEAR; ABNORMALITIES; INDIVIDUALS; HIPPOCAMPUS; MECHANISMS AB Objectives: Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses to sensory stimuli in youth with and without ASD. Method: A total of 25 high-functioning youth with ASD and 25 age- and IQ-equivalent typically developing (IT)) youth were presented with mildly aversive auditory and visual stimuli during a functional magnetic resonance imaging (fMRI) scan. Parents provided ratings of children's SOR and anxiety symptom severity. Results: Compared to TD participants, ASD participants displayed greater activation in primary sensory cortical areas as well as amygdala, hippocampus, and orbital-frontal cortex. In both groups, the level of activity in these areas was positively correlated with level of SOR severity as rated by parents, over and above behavioral ratings of anxiety. Conclusions: This study demonstrates that youth with ASD show neural hyper-responsivity to sensory stimuli, and that behavioral symptoms of SOR may be related to both heightened responsivity in primary sensory regions as well as areas related to emotion processing and regulation. C1 [Green, Shulamite A.; Wood, Jeffrey J.; Tottenham, Nim] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Rudie, Jeffrey D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Colich, Natalie L.] Stanford Univ, Stanford, CA 94305 USA. [Shirinyan, David] Santa Monica Coll, Santa Monica, CA USA. [Hernandez, Leanna; Dapretto, Mirella; Bookheimer, Susan Y.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Green, SA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA. EM shulamite@ucla.edu FU National Institute of Child Health and Human Development [P50 HD055784]; National Institute of Mental Health [1R01 HD065280-01]; National Research Service Award predoctoral fellowship [F31 MH093999-01A1] FX This work was supported in part by grants from the National Institute of Child Health and Human Development (P50 HD055784) and the National Institute of Mental Health (1R01 HD065280-01) as well as a National Research Service Award predoctoral fellowship to S.G. 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Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2013 VL 52 IS 11 BP 1158 EP 1172 DI 10.1016/j.jaac.2013.08.004 PG 15 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 245RF UT WOS:000326480800007 PM 24157390 ER PT J AU Doughty, AH Giorno, KG Miller, HL AF Doughty, Adam H. Giorno, Kenneth G. Miller, Hannah L. TI EFFECTS OF REINFORCER MAGNITUDE ON REINFORCED BEHAVIORAL VARIABILITY SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE behavioral variability; reinforcer magnitude; induction; pigeon; key peck ID RESPONSE VARIABILITY; OPERANT VARIABILITY; SCHEDULE; AUTISM; FOOD; PROBABILITY; PERFORMANCE; CONTINGENCY; REPETITION; INTERVAL AB Eight pigeons were exposed to a two-component multiple schedule. In each component, four-peck sequences across left and right keys were reinforced according to a variability threshold contingency. In one condition, only infrequently occurring response sequences were reinforced in each component, thereby generating highly variable sequences. In a separate condition, when the variability threshold contingency was lenient in each component, sequences were much less variable. In each condition, reinforcer magnitude was manipulated across components, and the larger reinforcer magnitude produced less variability than the smaller reinforcer magnitude. These results suggest that larger reinforcers hinder the reinforcement of behavioral variability. The results are interpretable in terms of the larger reinforcer inducing a greater level of behavioral repetition, particularly as the time to reinforcement was approached. This effect may have implications for reinforcing behavioral variability in humans. C1 [Doughty, Adam H.; Giorno, Kenneth G.; Miller, Hannah L.] Coll Charleston, Charleston, SC 29424 USA. RP Doughty, AH (reprint author), Coll Charleston, Dept Psychol, 57 Coming St, Charleston, SC 29424 USA. EM doughtya@cofc.edu FU SURF (Summer Undergraduate Research with Faculty) grant; Faculty Research and Development grant; College of Charleston FX Portions of this research were supported by a SURF (Summer Undergraduate Research with Faculty) grant as well as a Faculty Research and Development grant, both through the College of Charleston. The authors thank several students for their contributions to this research, particularly Nina Deese. 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Livas, Christos TI Management of children with autism spectrum disorder in the dental setting: Concerns, behavioural approaches and recommendations SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Autism spectrum disorder; dental management; children ID ORAL-HEALTH STATUS; CARIES EXPERIENCE; CARE NEEDS; DENTISTRY; EDUCATION; PARENTS; SCHOOLS AB Objectives: This article reviews the present literature on the issues encountered while coping with children with autistic spectrum disorder from the dental perspective. The autistic patient profile and external factors affecting the oral health status of this patient population are discussed upon the existing body of evidence. Material and Methods: The MEDLINE database was searched using the terms 'Autistic Disorder', 'Behaviour Control/methods', 'Child', 'Dental care for disabled', 'Education', 'Oral Health', and 'Pediatric Dentistry' to locate related articles published up to January 2013. Results: Most of the relevant studies indicate poor oral hygiene whereas they are inconclusive regarding the caries incidence in autistic individuals. Undergraduate dental education appears to determine the competence of dental professionals to treat developmentally disabled children and account partly for compromised access to dental care. Dental management of an autistic child requires in-depth understanding of the background of the autism and available behavioural guidance theories. The dental professional should be flexible to modify the treatment approach according to the individual patient needs. C1 [Delli, Konstantina] Univ Groningen, Univ Med Ctr Groningen, Dept Oral & Maxillofacial Surg, NL-9700 RB Groningen, Netherlands. [Bornstein, Michael M.] Univ Bern, Sch Dent Med, Dept Oral Surg & Stomatol, CH-3012 Bern, Switzerland. [Livas, Christos] Univ Groningen, Univ Med Ctr Groningen, Dept Orthodont, NL-9700 RB Groningen, Netherlands. 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Skov, Liselotte Brondum-Nielsen, Karen Tumer, Zeynep TI Chromosomal rearrangements in Tourette syndrome: implications for identification of candidate susceptibility genes and review of the literature SO NEUROGENETICS LA English DT Review DE Chromosome rearrangement; Cytogenetics; Tourette syndrome ID AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIANTS; LA-TOURETTE; TRANSLOCATION BREAKPOINT; LANGUAGE DISORDER; LINKAGE ANALYSIS; MENKES DISEASE; MULTIPLE TICS; FAMILY; DISRUPTION AB Tourette syndrome (TS) is a childhood-onset complex neurobiological disorder characterized by a combination of persistent motor and vocal tics and frequent presence of other neuropsychiatric comorbidities. TS shares the fate of other complex disorders, where the genetic etiology is largely unknown, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS susceptibility genes. C1 [Bertelsen, Birgitte; Brondum-Nielsen, Karen; Tumer, Zeynep] Copenhagen Univ Hosp, Rigshosp, Kennedy Ctr, DK-2600 Glostrup, Denmark. [Debes, Nanette Mol; Skov, Liselotte] Herlev Univ Hosp, Tourette Clin, Dept Pediat, DK-2730 Herlev, Denmark. 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Calahorro, Fernando Ruiz-Rubio, Manuel TI Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal pathways of C. elegans SO NEUROGENETICS LA English DT Article DE Neuroligins; Dopamine; Serotonin; Methylphenidate; Fluoxetine; Caenorhabditis elegans ID CAENORHABDITIS-ELEGANS; DEFICIENT MUTANTS; AUTISM; TRANSPORTER; NLGN4; GENE; METHYLPHENIDATE; DISORDERS; RECEPTOR; SYNAPSE AB Neuroligins are neuronal and neuromuscular transmembrane proteins that have been implicated in autism spectrum disorder and other cognitive diseases. The nlg-1 gene from Caenorhabditis elegans is orthologous to human neuroligin genes. In the nematode, the locomotory rate is mediated by dopaminergic and serotonergic pathways, which result in two different behavioral responses known as basal slowing response (BSR) and enhanced slowing response (ESR), respectively. We report that nlg-1-deficient mutants are defective in both the BSR and ESR behaviors. In addition, we demonstrate that methylphenidate (a dopamine reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor), two drugs widely used for the treatment of behavioral disorders in humans, are able to restore the BSR and ESR wild type phenotypes, respectively, in nlg-1 defective mutant nematodes. The abnormal locomotory behavior patterns were rescued in nlg-1-deficient mutant by expressing a cDNA from the human NLGN1 gene under the C. elegans nlg-1 promoter. However, human NLGN1 (R453C) and NLGN1 (D432X) mutant alleles did not rescue any of the two mutant phenotypes. The results indicate that neuroligin is involved in modulating the action of dopamine and serotonin in the nematode and suggest that the functional mechanism underpinning both methylphenidate and fluoxetine in C. elegans might be comparable to that in humans. The neuroligin-deficient mutants may undergo inefficient synaptic transmissions which could affect different traits in the nervous system. In particular, neuroligin might be required for normal neurotransmitters release. The understanding of the mechanisms by which methylphenidate and fluoxetine are able to restore the behavior of these mutants could help to explain the etiology of some human neurological diseases. C1 [Izquierdo, Patricia G.; Calahorro, Fernando; Ruiz-Rubio, Manuel] Univ Cordoba, Dept Genet, E-14071 Cordoba, Spain. [Izquierdo, Patricia G.; Calahorro, Fernando; Ruiz-Rubio, Manuel] Hosp Univ Reina Sofia, Cordoba, Spain. [Izquierdo, Patricia G.; Calahorro, Fernando; Ruiz-Rubio, Manuel] Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain. RP Ruiz-Rubio, M (reprint author), Univ Cordoba, Dept Genet, E-14071 Cordoba, Spain. EM ge1rurum@uco.es FU Consejeria de Salud, Junta de Andalucia, Spain [PI0197] FX We thank the Caenorhabditis Genetics Center, the Japanese National Bioresource Project, Antonio Miranda-Vizuete, Julian Ceron, Thomas Dresbach, Peter Askjaer, Juan Cabello, Noemi Cabrera-Poch, Rosina Giordano, and Denis Dupuy for sharing worm strains and plasmids. We are thankful to Jim Rand for the information about the C. elegans nlg-1 promoter, to Randy Blakely for the SWIP assay protocol, and to Antonio Miranda-Vizuete and Elena P. Nadales for critical reading of the manuscript. We also thank Justo P. Castano for giving us the opportunity to use the microinjection station in his lab. Comments from Encarna Alejandre and assistance from Isabel Caballero are sincerely acknowledged. This work was supported by grant PI0197 from the Consejeria de Salud, Junta de Andalucia, Spain. 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A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes. C1 [Weber, Axel; Koehler, Angelika; Mueller, Ulrich] Univ Giessen, Inst Humangenet, D-35390 Giessen, Germany. [Hahn, Andreas; Neubauer, Bernd] Zentrum Kinderheilkunde & Jugendmed, Abt Neuropadiatrie Sozialpadiatrie & Epileptol, Giessen, Germany. RP Weber, A (reprint author), Univ Giessen, Inst Humangenet, D-35390 Giessen, Germany. 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According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements. Methods: Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk. Results: In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types. Conclusions: In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking. C1 [Benros, Michael Eriksen; Laursen, Thomas Munk; Mortensen, Preben Bo] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark. [Benros, Michael Eriksen; Nordentoft, Merete] Univ Copenhagen, Fac Hlth Sci, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark. [Benros, Michael Eriksen; Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark. [Dalton, Susanne Oksbjerg] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Benros, ME (reprint author), Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark. EM Benros@ncrr.dk FU Stanley Medical Research Institute; ERC [294838]; Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH FX The study was supported financially by a grant from the Stanley Medical Research Institute, ERC Advanced Grant Project no. 294838 and the Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI Health, Chronic Conditions, and Behavioral Risk Disparities Among US Immigrant Children and Adolescents SO PUBLIC HEALTH REPORTS LA English DT Article ID CAUSE-SPECIFIC MORTALITY; UNITED-STATES; OVERWEIGHT PREVALENCE; ETHNIC-IMMIGRANT; NONCOVERAGE BIAS; OBESITY; ACCULTURATION; ASSOCIATIONS; BORN; DETERMINANTS AB Objective. We examined differentials in the prevalence of 23 parent-reported health, chronic condition, and behavioral indicators among 91,532 children of immigrant and U.S.-born parents. Methods. We used the 2007 National Survey of Children's Health to estimate health differentials among 10 ethnic-nativity groups. Logistic regression yielded adjusted differentials. Results. Immigrant children in each racial/ethnic group had a lower prevalence of depression and behavioral problems than native-born children. The prevalence of autism varied from 0.3% among immigrant Asian children to 1.3%-1.4% among native-born non-Hispanic white and Hispanic children. Immigrant children had a lower prevalence of asthma, attention deficit disorder/attention deficit hyperactivity disorder; developmental delay; learning disability; speech, hearing, and sleep problems; school absence; and chronic condition than native-born children, with health risks increasing markedly in relation to mother's duration of residence in the U.S. Immigrant children had a substantially lower exposure to environmental tobacco smoke, with the odds of exposure being 60%-95% lower among immigrant non-Hispanic black, Asian, and Hispanic children compared with native non-Hispanic white children. Obesity prevalence ranged from 7.7% for native-born Asian children to 24.9%-25.1% for immigrant Hispanic and native-born non-Hispanic black children. Immigrant children had higher physical inactivity levels than native-horn children; however, inactivity rates declined with each successive generation of immigrants. Immigrant Hispanic children were at increased risk of obesity and sedentary behaviors. Ethnic-nativity differentials in health and behavioral indicators remained marked after covariate adjustment. Conclusions. Immigrant patterns in child health and health-risk behaviors vary substantially by ethnicity, generational status, and length of time since immigration. Public health programs must target at-risk children of both immigrant and U.S.-born parents. C1 [Singh, Gopal K.; Yu, Stella M.; Kogan, Michael D.] US Hlth Resources & Serv Adm, US Dept HHS, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. RP Singh, GK (reprint author), US Hlth Resources & Serv Adm, US Dept HHS, Maternal & Child Hlth Bur, 5600 Fishers Ln,Room 18-41, Rockville, MD 20857 USA. EM gsingh@hrsa.gov CR Bloom B, 2011, VITAL HLTH STAT, V10 Blumberg S. 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S. Department of Health and Human Services. Office of Disease Prevention and Health Promotion, HLTH PEOPL 2020 US Department of Health and Human Services (HHS) Office of Disease Prevention and Health Promotion, 2010, HLTH PEOPL 2010 MIDC Walters N. P., 2011, NEWLY ARRIVED FOREIG NR 46 TC 3 Z9 3 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2013 VL 128 IS 6 BP 463 EP 479 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 247IP UT WOS:000326611400006 PM 24179258 ER PT J AU Horovitz, M Matson, JL AF Horovitz, Max Matson, Johnny L. TI The Baby and Infant Screen for Children with aUtIsm Traits-Part 3: The development of age-based scoring procedures SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE BISCUIT; Autism; ASD; Challenging behaviors; Cutoffs; Psychometric properties ID SELF-INJURIOUS-BEHAVIOR; SPECTRUM DISORDERS; YOUNG-CHILDREN; CHALLENGING BEHAVIORS; INTELLECTUAL DISABILITY; PDD-NOS; MENTAL-RETARDATION; EARLY INTERVENTION; COMMUNICATION DEVELOPMENT; FUNCTIONAL-ANALYSIS AB The objective of the current study was to develop age-based scoring procedures for the BISCUIT-Part 3, an assessment measure of challenging behaviors in infants and toddlers aged 17-37 months. Separate age-based cutoffs were developed for those with an autism spectrum disorder (ASD) and those with non-ASD related developmental delays, using the standard deviation from the mean method. The sample consisted of 3022 infants and toddlers and their parents. As age increased in those with ASD, higher cutoff scores were required. Less variation was seen in the cutoff scores established for those with non-ASD related delays. The findings suggest that as children with ASD grow older, challenging behaviors become more frequent and severe. Additionally, they become easier to detect in comparison to same-aged peers. The implications of these results are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Horovitz, Max; Matson, Johnny L.] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Matson, JL (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Eldevik, Sigmund TI Training discrete trials teaching skills using videoconference SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Discrete trials teaching; Videoconference; Staff training; Autism ID INTENSIVE BEHAVIORAL TREATMENT; FUNCTIONAL-ANALYSIS; DEVELOPMENTAL-DISABILITIES; SELF-INJURY; AUTISM; ASSESSMENTS; CHILDREN; INTERVENTION; TELEMEDICINE; STUDENTS AB This study investigated the effect of videoconferencing in training staff to implement discrete trial teaching in real life settings with children with autism. Fourteen participants were randomly assigned to two groups. One group received training on-site and the other group received training via videoconference. The participants in both groups received 3x 15 min of training on three different teaching programs: matching, receptive and expressive labeling. The results showed no significant differences between the groups in the post-test whilst both groups improved significantly following training. Although preliminary, these results suggest that videoconferencing can be a cost-saving way to train staff in how to implement discrete trial teaching. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Hay-Hansson, Aina W.] Vestre Viken Hosp Trust, Drammen Hosp, Ctr Habilitat Rehabil, N-3019 Drammen, Norway. [Eldevik, Sigmund] Oslo & Akershus Univ Coll Appl Sci, NO-0130 Oslo, Norway. RP Hay-Hansson, AW (reprint author), Vestre Viken Hosp Trust, Drammen Hosp, Ctr Habilitat Rehabil, Konggata 51, N-3019 Drammen, Norway. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1300 EP 1309 DI 10.1016/j.rasd.2013.07.022 PG 10 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500002 ER PT J AU Weiss, JA Robinson, S Fung, S Tint, A Chalmers, P Lunsky, Y AF Weiss, Jonathan A. Robinson, Suzanne Fung, Stephanie Tint, Ami Chalmers, Philip Lunsky, Yona TI Family hardiness, social support, and self-efficacy in mothers of individuals with Autism Spectrum Disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Family hardiness; Mothers; Social support; Self-efficacy; Autism Spectrum Disorders; Stress ID FRAGILE-X-SYNDROME; DOUBLE ABCX MODEL; DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITIES; MENTAL-HEALTH; BEHAVIOR PROBLEMS; DOWN-SYNDROME; POSITIVE PSYCHOLOGY; CHILDREN; STRESS AB Family hardiness is an important construct to understand coping in parents of individuals with Autism Spectrum Disorders (ASD), who are often at risk for considerable distress in the face of multiple stressors. The current study examined family hardiness, perceived social support and parent self-efficacy as predictors of family distress in 138 mothers of individuals with ASD, 4-41 years of age. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1310 EP 1317 DI 10.1016/j.rasd.2013.07.016 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500003 ER PT J AU Matson, JL Cervantes, PE AF Matson, Johnny L. Cervantes, Paige E. TI Comorbidity among persons with intellectual disabilities SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Review DE Comorbid; Intellectual disabilities; Challenging behaviors; Health problems; Psychopathology ID AUTISM SPECTRUM DISORDERS; SEVERE RETARDATION MESSIER; PROFOUND MENTAL-RETARDATION; SELF-INJURIOUS-BEHAVIOR; II DASH-II; SOCIAL-SKILLS; MATSON EVALUATION; DIAGNOSTIC-ASSESSMENT; INDIVIDUALS; ADULTS AB Within the last three decades, the study of conditions that co-occur with intellectual disabilities has flourished. The present paper provides an analysis of the content of 405 papers that were reviewed on the topic. From these papers, trends emerged. The papers fell into one of three broad categories; comorbid psychopathology, comorbid medical problems, and comorbid challenging behaviors. Also, the volume of studies has been increasing rapidly. Implications of these and related issues are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Matson, Johnny L.; Cervantes, Paige E.] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Cervantes, PE (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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PD NOV PY 2013 VL 7 IS 11 BP 1318 EP 1322 DI 10.1016/j.rasd.2013.07.018 PG 5 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500004 ER PT J AU Hesse, TL Danko, CM Budd, KS AF Hesse, Tessa L. Danko, Christina M. Budd, Karen S. TI Siblings of children with autism: Predictors of adjustment SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Adjustment; Siblings; Autism spectrum disorder; Parents; Sibling adjustment; Parent satisfaction ID MATERNAL SELF-EFFICACY; BEHAVIORAL INTERVENTION; DIFFICULTIES QUESTIONNAIRE; SPECTRUM DISORDERS; PARENTING STRESS; SATISFACTION; MOTHERS; STRATEGIES; STRENGTHS; PROGRAMS AB As the prevalence of autism increases, so does the need to examine the effects of autism on family members of children with autism. The current study evaluated possible predictors of adjustment in siblings of children with autism. Aspects of the parents' functioning as caregivers for a child with autism were examined to determine whether they predicted the adjustment of the child's sibling. Two hundred caregivers of 4-10-year-old children with autism who had at least one sibling without autism participated by filling out questionnaires online. Parental satisfaction with the role of caregiver for the child with autism was negatively correlated with difficulties in sibling adjustment, and it was the only significant predictor of sibling adjustment in a hierarchical regression analysis. Parental stress and parental self-efficacy were not unique contributors to sibling adjustment when other parental variables were considered. No significant relationship was found between parental therapy involvement and sibling adjustment, or between parental educational involvement and sibling adjustment. The lack of parental involvement as a predictor of sibling adjustment adds new findings to the current literature, which had found such a relationship in a previous study with a smaller sample. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hesse, Tessa L.] Univ Calif Davis, Dept Human Ecol, Davis, CA 95616 USA. [Danko, Christina M.; Budd, Karen S.] Depaul Univ, Dept Psychol, Chicago, IL 60614 USA. RP Hesse, TL (reprint author), Univ Calif Davis, Dept Human Ecol, 1 Shields Ave, Davis, CA 95616 USA. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1323 EP 1331 DI 10.1016/j.rasd.2013.07.024 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500005 ER PT J AU Akoury-Dirani, L Alameddine, M Salamoun, M AF Akoury-Dirani, Leyla Alameddine, Maysam Salamoun, Mariana TI Validation of the Lebanese Childhood Autism Rating Scale - Second Edition - High Functioning Version SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE CARS2; Validation; High Functioning Autism; Lebanon ID SPECTRUM DISORDERS; ASPERGERS-DISORDER; CRITERIA; DSM-5; CHILDREN AB This paper presents the psychometric properties of the Lebanese version of the Childhood Autism Rating Scale Second Edition, High Functioning Version (CARS2-HF). The participants consisted of 30 children aged 6-18 years among which 24 had a clinical diagnosis of Asperger disorder or Pervasive Developmental Disorder-Not Otherwise Specified and 6 had a clinical diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). All participants were verbally fluent and had IQ estimates of 80 or higher, determined with the Wechsler Nonverbal Scale of Ability (WNV). Forward and backward translation of the CARS2-HF and the Childhood Autism Rating Scale Second Edition, Questionnaire for Parents or Caregivers (CARS2-QPC) was completed before the administration of the scales. The results of this study showed that the Lebanese CARS2-HF has a high degree of internal consistency (.92), inter-rater reliability (.97), and test-retest reliability (.99). Receiver Operating Characteristic (ROC) analysis determined that individuals with total raw scores below 26 are less likely - to be in the autism spectrum. This instrument can be used in screening and assessing for ASD in high-functioning Lebanese and Arab speaking individuals. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Akoury-Dirani, Leyla; Alameddine, Maysam; Salamoun, Mariana] Amer Univ Beirut, Dept Psychiat, Beirut 11072020, Lebanon. RP Akoury-Dirani, L (reprint author), Amer Univ Beirut, Dept Psychiat, Mail Box Riad El Solh, Beirut 11072020, Lebanon. 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PD NOV PY 2013 VL 7 IS 11 BP 1332 EP 1338 DI 10.1016/j.rasd.2013.08.001 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500006 ER PT J AU Konst, MJ Matson, JL Turygin, N AF Konst, Matthew J. Matson, Johnny L. Turygin, Nicole TI Comparing the rates of tantrum behavior in children with ASD and ADHD as well as children with comorbid ASD and ADHD diagnoses SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorders; Tantrum behavior; Autism Spectrum Disorders-Comorbidity for Children (ASD-CC); Comorbidity ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; CHALLENGING BEHAVIORS; INTELLECTUAL DISABILITY; DIFFERENTIAL-DIAGNOSIS; PSYCHIATRIC-DISORDERS; FUNCTIONAL ASSESSMENT; TRAITS BISCUIT; SOCIAL-SKILLS; INFANT SCREEN AB The current study investigated the presentation of tantrum behaviors in individuals with an autism spectrum disorder (ASD) diagnosis with and without a comorbid diagnosis of attention deficit hyperactivity disorder (ADHD). Participants included 347 children ranging in age from 2 to 18 years old. Diagnostic categories in the current study were based upon clinical diagnosis. The severity of ASD symptomology was measured by the Autism Spectrum Disorder-Diagnostic Child Version (ASD-DC). The presence and severity of tantrum behaviors were measured by the Tantrum behavior subscale of the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). The influence of diagnosis and ASD symptomology had upon the expression of tantrum behaviors were examined, controlling for participant age. Initial analysis revealed significant differences in the expression of tantrum behavior between the ASD, ADHD and ASD/ADHD groups. However, age did not have a significant influence on the exhibition of tantrum behaviors. Follow-up analyses demonstrated that those individuals diagnosed with an ASD and a comorbid ADHD diagnosis exhibited significantly greater tantrum behavior. Post hoc analyses identified a significant positive correlation between increases in ASD symptomology and elevations of the severity of tantrum behaviors for each group. The observed correlation for the ADHD group was found to be significantly greater than the ASD group. Correlations for individual item responses of the ASD-CC were also computed and discussed for each diagnostic group. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Konst, Matthew J.; Matson, Johnny L.; Turygin, Nicole] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Konst, MJ (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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S., 2000, J ABNORMAL CHILD PSY, V28, P33 NR 60 TC 4 Z9 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1339 EP 1345 DI 10.1016/j.rasd.2013.07.023 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500007 ER PT J AU Alexander, JL Ayres, KM Smith, KA Shepley, SB Mataras, TK AF Alexander, Jennifer L. Ayres, Kevin M. Smith, Katie A. Shepley, Sally B. Mataras, Theologia K. TI Using video modeling on an iPad to teach generalized matching on a sorting mail task to adolescents with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Generalized matching; Technology; Video modeling; Vocational skills ID MODERATE INTELLECTUAL DISABILITIES; CHILDREN; INDIVIDUALS; INSTRUCTION; STUDENTS; SELF; INTERVENTION; BEHAVIOR; SKILLS; DISCRIMINATION AB Two multiple probe designs across three and four participants evaluated the effects of video modeling to teach a matching response (sorting mail) to seven adolescents with autism. Participants were instructed on one set of responses (five mail pieces) using video modeling, while concurrently monitoring two other sets for generalization effects. Results indicated that three participants learned their target set and generalized to the untrained sets, and two participants required an error correction procedure to achieve or approach mastery on their target set. Two participants did not acquire target sets with video based instruction. Data on setting generalization and maintenance are also provided for the participants who reached mastery. Participant variables that may relate to responding, limitations to the study, and directions for future research on video based instruction are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Alexander, Jennifer L.; Ayres, Kevin M.; Smith, Katie A.; Shepley, Sally B.; Mataras, Theologia K.] Univ Georgia, Athens, GA 30606 USA. RP Alexander, JL (reprint author), Univ Georgia, 516 Aderhold Hall, Athens, GA 30606 USA. EM jenlenz@uga.edu CR Ayres K. M., 2010, SINGLE SUBJECT RES M, P329 Ayres KM, 2005, EDUC TRAIN DEV DISAB, V40, P183 BAER DM, 1968, J APPL BEHAV ANAL, V1, P91, DOI 10.1901/jaba.1968.1-91 Becker W. 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PD NOV PY 2013 VL 7 IS 11 BP 1346 EP 1357 DI 10.1016/j.rasd.2013.07.021 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500008 ER PT J AU Vasa, RA Kalb, L Mazurek, M Kanne, S Freedman, B Keefer, A Clemons, T Murray, D AF Vasa, Roma A. Kalb, Luther Mazurek, Micah Kanne, Stephen Freedman, Brian Keefer, Amy Clemons, Traci Murray, Donna TI Age-related differences in the prevalence and correlates of anxiety in youth with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Anxiety; Prevalence; Correlate; Age group ID PERVASIVE DEVELOPMENTAL DISORDERS; CHILD-BEHAVIOR CHECKLIST; HIGH-FUNCTIONING AUTISM; PROSPECTIVE-LONGITUDINAL COMMUNITY; SENSORY OVER-RESPONSIVITY; ASPERGER-SYNDROME; INTELLECTUAL DISABILITIES; PSYCHIATRIC-DISORDERS; ADOLESCENTS; SYMPTOMS AB Age-related differences in the prevalence and correlates of anxiety were cross-sectionally examined in 1316 children and adolescents with autism spectrum disorder (ASD) who presented for initial evaluation at 14 outpatient autism centers around the country and in Canada. The prevalence of clinical and subclinical anxiety as well as the correlates of anxiety were examined in three age groups of children: preschool, school age and adolescents. Findings showed that the prevalence of anxiety in each age group exceeded the prevalence of anxiety in the general population. Adolescents and school age children had the highest prevalence of clinical (40%) and subclinical anxiety (26%), respectively. Higher IQ and less ASD severity were each weakly correlated with more anxiety in preschool and school age children. Affective symptoms were strongly associated with anxiety in each age group. Age specific psychiatric comorbidities were also present. Anxiety was associated with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in the preschool group, ODD and somatic symptoms in the school age children, and ADHD symptoms in adolescents. These data underscore the need for prevention and treatment of anxiety as well as research examining the characteristics of anxiety in children with ASD using a developmental framework. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Vasa, Roma A.] Johns Hopkins Univ, Sch Med, Ctr Autism & Related Disorders, Kennedy Krieger Inst,Dept Psychiat, Baltimore, MD 21211 USA. [Kalb, Luther; Keefer, Amy] Ctr Autism & Related Disorders, Kennedy Krieger Inst, Baltimore, MD 21211 USA. [Mazurek, Micah; Kanne, Stephen] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Dept Hlth Psychol, Columbia, MO 65201 USA. [Freedman, Brian] Univ Delaware, Ctr Disabil Studies, Newark, DE 19716 USA. [Clemons, Traci] EMMES Corp, Rockville, MD 20850 USA. [Murray, Donna] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1358 EP 1369 DI 10.1016/j.rasd.2013.07.005 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500009 ER PT J AU Kornacki, LT Ringdahl, JE Sjostrom, A Nuernberger, JE AF Kornacki, Lisa T. Ringdahl, Joel E. Sjostrom, Anna Nuernberger, Jodi E. TI A component analysis of a behavioral skills training package used to teach conversation skills to young adults with autism spectrum and other developmental disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Social skills; Conversation; Behavioral skills training; Task analysis ID DISABILITIES; MODEL AB We conducted a component analysis of a behavioral skills training (BST) package to teach conversation skills to young adults with autism and/or developmental disorders. Performance following each component of the package was compared to a task analysis that included both vocal and non-vocal conversation skills, such as making comments related to the conversation topic, maintaining eye contact, maintaining and appropriate distance from the conversation partner. The components of the BST package included instructions, modeling of an appropriate conversation, rehearsal, rehearsal with feedback, in situ training with feedback provided to the participants in a private training room, and in situ training with feedback plus reinforcement. Results suggested unique components were correlated with acquisition of the conversation skills across participants. Results are presented as they relate to effective components of BST and implications for providing BST to individuals in clinical contexts. (C) 2013 Published by Elsevier Ltd. C1 [Kornacki, Lisa T.; Ringdahl, Joel E.; Sjostrom, Anna; Nuernberger, Jodi E.] So Illinois Univ, Carbondale, IL 62901 USA. 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Turygin, Nicole Macmillan, Katie TI Rates of psychotropic medication use in children with ASD compared to presence and severity of problem behaviors SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Psychotropic medication; Autism spectrum disorder; Externalizing behaviors; Autism Spectrum Disorders - Behavior; Problem Child (ASD-BPC) ID AUTISM-SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDER; SOCIAL-SKILLS; ADULTS; PSYCHOPATHOLOGY; SYMPTOMS; DISABILITIES; ADOLESCENTS; RELIABILITY; MANAGEMENT AB There is a scarcity of research on the relationship between presence of problem behaviors and psychotropic medication use in children with autism spectrum disorder (ASD). Participants in the current study were children and adolescents ages 3-17 years who were sorted into four groups: ASD on psychotropic medication (N = 100), ASD not on psychotropic medication (N = 147), typically developing on medication (N = 48), and typically developing not on medication (N = 168). A one-way multivariate analysis of covariance (MANCOVA) was conducted to determine the relationship between medication use and rates of internalizing and externalizing behaviors. Post hoc analyses revealed that children with ASD on psychotropic medication evinced significantly more externalizing behaviors than children with ASD not on medication. However, the two groups did not significantly differ on rates of internalizing behaviors. These results suggest that psychotropic medications may often be prescribed to manage externalizing behaviors. Implications of these findings are discussed in relation to the existing literature. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tureck, Kim; Matson, Johnny L.; Turygin, Nicole; Macmillan, Katie] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Tureck, K (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1377 EP 1382 DI 10.1016/j.rasd.2013.08.003 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500011 ER PT J AU MacDonald, M Lord, C Ulrich, D AF MacDonald, Megan Lord, Catherine Ulrich, Dale TI The relationship of motor skills and adaptive behavior skills in young children with autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Motor skills; Young children; Adaptive behavior ID DIAGNOSTIC OBSERVATION SCHEDULE; INFANTS; INTERVENTIONS; TODDLERS AB Objective: To determine the relationship of motor skills and adaptive behavior skills in young children with autism. Design: A multiple regression analysis tested the relationship of motor skills on the adaptive behavior composite, daily living, adaptive social and adaptive communicative skills holding constant age, non-verbal problem solving, and calibrated autism severity. Setting: Majority of the data collected took place in an autism clinic. Participants: A cohort of 233 young children with ASD (n = 172), PDD-NOS (n = 22) and non-ASD (developmental delay, n = 39) between the ages of 14-49 months were recruited from early intervention studies and clinical referrals. Children with non-ASD (developmental delay) were included in this study to provide a range of scores indicted through calibrated autism severity. Interventions: Not applicable. Main outcome measures: The primary outcome measures in this study were adaptive behavior skills. Results: Fine motor skills significantly predicted all adaptive behavior skills (p <0.01). Gross motor skills were predictive of daily living skills (p <0.05). Children with weaker motor skills displayed greater deficits in adaptive behavior skills. Conclusions: The fine and gross motor skills are significantly related to adaptive behavior skills in young children with autism spectrum disorder. There is more to focus on and new avenues to explore in the realm of discovering how to implement early intervention and rehabilitation for young children with autism and motor skills need to be a part of the discussion. (C) 2013 Elsevier Ltd. All rights reserved. C1 [MacDonald, Megan] Oregon State Univ, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA. [Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, Ctr Autism & Dev Brain, White Plains, NY 10605 USA. [Ulrich, Dale] Univ Michigan, Sch Kinesiol, Ann Arbor, MI 48109 USA. RP MacDonald, M (reprint author), Oregon State Univ, Sch Biol & Populat Hlth Sci, 202 Womens Bldg, Corvallis, OR 97331 USA. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1383 EP 1390 DI 10.1016/j.rasd.2013.07.020 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500012 ER PT J AU Nordahl-Hansen, A Kaale, A Ulvund, SE AF Nordahl-Hansen, Anders Kaale, Anett Ulvund, Stein Erik TI Inter-rater reliability of parent and preschool teacher ratings of language in children with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Language; Autism; Inter-rater reliability; MacArthur CDI; Parents; Preschool teachers ID COMMUNICATIVE DEVELOPMENT INVENTORIES; SPECTRUM DISORDERS; PREDICTIVE-VALIDITY; VOCABULARY SPURT; YOUNG-CHILDREN; COMPREHENSION; ACQUISITION; ABILITY; CDI AB Parent reports such as MacArthur-Bates Communicative Development Inventories (CDIs) have been suggested as a measure of language in young children with autism since this group often score below base levels of direct tests. However, questions have been raised concerning the reliability of report-based assessments. Parents and preschool teachers filled out the CDI-Words & Gestures for 55 children diagnosed with autistic disorder. Inter-rater reliability analyses were done for the whole sample and a subgroup of minimally verbal children (n = 28). Further, potential over- or under-estimation, comparing the raters was analyzed. Results suggested excellent to fair inter-rater reliability between parent and preschool teacher. Parents tended to rate the children slightly higher than preschool teachers. However, the differences were small, and most likely due to contextual variations. These findings suggest that parents can be reliable sources of information about language abilities in children with autism. Therefore, when children are difficult to assess through direct tests, parent reports such as the CDI can be a good alternative.(C) 2013 Elsevier Ltd. All rights reserved. C1 [Nordahl-Hansen, Anders; Ulvund, Stein Erik] Univ Oslo, Dept Educ, N-0317 Oslo, Norway. [Kaale, Anett] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway. RP Nordahl-Hansen, A (reprint author), Univ Oslo, Dept Educ, POB 1092, N-0317 Oslo, Norway. EM a.j.n.hansen@ped.uio.no CR Adamson LB, 2009, J AUTISM DEV DISORD, V39, P84, DOI 10.1007/s10803-008-0601-7 Bornstein MH, 1998, CHILD DEV, V69, P654, DOI 10.2307/1132196 Charman T, 2003, J CHILD LANG, V30, P213, DOI 10.1017/S0305000902005482 Charman T, 2005, J CHILD PSYCHOL PSYC, V46, P500, DOI 10.1111/j.1469-7610.2004.00377.x Charman T, 2004, J AUTISM DEV DISORD, V34, P59, DOI 10.1023/B:JADD.0000018075.77941.60 Chiat S, 2007, J SPEECH LANG HEAR R, V50, P429, DOI 10.1044/1092-4388(2007/030) Cicchetti D. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1391 EP 1396 DI 10.1016/j.rasd.2013.08.006 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500013 ER PT J AU Zachor, DA Ben-Shachar, S Ben-Itzchak, E AF Zachor, Ditza A. Ben-Shachar, Shay Ben-Itzchak, Esther TI Do risk factors for autism spectrum disorders affect gender representation? SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Gender; Male:female ratio; Risk factors; Low birth weight; Multiplex families ID BIRTH-WEIGHT; PATERNAL AGE; CHILDREN; PSYCHOPATHOLOGY; COMPLICATIONS; EPIDEMIOLOGY; PREVALENCE; RECURRENCE; TWIN AB To examine the M:F ratio in several known risk factors to demonstrate insights regarding autism spectrum disorders (ASD) etiology and sex. The study included 615 participants aged 18 months to 18 years age (mean = 49.8 months, SD = 28.4 months) diagnosed with ASD. Cognitive, adaptive and assessment of ASD were obtained using standardized tests. Detailed birth, familial, medical and developmental histories were obtained from the parents. Risk factors included ASD in the family (having a first-order family member with ASD); advanced maternal age (>= 35 years); advanced paternal age (>= 38 years); birth order (first-born versus third-born); low birth weight (LBW) (<2500 g); prematurity (gestational age <36 weeks). The M:F ratio (4.4:1) in the LBW group was lower than the M:F ratio (7.1:1) in the >2500 g group; however the difference showed only a statistical trend. No significant differences in M:F ratio were found between the ASD groups with and without the other examined risk factors. It is possible that the absence of a major association between most of the examined risk factors and sex representation points to the relatively minor role of these risk factors in ASD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Zachor, Ditza A.; Ben-Itzchak, Esther] Assaf Harofeh Med Ctr, Autism Ctr, Dept Pediat, IL-70300 Zerifin, Israel. [Zachor, Ditza A.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Ben-Shachar, Shay] Sourasky Med Ctr, Genet Inst, IL-64238 Tel Aviv, Israel. [Ben-Itzchak, Esther] Ariel Univ Ctr Samaria, Dept Commun Disorders, IL-40700 Ariel, Israel. RP Zachor, DA (reprint author), Assaf Harofeh Med Ctr, Autism Ctr, IL-70300 Zerifin, Israel. 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PD NOV PY 2013 VL 7 IS 11 BP 1397 EP 1402 DI 10.1016/j.rasd.2013.08.008 PG 6 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500014 ER PT J AU Inokuchi, E Kamio, Y AF Inokuchi, Eiko Kamio, Yoko TI Qualitative analyses of verbal fluency in adolescents and young adults with high-functioning autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE High-functioning autism spectrum disorders; Verbal fluency; Action fluency; Semantic strategy; Cognitive flexibility; Generativity ID EXECUTIVE DYSFUNCTION; PARKINSONS-DISEASE; WORD FLUENCY; FRONTAL-LOBE; CHILDREN; INDIVIDUALS; PERFORMANCE; LANGUAGE; DEFICITS; MEMORY AB Systematic qualitative analyses of verbal fluency might aid our understanding of the characteristic cognitive processes in individuals with autism spectrum disorder (ASD). In this study, we compared through qualitative and quantitative analyses performance on letter fluency (LF), category fluency (CF), and action fluency (AF) in adolescents and young adults with high-functioning autism spectrum disorders (HFASD) with that of an age-, gender-, and IQ-matched control group. Quantitative analyses revealed significantly fewer correct responses on category and action fluency and significantly more intrusions on category fluency in individuals with HFASD than in control participants. Qualitative analyses revealed significantly fewer semantic clusters and significantly more phonemic clusters during action fluency in individuals with HFASD compared to control participants. With respect to action fluency, the number of correct responses and clusters were related to verbal IQ for individuals with HFASD but not for control participants. We discuss these results in terms of abnormalities in semantic/phonemic strategy choice, cognitive flexibility, and generativity in ASD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Inokuchi, Eiko; Kamio, Yoko] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Child & Adolescent Mental Hlth, Kodaira, Tokyo 1878553, Japan. RP Kamio, Y (reprint author), Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Child & Adolescent Mental Hlth, 4-1-1 Ogawa Higashi, Kodaira, Tokyo 1878553, Japan. EM kamio@ncnp.go.jp CR Abwender DA, 2001, ASSESSMENT, V8, P323, DOI 10.1177/107319110100800308 (APA) APA, 2000, DIAGN STAT MAN MENT Barnard L, 2008, AUTISM, V12, P125, DOI 10.1177/1362361307088486 BOUCHER J, 1988, J AUTISM DEV DISORD, V18, P637, DOI 10.1007/BF02211881 Carper RA, 2000, BRAIN, V123, P836, DOI 10.1093/brain/123.4.836 Courchesne E, 2011, BRAIN RES, V1380, P138, DOI 10.1016/j.brainres.2010.09.101 Crowford J. 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PD NOV PY 2013 VL 7 IS 11 BP 1403 EP 1410 DI 10.1016/j.rasd.2013.08.010 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500015 ER PT J AU Yi, L Fan, YB Zhao, J Huang, D Li, YY Zou, XB AF Yi, Li Fan, Yuebo Zhao, Jing Huang, Dan Li, Yunyi Zou, Xiaobing TI Atypical understanding of mental terms in Chinese-speaking children with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Mental terms; Verb factivity; Theory of mind; Autism spectrum disorder; Chinese ID EXECUTIVE FUNCTION; INDIVIDUAL-DIFFERENCES; YOUNG-CHILDREN; FALSE BELIEFS; MIND; ACQUISITION; LANGUAGE; STATES; PRESCHOOLERS; ABILITY AB The present study investigated how Chinese children with autism spectrum disorder (ASD) understand mental terms, especially their knowledge of verb factivity. We examined these children's ability to understand mental terms representing true belief (i.e., zhi1dao4, know) and false belief (i.e., yi3wei2, thought) and compared their ability with that of typically developing (TD) children matched with age, and TD children matched with verbal mental age (VMA). Children were asked to participate in a game to find a toy according to the experimenter's testimony, which involved these mental terms. Results showed that all children from these three groups understood zhi1dao4 better than yi3wei2. Particularly, children with ASD performed statistically significantly worse in understanding mental terms than their age-matched TO children, but not differently from VMA-matched TD children. The understanding of mental verbs was correlated with the language ability of children with ASD, and with age, language ability and executive function of TO children. After controlling for the effects of age, general language ability, and executive functions, the group difference of mental verb understanding still existed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Yi, Li; Li, Yunyi] Sun Yat Sen Univ, Dept Psychol, Guangzhou 510275, Guangdong, Peoples R China. [Fan, Yuebo; Huang, Dan] Guangzhou Cana Sch, Guangzhou, Guangdong, Peoples R China. [Fan, Yuebo; Huang, Dan] Guangzhou Rehabil & Res Ctr Children ASD, Guangzhou, Guangdong, Peoples R China. [Zhao, Jing] Sun Yat Sen Univ, Dept English, Guangzhou 510275, Guangdong, Peoples R China. [Zou, Xiaobing] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China. RP Yi, L (reprint author), Sun Yat Sen Univ, Dept Psychol, 135 Xingang West Rd, Guangzhou 510275, Guangdong, Peoples R China. EM yili5@mail.sysu.edu.cn CR American Psychiatric Association (APA), 1994, DIAGN STAT MAN MENT, V4th Astington J. 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TI Pilot randomized controlled trial of a Functional Behavior Skills Training program for young children with Autism Spectrum Disorder who have significant early learning skill impairments and their families SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorder; Functional behavior skills; Early learning skill impairment; Parent training; Randomized controlled trial ID PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE EARLY INTERVENTION; PROFOUND MENTAL-RETARDATION; INDEPENDENT-LIVING SKILLS; CHALLENGING BEHAVIORS; INTELLECTUAL DISABILITY; FOLLOW-UP; INDIVIDUALS; STRESS; METAANALYSIS AB Many children with Autism Spectrum Disorder (ASD) possess early learning skill deficits and, do not achieve significant cognitive and adaptive gains following intensive behavioral intervention. This pilot randomized controlled trial investigated the effectiveness of a Functional Behavior Skills Training (FBST) program in improving children's performance on functional skills and communication, mitigating children's problem behaviors, and improving parents' strain, sense of competence, and, knowledge of Applied Behavior Analysis (ABA). Fifteen children with ASD who demonstrated early, learning skill impairments (ages between 38 and 82 months) were recruited from a community-based, IBI program or its waitlist. Children and their parents were randomized to a treatment group who, received FBST for four months or a control group who received their treatment as usual. Children who, received FBST improved on targeted functional skills and communication and demonstrated lower, levels of disruptive behavior. Meanwhile, parents who received FBST improved in their knowledge of, ABA. Overall, preliminary findings suggest that FBST is a feasible and promising behavioral, intervention for children with ASD who have early learning skill impairments. FBST promotes the, development of functional behavior and communication which can direct children onto a path of, appropriate skill development and meaningful interactions in the real world. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Reitzel, J.; Summers, J.] McMaster Univ, Hamilton, ON, Canada. [Reitzel, J.; Summers, J.; Lorv, B.] McMaster Childrens Hosp, Hamilton, ON, Canada. [Georgiades, S.; Duku, E.] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON, Canada. [Szatmari, P.] Univ Toronto, Toronto, ON, Canada. [Zwaigenbaum, L.] Univ Alberta, Edmonton, AB, Canada. RP Reitzel, J (reprint author), 555 Sanat Rd, Hamilton, ON L9C 0C4, Canada. 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Goldin, Rachel L. TI The relationship between race and comorbid symptoms in infants and toddlers with autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Comorbidity; The Baby and Infant Screen for Children with aUtIsm Traits - Part 2; Race ID CHALLENGING BEHAVIORS; PSYCHIATRIC-DISORDERS; INTELLECTUAL DISABILITY; TRAITS BISCUIT; DSM-5 CRITERIA; SOCIAL-SKILLS; PDD-NOS; CHILDREN; ASD; PSYCHOPATHOLOGY AB Researchers have indicated that persons with autism spectrum disorder (ASD) population evince higher rates of comorbid symptoms. While the relationship between comorbid symptoms and factors such as autism symptom severity, IQ level, age, communication abilities, and degree of social impairment were previously examined, there has been limited research on the effect of race in this area. The current study examined the potential role of race in comorbid symptoms in toddlers with ASD and atypically developing toddlers without a diagnosis of ASD using The Baby and Infant Screen for Children with aUtIsm Traits Part 2 (BISCUIT-Part 2). Based on the current findings, African-American toddlers evinced higher rates of comorbid symptoms than Caucasian toddlers and toddlers of other races. In addition, toddlers with ASD evinced higher rates of comorbid symptoms than atypically developing toddlers without a diagnosis of ASD. Implications regarding these findings are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jang, Jina; Matson, Johnny L.; Cervantes, Paige E.; Goldin, Rachel L.] Louisiana State Univ, Baton Rouge, LA 70803 USA. RP Jang, J (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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However, adolescents with ASDs may face age-specific challenges necessitating the need for contextually relevant and effective interventions. This systematic review examined peer-reviewed intervention research for adolescents (ages 12-21) with ASD. Electronic database searches and ancestral searches were used to identify studies published between 1980 and 2011. 102 studies were identified. A variety of interventions were implemented in these studies to address a wide range of targeted skills and behaviors. Reviewed studies were categorized into seven domains based on the skills and behaviors targeted: (a) social skills; (b) communication skills; (c) challenging behavior; (d) academic skills; (e) vocational skills; (f) independence and self-care; and (g) physical development. Results indicate that effective interventions exist in each category. 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TI Using a Nuk (R) brush to increase acceptance of solids and liquids for two children diagnosed with autism SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Feeding disorders; Escape extinction; Physical guidance; Autism ID FOOD REFUSAL; ESCAPE EXTINCTION; POSITIVE REINFORCEMENT; FUNCTIONAL-ANALYSIS; VARIETY AB Escape extinction (EE) procedures, such as non-removal of the spoon (NRS) and physical guidance, have been shown to be effective for increasing the acceptance of previously refused foods in children with feeding disorders. NRS typically involves presenting a utensil at a child's lips until he/she accepts a bite/drink or until an arbitrary meal duration is met. As a result, some children may learn to "wait out" the meal duration thus avoiding bites/drinks altogether. Physical guidance procedures are implemented in a similar manner but also include physically guiding the child's mouth open by applying pressure on the mandibular joint (i.e., jaw prompt). In some cases, the jaw prompt may harm the child if too much pressure is applied to his/her face. Due to the limitations of these procedures we evaluated an alternative PG strategy by using a Nuk (R) brush to increase the acceptance of bites and drinks in two participants. Published by Elsevier Ltd. C1 [Kadey, Heather J.; Roane, Henry S.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Diaz, Janet C.; McCarthy, Christie M.] Kelherman Behav & Feeding Program, Utica, NY 13501 USA. RP Kadey, HJ (reprint author), SUNY Upstate Med Univ, 600 East Genesee St,Suite 124, Syracuse, NY 13210 USA. 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M., 2012, HDB EVIDENCE BASED P Volkert VM, 2010, J APPL BEHAV ANAL, V43, P155, DOI 10.1901/jaba.2010.43-155 NR 29 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1461 EP 1480 DI 10.1016/j.rasd2013.07.017 PG 20 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500020 ER PT J AU Murray, C Healy, O AF Murray, Clodagh Healy, Olive TI Increasing response variability in children with autism spectrum disorder using lag schedules of reinforcement SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Response variability; Lag schedules; Reinforcement; U-Value statistic ID CONTINGENCY; EXTINCTION AB Individuals with autism spectrum disorder (ASD) often present with deficits in variability in responding across multiple repertoires. However, research to date has resulted in little empirical evaluation of remediation strategies for such deficits. We investigated the effects of lag schedules of reinforcement on response variability using a computer-based task designed for the purpose of the study. The U-value statistic was used as a measure of variability in responding to determine if increasing the lag criterion would correspondingly increase levels of variability. Participants included children with ASD (Group 1) and neurotypical children (Group 2). Results showed that U-values were higher when reinforcement was contingent on increased variability, indicating the effectiveness of higher lag values on response variability. A significant difference in response variability between groups provided evidence for the disparity in such responding in children with ASD compared to their neurotypical peers. Group 1 showed consistently lower U-values than Group 2 indicating lower response variability. However, data from this study clearly show that lag schedules of reinforcement may be employed to increase response variability in ASD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Murray, Clodagh; Healy, Olive] Natl Univ Ireland Galway, Galway, Ireland. RP Healy, O (reprint author), Natl Univ Ireland, Sch Psychol, Univ Rd, Galway, Ireland. 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Autism Spectr. Disord. PD NOV PY 2013 VL 7 IS 11 BP 1481 EP 1488 DI 10.1016/j.rasd.2013.08.004 PG 8 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 247JK UT WOS:000326613500021 ER PT J AU Meyers, OI AF Meyers, O., I TI THE IMPACT OF DSM-5 ON THE DEVELOPMENT OF DRUGS TO TREAT AUTISM SPECTRUM DISORDER SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Meyers, O., I] Truven Hlth Analyt, Cleveland, OH 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD NOV PY 2013 VL 16 IS 7 BP A607 EP A607 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 242MY UT WOS:000326247602337 ER PT J AU Vohra, R Madhavan, S Sambamoorthi, U AF Vohra, R. Madhavan, S. Sambamoorthi, U. TI IMPACT OF AUTISM SPECTRUM DISORDERS ON THE FAMILY - A NATIONAL PERSPECTIVE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Vohra, R.; Madhavan, S.; Sambamoorthi, U.] W Virginia Univ, Sch Pharm, Morgantown, WV 26506 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD NOV PY 2013 VL 16 IS 7 BP A553 EP A554 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 242MY UT WOS:000326247602044 ER PT J AU Mohiuddin, S Ghaziuddin, M AF Mohiuddin, Sarah Ghaziuddin, Mohammad TI Psychopharmacology of autism spectrum disorders: A selective review SO AUTISM LA English DT Article DE autism; psychopharmacology; comorbidity ID PERVASIVE DEVELOPMENTAL DISORDERS; DOUBLE-BLIND; ATYPICAL ANTIPSYCHOTICS; SCHIZOPHRENIC CHILDREN; REPETITIVE BEHAVIORS; ADOLESCENT AUTISM; CROSSOVER TRIAL; PLACEBO; IRRITABILITY; RISPERIDONE AB While there is no cure for autism spectrum disorder, psychopharmacologic agents are often used with behavioral and educational approaches to treat its comorbid symptoms of hyperactivity, irritability, and aggression. Studies suggest that at least 50% of persons with autism spectrum disorder receive psychotropic medications during their life span. This selective review examines recent studies about the use of psychotropic medications in persons with autism spectrum disorder. The aim was to focus on randomized controlled trials conducted from 1990 to 2010 on this topic. A comprehensive literature search was performed using PubMed and Cochrane databases. Out of 105 studies identified for the review, only 24 were randomized controlled trials. Thus, despite the common use of these medications in autism spectrum disorder, more controlled studies are needed to determine their long-term efficacy and safety. C1 [Mohiuddin, Sarah; Ghaziuddin, Mohammad] Univ Michigan, Ann Arbor, MI 48109 USA. RP Ghaziuddin, M (reprint author), Univ Michigan, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. 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Nowlin, Rachel B. Pinkham, Amy E. TI Social cognition, social skill, and the broad autism phenotype SO AUTISM LA English DT Article DE broad autism phenotype; social cognition; social functioning; social skill ID GENERAL-POPULATION; SPECTRUM DISORDERS; FUNCTIONING AUTISM; TRAITS; SCHIZOPHRENIA; INDIVIDUALS; RECOGNITION; ASSOCIATION; PREDICTORS; FAMILY AB Social-cognitive deficits differentiate parents with the broad autism phenotype from non-broad autism phenotype parents more robustly than other neuropsychological features of autism, suggesting that this domain may be particularly informative for identifying genetic and brain processes associated with the phenotype. The current study examined whether the social-cognitive deficits associated with the broad autism phenotype extend to the general population and relate to reduced social skill. A total of 74 undergraduates completed the Broad Autism Phenotype Questionnaire, three standardized social-cognitive tasks, and a live social interaction with an unfamiliar research assistant. Social broad autism phenotype traits were significantly associated with deficits in social cognition and reduced social skill. In addition, the relationship between social broad autism phenotype traits and social skill was partially mediated by social cognition, suggesting that the reduced interpersonal ability associated with the broad autism phenotype occurs in part because of poorer social-cognitive ability. Together, these findings indicate that the impairments in social cognition and social skill that characterize autism spectrum disorder extend in milder forms to the broad autism phenotype in the general population and suggest a framework for understanding how social broad autism phenotype traits may manifest in diminished social ability. C1 [Sasson, Noah J.; Nowlin, Rachel B.] Univ Texas Dallas, Richardson, TX 75080 USA. [Pinkham, Amy E.] So Methodist Univ, Dallas, TX 75275 USA. RP Sasson, NJ (reprint author), Univ Texas Dallas, Sch Behav & Brain Sci, GR41,800 W Campbell Rd, Richardson, TX 75080 USA. 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S., 1993, WIDE RANGE ACHIEVEME NR 42 TC 4 Z9 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD NOV PY 2013 VL 17 IS 6 BP 655 EP 667 DI 10.1177/1362361312455704 PG 13 WC Psychology, Developmental SC Psychology GA 241FF UT WOS:000326151100003 PM 22987889 ER PT J AU Poljac, E Poljac, E Wagemans, J AF Poljac, Ervin Poljac, Edita Wagemans, Johan TI Reduced accuracy and sensitivity in the perception of emotional facial expressions in individuals with high autism spectrum traits SO AUTISM LA English DT Article DE Autism spectrum quotient; Broader autistic phenotype; Face perception; Emotion recognition; Facial expression ID RECOGNITION ABILITY; FUNCTIONING AUTISM; FACE RECOGNITION; BASIC EMOTIONS; QUOTIENT AQ; DISORDERS; CHILDREN; PHENOTYPE AB Autism spectrum disorder (ASD) is among other things characterized by specific impairments in emotion processing. It is not clear, however, to what extent the typical decline in affective functioning is related to the specific autistic traits. We employed The Autism Spectrum-Quotient (AQ) to quantify autistic traits in a group of 500 healthy individuals and investigate whether we could detect similar difficulties in the perception of emotional expressions in a broader autistic phenotype. The group with high AQ score was less accurate and needed higher emotional content to recognize emotions of anger, disgust, and sadness. Our findings demonstrate a selective impairment in identification of emotional facial expressions in healthy individuals that is primarily related to the extent of autistic traits. C1 [Poljac, Ervin; Wagemans, Johan] Univ Leuven, Louvain, Belgium. [Poljac, Edita] Univ Oxford, Oxford OX1 2JD, England. RP Poljac, E (reprint author), Univ Leuven KU Leuven, Expt Psychol Lab, Tiensestr 102,Bus 3711, BE-3000 Louvain, Belgium. 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A. Deutschman, Amber A. C. G. Bogels, Susan M. TI Examining the Screen for Child Anxiety-Related Emotional Disorder-71 as an assessment tool for anxiety in children with high-functioning autism spectrum disorders SO AUTISM LA English DT Article DE ASD; anxiety; self-report; child-parent agreement ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; RANDOMIZED-TRIAL; ADOLESCENTS; INTERVIEW; SYMPTOMS; RELIABILITY; THERAPY; SAMPLE; YOUTH AB The psychometric properties of a questionnaire developed to assess symptoms of anxiety disorders (SCARED-71) were compared between two groups of children: children with high-functioning autism spectrum disorder and comorbid anxiety disorders (ASD-group; n = 115), and children with anxiety disorders (AD-group; n = 122). Anxiety disorders were established with a semi-structured interview (ADIS-C/P), using child- as well as parent-report. Internal consistency, construct validity, sensitivity, specificity, and discriminant validity of the SCARED-71 was investigated. Results revealed that the psychometric properties of the SCARED-71 for the ASD-group were quite comparable to the AD-group, however, the discriminant validity of the SCARED-71 child-report was less in the ASD-group. Raising the parental cutoffs of the SCARED-71 resulted in higher specificity rates, which suggests that research should focus more on establishing alternative cutoffs for the ASD-population. C1 [van Steensel, Francisca J. A.; Deutschman, Amber A. C. G.; Bogels, Susan M.] Univ Amsterdam, NL-1018 VZ Amsterdam, Netherlands. RP van Steensel, FJA (reprint author), Univ Amsterdam, Res Inst Child Dev & Educ, Nieuwe Prinsengracht 130, NL-1018 VZ Amsterdam, Netherlands. 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The distress a family may encounter with regard to inability to access recommended services is also poorly understood. In this study, we present preliminary data regarding implementation of clinical recommendations following autism spectrum disorder diagnosis as well as associations of implementation with maternal functioning. In total, 75 mothers of young children diagnosed with autism spectrum disorder through a university-based preschool autism clinic returned surveys regarding access to recommended services as well as maternal mental health and distress. Results indicate that while families were able to implement numerous recommendations, specific categories of intervention were less likely to be received. Challenges implementing recommended services were not related to increased maternal distress. 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E., 2011, AUTISM SPECTRUM DISO, P1269 NR 24 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD NOV PY 2013 VL 17 IS 6 BP 693 EP 700 DI 10.1177/1362361312453881 PG 8 WC Psychology, Developmental SC Psychology GA 241FF UT WOS:000326151100006 PM 23045221 ER PT J AU Yudell, M Tabor, HK Dawson, G Rossi, J Newschaffer, C AF Yudell, Michael Tabor, Holly K. Dawson, Geraldine Rossi, John Newschaffer, Craig CA Working Grp Autism Risk Commun Eth TI Priorities for autism spectrum disorder risk communication and ethics SO AUTISM LA English DT Article DE autism; ethics; risk communication ID RESEARCH PARTICIPANTS; UNDERSTANDING AUTISM; WORKING GROUP; HEALTH; PREVALENCE; PERCEPTION; CHILDREN; ISSUES; ASSOCIATION; INFORMATION AB Autism spectrum disorders are an issue of increasing public health significance. The incidence of autism spectrum disorders has been increasing in recent years, and they are associated with significant personal and financial impacts for affected persons and their families. In recent years, a large number of scientific studies have been undertaken, which investigate genetic and environmental risk factors for autism, with more studies underway. At present, much remains unknown regarding autism spectrum disorder risk factors, but the emerging picture of causation is in many cases complex, with multiple genes and gene-environment interactions being at play. The complexity and uncertainty surrounding autism spectrum disorder risk factors raise a number of questions regarding the ethical considerations that should be taken into account when undertaking autism spectrum disorder risk communication. At present, however, little has been written regarding autism spectrum disorder risk communication and ethics. This article summarizes the findings of a recent conference investigating ethical considerations and policy recommendations in autism spectrum disorder risk communication, which to the authors' knowledge is the first of its kind. Here, the authors discuss a number of issues, including uncertainty; comprehension; inadvertent harm; justice; and the appropriate roles of clinicians, scientists, and the media in autism spectrum disorder risk communication. C1 [Yudell, Michael; Rossi, John; Newschaffer, Craig] Drexel Univ, Philadelphia, PA 19102 USA. [Tabor, Holly K.] Univ Washington, Seattle, WA 98195 USA. [Tabor, Holly K.] Seattle Childrens Res Inst, Seattle, WA USA. [Dawson, Geraldine] Univ N Carolina, Chapel Hill, NC 27515 USA. RP Yudell, M (reprint author), Drexel Univ, Sch Publ Hlth, 1505 Race St,MS 1032, Philadelphia, PA 19102 USA. 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A. Verhulst, Frank C. Greaves-Lord, Kirstin TI The association of quality of social relations, symptom severity and intelligence with anxiety in children with autism spectrum disorders SO AUTISM LA English DT Article DE anxiety; autism spectrum disorders; intelligence; social relations; symptom severity ID PERVASIVE DEVELOPMENTAL DISORDERS; PDD-NOS; INTERNALIZING SYMPTOMS; PSYCHIATRIC-DISORDERS; ADOLESCENTS; VALIDITY; IV; DISABILITIES; CHILDHOOD; DIAGNOSES AB Limited quality of social relations, milder symptom severity and higher intelligence were shown to account for higher anxiety levels in autism spectrum disorders. The current study replicated and extended earlier findings by combining these three determinants of anxiety in autism spectrum disorders in one study. The sample consisted of 134 school-aged children with autism spectrum disorders, of whom 58 (43%) had a co-morbid anxiety disorder according to the Diagnostic Interview Schedule for Children-Parent version. In this sample, we tested associations between these determinants and anxiety univariately and multivariately to clarify the unique contribution of all determinants. Since we hypothesized that the association between limited quality of social relations and anxiety would be amplified by low symptom severity and/or high intelligence, we additionally tested for moderating effects. We found that higher anxiety levels were associated with a lower quality of social relations and lower symptom severity. In this mainly high-functioning sample, intelligence was not related to anxiety levels. No moderation effects were found. Since lower quality of social relations and lower symptom severity are associated with higher anxiety levels in children with autism spectrum disorders, therapeutic interventions aimed at reducing anxiety in autism spectrum disorders should pay attention to improving social relations, and presumably children with a lower symptom severity could benefit most from such interventions. C1 [Verheij, Fop; De Nijs, Pieter F. A.; Verhulst, Frank C.; Greaves-Lord, Kirstin] Sophia Childrens Univ Hosp, Erasmus Med Ctr Rotterdam, NL-3015 GJ Rotterdam, Netherlands. RP Greaves-Lord, K (reprint author), Sophia Childrens Univ Hosp, Erasmus Med Ctr Rotterdam, Dept Child & Adolescent Psychiat, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. 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Murray, Michael J. Smith, Laura A. Arnold, Mariah TI Assessing adolescent social competence using the Social Responsiveness Scale: Should we ask both parents or will just one do? SO AUTISM LA English DT Article DE assessment; autism spectrum disorder; interrater reliability; parent agreement; Social Responsiveness Scale ID AGREEMENT AB There is a paucity of instruments designed to measure social competence of adolescents with autism spectrum disorders. The Social Responsiveness Scale is one of a few that can be used. This study compared differences between mother and father reports of social competence of adolescents. Data were collected from parents of 50 adolescents with and without an autism spectrum disorder diagnosis between the ages of 12 and 17 years. The Social Responsiveness Scale demonstrated high interrater reliability between parents. These results suggest that the Social Responsiveness Scale is an efficient and valuable tool for researchers and clinicians to obtain a more comprehensive understanding of an individual's social skills deficits. Additionally, given the extremely high agreement between mothers and fathers on the ratings of their children's social competence, obtaining data from either parent is sufficient to provide an accurate reflection of social competence at home. C1 [Pearl, Amanda M.; Murray, Michael J.; Arnold, Mariah] Penn State Univ, Coll Med, University Pk, PA 16802 USA. [Smith, Laura A.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP Pearl, AM (reprint author), Penn State Coll Med, Dept Psychiat, Penn State Milton S Hershey Med Ctr, 500 Univ Dr, Hershey, PA 17033 USA. EM apearl@hmc.psu.edu CR ACHENBACH TM, 1987, PSYCHOL BULL, V101, P213, DOI 10.1037/0033-2909.101.2.213 [Anonymous], 2009, MMWR SURVEILL SUMM, V58, P1 Constantino JN, 2003, J AUTISM DEV DISORD, V33, P427, DOI 10.1023/A:1025014929212 Constantino JN, 2005, SOCIAL RESPONSIVENES De Los Reyes A, 2005, PSYCHOL BULL, V131, P483, DOI DOI 10.1037/0033-2909.131.4.483 De Los Reyes A, 2004, PSYCHOL ASSESSMENT, V16, P330, DOI DOI 10.1037/1040-3590.16.3.330 Duhig AM, 2000, CLIN PSYCHOL-SCI PR, V7, P435, DOI 10.1093/clipsy/7.4.435 Moreno J, 2008, J FAM PSYCHOL, V22, P915, DOI 10.1037/a0014097 Pearl AM, 2010, PENNS PSYCH ASS HARR Posserud MB, 2006, J CHILD PSYCHOL PSYC, V47, P167, DOI 10.1111/j.1469-7610.2005.01462.x Rutter M., 2003, AUTISM DIAGNOSTIC IN Schroeder JF, 2010, J CHILD FAM STUD, V19, P646, DOI 10.1007/s10826-010-9352-0 STOKES TF, 1977, J APPL BEHAV ANAL, V10, P349, DOI 10.1901/jaba.1977.10-349 NR 13 TC 1 Z9 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD NOV PY 2013 VL 17 IS 6 BP 736 EP 742 DI 10.1177/1362361312453349 PG 7 WC Psychology, Developmental SC Psychology GA 241FF UT WOS:000326151100009 PM 22914777 ER PT J AU Milne, SL McDonald, JL Comino, EJ AF Milne, Susan L. McDonald, Jenny L. Comino, Elizabeth J. TI Adaptive function in preschoolers in relation to developmental delay and diagnosis of autism spectrum disorders: Insights from a clinical sample SO AUTISM LA English DT Article DE adaptive behaviour; Adaptive Behaviour Assessment System-Second Edition; autism; developmental disability; preschoolers ID BEHAVIOR DOMAINS; DOWN-SYNDROME; CHILDREN; VINELAND; INDIVIDUALS; SCALES AB This study aims to explore the relationship between developmental ability, autism and adaptive skills in preschoolers. Adaptive function was assessed in 152 preschoolers with autism, with and without developmental delay, and without autism, with and without developmental delay. Their overall adaptive function, measured by the general adaptive composite on the Adaptive Behaviour Assessment System, was closely correlated to developmental ability as measured by the general quotient on the Griffith Mental Development Scales. Children with autism performed significantly less well on both scales. Domain scores discriminated between children with and without autism, with poorer performance on both the social and practical domain scores for children with autism, even when controlling for the effects of development. Children with average development, both with and without autism, had lower adaptive skills than expected for their developmental level. The importance of considering domain scores as well as the general adaptive composite when determining support needs is emphasised. C1 [Milne, Susan L.; McDonald, Jenny L.] Campbelltown Hosp, Campbelltown, NSW 2560, Australia. [Comino, Elizabeth J.] Univ NSW, Sydney, NSW, Australia. RP Milne, SL (reprint author), Campbelltown Hosp, Paediat Allied Hlth Unit, POB 149, Campbelltown, NSW 2560, Australia. 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TI Spontaneous attention to faces in Asperger syndrome using ecologically valid static stimuli SO AUTISM LA English DT Article DE Asperger syndrome; Autism; eye tracking; face perception; social attention ID WILLIAMS-SYNDROME; AUTISM; FIXATION; CHILDREN; INDIVIDUALS; COMPETENCE; DISORDERS; PATTERNS AB Previous eye tracking research on the allocation of attention to social information by individuals with autism spectrum disorders is equivocal and may be in part a consequence of variation in stimuli used between studies. The current study explored attention allocation to faces, and within faces, by individuals with Asperger syndrome using a range of static stimuli where faces were either viewed in isolation or viewed in the context of a social scene. Results showed that faces were viewed typically by the individuals with Asperger syndrome when presented in isolation, but attention to the eyes was significantly diminished in comparison to age and IQ-matched typical viewers when faces were viewed as part of social scenes. We show that when using static stimuli, there is evidence of atypicality for individuals with Asperger syndrome depending on the extent of social context. Our findings shed light on the previous explanations of gaze behaviour that have emphasised the role of movement in atypicalities of social attention in autism spectrum disorders and highlight the importance of consideration of the realistic portrayal of social information for future studies. C1 [Hanley, Mary; McPhillips, Martin; Mulhern, Gerry] Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. [Riby, Deborah M.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Hanley, M (reprint author), Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland. 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Gray, Kylie M. TI The relationship between emotion recognition ability and social skills in young children with autism SO AUTISM LA English DT Article DE Autism; emotion recognition; social skills ID SPECTRUM DISORDERS AB This study assessed the relationship between emotion recognition ability and social skills in 42 young children with autistic disorder aged 4-7 years. The analyses revealed that accuracy in recognition of sadness, but not happiness, anger or fear, was associated with higher ratings on the Vineland-II Socialization domain, above and beyond the influence of chronological age, cognitive ability and autism symptom severity. These findings extend previous research with adolescents and adults with autism spectrum disorders, suggesting that sadness recognition is also associated with social skills in children with autism. C1 [Williams, Beth T.; Gray, Kylie M.] Monash Univ, Sch Psychol & Psychiat, Ctr Dev Psychiat & Psychol, Clayton, Vic 3800, Australia. RP Gray, KM (reprint author), Monash Med Ctr, ELMHS, 246 Clayton Rd, Melbourne, Vic 3168, Australia. EM kylie.gray@monash.edu RI Gray, Kylie/H-3345-2014 OI Gray, Kylie/0000-0001-6518-4240 CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baron-Cohen S, 2009, PHILOS T R SOC B, V364, P3567, DOI 10.1098/rstb.2009.0191 Bauminger N, 2002, J AUTISM DEV DISORD, V32, P283, DOI 10.1023/A:1016378718278 Boraston Z, 2007, NEUROPSYCHOLOGIA, V45, P1501, DOI 10.1016/j.neuropsychologia.2006.11.010 Constantino JN, 2005, SOCIAL RESPONSIVENES Ekman P., 1976, PICTURES FACIAL AFFE Garcia-Villamisar D, 2010, RES AUTISM SPECT DIS, V4, P755, DOI 10.1016/j.rasd.2010.01.016 Gotham K, 2009, J AUTISM DEV DISORD, V39, P693, DOI 10.1007/s10803-008-0674-3 Harms MB, 2010, NEUROPSYCHOL REV, V20, P290, DOI 10.1007/s11065-010-9138-6 Harrison P., 2003, ADAPTIVE BEHAV ASSES, V2nd Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Rogers J, 2006, PSYCHOL MED, V36, P1789, DOI 10.1017/S0033291706008853 Sparrow SS, 2005, VINELAND ADAPTIVE BE Wallace GL, 2011, J AUTISM DEV DISORD, V41, P1475, DOI 10.1007/s10803-010-1170-0 Wechsler D., 2002, WECHSLER PRESCHOOL P, V3rd Wright B, 2008, AUTISM, V12, P607, DOI 10.1177/1362361308097118 NR 16 TC 2 Z9 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD NOV PY 2013 VL 17 IS 6 BP 762 EP 768 DI 10.1177/1362361312465355 PG 7 WC Psychology, Developmental SC Psychology GA 241FF UT WOS:000326151100012 PM 23175751 ER PT J AU [Anonymous] AF [Anonymous] TI Psychopharmacology of autism spectrum disorders: A selective review SO AUTISM LA English DT Meeting Abstract NR 0 TC 0 Z9 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD NOV PY 2013 VL 17 IS 6 BP 769 EP 774 DI 10.1177/1362361313508671 PG 6 WC Psychology, Developmental SC Psychology GA 241FF UT WOS:000326151100013 ER PT J AU Grigg-Damberger, M Ralls, F AF Grigg-Damberger, Madeleine Ralls, Frank TI Treatment strategies for complex behavioral insomnia in children with neurodevelopmental disorders SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE circadian rhythm; clock genes; insomnia; melatonin; neurodevelopmental disorders ID AUTISM SPECTRUM DISORDERS; SMITH-MAGENIS-SYNDROME; PLACEBO-CONTROLLED TRIAL; RETT-SYNDROME; SLEEP PROBLEMS; ANGELMAN-SYNDROME; WILLIAMS-SYNDROME; BETA(1)-ADRENERGIC ANTAGONISTS; REPETITIVE BEHAVIORS; TYPICAL DEVELOPMENT AB Purpose of reviewThis review describes recent research in pediatric behavioral insomnias in neurodevelopmental disorders and their treatment.Recent findingsInsomnia in children with autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs) is typically complex, chronic, and difficult to adequately control. Abnormalities in genetic and/or epigenetic regulation of sleep/wakefulness and its timing predispose patients with NDD to insomnia, although poor sleep hygiene, maladaptive associations, and limit-setting are likely to contribute. Parents are agents for change in problematic sleep behaviors in patients with NDD. We review the benefits of behavioral therapies and melatonin to treat sleep problems in children with NDD. Problematic sleep is so prevalent in some neurodevelopmental syndromes (Rett, Angelman, Williams, and Smith-Magenis) that it is part of their diagnostic criteria.SummaryChildren and adolescents with neurological disorders frequently have complex sleep disorders that require treatment. Understanding the basic pathology and treatment strategies provides an opportunity to improve well being and quality of life in those affected by NDD and their families. C1 [Grigg-Damberger, Madeleine] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. [Grigg-Damberger, Madeleine] Univ New Mexico, Med Ctr, Univ Hosp Sleep Disorders Ctr, Pediatr Sleep Med Serv, Albuquerque, NM 87131 USA. [Grigg-Damberger, Madeleine] Univ New Mexico, Med Ctr, Clin Neurodiagnost Lab, Albuquerque, NM 87131 USA. [Ralls, Frank] Univ New Mexico Hosp, Sleep Disorders Ctr, Dept Internal Med, Albuquerque, NM USA. [Ralls, Frank] Univ New Mexico Hosp, Adult Sleep Med Serv, Sleep Disorders Ctr, Albuquerque, NM USA. [Ralls, Frank] Univ New Mexico Hosp, Program Sleep Med, Sleep Disorders Ctr, Albuquerque, NM USA. RP Grigg-Damberger, M (reprint author), One Univ New Mexico, Dept Neurol, MSC10 5620, Albuquerque, NM 87131 USA. 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Opin. Pulm. Med. PD NOV PY 2013 VL 19 IS 6 BP 616 EP 625 DI 10.1097/MCP.0b013e328365ab89 PG 10 WC Respiratory System SC Respiratory System GA 247FW UT WOS:000326602900005 PM 24055857 ER PT J AU Karanth, P Chandhok, T AF Karanth, Prathibha Chandhok, Tanushree Saxena TI Impact of Early Intervention on Children with Autism Spectrum Disorders as Measured by Inclusion and Retention in Mainstream Schools SO INDIAN JOURNAL OF PEDIATRICS LA English DT Article DE Autism; Early intervention; Impact; Mainstreaming ID YOUNG-CHILDREN AB To follow up the school/educational status of children with a primary diagnosis of Autism Spectrum Disorders (ASD), who had been enrolled in an Early Intervention (EI) program for 1-3 y, before the age of 6. Data was collected through a questionnaire covering three specific areas-the families' success in following the recommendation given on completion of the EI program, issues in schooling and feedback on the EI program. The contact modes included email, post, telephonic interviews and face-to-face interviews. One hundred and two of the 296 children responded to the questionnaire. The responses were analyzed to identify, the number of families who had completed the program and were able to follow through with the recommendation given on completion of the EI program, difficulties faced if any, family feedback on the program and the additional help that they would have liked to receive. The reasons for failure to comply with the recommendations were analyzed. Of the 102 children who responded seven had dropped out midway through the program and 10 had discontinued after one year. Of the remaining 85 who completed the program, 71 were advised mainstreaming (83.5 %) and 14 were advised special school (16.5 %). Sixty-five of the 71 children, who were advised to enroll their child in the mainstream, were in regular school. 76.5 % of the children who completed the EI program were integrated in regular schools, 2 to 7 y after having completed the program. EI helps in enrolment and retention of substantial numbers of children with ASD in mainstream schools. C1 [Karanth, Prathibha; Chandhok, Tanushree Saxena] Com DEALL Trust, Dept Speech Language Pathol, Bangalore 560084, Karnataka, India. RP Karanth, P (reprint author), Com DEALL Trust, Dept Speech Language Pathol, 47 Hutchins Rd II Cross, Bangalore 560084, Karnataka, India. EM communicationdeall@gmail.com FU Navajbai Ratan Tata Trust FX The authors would like to thank Navajbai Ratan Tata Trust for providing the financial support to employ a research assistant for this study. They would like to thank Lathina Lawrence who served as the Research Assistant for collection of data, Dr Subbakrishna for guidance in statistical analysis and all of the staff of Com DEALL at Bangalore-past and present for their contribution to the success of the children. CR [Anonymous], 1999, J AM ACAD CHILD ADOL, V38, p32S Bimbrauer J. 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PD NOV PY 2013 VL 80 IS 11 BP 911 EP 919 DI 10.1007/s12098-013-1014-y PG 9 WC Pediatrics SC Pediatrics GA 244GY UT WOS:000326376900006 PM 23686797 ER PT J AU Yi, L Pan, JH Fan, YB Zou, XB Wang, XM Lee, K AF Yi, Li Pan, Junhao Fan, Yuebo Zou, Xiaobing Wang, Xianmai Lee, Kang TI Children with autism spectrum disorder are more trusting than typically developing children SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE Autism spectrum disorder; Trust Distrust; Deception; Selective trust; Children; Development ID OF-MIND DEVELOPMENT; FALSE-BELIEF; MENTAL MODELS; DECEPTION; ABILITY; BEHAVIOR; PRESCHOOLERS; METAANALYSIS; INDIVIDUALS; DEAFNESS AB The current study examined whether children with autism spectrum disorder (ASD) had an indiscriminate trust bias whereby they would believe any information provided by an unfamiliar adult with whom they had no interactive history. Young school-aged children with ASD and their age- and ability-matched typically developing (TD) peers participated in a simple hide-and-seek game. In the game, an experimenter with whom the children had no previous interactive history pointed to or left a marker on a box to indicate the whereabouts of a hidden reward. Results showed that although young school-aged ASD children did not blindly trust any information provided by the unfamiliar adult, they appeared to be more trusting in the adult informant than did their age- and ability-matched TO children. (C) 2013 Elsevier Inc. All rights reserved. C1 [Yi, Li; Pan, Junhao] Sun Yat Sen Univ, Dept Psychol, Guangzhou 510275, Guangdong, Peoples R China. [Fan, Yuebo] Guangzhou Cana Sch, Guangzhou 510540, Guangdong, Peoples R China. [Fan, Yuebo] Guangzhou Rehabil & Res Ctr Children ASD, Guangzhou 510540, Guangdong, Peoples R China. [Zou, Xiaobing] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China. [Wang, Xianmai] Jinan Univ, Sch Management, Guangzhou 510632, Guangdong, Peoples R China. [Lee, Kang] Univ Toronto, Dr Eric Jackman Inst Child Study, Toronto, ON M5R 2X2, Canada. [Lee, Kang] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Yi, L (reprint author), Sun Yat Sen Univ, Dept Psychol, 135 Xingang West Rd, Guangzhou 510275, Guangdong, Peoples R China. 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Exp. Child Psychol. PD NOV PY 2013 VL 116 IS 3 BP 755 EP 761 DI 10.1016/j.jecp.2013.05.005 PG 7 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 243KP UT WOS:000326315600014 PM 23810631 ER PT J AU Pinto, WBVD Pedroso, JL de Souza, PVS Oliveira, ASB Barsottini, OGP AF Vieira de Rezende Pinto, Wladimir Bocca Pedroso, Jose Luiz Sgobbi de Souza, Paulo Victor Bulle Oliveira, Acary Souza Povoas Barsottini, Orlando Graziani TI Phelan-McDermid syndrome presenting with autistic spectrum: are we underdiagnosing chromosomal diseases in patients with autism? SO JOURNAL OF NEUROLOGY LA English DT Letter ID 22Q13 DELETION SYNDROME; DISORDERS; SPEECH; DELAY C1 [Vieira de Rezende Pinto, Wladimir Bocca; Pedroso, Jose Luiz; Sgobbi de Souza, Paulo Victor; Bulle Oliveira, Acary Souza; Povoas Barsottini, Orlando Graziani] Univ Fed Sao Paulo, Dept Neurol, Sao Paulo, Brazil. RP Pinto, WBVD (reprint author), Univ Fed Sao Paulo, Dept Neurol, Botucatu St,740,Vila Clementino, Sao Paulo, Brazil. EM wladimirbvrpinto@gmail.com RI Barsottini, O/E-9117-2010; Pedroso, Jose/F-1757-2013; Souza, Paulo Victor Sgobbi /N-2958-2014; Pinto, Wladimir/J-6555-2014 OI Souza, Paulo Victor Sgobbi /0000-0002-7416-7108; Pinto, Wladimir/0000-0002-0150-525X CR Cusmano-Ozog K, 2007, AM J MED GENET C, V145C, P393, DOI 10.1002/ajmg.c.30155 Leung Alexander K C, 2007, J Pediatr Health Care, V21, P108, DOI 10.1016/j.pedhc.2006.05.004 Merwick A, 2012, EPILEPSIA, V53, P81, DOI 10.1111/j.1528-1167.2012.03617.x NESSLINGER NJ, 1994, AM J HUM GENET, V54, P464 Persico AM, 2013, BEHAV BRAIN RES, V251, P95, DOI 10.1016/j.bbr.2013.06.012 Phelan K, 2012, MOL SYNDROMOL, V2-5, P186, DOI DOI 10.1159/000334260 Phelan MC, 2008, ORPHANET J RARE DIS, V3, DOI 10.1186/1750-1172-3-14 Sarasua SM, 2011, J MED GENET, V48, P761, DOI 10.1136/jmedgenet-2011-100225 Strenge S, 2008, KLIN PADIATR, V220, P318, DOI 10.1055/s-2007-977733 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 Zafeiriou DI, 2013, AM J MED GENET B, V162B, P327, DOI 10.1002/ajmg.b.32152 NR 12 TC 0 Z9 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD NOV PY 2013 VL 260 IS 11 BP 2900 EP 2902 DI 10.1007/s00415-013-7127-4 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 244PF UT WOS:000326400800028 ER PT J AU Knapp, C Woodworth, L Fernandez-Baca, D Baron-Lee, J Thompson, L Hinojosa, M AF Knapp, Caprice Woodworth, Lindsey Fernandez-Baca, Daniel Baron-Lee, Jacqueline Thompson, Lindsay Hinojosa, Melanie TI Factors Associated with a Patient-Centered Medical Home Among Children with Behavioral Health Conditions SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE ADHD; Autism; Depression; Medical home; Child health outcomes; Survey ID UNITED-STATES; ACCESS; CARE; SERVICES; DISPARITIES; INSURANCE AB At some point in their lives, nearly one-half of all American children will have a behavioral health condition. Many will not receive the care they need from a fragmented health delivery system. The patient-centered medical home is a promising model to improve their care; however, little evidence exists. Our study aim was to examine the association between several behavioral health indicators and having a patient-centered medical home. 91,642 children's parents or guardians completed the 2007 National Survey of Children's Health. An indicator for patient-centered medical home was included in the dataset. Descriptive statistics, bivariate tests, and multivariate regression models were used in the analyses. Children in the sample were mostly Male (52 %), White (78 %), non-Hispanic (87 %), and did not have a special health care need (80 %). 6.2 % of the sample had at least one behavioral health condition. Conditions ranged from ADHD (6 %) to Autism Spectrum Disorder (ASD) (1 %). Frequency of having a patient-centered medical home also varied for children with a behavioral health condition (49 % of children with ADHD and 33 % of children with ASD). Frequency of having a patient-centered medical home decreased with multiple behavioral health conditions. Higher severity of depression, anxiety, and conduct disorder were associated with a decreased likelihood of a patient-centered medical home. Results from our study can be used to target patient-centered medical home interventions toward children with one or more behavioral health conditions and consider that children with depression, anxiety, and conduct disorder are more vulnerable to these disparities. C1 [Knapp, Caprice; Woodworth, Lindsey; Fernandez-Baca, Daniel; Baron-Lee, Jacqueline; Hinojosa, Melanie] Univ Florida, Dept Hlth Outcomes & Policy, Gainesville, FL 32610 USA. [Thompson, Lindsay] Univ Florida, Dept Pediat, Gainesville, FL USA. RP Knapp, C (reprint author), Univ Florida, Dept Hlth Outcomes & Policy, 1329 SW 16th St, Gainesville, FL 32610 USA. 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Controlling for frequency, familiarity, length and imageability, Colorado Meaningfulness played a hitherto unremarked role in the vocabularies of children with ASD. High Colorado Meaningful words were underrepresented in the comprehension vocabularies of 2- to 12-year-olds with ASD. The Colorado Meaningfulness of a word is a measure of how many words can be associated with it. Situations in which high Colorado Meaningfulness words are encountered are typically highly variable, and words with High Colorado Meaningfulness often involve extensive use of context. Our data suggest that the number of contexts in which a particular word can appear has a role in determining vocabulary in ASD. This suggestion is consistent with the weak central coherence theory of autism. C1 [Schafer, Graham; Williams, Tim I.; Smith, Philip T.] Univ Reading, Dept Psychol, Reading RG6 6AL, Berks, England. RP Schafer, G (reprint author), Univ Reading, Dept Psychol, Reading RG6 6AL, Berks, England. 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Drmanac, Radoje Beaudet, Arthur L. Caskey, C. Thomas Yang, Yaping TI Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism SO NATURE GENETICS LA English DT Article ID DE-NOVO MUTATIONS; SPECTRUM DISORDERS; GENE; DELETION; CLUSTER; MODELS AB Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed, maternally silenced genes at 15q11-q13. We report four individuals with truncating mutations on the paternal allele of MAGEL2, a gene within the PWS domain. The first subject was ascertained by whole-genome sequencing analysis for PWS features. Three additional subjects were identified by reviewing the results of exome sequencing of 1,248 cases in a clinical laboratory. All four subjects had autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of PWS. 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EM schaaf@bcm.edu; manuel.l.gonzalezgaray@uth.tmc.edu FU US National Institutes of Health grant [HD037283]; Joan and Stanford Alexander family; Doris Duke Charitable Foundation; Cullen Foundation for Higher Education; Houston Foundation FX We are indebted to the patients and their families for their willingness to participate in our research study. We thank P. Zimmerman and E. Austin for clinical assistance. C.P.S. is generously supported by the Joan and Stanford Alexander family. C.P.S. is a recipient of a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. M.L.G.- G. and C.T.C. are generously supported by the Cullen Foundation for Higher Education and the Houston Foundation. A.L.B. is supported by US National Institutes of Health grant HD037283. 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TI Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology SO NATURE MEDICINE LA English DT Article ID MENTAL-RETARDATION PROTEIN; XENOPUS OOCYTE MATURATION; LONG-TERM POTENTIATION; CAMKII MESSENGER-RNA; T-MAZE ALTERNATION; CYTOPLASMIC POLYADENYLATION; SYNAPTIC PLASTICITY; TRANSLATIONAL CONTROL; WORKING-MEMORY; MOUSE MODEL AB Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice rescued working memory deficits, demonstrating reversal of this FXS phenotype. Finally, we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function. C1 [Udagawa, Tsuyoshi; Farny, Natalie G.; Ivshina, Maria; Nagaoka, Kentaro; Lorenz, Lori J.; Richter, Joel D.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Jakovcevski, Mira; Akbarian, Schahram] Univ Massachusetts, Sch Med, Brudnik Neuropsychiat Res Inst, Dept Psychiat, Worcester, MA USA. [Kaphzan, Hanoch; Klann, Eric] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Alarcon, Juan Marcos] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Anilkumar, Shobha; Chattarji, Sumantra] Inst Stem Cell Biol & Regenerat Med, Ctr Brain Dev & Repair, Bangalore, Karnataka, India. [Anilkumar, Shobha; Chattarji, Sumantra] Natl Ctr Biol Sci, Bangalore, Karnataka, India. [Hurt, Jessica A.] MIT, Dept Biol, Cambridge, MA USA. [Nalavadi, Vijayalaxmi C.; Bassell, Gary J.] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA USA. RP Richter, JD (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. EM joel.richter@umassmed.edu RI Nagaoka, Kentaro/C-2019-2013 OI Nagaoka, Kentaro/0000-0003-1038-1380 FU FRAXA Research Foundation; US National Institutes of Health NRSA [F32GM095060]; NIH [GM46779, NS079415, MH086509] FX We thank N. Dawra for technical assistance, P. Lombroso (Yale University) and C. Proud (University of Southampton) for kind gifts of antibodies (STEP and eEF2, respectively), J. Pelletier (McGill University) for the kind gift of hippuristanol and members of the Richter lab for helpful discussions. T.U. and N.G.F. gratefully acknowledge fellowships from the FRAXA Research Foundation. J.A.H. was supported by US National Institutes of Health NRSA Postdoctoral Fellowship F32GM095060. This work was supported by NIH grants GM46779 and NS079415 to J.D.R. and MH086509 to S. Akbarian. 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PD NOV PY 2013 VL 8 IS 6 BP 670 EP 672 DI 10.1177/1745691613507457 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 246KV UT WOS:000326537700007 ER PT J AU Healey, KM Penn, DL Perkins, D Woods, SW Addington, J AF Healey, Kristin M. Penn, David L. Perkins, Diana Woods, Scott W. Addington, Jean TI Theory of mind and social judgments in people at clinical high risk of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Clinical high risk; Schizophrenia; Social cognition; Theory of mind; Social judgments; Longitudinal study ID ULTRA-HIGH-RISK; HIGH-FUNCTIONING AUTISM; PERSECUTORY DELUSIONS; SCHIZOPHRENIA; COGNITION; INDIVIDUALS; PREDICTORS; RELATIVES; AMYGDALA AB Background: Social cognitive deficits are consistently reported in psychotic populations. Few studies have longitudinally investigated social cognition in clinical high-risk (CHR) populations. Aims: Longitudinally examine theory of mind (ToM) and social judgments in a CHR sample to investigate the stability of performance over time and potential ability to predict conversion to psychosis. Method: 147 CHR individuals and 85 help seeking controls (HSC) were assessed for up to 2 years; 28 participants developed psychosis across both groups. Generalized linear mixed models for repeated measures were used to examine change over time for ratings on the three social cognitive indices of ToM, trustworthiness, and approachability. Hierarchical regression was used to test whether social cognitive variables explain more variance in conversion than IQ. Results: CHR individuals showed a positive bias in approachability judgments over time compared to HSC. Baseline ToM performance significantly (p < .05) predicted later conversion beyond IQ scores. These results were attenuated when controlling for baseline symptom level. Conclusions: Although ToM deficits might predate conversion to psychosis, one must consider initial symptoms as well. Social judgments were not associated with conversion to schizophrenia. (C) 2013 Elsevier B. V. All rights reserved. C1 [Healey, Kristin M.; Penn, David L.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Perkins, Diana] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Addington, Jean] Univ Calgary, Fac Med, Dept Psychiat, Calgary, AB, Canada. RP Penn, DL (reprint author), Univ N Carolina, Dept Psychol, 250 Davie Hall, Chapel Hill, NC 27599 USA. EM kmhealey@email.unc.edu; dpenn@email.unc.edu; diana_perkins@unc.edu; scott.woods@yale.edu; jmadding@ucalgary.ca FU NIMH [U01U01MH066134-02, U01 MH066069-04, U01MH066160] FX This study was supported by the following NIMH grants: U01U01MH066134-02 to J. Addington, U01 MH066069-04 to D. Perkins, and U01MH066160 to S. Woods. 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The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a "high" and "low" Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the "high Al" group showed significant weight gains following treatment up to sacrifice at 6 months of age. Male mice in the "high Al" group showed significant changes in light-dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light-dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shaw, C. A.; Li, Y.; Tomljenovic, L.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Shaw, C. A.] Univ British Columbia, Program Expt Med, Vancouver, BC V5Z 1M9, Canada. [Shaw, C. A.] Univ British Columbia, Program Neurosci, Vancouver, BC V5Z 1M9, Canada. RP Shaw, CA (reprint author), Neural Dynam Res Grp, 828 W 10th Ave, Vancouver, BC V5Z1L8, Canada. EM cashawlab@gmail.com FU Dwoskin Family Foundation; Katlyn Fox Foundation FX The authors thank the Dwoskin Family Foundation and the Katlyn Fox Foundation for their financial support. We are also grateful to Agripina Suarez and other laboratory members for their assistance. 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TC 7 Z9 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 EI 1873-3344 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD NOV PY 2013 VL 128 SI SI BP 237 EP 244 DI 10.1016/j.jinorgbio.2013.07.022 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 239YB UT WOS:000326060800030 PM 23932735 ER PT J AU Gogolinska, A Nowak, W AF Gogolinska, Anna Nowak, Wieslaw TI Molecular basis of lateral force spectroscopy nano-diagnostics: computational unbinding of autism related chemokine MCP-1 from IgG antibody SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE Atomic force microscopy; Bionanomechanics; IgG antibody; Monocyte-chemoatractant protein-1; Steered molecular dynamics ID CHEMOATTRACTANT PROTEIN-1 MCP-1; MONOCYTE CHEMOATTRACTANT; RECOGNITION EVENTS; ALIGNMENT EDITOR; MICROSCOPY; DYNAMICS; ELECTROSTATICS; PDB2PQR; BRAIN; CCR2 AB Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, is a potent chemoattractant of T cells and monocytes, involved in inflammatory and angio-proliferative brain and retinal diseases. Higher expression of MCP-1 is observed in metastatic tumors. Unusual levels of MCP-1 in the brain may be correlated with autism. Immunochemistry where atomic force microscope (AFM) tips functionalized with appropriate antibodies against MCP-1 are used could in principle support medical diagnostics. Useful signals from single molecule experiments may be generated if interaction forces are large enough. The chemokine-antibody unbinding force depends on a relative motion of the interacting fragments of the complex. In this paper the stability of the medically important MCP-1- immunoglobulin G antibody Fab fragment complex has been studied using steered molecular dynamics (SMD) computer simulations with the aim to model possible arrangements of nano-diagnostics experiments. Using SMD we confirm that molecular recognition in MCP1-IgG is based mainly on six pairs of residues: Glu39A - Arg98H, Lys56A - Asp52H, Asp65A - Arg32L, Asp68A - Arg32L, Thr32A - Glu55L, Gln61A - Tyr33H. The minimum external force required for mechanical dissociation of the complex depends on a direction of the force. The pulling of the MCP-1 antigen in the directions parallel to the antigen-antibody contact plane requires forces about 20 %-40 % lower than in the perpendicular one. Fortunately, these values are large enough that the fast lateral force spectroscopy may be used for effective nano-diagnostics purposes. We show that molecular modeling is a useful tool in planning AFM force spectroscopy experiments. C1 [Gogolinska, Anna; Nowak, Wieslaw] Nicholas Copernicus Univ, Fac Phys Astron & Informat, PL-87100 Torun, Poland. [Gogolinska, Anna] Nicholas Copernicus Univ, Fac Math & Comp Sci, PL-87100 Torun, Poland. [Nowak, Wieslaw] Inst Fizyki UMK, PL-87100 Torun, Poland. RP Nowak, W (reprint author), Inst Fizyki UMK, Ul Grudziadzka 5, PL-87100 Torun, Poland. EM wiesiek@fizyka.umk.pl FU Polish Funds for Science [N519 578138, N202 262038] FX This work was supported by Polish Funds for Science - grant no. N519 578138 and grant no. N202 262038. 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PD NOV PY 2013 VL 19 IS 11 BP 4773 EP 4780 DI 10.1007/s00894-013-1972-z PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 241UH UT WOS:000326193200017 PM 24061853 ER PT J AU Helander, A Stodberg, T Jaeken, J Matthijs, G Eriksson, M Eggertsen, G AF Helander, Anders Stodberg, Tommy Jaeken, Jaak Matthijs, Gert Eriksson, Maud Eggertsen, Gosta TI Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Congenital disorder of glycosylation; Dolichol kinase; DOLK-CDG; Transferrin glycosylation; Carbohydrate-deficient transferrin ID CAPILLARY-ZONE-ELECTROPHORESIS; CONGENITAL DISORDERS; SERUM TRANSFERRIN; GLYCOSYLATION; DIAGNOSIS AB A 4-month old boy presented with multiple epileptic seizure types including West syndrome. Screening for infectious and structural etiologies showed normal results. A metabolic investigation was undertaken to investigate the cause of his neurological disease. Screening for congenital disorders of glycosylation (CDG) by HPLC analysis of serum carbohydrate-deficient transferrin (CDT) showed a type 1 pattern with 18% disialotransferrin (reference < 2%) and 2% asialotransferrin (reference 0). An undiagnosed 10-year old sister with a similar clinical history with infantile spasms at age 4 months, intellectual disability and an autism spectrum disorder, also showed a type 1 CDT pattern. Both siblings lacked dysmorphic features and extra-cerebral symptoms. The boy had cytotoxic edema of the thalamus and mesencephalon on MRI at age 7 months, whereas the girl had normal MM at age 8 months. Phosphomannomutase (PMM) and phosphomannose isomerase (MPI) activities in cultured fibroblasts were normal, excluding PMM2-CDG and MPI-CDG. Fibroblast lipid-linked oligosaccharide analysis was also normal, suggesting an early defect in glycan assembly. Sequence analysis of the dolichol kinase gene revealed a homozygous new missense mutation (p.M1?; c.2 T>C) in both siblings. In conclusion, two siblings were demonstrated to suffer from DOLK-CDG (MIM 610768) and to be homozygous for a new mutation. They presented with West syndrome and so far show a purely neurological phenotype. (C) 2013 Elsevier Inc. All rights reserved. C1 [Helander, Anders; Eggertsen, Gosta] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Helander, Anders; Eggertsen, Gosta] Karolinska Univ Lab, SE-14186 Stockholm, Sweden. [Stodberg, Tommy; Eriksson, Maud] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Neuropediat Unit, Stockholm, Sweden. [Jaeken, Jaak] Univ Hosp Gasthuisberg, Ctr Metabol Dis, B-3000 Louvain, Belgium. [Matthijs, Gert] Univ Hosp Gasthuisberg, Ctr Human Genet, B-3000 Louvain, Belgium. RP Helander, A (reprint author), Karolinska Univ Lab, C1-74, SE-14186 Stockholm, Sweden. 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Genet. Metab. PD NOV PY 2013 VL 110 IS 3 BP 342 EP 344 DI 10.1016/j.ymgme.2013.07.002 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Genetics & Heredity; Research & Experimental Medicine GA 239WZ UT WOS:000326058000023 PM 23890587 ER PT J AU Ruiz-Robledillo, N Moya-Albiol, L AF Ruiz-Robledillo, N. Moya-Albiol, L. TI Self-reported health and cortisol awakening response in parents of people with asperger syndrome: The role of trait anger and anxiety, coping and burden SO PSYCHOLOGY & HEALTH LA English DT Article DE family caregivers; ASPERGER syndrome; health; cortisol awakening response ID AUTISM SPECTRUM DISORDER; QUALITY-OF-LIFE; SALIVARY CORTISOL; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; BEHAVIORAL-PROBLEMS; PERCEIVED STRESS; CHILDREN; CAREGIVERS; STRATEGIES AB Caring for offspring with autism spectrum disorders entails high levels of stress for a long period of time and is associated with several types of health complaints. Few studies have focused on specific effects of particular disorders in the spectrum. This study was carried out with the aim of evaluating the global health of parents of people with Asperger syndrome (N=53) compared to those of typically developing children (N=54) through self-reported measures (medication consumption and somatic symptoms) and biological markers (cortisol awakening response [CAR]). Additionally, we analysed various psychological variables as potential predictors of caregiver health. We found that caregivers take more medication and have worse self-reported health than controls, but there were no significant differences in CAR between the groups. However, after controlling for negative affect, differences between groups in CAR reached significance. With regards to predictor variables, anxiety trait, cognitive-coping style, burden and anger temperament were significantly associated with caregiver's self-reported health. These findings underline the need to develop interventions that foster improvements in the health of caregivers, reduce their burden and enhance their quality of life. C1 [Ruiz-Robledillo, N.; Moya-Albiol, L.] Univ Valencia, Fac Psychol, Dept Psychobiol, Valencia, Spain. RP Moya-Albiol, L (reprint author), Univ Valencia, Fac Psychol, Dept Psychobiol, Valencia, Spain. 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Health PD NOV 1 PY 2013 VL 28 IS 11 BP 1246 EP 1264 DI 10.1080/08870446.2013.800517 PG 19 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA 242DU UT WOS:000326218400002 PM 23713979 ER PT J AU Mason, RA Davis, HS Boles, MB Goodwyn, F AF Mason, Rose A. Davis, Heather S. Boles, Margot B. Goodwyn, Fara TI Efficacy of Point-of-View Video Modeling: A Meta-Analysis SO REMEDIAL AND SPECIAL EDUCATION LA English DT Article DE autism; exceptionalities; meta-analysis; research methodology; video modeling; point-of-view modeling; developmental disabilities ID AUTISM SPECTRUM DISORDERS; DAILY LIVING SKILLS; SINGLE-CASE-RESEARCH; MODERATE INTELLECTUAL DISABILITIES; DEVELOPMENTAL-DISABILITIES; QUANTITATIVE SYNTHESIS; CONFIDENCE-INTERVALS; SUBJECT RESEARCH; THE-LITERATURE; STUDENTS AB Point-of-view video modeling (POV), a variation of video-based modeling interventions, involves creating a video exemplar from a first-person perspective. The advantage is a significant reduction in extraneous stimuli, as well as increased efficiency in production. However, the lack of systematic analysis to evaluate differential impact on targeted outcomes for individuals with disabilities limits the identification of the population for whom POV is most appropriate, as well as the most efficacious implementation procedure. Through meta-analysis of single-subject studies using POV to improve targeted outcomes, this study identifies differential effects of participant characteristics, implementation procedures, and targeted outcomes. Results of the systematic search reveal that POV has only been implemented with individuals with developmental disabilities or an autism spectrum disorder. Analysis yielded an overall improvement rate difference (IRD) effect size of .78 (83.4% confidence interval [CI] = [.76, .80]). Furthermore, age, disability, and implementation variables moderate outcomes. Areas of future research and implications for practice are discussed. C1 [Mason, Rose A.] Univ Kansas, Kansas City, KS 66101 USA. 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PD NOV PY 2013 VL 34 IS 6 BP 333 EP 345 DI 10.1177/0741932513486298 PG 13 WC Education, Special SC Education & Educational Research GA 242KR UT WOS:000326240500002 ER PT J AU Mechling, LC Ayres, KM Foster, AL Bryant, KJ AF Mechling, Linda C. Ayres, Kevin M. Foster, Ashley L. Bryant, Kathryn J. TI Comparing the Effects of Commercially Available and Custom-Made Video Prompting for Teaching Cooking Skills to High School Students With Autism SO REMEDIAL AND SPECIAL EDUCATION LA English DT Article DE special education; classroom; life skills; curriculum; education; adults ID DAILY LIVING SKILLS; MODERATE INTELLECTUAL DISABILITIES; DEVELOPMENTAL-DISABILITIES; MODELING INTERVENTIONS; SPECTRUM DISORDERS; TASK COMPLETION; YOUNG-ADULTS; INDIVIDUALS; SELF; INSTRUCTION AB The study compared the effects of using commercially available and custom-made video prompts on the completion of cooking recipes by four high school age males with a diagnosis of autism. An adapted alternating treatments design with continuous baseline, comparison, final treatment, and best treatment condition was used to compare the two procedures. Gains were made by each participant when using both video procedures. However, results indicate that all students performed more steps independently correct when completing recipes with the custom-made video prompts during the comparison condition. During the best treatment condition, recipes initially prepared using the commercially available video prompts in the comparison condition were performed at criterion levels when completed with the custom-made videos prompts. Implications for use and development of commercial and customized video products with attention to the salient features of video prompts are presented. C1 [Mechling, Linda C.; Foster, Ashley L.; Bryant, Kathryn J.] Univ N Carolina, Wilmington, NC 28403 USA. [Ayres, Kevin M.] Univ Georgia, Athens, GA 30602 USA. 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Cantor-Graae, Elizabeth TI The Social Defeat Hypothesis of Schizophrenia: An Update SO SCHIZOPHRENIA BULLETIN LA English DT Article DE genetics; epidemiology; dopamine; social exclusion; migration; intelligence ID INDUCED DOPAMINE RELEASE; PSYCHOTIC-DISORDERS; RISK-FACTOR; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL STRESS; ETHNIC DENSITY; COHORT; METAANALYSIS; IMMIGRANTS; MIGRATION AB According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding. C1 [Selten, Jean-Paul; van der Ven, Elsje; Rutten, Bart P. F.] Maastricht Univ, Sch Mental Hlth & Neurosci, Maastricht, Netherlands. [Selten, Jean-Paul; van der Ven, Elsje] Rivierduinen Psychiat Inst, Leiden, Netherlands. [Cantor-Graae, Elizabeth] Lund Univ, Sect Social Med & Global Hlth, Malmo, Sweden. [Cantor-Graae, Elizabeth] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden. RP Selten, JP (reprint author), GGZ Leiden, Sandifortdreef 19, NL-2333 ZZ Leiden, Netherlands. EM j.selten@ggzleiden.nl FU European Community's Seventh Framework Programme [HEALTH-F2-2010-241909] FX European Community's Seventh Framework Programme under grant agreement no. HEALTH-F2-2010-241909 (Project EU-GEI). 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Bull. PD NOV PY 2013 VL 39 IS 6 BP 1180 EP 1186 DI 10.1093/schbul/sbt134 PG 7 WC Psychiatry SC Psychiatry GA 241TC UT WOS:000326189700003 PM 24062592 ER PT J AU Gordon, I Eilbott, JA Feldman, R Pelphrey, KA Vander Wyk, BC AF Gordon, Ilanit Eilbott, Jeffrey A. Feldman, Ruth Pelphrey, Kevin A. Vander Wyk, Brent C. TI Social, reward, and attention brain networks are involved when online bids for joint attention are met with congruent versus incongruent responses SO SOCIAL NEUROSCIENCE LA English DT Article DE Joint attention; fMRI; Eye tracking ID ANTERIOR CINGULATE CORTEX; TEMPORO-PARIETAL JUNCTION; NEURAL BASIS; FUSIFORM GYRUS; COGNITION; AUTISM; FMRI; FACE; MIND; CONTRIBUTE AB Joint attention (JA) is a cornerstone of adaptive human social functioning. Little functional magnetic resonance imaging (fMRI) research has examined, in interactive paradigms, neural activation underlying bids for JA, met with a congruent or an incongruent social response. We developed a highly naturalistic fMRI paradigm utilizing eye-tracking to create real-time, contingent social responses to participant-initiated JA. During congruent responses to JA bids, we observed increased activation in the right amygdala, the right fusiform gyrus, anterior and dorsal anterior cingulate cortices, striatum, ventral tegmental area, and posterior parietal cortices. Incongruent responses to JA bids elicited increased activity localized to the right temporoparietal junction (TPJ) and bilateral cerebellum. No differences in eye-gaze patterns were observed during congruent or incongruent trials. Our results highlight the importance of utilizing interactive fMRI paradigms in social neuroscience and the impact of congruency in recruiting integrated social, reward, and attention circuits for processing JA. C1 [Gordon, Ilanit; Eilbott, Jeffrey A.; Pelphrey, Kevin A.; Vander Wyk, Brent C.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Feldman, Ruth] Bar Ilan Univ, Dept Psychol, IL-52900 Ramat Gan, Israel. [Feldman, Ruth] Bar Ilan Univ, Gonda Brain Res Ctr, IL-52900 Ramat Gan, Israel. RP Gordon, I (reprint author), Yale Univ, Ctr Child Study, 230 South Frontage Rd, New Haven, CT 06520 USA. 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Neurosci. PD NOV 1 PY 2013 VL 8 IS 6 BP 544 EP 554 DI 10.1080/17470919.2013.832374 PG 11 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 243YE UT WOS:000326353500003 PM 24044427 ER PT J AU Tunc-Ozcan, E Ullmann, TM Shukla, PK Redei, EE AF Tunc-Ozcan, Elif Ullmann, Timothy M. Shukla, Pradeep K. Redei, Eva E. TI Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Fetal Alcohol Spectrum Disorders; Autism Spectrum Disorders; Social Interaction; Social Memory; Thyroxine ID THYROID-HORMONE LEVELS; SPECTRUM DISORDERS; ANIMAL-MODELS; PRENATAL EXPOSURE; ETHANOL EXPOSURE; RECEPTOR; BRAIN; RATS; POPULATION; PROFILES AB Background Fetal alcohol spectrum disorder (FASD) is characterized by neurodevelopmental anomalies manifesting in cognitive and behavioral deficits in the offspring with diverse severities. Social behavior is affected in FASD, and these deficits overlap with those of autism spectrum disorder (ASD). Identifying some of the molecular characteristics related to ASD in an animal model of FASD could ultimately provide details on the underlying molecular mechanisms of both disorders that could lead to novel treatments. MethodsPregnant Sprague-Dawley rats received the following diets: control (C; ad libitum standard laboratory chow), nutritional control pair-fed (PF), ethanol (EtOH), or an EtOH diet supplemented with 0.3, 1.5, or 7.5mg thyroxine (T4)/l in the diet. Social behavior and memory were tested in the adult offspring. Plasma total T4, free T3 (fT3), and thyroid-stimulating hormone (TSH) levels were measured. Hippocampal expression of Gabrb3,Ube3a,Nr2b, Rasgrf1, and Dio3 were measured by RT-qPCR and protein levels of Mecp2 and Slc25a12 by Western blotting. ResultsAdult male offspring of EtOH dams showed elevated fT3 and low TSH levels. Adult male, but not female, offspring of EtOH dams exhibited social behavior and memory deficits. Expression of autism candidates, Gabrb3,Ube3a, Mecp2, and Slc25a12, was significantly increased in the hippocampus of male offspring of EtOH dams. Hippocampal Nr2b and Dio3 were also increased, while Rasgrf1 was decreased in the same population. Peripheral thyroid function, social behavioral deficits, and altered expression of the above genes were normalized by simultaneous administration of 0.3mg/l T4 in the EtOH diet. ConclusionsOur data suggest that social interaction deficits of FASD share molecular mechanism with ASD by showing altered hippocampal expression of several ASD candidate genes. Social interaction deficits as well as the gene expression changes in the offspring of EtOH-consuming dams can be reversed by low dose of thyroid hormone supplementation to the mothers. C1 [Tunc-Ozcan, Elif; Ullmann, Timothy M.; Shukla, Pradeep K.; Redei, Eva E.] Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. RP Redei, EE (reprint author), Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. EM e-redei@northwestern.edu FU NIH [AA013452, AA017978] FX This study was funded by NIH AA013452 and AA017978 to EER. 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TI Reduced interhemispheric interaction in non-autistic individuals with normal but high levels of autism traits SO BRAIN AND COGNITION LA English DT Article DE Autism; AQ; Weak central coherence; Interhemispheric interaction ID EMBEDDED FIGURES TASK; PERVASIVE DEVELOPMENTAL DISORDERS; WEAK CENTRAL COHERENCE; SPECTRUM QUOTIENT AQ; CORPUS-CALLOSUM; FUNCTIONING AUTISM; CHILDREN; HEMISPHERES; PERFORMANCE; DEFICITS AB People with autism spectrum disorder (ASD) show superior performance for tasks requiring detail-focused processing. Atypical neural connectivity and reduced interhemispheric communication are posited to underlie this cognitive advantage. Given recent conceptualization of autism as a continuum, we sought to investigate whether people with normal but high levels of autism like traits (AQ) also exhibit reduced hemispheric interaction. Sixty right-handed participants completed the AQ questionnaire (Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001) and a lateralised letter matching task that assessed unilateral and bilateral performance in response to simple (physical) and complex (identity) matches. Whereas people with low self-rated AQ scores showed a bilateral advantage for the more complex task, indicating normal interhemispheric interaction, people in the high AQ group failed to show a bilateral gain for the computationally demanding stimuli. This finding of disrupted interhemispheric interaction converges with a dimensional conceptualisation of ASD, suggesting that the structural anomalies of ASD extend to non-autistic individuals with high levels of autism traits. (c) 2013 Elsevier Inc. All rights reserved. C1 [O'Keefe, Natalie; Lindell, Annukka K.] La Trobe Univ, Sch Psychol Sci, Melbourne, Vic, Australia. RP O'Keefe, N (reprint author), 30 McNamara St, Preston, Vic 3072, Australia. 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PD NOV PY 2013 VL 83 IS 2 BP 183 EP 189 DI 10.1016/j.bandc.2013.08.005 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 235SI UT WOS:000325740600004 PM 24056118 ER PT J AU Kenworthy, L Wallace, GL Birn, R Milleville, SC Case, LK Bandettini, PA Martin, A AF Kenworthy, Lauren Wallace, Gregory L. Birn, Rasmus Milleville, Shawn C. Case, Laura K. Bandettini, Peter A. Martin, Alex TI Aberrant neural mediation of verbal fluency in autism spectrum disorders SO BRAIN AND COGNITION LA English DT Article DE Autism; Verbal fluency; fMRI; Executive function; Left inferior frontal gyrus ID HIGH-FUNCTIONING AUTISM; VENTROLATERAL PREFRONTAL CORTEX; FRONTAL-LOBE LESIONS; WORKING-MEMORY TASK; EXECUTIVE FUNCTIONS; REPETITIVE BEHAVIOR; BRAIN ACTIVATION; SENTENCE COMPREHENSION; ASPERGERS-DISORDER; COGNITIVE CONTROL AB Objective: Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD). Method: We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n = 17, mean verbal IQ = 117) and neurotypical (NT; n = 20, mean verbal IQ = 112) adolescent and young adult males (12-23 years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency. Results: Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand. Conclusions: These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses. Published by Elsevier Inc. C1 [Kenworthy, Lauren; Wallace, Gregory L.; Birn, Rasmus; Milleville, Shawn C.; Case, Laura K.; Bandettini, Peter A.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA. RP Kenworthy, L (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA. EM lkenwort@cnmc.org; gregwallace@mail.nih.-gov; rbirn@wisc.edu; millevis@mail.nih.gov; lkcase@gmail.com; bandettp@mail.nih.gov; alexmar-tin@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health, Division of Intramural Research under National Institutes of Health [10-M-0027]; Guldelsky Family Foundation FX This study was supported by the National Institute of Mental Health, National Institutes of Health, Division of Intramural Research, and it was conducted under National Institutes of Health Clinical Study Protocol 10-M-0027 (ClinicalTrials.gov ID NCT01031407). In addition, Lauren Kenworthy received support from the Guldelsky Family Foundation. The authors thank the children and their families who participated in the investigation, Ben Yerys for valuable feedback regarding the manuscript, and Eunice Dixon for editorial assistance. 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Nash, Kelly Koren, Gideon Rovet, Joanne TI Autism characteristics in children with fetal alcohol spectrum disorders SO CHILD NEUROPSYCHOLOGY LA English DT Article DE Fetal alcohol spectrum disorders; Autism spectrum disorder ID HYPERACTIVITY DISORDER; BEHAVIORAL-PHENOTYPE; ATTENTION-DEFICIT; EXPOSURE; MOTHERS; SKILLS AB Background: Children with fetal alcohol spectrum disorders (FASD) exhibit difficulties in many cognitive and behavioral domains and also have high comorbidity with other disorders such as attention deficit/hyperactivity disorder (ADHD) and conduct disorder as well as autism. Although the FASD profile is shown to be distinct from ADHD and conduct disorder, far less is known about the commonalities with autism. The current study used a parent-rated questionnaire containing an autism subscale to explore the autistic-like features that children with FASD exhibit. Methods: Studied were 25 children with FASD (age: M = 10.3 years) and 17 normal controls (NCs; age: M = 10.2 years). As part of a larger study, all parents/caregivers completed the Social Skills Improvement System (SSIS; Gresham & Elliot, 2008), which in addition to evaluating social skills and behavior problems globally, includes an Autism subscale. Results: Between-group comparisons showed the FASD group not only scored significantly lower in social skills and significantly higher in behavior problems than the NC group but children with FASD also scored significantly higher on the Autism subscale. Item analysis revealed they showed the most difficulty in terms of social and communicative functioning and the least in repetitive and restrictive behaviors. Conclusion: Current findings signify that FASD and autism share similarities with regard to social and communicative functioning. These findings, which further our knowledge of the FASD phenotype, may be useful in specifying the particular interventions these children need. C1 [Stevens, Sara A.; Nash, Kelly; Rovet, Joanne] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Stevens, Sara A.; Rovet, Joanne] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Nash, Kelly] Univ Toronto, Ontario Inst Studies Educ, Toronto, ON, Canada. [Koren, Gideon; Rovet, Joanne] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Koren, Gideon] Hosp Sick Children, Motherisk Program, Toronto, ON M5G 1X8, Canada. RP Stevens, SA (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM sara.stevens@utoronto.ca FU Canadian Institutes of Health Research (CIHR); Canadian Foundation on Fetal Alcohol Research (CFFAR) FX The authors gratefully appreciate the FASD diagnostic clinics staff for assistance in recruiting. We also wish to acknowledge the anonymous reviewers for their insightful comments and suggestions. This work was supported by the Canadian Institutes of Health Research (CIHR) and Canadian Foundation on Fetal Alcohol Research (CFFAR). 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In addition, to control for possibly related basic cognitive development, working memory, speed of processing, and verbal ability were assessed. A strong age effect was revealed across both measures of social cognition. Adolescents performed with a lower accuracy than adults. Further analyses indicated that those age differences remained significant even after controlling for basic cognitive abilities. Exploratory analyses indicated no influence of pubertal phase on social cognition. Results suggest ongoing development of social cognition across adolescence, independent of individual differences in more basic cognitive abilities. C1 [Vetter, Nora C.; Altgassen, Mareike] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. [Leipold, Kristina] Tech Univ Dresden, Dept Business & Econ, D-01062 Dresden, Germany. [Kliegel, Matthias] Univ Geneva, Dept Psychol, Geneva, Switzerland. [Phillips, Louise H.] Univ Aberdeen, Sch Psychol, Aberdeen, Scotland. RP Vetter, NC (reprint author), Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. 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PD NOV 1 PY 2013 VL 19 IS 6 BP 615 EP 629 DI 10.1080/09297049.2012.718324 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 240BY UT WOS:000326070900005 PM 22934659 ER PT J AU Young, WS AF Young, W. Scott TI Shedding Heat on Oxytocin SO ENDOCRINOLOGY LA English DT Editorial Material ID RECEPTOR-DEFICIENT MICE; SOCIAL RECOGNITION; AUTISM LOCI; GENOME-WIDE; PARTURITION; MOUSE; BEHAVIOR; IMPAIRS; SEARCH; GENES C1 NIMH, NIH, Dept Hlth & Human Serv, Sect Neural Gene Express, Bethesda, MD 20892 USA. RP Young, WS (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Sect Neural Gene Express, Bethesda, MD 20892 USA. 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The identification of neural correlates and novel agents to transform treatment has become priority avenues for research. Oxytocin (OT) is a neuropeptide whose emerging sphere of influence on mammalian behaviour and demonstrated impact on psychiatric illness suggest it may have potential in AN. In this paper, we undertake a targeted summary of the existing literature on OT research as it pertains to brain based behaviour and psychiatric dysfunction. Then, we conduct a systematic review of OT in AN. Papers that addressed any aspect of the OT system in AN were examined. The existing literature, although limited and based on small sample sizes, suggests a derangement of the OT system in AN that may normalise upon recovery. Preliminary pilot data from unpublished studies suggest a potential effect of OT administration on eating-related indices. Copyright (c) 2013 John Wiley & Sons, Ltd and Eating Disorders Association. C1 [Maguire, Sarah; O'Dell, Adrienne; Touyz, Lauren; Russell, Janice] Univ Sydney, Boden Inst, Ctr Eating & Dieting Disorders, Sydney, NSW 2006, Australia. [Russell, Janice] Northside Clin, Eating Disorders Unit, Sydney, NSW, Australia. RP Maguire, S (reprint author), Univ Sydney, Boden Inst, Ctr Eating & Dieting Disorders, Med Fdn Bldg,K25, Sydney, NSW 2006, Australia. 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Eat. Disord. Rev. PD NOV PY 2013 VL 21 IS 6 SI SI BP 475 EP 478 DI 10.1002/erv.2252 PG 4 WC Psychology, Clinical SC Psychology GA 239LS UT WOS:000326026600006 PM 24115458 ER PT J AU de Sampaio, FTP Soneira, S Aulicino, A Allegri, RF AF Tapajoz Pereira de Sampaio, Fernanda Soneira, Sebastian Aulicino, Alfredo Allegri, Ricardo F. TI Theory of Mind in Eating Disorders and Their Relationship to Clinical Profile SO EUROPEAN EATING DISORDERS REVIEW LA English DT Article DE anorexia; bulimia; theory of mind; social cognition; clinical profile ID OBSESSIVE-COMPULSIVE INVENTORY; HIGH-FUNCTIONING AUTISM; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; COGNITIVE REMEDIATION; EMOTION RECOGNITION; ASPERGER-SYNDROME; CENTRAL COHERENCE; CASE-SERIES; VERSION AB ObjectiveThis study aimed to assess cognitive and affective theory of mind (ToM) in patients with eating disorders and to explore its relationship with the clinical and psychopathological profile. MethodTheory of mind was assessed in 65 women, consisting of 22 with anorexia nervosa (AN), 19 with bulimia nervosa (BN), and 24 healthy controls (HC), using the Reading the Mind in the Eyes Test and the Faux Pas Test. These tasks evaluate affective and cognitive ToM, respectively. We also examined the correlations between performance on ToM tasks and the clinical psychopathological profile, which was extensively evaluated through self-report instruments and clinical interviews. ResultsPatients with AN had poorer performance than BN patients and HCs had in the affective ToM task, particularly in recognizing negative emotions and emotions in male eyes. Moreover, this deficit showed no correlation with the psychopathological profile. Performance in the BN group was equivalent to that of HCs in both tasks. ConclusionsIn this study, patients with AN showed an impairment in affective ToM, independent of their clinical status. Consistent with other studies, our findings demonstrate a specific difficulty in social cognition in patients with AN. This may be a trait marker in this population and should be considered in treatment. Furthermore, patients with AN and BN have different difficulty profiles in this domain of social cognition. Copyright (c) 2013 John Wiley & Sons, Ltd and Eating Disorders Association. C1 [Tapajoz Pereira de Sampaio, Fernanda; Allegri, Ricardo F.] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina. [Tapajoz Pereira de Sampaio, Fernanda; Allegri, Ricardo F.] Inst Invest Neurol Raul Carrea FLENI, Dept Cognit Neurol Neuropsychol & Neuropsychiat, Buenos Aires, DF, Argentina. [Soneira, Sebastian] Inst Dr Cormillot, Nutr & Hlth Clin, Buenos Aires, DF, Argentina. [Tapajoz Pereira de Sampaio, Fernanda; Aulicino, Alfredo] Hosp Gen Cosme Argerich, Sect Eating Disorders, Buenos Aires, DF, Argentina. 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Eat. Disord. Rev. PD NOV PY 2013 VL 21 IS 6 SI SI BP 479 EP 487 DI 10.1002/erv.2247 PG 9 WC Psychology, Clinical SC Psychology GA 239LS UT WOS:000326026600007 ER PT J AU Zhang, T Zhang, Q Li, YY Long, CQ Li, H AF Zhang, Ting Zhang, Qin Li, Yiyuan Long, Changquan Li, Hong TI Belief and sign, true and false: the unique of false belief reasoning SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE False belief reasoning; True belief reasoning; False sign reasoning; N2; Late slow wave ID MIND; BRAIN; CHILDREN; ERP; CATEGORIZATION; COMPONENT; AUTISM; TASK AB For a long time, a controversy has been proposed that whether the process of theory of mind is a result of domain-specific or domain-general changes (Wellman in The handbook of childhood cognitive development. Blackwell Publication, New Jersey, 2011). This event-related potential study explored the neural time course of domain-general and domain-specific components in belief reasoning. Fourteen participants completed location transfer false belief (FB), true belief (TB), false sign (FS) and true sign (TS) tasks, in which two pictures told a story related to a dog that ran from a green into a red box. In the TB and FB tasks, a boy saw or did not see the transfer of the dog, respectively. In the FS and TS tasks, an arrow that pointed to the green box either altered its direction to the red box or did not alter following the transfer of the dog. Participants then inferred where the boy thought of, or the arrow indicated the location of the dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning, which is associated with domain-general components, the detection, and classification. The late slow wave (LSW) for FB was more positive at frontal, central, and parietal sites than FS because of the domain-specific component involved in FB reasoning. However, the LSW was less positive for TB than for FB but did not differ from the TS condition, which implies that mental representation might not be involved in TB reasoning. C1 [Zhang, Ting; Li, Yiyuan; Long, Changquan; Li, Hong] Southwest Univ, Fac Psychol, Chongqing 400715, Peoples R China. [Zhang, Qin] Univ Elect Sci & Technol China, Sch Polit Sci & Publ Adm, Chengdu 610054, Peoples R China. [Li, Yiyuan] Mianyang Normal Univ, Sch Educ Sci, Mianyang, Peoples R China. [Li, Hong] Niaoning Normal Univ, Sch Psychol, Niaoning, Peoples R China. RP Zhang, T (reprint author), Southwest Univ, Fac Psychol, Chongqing 400715, Peoples R China. EM scarletl312@gmail.com; lihongwrm@vip.sina.com FU Fundamental Research Funds for University [SWU 1009098]; [NSFC31200780] FX This study was supported by the Fundamental Research Funds for University (SWU 1009098) and NSFC31200780. We would like to appreciate Dr. Qu Li from Nanyang Technological University for her valuable suggestion. 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PD NOV PY 2013 VL 231 IS 1 BP 27 EP 36 DI 10.1007/s00221-013-3661-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 238SQ UT WOS:000325969600004 PM 23975150 ER PT J AU Hirata, S Okuzumi, H Kitajima, Y Hosobuchi, T Kokubun, M AF Hirata, Shogo Okuzumi, Hideyuki Kitajima, Yoshio Hosobuchi, Tomio Kokubun, Mitsuru TI Speed and accuracy of motor and cognitive control in children with intellectual disabilities SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES LA English DT Article DE motor control; cognitive control; intellectual disability; speed and accuracy ID 6-YEAR-OLD CHILDREN; MENTAL-RETARDATION; RETARDED-CHILDREN; DOWN-SYNDROME; PERFORMANCE; DISORDER; ATTENTION; HYPERACTIVITY; PROFICIENCY; PERCEPTION AB Objectives: The purpose of this study was to investigate the relationship between motor and cognitive control in children with intellectual disabilities (ID), focusing on the two aspects of speed and accuracy. Methods: The subjects were 39 children with ID aged 8-15 years. Their Intelligence Quotient (IQ) ranged from 13 to 71. The children with ID included 12 children with Down's syndrome and 10 children with autism. We conducted three tasks: seal affixation task, tray-carrying task, and the Matching Familiar Figures Test (MFFT). The seal affixation and tray-carrying tasks are motor tasks we devised that can separately measure the speed and accuracy of motor control. MFFT is a cognitive control task that can be used to evaluate cognitive styles, such as impulsive-reflective. Results: In the children with ID in this study, motor speed and accuracy were related to cognitive speed and accuracy. Moreover, these children could be classified into four groups based on their MFFT performance, with the motor performances of each group corresponding to the characteristics of that group seen on MFFT. Discussion: These results suggest the possibility that a motor-cognitive control link exists in children with ID. C1 [Hirata, Shogo; Kitajima, Yoshio] Chiba Univ, Fac Educ, Chiba 2638522, Japan. [Hirata, Shogo] Japan Soc Promot Sci, Tokyo, Japan. [Okuzumi, Hideyuki; Kokubun, Mitsuru] Tokyo Gakugei Univ, Fac Educ, Tokyo, Japan. [Hosobuchi, Tomio] Saitama Univ, Fac Educ, Saitama, Japan. RP Hirata, S (reprint author), Chiba Univ, Dept Educ, Inage Ku, Yayoi Machi, Chiba 2638522, Japan. 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PD NOV PY 2013 VL 59 IS 3 BP 192 EP 192 PG 1 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 239JD UT WOS:000326017900006 ER PT J AU Godbee, K Porter, M AF Godbee, Kali Porter, Melanie TI Comprehension of sarcasm, metaphor and simile in Williams syndrome SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE Williams syndrome; sarcasm; metaphor; simile; cognition ID FRENCH-SPEAKING CHILDREN; VERBAL IRONY; LANGUAGE; AUTISM; ADOLESCENTS; DISORDERS; IDIOMS; MIND; HYPERSOCIABILITY; PRAGMATICS AB BackgroundAlthough people with Williams syndrome (WS) are often characterized as friendly and sociable with relatively good general language abilities, there is emerging evidence of pragmatic difficulties and trouble comprehending aspects of non-literal language. AimsThe main aim was to investigate the comprehension of sarcasm, metaphor and simile in WS relative to typically developing controls. A secondary aim was to examine the association between non-literal language comprehension and a range of other cognitive abilities, both in WS and in the typically developing population. Methods & ProceduresTwenty-six participants with WS were compared with 26 typically developing chronological age-matched controls (TDCA) and 26 typically developing mental age-matched controls (TDMA). Participants listened to stories in which characters made non-literal comments. They were then asked what each character meant by their comment. In order to investigate the second aim of the study, cognitive abilities were also assessed using the Woodcock-Johnson (Revised) Tests of Cognitive Ability, including expressive vocabulary, verbal working memory, perceptual integration, inferential reasoning and overall cognitive ability. Outcomes & ResultsComprehension of non-literal language in WS was significantly below TDCA levels, but was not significantly different to TDMA levels. For typically developing controls, each of the cognitive measures was strongly correlated with each of the measures of non-literal language comprehension. The same relationships were not always found for participants with WS. In particular, sarcasm comprehension in WS was not significantly correlated with any of the assessed cognitive abilities, and expressive vocabulary was not significantly correlated with any measure of non-literal comprehension. Conclusions & ImplicationsComprehension of simile in WS is below TDCA levels but seems on par with their mental age level. It appears that comprehension of sarcasm and metaphors is above the cognitive capabilities and mental age level of most individuals with WS. 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J. Lang. Commun. Disord. PD NOV PY 2013 VL 48 IS 6 BP 651 EP 665 DI 10.1111/1460-6984.12037 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 239WU UT WOS:000326057500005 PM 24165362 ER PT J AU Tadic, V Pring, L Dale, N AF Tadic, Valerija Pring, Linda Dale, Naomi TI Story discourse and use of mental state language between mothers and school-aged children with and without visual impairment SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE visual impairment; mental state language; mother-child discourse ID MATERNAL MIND-MINDEDNESS; YOUNG-CHILDREN; BLIND-CHILDREN; FALSE BELIEF; COMMUNICATION; DIRECTIVES; INFANTS; AUTISM; INPUT; TALK AB BackgroundLack of sight compromises insight into other people's mental states. Little is known about the role of maternal language in assisting the development of mental state language in children with visual impairment (VI). AimsTo investigate mental state language strategies of mothers of school-aged children with VI and to compare these with mothers of comparable children with typically developing vision. To investigate whether the characteristics of mother-child discourse were associated with the child's socio-communicative competence. Methods & ProceduresMother-child discourse with twelve 6-12-year-old children with VI was coded during a shared book-reading narrative and compared with 14 typically sighted children matched in age and verbal ability. Outcomes & ResultsMothers of children with VI elaborated more and made significantly more references to story characters' mental states and descriptive elaborations than mothers of sighted children. Mental state elaborations of mothers in the VI group related positively with the level produced by their children, with the association remaining after mothers' overall verbosity and children's developmental levels were controlled for. Frequency of maternal elaborations, including their mental state language, was related to socio-communicative competence of children with VI. Conclusions & ImplicationsThe findings offer insights into the potential contribution of maternal verbal scaffolding to mentalistic language and social-communicative competences of children with VI. C1 [Tadic, Valerija] UCL Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, Ctr Paediat Epidemiol & Biostat, London WC1N 1EH, England. [Pring, Linda] Univ London, Dept Psychol, London, England. [Dale, Naomi] Great Ormond St Hosp Children NHS Fdn Trust, Wolfson Neurodisabil Serv, London, England. 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J. Lang. Commun. Disord. PD NOV PY 2013 VL 48 IS 6 BP 679 EP 688 DI 10.1111/1460-6984.12040 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 239WU UT WOS:000326057500007 PM 24165364 ER PT J AU Andres-Roqueta, C Adrian, JE Clemente, RA Katsos, N AF Andres-Roqueta, Clara Adrian, Juan E. Clemente, Rosa A. Katsos, Napoleon TI Which are the best predictors of theory of mind delay in children with specific language impairment? SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE theory of mind (ToM); specific language impairment (SLI); pragmatic language impairment (PLI); information processing; language disorder ID FALSE-BELIEF; SOCIAL COGNITION; PSYCHOLINGUISTIC MARKERS; EXECUTIVE FUNCTION; AUTISM; SLI; DISORDER; DIFFICULTIES; METAANALYSIS AB BackgroundThe relationship between language and theory of mind (ToM) development in participants with specific language impairment (SLI) it is far from clear due to there were differences in study design and methodologies of previous studies. AimsThis research consisted of an in-depth investigation of ToM delay in children with SLI during the typical period of acquisition, and it studied whether linguistic or information-processing variables were the best predictors of this process. It also took into account whether there were differences in ToM competence due to the degree of pragmatic impairment within the SLI group. Methods & ProceduresThirty-one children with SLI (3;5-7;5 years old) and two control groups (age matched and language matched) were assessed with False Belief (FB) tasks, a wide battery of language measures and additional information-processing measures. Outcomes & ResultsThe members of the SLI group were less competent than their age-matched peers at solving FB tasks, but they performed similarly to the language-matched group. Regression analysis showed that overall linguistic skills of children with SLI were the best predictor of ToM performance, and especially grammar abilities. No differences between SLI subgroups were found according to their pragmatic level. Conclusions & ImplicationsA delay in ToM development in children with SLI around the critical period of acquisition is confirmed more comprehensively, and it is shown to be more strongly related to their general linguistic level than to their age and other information-processing faculties. This finding stresses the importance of early educational and clinical programmes aimed at reducing deleterious effects in later development. C1 [Andres-Roqueta, Clara; Adrian, Juan E.; Clemente, Rosa A.] Univ Jaume I Castello, Dept Educ & Dev Psychol, Castellon de La Plana 12071, Spain. [Katsos, Napoleon] Univ Cambridge, Dept Theoret & Appl Linguist, Cambridge, England. RP Andres-Roqueta, C (reprint author), Univ Jaume I Castello, Dept Educ & Dev Psychol, Av Sos Baynat S-N, Castellon de La Plana 12071, Spain. EM candres@uji.es FU Fundacio Caixa-Castello [P1-1B2010-16]; Spanish Ministerio de Ciencia e Innovacion [EDU2010-21791] FX The authors would like to thank the children who took part in this study; and also express their gratitude for financial support provided by Grant Number P1-1B2010-16 from Fundacio Caixa-Castello, and Grant Number EDU2010-21791 from the Spanish Ministerio de Ciencia e Innovacion. Declaration of interest: The authors report no conflicts of interest. 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M., 2011, CANADIAN SOCIAL SCI, V7, P183 NR 124 TC 8 Z9 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0149-2063 EI 1557-1211 J9 J MANAGE JI J. Manag. PD NOV PY 2013 VL 39 IS 7 BP 1760 EP 1798 DI 10.1177/0149206312471393 PG 39 WC Business; Psychology, Applied; Management SC Business & Economics; Psychology GA 229JG UT WOS:000325258500007 ER PT J AU Hiroi, N Takahashi, T Hishimoto, A Izumi, T Boku, S Hiramoto, T AF Hiroi, N. Takahashi, T. Hishimoto, A. Izumi, T. Boku, S. Hiramoto, T. TI Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders SO MOLECULAR PSYCHIATRY LA English DT Review DE autism; copy number variant; intellectual disability; mouse model; schizophrenia; ADHD ID CARDIO-FACIAL-SYNDROME; AUTISM SPECTRUM DISORDERS; DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD-ONSET SCHIZOPHRENIA; CATECHOL-O-METHYLTRANSFERASE; MICRORNA MACHINERY GENES; DELETION SYNDROME; VELOCARDIOFACIAL SYNDROME; WORKING-MEMORY; MICRODUPLICATION 22Q11.2 AB Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders. C1 [Hiroi, N.; Takahashi, T.; Hishimoto, A.; Izumi, T.; Boku, S.; Hiramoto, T.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA. [Hiroi, N.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. [Hiroi, N.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. RP Hiroi, N (reprint author), Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Dominick P Purpura Dept Neurosci, Dept Genet, Golding 104,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM noboru.hiroi@einstein.yu.edu FU NIH [R21HD05311, R01MH099660]; NARSAD Independent Investigator Award; Maltz Foundation; Ministry of Defense, Japan; Uehara fellowship; Senshin Medical Research Foundation fellowship, Japan; Kobe University Graduate School of Medicine; Society for Promotion of Science, Japan [24591674] FX We thank Drs Herb Lachman, Santhosh Girirajan and Edward Brodkin for their invaluable comments on an early draft of this paper. This work was supported by the NIH (R21HD05311 and R01MH099660), NARSAD Independent Investigator Award and the Maltz Foundation to NH; funds from the Ministry of Defense, Japan, to TT; the Uehara fellowship and a Senshin Medical Research Foundation fellowship, Japan, to SB; funds from Kobe University Graduate School of Medicine to AH; and Grants-in-Aid for Scientific Research (24591674) from the Society for Promotion of Science, Japan, to TI. 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11 PU NATURE 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 NOV PY 2013 VL 18 IS 11 BP 1153 EP 1165 DI 10.1038/mp.2013.92 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 240KN UT WOS:000326094800004 PM 23917946 ER PT J AU Brimberg, L Sadiq, A Gregersen, PK Diamond, B AF Brimberg, L. Sadiq, A. Gregersen, P. K. Diamond, B. TI Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE anti-brain antibodies; ASD; autoimmunity; maternal ID FETAL-BRAIN; ANTIBODIES; DISEASES; AUTOANTIBODIES; AUTOANTIGENS; RESOURCE; GENETICS; PROTEIN; FAMILY; LUPUS AB It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder. C1 [Brimberg, L.; Sadiq, A.; Diamond, B.] Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY USA. [Gregersen, P. K.] Feinstein Inst Med Res, Ctr Genom & Human Genet, Manhasset, NY 11030 USA. RP Diamond, B (reprint author), Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, 350 Community Dr, Manhasset, NY 11030 USA. EM bdiamond@nshs.edu FU Bradley; Simons Foundation, Autism Speaks FX We thank Dr Marta Benedetti at the Simons Foundation and William Jensen at Prometheus Research for assistance with obtaining and analyzing clinical data on the Simons collection. We also thank Matt State for access to genetic data on mothers in the Simons Collection; Bradley and Jennifer Marsh for seed funding for this project. This work was supported by Simons Foundation, Autism Speaks. 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Psychiatr. PD NOV PY 2013 VL 18 IS 11 BP 1171 EP 1177 DI 10.1038/mp.2013.101 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 240KN UT WOS:000326094800006 PM 23958959 ER PT J AU Szatkiewicz, JP Neale, BM O'Dushlaine, C Fromer, M Goldstein, JI Moran, JL Chambert, K Kahler, A Magnusson, PKE Hultman, CM Sklar, P Purcell, S McCarroll, SA Sullivan, PF AF Szatkiewicz, J. P. Neale, B. M. O'Dushlaine, C. Fromer, M. Goldstein, J. I. Moran, J. L. Chambert, K. Kahler, A. Magnusson, P. K. E. Hultman, C. M. Sklar, P. Purcell, S. McCarroll, S. A. Sullivan, P. F. TI Detecting large copy number variants using exome genotyping arrays in a large Swedish schizophrenia sample SO MOLECULAR PSYCHIATRY LA English DT Article DE copy number variation; exome array; genotyping; Illumina; schizophrenia; structural variation ID CHROMOSOME 16P11.2; ASSOCIATION; GENOME; DUPLICATIONS; DELETIONS; DISEASE; AUTISM AB Although copy number variants (CNVs) are important in genomic medicine, CNVs have not been systematically assessed for many complex traits. Several large rare CNVs increase risk for schizophrenia (SCZ) and autism and often demonstrate pleiotropic effects; however, their frequencies in the general population and other complex traits are unknown. Genotyping large numbers of samples is essential for progress. Large cohorts from many different diseases are being genotyped using exome-focused arrays designed to detect uncommon or rare protein-altering sequence variation. Although these arrays were not designed for CNV detection, the hybridization intensity data generated in each experiment could, in principle, be used for gene-focused CNV analysis. Our goal was to evaluate the extent to which CNVs can be detected using data from one particular exome array (the Illumina Human Exome Bead Chip). We genotyped 9100 Swedish subjects (3962 cases with SCZ and 5138 controls) using both standard genome-wide association study (GWAS) and exome arrays. In comparison with CNVs detected using GWAS arrays, we observed high sensitivity and specificity for detecting genic CNVs >= 400 kb including known pathogenic CNVs along with replicating the literature finding that cases with SCZ had greater enrichment for genic CNVs. Our data confirm the association of SCZ with 16p11.2 duplications and 22q11.2 deletions, and suggest a novel association with deletions at 11q12.2. Our results suggest the utility of exome-focused arrays in surveying large genic CNVs in very large samples; and thereby open the door for new opportunities such as conducting well-powered CNV assessment and comparisons between different diseases. The use of a single platform also minimizes potential confounding factors that could impact accurate detection. C1 [Szatkiewicz, J. P.; Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Neale, B. M.; Goldstein, J. I.; Purcell, S.] Harvard Univ, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. [Neale, B. M.; O'Dushlaine, C.; Fromer, M.; Moran, J. L.; Chambert, K.; McCarroll, S. A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Fromer, M.; Sklar, P.; Purcell, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Kahler, A.; Magnusson, P. K. E.; Hultman, C. M.; Sullivan, P. F.] Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. [McCarroll, S. A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264,5097 Genom Med Bldg, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu RI Kahler, Anna/J-2874-2012 FU Stanley Center for Psychiatric Research; Karolinska Institutet; Karolinska University Hospital,; Swedish Research Council; Swedish County Council; Soderstrom Konigska Foundation; Sylvan Herman Foundation; [K01 MH093517]; [R01 MH077139] FX Funding was from K01 MH093517 (JPS), R01 MH077139 (PFS), the Stanley Center for Psychiatric Research, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, an ALF grant from Swedish County Council, the Soderstrom Konigska Foundation and the Sylvan Herman Foundation. This study makes use of data generated by the DECIPHER Consortium. A full list of centers who contributed to the generation of the data is available from http://decipher.sanger.ac.uk or from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust. We thank two anonymous reviewers for their helpful comments. All authors reviewed and approved the final version of the manuscript. The corresponding authors had access to the full data set. 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Psychiatr. PD NOV PY 2013 VL 18 IS 11 BP 1178 EP 1184 DI 10.1038/mp.2013.98 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 240KN UT WOS:000326094800007 PM 23938935 ER PT J AU Bernard, PB Castano, AM O'Leary, H Simpson, K Browning, MD Benke, TA AF Bernard, Paul B. Castano, Anna M. O'Leary, Heather Simpson, Kameron Browning, Michael D. Benke, Tim A. TI Phosphorylation of FMRP and alterations of FMRP complex underlie enhanced mLTD in adult rats triggered by early life seizures SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Seizure; Long-term depression (LTD); Metabotropic glutamate receptor (mGluR); Fragile X Mental Retardation Protein (FMRP); Protein phosphatase 2A (PP2A); Striatal-enriched tyrosine protein phosphatase (STEP) ID LONG-TERM DEPRESSION; FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; TYROSINE PHOSPHATASE STEP; KINASE ANCHORING PROTEIN; MESSENGER-RNA GRANULES; BRAIN DAMAGE SYNDROME; MOUSE MODEL; NEONATAL SEIZURES; NMDA RECEPTOR AB Outside of Fragile X syndrome (FXS), the role of Fragile-X Mental Retardation Protein (FMRP) in mediating neuropsychological abnormalities is not clear. FMRP, p70-S6 kinase (S6K) and protein phosphatase 2A (PP2A) are thought to cooperate as a dynamic signaling complex. In our prior work, adult rats have enhanced CA1 hippocampal long-term depression (LTD) following an early life seizure (ELS). We now show that mGluR-mediated LTD (mLTD) is specifically enhanced following ELS, similar to FMRP knock-outs. Total FMRP expression is unchanged but S6K is hyperphosphorylated, consistent with S6K overactivation. We postulated that either disruption of the FMRP-S6K-PP2A complex and/or removal of this complex from synapses could explain our findings. Using subcellular fractionation, we were surprised to find that concentrations of FMRP and PP2A were undisturbed in the synaptosomal compartment but reduced in parallel in the cytosolic compartment. Following ELS FMRP phosphorylation was reduced in the cytosolic compartment and increased in the synaptic compartment, in parallel with the compartmentalization of S6K activation. Furthermore, FMRP and PP2A remain bound following ELS. In contrast, the interaction of S6K with FMRP is reduced by ELS. Blockade of PP2A results in enhanced mLTD; this is occluded by ELS. This suggests a critical role for the location and function of the FMRP-S6K-PP2A signaling complex in limiting the amount of mLTD. Specifically, non-synaptic targeting and the function of the complex may influence the "set-point" for regulating mLTD. Consistent with this, striatal-enriched protein tyrosine phosphatase (STEP), an FMRP "target" which regulates mLTD expression, is specifically increased in the synaptosomar compai Unent following ELS. Further, we provide behavioral data to suggest that FMRP complex dysfunction may underlie altered socialization, a symptom associated and observed in other rodent models of autism, including FXS. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bernard, Paul B.; Castano, Anna M.; O'Leary, Heather; Benke, Tim A.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80202 USA. [Benke, Tim A.] Univ Colorado, Sch Med, Grad Program Neurosci, Denver, CO 80202 USA. [Simpson, Kameron; Browning, Michael D.] PhosphoSolutions, Aurora, CO USA. [Benke, Tim A.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. [Benke, Tim A.] Univ Colorado, Sch Med, Dept Pharmacol, Denver, CO 80262 USA. [Benke, Tim A.] Univ Colorado, Sch Med, Dept Otolaryngol, Denver, CO 80202 USA. RP Benke, TA (reprint author), Univ Colorado, Sch Med, 12800 E 19th,MS8102, Denver, CO 80045 USA. EM tim.benke@ucdenver.edu FU Children's Hospital Colorado Research Institute; Epilepsy Foundation; NIH-NINDS [R01 NS076577] FX Special thanks to, Ulli Bayer, Mark Dell'Acqua, Steve Coultrap and other members of the Benke, Bayer and Dell'Acqua labs, Ms. Vivian Carlson and Ms. Christy Beitzel for behavioral analysis, Dr. Yogi Raol and the UC Rodent In Vivo Neurophysiology Core, the IDDRC behavior core, the UC Pharmacology Microscopy Core and Dr Tom Finger and the UC CDB Microscopy core. Thanks to Dr. Stephen Warren, Emory University, for supplying the FMRP-wild-type and S499A-FMR1 plasmids. Funding provided by the Children's Hospital Colorado Research Institute, Epilepsy Foundation, and NIH-NINDS (R01 NS076577). The content is solely the responsibility of the authors and does not necessarily represent the official views of NINDS or NIH. 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Dis. PD NOV PY 2013 VL 59 BP 1 EP 17 DI 10.1016/j.nbd.2013.06.013 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 221MV UT WOS:000324663900001 PM 23831253 ER PT J AU Nilsen, RM Suren, P Gunnes, N Alsaker, ER Bresnahan, M Hirtz, D Hornig, M Lie, KK Lipkin, WI Reichborn-Kjennerud, T Roth, C Schjolberg, S Smith, GD Susser, E Vollset, SE Oyen, AS Magnus, P Stoltenberg, C AF Nilsen, Roy M. Suren, Pal Gunnes, Nina Alsaker, Elin R. Bresnahan, Michaeline Hirtz, Deborah Hornig, Mady Lie, Kari Kveim Lipkin, W. Ian Reichborn-Kjennerud, Ted Roth, Christine Schjolberg, Synnve Smith, George Davey Susser, Ezra Vollset, Stein Emil Oyen, Anne-Siri Magnus, Per Stoltenberg, Camilla TI Analysis of Self-selection Bias in a Population-based Cohort Study of Autism Spectrum Disorders SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE Autism; cohort; Norway; pregnancy; selection bias ID FOLIC-ACID SUPPLEMENTS; PERINATAL RISK-FACTORS; INFANTILE-AUTISM; CHILDREN; PARTICIPATION; ASSOCIATION; PREVALENCE; REGISTRY; CHARGE; DELAY AB BackgroundThis study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs). MethodsThe cohort sample (n=89836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n=507856). The children were born in 1999-2007, and seven prenatal and perinatal exposures were selected for analyses. ResultsASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04. ConclusionsAssociations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study. C1 [Nilsen, Roy M.; Vollset, Stein Emil; Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, N-0316 Oslo, Norway. [Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway. [Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. [Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England. RP Nilsen, RM (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Kalfarveien 31, N-5018 Bergen, Norway. EM roy.nilsen@uib.no FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of Education and Research; Research Council of Norway/FUGE [151918]; National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [NS47537]; National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA [NO-ES-75558]; NINDS [NS47537]; Faculty of Medicine and Dentistry, University of Bergen, Norway FX The authors are indebted to Ane Johannessen for her valuable comments on previous versions of this manuscript. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway/FUGE (grant 151918), the National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [grant NS47537 (Lipkin)], and the National Institute of Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC, USA (contract NO-ES-75558). The Autism Birth Cohort study is funded by the NINDS [grant NS47537 (Lipkin)]. The current work was supported by the Faculty of Medicine and Dentistry, University of Bergen, Norway. 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PD NOV PY 2013 VL 27 IS 6 BP 553 EP 563 DI 10.1111/ppe.12077 PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 238WZ UT WOS:000325983800006 PM 23919580 ER PT J AU Dolique, T Favereaux, A Roca-Lapirot, O Roques, V Leger, C Landry, M Nagy, F AF Dolique, Tiphaine Favereaux, Alexandre Roca-Lapirot, Olivier Roques, Virginie Leger, Claire Landry, Marc Nagy, Frederic TI Unexpected association of the "inhibitory" neuroligin 2 with excitatory PSD95 in neuropathic pain SO PAIN LA English DT Article DE Dorsal horn; Neuroligin; Neuropathic pain; Painful sensitization; Spinal cord ID CELL-ADHESION MOLECULE; SYNAPSE FORMATION; GLUTAMATERGIC SYNAPSES; VARIABLE PHENOTYPE; SPINAL MOTONEURONS; ALPHA-NEUREXINS; BETA-NEUREXINS; EXPRESSION; PSD-95; AUTISM AB In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. In control animals, intrathecal injections of small interfering RNA (siRNA) targeting NL2 increased mechanical sensitivity, which confirmed the association of NL2 with inhibition. By contrast, siRNA application produced antinociceptive effects in SNL rats. Regarding NL partners, expression of the excitatory postsynaptic scaffolding protein PSD95 unexpectedly covaried with NL2 overexpression, and NL2/PSD95 protein interaction and colocalization increased. Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(-) isoform. Our data showed unexpected upregulation and pronociceptive effects of the "inhibitory" NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Dolique, Tiphaine; Favereaux, Alexandre; Roca-Lapirot, Olivier; Landry, Marc; Nagy, Frederic] CNRS, UMR5297, IINS, F-33077 Bordeaux, France. [Dolique, Tiphaine; Favereaux, Alexandre; Roca-Lapirot, Olivier; Roques, Virginie; Leger, Claire; Landry, Marc; Nagy, Frederic] Univ Bordeaux, F-33077 Bordeaux, France. [Roques, Virginie; Leger, Claire] INSERM, U862, Neuroctr Magendie, F-33077 Bordeaux, France. [Dolique, Tiphaine] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. RP Landry, M (reprint author), Univ Bordeaux 2, CNRS UMR5297, IINS, 146 Rue Leo Saignat, F-33077 Bordeaux, France. EM marc.landry@u-bordeaux2.fr FU ARC-INCa [07/3D1616/IABC-23-7/NC-NG]; Agence Nationale pour la Recherche [ANR-07-NEURO-015-01]; Conseil Regional d'Aquitaine [2008/30/023]; French Ministry for Research; Fondation pour la Recherche Medicale FX We are very grateful to Dr F. Varoqueaux (Max-Planck-Institute, Goettingen, Germany) for providing us with the anti-NL2 antibody and for helpful scientific discussion. We thank the Bordeaux Imaging Center and especially C. Poujol for help in image analysis. This work was supported by ARC-INCa (07/3D1616/IABC-23-7/NC-NG), Agence Nationale pour la Recherche (ANR-07-NEURO-015-01), Conseil Regional d'Aquitaine (2008/30/023), and studentships from the French Ministry for Research and Fondation pour la Recherche Medicale to TD. 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Harvested cells were stained using giemsa and a total of 1000 BN cells were scored for all the subjects. All the patients were analyzed cytogenetically and categorized clinically using the DSM-IV manual. Patients with PDD, ADHD, MR, AS and both PDD/ADHD, showed significant proportion of DNA damage which was statistically significant when compared with age and sex matched controls. This study shows a significant level of DNA damage in ASD patients when compared to controls. To an extent, environmental, occupational exposures, lifestyle factors, dietary deficiencies and different diseases have also added up to the rise. Important knowledge gap still remains about the characteristics of micronuclei and other nuclear abnormalities, including the basic biology explaining the appearance of various cell types in autism patients which may be addressed by further studies. C1 [Sundaramoorthy, Rajiv; Rao, Kavya M.; Abilash, Valsala Gopalakrishnan] VIT Univ, Div Biomol & Genet, Sch Biosci & Technol, Vellore 632014, Tamil Nadu, India. RP Abilash, VG (reprint author), VIT Univ, Div Biomol & Genet, Sch Biosci & Technol, Vellore 632014, Tamil Nadu, India. EM abilash.vg@vit.ac.in FU VIT University FX The authors are indebted to patients and family members for providing us with blood samples. The authors would also like to thank the management of VIT University for providing the facilities to carry out this work. The author S.Rajiv is grateful to VIT University for providing the financial assistance during this tenure. 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Following functional analyses that suggested that challenging behavior served multiple functions for both participants, we implemented FCT in which mands for a discriminative stimulus (S-D; wristband) were reinforced with access to the S-D and all three functional reinforcers. Next, we modified the procedure by incorporating delays to increase ease of implementation and promote toleration of delays to reinforcement. Last, we made additional modifications to the procedure by incorporating a chained schedule of reinforcement such that (a) mands for the wristband were reinforced with access to the wristband and (b) specific mands for respective functional reinforcers were reinforced in the presence of the wristband. The results showed that the procedure successfully treated challenging behavior with multiple functions. Future directions in the evaluation and development of treatments that simultaneously address multiple functions are discussed. 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PD NOV PY 2013 VL 14 IS 4 BP 323 EP 331 DI 10.1007/s10339-013-0566-0 PG 9 WC Psychology, Experimental SC Psychology GA 235FM UT WOS:000325702200001 PM 23689878 ER PT J AU LeBarton, ES Iverson, JM AF LeBarton, Eve Sauer Iverson, Jana M. TI Fine motor skill predicts expressive language in infant siblings of children with autism SO DEVELOPMENTAL SCIENCE LA English DT Article ID COMMUNICATIVE DEVELOPMENT INVENTORY; SPECTRUM DISORDERS; IMPAIRMENT; DYSPRAXIA; TODDLERS; DEFICITS; RISK AB We investigated whether fine motor and expressive language skills are related in the later-born siblings of children with autism (heightened-risk, HR infants) who are at increased risk for language delays. We observed 34 HR infants longitudinally from 12 to 36months. We used parent report and standardized observation measures to assess fine motor skill from 12 to 24months in HR infants (Study 1) and its relation to later expressive vocabulary at 36months in HR infants (Study 2). In Study 1, we also included 25 infants without a family history of autism to serve as a normative comparison group for a parent-report fine motor measure. We found that HR infants exhibited fine motor delays between 12 and 24months and expressive vocabulary delays at 36months. Further, fine motor skill significantly predicted expressive language at 36months. Fine motor and expressive language skills are related early in development in HR infants, who, as a group, exhibit risk for delays in both. Our findings highlight the importance of considering fine motor skill in children at risk for language impairments and may have implications for early identification of expressive language difficulties. C1 [LeBarton, Eve Sauer; Iverson, Jana M.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP LeBarton, ES (reprint author), Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. 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PD NOV PY 2013 VL 16 IS 6 BP 815 EP 827 DI 10.1111/desc.12069 PG 13 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 233EP UT WOS:000325549300003 PM 24118709 ER PT J AU Hermann, I Haser, V van Elst, LT Ebert, D Muller-Feldmeth, D Riedel, A Konieczny, L AF Hermann, Ismene Haser, Verena van Elst, Ludger Tebartz Ebert, Dieter Mueller-Feldmeth, Daniel Riedel, Andreas Konieczny, Lars TI Automatic metaphor processing in adults with Asperger syndrome: a metaphor interference effect task SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Asperger syndrome; Nonliteral language; Novel metaphors; Metaphor comprehension; Metaphor interference effect; Autism spectrum disorders (ASD); Pragmatic language ID HIGH-FUNCTIONING AUTISM; DIAGNOSTIC INTERVIEW; SPECTRUM DISORDER; LITERAL LANGUAGE; RATING-SCALE; CHILDREN; COMPREHENSION; INDIVIDUALS; COMMUNICATION; INFORMATION AB This paper investigates automatic processing of novel metaphors in adults with Asperger Syndrome (AS) and typically developing controls. We present an experiment combining a semantic judgment task and a recognition task. Four types of sentences were compared: Literally true high-typical sentences, literally true low-typical sentences, apt metaphors, and scrambled metaphors (literally false sentences which are not readily interpretable as metaphors). Participants were asked to make rapid decisions about the literal truth of such sentences. The results revealed that AS and control participants showed significantly slower RTs for metaphors than for scrambled metaphors and made more mistakes in apt metaphoric sentences than in scrambled metaphors. At the same time, there was higher recognition of apt metaphors compared with scrambled metaphors. The findings indicate intact automatic metaphor processing in AS and replicate previous findings on automatic metaphor processing in typically developing individuals. C1 [Hermann, Ismene; van Elst, Ludger Tebartz; Ebert, Dieter; Riedel, Andreas] Univ Med Ctr Freiburg, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany. [Haser, Verena] Univ Freiburg, Dept English Linguist, D-79106 Freiburg, Germany. [Mueller-Feldmeth, Daniel; Konieczny, Lars] Univ Freiburg, Ctr Cognit Sci, D-79106 Freiburg, Germany. RP Riedel, A (reprint author), Univ Med Ctr Freiburg, Dept Psychiat & Psychotherapy, Hauptstr 5, D-79104 Freiburg, Germany. EM andreas.riedel@uniklinik-freiburg.de FU German Association for Psychiatry and Psychotherapy (DGPPN) FX This article is part of the supplement "Bridging the gap between Neurobiology and Psychosocial Medicine". This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN). 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Arch. Psych. Clin. Neurosci. PD NOV PY 2013 VL 263 SU 2 BP S177 EP S187 DI 10.1007/s00406-013-0453-9 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 238KC UT WOS:000325944100007 PM 24081827 ER PT J AU Montag, C Sauer, C Reuter, M Kirsch, P AF Montag, Christian Sauer, Carina Reuter, Martin Kirsch, Peter TI An interaction between oxytocin and a genetic variation of the oxytocin receptor modulates amygdala activity toward direct gaze: evidence from a pharmacological imaging genetics study SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Oxytocin; Gaze; Amygdala; Oxytocin receptor gene; Imaging genetics ID INTRANASAL OXYTOCIN; SOCIAL COGNITION; NEURAL CIRCUITRY; AUTISM; HUMANS; VASOPRESSIN; FACES; OXTR; ASSOCIATION; BEHAVIOR AB The neuropeptide oxytocin plays an important role in social cognition. One valuable tool to study social cognition in healthy and autistic humans in a neuroscientific context is the investigation of gaze toward another person. Of importance, it has been demonstrated that pronounced amygdala activation could be observed, when participants are confronted with direct gaze pictures in an fMRI setting, an effect that can be particularly observed in autistic individuals. In the present study, a combined pharmacological imaging genetics study has been conducted to further investigate the biological basis of direct gaze processing. N = 55 healthy males were invited to an oxytocin challenge study administered while watching direct vs. averted gaze pictures in an fMRI setting. In addition, the promoter region of the oxytocin receptor (OXTR) gene of the participants was investigated to search for individual differences in the recorded BOLD signal. The main result revealed that a genetic variation of the OXTR gene (rs401015) modulated the right amygdala activity for the fMRI contrast "direct < averted gaze" under the influence of the neuropeptide oxytocin. Here, carriers of the heterozygous CT variant showed higher activity compared to the TT group. The present study highlights the role of individual differences in a genetic variant of the OXTR gene for amygdala activation during processing of direct gaze pictures after intranasal oxytocin administration. In sum, the study shows the importance of combining a pharmacological challenge with genetic imaging to better understand the biological basis of social cognition. C1 [Montag, Christian; Reuter, Martin] Univ Bonn, Dept Psychol, Bonn, Germany. [Montag, Christian; Reuter, Martin] Univ Bonn, Neurogenet Lab, Bonn, Germany. [Montag, Christian; Reuter, Martin] Univ Bonn, Ctr Econ & Neurosci, Bonn, Germany. [Sauer, Carina; Kirsch, Peter] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Clin Psychol, D-68159 Mannheim, Germany. RP Kirsch, P (reprint author), Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Clin Psychol, J5, D-68159 Mannheim, Germany. EM peter.kirsch@zi-mannheim.de FU Deutsche Forschungsgemeinschaft (German Research Association, DFG) [KI 576/10-1, RE 1692/4-1] FX This research was supported by a research grant from the Deutsche Forschungsgemeinschaft (German Research Association, DFG) to PK (KI 576/10-1) and MR (RE 1692/4-1). We thank Christiane Worner, Andre Spachmann and Dagmar Gass for their assistance during data collection and analysis. 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Arch. Psych. Clin. Neurosci. PD NOV PY 2013 VL 263 SU 2 BP S169 EP S175 DI 10.1007/s00406-013-0452-x PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 238KC UT WOS:000325944100006 PM 24071915 ER PT J AU van Elst, LT Pick, M Biscaldi, M Fangmeier, T Riedel, A AF van Elst, Ludger Tebartz Pick, Marion Biscaldi, Monica Fangmeier, Thomas Riedel, Andreas TI High-functioning autism spectrum disorder as a basic disorder in adult psychiatry and psychotherapy: psychopathological presentation, clinical relevance and therapeutic concepts SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Review DE Autism; High-functioning autism; Asperger's syndrome; Classification; Adults; Therapy; Comorbidity ID ASPERGER SYNDROME; DIAGNOSIS; CHILDHOOD; COMMUNITY; ETIOLOGY; GENETICS AB Autism spectrum disorder (ASD) is characterized by deficits in social cognition and competence, communication, highly circumscribed interests and a strong desire for routines. Besides, there are specific abnormalities in perception and language. Typical symptoms are already present in early childhood. Traditionally autism has been regarded as a severe form of neurodevelopmental disorder which goes along with overtly abnormal language, learning difficulties and low IQ in the majority of cases. However, over the last decades, it has become clear that there are also many patients with high-functioning variants of ASD. These are patients with normal language at a superficial level of description and normal and sometimes above average intelligence. In high-functioning variants of the disease, they may run unrecognized until late in adult life. High-functioning ASD is associated with a very high prevalence of comorbid classical psychiatric disorders such as depression, anxiety, ADHD, tics, psychotic symptoms or emotionally unstable syndromes. In many such cases, there is a causal relationship between ASD and the comorbid psychiatric conditions in that the specific ASD symptoms result in chronic conflicts, misunderstandings and failure in private and vocational relationships. These problems in turn often lead to depression, anxiety and sometimes psychosis-like stress reactions. In this constellation, ASD has to be regarded as a basic disorder with causal relevance for secondary psychiatric syndromes. In this paper, we summarize the classical presentation of high-functioning ASD in adult psychiatry and psychotherapy and suggest a nosological model to classify different ASD conditions instead. To conclude, we outline first treatment concepts in out-and in-patient settings. C1 [van Elst, Ludger Tebartz; Pick, Marion; Fangmeier, Thomas; Riedel, Andreas] Univ Med Ctr Freiburg, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany. [Biscaldi, Monica] Univ Med Ctr Freiburg, Dept Child & Adolescent Psychiat & Psychotherapy, D-79104 Freiburg, Germany. RP van Elst, LT (reprint author), Univ Med Ctr Freiburg, Dept Psychiat & Psychotherapy, Hauptstr 5, D-79104 Freiburg, Germany. EM tebartzvanelst@uniklinik-freiburg.de; andreas.riedel@uniklinik-freiburg.de FU UCB; GSK; Lilly; Janssen CilAG; Lundbeck; German Association for Psychiatry and Psychotherapy (DGPPN) FX LTvE has given lectures and workshops on the issues of autism, schizophrenia, depression, brain imaging, psychotherapy, epilepsy, etc. which were at least in part supported by the following companies: UCB, GSK, Lilly, Janssen CilAG, Lundbeck. He has been advisor to UCB with respect to psychiatric aspects in epilepsy. The other authors declare that they have no conflict of interest.This article is part of the supplement "Bridging the gap between Neurobiology and Psychosocial Medicine." This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN). 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Arch. Psych. Clin. Neurosci. PD NOV PY 2013 VL 263 SU 2 BP S189 EP S196 DI 10.1007/s00406-013-0459-3 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 238KC UT WOS:000325944100008 ER PT J AU Vogeley, K Kirchner, JC Gawronski, A van Elst, LT Dziobek, I AF Vogeley, K. Kirchner, J. C. Gawronski, A. van Elst, L. Tebartz Dziobek, I. TI Toward the development of a supported employment program for individuals with high-functioning autism in Germany SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Review DE High-functioning autism (HFA); Asperger syndrome; Supported employment program ID QUALITY-OF-LIFE; SPECTRUM DISORDERS; ASPERGER-SYNDROME; VIRTUAL-REALITY; YOUNG-ADULTS; DISABILITIES; SERVICES; CHILDREN AB Human-human interactions are of central relevance for the success in professional and occupational environments, which also substantially influence quality of life. This is especially true in the case of individuals with high-functioning autism (HFA), who experience deficits in social cognition that often lead to social exclusion and unemployment. Despite good education and high motivation, individuals with HFA do not reach employment rates that are substantially higher than 50 %. This is an alarmingly high rate of unemployment considering that the United Nations have recently emphasized the inclusion of handicapped persons as a mandatory human right. To date, the specific needs of autistic persons with respect to their working environment are largely unexplored. It remains moreover an open question how support systems and activities, including newly developed communication devices for professional environments of individuals with HFA, should look like. The German health and social care systems are not adequately prepared for the proper support of this population. This leads us to suggest that supported employment programs should be developed for adults with HFA that specifically address their needs and requirements. Such programs should comprise (1) the adequate assessment of HFA, including a neuropsychological profile and an individual matching of persons' preferences with requirements of the working place, (2) on-the-job coaching activities that include systematic communication and interaction training, and (3) instruction of non-autistic peers, including colleagues and supervisors, about weaknesses and strengths of HFA. C1 [Vogeley, K.; Gawronski, A.] Univ Hosp Cologne, Dept Psychiat, D-50924 Cologne, Germany. [Vogeley, K.] Res Ctr Juelich, Inst Neurosci & Med, Julich, Germany. [Kirchner, J. C.; Dziobek, I.] Free Univ Berlin, Cluster Excellence Languages Emot, Berlin, Germany. [van Elst, L. Tebartz] Univ Hosp Freiburg, Clin Psychiat & Psychotherapy, Freiburg, Germany. RP Vogeley, K (reprint author), Univ Hosp Cologne, Dept Psychiat, Kerpener Str 62, D-50924 Cologne, Germany. EM kai.vogeley@uk-koeln.de RI Vogeley, K/E-4860-2012 OI Vogeley, K/0000-0002-5891-5831 FU German Association for Psychiatry and Psychotherapy (DGPPN) FX This article is part of the supplement "Bridging the gap between Neurobiology and Psychosocial Medicine." This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN). 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Arch. Psych. Clin. Neurosci. PD NOV PY 2013 VL 263 SU 2 BP S197 EP S203 DI 10.1007/s00406-013-0455-7 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 238KC UT WOS:000325944100009 PM 24077909 ER PT J AU Mizutani, S Tsunemi, T Mizutani, E Hattori, A Tsujimoto, M Kobayashi, H AF Mizutani, Shigehiko Tsunemi, Taihei Mizutani, Eita Hattori, Akira Tsujimoto, Masafumi Kobayashi, Hiroshi TI New insights into the role of aminopeptidases in the treatment for both preeclampsia and preterm labor SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE aminopeptidase A; angiotensin; autism; beta-2 stimulant; cardiomyopathy; fetal peptide hormone; magnesium sulfate; oxytocin; placental leucine aminopeptidase; preeclampsia; preterm labor; vasopressin ID SPONTANEOUSLY HYPERTENSIVE-RATS; PURIFIED PLACENTAL AMINOPEPTIDASES; REGULATED MEMBRANE AMINOPEPTIDASE; ANGIOTENSIN-II RECEPTOR; IN-VITRO DEGRADATION; P-LAP; SUBCELLULAR-FRACTIONS; ANTAGONIST ATOSIBAN; PREGNANCY SERUM; DEFICIENT MICE AB Introduction: Evidence elucidating the pathophysiology and pharmacology of conventional drugs, beta-2 stimulants and magnesium sulfate, on safety and effectiveness for preeclampsia and preterm labor are rarely found. Both compounds pass through the placental barrier and could exert their adverse effects on the fetus. Exposure to these agents could be problematic long after the birth, and possibly result in diseases such as autism and cardiomyopathy. Since 1970 the possible roles of placental aminopeptidases, which degrade peptide hormones, in preeclampsia and preterm labor have been studied. Areas covered: Many studies reveal that the fetus secretes peptide hormones, such as angiotensin II, vasopressin, and oxytocin, under hypoxia (stress) during the course of its growth, suggesting the critical effects these hormones have during pregnancy. The roles of placental aminopeptidases, the enzymes which degrade fetal hormones without passing through the placental barrier, were clarified. A first-step production system for recombinant aminopeptidases was established, by which engineered recombinant aminopeptidases were used for further experiments testing expected efficacy on controlling the level of hormones. Expert opinion: The authors conclude that both aminopeptidase A and placental leucine aminopeptidase could be potentially safe and effective drugs for patients and their babies in the treatment of preeclampsia and preterm labor. C1 [Mizutani, Shigehiko; Mizutani, Eita] Daiya Bldg Ladys Clin, Nakamura Ku, Nagoya, Aichi 4500002, Japan. [Mizutani, Shigehiko] Protect Neonates & Mother Preterm Birth & Preecla, Nakamura Ku, Nagoya, Aichi 4500002, Japan. [Tsunemi, Taihei; Kobayashi, Hiroshi] Nara Med Univ, Dept Obstet & Gynecol, Kashihara, Nara 6348522, Japan. [Hattori, Akira] Kyoto Univ, Sch Pharmaceut Sci, Div Bioinformat & Chem Genom Grad, Dept Syst Chemotherapy & Mol Sci,Sakyo Ku, Kyoto 6068501, Japan. [Tsujimoto, Masafumi] Teikyo Heisei Univ, Fac Pharmaceut Sci, Nakano Ku, Tokyo 1648530, Japan. RP Kobayashi, H (reprint author), Nara Med Univ, Dept Obstet & Gynecol, 840 Shijo Cho, Kashihara, Nara 6348522, Japan. EM hirokoba@naramed-u.ac.jp FU ministry of Education, Science and Culture of Japan FX The paper was supported by a grant in aid of scientific research from the ministry of Education, Science and Culture of Japan. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2502 EP 2514 DI 10.1007/s10803-013-1797-8 PG 13 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000002 PM 23532347 ER PT J AU Wilson, CE Gillan, N Spain, D Robertson, D Roberts, G Murphy, CM Maltezos, S Zinkstok, J Johnston, K Dardani, C Ohlsen, C Deeley, PQ Craig, M Mendez, MA Happe, F Murphy, DGM AF Wilson, C. Ellie Gillan, Nicola Spain, Deborah Robertson, Dene Roberts, Gedeon Murphy, Clodagh M. Maltezos, Stefanos Zinkstok, Janneke Johnston, Katie Dardani, Christina Ohlsen, Chris Deeley, P. Quinton Craig, Michael Mendez, Maria A. Happe, Francesca Murphy, Declan G. M. TI Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism Spectrum Disorder; Diagnosis; Prevalence; DSM-5 ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE INVENTORY; CRITERIA; VALIDATION; INTERVIEW; VERSION; SAMPLE AB An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56 % met DSM-5 ASD criteria. A further 19 % met DSM-5 (draft) criteria for Social Communication Disorder. Of those diagnosed with Autistic Disorder/Asperger Syndrome on DSM-IV-TR, 78 % met DSM-5 ASD criteria. Sensitivity of DSM-5 was significantly increased by reducing the number of criteria required for a DSM-5 diagnosis, or by rating 'uncertain' criteria as 'present', without sacrificing specificity. Reduced rates of ASD diagnosis may mean some ASD individuals will be unable to access clinical services. C1 [Wilson, C. Ellie; Gillan, Nicola; Spain, Deborah; Roberts, Gedeon; Murphy, Clodagh M.; Maltezos, Stefanos; Zinkstok, Janneke; Dardani, Christina; Deeley, P. Quinton; Craig, Michael; Mendez, Maria A.; Murphy, Declan G. M.] Kings Coll London, Dept Forens & Neurodev Sci, Inst Psychiat, London SE5 8AF, England. [Wilson, C. Ellie; Gillan, Nicola; Spain, Deborah; Robertson, Dene; Roberts, Gedeon; Murphy, Clodagh M.; Maltezos, Stefanos; Zinkstok, Janneke; Johnston, Katie; Ohlsen, Chris; Deeley, P. Quinton; Craig, Michael; Mendez, Maria A.; Murphy, Declan G. M.] South London & Maudsley NHS Fdn Trust, Behav Genet Clin, Maudsley Hosp, London SE5 8AZ, England. [Happe, Francesca] Kings Coll London, Dept Social Genet Dev & Psychiat Ctr, Inst Psychiat, London SE5 8AF, England. RP Wilson, CE (reprint author), Kings Coll London, Dept Forens & Neurodev Sci, Inst Psychiat, London SE5 8AF, England. EM ellie.wilson@kcl.ac.uk CR Abramowitz JS, 2006, J ANXIETY DISORD, V20, P1016, DOI 10.1016/j.janxdis.2006.03.001 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baird G, 2000, J AM ACAD CHILD PSY, V39, P694, DOI 10.1097/00004583-200006000-00007 Barkley R. A., 2005, ATTENTION DEFICIT HY, V2 Barkley R. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2515 EP 2525 DI 10.1007/s10803-013-1799-6 PG 11 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000003 PM 23504376 ER PT J AU Lampi, KM Hinkka-Yli-Salomaki, S Lehti, V Helenius, H Gissler, M Brown, AS Sourander, A AF Lampi, Katja M. Hinkka-Yli-Salomaki, Susanna Lehti, Venla Helenius, Hans Gissler, Mika Brown, Alan S. Sourander, Andre TI Parental Age and Risk of Autism Spectrum Disorders in a Finnish National Birth Cohort SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Epidemiology; Autism spectrum disorders; Parental age ID PERVASIVE DEVELOPMENTAL DISORDER; DE-NOVO MUTATIONS; PERINATAL FACTORS; PATERNAL AGE; ASPERGER-SYNDROME; CONDUCT DISORDER; POPULATION; SCHIZOPHRENIA; EPIGENETICS; PREGNANCY AB Aim of the study was to examine the associations between parental age and autism spectrum disorders (ASD). Data were based on the FIPS-A (Finnish Prenatal Study of Autism and Autism Spectrum Disorders), a case-control study with a total of 4,713 cases with childhood autism (n = 1,132), Asperger's syndrome (n = 1,785) or other pervasive developmental disorder (PDD) (n = 1,796), which were ascertained from the Finnish Hospital Discharge Register. Controls were selected from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Advanced paternal age (35-49 years) was associated with childhood autism in offspring, whereas advanced maternal age was associated with both Asperger's syndrome and PDD in offspring (35 years or more and 40 years or more, respectively). Teenage motherhood (19 years or less) was associated with PDD in offspring. The main finding was that maternal and paternal ages were differentially associated with ASD subtypes. In addition to advanced parental age, teenage pregnancy seems to incur a risk for PDD in offspring. C1 [Lampi, Katja M.; Hinkka-Yli-Salomaki, Susanna; Lehti, Venla; Gissler, Mika; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku, Finland. [Helenius, Hans] Univ Turku, Dept Biostat, Turku, Finland. [Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Gissler, Mika] Nord Sch Publ Hlth, Gothenburg, Sweden. [Brown, Alan S.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Brown, Alan S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Sourander, Andre] Turku Univ Hosp, Dept Child Psychiat, Turku 20014, Finland. RP Sourander, A (reprint author), Turku Univ Hosp, Dept Child Psychiat, Itainen Pitkakatu 1 Varia, Turku 20014, Finland. 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TI The Influences of Face Inversion and Facial Expression on Sensitivity to Eye Contact in High-Functioning Adults with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Gaze; Eye contact; Cone of gaze; Facial expression; Face inversion ID FINE-GRAINED SENSITIVITY; GAZE-DIRECTION; ASPERGER-SYNDROME; BIOLOGICAL MOTION; NEURAL CIRCUITRY; PERCEPTION; CHILDREN; LOOKING; AMYGDALA; ME AB We examined the influences of face inversion and facial expression on sensitivity to eye contact in high-functioning adults with and without an autism spectrum disorder (ASD). Participants judged the direction of gaze of angry, fearful, and neutral faces. In the typical group only, the range of directions of gaze leading to the perception of eye contact (the cone of gaze) was narrower for upright than inverted faces. In both groups, the cone of gaze was wider for angry faces than for fearful or neutral faces. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2536 EP 2548 DI 10.1007/s10803-013-1802-2 PG 13 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000005 PM 23471478 ER PT J AU Cashon, CH Ha, OR DeNicola, CA Mervis, CB AF Cashon, Cara H. Ha, Oh-Ryeong DeNicola, Christopher A. Mervis, Carolyn B. TI Toddlers with Williams Syndrome Process Upright but not Inverted Faces Holistically SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Face perception; Holistic processing; Inversion effect; Perceptual expertise; Williams syndrome; Developmental disability ID RECOGNITION; INVERSION; INFANTS; AUTISM; HYPERSOCIABILITY; INFORMATION; PERCEPTION; CHILDREN AB Holistic processing of upright, but not inverted, faces is a marker of perceptual expertise for faces. This pattern is shown by typically developing individuals beginning at age 7 months. Williams syndrome (WS) is a rare neurogenetic developmental disorder characterized by extreme interest in faces from a very young age. Research on the effects of inversion on holistic processing of faces by older children and adults with WS has produced mixed results. Younger children with WS were not included in these previous studies. Using the habituation switch paradigm, we demonstrated that 15-35-month-olds with WS process upright, but not inverted, faces holistically. This study provides evidence of perceptual expertise for faces in individuals with WS early in life. C1 [Cashon, Cara H.; Ha, Oh-Ryeong; DeNicola, Christopher A.; Mervis, Carolyn B.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. RP Cashon, CH (reprint author), Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2549 EP 2557 DI 10.1007/s10803-013-1804-0 PG 9 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000006 PM 23494560 ER PT J AU Terrett, G Rendell, PG Raponi-Saunders, S Henry, JD Bailey, PE Altgassen, M AF Terrett, Gill Rendell, Peter G. Raponi-Saunders, Sandra Henry, Julie D. Bailey, Phoebe E. Altgassen, Mareike TI Episodic Future Thinking in Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Episodic future thinking; Imagining the future; Episodic memory; Executive functioning; Children ID MENTAL TIME-TRAVEL; AUTOBIOGRAPHICAL MEMORY; EXECUTIVE CONTROL; ADULTS; CONSTRUCTION; SIMULATION; EVOLUTION; EVENTS AB The capacity to imagine oneself experiencing future events has important implications for effective daily living but investigation of this ability in autism spectrum disorder (ASD) is limited. This study investigated future thinking in 30 children with high functioning ASD (IQ > 85) and 30 typically developing children. They completed the Adapted Autobiographical Interview, a measure which required participants to describe personal past events (indexing episodic memory) and plausible future events (indexing episodic future thinking). The results showed that there are ASD-related deficits in future thinking, and also provided preliminary evidence regarding cognitive mechanisms that may (and may not) contribute to these difficulties. The theoretical and practical implications of these results are discussed. C1 [Terrett, Gill; Rendell, Peter G.; Raponi-Saunders, Sandra] Australian Catholic Univ, Sch Psychol, Fitzroy, Vic 3065, Australia. [Henry, Julie D.] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia. [Bailey, Phoebe E.] Univ Western Sydney, Sch Social Sci & Psychol, Sydney, NSW, Australia. 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The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on the lower-functioning end of the spectrum appear to be more severely affected, an altered clinical manifestation of the disorder among high-functioning females may consequently result in many being un or misdiagnosed. To date, there is strong bias in the literature towards the clinical presentation of ASD in males. It is imperative that future research explores gender differences across the autism spectrum, in order to improve researchers', clinicians' and the publics' understanding of this debilitating disorder. C1 [Kirkovski, Melissa; Enticott, Peter G.; Fitzgerald, Paul B.] Monash Univ, Alfred & Cent Clin Sch, Monash Alfred Psychiat Res Ctr, Melbourne, Vic 3004, Australia. 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Survey data regarding respite care, marital quality, and daily hassles and uplifts were obtained from 101 mother-father dyads who were together raising at least one child with ASD (total # of children = 118). Number of hours of respite care was positively related to improved marital quality for both husbands and wives, such that a 1-h increase in weekly respite care was associated with a one-half standard deviation increase in marital quality. This relationship was significantly mediated by perceived daily stresses and uplifts in both husbands and wives. More respite care was associated with increased uplifts and reduced stress; increased uplifts were associated with improved marital quality; and more stress was associated with reduced marital quality. The number of children in the family was associated with greater stress, and reduced relational quality and daily uplifts. Results suggest policymakers and practitioners should develop supports for providing respite for families raising children with ASD. C1 [Harper, Amber] Wasatch Mental Hlth, Giant Steps, Orem, UT 84097 USA. [Dyches, Tina Taylor] Brigham Young Univ, Dept Counseling Psychol & Special Educ, Provo, UT 84602 USA. [Harper, James; Roper, Susanne Olsen] Brigham Young Univ, Sch Family Life, Provo, UT 84602 USA. [South, Mikle] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [South, Mikle] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. RP Dyches, TT (reprint author), Brigham Young Univ, Dept Counseling Psychol & Special Educ, 340 F McKay Bldg, Provo, UT 84602 USA. 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PD NOV PY 2013 VL 43 IS 11 BP 2604 EP 2616 DI 10.1007/s10803-013-1812-0 PG 13 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000010 PM 23529841 ER PT J AU Byers, ES Nichols, S Voyer, SD AF Byers, E. Sandra Nichols, Shana Voyer, Susan D. TI Challenging Stereotypes: Sexual Functioning of Single Adults with High Functioning Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Sexuality; Autism spectrum disorder; Asperger syndrome ID GENDER-DIFFERENCES; ASPERGER-SYNDROME; RESPONSE RATES; HELP-SEEKING; ADOLESCENTS; SATISFACTION; EXPERIENCE; CHILDREN; BEHAVIOR; SAMPLE AB This study examined the sexual functioning of single adults (61 men, 68 women) with high functioning autism and Asperger syndrome living in the community with and without prior relationship experience. Participants completed an on-line questionnaire assessing autism symptoms, psychological functioning, and various aspects of sexual functioning. In general participants reported positive sexual functioning. Participants without prior relationship experience were significantly younger and more likely to be male and identify as heterosexual. They reported significantly higher sexual anxiety, lower sexual arousability, lower dyadic desire, and fewer positive sexual cognitions. The men reported better sexual function than did the women in a number of areas. These results counter negative societal perceptions about the sexuality of high functioning individuals on the autism spectrum. C1 [Byers, E. Sandra; Voyer, Susan D.] Univ New Brunswick, Dept Psychol, Fredericton, NB E3B 5A3, Canada. [Nichols, Shana] Fay J Lindner Ctr Autism, Bethpage, NY USA. RP Byers, ES (reprint author), Univ New Brunswick, Dept Psychol, POB 4400, Fredericton, NB E3B 5A3, Canada. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2617 EP 2627 DI 10.1007/s10803-013-1813-z PG 11 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000011 PM 23526036 ER PT J AU Knight, V McKissick, BR Saunders, A AF Knight, Victoria McKissick, Bethany R. Saunders, Alicia TI A Review of Technology-Based Interventions to Teach Academic Skills to Students with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Review DE Technology; Evidence-based practices; Individuals with autism spectrum disorder ID MODERATE INTELLECTUAL DISABILITIES; COMPUTER-ASSISTED-INSTRUCTION; SPECIAL-EDUCATION; ANIMATED TUTOR; CHILDREN; VOCABULARY; PROGRAM; CONSTRUCTION; ACQUISITION; MULTIMEDIA AB A comprehensive review of the literature was conducted for articles published between 1993 and 2012 to determine the degree to which technology-based interventions can be considered an evidence-based practice to teach academic skills to individuals with Autism Spectrum Disorder (ASD). Criteria developed by Horner et al. (Except Child 71:165-178, 2005) and Gersten et al. (Except Child 71:149-164, 2005) were used to determine the quality of single-subject research studies and group experimental research studies respectively. A total of 25 studies met inclusion criteria. Of these studies, only three single-subject studies and no group studies met criteria for quality or acceptable studies. Taken together, the results suggest that practitioners should use caution when teaching academic skills to individuals with ASD using technology-based interventions. Limitations and directions for future research are discussed. C1 [Knight, Victoria] Vanderbilt Univ, Peabody Coll, Nashville, TN 37203 USA. [McKissick, Bethany R.] Mississippi State Univ, Starkville, MS 39762 USA. [Saunders, Alicia] Univ N Carolina, Charlotte, NC 28223 USA. RP McKissick, BR (reprint author), Mississippi State Univ, 310 Allen Hall,Box 9705, Starkville, MS 39762 USA. 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Gissler, Mika Gronborg, Therese K. Gross, Raz Gunnes, Nina Hornig, Mady Hultman, Christina M. Langridge, Amanda Lauritsen, Marlene B. Leonard, Helen Parner, Erik T. Reichenberg, Abraham Sandin, Sven Sourander, Andre Stoltenberg, Camilla Suominen, Auli Suren, Pal Susser, Ezra TI The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Epidemiology; Study methods; Risk factors; Multinational ID TWIN PAIRS; DISORDERS; DATABASE; EUROPE AB The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in multinational collaboration concerning data access security, confidentiality and management. Data are obtained by integrating existing national or state-wide, population-based, individual-level data systems and undergo rigorous harmonization and quality control processes. Analyses are performed using database federation via a computational infrastructure with a secure, web-based, interface. iCARE provides a unique, unprecedented resource in autism research that will significantly enhance the ability to detect environmental and genetic contributions to the causes and life course of autism. C1 [Schendel, Diana E.] Univ Aarhus, Dept Publ Hlth, DK-8000 Aarhus C, Denmark. [Schendel, Diana E.] Univ Aarhus, Dept Econ & Business, DK-8000 Aarhus C, Denmark. [Bresnahan, Michaeline; Hornig, Mady; Susser, Ezra] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Carter, Kim W.; Francis, Richard W.; Langridge, Amanda; Leonard, Helen] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Perth, WA 6009, Australia. [Gissler, Mika] Natl Inst Hlth & Welf, Helsinki, Finland. [Gissler, Mika] Nord Sch Publ Hlth, Gothenburg, Sweden. [Gissler, Mika] Turku Univ, Turku, Finland. [Gronborg, Therese K.; Parner, Erik T.] Univ Aarhus, Dept Publ Hlth, Aarhus, Denmark. [Gross, Raz] Chaim Sheba Med Ctr, Div Psychiat, IL-52621 Tel Hashomer, Israel. [Gross, Raz] Tel Aviv Univ, Dept Epidemiol & Prevent Med, Sackler Fac Med, Ramat Aviv, Israel. [Gunnes, Nina; Stoltenberg, Camilla; Suren, Pal] Norwegian Inst Publ Hlth, Oslo, Norway. [Hornig, Mady] Columbia Univ, Ctr Infect & Immun, Mailman Sch Publ Hlth, New York, NY USA. [Hultman, Christina M.; Sandin, Sven] Karolinska Inst, Stockholm, Sweden. [Lauritsen, Marlene B.] Aarhus Univ Hosp, Res Unit Child & Adolescent Psychiat, Aalborg Psychiat Hosp, Aalborg, Denmark. [Reichenberg, Abraham] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London, England. [Reichenberg, Abraham] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sourander, Andre] Turku Univ, Dept Child Psychiat, Child Psychiat Res Ctr, Turku, Finland. [Sourander, Andre] Turku Univ Hosp, FIN-20520 Turku, Finland. [Suominen, Auli] Turku Univ, Dept Child Psychiat, Turku, Finland. RP Schendel, DE (reprint author), Univ Aarhus, Dept Publ Hlth, DK-8000 Aarhus C, Denmark. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2650 EP 2663 DI 10.1007/s10803-013-1815-x PG 14 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000013 PM 23563868 ER PT J AU Teatero, ML Netley, C AF Teatero, Missy L. Netley, Charles TI A Critical Review of the Research on the Extreme Male Brain Theory and Digit Ratio (2D:4D) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Review DE Extreme male brain; Autism spectrum; Empathizing; Systemizing; Digit ratio; 2D:4D ID HIGH-FUNCTIONING AUTISM; FINGER LENGTH RATIO; CONGENITAL ADRENAL-HYPERPLASIA; NORMAL SEX-DIFFERENCES; SPECTRUM QUOTIENT AQ; FETAL TESTOSTERONE; ASPERGER-SYNDROME; SYSTEMATIZING QUOTIENT; EMPATHY QUOTIENT; EYES TEST AB Boys are more likely than girls to be diagnosed with an autism spectrum disorder (ASD). The extreme male brain (EMB) theory of ASD suggests that fetal testosterone (FT) exposure may underlie sex differences in autistic traits. A link between the organizational effects of FT on the brain and ASD is often drawn based on research using digit ratio (2D:4D), a putative biomarker, without a full survey of the findings. This paper critically and quantitatively reviews the research on the relationship between 2D:4D and ASD as well as autism spectrum, empathizing, and systemizing measures in neurotypical populations. Overall, there is some support for the EMB theory in all four areas, particularly the 2D:4D-ASD relationship. Recommendations for future research are provided. C1 [Teatero, Missy L.] Lakehead Univ, Dept Psychol, Hlth Hormones & Behav Lab, Thunder Bay, ON P7B 5E1, Canada. [Netley, Charles] Lakehead Univ, Dept Psychol, Thunder Bay, ON P7B 5E1, Canada. RP Teatero, ML (reprint author), Lakehead Univ, Dept Psychol, Hlth Hormones & Behav Lab, 995 Oliver Rd, Thunder Bay, ON P7B 5E1, Canada. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2664 EP 2676 DI 10.1007/s10803-013-1819-6 PG 13 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000014 PM 23575643 ER PT J AU Stein, TP Schluter, MD Steer, RA Ming, X AF Stein, T. Peter Schluter, Margaret D. Steer, Robert A. Ming, Xue TI Autism and Phthalate Metabolite Glucuronidation SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Diethylhexyl phthalate; Phthalates; Autism; Glucuronidation ID HAZARDOUS AIR-POLLUTANTS; SPECTRUM DISORDERS; DI(2-ETHYLHEXYL)PHTHALATE DEHP; UDP-GLUCURONOSYLTRANSFERASES; URINARY CONCENTRATIONS; PERINATAL EXPOSURE; UNITED-STATES; BISPHENOL-A; CHILDREN; PHYTOESTROGENS AB Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were collected and analyzed for the fraction of each metabolite conjugated by isotope dilution-liquid chromatography mass spectrometry-mass spectrometry. The degree of glucuronidation was lower with the ASD group. The glucuronidation pathway may differ in some children with ASD. C1 [Stein, T. Peter; Schluter, Margaret D.] Univ Med & Dent New Jersey, Dept Surg, Sch Osteopath Med, Stratford, NJ 08084 USA. [Steer, Robert A.] Univ Med & Dent New Jersey, Dept Psychiat, Sch Osteopath Med, Stratford, NJ 08084 USA. [Ming, Xue] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol, Newark, NJ 07103 USA. [Ming, Xue] JFK Med Ctr, New Jersey Neurosci Inst, Dept Neurol, Edison, NJ 08817 USA. 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PD NOV PY 2013 VL 43 IS 11 BP 2677 EP 2685 DI 10.1007/s10803-013-1822-y PG 9 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000015 PM 23575644 ER PT J AU Siniscalco, D Sapone, A Giordano, C Cirillo, A de Magistris, L Rossi, F Fasano, A Bradstreet, JJ Maione, S Antonucci, N AF Siniscalco, Dario Sapone, Anna Giordano, Catia Cirillo, Alessandra de Magistris, Laura Rossi, Francesco Fasano, Alessio Bradstreet, James Jeffrey Maione, Sabatino Antonucci, Nicola TI Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic disorders; Cannabinoid system; Gene expression; PBMCs ID MESSENGER-RNA TURNOVER; ENDOCANNABINOID SYSTEM; SPECTRUM DISORDERS; IMMUNE-RESPONSE; GENE-EXPRESSION; CB2; PROTEIN; MODULATION; ACTIVATION; ACETAMINOPHEN AB Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3-9 years; mean age: 6.06 +/- A 1.52 vs. 6.14 +/- A 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean +/- A SE of arbitrary units: 0.34 +/- A 0.03 vs. 0.23 +/- A 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean +/- A SE of arbitrary units: 33.5 +/- A 1.32 vs. 6.70 +/- A 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care. C1 [Siniscalco, Dario; Giordano, Catia; Rossi, Francesco; Maione, Sabatino] Univ Naples 2, Div Pharmacol, Dept Expt Med, I-80138 Naples, Italy. [Siniscalco, Dario] La Forza del Silenzio, Ctr Autism, Caserta, Italy. [Sapone, Anna; de Magistris, Laura] Univ Naples 2, Dept Internal & Expt Med Magrassi Lanzara, I-80138 Naples, Italy. [Sapone, Anna; Fasano, Alessio] Massachusetts Gen Hosp E, Ctr Celiac Res, Charlestown, MA USA. [Sapone, Anna; Fasano, Alessio] Massachusetts Gen Hosp E, Mucosal Immunol & Biol Res Ctr, Charlestown, MA USA. [Cirillo, Alessandra] Univ Naples 2, Div Biotechnol & Mol Biol A Cascino, Dept Expt Med, I-80138 Naples, Italy. [Fasano, Alessio] MassGen Hosp Children, Boston, MA USA. [Bradstreet, James Jeffrey] Int Child Dev Resource Ctr, Cumming, GA USA. [Antonucci, Nicola] Biomed Ctr Autism Res & Treatment, Bari, Italy. RP Siniscalco, D (reprint author), Univ Naples 2, Div Pharmacol, Dept Expt Med, Via S Maria Costantinopoli 16, I-80138 Naples, Italy. 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Abbeduto, Leonard TI Receptive Vocabulary in Boys with Autism Spectrum Disorder: Cross-Sectional Developmental Trajectories SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Language development; Comprehension; Production; Vocabulary; Trajectory ID EARLY LANGUAGE; COMMUNICATIVE DEVELOPMENT; METHODOLOGICAL ISSUES; EXPRESSIVE LANGUAGE; PRESCHOOL-CHILDREN; IMPAIRMENT; PREDICTORS; ACQUISITION; PHENOTYPES; TODDLERS AB In light of evidence that receptive language may be a relative weakness for individuals with autism spectrum disorder (ASD), this study characterized receptive vocabulary profiles in boys with ASD using cross-sectional developmental trajectories relative to age, nonverbal cognition, and expressive vocabulary. Participants were 49 boys with ASD (4-11 years) and 80 typically developing boys (2-11 years). Receptive vocabulary, assessed with the Peabody Picture Vocabulary Test, was a weakness for boys with ASD relative to age and nonverbal cognition. Relative to expressive vocabulary, assessed with the Expressive Vocabulary Test, receptive vocabulary increased at a lower rate for boys with ASD. Vocabulary trajectories in ASD are distinguished from typical development; however, nonverbal cognition largely accounts for the patterns observed. C1 [Kover, Sara T.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [McDuffie, Andrea S.; Hagerman, Randi J.; Abbeduto, Leonard] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [McDuffie, Andrea S.; Abbeduto, Leonard] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Hagerman, Randi J.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. RP Kover, ST (reprint author), Univ Wisconsin, Waisman Ctr, Room 475,1500 Highland Ave, Madison, WI 53705 USA. 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T., 1997, EXPRESSIVE VOCABULAR Zimmerman I., 2002, PRESCHOOL LANGUAGE S, V4th NR 51 TC 7 Z9 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2696 EP 2709 DI 10.1007/s10803-013-1823-x PG 14 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000017 PM 23588510 ER PT J AU Orsmond, GI Shattuck, PT Cooper, BP Sterzing, PR Anderson, KA AF Orsmond, Gael I. Shattuck, Paul T. Cooper, Benjamin P. Sterzing, Paul R. Anderson, Kristy A. TI Social Participation Among Young Adults with an Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Social participation; Young adulthood ID ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; OUTCOMES; FRIENDSHIP; PREVALENCE; COMMUNITY; EDUCATION; SYMPTOMS; YOUTH AB Investigating social participation of young adults with an autism spectrum disorder (ASD) is important given the increasing number of youth aging into young adulthood. Social participation is an indicator of life quality and overall functioning. Using data from the National Longitudinal Transition Study 2, we examined rates of participation in social activities among young adults who received special education services for autism (ASD group), compared to young adults who received special education for intellectual disability, emotional/behavioral disability, or a learning disability. Young adults with an ASD were significantly more likely to never see friends, never get called by friends, never be invited to activities, and be socially isolated. Among those with an ASD, lower conversation ability, lower functional skills, and living with a parent were predictors of less social participation. C1 [Orsmond, Gael I.] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. [Shattuck, Paul T.; Cooper, Benjamin P.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Sterzing, Paul R.] Univ Calif Berkeley, Sch Social Welf, Berkeley, CA 94720 USA. [Anderson, Kristy A.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. RP Orsmond, GI (reprint author), Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. 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PD NOV PY 2013 VL 43 IS 11 BP 2710 EP 2719 DI 10.1007/s10803-013-1833-8 PG 10 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000018 PM 23615687 ER PT J AU Butterly, F Percy, C Ward, G AF Butterly, Felicity Percy, Carol Ward, Gillian TI Brief Report: Do Service Dog Providers Placing Dogs with Children with Developmental Disabilities Use Outcome Measures and, If So, What Are they? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Assistance Dogs; Service providers; Outcome measures; Developmental disability ID FAMILIES; HEALTH AB The aim of this study was to identify the outcomes expected and assessed by those providing service dogs to children with developmental disabilities. Seventeen registered service dog providers were invited to complete a mixed methods online survey. Five providers, who prepared dogs to work with a wide range of conditions and behaviours, mainly Asperger's syndrome, autism and communication disorders, completed the survey. All five participants reported that they expected to see positive changes as a consequence of the service dog placement, in both the recipient child and their family, including improvements in attention span and language skills, as well as increased familial cohesion. Survey responses indicated that not all desired outcomes were routinely assessed. The range of assessments used were interviews, intake conversations, pre-placement questionnaires, child social dairies filled in by parents, follow up surveys after placement, and child observation by parents. No specifically named valid and reliable clinical or research measures were referred to, showing an emphasis on assessments from parents and service dog providers. It is not clear whether pre-intervention assessments are repeated systematically at follow-up, which could show robust intervention effects. There is scope for professionals in developmental disability to work with service dog providers to improve the evidence base in this field. C1 [Butterly, Felicity] Coventry Univ, Fac Hlth & Life Sci, Occupat Therapy & Psychol Dept, Coventry CV1 5FB, W Midlands, England. [Percy, Carol; Ward, Gillian] Coventry Univ, Coventry CV1 5FB, W Midlands, England. RP Butterly, F (reprint author), Coventry Univ, Fac Hlth & Life Sci, Occupat Therapy & Psychol Dept, Priory St, Coventry CV1 5FB, W Midlands, England. EM butterlf@uni.coventry.ac.uk; c.percy@coventry.ac.uk; g.ward@coventry.ac.uk CR Burghardt WF, 2003, VET CLIN N AM-SMALL, V33, P417, DOI 10.1016/S0195-5616(02)00133-X Burrows KE, 2008, QUAL HEALTH RES, V18, P1642, DOI 10.1177/1049732308327088 Burrows KE, 2008, J APPL ANIM WELF SCI, V11, P42, DOI 10.1080/10888700701555550 Davis D., 2006, CHALLENGED AUTISM OT Esposito L, 2011, CHILD DEV PERSPECT, V5, P205, DOI 10.1111/j.1750-8606.2011.00175.x Eva KW, 2005, ACAD MED, V80, pS46, DOI 10.1097/00001888-200510001-00015 Fife-Schaw C., 2006, RES METHODS PSYCHOL, P210 Fine A. H., 2000, ANIMAL ASSISTED THER Fombonne E., 2006, PEDIATRICS, V118, P139 Gardner D., 2007, FRIEND HENRY Slevin E., 2010, LEARNING DISABILITY, V13, P12 Thomas KC, 2007, J AUTISM DEV DISORD, V37, P818, DOI 10.1007/s10803-006-0208-9 Viau R, 2010, PSYCHONEUROENDOCRINO, V35, P1187, DOI 10.1016/j.psyneuen.2010.02.004 NR 13 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 NOV PY 2013 VL 43 IS 11 BP 2720 EP 2725 DI 10.1007/s10803-013-1803-1 PG 6 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000019 PM 23479076 ER PT J AU Brock, J Bzishvili, S Reid, M Hautus, M Johnson, BW AF Brock, Jon Bzishvili, Samantha Reid, Melanie Hautus, Michael Johnson, Blake W. TI Brief Report: Atypical Neuromagnetic Responses to Illusory Auditory Pitch in Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Auditory evoked potentials; Auditory perception; Autism; MEG ID SPEECH; POTENTIALS; PERCEPTION; DISCRIMINATION; CORTEX AB Atypical auditory perception is a widely recognised but poorly understood feature of autism. In the current study, we used magnetoencephalography to measure the brain responses of 10 autistic children as they listened passively to dichotic pitch stimuli, in which an illusory tone is generated by sub-millisecond inter-aural timing differences in white noise. Relative to control stimuli that contain no inter-aural timing differences, dichotic pitch stimuli typically elicit an object related negativity (ORN) response, associated with the perceptual segregation of the tone and the carrier noise into distinct auditory objects. Autistic children failed to demonstrate an ORN, suggesting a failure of segregation; however, comparison with the ORNs of age-matched typically developing controls narrowly failed to attain significance. More striking, the autistic children demonstrated a significant differential response to the pitch stimulus, peaking at around 50 ms. This was not present in the control group, nor has it been found in other groups tested using similar stimuli. This response may be a neural signature of atypical processing of pitch in at least some autistic individuals. C1 [Brock, Jon; Bzishvili, Samantha; Reid, Melanie; Johnson, Blake W.] Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. [Brock, Jon; Johnson, Blake W.] Australian Res Council, Ctr Excellence Cognit & Its Disorders, Sydney, NSW, Australia. [Hautus, Michael] Univ Auckland, Dept Psychol, Auckland, New Zealand. RP Brock, J (reprint author), Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. 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Autism Dev. Disord. PD NOV PY 2013 VL 43 IS 11 BP 2726 EP 2731 DI 10.1007/s10803-013-1805-z PG 6 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000020 PM 23543291 ER PT J AU Staples, KL AF Staples, Kerri L. TI Commentary: The Motor Skills of 7-10 Year Old Children Diagnosed with ASD. Are the Comparison Groups and Assessments Being Used Appropriate for the Research Questions Being Asked? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Editorial Material ID AUTISM SPECTRUM DISORDER; IMPAIRMENT C1 Univ Regina, Fac Kinesiol & Hlth Studies, Regina, SK S4S 0A2, Canada. RP Staples, KL (reprint author), Univ Regina, Fac Kinesiol & Hlth Studies, Regina, SK S4S 0A2, Canada. 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A., 2000, TEST GROSS MOTOR DEV Whyatt CP, 2012, J AUTISM DEV DISORD, V42, P1799, DOI 10.1007/s10803-011-1421-8 NR 23 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 NOV PY 2013 VL 43 IS 11 BP 2732 EP 2736 DI 10.1007/s10803-013-1809-8 PG 5 WC Psychology, Developmental SC Psychology GA 234HH UT WOS:000325633000021 PM 23504378 ER PT J AU Hallett, V Ronald, A Colvert, E Ames, C Woodhouse, E Lietz, S Garnett, T Gillan, N Rijsdijk, F Scahill, L Bolton, P Happe, F AF Hallett, Victoria Ronald, Angelica Colvert, Emma Ames, Catherine Woodhouse, Emma Lietz, Stephanie Garnett, Tracy Gillan, Nicola Rijsdijk, Fruhling Scahill, Lawrence Bolton, Patrick Happe, Francesca TI Exploring anxiety symptoms in a large-scale twin study of children with autism spectrum disorders, their co-twins and controls SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorders; anxiety; twin; siblings; comorbidity ID PERVASIVE DEVELOPMENTAL DISORDERS; ASPERGER-SYNDROME TEST; SCHOOL-AGE-CHILDREN; PSYCHIATRIC-DISORDERS; BEHAVIOR PROBLEMS; DEPRESSION SCALE; CHILDHOOD; ASSOCIATION; PREVALENCE; LANGUAGE AB BackgroundAlthough many children with autism spectrum disorders (ASDs) experience difficulties with anxiety, the manifestation of these difficulties remains unresolved. The current study assessed anxiety in a large population-based twin sample, aged 10-15years. Phenotypic analyses were used to explore anxiety symptoms in children with ASDs, their unaffected co-twins and a control sample. MethodsParticipants included 146 families from the Twins Early Development Study (TEDS) where one or both children had a suspected ASD. Eighty control families were also included. The Revised Child Anxiety and Depression scale (Chorpita, Yim, Moffitt, Umemoto & Francis, 2000) was completed (self- and parent-report), along with diagnostic and cognitive tests. Children were categorized into four groups (a) ASD (b) Broader Autism Phenotype (BAP: mainly co-twins of children with ASDs, with high subclinical autistic traits) (c) unaffected co-twins (with neither ASDs nor BAP) (d) controls. ResultsChildren in the ASD and BAP groups scored significantly higher than controls for all parent-rated (although not child-rated) anxiety subscales. There were no significant differences between the ASD and BAP groups for any of the parent-rated anxiety subscales. Compared with controls, unaffected co-twins showed significantly heightened Social Anxiety, Generalized Anxiety, and Panic symptoms. Significant associations were observed between certain anxiety subscales and both IQ and ASD symptoms. For example, greater parent-rated Social Anxiety was associated with higher IQ and increased social and communicative impairments. Significant interrater correlations were observed for anxiety reports in children with ASDs (r=.27-.54; p<.01), their unaffected co-twins (r=.32-.63; p<.01) and controls (r=.23-.43; p<.01) suggesting that children in this sample with and without ASD symptoms were able to report on their anxiety symptoms with some accuracy. ConclusionsThese findings support previous reports of heightened anxiety in children with ASDs, at least on parent-reported measures. Unaffected co-twins of children with ASDs also showed increased anxiety, generating questions about the potential etiological overlap between ASDs and anxiety. Progress in this area now depends on more refined anxiety measurement in ASDs and continued investigation of interrater differences. C1 [Hallett, Victoria; Ames, Catherine] Kings Coll London, Inst Psychiat, Dept Psychol, London, England. [Ronald, Angelica] Univ London, Dept Psychol Sci, London, England. [Colvert, Emma; Woodhouse, Emma; Lietz, Stephanie; Rijsdijk, Fruhling; Bolton, Patrick; Happe, Francesca] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. [Garnett, Tracy; Gillan, Nicola] South London & Maudsley NHS Fdn Trust, Denmark Hill, England. [Scahill, Lawrence] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Hallett, V (reprint author), Inst Psychiat, Addiction Sci Bldg,4 Windsor Walk, Denmark Hill SE5 8AF, England. EM victoria.v.hallett@kcl.ac.uk RI Ronald, Angelica/C-7812-2009; Bolton, Patrick/E-8501-2010 OI Ronald, Angelica/0000-0002-9576-2176; Bolton, Patrick/0000-0002-5270-6262 FU National Institute of Health Research (UK); Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London; Shire; Roche; Pfizer; Autism Speaks FX The authors would also like to thank Hannah Wiltshire, Rosemary Jessop, Bethan Corlett, and Jana Caemmerer for data collection and input assistance. This research was supported by a grant to P. B. from Autism Speaks. P. B. is supported by a National Institute of Health Research (UK) Senior Investigator award and the Biomedical Research Centre in Mental Health at the South London & Maudsley NHS Trust Hospital, London. L. S. acts as a consultant for Roche, Pfizer, Brachet, and BioMarin. He also receives research support from Shire, Roche, and Pfizer. The other authors have no conflicts of interests to declare. CR Bolton PF, 1998, PSYCHOL MED, V28, P385, DOI 10.1017/S0033291797006004 Chorpita BF, 2000, BEHAV RES THER, V38, P835, DOI 10.1016/S0005-7967(99)00130-8 Chorpita BF, 2005, BEHAV RES THER, V43, P309, DOI 10.1016/j.brat.2004.02.004 Costello EJ, 2005, CHILD ADOL PSYCH CL, V14, P631, DOI 10.1016/j.chc.2005.06.003 Dunn L. M., 1997, BRIT PICTURE VOCABUL, V2nd Farrugia S., 2006, FOCUS AUTISM OTHER D, V21, P35 Gadow KD, 2005, AUTISM, V9, P392, DOI 10.1177/1362361305056079 Gillott A, 2001, AUTISM, V5, P277, DOI 10.1177/1362361301005003005 Goodman R, 2000, J CHILD PSYCHOL PSYC, V41, P645, DOI 10.1111/j.1469-7610.2000.tb02345.x Gotham K, 2007, J AUTISM DEV DISORD, V37, P613, DOI 10.1007/s10803-006-0280-1 Gregory AM, 2007, CLIN CHILD FAM PSYCH, V10, P199, DOI 10.1007/s10567-007-0022-8 Hallett V, 2010, AM J PSYCHIAT, V167, P809, DOI 10.1176/appi.ajp.2009.09070990 Howlin P, 2000, J CHILD PSYCHOL PSYC, V41, P561, DOI 10.1017/S0021963099005806 Jacob S, 2009, AUTISM RES, V2, P293, DOI 10.1002/aur.108 Kanner L, 1943, NERV CHILD, V2, P217 Le Couteur A., 2003, AUTISM DIAGNOSTIC IN Lecavalier L, 2006, AM J MENT RETARD, V111, P199, DOI 10.1352/0895-8017(2006)111[199:VOTADI]2.0.CO;2 Lecavalier L, 2006, J AUTISM DEV DISORD, V36, P1101, DOI 10.1007/s10803-006-0147-5 Leyfer OT, 2006, J AUTISM DEV DISORD, V36, P849, DOI 10.1007/s10803-006-0123-0 Mazefsky CA, 2008, AUTISM RES, V1, P193, DOI 10.1002/aur.23 Muris P, 1998, J ANXIETY DISORD, V12, P387, DOI 10.1016/S0887-6185(98)00022-X Neale M. 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C., 1958, RAVENS STANDARD PROG Russell E, 2005, AUST NZ J PSYCHIAT, V39, P633, DOI 10.1080/j.1440-1614.2005.01637.x Scott FJ, 2002, AUTISM, V6, P9, DOI 10.1177/1362361302006001003 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f SMALLEY SL, 1995, AM J MED GENET, V60, P19, DOI 10.1002/ajmg.1320600105 Sukhodolsky DG, 2008, J ABNORM CHILD PSYCH, V36, P117, DOI 10.1007/s10802-007-9165-9 Trouton A, 2002, TWIN RES, V5, P444, DOI 10.1375/136905202320906255 van Steensel FJA, 2011, CLIN CHILD FAM PSYCH, V14, P302, DOI 10.1007/s10567-011-0097-0 Wechsler D, 1999, WECHSLER ABBREVIATED Weisbrot DM, 2005, J CHILD ADOL PSYCHOP, V15, P477, DOI 10.1089/cap.2005.15.477 White SW, 2009, CLIN PSYCHOL REV, V29, P216, DOI 10.1016/j.cpr.2009.01.003 Willemsen-Swinkels SHN, 1998, J AUTISM DEV DISORD, V28, P547, DOI 10.1023/A:1026008313284 Williams J, 2006, AUTISM, V10, P415, DOI 10.1177/1362361306066612 Wren FJ, 2004, J AM ACAD CHILD PSY, V43, P1364, DOI 10.1097/01.chi.0000138350.60487.d3 NR 41 TC 7 Z9 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2013 VL 54 IS 11 BP 1176 EP 1185 DI 10.1111/jcpp.12068 PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 234DT UT WOS:000325621700003 PM 24273800 ER PT J AU Gibson, J Adams, C Lockton, E Green, J AF Gibson, Jenny Adams, Catherine Lockton, Elaine Green, Jonathan TI Social communication disorder outside autism? A diagnostic classification approach to delineating pragmatic language impairment, high functioning autism and specific language impairment SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Social communication disorder; high functioning autism; language impairment; pragmatics; restricted and repetitive behaviours and interests; social functioning; diagnosis ID SPECTRUM DISORDER; REPETITIVE BEHAVIOR; CHILDREN; INTERVENTION; PRESCHOOLERS; BORDERLANDS; CRITERIA; OUTCOMES; SLI; AGE AB BackgroundDevelopmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. MethodsSix to eleven year olds diagnosed with pragmatic language impairment (PLI), high functioning autism (HFA) or specific language impairment (SLI) were compared on measures of social interaction with peers (PI), restricted and repetitive behaviours/interests (RRBIs) and language ability. Odds ratios (OR) from a multinomial logistic regression were used to determine the importance of each measure to diagnostic grouping. MANOVA was used to investigate differences in subscale scores for the PI measure. ResultsGreater degrees of PI difficulties (OR=1.22, 95% CI=1.05-1.41), RRBI (OR=1.23, 95% CI=1.06-1.42) and expressive language ability (OR=1.16, 95% CI=1.03-1.30) discriminated HFA from PLI. PLI was differentiated from SLI by elevated PI difficulties (OR=0.82, 95% CI=0.70-0.96) and higher expressive language ability (OR=0.88, 95% CI=0.77-0.98), but indistinguishable from SLI using RRBI (OR=1.01, 95% CI=0.94-1.09). A significant effect of group on PI subscales was observed (=1.38, F(4, 56)=19.26, p<.01) and PLI and HFA groups shared a similar PI subscale profile. ConclusionsResults provide empirical support for a conceptualisation of PLI as a developmental impairment distinguishable from HFA by absence of RRBIs and by the presence of expressive language difficulties. PI difficulties appear elevated in PLI compared with SLI, but may be less pervasive than in HFA. Findings are discussed with reference to the proposed new category of social communication disorder' in DSM-5. C1 [Gibson, Jenny] Univ Cambridge, Dept Dev Psychiat, Cambridge, England. [Adams, Catherine; Lockton, Elaine; Green, Jonathan] Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England. RP Gibson, J (reprint author), Dept Dev Psychiat, Douglas House,18B Trumpington Rd, Cambridge CB2 2AH, England. EM jlg53@medschl.cam.ac.uk FU MRC/ESRC; Kids Company charity FX Jenny Gibson carried out this research at University of Manchester while supported by an MRC/ESRC interdisciplinary PhD studentship. Thanks to all participating children and families. Thanks to children and staff at Moor House School. Jenny Gibson is currently supported by a grant made by Kids Company charity to University of Cambridge. CR Adams C, 2001, INT J LANG COMM DIS, V36, P289, DOI 10.1080/13682820119881 Adams C., 2001, ASSESSMENT COMPREHEN Adams C, 2012, INT J LANG COMM DIS, V47, P233, DOI 10.1111/j.1460-6984.2011.00146.x Baron-Cohen S, 2001, INT REV RES MENT RET, V23, P169 Barrett S, 2004, AUTISM, V8, P61, DOI 10.1177/1362361304040640 Bishop D., 2000, SPEECH LANGUAGE IMPA, P99 Bishop D. V. M., 2003, CHILDRENS COMMUNICAT Bishop D. V. 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Psychiatry PD NOV PY 2013 VL 54 IS 11 BP 1186 EP 1197 DI 10.1111/jcpp.12079 PG 12 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 234DT UT WOS:000325621700004 PM 23639107 ER PT J AU Gadow, KD Kaat, AJ Lecavalier, L AF Gadow, Kenneth D. Kaat, Aaron J. Lecavalier, Luc TI Relation of symptom-induced impairment with other illness parameters in clinic-referred youth SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Psychiatric disorder; impairment; diagnosis; children; ADHD ID OPPOSITIONAL DEFIANT DISORDER; AUTISM SPECTRUM DISORDER; MULTIPLE TIC DISORDER; FUNCTIONAL IMPAIRMENT; SCHIZOPHRENIA SPECTRUM; PSYCHIATRIC-SYMPTOMS; CHILDREN; ADHD; METHYLPHENIDATE; ADOLESCENTS AB ObjectiveTo examine the relation of caregiver ratings of psychiatric symptom-induced impairment with number and severity of symptoms and informant agreement in consecutive child psychiatry outpatient referrals. MethodsParents and teachers completed a broadband DSM-IV-referenced rating scale with disorder-specific impairment for 636 youth (6-18years). Illness parameters included impairment, number and severity of symptoms, and their combination (symptom+impairment) as well as categorical (cut-off) and dimensional scoring. ResultsAgreement between impairment and other illness parameters showed considerable variation as a function of type of parameter, disorder, and informant, but to lesser extent age and gender. Many youth who met impairment cut-off for specific disorders did not meet symptom cut-off. Conversely, most youth who met symptom cut-off were impaired. Symptom cut-off evidenced greater convergence with impairment cut-off than combined symptom+impairment cut-offs. Severity of impairment was moderately to highly correlated with number and severity of symptoms. Parents' and teachers' ratings indicated little disorder-specific agreement about youth who met impairment cut-off, symptom cut-off, or combined symptom+impairment cut-off. Therefore, sole reliance on one informant greatly underestimates the pervasiveness of impairment. ConclusionFindings are consistent with the notion that each illness parameter represents a unique conceptual construct, which has important clinical and research implications. C1 [Gadow, Kenneth D.] SUNY Stony Brook, Dept Psychiat & Behav Sci, New York, NY USA. [Kaat, Aaron J.; Lecavalier, Luc] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Kaat, Aaron J.; Lecavalier, Luc] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Lecavalier, Luc] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. RP Gadow, KD (reprint author), SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. 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Psychiatry PD NOV PY 2013 VL 54 IS 11 BP 1198 EP 1207 DI 10.1111/jcpp.12077 PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 234DT UT WOS:000325621700005 PM 23586345 ER PT J AU Kent, RG Carrington, SJ Le Couteur, A Gould, J Wing, L Maljaars, J Noens, I van Berckelaer-Onnes, I Leekam, SR AF Kent, Rachel G. Carrington, Sarah J. Le Couteur, Ann Gould, Judith Wing, Lorna Maljaars, Jarymke Noens, Ilse van Berckelaer-Onnes, Ina Leekam, Susan R. TI Diagnosing Autism Spectrum Disorder: who will get a DSM-5 diagnosis? SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE DSM-5; diagnosis; ASD; DISCO ID COMMUNICATION DISORDERS; INTERVIEW; CRITERIA; CHILDREN; IV; ABNORMALITIES; VALIDATION AB BackgroundIntroduction of proposed criteria for DSM-5 Autism Spectrum Disorder (ASD) has raised concerns that some individuals currently meeting diagnostic criteria for Pervasive Developmental Disorder (PDD; DSM-IV-TR/ICD-10) will not qualify for a diagnosis under the proposed changes. To date, reports of sensitivity and specificity of the new criteria have been inconsistent across studies. No study has yet considered how changes at the sub domain' level might affect overall sensitivity and specificity, and few have included individuals of different ages and ability levels. MethodsA set of DSM-5 ASD algorithms were developed using items from the Diagnostic Interview for Social and Communication Disorders (DISCO). The number of items required for each DSM-5 subdomain was defined either according to criteria specified by DSM-5 (Initial Algorithm), a statistical approach (Youden J Algorithm), or to minimise the number of false positives while maximising sensitivity (Modified Algorithm). The algorithms were designed, tested and compared in two independent samples (Sample 1, N=82; Sample 2, N=115), while sensitivity was assessed across age and ability levels in an additional dataset of individuals with an ICD-10 PDD diagnosis (Sample 3, N=190). ResultsSensitivity was highest in the Initial Algorithm, which had the poorest specificity. Although Youden J had excellent specificity, sensitivity was significantly lower than in the Modified Algorithm, which had both good sensitivity and specificity. Relaxing the domain A rules improved sensitivity of the Youden J Algorithm, but it remained less sensitive than the Modified Algorithm. Moreover, this was the only algorithm with variable sensitivity across age. All versions of the algorithm performed well across ability level. ConclusionsThis study demonstrates that good levels of both sensitivity and specificity can be achieved for a diagnostic algorithm adhering to the DSM-5 criteria that is suitable across age and ability level. C1 [Kent, Rachel G.; Carrington, Sarah J.; Leekam, Susan R.] Cardiff Univ, Sch Psychol, Wales Autism Res Ctr, Cardiff CF10 3AT, S Glam, Wales. [Le Couteur, Ann] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Gould, Judith; Wing, Lorna] Natl Autist Soc, Lorna Wing Ctr, Bromley, England. [Maljaars, Jarymke; Noens, Ilse] Univ Leuven KU Leuven, Louvain, Belgium. [Maljaars, Jarymke; van Berckelaer-Onnes, Ina] Leiden Univ, Leiden, Netherlands. RP Leekam, SR (reprint author), Cardiff Univ, Sch Psychol, Wales Autism Res Ctr, Tower Bldg,Pk Pl, Cardiff CF10 3AT, S Glam, Wales. EM LeekamSR@cardiff.ac.uk RI Carrington, Sarah/C-1246-2010 OI Carrington, Sarah/0000-0001-5548-8793 FU Economic and Social Research Council [ES/G039399/1]; Wales Autism Research Centre; Autism Cymru; Autistica FX This research was supported by an Economic and Social Research Council PhD award ES/G039399/1 to R. K. and by Wales Autism Research Centre funding led by Autism Cymru and Autistica that supported S. C. and S. L. 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M., 2007, CONJOINT BEHAV CONSU NR 6 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 863 EP 865 DI 10.1002/pits.21714 PG 3 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300001 ER PT J AU Tullis, CA Zangrillo, AN AF Tullis, Christopher A. Zangrillo, Amanda N. TI SEXUALITY EDUCATION FOR ADOLESCENTS AND ADULTS WITH AUTISM SPECTRUM DISORDERS SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID HIGH-FUNCTIONING AUTISM; SOCIAL STORIES; INTELLECTUAL DISABILITIES; SKILLS; INDIVIDUALS; ATTITUDES; BEHAVIOR AB As people with autism spectrum disorders (ASD) mature from adolescents into adults, social deficits may become more pronounced and apparent in new areas (e.g., social functioning and sexuality). Like neurotypicals, sexuality may be directly related to quality of life for people with ASD. Current practice for addressing sexuality in the ASD population includes some curricula that may be beneficial for teaching skills related to sexuality, but the scientific support for such curricula is absent. Typically sexuality education is only implemented when a behavior is demonstrated that is considered deviant or problematic. Although reactive education may be a common practice, a strategy that includes proactive sexuality education may be more beneficial for the long-term quality of life for people with ASD. The current paper will highlight some of the areas for further investigation and program development for adolescents and adults with ASD. (C) 2013 Wiley Periodicals, Inc. C1 [Tullis, Christopher A.; Zangrillo, Amanda N.] Ball State Univ, Muncie, IN 47306 USA. RP Tullis, CA (reprint author), Ball State Univ, 2000 West Univ Ave, Muncie, IN 47306 USA. 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Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 866 EP 875 DI 10.1002/pits.21713 PG 10 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300002 ER PT J AU Wilczynski, SM Trammell, B Clarke, LS AF Wilczynski, Susan M. Trammell, Beth Clarke, Laura S. TI IMPROVING EMPLOYMENT OUTCOMES AMONG ADOLESCENTS AND ADULTS ON THE AUTISM SPECTRUM SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID INDEPENDENT TASK-PERFORMANCE; COMPUTER-AIDED SYSTEM; INTELLECTUAL DISABILITIES; SUPPORTED EMPLOYMENT; YOUNG-ADULTS; DEVELOPMENTAL-DISABILITIES; MENTAL-RETARDATION; PROMPTING SYSTEM; DISORDERS; JOB AB As the number of diagnosed cases of ASD increases, school professionals must consider not only efficacious teaching approaches for improving academic goals, but also what systems must be in place to address one of the most important jobs of the school systems: preparing capable citizens. For more than 160 years, schools have been tasked with preparing good citizens who are capable of contributing to society through work. Given the fact that schools have been required to provide appropriate educational programming to students with disabilities for decades and that this includes planning for the transition to adulthood, the staggeringly poor employment outcomes of individuals on the autism spectrum should be a cause for concern. The present article reviews the significant problem of unemployment as well as employment supports for individuals with ASD. These supports include both the natural supports (scaffolding to enhance success in obtaining and maintaining employment) as well as technological advances that may minimize ostracization in the workplace. Lastly, recommendations for school psychologists who seek to play a vital role in this critical area are offered. (C) 2013 Wiley Periodicals, Inc. 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A., 1999, FOCUS AUTISM OTHER D, V14, P159, DOI 10.1177/108835769901400305 Taylor JL, 2011, J AUTISM DEV DISORD, V41, P566, DOI 10.1007/s10803-010-1070-3 Trach JS, 1997, J REHABIL, V63, P43 NR 66 TC 1 Z9 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 876 EP 887 DI 10.1002/pits.21718 PG 12 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300003 ER PT J AU Carter, EW Harvey, MN Taylor, JL Gotham, K AF Carter, Erik W. Harvey, Michelle N. Taylor, Julie Lounds Gotham, Katherine TI CONNECTING YOUTH AND YOUNG ADULTS WITH AUTISM SPECTRUM DISORDERS TO COMMUNITY LIFE SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID NATIONAL LONGITUDINAL TRANSITION; HIGH-FUNCTIONING CHILDREN; POSTSECONDARY EDUCATION; INTELLECTUAL DISABILITY; EMPLOYMENT; STUDENTS; INDIVIDUALS; ADOLESCENTS; OUTCOMES; SCHOOL AB Equipping youth with autism spectrum disorders (ASD) to flourish during and after high school is central to the purpose and practice of special education. However, many students with ASD are leaving high school without the preparation and connections needed to engage meaningfully in their communities. This article reviews research-based approaches for connecting adolescents with ASD to life beyond the classroom by describing promising practices for fostering inclusion in postsecondary education and community activities. Recognizing that relationships are at the core of community life, emphasis is placed on fostering social connections as an essential aspect of helping young people with ASD thrive in these settings. We conclude with suggestions for school staff to support the successful transitions of young people with ASD. (C) 2013 Wiley Periodicals, Inc. C1 [Carter, Erik W.; Harvey, Michelle N.; Taylor, Julie Lounds; Gotham, Katherine] Vanderbilt Univ, Nashville, TN 37072 USA. RP Carter, EW (reprint author), Vanderbilt Univ, Nashville, TN 37072 USA. EM erik.carter@vanderbilt.edu CR Adreon D, 2007, INTERV SCH CLIN, V42, P271, DOI 10.1177/10534512070420050201 Aud S., 2011, AM YOUTH TRANSITIONS Ault MJ, 2013, INTELLECT DEV DISAB, V51, P48, DOI 10.1352/1934-9556-51.01.048 Baum S., 2010, ED PAYS 2010 BENEFIT Bauminger N, 2000, CHILD DEV, V71, P447, DOI 10.1111/1467-8624.00156 Blackorby J, 1996, EXCEPT CHILDREN, V62, P399 Carter E, 2012, RES PRACT PERS SEV D, V37, P9 Carter E. W., 2012, TEACHING EXCEPTIONAL, V44, P46 Carter E. W., 2012, TREATMENT AUTISM SPE, P221 Carter EW, 2013, AJIDD-AM J INTELLECT, V118, P16, DOI 10.1352/1944-7558-118.1.16 Carter EW, 2010, RES PRACT PERS SEV D, V35, P63 Carter EW, 2010, EXCEPT CHILDREN, V76, P194 Carter EW, 2012, J DISABIL POLICY STU, V23, P50, DOI 10.1177/1044207311414680 Carter EW, 2010, INTERV SCH CLIN, V45, P275, DOI 10.1177/1053451209359077 Chiang HM, 2012, J AUTISM DEV DISORD, V42, P685, DOI 10.1007/s10803-011-1297-7 Datillo J., INCLUSION IN PRESS, V1, P76, DOI [10.1352/2326-6988-1.1.076, DOI 10.1352/2326-6988-1.1.076] Fives CJ, 2008, PSYCHOL SCHOOLS, V45, P508, DOI 10.1002/pits.20320 Giangreco M. 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W., 2009, CAREER DEV EXCEPTION, V32, P115, DOI [10.1177/0885728809336859, DOI 10.1177/0885728809336859] Trainor AA, 2008, J SPEC EDUC, V42, P148, DOI 10.1177/0022466907313346 Veenstra-VanderWeele J., 2012, AGENCY HEALTHCARE RE Wagner M., 2004, NLTS2 DATA BRIEF, V3, P1 Walton KM, 2013, J AUTISM DEV DISORD, V43, P594, DOI 10.1007/s10803-012-1601-1 NR 41 TC 2 Z9 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 888 EP 898 DI 10.1002/pits.21716 PG 11 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300004 ER PT J AU Koegel, LK Ashbaugh, K Koegel, RL Detar, WJ Regester, A AF Koegel, Lynn Kern Ashbaugh, Kristen Koegel, Robert L. Detar, Whitney J. Regester, April TI INCREASING SOCIALIZATION IN ADULTS WITH ASPERGER'S SYNDROME SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID HIGH-FUNCTIONING AUTISM; CHILDREN; DISABILITIES; ADOLESCENTS AB Difficulties engaging in social activities are considered to be a core symptom of individuals with autism spectrum disorder (ASD). Both the literature and our clinical observations suggest that most individuals with ASD have a desire to engage in social activities, but social skill deficits make social interaction challenging, and in turn can lead to feelings of loneliness and isolation. Currently there are few resources to support adult students with ASD in forming friendships and involvement in the college community. Using a multiple baseline design over a 33-week period, this study evaluated the effectiveness of structured social planning for college students with ASD. Intervention included weekly sessions that included providing step-by-step social planning related to their interests, and feedback regarding their participation in social activities. In addition, training in specific organizational skills was implemented, such as determining activities, using a planner to ensure participation in the activities, inviting peers to activities, arranging for transportation, and so on. Results demonstrated that participants were not attending any social events throughout the baseline period. Following intervention, all participants increased the number of social events attended per week. Further, quality of life and satisfaction questionnaires all reported a higher satisfaction with their college experience and peer interactions following intervention. Finally, improvements were seen in other untargeted areas, including increases in non-structured social interactions, improvements in grade point averages, and employment. Results are discussed in regards to a creating a social support program for college students with ASD. (C) 2013 Wiley Periodicals, Inc. C1 [Koegel, Lynn Kern; Ashbaugh, Kristen; Koegel, Robert L.; Detar, Whitney J.] Univ Calif Santa Barbara, Eli & Edythe L Broad Asperger Res Ctr, Santa Barbara, CA 93106 USA. [Regester, April] Univ Missouri, St Louis, MO 63121 USA. RP Koegel, LK (reprint author), Univ Calif Santa Barbara, Koegel Autism Ctr, Clin & Sch Psychol Dept, Santa Barbara, CA 93106 USA. EM Lynnk@education.ucsb.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baker MJ, 1998, J ASSOC PERS SEVERE, V23, P300, DOI 10.2511/rpsd.23.4.300 Barnhill G., 2001, FOCUS AUTISM OTHER D, V22, P116 Bauminger N, 2000, CHILD DEV, V71, P447, DOI 10.1111/1467-8624.00156 Dillon M. R., 2007, COLL STUDENT J, V41, P499 Fitzgerald M., 2004, AUTISM CREATIVITY IS Glennon T. 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S., 2001, FOCUS AUTISM OTHER D, V16, P120, DOI DOI 10.1177/108835760101600208 Tse J, 2007, J AUTISM DEV DISORD, V37, P1960, DOI 10.1007/s10803-006-0343-3 WEST M, 1993, EXCEPT CHILDREN, V59, P456 NR 20 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 899 EP 909 DI 10.1002/pits.21715 PG 11 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300005 ER PT J AU Rubenstein, LD Pierson, EE Wilczynski, SM Connolly, SC AF Rubenstein, Lisa Davia Pierson, Eric E. Wilczynski, Susan M. Connolly, Sarah C. TI FITTING THE HIGH ABILITY PROGRAM TO THE NEEDS OF INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID ASPERGER SYNDROME; GIFTED STUDENTS; CHILDREN AB As the number of individuals diagnosed with Autism Spectrum Disorders grows, leaders are increasingly recognizing the limitations of the existing literature base to serve unique subsets of students on the spectrum. To date, there is a dearth of research regarding individuals who are both diagnosed on the spectrum and identified as gifted or high ability. This article provides a theoretical structure to guide professionals working with this population, as well as recommendations for further research. The High Ability/Autism puzzle includes three interlocking pieces that must be connected. First, this population must be appropriately defined, and then second, that definition must guide how professionals identify members of this population. Third, identification methods must inform the educational programming decisions to best serve the High Ability/Autism population. The definition, identification, and available programs must be interrelated to provide appropriate support and guidance for this unique population. This article will outline this process and make recommendations for both practitioners and researchers committed to gifted individuals on the spectrum. (C) 2013 Wiley Periodicals, Inc. C1 [Rubenstein, Lisa Davia; Pierson, Eric E.; Wilczynski, Susan M.; Connolly, Sarah C.] Ball State Univ, Muncie, IN 47306 USA. RP Rubenstein, LD (reprint author), Ball State Univ, Teachers Coll, Room 524, Muncie, IN 47306 USA. EM lmrubenstein@bsu.edu CR Amend E. R., 2009, GIFTED CHILD TODAY, V32, P57 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Arnold K. D., 1995, LIVES PROMISE Assouline S. G., 2007, NAGC COMMUNIQUE SPR, P9 Assouline S. 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L., 1993, REGULAR CLASSROOM PR YOUNG JM, 1994, J APPL BEHAV ANAL, V27, P685, DOI 10.1901/jaba.1994.27-685 NR 67 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 910 EP 922 DI 10.1002/pits.21719 PG 13 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300006 ER PT J AU Scattone, D Mong, M AF Scattone, Dorothy Mong, Michael TI COGNITIVE BEHAVIOR THERAPY IN THE TREATMENT OF ANXIETY FOR ADOLESCENTS AND ADULTS WITH AUTISM SPECTRUM DISORDERS SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID HIGH-FUNCTIONING AUTISM; CHILDREN; SYMPTOMS; TRIAL; QUESTIONNAIRE; REPLICATION; PARENT AB Important areas of treatment for individuals with autism spectrum disorders (ASD) have only begun to be explored empirically in the last decade. Fortunately, there has been growing interest in identifying how to best adapt treatments that have been demonstrated to be efficacious with broader populations to individuals with ASD. This article provides a review of the literature for cognitive behavior therapy (CBT) in the treatment of anxiety and mood disorders with modifications for adolescents and adults diagnosed with ASD. The majority of these studies incorporated manualized procedures, structured sessions, visual aids, use of worksheets, and an opportunity for social engagement, in addition to regular practice and feedback within a supportive environment. Treatment has been provided primarily in groups; however, researchers are beginning to explore the advantages of individualized treatment. Although only a handful of studies have been published on the use of CBT with adolescents or adults with ASD, results are promising. School psychologists will want to familiarize themselves with this literature to best meet the needs of students in their care. Implications and directions for future research are discussed. (C) 2013 Wiley Periodicals, Inc. C1 [Scattone, Dorothy] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Mong, Michael] Univ So Mississippi, Hattiesburg, MS 39406 USA. RP Scattone, D (reprint author), Univ Mississippi, Med Ctr Child Dev, Jackson, MS 39216 USA. EM dscattone@umc.edu CR Albano AM, 2002, INT REV PSYCHIATR, V14, P129, DOI 10.1080/09540260220132644 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Attwood T, 2004, BEHAV CHANGE, V21, P147, DOI 10.1375/bech.21.3.147.55995 Barlow D., 2009, SINGLE CASE EXPT DES Baron-Cohen S, 2005, J AUTISM DEV DISORD, V35, P807, DOI 10.1007/s10803-005-0026-5 BARONCOHEN S, 1985, COGNITION, V21, P37, DOI 10.1016/0010-0277(85)90022-8 Beck A. 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Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 923 EP 935 DI 10.1002/pits.21717 PG 13 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300007 ER PT J AU Trammell, B Wilczynski, SM Dale, B Mcintosh, DE AF Trammell, Beth Wilczynski, Susan M. Dale, Brittany Mcintosh, David E. TI ASSESSMENT AND DIFFERENTIAL DIAGNOSIS OF COMORBID CONDITIONS IN ADOLESCENTS AND ADULTS WITH AUTISM SPECTRUM DISORDERS SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID ASPERGER-SYNDROME; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; INDIVIDUALS; POPULATION; CHILDREN; SCALE; CHALLENGES; PREVALENCE; RATES AB Successful treatment of individuals with autism spectrum disorders (ASD) is entirely contingent on an accurate diagnosis. Although many resources exist to help the clinician with differential diagnosis of children, particularly in early childhood, the resources available for evaluating adolescents and adults is far less prevalent. Clinicians often rely on multiple forms of data from numerous sources to make accurate diagnoses, which for adults is a complex process. Lack of availability of instruments that have been normed with individuals with ASD creates limitations for the clinician. In addition, gathering background information from adolescents and adults on the spectrum can be challenging for a number of reasons, including poor self-reporting and poor memory for events from parents or caregivers. To further complicate the matter, comorbid conditions become more and more common as the individual with ASD goes through adolescence and adulthood. This article aims to identify the challenges related to the evaluation of adolescents and adults with ASD, noting particular attention to the differential diagnosis of common comorbid conditions. Recommendations for how to conduct a thorough psychological evaluation with an adolescent or adult with an ASD are made. (C) 2013 Wiley Periodicals, Inc. C1 [Trammell, Beth] Indiana Univ East, Richmond, IN 47374 USA. [Wilczynski, Susan M.; Dale, Brittany; Mcintosh, David E.] Ball State Univ, Muncie, IN 47306 USA. RP Trammell, B (reprint author), Indiana Univ East, Dept Social Sci, 2325 Chester Blvd, Richmond, IN 47374 USA. EM batramme@iue.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2013, DIAGN STAT MAN MENT Barnhill G. P., 2007, FOCUS AUTISM OTHER D, V22, P116, DOI DOI 10.1177/10883576070220020301 Bastiaansen JA, 2011, J AUTISM DEV DISORD, V41, P1256, DOI 10.1007/s10803-010-1157-x Beck A. T., 1996, BECK DEPRESSION INVE, V2nd Billstedt E, 2005, J AUTISM DEV DISORD, V35, P351, DOI 10.1007/s10803-005-3302-5 Bradley EA, 2004, J AUTISM DEV DISORD, V34, P151, DOI 10.1023/B:JADD.0000022606.97580.19 Causton-Theoharis J, 2009, INTELLECT DEV DISAB, V47, P84, DOI 10.1352/1934-9556-47.2.84 Deprey L., 2009, ASSESSMENT AUTISM SP, P290 Francis K, 2012, Psychiatriki, V23 Suppl 1, P66 Frazier J. 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P., 2010, REDPATH SOCIAL UNPUB Tantam D., 2000, AUTISM INT J RES PRA, V4, P47, DOI DOI 10.1177/1362361300004001004 Tonge BJ, 2003, INT REV RES MENT RET, V26, P61, DOI 10.1016/S0074-7750(03)01002-4 White SW, 2009, CLIN PSYCHOL REV, V29, P216, DOI 10.1016/j.cpr.2009.01.003 WING L, 1981, PSYCHOL MED, V11, P115 NR 49 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3085 EI 1520-6807 J9 PSYCHOL SCHOOLS JI Psychol. Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 936 EP 946 DI 10.1002/pits.21720 PG 11 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300008 ER PT J AU Rue, HC Knox, M AF Rue, Hanna C. Knox, Maria TI CAPACITY BUILDING: EVIDENCE-BASED PRACTICE AND ADOLESCENTS ON THE AUTISM SPECTRUM SO PSYCHOLOGY IN THE SCHOOLS LA English DT Article ID IMPLEMENTATION INTEGRITY; TEACHER; PERFORMANCE; DISORDERS; EDUCATION; MEDICINE; FEEDBACK; STUDENTS; BEHAVIOR; CHILDREN AB Empirical research in the treatment of autism spectrum disorders (ASDs) has resulted in the identification of numerous evidence-based interventions (EBIs). Adolescents with an ASD are faced with unique academic challenges, complex social environments, and physiological changes. They often require interventions to aid in acclimating to their evolving social environments and physical changes. One of the many challenges for practitioners working with adolescents is turning research findings into practice. We provide a framework to build capacity within a middle or high-school setting to implement EBIs for adolescent students with an ASD. Key elements of implementing EBIs in the school setting include: developing a team of professionals dedicated to achieving a system change, a systematic plan, monitoring progress, and a plan for sustainability. Teacher training is an essential part of implementing EBIs in an educational setting. Empirical evidence suggests that teacher training consists of different strategies including in-vivo training. Accessing resources outside of the school system, such as professionals at universities and teaching hospitals, can aid in training and other aspects of implementing EBIs in the classroom. (C) 2013 Wiley Periodicals, Inc. RP Rue, HC (reprint author), May Inst, 41 Pacella Pk Dr, Randolph, MA 02368 USA. EM hrue@mayinstitute.org CR Albuquerque Kevin V, 2011, J Oncol Pract, V7, P222, DOI 10.1200/JOP.2011.000237 Allsop SJ, 2009, DRUG ALCOHOL REV, V28, P541, DOI 10.1111/j.1465-3362.2009.00110.x American Academy of Child & Adolescent Psychiatry, 2011, FACTS FAM NORM AD 1 American Academy of Child & Adolescent Psychiatry, 2011, FACTS FAM NORM AD 2 American Psychological Association, 2002, REF PROF DEV AD AYRES BJ, 1994, J ASSOC PERS SEVERE, V19, P84 Caterino L. 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Schools PD NOV PY 2013 VL 50 IS 9 SI SI BP 947 EP 956 DI 10.1002/pits.21712 PG 10 WC Psychology, Educational SC Psychology GA 234HK UT WOS:000325633300009 ER PT J AU de Boer, A Pijl, SJ Post, W Minnaert, A AF de Boer, Anke Pijl, Sip Jan Post, Wendy Minnaert, Alexander TI Peer Acceptance and Friendships of Students with Disabilities in General Education: The Role of Child, Peer, and Classroom Variables SO SOCIAL DEVELOPMENT LA English DT Article DE peer acceptance; attitudes; behaviour disorders; autistic spectrum disorders ID SPECIAL NEEDS; SOCIAL-PARTICIPATION; INCLUSIVE EDUCATION; REGULAR SCHOOLS; PUPILS; ATTITUDES; QUESTIONNAIRE; ATTENTION; AUTISM; GENDER AB To understand the difficulties students with disabilities experience in their social participation in general education, this study examined which child, peer, and class variables relate to peer acceptance and friendships. In a cross-sectional study, sociometric data were gathered for students without disabilities (N = 985) and students with disabilities (N = 65), together with personal related variables of students with disabilities, attitudes of peers towards students with disabilities, and classroom information. Using separate social networks for both boys and girls, the findings of the logistic multilevel regression analyses showed different outcomes for peer acceptance of boys and girls with disabilities. The implications of the findings are discussed in the light of possible interventions to improve peer acceptance and friendships of students with disabilities in general primary education. C1 [de Boer, Anke; Pijl, Sip Jan; Post, Wendy; Minnaert, Alexander] Univ Groningen, NL-9712 TJ Groningen, Netherlands. [Pijl, Sip Jan] Norwegian Univ Sci & Technol, Trondheim, Norway. RP de Boer, A (reprint author), Univ Groningen, Dept Special Educ, Grote Rozenstr 38, NL-9712 TJ Groningen, Netherlands. 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PD NOV PY 2013 VL 22 IS 4 BP 831 EP 844 DI 10.1111/j.1467-9507.2012.00670.x PG 14 WC Psychology, Developmental SC Psychology GA 232NM UT WOS:000325500700011 ER PT J AU Pignatelli, M Feligioni, M Piccinin, S Molinaro, G Nicoletti, F Nistico, R AF Pignatelli, Marco Feligioni, Marco Piccinin, Sonia Molinaro, Gemma Nicoletti, Ferdinando Nistico, Robert TI Synaptic Plasticity as a Therapeutic Target in the Treatment of Autism-related Single-gene Disorders SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Synaptic plasticity; long-term potentiation; long-term depression; monogenic autism; mGLURs ID FRAGILE-X-SYNDROME; METABOTROPIC GLUTAMATE-RECEPTOR; TUBEROUS SCLEROSIS COMPLEX; LONG-TERM POTENTIATION; MENTAL-RETARDATION PROTEIN; CPG-BINDING PROTEIN-2; MOUSE MODEL; RETT-SYNDROME; ANGELMAN-SYNDROME; UBIQUITIN LIGASE AB The term "Autism Spectrum" is often used to describe disorders that are currently classified as Pervasive Developmental Disorders. These disorders are typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and/or cognitive delays or mental retardation; sometimes they present high comorbidity rates with epilepsy. Although these diagnoses share some common features, individuals with these disorders are thought to be "on the spectrum" because of differences in severity across these domains. Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. Of particular interest are transgenic technologies that allowed the engineering of several mouse models mimicking different kinds of monogenic heritable forms of ASDs. These transgenic models provide excellent opportunities to explore in detail cellular and molecular mechanisms underlying disease pathology and to identify novel targets for therapeutic intervention. Increasing evidence suggests that the pathophysiological core of the murine model is primarily due to changes in normal synaptic transmission and plasticity. Here, we will extensively review the synaptic alterations across different animal models of ASDs and recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. We describe how pharmacological modulation of mGlu5 receptor, through the use of positive or negative allosteric modulators (depending on the specific disorder), may represent a promising therapeutic strategy for ASDs treatment. C1 [Pignatelli, Marco; Feligioni, Marco; Piccinin, Sonia] European Brain Res Inst, Pharmacol Synapt Plast Unit, I-00143 Rome, Italy. [Pignatelli, Marco; Piccinin, Sonia; Nicoletti, Ferdinando; Nistico, Robert] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy. [Molinaro, Gemma; Nicoletti, Ferdinando] IRCCS Neuromed, I-86077 Pozzilli, Italy. [Nistico, Robert] IRCCS S Lucia Fdn, I-00143 Rome, Italy. RP Pignatelli, M (reprint author), Univ Roma La Sapienza, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM marco.pignatelli@hotmail.it; robert.nistico@uniroma1.it FU PRIN FX This work was supported by PRIN 2009 to RN. 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Pharm. Design PD NOV PY 2013 VL 19 IS 36 BP 6480 EP 6490 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 227YT UT WOS:000325152300008 PM 23432715 ER PT J AU Fanelli, F Marino, R Keller, F AF Fanelli, Francesca Marino, Ramona Keller, Flavio TI Focusing on the Interactions between the GABAergic System and Neurosteroids in Neurodevelopmental Disorders SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Brain sexual dimorphism; neurosteroids; neurodevelopmental disorders; GABA receptors; autism; synaptic plasticity; estrogen; androgen ID CA1 HIPPOCAMPAL SUBFIELD; OVARIECTOMIZED FEMALE RATS; NORMAL SEXUAL-DIMORPHISM; SPINE SYNAPSE FORMATION; GAD65 MESSENGER-RNA; NEUROACTIVE STEROIDS; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; BIPOLAR DISORDER; BASAL GANGLIA AB Neurosteroids play essential roles in the control of central nervous system functions during physiological and pathological conditions. Increasing evidences show gender differences in the pathogenesis and clinical manifestations of several neurodevelopmental conditions, including Autism Spectrum Disorders (ASD), possibly due to the action of sex hormones during critical periods of brain development. Furthermore, it is known that neuroactive steroids contribute to neuroprotection, spinogenesis, synaptogenesis, as well as to modulation of neuronal excitability via their interaction with GABA receptors. Dysfunctions of GABAergic signaling early in development lead to a severe excitation-inhibition unbalance in neuronal circuits, which may contribute to the pathophysiology of autism. In this review, we summarize recent data concerning the functional role of neurosteroids and their relationship with the GABAergic system, focusing on GABA-mediated neurotrasmission alterations characterizing some neurodevelopmental disorders. C1 [Fanelli, Francesca; Marino, Ramona; Keller, Flavio] Univ Campus Biomed, Lab Dev Neurosci & Neural Plast, I-00128 Rome, Italy. RP Keller, F (reprint author), Univ Campus Biomed, Lab Dev Neurosci & Neural Plast, Via Alvaro Portillo 21, I-00128 Rome, Italy. EM f.keller@unicampus.it FU Autism Speaks [4191]; MIUR [PRIN 2009P9CE2R] FX The preparation of this manuscript was partly supported by grants from Autism Speaks (4191) and MIUR (PRIN 2009P9CE2R) to F. K. 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CA NEAD Study Grp TI Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years SO EPILEPSY & BEHAVIOR LA English DT Article DE Antiepileptic drugs; Child development; Behavioral neurology; Epilepsy; Pregnancy; Valproate ID DEVELOPING RAT-BRAIN; SPECTRUM DISORDERS; OUTCOMES; CHILDREN; AUTISM; PREGNANCY; EPILEPSY AB The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6 years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System-Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more a typical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain. (C) 2013 Elsevier Inc. All rights reserved. C1 [Cohen, Morris J.] Georgia Regents Univ, Augusta, GA 30912 USA. [Meador, Kimford J.; Loring, David W.] Emory Univ, Atlanta, GA 30322 USA. [Browning, Nancy; May, Ryan] EMMES Corp, Rockville, MD USA. [Baker, Gus A.] Univ Liverpool, Walton Ctr Neurol & Neurosurg, Liverpool L69 3BX, Merseyside, England. [Clayton-Smith, Jill] St Marys Hosp, Manchester M13 0JH, Lancs, England. [Kalayjian, Laura A.] Univ So Calif, Los Angeles, CA USA. [Kanner, Andres] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Liporace, Joyce D.] Riddle Hlth Care, Media, PA USA. [Pennell, Page B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Privitera, Michael] Univ Cincinnati, Cincinnati, OH USA. RP Cohen, MJ (reprint author), Georgia Regents Univ, Childrens Med Ctr, Dept Neurol, BT-2601,1446 Harper St, Augusta, GA 30912 USA. EM mcohen@gru.edu FU National Institutes of Health [2RO1-NS038455, R01NS050659]; United Kingdom Epilepsy Research Foundation [RB219738] FX This work was supported by the National Institutes of Health [2RO1-NS038455 to K. M., R01NS050659 to N.B.] and the United Kingdom Epilepsy Research Foundation [RB219738 to G.B.]. 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Blue-Banning, Martha Haines, Shana TI Increasing the Social Skills of a Student With Autism Through a Literacy-Based Behavioral Intervention SO INTERVENTION IN SCHOOL AND CLINIC LA English DT Article DE autism; social skills; behavioral intervention ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; CHILDREN; STORIES AB Social skills instruction is as important for many students with disabilities as instruction in core academic subjects. Frequently, students with autism require individualized social skills instruction to experience success in general education settings. Literacy-based behavioral Interventions (LBBIs) are an effective intervention that instructors may use to increase positive social skills among students. This article describes LBBIs, provides step-by-step instructions for creating an LBBI, and describes the benefits of LBBIs. C1 [Francis, Grace L.; Blue-Banning, Martha; Haines, Shana] Univ Kansas, Lawrence, KS 66045 USA. [McMullen, Victoria B.] Webster Univ, St Louis, MO USA. RP Francis, GL (reprint author), Univ Kansas, 1200 Sunnyside Ave,3125 Haworth Hall, Lawrence, KS 66045 USA. EM glucyf@ku.edu CR Bucholz J. 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Sch. Clin. PD NOV PY 2013 VL 49 IS 2 BP 77 EP 83 DI 10.1177/1053451213493168 PG 7 WC Education, Special SC Education & Educational Research GA 225VX UT WOS:000324994200002 ER PT J AU Ghanizadeh, A AF Ghanizadeh, Ahmad TI Atomoxetine for Treating ADHD Symptoms in Autism: A Systematic Review SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; autism; atomoxetine; treatment ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; TOURETTE SYNDROME; EXTRACELLULAR LEVELS; PREFRONTAL CORTEX; OPEN-LABEL; CHILDREN; ADOLESCENTS; EFFICACY AB Objective: This study systematically reviews the current literature on the administration of atomoxetine for treating children and adolescents with comorbidity on autism spectrum disorder (ASD) and ADHD. Method: PubMed/Medline and Google Scholar databases were electronically searched to find the published trials on atomoxetine and ASD. Results: Six articles reported the clinical trials of atomoxetine for treatment of ADHD symptoms in patients with autism or pervasive development disorders. Only one study that was placebo-controlled crossover pilot trial reported that it is effective. Atomoxetine may be effective in high-functioning patients with autism or patients with low severity. Those with high severity of ASD may be more vulnerable to the adverse effects of atomoxetine. Conclusion: There are not enough controlled clinical trials for showing the efficacy of atomoxetine for treatment of ADHD symptoms in autism. Although evidence suggests potential efficacy of atomoxetine, the current evidences are not conclusive. C1 [Ghanizadeh, Ahmad] Shiraz Univ Med Sci, Sch Med, Hafez Hosp, Shiraz, Iran. RP Ghanizadeh, A (reprint author), Shiraz Univ Med Sci, Sch Med, Res Ctr Psychiat & Behav Sci, Hafez Hosp, Shiraz, Iran. 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Atten. Disord. PD NOV PY 2013 VL 17 IS 8 BP 635 EP 640 DI 10.1177/1087054712443154 PG 6 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA 231LZ UT WOS:000325419400001 PM 22544388 ER PT J AU Kenny, MC Bennett, KD Dougery, J Steele, F AF Kenny, Maureen C. Bennett, Kyle D. Dougery, Jonelle Steele, Francesca TI Teaching General Safety and Body Safety Training Skills to a Latino Preschool Male with Autism SO JOURNAL OF CHILD AND FAMILY STUDIES LA English DT Article DE Childhood sexual abuse prevention; Autism; Disabilities; Body safety training; Injuries ID SEXUAL-ABUSE PREVENTION; YOUNG-CHILDREN; MENTAL-RETARDATION; PROGRAM; DISABILITIES; PREVALENCE; PARENTS; INSTRUCTORS; DISORDERS; EDUCATION AB This case study describes the implementation of a safety training program with a 5-year-old Latino boy diagnosed with Autism Spectrum Disorder. The program focused on teaching him general safety rules and body safety in an effort to reduce his likelihood of sexual victimization and injury. The boy was treated in conjunction with another child by two therapists, while his caretakers participated in a caretaker group. Both groups consisted of 10 h of safety education instruction. Results show that the boy was able to learn a few safety concepts as well as increase his knowledge of personal safety. Caregiver data revealed a minor increase in knowledge of general safety and an increase in family communication regarding safety issues. However, upon a 3-month follow-up, the boy appeared to lose some knowledge. Recommendations for implementing the Body Safety Training program with children with disabilities and providing their caretakers with information regarding the risk of child sexual abuse is provided. C1 [Kenny, Maureen C.; Bennett, Kyle D.; Dougery, Jonelle; Steele, Francesca] Florida Int Univ, Coll Educ, Miami, FL 33199 USA. 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PD NOV PY 2013 VL 22 IS 8 BP 1092 EP 1102 DI 10.1007/s10826-012-9671-4 PG 11 WC Family Studies; Psychology, Developmental; Psychiatry SC Family Studies; Psychology; Psychiatry GA 229FP UT WOS:000325247500007 ER PT J AU Carr, A AF Carr, Alan TI Thematic review of Family Therapy Journals 2012 SO JOURNAL OF FAMILY THERAPY LA English DT Article ID INTIMATE PARTNER VIOLENCE; EMOTIONALLY FOCUSED THERAPY; RANDOMIZED CONTROLLED-TRIAL; COUPLE-BASED INTERVENTIONS; MENTAL-HEALTH RECOVERY; TREATMENT FOSTER-CARE; RELATIONSHIP EDUCATION; COMMON FACTORS; MULTISYSTEMIC THERAPY; FUTURE-DIRECTIONS AB In this article the contents of the principal English-language family therapy journals, and key family therapy articles published in other journals in 2012 are reviewed under these headings: therapy processes in the treatment of child-focused problems, autism, adolescent substance use, human immunodeficiency virus, depression and grief, fragile families, mental health recovery, medical family therapy, family business and systemic practice, couple therapy, intimate partner violence, key issues in theory and practice, research, diversity, international perspectives, interviews, and deaths. C1 Univ Coll Dublin, Sch Psychol, Dublin 4, Ireland. RP Carr, A (reprint author), Univ Coll Dublin, Sch Psychol, Newman Bldg, Dublin 4, Ireland. 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SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; CYP1A2; melatonin; polymorphism; poor metaboliser ID CAFFEINE URINARY METABOLITES; PLACEBO-CONTROLLED TRIAL; SLEEP-ONSET INSOMNIA; INTELLECTUAL DISABILITY; EXOGENOUS MELATONIN; CYTOCHROME-P450 1A2; CHILDREN; GENE; EXPRESSION; HUMANS AB Background In some of our patients with intellectual disabilities (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment. In these patients melatonin levels at noon were extremely high (>50pg/ml). We hypothesise that the disappearing effectiveness is associated with slow metabolisation of melatonin because of a single nucleotide polymorphism (SNP) of CYP1A2. Method In this pilot study we analysed DNA extracted from saliva samples of 15 consecutive patients with disappearing effectiveness of melatonin. Saliva was collected at noon and 4 pm for measuring melatonin levels. Results In all patients' salivary melatonin levels at noon were >50 or melatonin half time was >5h. A SNP was found in eight of 15 patients. The allele *1C was found in two patients and in six patients the *1F allele was found. Conclusions Of 15 patients with disappearing effectiveness of melatonin, seven were diagnosed with autism spectrum disorder, and in four of them a SNP was found. The other eight patients were known with a genetic syndrome. In six of them behaviour was considered to be autistic-type and in three of them a SNP was found. This finding may give a new direction for research into the genetic background of autism. C1 [Braam, W.] S Heeren Loo Zuid Veluwe, Dept Advisium, Wekerom, Netherlands. [Keijzer, H.] Rijnstate Hosp, Dept Clin Chem, Arnhem, Netherlands. [Boudier, H. Struijker] Maastricht Univ, Dept Pharmacol & Toxicol, Maastricht, Netherlands. [Didden, R.] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands. 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Intell. Disabil. Res. PD NOV PY 2013 VL 57 IS 11 BP 993 EP 1000 DI 10.1111/j.1365-2788.2012.01595.x PG 8 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 224VV UT WOS:000324920100001 PM 22823064 ER PT J AU Cascio, C Gribbin, M Gouttard, S Smith, RG Jomier, M Field, S Graves, M Hazlett, HC Muller, K Gerig, G Piven, J AF Cascio, C. Gribbin, M. Gouttard, S. Smith, R. G. Jomier, M. Field, S. Graves, M. Hazlett, H. C. Muller, K. Gerig, G. Piven, J. TI Fractional anisotropy distributions in 2-to 6-year-old children with autism SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; brain; developmental; diffusion tensor imaging; fractional anisotropy; white matter ID VOXEL-BASED MORPHOMETRY; WHITE-MATTER; SPECTRUM DISORDER; SPATIAL-STATISTICS; ASPERGER-SYNDROME; CORPUS-CALLOSUM; FRONTAL-CORTEX; YOUNG-CHILDREN; DIFFUSION; BRAIN AB Background Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. Methods A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating , the estimated mean and standard deviation of the approximating F for each distribution. Results The estimated delta parameter, delta d, was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of delta d across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of delta was the driving force behind these results. Conclusions While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition. C1 [Cascio, C.] Vanderbilt Univ, Nashville, TN 37235 USA. [Cascio, C.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37235 USA. [Gribbin, M.] Human Genome Sci, Dept Biostat, Rockville, MD USA. [Gouttard, S.] Univ Utah, Dept Comp Sci, Salt Lake City, UT 84112 USA. [Smith, R. G.; Graves, M.; Hazlett, H. C.; Piven, J.] Univ N Carolina, Psychiat Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Jomier, M.] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA. [Field, S.] Univ N Carolina, Frank Porter Graham Child Dev Ctr, Chapel Hill, NC USA. [Muller, K.] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. RP Piven, J (reprint author), Univ N Carolina, Psychiat Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. 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Intell. Disabil. Res. PD NOV PY 2013 VL 57 IS 11 BP 1037 EP 1049 DI 10.1111/j.1365-2788.2012.01599.x PG 13 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 224VV UT WOS:000324920100005 PM 22998325 ER PT J AU Vemuri, M AF Vemuri, Murali TI Autism Spectrum Disorders Through the Life Span SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Book Review C1 [Vemuri, Murali] Brooklands Hosp, New York, NY USA. RP Vemuri, M (reprint author), Brooklands Hosp, New York, NY USA. CR Deb S, 2009, WORLD PSYCHIATRY, V8, P181 TANTAM D, 2012, AUTISM SPECTRUM DISO NR 2 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD NOV PY 2013 VL 57 IS 11 BP 1088 EP 1090 DI 10.1111/j.1365-2788.2012.01622.x PG 3 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 224VV UT WOS:000324920100010 ER PT J AU Richman, DM Barnard-Brak, L Bosch, A Thompson, S Grubb, L Abby, L AF Richman, D. M. Barnard-Brak, L. Bosch, A. Thompson, S. Grubb, L. Abby, L. TI Predictors of self-injurious behaviour exhibited by individuals with autism spectrum disorder (vol 57, pg 429, 2013) SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Correction CR Richman DM, 2013, J INTELL DISABIL RES, V57, P429, DOI 10.1111/j.1365-2788.2012.01628.x NR 1 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD NOV PY 2013 VL 57 IS 11 BP 1091 EP 1091 DI 10.1111/jir.12094 PG 1 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 224VV UT WOS:000324920100011 ER PT J AU Mechling, LC Swindle, CO AF Mechling, Linda C. Swindle, Catherine O. TI Fine and Gross Motor Task Performance When Using Computer-Based Video Models by Students With Autism and Moderate Intellectual Disability SO JOURNAL OF SPECIAL EDUCATION LA English DT Article DE video modeling; fine motor; gross motor; autism spectrum disorders; moderate intellectual disability ID OF-THE-LITERATURE; SPECTRUM DISORDERS; CHILDREN; INTERVENTION; INDIVIDUALS; INSTRUCTION; SKILLS AB This investigation examined the effects of video modeling on the fine and gross motor task performance by three students with a diagnosis of moderate intellectual disability (Group 1) and by three students with a diagnosis of autism spectrum disorder (Group 2). Using a multiple probe design across three sets of tasks, the study examined the effectiveness of video modeling across differing types of motor response requirements (fine and gross motor) and whether effects would differ across disability groups. Results indicate an increase in the number of fine and gross motor tasks correctly performed following the introduction of video modeling. As a whole, students across both groups performed more gross motor than fine motor tasks independently correct and students in Group 1 performed more tasks independently correct than those in Group 2. Implications are discussed concerning evaluation of task requirements and the development of video models. C1 [Mechling, Linda C.; Swindle, Catherine O.] Univ N Carolina, Wilmington, NC 28403 USA. RP Mechling, LC (reprint author), Univ N Carolina, Dept Early Childhood & Special Educ, 601 S Coll Rd, Wilmington, NC 28403 USA. EM mechlingl@uncw.edu CR ALCANTARA PR, 1994, EXCEPT CHILDREN, V61, P40 Ayres Kevin M., 2007, Journal of Special Education Technology, V22 Ayres KM, 2005, EDUC TRAIN DEV DISAB, V40, P183 Bellini S, 2007, EXCEPT CHILDREN, V73, P264 BILLINGSLEY F, 1980, BEHAV ASSESS, V2, P229 Cihak David F, 2008, Journal of Special Education Technology, V23 Delano ME, 2007, REM SPEC EDUC, V28, P33, DOI 10.1177/07419325070280010401 Gast D. L., 2010, SINGLE SUBJECT RES M, P276 Hammond DL, 2010, EDUC TRAIN AUTISM DE, V45, P525 Hermansen E, 2007, ED TREATMENT CHILDRE, V30, P183, DOI DOI 10.1353/ETC.2007.0029 Hitchcock CH, 2003, REM SPEC EDUC, V24, P36, DOI 10.1177/074193250302400104 Kaufman A. S., 1993, KAUFMAN ACAD LANGUAG Mechling L., 2005, Journal of Special Education Technology, V20 Mechling L. C., 2011, TASK PERFORMAN UNPUB Mechling LC, 2009, EDUC TRAIN DEV DISAB, V44, P67 Mechling LC, 2003, EDUC TRAIN MENT RET, V38, P62 Murzynski NT, 2007, BEHAV INTERVENT, V22, P147, DOI 10.1002/bin.224 Qu XL, 2008, NEURAL REGEN RES, V3, P341 Rayner C, 2009, RES AUTISM SPECT DIS, V3, P291, DOI 10.1016/j.rasd.2008.09.001 Seitz J, 2006, NEUROPEDIATRICS, V37, P6, DOI 10.1055/s-2006-923840 Shipley-Benamou R, 2002, J POSIT BEHAV INTERV, V4, P165 Shukla-Mehta S, 2010, FOCUS AUTISM DEV DIS, V25, P23, DOI 10.1177/1088357609352901 Taber-Doughty Teresa, 2008, Journal of Special Education Technology, V23 Van Laarhoven T., 2007, ASSIST TECHNOL, V14, P28 NR 24 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-4669 J9 J SPEC EDUC JI J. Spec. Educ. PD NOV PY 2013 VL 47 IS 3 BP 135 EP 147 DI 10.1177/0022466911433859 PG 13 WC Education, Special SC Education & Educational Research GA 227SG UT WOS:000325133800001 ER PT J AU Cho, HJ Kingston, N AF Cho, Hyun-Jeong Kingston, Neal TI Why IEP Teams Assign Low Performers With Mild Disabilities to the Alternate Assessment Based on Alternate Achievement Standards SO JOURNAL OF SPECIAL EDUCATION LA English DT Article DE alternate assessment based on alternate achievement standards; test-type misassignment; eligibility guidelines; accountability system; significant cognitive disability; IEP team ID MENTALLY-RETARDED CHILDREN; INTELLECTUAL DISABILITY; ACTIVE EPILEPSY; STUDENTS; AUTISM; DIAGNOSIS; ACCOMMODATIONS; PARTICIPATION; INTERVENTIONS; RETARDATION AB The purpose of this case study was to determine teachers' rationales for assigning students with mild disabilities to alternate assessment based on alternate achievement standards (AA-AAS). In interviews, special educators stated that their primary considerations in making the assignments were low academic performance, student use of extended standard modifications, and the inflexible 1% cap. None of the teachers provided their students with grade-level content or appropriate modifications. Some students were competent in grade-level reading, but were assigned to the 2010 AA-AAS because read-aloud accommodation is not permitted in the reading passages of the general assessment. Findings raised concerns about the susceptibility of eligibility guidelines to lead to subjective decisions. Future research, implications of these findings, and limitations of the study are discussed. C1 [Cho, Hyun-Jeong; Kingston, Neal] Univ Kansas, Lawrence, KS 66047 USA. RP Cho, HJ (reprint author), Univ Kansas, Ctr Educ Testing & Evaluat, 1122 West Campus Rd,735 Joseph R Pearson Hall, Lawrence, KS 66047 USA. EM chohj@ku.edu CR American Association on Intellectual and Developmental Disabilities, 2010, INTELLECTUAL DISABIL American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Cascella PW, 1999, CHILD ADOL PSYCH CL, V8, P61 Cho H.-J., 2011, EXAMINING IEP TEAM D Cho HJ, 2011, EXCEPT CHILDREN, V78, P58 Creswell JW, 2007, COUNS PSYCHOL, V35, P236, DOI 10.1177/0011000006287390 Destefano L, 2001, EXCEPT CHILDREN, V68, P7 Dominick KC, 2007, RES DEV DISABIL, V28, P145, DOI 10.1016/j.ridd.2006.02.003 Ferrell Richard B, 2004, Curr Psychiatry Rep, V6, P380, DOI 10.1007/s11920-004-0025-9 Filbin J., 2008, LESSONS INITIAL PEER Fuller CG, 1998, J CLIN PSYCHOL, V54, P1, DOI 10.1002/(SICI)1097-4679(199801)54:1<1::AID-JCLP1>3.0.CO;2-X Helwig R, 2003, EXCEPT CHILDREN, V69, P211 Horner RH, 2002, J AUTISM DEV DISORD, V32, P423, DOI 10.1023/A:1020593922901 Jansen DEMC, 2004, J INTELL DISABIL RES, V48, P93, DOI 10.1111/j.1365-2788.2004.00483.x Kearns JF, 2011, J SPEC EDUC, V45, P3, DOI 10.1177/0022466909344223 Ketterlin-Geller LR, 2007, REM SPEC EDUC, V28, P194, DOI 10.1177/07419325070280040101 Ketterlin-Geller LR, 2007, EXCEPT CHILDREN, V73, P331 Marshall C., 2006, DESIGNING QUALITATIV, V4th McBrien JA, 2003, J INTELL DISABIL RES, V47, P1, DOI 10.1046/j.1365-2788.2003.00455.x Merriam S. 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L., 2007, NO CHILD LEFT BEHIND, V22, P39 Towles-Reeves E, 2009, J SPEC EDUC, V42, P241, DOI 10.1177/0022466907313451 Tsatsanis KD, 2003, BIOL PSYCHIAT, V53, P121, DOI 10.1016/S0006-3223(02)01530-5 U.S. Department of Education, 2005, ALT ACH STAND STUD M U.S. Department of Education, 2007, ADD TITL 1 PROV INCL Yin R. K, 2003, CASE STUDY RES DESIG NR 39 TC 3 Z9 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-4669 J9 J SPEC EDUC JI J. Spec. Educ. PD NOV PY 2013 VL 47 IS 3 BP 162 EP 174 DI 10.1177/0022466911435416 PG 13 WC Education, Special SC Education & Educational Research GA 227SG UT WOS:000325133800003 ER PT J AU Hodgetts, S Nicholas, D Zwaigenbaum, L McConnell, D AF Hodgetts, Sandra Nicholas, David Zwaigenbaum, Lonnie McConnell, David TI Parents' and professionals' perceptions of family-centered care for children with autism spectrum disorder across service sectors SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Autism; Family-centered care; Services; Lifespan; Access; Canada AB Family-centered care (FCC) has been linked with improved parent and child outcomes, yet its implementation can be challenging due to family, professional, organizational and systemic factors and policies. This study aims to increase knowledge and understanding of how families with children with autism spectrum disorder (ASD) experience FCC in Alberta, Canada. 152 parents with a child with ASD completed the Measure of Processes of Care, separately for each utilized service sector, and 146 professionals working with persons with ASD completed the Measure of Processes of Care Service Providers. Additionally, in-depth interviews were conducted with a sub-sample of 19 parents, purposefully sampled for diversity in child and family characteristics. Data were collected in 2011. Descriptive and inferential statistics were used to analyze quantitative data. Interview transcripts were analyzed using grounded theory constant comparison methods, yielding a data generated theoretical model depicting families' experiences with FCC over time and across service sectors. There were no statistically significant differences in FCC scores across service sectors, but statistically significant differences in FCC scores between parents' and professionals' were found. Qualitative data revealed positive experiences and perceptions of receiving FCC from professionals "on the ground" across sectors, but negative experiences and perceptions of FCC at the systems level (i.e., administration, funders). These broad experiences emerged as a core theme "System of Exclusion", which integrated the key themes: (1) "The Fight", (2) "Roles and Restrictions of Care", and (3) "Therapeutic Rapport". Professionals and service providers can use findings to ensure that services reflect current conceptualizations of FCC, and decision and policy makers can use findings to recognize systemic barriers to implementing FCC and inform policy change. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hodgetts, Sandra; McConnell, David] Univ Alberta, Dept Occupat Therapy, Edmonton, AB T6G 2G4, Canada. [Nicholas, David] Univ Calgary Edmonton Reg, Fac Social Work, Edmonton, AB, Canada. [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2G4, Canada. RP Hodgetts, S (reprint author), Univ Alberta, Dept Occupat Therapy, 2-64 Corbett Hall, Edmonton, AB T6G 2G4, Canada. EM sandra.hodgetts@ualberta.ca FU Alberta Centre for Child, Family and Community Research (ACCFCR) FX We thank the parents for taking the time in their busy lives to participate in this study, and the Autism Clinic at the Glenrose Rehabilitation Hospital, Autism Society of Edmonton and Area, Autism Calgary Association, and Foothills SNAPS for their assistance with participant recruitment. This study was supported by a grant from the Alberta Centre for Child, Family and Community Research (ACCFCR). Sandra Hodgetts was a Postdoctoral trainee in the CIHR Canadian Child Health Clinician Scientist Training Program. CR American Psychiatric Association, 1994, DIAGN STAT MAN MENT, VIV Beatson JE, 2008, TOP LANG DISORD, V28, P309 Blackmore A. 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PD NOV PY 2013 VL 96 SI SI BP 138 EP 146 DI 10.1016/j.socscimed.2013.07.012 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 225LN UT WOS:000324964500017 PM 24034961 ER PT J AU Katz, E Girolametto, L AF Katz, Esther Girolametto, Luigi TI Peer-Mediated Intervention for Preschoolers With ASD Implemented in Early Childhood Education Settings SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE peer interactions; autism spectrum disorder; preschoolers; peer-mediated intervention; single-subject design ID AUTISM SPECTRUM DISORDERS; YOUNG-CHILDREN; SOCIAL-SKILLS; COMMUNICATION INTERVENTION; DISABILITIES; VALIDITY; ISSUES; PLAY; COMPETENCE; CONCURRENT AB The purpose of this study was to investigate the effects of peer intervention on the social interactions of children with autism spectrum disorder (ASD). 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Early Child. Spec. Educ. PD NOV PY 2013 VL 33 IS 3 BP 144 EP 152 DI 10.1177/0271121412446204 PG 9 WC Education, Special SC Education & Educational Research GA 227SM UT WOS:000325134600004 ER PT J AU Pizur-Barnekow, K Muusz, M McKenna, C O'Connor, E Cutler, A AF Pizur-Barnekow, Kris Muusz, Marta McKenna, Catherine O'Connor, Emily Cutler, Ann TI Service Coordinators' Perceptions of Autism-Specific Screening and Referral Practices in Early Intervention SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE screening; assessment; autism spectrum disorder (ASD); disability populations; personnel; survey methodologies; descriptive studies; research methodologies ID SPECTRUM DISORDERS; YOUNG-CHILDREN; DEVELOPMENTAL DISORDERS; MODIFIED CHECKLIST; IDENTIFICATION; SURVEILLANCE; DIAGNOSIS; TODDLERS AB Service coordinators in a statewide early intervention program were surveyed to develop an understanding of screening and referral practices to identify children on the autism spectrum. Quantitative and qualitative data summarizing autism-specific screening and referral practices are reported. More than 50% of the respondents reported that they had never received a referral from a physician or another early intervention provider because a child has failed an autism-specific screening. While service coordinators identified that early intervention providers have a role in conducting autism-specific screening, more than 50% of the respondents indicated that they do not see autism-specific screening completed in early intervention settings. More than 80% of the respondents identified a lack of knowledge as the most significant barrier to autism-specific screening. Together, these findings suggest that early intervention providers may benefit from professional development that imparts knowledge, teaches skills, and addresses potential concerns of parents related to autism. C1 [Pizur-Barnekow, Kris] Univ Wisconsin, Milwaukee, WI 53221 USA. [Muusz, Marta; McKenna, Catherine; O'Connor, Emily; Cutler, Ann] Univ Illinois, Chicago, IL USA. RP Pizur-Barnekow, K (reprint author), Univ Wisconsin, Dept Occupat Sci & Technol, Milwaukee, WI 53221 USA. EM krisb@uwm.edu CR Al-Qabandi M, 2011, PEDIATRICS, V128, pE211, DOI 10.1542/peds.2010-1881 CDC, 2012, MMWR SURVEILL SUMM, V61, P1 Centers for Disease Control and Prevention, 2009, MMWR-MORBID MORTAL W, V58, P1 Duby JC, 2006, PEDIATRICS, V118, P405, DOI 10.1542/peds.2006-1231 Dawson G, 2010, PEDIATRICS, V125, pE17, DOI 10.1542/peds.2009-0958 Dosreis S, 2006, J DEV BEHAV PEDIATR, V27, pS88, DOI 10.1097/00004703-200604002-00006 Dumont-Mathieu T, 2005, MENT RETARD DEV D R, V11, P253, DOI 10.1002/mrdd.20072 Filipek PA, 2000, NEUROLOGY, V55, P468 Fowler F. 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A., 2012, DIAGNOSTIC HIST TREA Robins D., 1999, MODIFIED CHECKLIST A Robins DL, 2001, J AUTISM DEV DISORD, V31, P131, DOI 10.1023/A:1010738829569 Robins DL, 2008, AUTISM, V12, P537, DOI 10.1177/1362361308094502 Self Trisha L, 2010, J Allied Health, V39, P165 Shattuck PT, 2009, J AM ACAD CHILD PSY, V48, P474, DOI 10.1097/CHI.0b013e31819b3848 Siegel B., 2011, PERVASIVE DEV DISORD Stahmer AC, 2007, ADM POLICY MENT HLTH, V34, P29, DOI 10.1007/s10488-006-0060-4 Virues-Ortega J, 2010, CLIN PSYCHOL REV, V30, P387, DOI 10.1016/j.cpr.2010.01.008 Wetherby AM, 2002, COMMUNICATION SYMBOL NR 23 TC 0 Z9 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-1214 J9 TOP EARLY CHILD SPEC JI Top. Early Child. Spec. Educ. PD NOV PY 2013 VL 33 IS 3 BP 153 EP 161 DI 10.1177/0271121412463086 PG 9 WC Education, Special SC Education & Educational Research GA 227SM UT WOS:000325134600005 ER PT J AU Jeans, LM Santos, RM Laxman, DJ McBride, BA Dyer, WJ AF Jeans, Laurie M. Santos, Rosa Milagros Laxman, Daniel J. McBride, Brent A. Dyer, W. Justin TI Examining ECLS-B: Maternal Stress and Depressive Symptoms When Raising Children With ASD SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE Autism Spectrum Disorder; maternal stress; depression; ECLS-B ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; PARENTING STRESS; PRESCHOOL-CHILDREN; MENTAL-HEALTH; BEHAVIOR PROBLEMS; SOCIAL SUPPORT; DOWN-SYNDROME; MOTHERS; TODDLERS AB Using the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B), a nationally representative data set, we examined the extent to which mothers of preschool children with and without the diagnosis of an Autism Spectrum Disorder (ASD) reported stress and depressive symptoms prior to and following diagnosis of ASD. At 4 years, approximately 100 children were parent-identified as diagnosed with ASD. Mothers of children with ASD at 9 months and 4 years had significantly higher incidence of depressive symptoms and stress than mothers of typically developing children. Mothers of children with ASD experienced higher levels of depressive symptoms than mothers of children with disabilities, but the difference was not statistically significant. Using linear regression, a within-group comparison of depressive symptoms of mothers of children with ASD indicated no differences based on child gender, ethnicity, number of children in the family, or partnership status. Implications are presented. C1 [Jeans, Laurie M.; Santos, Rosa Milagros; Laxman, Daniel J.; McBride, Brent A.] Univ Illinois, Urbana, IL 61801 USA. [Dyer, W. Justin] Brigham Young Univ, Provo, UT 84602 USA. RP Jeans, LM (reprint author), Univ Illinois, 1310 South 6th St,MC 288, Champaign, IL 61820 USA. EM ljeans2@illinois.edu CR Abidin R, 1990, PARENTING STRESS IND Baker-Ericzen MJ, 2005, RES PRACT PERS SEV D, V30, P194, DOI 10.2511/rpsd.30.4.194 Boyd B. 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Early Child. Spec. Educ. PD NOV PY 2013 VL 33 IS 3 BP 162 EP 171 DI 10.1177/0271121413481680 PG 10 WC Education, Special SC Education & Educational Research GA 227SM UT WOS:000325134600006 ER PT J AU McDuffie, A Machalicek, W Oakes, A Haebig, E Weismer, SE Abbeduto, L AF McDuffie, Andrea Machalicek, Wendy Oakes, Ashley Haebig, Eileen Weismer, Susan Ellis Abbeduto, Leonard TI Distance Video-Teleconferencing in Early Intervention: Pilot Study of a Naturalistic Parent-Implemented Language Intervention SO TOPICS IN EARLY CHILDHOOD SPECIAL EDUCATION LA English DT Article DE parent-child interaction; autism spectrum disorder; language; communication intervention; parent education; naturalistic; video-teleconference ID VERBAL RESPONSIVENESS; YOUNG-CHILDREN; AUTISM; COMMUNICATION; PRESCHOOLERS; ACQUISITION; STRATEGIES; PREDICT AB Maternal verbal responsiveness in naturally occurring interactions is known to facilitate language development for children with neurodevelopmental disorders. The present study used a series of A-B replications to examine proximal effects of a naturalistic language intervention on the use of specific language support strategies by mothers of eight young children with an autism spectrum disorder (ASD). Distal effects on child communication also were examined. The intervention consisted of four monthly parent education lessons, each paired with face-to-face clinician coaching of a play-based parent-child interaction. In addition, 12 distance coaching sessions were implemented via desktop video-teleconferencing (VTC). Parents increased their use of verbal responses that followed into their child's focus of attention and responded to child communication acts. Parents also increased the frequency with which they prompted child communication. Increases in parent strategy use were observed during both on-site and distance coaching sessions. Implications for future research are discussed. 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Early Child. Spec. Educ. PD NOV PY 2013 VL 33 IS 3 BP 172 EP 185 DI 10.1177/0271121413476348 PG 14 WC Education, Special SC Education & Educational Research GA 227SM UT WOS:000325134600007 ER PT J AU Wang, JP Qin, W Liu, B Wang, DW Zhang, YT Jiang, TZ Yu, CS AF Wang, Junping Qin, Wen Liu, Bing Wang, Dawei Zhang, Yunting Jiang, Tianzi Yu, Chunshui TI Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects SO NEUROIMAGE LA English DT Article DE Oxytocin receptor; Single nucleotide polymorphism; Autism; Hypothalamus; Functional connectivity ID AUTISM SPECTRUM DISORDERS; OXYTOCIN RECEPTOR OXTR; VASOPRESSIN; MRI; THERAPEUTICS; ASSOCIATION; POPULATION; BEHAVIOR; MATTER; MEMORY AB The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wang, Junping; Qin, Wen; Wang, Dawei; Zhang, Yunting; Yu, Chunshui] Tianjin Med Univ, Gen Hosp, Dept Radiol, Tianjin 300052, Peoples R China. [Liu, Bing; Jiang, Tianzi] Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, LIAMA Ctr Computat Med, Beijing 100190, Peoples R China. RP Jiang, TZ (reprint author), Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China. EM jiangtz@nlpr.ia.ac.cn; chunshuiyu@yahoo.cn RI Liu, Bing/C-5758-2014; Jiang, Tianzi/I-4256-2012 FU Natural Science Foundation of China [81271551]; National Basic Research Program of China (973 Program) [2011CB707801]; International Cooperation and Exchanges NSFC [81061120533] FX This work was supported by the Natural Science Foundation of China (No. 81271551), the National Basic Research Program of China (973 Program, No. 2011CB707801), and the International Cooperation and Exchanges NSFC (No. 81061120533). 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PD OCT 30 PY 2013 VL 5 IS 209 AR 209ed18 DI 10.1126/scitranslmed.3007340 PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 245YR UT WOS:000326501700001 PM 24174324 ER PT J AU McCarroll, SA Hyman, SE AF McCarroll, Steven A. Hyman, Steven E. TI Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology SO NEURON LA English DT Review ID DE-NOVO MUTATIONS; AUTISM SPECTRUM DISORDERS; RETT-SYNDROME; HUMAN GENOME; INTELLECTUAL DISABILITY; PSYCHIATRIC-DISORDERS; POPULATION-SCALE; BIPOLAR DISORDER; COMMON SNPS; RISK LOCI AB Advances in genome analysis, accompanied by the assembly of large patient cohorts, are making possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders. C1 [McCarroll, Steven A.; Hyman, Steven E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02141 USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Hyman, Steven E.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP McCarroll, SA (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02141 USA. EM mccarroll@genetics.med.harvard.edu; seh@harvard.edu FU Stanley Medical Research Institute; NIH [R01 HG006855] FX This work was made possible by funding from the Stanley Medical Research Institute and by NIH grant R01 HG006855 to S.A.M. We also thank Janet Theurer and Pat Rossi for the artwork. S.E.H. discloses that he serves on the Novartis Science Board and has advised AstraZeneca. 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Doherty, James J. Robichaud, Albert J. Belfort, Gabriel M. Chow, Brian Y. Hammond, Rebecca S. Crawford, Devon C. Linsenbardt, Andrew J. Shu, Hong-Jin Izumi, Yukitoshi Mennerick, Steven J. Zorumski, Charles F. TI The Major Brain Cholesterol Metabolite 24(S)-Hydroxycholesterol Is a Potent Allosteric Modulator of N-Methyl-D-Aspartate Receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; PREGNENOLONE SULFATE; NMDA RECEPTORS; HIPPOCAMPAL-NEURONS; SYNAPTIC TRANSMISSION; GABA(A) RECEPTOR; MOUSE-BRAIN; IN-VITRO; STEROIDS; RAT AB N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABA(A) receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations <= 10 mu M. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development. C1 [Paul, Steven M.; Doherty, James J.; Robichaud, Albert J.; Belfort, Gabriel M.; Chow, Brian Y.; Hammond, Rebecca S.] Sage Therapeut, Cambridge, MA 02142 USA. [Paul, Steven M.] Weill Cornell Med Coll, Dept Psychiat, Brain & Mind Res Inst, Appel Alzheimers Dis Res Inst, New York, NY 10065 USA. [Paul, Steven M.] Weill Cornell Med Coll, Dept Pharmacol, Brain & Mind Res Inst, Appel Alzheimers Dis Res Inst, New York, NY 10065 USA. [Crawford, Devon C.; Linsenbardt, Andrew J.; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J.; Zorumski, Charles F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Crawford, Devon C.; Linsenbardt, Andrew J.; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J.; Zorumski, Charles F.] Washington Univ, Sch Med, Taylor Family Inst Innovat Psychiat Res, St Louis, MO 63110 USA. RP Paul, SM (reprint author), Cornell Univ, Weill Cornell Med Coll, Brain & Mind Res Inst, Appel Alzheimers Dis Res Inst, 1300 York Ave, New York, NY 10065 USA. EM smpaulmd@med.cornell.edu FU Sage Therapeutics; National Institutes of Health [MH078823, MH077791, GM47969, AA017413]; Bantly Foundation FX This work was supported by Sage Therapeutics and National Institutes of Health Grants MH078823, MH077791, GM47969, and AA017413, and the Bantly Foundation. We thank J.C. Dodart, Frank Salituro, Gabriel Botella, Kiran Reddy, Carlos Loya, Ann Benz, and Amanda Taylor for their technical support and suggestions. 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Neurosci. PD OCT 30 PY 2013 VL 33 IS 44 BP 17290 EP 17300 DI 10.1523/JNEUROSCI.2619-13.2013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 246BB UT WOS:000326509800007 PM 24174662 ER PT J AU Guariglia, SR Chadman, KK AF Guariglia, Sara Rose Chadman, Kathryn K. TI Water T-maze: A useful assay for determination of repetitive behaviors in mice SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Reversal learning; Water T-maze; Repetitive behavior; Autism; BTBR T(+)tf/J ID AUTISTIC-LIKE BEHAVIORS; TF/J MOUSE MODEL; PLUS TF/J; REVERSAL; CHILDREN; STRAINS; HIPPOCAMPAL; DYSFUNCTION; PHENOTYPES; C57BL/6J AB Background: Repetitive behavior is a term used to describe a wide variety of invariant and inappropriate behaviors that occur in many diverse conditions, including autism. It is necessary to utilize and/or design rodent behavioral assays that exploit individual types of repetitive behavior so that underlying pathology and therapeutic measures can be determined. A variety of high-throughput assays to investigate lower order repetitive behaviors are available for rodents, whereas, fewer assays are available to investigate higher order repetitive behaviors, such as perseverative behavior. BTBR T(+)tf/J (BTBR) mice, harbor behavioral deficits that share similarity to the core deficits found in autism, yet have not conclusively demonstrated deficits in conventional reversal learning tasks (i.e. Morris water maze (MWM), T-maze) which are typically used to examine perseverance. New method: By combining elements of both the MWM and T-maze, we designed a water T-maze assay to determine if perseverative behavior could become perceptible in BTBR mice. Results: We found that BTBR mice show a significant impairment in reversal learning as compared to C57BL/6J (B6) mice in our water-T-maze reversal learning assay. 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Although most neuroimaging studies in ASD have been designed to identify commonalities among affected individuals, rather than differences, some studies have explored variation within ASD. There have been two general types of approaches used for this in the neuroimaging literature to date: comparison of subgroups within ASD, and analyses using dimensional measures to link clinical variation to brain differences. This review focuses on structural and functional magnetic resonance imaging studies that have used these approaches to begin to explore heterogeneity between individuals with ASD. Although this type of data is yet sparse, recognition is growing of the limitations of behaviorally defined categorical diagnoses for understanding neurobiology. Study designs that are more informative regarding the sources of heterogeneity in ASD have the potential to improve our understanding of the neurobiological processes underlying ASD. C1 [Lenroot, Rhoshel K.; Yeung, Pui Ka] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Lenroot, Rhoshel K.; Yeung, Pui Ka] Neurosci Res Australia, Sydney, NSW 2031, Australia. RP Lenroot, RK (reprint author), Neurosci Res Australia, Hosp Rd, Sydney, NSW 2031, Australia. 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Hum. Neurosci. PD OCT 30 PY 2013 VL 7 AR 733 DI 10.3389/fnhum.2013.00733 PG 16 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 242UU UT WOS:000326269100001 PM 24198778 ER PT J AU Tuchman, R Hirtz, D Mamounas, LA AF Tuchman, Roberto Hirtz, Deborah Mamounas, Laura A. TI NINDS epilepsy and autism spectrum disorders workshop report SO NEUROLOGY LA English DT Review ID FRAGILE-X-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; TARGETED TREATMENT TRIALS; RETT-SYNDROME; INTELLECTUAL DISABILITY; CHILDREN; BRAIN; DYSFUNCTION; SEIZURES; MECP2 AB The association of epilepsy and autism spectrum disorders (ASD), although well-recognized, is poorly understood. The purpose of this report is to summarize the discussion of a workshop sponsored by the National Institute of Neurological Disorders and Stroke, with support from the National Institute of Child Health and Human Development, Autism Speaks, and Citizens United for Research in Epilepsy, that took place in Bethesda, Maryland, on May 29 and 30, 2012. The goals of this workshop were to highlight the clinical and biological relationships between ASD and epilepsy, to determine both short- and long-term goals that address research and treatment conundrums in individuals with both ASD and epilepsy, and to identify resources that can further both clinical and basic research. Topics discussed included epidemiology, genetics, environmental factors, common mechanisms, neuroimaging, neuropathology, neurophysiology, treatment, and research gaps and challenges in this unique population. C1 [Tuchman, Roberto] Miami Childrens Hosp Dan Marino Ctr, Dept Neurol, Weston, FL 33331 USA. [Hirtz, Deborah; Mamounas, Laura A.] NINDS, NIH, Bethesda, MD 20892 USA. RP Tuchman, R (reprint author), Miami Childrens Hosp Dan Marino Ctr, Dept Neurol, Weston, FL 33331 USA. 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Green, Peter H. R. Hellberg, Dan Higgins, Joseph J. Rajadhyaksha, Anjali M. Alaedini, Armin TI LACK OF ASSOCIATION BETWEEN AUTISM AND ANTI-GM1 GANGLIOSIDE ANTIBODY SO NEUROLOGY LA English DT Editorial Material ID NEUROPATHY C1 [Moeller, Sina; Lau, Nga M.; Green, Peter H. R.; Alaedini, Armin] Columbia Univ, Dept Med, Med Ctr, New York, NY 10027 USA. [Hellberg, Dan] Uppsala Univ, Clin Res Ctr, Falun, Sweden. [Higgins, Joseph J.; Rajadhyaksha, Anjali M.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA. [Rajadhyaksha, Anjali M.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY USA. RP Alaedini, A (reprint author), Columbia Univ, Dept Med, Med Ctr, New York, NY 10027 USA. 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Synaptic (phasic) inhibition is spatially and temporally precise compared with tonic inhibition, which provides blunt yet strong integral inhibitory force by shunting electrical signaling. Although effects of acute modification of tonic inhibition are known, its pathophysiological significance remains unclear because homeostatic regulation of neuronal excitability can compensate for long-term deficit of extrasynaptic GABA(A) receptor activation. Nevertheless, tonic inhibition is of great interest for its pathophysiological involvement in central nervous system (CNS) diseases and thus as a therapeutic target. Together with the development of experimental models for various pathological states, recent evidence demonstrates such pathological involvements of tonic inhibition in neuronal dysfunction. This review focuses on the recent progress of tonic activation of GABA(A) conductance on the development and pathology of the CNS. Findings indicate that neuronal function in various brain regions are exacerbated with a gain or loss of function of tonic inhibition by GABA spillover. Disturbance of tonic GABA(A) conductance mediated by non-synaptic ambient GABA may result in brain mal-development. Therefore, various pathological states (epilepsy, motor dysfunctions, psychiatric disorders, and neurodevelopmental disorders) may be partly attributable to abnormal tonic GABA(A) conductances. Thus, the tone of tonic conductance and level of ambient GABA may be precisely tuned to maintain the regular function and development of the CNS. Therefore, receptor expression and factors for regulating the ambient GABA concentration are highlighted to gain a deeper understanding of pathology and therapeutic strategy for CNS diseases. C1 [Egawa, Kiyoshi] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Egawa, Kiyoshi] Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. 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Neural Circuits PD OCT 24 PY 2013 VL 7 AR 170 DI 10.3389/fncir.2013.00170 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 269XG UT WOS:000328276500001 PM 24167475 ER PT J AU Rivest, JB Jemel, B Bertone, A McKerral, M Mottron, L AF Rivest, Jessica B. Jemel, Boutheina Bertone, Armando McKerral, Michelle Mottron, Laurent TI Luminance- and Texture-Defined Information Processing in School-Aged Children with Autism SO PLOS ONE LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDER; TRAUMATIC BRAIN-INJURY; HUMAN VISUAL-CORTEX; 2ND-ORDER MOTION; SPECTRUM DISORDER; 1ST-ORDER MOTION; SELECTIVE IMPAIRMENT; CONTRAST MODULATIONS; PERCEPTION; VEP AB According to the complexity-specific hypothesis, the efficacy with which individuals with autism spectrum disorder (ASD) process visual information varies according to the extensiveness of the neural network required to process stimuli. Specifically, adults with ASD are less sensitive to texture-defined (or second-order) information, which necessitates the implication of several cortical visual areas. Conversely, the sensitivity to simple, luminance-defined (or first-order) information, which mainly relies on primary visual cortex (V1) activity, has been found to be either superior (static material) or intact (dynamic material) in ASD. It is currently unknown if these autistic perceptual alterations are present in childhood. In the present study, behavioural (threshold) and electrophysiological measures were obtained for static luminance-and texture-defined gratings presented to school-aged children with ASD and compared to those of typically developing children. Our behavioural and electrophysiological (P140) results indicate that luminance processing is likely unremarkable in autistic children. With respect to texture processing, there was no significant threshold difference between groups. However, unlike typical children, autistic children did not show reliable enhancements of brain activity (N230 and P340) in response to texture-defined gratings relative to luminance-defined gratings. This suggests reduced efficiency of neuro-integrative mechanisms operating at a perceptual level in autism. These results are in line with the idea that visual atypicalities mediated by intermediate-scale neural networks emerge before or during the school-age period in autism. C1 [Rivest, Jessica B.; Bertone, Armando; Mottron, Laurent] Univ Montreal, Ctr Excellence Pervas Dev Disorders CETEDUM, Montreal, PQ, Canada. [Rivest, Jessica B.; McKerral, Michelle] Univ Montreal, Ctr Rech Neuropsychol & Cognit CERNEC, Montreal, PQ, Canada. [Rivest, Jessica B.; McKerral, Michelle] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Jemel, Boutheina] Univ Montreal, Riviere des Prairies Hosp, Res Lab Neurosci & Cognit Electrophysiol, Montreal, PQ, Canada. RP Mottron, L (reprint author), Univ Montreal, Ctr Excellence Pervas Dev Disorders CETEDUM, Montreal, PQ, Canada. EM Laurent.mottron@gmail.com FU Canadian Institutes of Health Research (CIHR) [200703MOP-171795-BSB-CFCA-4239]; Natural Sciences and Engineering Research Council of Canada (NSERC) [327504-2006 RGPIN]; NSCERC; Autism Research Training (ART) program in Canada FX This work was supported by a grant to LM from the Canadian Institutes of Health Research (CIHR) (grant number 200703MOP-171795-BSB-CFCA-4239), by a grant to MM from the Natural Sciences and Engineering Research Council of Canada (NSERC) (grant number 327504-2006 RGPIN), as well as scholarships to JBR from NSCERC and the Autism Research Training (ART) program in Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Croen, Lisa A. Torres, Anthony R. Kharrazi, Martin Delorenze, Gerald N. Windham, Gayle C. Yoshida, Cathleen K. Zerbo, Ousseny Weiss, Lauren A. TI A Genome-Wide Survey of Transgenerational Genetic Effects in Autism SO PLOS ONE LA English DT Article ID SPECTRUM DISORDERS; FETAL MICROCHIMERISM; EARLY MARKERS; RISK-FACTORS; TWIN PAIRS; BRAIN; ASSOCIATION; VARIANTS; PROGENITOR; PREGNANCY AB Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4)) that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted. C1 [Tsang, Kathryn M.; Weiss, Lauren A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Tsang, Kathryn M.; Weiss, Lauren A.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Croen, Lisa A.; Delorenze, Gerald N.; Yoshida, Cathleen K.; Zerbo, Ousseny] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Torres, Anthony R.] Utah State Univ, Ctr Persons Disabil, Logan, UT 84322 USA. [Kharrazi, Martin] Calif Dept Hlth Serv, Genet Dis Screening Program, Richmond, CA USA. [Windham, Gayle C.] Calif Dept Hlth Serv, Div Environm & Occupat Dis Control, Richmond, CA USA. RP Weiss, LA (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM Lauren.Weiss@ucsf.edu FU National Institute of environmental Health Sciences [R01-ES016669]; National Institute of Health [MH52708, MH39437, MH00219, MH00980, MH64547]; National Health Medical Research Council [0034328]; Scottish Rite; Spunk Fund, Inc.; Rebecca and Solomon Baker Fund; APEX Foundation; National Alliance for Research in Schizophrenia and Affective Disorders; Nancy Pritzker Laboratory (Stanford); Cure Autism Now Foundation; National Institute of Mental Health [1U24MH081810]; Medical Research Council [G0601030]; Wellcome Trust [075491/Z/04] FX This study was supported by the National Institute of environmental Health Sciences (http://www.niehs.nih.gov/- R01-ES016669). The collection of data and biomaterials that participated in the National Institute of Mental Health Autism Genetics Initiative has been supported by National Institute of Health grants MH52708, MH39437, MH00219 and MH00980; National Health Medical Research Council grant 0034328; and by grants from the Scottish Rite, the Spunk Fund, Inc., the Rebecca and Solomon Baker Fund, the APEX Foundation, the National Alliance for Research in Schizophrenia and Affective Disorders, the endowment fund of the Nancy Pritzker Laboratory (Stanford), by gifts from the Autism Society of America, the Janet M. Grace Pervasive Developmental Disorders Fund, and families and friends of individuals with autism. The collection data and biomaterials also come from the Autism Genetic Resource Exchange (AGRE) collection supported by a National Institute of Health grant MH64547 and the Cure Autism Now Foundation. AGRE is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Haditsch, Ursula Braun, Amy E. Cantu, Andrea V. Moon, Hyang Mi Price, Robin O. Anderson, Matthew P. Saravanapandian, Vidya Ismail, Khadija Rivera, Moises Weimann, James M. Palmer, Theo D. TI Stereotypical Alterations in Cortical Patterning Are Associated with Maternal Illness-Induced Placental Dysfunction SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; PRENATAL IMMUNE CHALLENGE; CAJAL-RETZIUS CELLS; PROJECTION NEURON IDENTITY; AUTISM SPECTRUM DISORDERS; MOUSE; PREGNANCY; BRAIN; SCHIZOPHRENIA; EXPRESSION AB We have previously shown in mice that cytokine-mediated damage to the placenta can temporarily limit the flow of nutrients and oxygen to the fetus. The placental vulnerability is pronounced before embryonic day 11, when even mild immune challenge results in fetal loss. As gestation progresses, the placenta becomes increasingly resilient to maternal inflammation, but there is a narrow window in gestation when the placenta is still vulnerable to immune challenge yet resistant enough to allow for fetal survival. This gestational window correlates with early cortical neurogenesis in the fetal brain. Here, we show that maternal illness during this period selectively alters the abundance and laminar positioning of neuronal subtypes influenced by the Tbr1, Satb2, and Ctip2/Fezf2 patterning axis. The disturbances also lead to a laminar imbalance in the proportions of projection neurons and interneurons in the adult and are sufficient to cause changes in social behavior and cognition. These data illustrate how the timing of an illness-related placental vulnerability causes developmental alterations in neuroanatomical systems and behaviors that are relevant to autism spectrum disorders. C1 [Carpentier, Pamela A.; Haditsch, Ursula; Braun, Amy E.; Cantu, Andrea V.; Moon, Hyang Mi; Price, Robin O.; Anderson, Matthew P.; Saravanapandian, Vidya; Ismail, Khadija; Rivera, Moises; Weimann, James M.; Palmer, Theo D.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. RP Palmer, TD (reprint author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, 265 Campus Dr,Room 1141, Stanford, CA 94305 USA. EM tpalmer@stanford.edu FU March of Dimes; Autism Speaks; Simons Foundation; National Institutes of Health (NIH)/National Institute of Mental Health [1R01MH096815]; NIH (National Institute of Neurological Disorders and Stroke) [5F32NS60427]; Lucile Packard Foundation FX This work was supported by grants to T.D.P. from the March of Dimes, Autism Speaks, Simons Foundation, and National Institutes of Health (NIH)/National Institute of Mental Health (1R01MH096815) and grants to P.A.C. from the NIH (National Institute of Neurological Disorders and Stroke, 5F32NS60427) and the Lucile Packard Foundation. We thank Elizabeth Alcamo and Susan McConnell for experimental advice and helpful comments. We also thank the Stanford Behavioral and Functional Neuroscience Service Center for technical assistance with PPI and Social Interaction paradigms. 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In binocular rivalry, two monocularly presented images compete, leading to a percept that alternates between them. In a series of trials, we presented separate images of objects (e.g., a baseball and a broccoli) to each eye using a mirror stereoscope and asked human participants with autism and matched control subjects to continuously report which object they perceived, or whether they perceived a mixed percept. Individuals with autism demonstrated a slower rate of binocular rivalry alternations than matched control subjects, with longer durations of mixed percepts and an increased likelihood to revert to the previously perceived object when exiting a mixed percept. Critically, each of these findings was highly predictive of clinical measures of autistic symptomatology. Control "playback" experiments demonstrated that differences in neither response latencies nor response criteria could account for the atypical dynamics of binocular rivalry we observed in autistic spectrum conditions. Overall, these results may provide an index of atypical cortical dynamics that may underlie both the social and nonsocial symptoms of autism. C1 [Robertson, Caroline E.; Kravitz, Dwight J.; Baker, Chris I.] NIMH, NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Robertson, Caroline E.; Freyberg, Jan; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 8AH, England. RP Robertson, CE (reprint author), Harvard Soc Fellows, 78 Mt Auburn St, Cambridge, MA 02138 USA. EM carolinerobertson@fas.harvard.edu FU National Institute of Mental Health; Gates-Cambridge Trust; National Institutes of Health-Cambridge Fellowship; Medical Research Council; Wellcome Trust FX This work was supported in part by the Intramural Research Program of the National Institute of Mental Health, and was conducted in association with the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough NHS Foundation Trust. This work was also supported by the Gates-Cambridge Trust and the National Institutes of Health-Cambridge Fellowship (C.E.R.). S.B.-C. was supported by the Medical Research Council and the Wellcome Trust during the period of this work. We thank John Mollon for the use of his mirror stereoscope; David Leopold, Carson Chow, Shashaank Vattikuti, Alex Martin, and Kate Plaisted-Grant for comments; and Carrie Allison for help with recruitment. 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However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. Methods: High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age-and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Results: Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Conclusions: Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD. C1 [Lukoshe, Akvile; Hokken-Koelega, Anita C.] Dutch Growth Res Fdn, NL-3001 KB Rotterdam, Netherlands. [Lukoshe, Akvile; Hokken-Koelega, Anita C.] Sophia Childrens Hosp Rotterdam, Erasmus Med Ctr Rotterdam, Dept Pediat, NL-3000 CB Rotterdam, Netherlands. [White, Tonya; Schmidt, Marcus N.] Sophia Childrens Hosp Rotterdam, Erasmus Med Ctr Rotterdam, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [White, Tonya; van der Lugt, Aad] Erasmus MC, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. RP Lukoshe, A (reprint author), Dutch Growth Res Fdn, Postbus 23068, NL-3001 KB Rotterdam, Netherlands. EM a.lukose@kindengroei.nl FU Foundation for Prader-Willi Research, Los Angeles, CA, USA; Dutch Growth Research Foundation, Rotterdam, The Netherlands FX We would like to thank parents and children for their participation. We also thank Afzal Bechan and Marielle van Eekelen for their assistance with the MRI acquisition, and Zyrhea Troeman for conducting the biannual IQ tests. This study was financially supported by the Foundation for Prader-Willi Research, Los Angeles, CA, USA, and Dutch Growth Research Foundation, Rotterdam, The Netherlands. 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I., 1967, REGIONAL DEV BRAIN E, P3 NR 65 TC 3 Z9 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1866-1947 EI 1866-1955 J9 J NEURODEV DISORD JI J. Neurodev. Disord. PD OCT 22 PY 2013 VL 5 AR 31 DI 10.1186/1866-1955-5-31 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 242ZX UT WOS:000326287000001 PM 24144356 ER PT J AU McFadden, K Minshew, NJ AF McFadden, Kathryn Minshew, Nancy J. TI Evidence for dysregulation of axonal growth and guidance in the etiology of ASD SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Review DE autism spectrum disorders; connectivity; neuritic outgrowth; axonal guidance; subplate ID AUTISM SPECTRUM DISORDERS; RECEPTOR TYROSINE KINASE; WHITE-MATTER COMPROMISE; HIGH-FUNCTIONING AUTISM; COPY NUMBER VARIATION; CEREBRAL-CORTEX; FRONTAL-CORTEX; DYNAMIC GENE; HUMAN BRAIN; SUBPLATE AB Current theories concerning the cause of autism spectrum disorders (ASDs) have converged on the concept of abnormal development of brain connectivity. This concept is supported by accumulating evidence from functional imaging, diffusion tensor imaging, and high definition fiber tracking studies which suggest altered microstructure in the axonal tracts connecting cortical areas may underly many of the cognitive manifestations of ASD. Additionally, large-scale genomic studies implicate numerous gene candidates known or suspected to mediate neuritic outgrowth and axonal guidance in fetal and perinatal life. Neuropathological observations in postmortem ASD brain samples further support this model and include subtle disturbances of cortical lamination and subcortical axonal morphology. Of note is the relatively common finding of poor differentiation of the gray-white junction associated with an excess superficial white matter or "interstitial" neurons (INs). INs are thought to be remnants of the fetal subplate, a transient structure which plays a key role in the guidance and morphogenesis of thalamocortical and cortico-cortical connections and the organization of cortical columnar architecture. While not discounting the importance of synaptic dysfunction in the etiology of ASD, this paper will briefly review the cortical abnormalities and genetic evidence supporting a model of dysregulated axonal growth and guidance as key developmental processes underlying the clinical manifestations of ASD. C1 [McFadden, Kathryn] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat & Neurol, Pittsburgh, PA 15213 USA. RP Minshew, NJ (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Webster Hall,Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu FU Pennsylvania Department of Health [4100047862]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD055748] FX The authors gratefully acknowledge support by the Pennsylvania Department of Health, grant 4100047862 (Kathryn McFadden and Nancy J. 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Hum. Neurosci. PD OCT 22 PY 2013 VL 7 AR 671 DI 10.3389/fnhum.2013.00671 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 238BZ UT WOS:000325917000001 PM 24155705 ER PT J AU Wong, M Guo, D AF Wong, M. Guo, D. TI DENDRITIC SPINE PATHOLOGY IN EPILEPSY: CAUSE OR CONSEQUENCE? SO NEUROSCIENCE LA English DT Article DE seizure; epilepsy; epileptogenesis; dendrite; actin ID TEMPORAL-LOBE EPILEPSY; DENTATE GRANULE CELLS; LASER-SCANNING MICROSCOPY; RAT PILOCARPINE MODEL; STATUS EPILEPTICUS; RETT-SYNDROME; IN-VIVO; SYNAPTIC PLASTICITY; TUBEROUS SCLEROSIS; HIPPOCAMPAL DENDRITES AB Abnormalities in dendritic spines have commonly been observed in brain specimens from epilepsy patients and animal models of epilepsy. However, the functional implications and clinical consequences of this dendritic pathology for epilepsy are uncertain. Dendritic spine abnormalities may promote hyperexcitable circuits and seizures in some types of epilepsy, especially in specific genetic syndromes with documented dendritic pathology, but in these cases it is difficult to differentiate their effects on seizures versus other comorbidities, such as cognitive deficits and autism. In other situations, seizures themselves may cause damage to dendrites and dendritic spines and this seizure-induced brain injury may then contribute to progressive epileptogenesis, memory problems and other neurological deficits in epilepsy patients. The mechanistic basis of dendritic spine abnormalities in epilepsy has begun to be elucidated and suggests novel therapeutic strategies for treating epilepsy and its complications. This article is part of a Special Issue entitled: Dendritic Spine Plasticity in Brain Disorders. (c) 2012 IBRO Published by Elsevier Ltd. All rights reserved. C1 [Wong, M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. 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THALAMIC LESION; SAVANT MEMORY; IN-VITRO; SYNAESTHESIA AB Though synesthesia research has seen a huge grow thin recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any) among developmental, acquired and drug-induced synesthesia. We know that many forms of synesthesia involve aberrant structural or functional brain connectivity. Proposed mechanisms include direct projection and disinhibited feedback mechanisms, in which information from two otherwise structurally or functionally separate brain regions mix. We also know that synesthesia sometimes runs in families. However, it is unclear what causes its on set. Studies of psychedelic drugs, such as psilocybin, LSD and mescaline, reveal that exposure to these drugs can induce synesthesia. One neurotransmitter suspected to be central to the perceptual changes is serotonin. Excessive serotonin in the brain may cause many of the characteristics of psychedelic in toxication. Excessive serotonin levels may also play a role in synesthesia acquired after brain injury. In brain injury sudden cell death floods local brain regions with serotonin and glutamate. This neurotransmitter flooding could perhaps result in unusual feature binding. Finally, developmental synesthesia that occurs in individuals with autism may be a result of alterations in the serotonergic system, leading to a blockage of regular gating mechanisms. I conclude on these grounds that one commonality among at least some cases of acquired, developmental and drug-induced synesthesia may be the presence of excessive levels of serotonin, which increases the excitability and connectedness of sensory brain regions. C1 [Brogaard, Berit] Univ Missouri, Dept Philosophy, St Louis, MO 63121 USA. [Brogaard, Berit] Univ Missouri, Ctr Neurodynam, St Louis, MO 63121 USA. RP Brogaard, B (reprint author), Univ Missouri, Dept Philosophy, St Louis, MO 63121 USA. 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Sourander, Andre TI The risk of childhood autism among second-generation migrants in Finland: a case-control study SO BMC PEDIATRICS LA English DT Article DE Autism; Risk factor; Parental; Migration; Epidemiology ID SPECTRUM DISORDERS; INFANTILE-AUTISM; VITAMIN-D; EPIDEMIOLOGY; ENVIRONMENT; EXPOSURE; ORIGIN AB Background: Studying second-generation immigrants can help in identifying genetic or environmental risk factors for childhood autism. Most previous studies have focused on maternal region of birth and showed inconsistent results. No previous study has been conducted in Finland. Methods: The study was a nested case-control study based on a national birth cohort. Children born in 1987-2005 and diagnosed with childhood autism by the year 2007 were identified from the Finnish Hospital Discharge Register. Controls were selected from the Finnish Medical Birth Register. Information on maternal and paternal country of birth and mother tongue was collected from the Finnish Central Population Register. There were 1132 cases and 4515 matched controls. The statistical test used was conditional logistic regression analysis. Results: Compared with children with two Finnish parents, the risk of childhood autism was increased for those whose parents are both immigrants (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.2-2.7) and for those with only an immigrant mother (aOR 1.8, 95% CI 1.2-2.7), but not for those with only an immigrant father. The risk was increased for those with a mother born in the former Soviet Union or Yugoslavia and for those with a mother or a father born in Asia. Specific parental countries of birth associated with an increased risk were the former Soviet Union, the former Yugoslavia and Vietnam. Conclusions: In Finland, children who are born to immigrant mothers with or without an immigrant partner, have an increased risk of childhood autism. The risk varies with immigrant parents' region of birth. The findings may help in identifying possible risk factors, which can be examined in future studies. C1 [Lehti, Venla; Hinkka-Yli-Salomaki, Susanna; Gissler, Mika; Sourander, Andre] Univ Turku, Dept Child Psychiat, Turku 20014, Finland. [Cheslack-Postava, Keely; Brown, Alan S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki 00271, Finland. [Gissler, Mika] Nord Sch Publ Hlth, SE-40242 Gothenburg, Sweden. [Brown, Alan S.; Sourander, Andre] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, Unit 23, New York, NY 10032 USA. RP Sourander, A (reprint author), Univ Turku, Dept Child Psychiat, Lemminkaisenkatu 3 Teutori, Turku 20014, Finland. EM andre.sourander@utu.fi FU Autism Speaks; National Institute of Mental Health (NIMH) [1K02-MH65422]; National Institute of Environmental Health Sciences [1R01ES019004] FX This study was supported by Autism Speaks, National Institute of Mental Health (NIMH) 1K02-MH65422, and National Institute of Environmental Health Sciences 1R01ES019004. The funding bodies had no role in the collection, analysis and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication. 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To assess its population impact we studied 2148 common single nucleotide polymorphisms (SNPs) using transmission disequilibrium test (TDT) across the entire similar to 3.3 Mb CNTNAP2 locus in 186 (408 trios) multiplex and 323 simplex families with autistic spectrum disorder (ASD). This analysis yielded two SNPs with nominal statistical significance (rs17170073, p = 2.0 x 10(-4); rs2215798, p = 1.6 x 10(-4)) that did not survive multiple testing. In a combined analysis of all families, two highly correlated (r(2) = 0.99) SNPs in intron 14 showed significant association with autism (rs2710093, p = 9.0 x 10(-6); rs2253031, p = 2.5 x 10(-5)). To validate these findings and associations at SNPs from previous autism studies (rs7794745, rs2710102 and rs17236239) we genotyped 2051 additional families (572 multiplex and 1479 simplex). None of these variants were significantly associated with ASD after corrections for multiple testing. 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EM aravinda@jhmi.edu FU Simons Foundation [SFARI 102882]; National Institutes of Health (ACE Genetics Consortium) [MH081754] FX This work was supported by grants from the Simons Foundation (SFARI 102882 to AC) and the National Institutes of Health (ACE Genetics Consortium, MH081754) to AC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Sreenivasan, Karthik R. Deshpande, Hrishikesh D. Kana, Rajesh K. TI Identification of neural connectivity signatures of autism using machine learning SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; effective connectivity; fMRI; classification; machine learning; theory-of-mind ID GRANGER CAUSALITY ANALYSIS; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDER; WHITE-MATTER; CORTICAL UNDERCONNECTIVITY; SENTENCE COMPREHENSION; SOCIAL-PERCEPTION; CORPUS-CALLOSUM; HEAD MOTION; FMRI DATA AB Alterations in interregional neural connectivity have been suggested as a signature of the pathobiology of autism. There have been many reports of functional and anatomical connectivity being altered while individuals with autism are engaged in complex cognitive and social tasks. Although disrupted instantaneous correlation between cortical regions observed from functional MRI is considered to be an explanatory model for autism, the causal influence of a brain area on another (effective connectivity) is a vital link missing in these studies. The current study focuses on addressing this in an fMRI study of Theory-of-Mind (ToM) in 15 high-functioning adolescents and adults with autism and 15 typically developing control participants. Participants viewed a series of comic strip vignettes in the MRI scanner and were asked to choose the most logical end to the story from three alternatives, separately for trials involving physical and intentional causality. The mean time series, extracted from 18 activated regions of interest, were processed using a multivariate autoregressive model (MVAR) to obtain the causality matrices for each of the 30 participants. These causal connectivity weights, along with assessment scores, functional connectivity values, and fractional anisotropy obtained from DTI data for each participant, were submitted to a recursive cluster elimination based support vector machine classifier to determine the accuracy with which the classifier can predict a novel participant's group membership (autism or control). We found a maximum classification accuracy of 95.9% with 19 features which had the highest discriminative ability between the groups. All of the 19 features were effective connectivity paths, indicating that causal information may be critical in discriminating between autism and control groups. These effective connectivity paths were also found to be significantly greater in controls as compared to ASD participants and consisted predominantly of outputs from the fusiform face area and middle temporal gyrus indicating impaired connectivity in ASD participants, particularly in the social brain areas. These findings collectively point toward the fact that alterations in causal connectivity in the brain in ASD could serve as a potential non-invasive neuroimaging signature for autism. C1 [Deshpande, Gopikrishna; Sreenivasan, Karthik R.] Auburn Univ, Dept Elect & Comp Engn, AU MRI Res Ctr, Auburn, AL 36849 USA. [Deshpande, Gopikrishna] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Libero, Lauren E.; Deshpande, Hrishikesh D.; Kana, Rajesh K.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. RP Kana, RK (reprint author), Univ Alabama Birmingham, Dept Psychol, CIRC 235G,1719 6th Ave South, Birmingham, AL 35294 USA. EM rkana@uab.edu FU Auburn University MRI Research Center FX The authors would like to thank the UAB department of Psychology and the Civitan-McNulty Scientist Award to Rajesh K. Kana as well as support from Auburn University MRI Research Center to Gopikrishna Deshpande as sources of funding support for this study. 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These tasks have been studied extensively using behavioral oculomotor, electrophysiological, and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18) of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields (SEFs), thalamus, striatum, and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade vs. prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network. C1 [Jamadar, Sharna D.; Egan, Gary F.] Monash Univ, Monash Biomed Imaging, Melbourne, Vic 3004, Australia. [Jamadar, Sharna D.; Fielding, Joanne; Egan, Gary F.] Monash Univ, Sch Psychol & Psychiat, Melbourne, Vic 3004, Australia. RP Jamadar, SD (reprint author), Monash Univ, Sch Psychol & Psychiat, Monash Biomed Imaging, 770 Blackburn Rd, Clayton, Vic 3800, Australia. 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Psychol. PD OCT 16 PY 2013 VL 4 DI 10.3389/fpsyg.2013.00749 PG 15 WC Psychology, Multidisciplinary SC Psychology GA AA6WH UT WOS:000331238400001 PM 24137150 ER PT J AU Wolfe, D Dudek, S Ritchie, MD Pendergrass, SA AF Wolfe, Daniel Dudek, Scott Ritchie, Marylyn D. Pendergrass, Sarah A. TI Visualizing genomic information across chromosomes with PhenoGram SO BIODATA MINING LA English DT Article DE Data visualization; Bioinformatics; Genome-wide association study; GWAS; Copy-number variants; CNV; SNP; Ideogram ID WIDE ASSOCIATION; AUTISM AB Background: With the abundance of information and analysis results being collected for genetic loci, user-friendly and flexible data visualization approaches can inform and improve the analysis and dissemination of these data. A chromosomal ideogram is an idealized graphic representation of chromosomes. Ideograms can be combined with overlaid points, lines, and/or shapes, to provide summary information from studies of various kinds, such as genome-wide association studies or phenome-wide association studies, coupled with genomic location information. To facilitate visualizing varied data in multiple ways using ideograms, we have developed a flexible software tool called PhenoGram which exists as a web-based tool and also a command-line program. Results: With PhenoGram researchers can create chomosomal ideograms annotated with lines in color at specific base-pair locations, or colored base-pair to base-pair regions, with or without other annotation. PhenoGram allows for annotation of chromosomal locations and/or regions with shapes in different colors, gene identifiers, or other text. PhenoGram also allows for creation of plots showing expanded chromosomal locations, providing a way to show results for specific chromosomal regions in greater detail. We have now used PhenoGram to produce a variety of different plots, and provide these as examples herein. These plots include visualization of the genomic coverage of SNPs from a genotyping array, highlighting the chromosomal coverage of imputed SNPs, copy-number variation region coverage, as well as plots similar to the NHGRI GWA Catalog of genome-wide association results. Conclusions: PhenoGram is a versatile, user-friendly software tool fostering the exploration and sharing of genomic information. Through visualization of data, researchers can both explore and share complex results, facilitating a greater understanding of these data. C1 [Wolfe, Daniel; Dudek, Scott; Ritchie, Marylyn D.; Pendergrass, Sarah A.] Penn State Univ, Eberly Coll Sci, Huck Inst Life Sci, Ctr Syst Genom,Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Ritchie, MD (reprint author), Penn State Univ, Eberly Coll Sci, Huck Inst Life Sci, Ctr Syst Genom,Dept Biochem & Mol Biol, 512 Wartik Lab, University Pk, PA 16802 USA. EM marylyn.ritchie@psu.edu FU [5U01 HG004798-03]; [5R01 LM010040-02]; [U19 HL065962-10] FX We would like to thank everyone who has had suggestions for improvements and additions to this software. This work was supported by the following funding agencies and grants: 5U01 HG004798-03, 5R01 LM010040-02, and U19 HL065962-10. CR Bickmore W. 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PD OCT 16 PY 2013 VL 6 AR 18 DI 10.1186/1756-0381-6-18 PG 12 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 279IY UT WOS:000328954800001 PM 24131735 ER PT J AU Dodero, L Damiano, M Galbusera, A Bifone, A Tsaftsaris, SA Scattoni, ML Gozzi, A AF Dodero, Luca Damiano, Mario Galbusera, Alberto Bifone, Angelo Tsaftsaris, Sotirios A. Scattoni, Maria Luisa Gozzi, Alessandro TI Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T plus TF/J Mouse Model of Autism SO PLOS ONE LA English DT Article ID VOXEL-BASED MORPHOMETRY; CEREBRAL BLOOD-VOLUME; CORPUS-CALLOSUM; CORTICAL THICKNESS; SPECTRUM DISORDERS; CHILDHOOD AUTISM; IMAGE REGISTRATION; SOCIAL COGNITION; INBRED STRAINS; PROBST BUNDLE AB BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations. C1 [Dodero, Luca; Damiano, Mario; Galbusera, Alberto; Bifone, Angelo; Gozzi, Alessandro] Ctr Neurosci & Cognit Syst UniTn, Ist Italiano Tecnol, Rovereto, Italy. [Tsaftsaris, Sotirios A.] Northwestern Univ, Dept Elect Engn & Comp Sci, Evanston, IL USA. [Scattoni, Maria Luisa] Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. RP Gozzi, A (reprint author), Ctr Neurosci & Cognit Syst UniTn, Ist Italiano Tecnol, Rovereto, Italy. EM alessandro.gozzi@iit.it FU Istituto Italiano di Tecnologia FX The study was funded by the Istituto Italiano di Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Dib-Hajj, Fadia Veeramah, Krishna R. Hammer, Michael F. Dib-Hajj, Sulayman D. Waxman, Stephen G. TI Multistate Structural Modeling and Voltage-Clamp Analysis of Epilepsy/Autism Mutation Kv10.2-R327H Demonstrate the Role of This Residue in Stabilizing the Channel Closed State SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; GO POTASSIUM CHANNELS; K+ CHANNEL; SODIUM-CHANNEL; SEIZURE LOCUS; EAG FAMILY; SENSOR; ACTIVATION; CHARGE; EXPRESSION AB Voltage-gated potassium channel Kv10.2 (KCNH5) is expressed in the nervous system, but its functions and involvement in human disease are poorly understood. We studied a human Kv10.2 channel mutation (R327H) recently identified in a child with epileptic encephalopathy and autistic features. Using multistate structural modeling, we demonstrate that the Arg327 residue in the S4 helix of voltage-sensing domain has strong ionic interactions with negatively charged residues within the S1-S3 helices in the resting (closed) and early-activation state but not in the late-activation and fully-activated (open) state. The R327H mutation weakens ionic interactions between residue 327 and these negatively charged residues, thus favoring channel opening. Voltage-clamp analysis showed a strong hyperpolarizing (similar to 70 mV) shift of voltage dependence of activation and an acceleration of activation. Our results demonstrate the critical role of the Arg327 residue in stabilizing the channel closed state and explicate for the first time the structural and functional change of a Kv10.2 channel mutation associated with neurological disease. C1 [Yang, Yang; Vasylyev, Dmytro V.; Dib-Hajj, Fadia; Dib-Hajj, Sulayman D.; Waxman, Stephen G.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Yang, Yang; Vasylyev, Dmytro V.; Dib-Hajj, Fadia; Dib-Hajj, Sulayman D.; Waxman, Stephen G.] Yale Univ, Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT 06510 USA. [Yang, Yang; Vasylyev, Dmytro V.; Dib-Hajj, Fadia; Dib-Hajj, Sulayman D.; Waxman, Stephen G.] Vet Affairs Connecticut Healthcare Syst, Rehabil Res Ctr, West Haven, CT 06516 USA. [Veeramah, Krishna R.; Hammer, Michael F.] Univ Arizona, Arizona Res Labs, Div Biotechnol, Tucson, AZ 85721 USA. RP Waxman, SG (reprint author), Vet Affairs Connecticut Healthcare Syst, Neurosci & Regenerat Res Ctr, 950 Campbell Ave,Bldg 34, West Haven, CT 06516 USA. EM stephen.waxman@yale.edu FU Medical Research Service, Department of Veterans Affairs; Rehabilitation Research Service, Department of Veterans Affairs; Connecticut Stem Cell Research Grants Program FX This work was supported by the Medical Research Service and Rehabilitation Research Service, Department of Veterans Affairs (S. G. W.). Y.Y. is supported by Connecticut Stem Cell Research Grants Program. The Center for Neuroscience and Regeneration Research is a Collaboration of the Paralyzed Veterans of America with Yale University. We thank Dr. Mark Estacion, Dr. Chongyang Han, and Dr. Jianying Huang for valuable comments. We thank Dr. David E. Shaw and Dr. Morten Jensen of D. E. Shaw Research for providing coordinates of their molecular dynamics simulation results and helpful discussion. 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TI A transcranial magnetic stimulation study of the effect of visual orientation on the putative human mirror neuron system SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE mirror neurons; transcranial magnetic stimulation; electromyography; associative learning; action observation; visual perspective ID AUTISM SPECTRUM DISORDERS; CORTICOSPINAL EXCITABILITY; MOTOR FACILITATION; MODULATION; IMITATION; OTHERS; DYSFUNCTION; EMOTIONS; CHILDREN; BIRTH AB Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding. There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric). Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimulation experiment that assessed corticospinal excitability whilst viewing transitive hand gestures from both egocentric (i.e., self) and allocentric (i.e., other) viewpoints. Although action observation was associated with increases in corticospinal excitability (reflecting putative human mirror neuron activity), there was no effect of visual perspective. These findings are discussed in the context of contemporary theories of mirror neuron ontogeny, including models concerning associative learning and evolutionary adaptation. C1 [Burgess, Jed D.; Arnold, Sara L.; Fitzgibbon, Bernadette M.; Fitzgerald, Paul B.; Enticott, Peter G.] Monash Univ, Monash Alfred Psychiat Res Ctr, Alfred & Cent Clin Sch, Fac Med Nursing & Hlth Sci, Melbourne, Vic 3004, Australia. RP Enticott, PG (reprint author), Monash Univ, Monash Alfred Psychiat Res Ctr, Alfred & Cent Clin Sch, Fac Med Nursing & Hlth Sci, Level 4,607 St Kilda Rd, Melbourne, Vic 3004, Australia. EM peter.enticott@monash.edu FU National Health and Medical Research Council (NHMRC) Career Development Fellowship; NHMRC Practitioner Fellowship; Australian Research Council (ARC) Discovery Project [DP120101738] FX Peter G. Enticott is supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship. Paul B. Fitzgerald is supported by a NHMRC Practitioner Fellowship. This research was supported by an Australian Research Council (ARC) Discovery Project awarded to Peter G. Enticott (DP120101738). 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Targeted genotyping arrays and next-generation sequencing technologies at the whole-genome sequencing (WGS) and whole-exome scales (WES) are increasingly employed to access sequence variation across the full minor allele frequency (MAF) spectrum. Different study design strategies that make use of diverse technologies, imputation and sample selection approaches are an active target of development and evaluation efforts. Initial insights into the contribution of rare variants in common diseases and medically relevant quantitative traits point to low-frequency and rare alleles acting either independently or in aggregate and in several cases alongside common variants. Studies conducted in population isolates have been successful in detecting rare variant associations with complex phenotypes. 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EM eleftheria@sanger.ac.uk FU Wellcome Trust [098051]; Arthritis Research UK [19542] FX K.P., I.T. and E.Z. are funded by the Wellcome Trust (098051). K.P. is funded by Arthritis Research UK (19542). Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust (098051). 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PD OCT 15 PY 2013 VL 110 IS 42 BP E3974 EP E3974 DI 10.1073/pnas.1313455110 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234HT UT WOS:000325634200002 PM 24278966 ER PT J AU Brock, J AF Brock, Jon TI Connectivity and cognition in autism spectrum disorders: Where are the links? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Brock, Jon] Macquarie Univ, Dept Cognit Sci, Sydney, NSW 2109, Australia. EM jon.brock@mq.edu.au CR Abrams DA, 2013, P NATL ACAD SCI USA, V110, P12060, DOI 10.1073/pnas.1302982110 Pelphrey KA, 2011, J CHILD PSYCHOL PSYC, V52, P631, DOI 10.1111/j.1469-7610.2010.02349.x NR 2 TC 1 Z9 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 2013 VL 110 IS 42 BP E3973 EP E3973 DI 10.1073/pnas.1311907110 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234HT UT WOS:000325634200001 PM 24101453 ER PT J AU Raznahan, A Wallace, GL Antezana, L Greenstein, D Lenroot, R Thurm, A Gozzi, M Spence, S Martin, A Swedo, SE Giedd, JN AF Raznahan, Armin Wallace, Gregory L. Antezana, Ligia Greenstein, Dede Lenroot, Rhoshel Thurm, Audrey Gozzi, Marta Spence, Sarah Martin, Alex Swedo, Susan E. Giedd, Jay N. TI Compared to What? Early Brain Overgrowth in Autism and the Perils of Population Norms SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; bias; CDC; head circumference; systematic review; WHO ID HEAD CIRCUMFERENCE GROWTH; PERVASIVE DEVELOPMENTAL DISORDERS; AGE 2 YEARS; SPECTRUM DISORDERS; 1ST YEAR; BIRTH COHORT; CHILDREN; LIFE; INFANTS; SIZE AB Background: Early brain overgrowth (EBO) in autism spectrum disorder (ASD) is among the best replicated biological associations in psychiatry. Most positive reports have compared head circumference (HC) in ASD (an excellent proxy for early brain size) with well-known reference norms. We sought to reappraise evidence for the EBO hypothesis given 1) the recent proliferation of longitudinal HC studies in ASD, and 2) emerging reports that several of the reference norms used to define EBO in ASD may be biased toward detecting HC overgrowth in contemporary samples of healthy children. Methods: Systematic review of all published HC studies in children with ASD. Comparison of 330 longitudinally gathered HC measures between birth and 18 months from male children with autism (n = 35) and typically developing control subjects (n = 22). Results: In systematic review, comparisons with locally recruited control subjects were significantly less likely to identify EBO in ASD than norm-based studies (p < .001). Through systematic review and analysis of new data, we replicate seminal reports of EBO in ASD relative to classical HC norms but show that this overgrowth relative to norms is mimicked by patterns of HC growth age in a large contemporary community-based sample of US children (n similar to 75,000). Controlling for known HC norm biases leaves inconsistent support for a subtle, later emerging and subgroup specific pattern of EBO in clinically ascertained ASD versus community control subjects. Conclusions: The best-replicated aspects of EBO reflect generalizable HC norm biases rather than disease-specific biomarkers. The potential HC norm biases we detail are not specific to ASD research but apply throughout clinical and academic medicine. C1 [Raznahan, Armin; Greenstein, Dede; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Wallace, Gregory L.; Antezana, Ligia; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Lenroot, Rhoshel] Univ New S Wales, Dept Psychiat, Sydney, NSW, Australia. [Thurm, Audrey; Gozzi, Marta; Swedo, Susan E.] NIMH, Pediat Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA. [Spence, Sarah] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp Boston, Boston, MA 02115 USA. RP Raznahan, A (reprint author), NIMH, NIH, Child Psychiat Branch, Room 4C108,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM raznahana@mail.nih.gov RI Giedd, Jay/B-7302-2012 OI Giedd, Jay/0000-0003-0827-3460 FU National Institutes of Health Intramural Research Program FX Financial support for this work was provided by the National Institutes of Health Intramural Research Program. 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Psychiatry PD OCT 15 PY 2013 VL 74 IS 8 BP 563 EP 575 DI 10.1016/j.biopsych.2013.03.022 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223OH UT WOS:000324814900003 PM 23706681 ER PT J AU Chaste, P Klei, L Sanders, SJ Murtha, MT Hus, V Lowe, JK Willsey, AJ Moreno-De-Luca, D Yu, TW Fombonne, E Geschwind, D Grice, DE Ledbetter, DH Lord, C Mane, SM Martin, CL Martin, DM Morrow, EM Walsh, CA Sutcliffe, JS State, MW Devlin, B Cook, EH Kim, SJ AF Chaste, Pauline Klei, Lambertus Sanders, Stephan J. Murtha, Michael T. Hus, Vanessa Lowe, Jennifer K. Willsey, A. Jeremy Moreno-De-Luca, Daniel Yu, Timothy W. Fombonne, Eric Geschwind, Daniel Grice, Dorothy E. Ledbetter, David H. Lord, Catherine Mane, Shrikant M. Martin, Christa Lese Martin, Donna M. Morrow, Eric M. Walsh, Christopher A. Sutcliffe, James S. State, Matthew W. Devlin, Bernie Cook, Edwin H., Jr. Kim, Soo-Jeong TI Adjusting Head Circumference for Covariates in Autism: Clinical Correlates of a Highly Heritable Continuous Trait SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ASD; autism spectrum disorder; body metrics; genetic ancestry; head circumference; IQ ID SPECTRUM DISORDERS; BRAIN VOLUME; 1ST YEAR; CHILDREN; GROWTH; BIRTH; AGE; SIZE; LIFE; ENLARGEMENT AB Background: Brain development follows a different trajectory in children with autism spectrum disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. Methods: We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. Results: Gender, age, height, weight, genetic ancestry, and ASD status were significant predictors of HC (estimate of the ASD effect = .2 cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. Conclusions: Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait, and population norms for HC would be far more accurate if covariates including genetic ancestry, height, and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation. C1 [Chaste, Pauline; Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Chaste, Pauline] FondaMental Fdn, Creteil, France. [Sanders, Stephan J.; Murtha, Michael T.; Moreno-De-Luca, Daniel; State, Matthew W.] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT USA. [Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA. [Sanders, Stephan J.; Moreno-De-Luca, Daniel; State, Matthew W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sanders, Stephan J.; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Hus, Vanessa] Univ Michigan, Dept Psychol, Ann Arbor, MI 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, Semel Inst, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA. [Yu, Timothy W.] Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Grice, Dorothy E.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Grice, Dorothy E.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA. [Ledbetter, David H.; Martin, Christa Lese] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA USA. [Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, White Plains, NY 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, Mol Med Lab, Dept Mol Biol, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Mol Med Lab, Inst Brain Sci, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Sch Med, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, East Providence, RI USA. [Morrow, Eric M.] Brown Univ, Sch Med, Dept Psychiat & Human Behav, East Providence, RI USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Boston, MA USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Psychiat, Nashville, TN 37235 USA. [State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Kim, Soo-Jeong] Univ Washington, Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98195 USA. [Kim, Soo-Jeong] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kim, SJ (reprint author), Seattle Childrens Res Inst, Ctr Integrat Brain Res, 1900 9th Ave, Seattle, WA 98101 USA. EM kimsooj@uw.edu RI Sutcliffe, James/C-1348-2012 OI Sutcliffe, James/0000-0001-5200-6007 FU Simons Foundation [SFARI 124827]; National Institutes of Health (NIH) [K23MH082883, NIH R01HD065272, NIH R01MH089390]; Fondamental Foundation FX 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 the Simons Foundation Autism Research Initiative (SFARI) Base. Approved researchers can obtain the SSC population data set described in this study (http://sfari.org/resources/sfari-base) by applying at https://base.sfari.org. This work was supported by a grant from the Simons Foundation (Grant No. SFARI 124827 to the investigators of the SSC Genetic Consortium), National Institutes of Health (NIH; Grant No. K23MH082883 (SJK), NIH R01HD065272 (CL), NIH R01MH089390 (CL), and Fondamental Foundation (PC). 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Methods: We assessed the relationship between the prevalence of ADHD and solar intensity (SI) (kilowatt hours/square meters/day) on the basis of multinational and cross-state studies. Prevalence data for the U.S. were based on self-report of professional diagnoses; prevalence data for the other countries were based on diagnostic assessment. The SI data were obtained from national institutes. Results: In three datasets (across 49 U.S. states for 2003 and 2007, and across 9 non-U.S. countries) a relationship between SI and the prevalence of ADHD was found, explaining 34%-57% of the variance in ADHD prevalence, with high SI having an apparent preventative effect. Controlling for low birth weight, infant mortality, average income (socioeconomic status), latitude, and other relevant factors did not change these findings. Furthermore, these findings were specific to ADHD, not found for the prevalence of autism spectrum disorders or major depressive disorder. Conclusions: In this study we found a lower prevalence of ADHD in areas with high SI for both U.S. and non-U.S. data. This association has not been reported before in the literature. The preventative effect of high SI might be related to an improvement of circadian clock disturbances, which have recently been associated with ADHD. These findings likely apply to a substantial subgroup of ADHD patients and have major implications in our understanding of the etiology and possibly prevention of ADHD by medical professionals, schools, parents, and manufacturers of mobile devices. C1 [Arns, Martijn; Kenemans, J. Leon] Univ Utrecht, Dept Expt Psychol, Utrecht, Netherlands. [Arns, Martijn] Res Inst Brainclin, NL-6524 AD Nijmegen, Netherlands. [van der Heijden, Kristiaan B.] Leiden Univ, Dept Clin Child & Adolescent Studies, Leiden Inst Brain & Cognit, Leiden, Netherlands. [Arnold, L. Eugene] Ohio State Univ, Columbus, OH 43210 USA. RP Arns, M (reprint author), Res Inst Brainclin, Dept Expt Psychol, Bijleveldsingel 34, NL-6524 AD Nijmegen, Netherlands. EM martijn@brainclinics.com FU AstraZeneca; Biomarin; CureMark; Lilly; Novartis; Noven; Seaside Therapeutics; Shire FX LEA has received research funding (to the university) or advisory board honoraria from AstraZeneca, Biomarin, CureMark, Lilly, Novartis, Noven, Seaside Therapeutics, and Shire and travel support from Noven. 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TI Shared and Distinct Intrinsic Functional Network Centrality in Autism and Attention-Deficit/Hyperactivity Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; amygdala; autism; caudate; functional connectivity; network centrality; precuneus; resting state fMRI ID RESTING-STATE FMRI; PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; DEFAULT-MODE NETWORK; SPECTRUM DISORDERS; CONNECTIVITY MRI; HUMAN BRAIN; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; YOUNG-CHILDREN AB Background: Individuals with autism spectrum disorders (ASD) often exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD and ADHD and typically developing children who completed a resting state functional magnetic resonance imaging scan. Methods: We measured voxelwise network centrality, functional connectivity metrics indexing local (degree centrality [DC]) and global (eigenvector centrality) functional relationships across the entire brain connectome, in resting state functional magnetic resonance imaging data from 56 children with ASD, 45 children with ADHD, and 50 typically developing children. A one-way analysis of covariance, with group as fixed factor (whole-brain corrected), was followed by post hoc pairwise comparisons. Results: Cortical and subcortical areas exhibited centrality abnormalities, some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD(+) and ASD(-), respectively) revealed that the ASD(+) group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level, eigenvector centrality group patterns were similar to DC. Conclusions: ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level. C1 [Di Martino, Adriana; Kelly, Clare; Grzadzinski, Rebecca; Mennes, Maarten; Schvarcz, Ariel; Castellanos, F. Xavier] Langone Med Ctr, Inst Pediat Neurosci, Ctr Child Study, New York, NY USA. [Zuo, Xi-Nian] Chinese Acad Sci, Key Lab Behav Sci, Inst Psychol, Lab Funct Connectome & Dev, Beijing, Peoples R China. [Castellanos, F. Xavier] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Schvarcz, Ariel] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Grzadzinski, Rebecca; Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, New York, NY USA. [Castellanos, F. Xavier; Milham, Michael P.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. [Milham, Michael P.] Child Mind Inst, Ctr Developing Brain, New York, NY USA. RP Milham, MP (reprint author), Child Mind Inst, Ctr Developing Brain, 445 Pk Ave, New York, NY 10022 USA. EM michael.milham@childmind.org RI Mennes, Maarten/C-9924-2011; Milham, Michael/K-9501-2014; Di Martino, Adriana/L-2497-2014 OI Mennes, Maarten/0000-0002-7279-3439; FU Brain & Behavior Research Foundation; National Institute of Mental Health [K23MH087770, R01MH081218]; National Institute of Child Health and Human Development [R01HD065282]; Autism Speaks; Stavros Niarchos Foundation; Leon Levy Foundation; Natural Science Foundation of China [81171409, 81220108014]; Chinese Academy of Sciences [KSZD-EW-TZ-002, Y0CX492S03, Y2CX112006] FX This work was supported by grants from the Brain & Behavior Research Foundation (previously known as National Alliance for Research in Schizophrenia and Affective Disorders) to ADM and National Institute of Mental Health (K23MH087770 to ADM; R01MH081218 to FXC); from the National Institute of Child Health and Human Development (R01HD065282), Autism Speaks, and the Stavros Niarchos Foundation, awarded to FXC; the Leon Levy Foundation awarded to MPM, ADM, and CK; the Natural Science Foundation of China (81171409, 81220108014) and the Chinese Academy of Sciences (KSZD-EW-TZ-002, Y0CX492S03, Y2CX112006) to X-NZ; and gifts from Joseph P. 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Psychiatry PD OCT 15 PY 2013 VL 74 IS 8 BP 623 EP 632 DI 10.1016/j.biopsych.2013.02.011 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223OH UT WOS:000324814900010 PM 23541632 ER PT J AU Sarachana, T Hu, VW AF Sarachana, Tewarit Hu, Valerie W. TI Differential recruitment of coregulators to the RORA promoter adds another layer of complexity to gene (dys) regulation by sex hormones in autism SO MOLECULAR AUTISM LA English DT Article DE Autism; RORA; Sex hormones; Nuclear receptor; Coregulator; Coactivator; Corepressor ID ESTROGEN-RECEPTOR-ALPHA; STAGGERER MUTANT MICE; SPECTRUM DISORDERS; FETAL TESTOSTERONE; ANDROGEN RECEPTOR; NUCLEAR RECEPTORS; SIGNALING ATLAS; DSM-IV; BRAIN; BETA AB Background: Our independent cohort studies have consistently shown the reduction of the nuclear receptor RORA (retinoic acid-related orphan receptor-alpha) in lymphoblasts as well as in brain tissues from individuals with autism spectrum disorder (ASD). Moreover, we have found that RORA regulates the gene for aromatase, which converts androgen to estrogen, and that male and female hormones regulate RORA in opposite directions, with androgen suppressing RORA, suggesting that the sexually dimorphic regulation of RORA may contribute to the male bias in ASD. However, the molecular mechanisms through which androgen and estrogen differentially regulate RORA are still unknown. Methods: Here we use functional knockdown of hormone receptors and coregulators with small interfering RNA (siRNA) to investigate their involvement in sex hormone regulation of RORA in human neuronal cells. Luciferase assays using a vector containing various RORA promoter constructs were first performed to identify the promoter regions required for inverse regulation of RORA by male and female hormones. Sequential chromatin immunoprecipitation methods followed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses of RORA expression in hormone-treated SH-SY5Y cells were then utilized to identify coregulators that associate with hormone receptors on the RORA promoter. siRNA-mediated knockdown of interacting coregulators was performed followed by qRT-PCR analyses to confirm the functional requirement of each coregulator in hormone-regulated RORA expression. Results: Our studies demonstrate the direct involvement of androgen receptor (AR) and estrogen receptor (ER) in the regulation of RORA by male and female hormones, respectively, and that the promoter region between -10055 bp and -2344 bp from the transcription start site of RORA is required for the inverse hormonal regulation. We further show that AR interacts with SUMO1, a reported suppressor of AR transcriptional activity, whereas ER alpha interacts with the coactivator NCOA5 on the RORA promoter. siRNA-mediated knockdown of SUMO1 and NCOA5 attenuate the sex hormone effects on RORA expression. Conclusions: AR and SUMO1 are involved in the suppression RORA expression by androgen, while ER alpha and NCOA5 collaborate in the up-regulation of RORA by estrogen. While this study offers a better understanding of molecular mechanisms involved in sex hormone regulation of RORA, it also reveals another layer of complexity with regard to gene regulation in ASD. Inasmuch as coregulators are capable of interacting with a multitude of transcription factors, aberrant expression of coregulator proteins, as we have seen previously in lymphoblasts from individuals with ASD, may contribute to the polygenic nature of gene dysregulation in ASD. C1 [Sarachana, Tewarit; Hu, Valerie W.] George Washington Univ, Dept Biochem & Mol Med, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Sarachana, Tewarit] Chulalongkorn Univ, Fac Allied Hlth Sci, Dept Clin Chem, Bangkok 10330, Thailand. RP Hu, VW (reprint author), George Washington Univ, Dept Biochem & Mol Med, Sch Med & Hlth Sci, 2300 1 St NW, Washington, DC 20037 USA. EM valhu@gwu.edu RI nakham, kwanphat/F-4661-2014 FU Simons Foundation [221192]; George Washington University; Office of the Commission on Higher Education of the Royal Thai Government, Thailand, through the Faculty of Allied Health Sciences, Chulalongkorn University FX We wish to thank Mr. Bren Belovarac for his assistance with the qRT-PCR analysis of siAR- and siER alpha-transfected cells. This study was supported in part by a generous gift from the LIFE Foundation (Aspen, CO, USA), a Simons Foundation grant number 221192 (VWH), and an intramural grant from The George Washington University (Medical Faculty Associates award). We also thank Turner Biosystems (now Promega, Madison, WI, USA) for the gift of the Veritas microplate luminometer to VWH for her research on autism. 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 OCT 11 PY 2013 VL 4 AR 39 DI 10.1186/2040-2392-4-39 PG 16 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254YK UT WOS:000327205800001 PM 24119295 ER PT J AU Jones, RM Cadby, G Melton, PE Abraham, LJ Whitehouse, AJ Moses, EK AF Jones, Rachel Maree Cadby, Gemma Melton, Phillip E. Abraham, Lawrence J. Whitehouse, Andrew J. Moses, Eric K. TI Genome-wide association study of autistic-like traits in a general population study of young adults SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autistic-like traits; genome-wide association; PRKCB1; autism spectrum disorder; autism spectrum quotient; CBLN1 ID SPECTRUM QUOTIENT AQ; COPY NUMBER VARIANTS; TOURETTE-SYNDROME; DISORDERS; PREVALENCE; BEHAVIORS; PHENOTYPE; CHILDREN; NEUREXIN; EMPATHY AB It has been proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD), representing the extreme end of this distribution. The current study undertook a genome-wide association (GWA) scan of 965 young Western Australian adults to identify novel risk variants associated with autistic-like traits. No associations reached genome-wide significance; however, a review of nominally associated single nucleotide polymorphisms (SNPs) indicated two positional candidate loci that have been previously implicated in autistic-like trait etiology. Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A GWA study using 2,462,046 SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine) Study. No SNP associations reached genome-wide significance (p < 5.0 x 10-8). However, investigations into nominal observed SNP associations (p < 1.0 x 10-5) add support to two positional candidate genes previously implicated in ASD etiology, PRKCB1, and CBLN1. The rs198198 SNP (p = 9.587 x 10-6), is located within an intron of the protein kinase C, beta 1 (PRKCB1) gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p = 1.78 x 10-6) is located in a region flanking the Cerebellin 1 (CBLN1) gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD. C1 [Jones, Rachel Maree; Cadby, Gemma; Melton, Phillip E.; Abraham, Lawrence J.; Moses, Eric K.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia. [Abraham, Lawrence J.] Univ Western Australia, Sch Chem & Biochem, Perth, WA 6009, Australia. [Whitehouse, Andrew J.] Telethon Inst Child Hlth Res, Perth, WA, Australia. RP Moses, EK (reprint author), Univ Western Australia, Ctr Genet Origins Hlth & Dis, 35 Stirling Highway, Perth, WA 6009, Australia. EM eric.moses@uwa.edu.au RI Melton, Phillip/A-5012-2013 OI Melton, Phillip/0000-0003-4026-2964 FU National Health and Medical Research Council [572613] FX Grant sponsor: National Health and Medical Research Council; Grant number: 572613. 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Hum. Neurosci. PD OCT 11 PY 2013 VL 7 AR 658 DI 10.3389/fnhum.2013.00658 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 232XE UT WOS:000325527000001 PM 24133439 ER PT J AU Schmidt, C AF Schmidt, Charles TI PSYCHIATRIC RESEARCH Severe Autism, Often Slighted, Now Targeted for Study SO SCIENCE LA English DT News Item NR 0 TC 0 Z9 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 11 PY 2013 VL 342 IS 6155 BP 179 EP 179 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232EV UT WOS:000325475200015 PM 24115416 ER PT J AU De Angelis, M Piccolo, M Vannini, L Siragusa, S De Giacomo, A Serrazzanetti, DI Cristofori, F Guerzoni, ME Gobbetti, M Francavilla, R AF De Angelis, Maria Piccolo, Maria Vannini, Lucia Siragusa, Sonya De Giacomo, Andrea Serrazzanetti, Diana Isabella Cristofori, Fernanda Guerzoni, Maria Elisabetta Gobbetti, Marco Francavilla, Ruggiero TI Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified SO PLOS ONE LA English DT Article ID HUMAN INTESTINAL BACTERIA; GUT MICROBIOTA; SPECTRUM DISORDERS; REGRESSIVE AUTISM; ONSET AUTISM; BEHAVIOR; DISEASE; HEALTH; MODEL; FLORA AB This study aimed at investigating the fecal microbiota and metabolome of children with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and autism (AD) in comparison to healthy children (HC). Bacterial tag-encoded FLX-titanium amplicon pyrosequencing (bTEFAP) of the 16S rDNA and 16S rRNA analyses were carried out to determine total bacteria (16S rDNA) and metabolically active bacteria (16S rRNA), respectively. The main bacterial phyla (Firmicutes, Bacteroidetes, Fusobacteria and Verrucomicrobia) significantly (P<0.05) changed among the three groups of children. As estimated by rarefaction, Chao and Shannon diversity index, the highest microbial diversity was found in AD children. Based on 16S-rRNA and culture-dependent data, Faecalibacterium and Ruminococcus were present at the highest level in fecal samples of PDD-NOS and HC children. Caloramator, Sarcina and Clostridium genera were the highest in AD children. Compared to HC, the composition of Lachnospiraceae family also differed in PDD-NOS and, especially, AD children. Except for Eubacterium siraeum, the lowest level of Eubacteriaceae was found on fecal samples of AD children. The level of Bacteroidetes genera and some Alistipes and Akkermansia species were almost the highest in PDD-NOS or AD children as well as almost all the identified Sutterellaceae and Enterobacteriaceae were the highest in AD. Compared to HC children, Bifidobacterium species decreased in AD. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of free amino acids and volatile organic compounds of fecal samples were markedly affected in PDD-NOS and, especially, AD children. If the gut microbiota differences among AD and PDD-NOS and HC children are one of the concomitant causes or the consequence of autism, they may have implications regarding specific diagnostic test, and/or for treatment and prevention. C1 [De Angelis, Maria; Piccolo, Maria; Siragusa, Sonya; Gobbetti, Marco] Univ Bari Aldo Moro, Dept Soil Plant & Food Sci, Bari, Italy. [Vannini, Lucia; Serrazzanetti, Diana Isabella] Univ Cesena, Interdept Ctr Ind Agri Food Res, Cesena, Italy. [Vannini, Lucia; Guerzoni, Maria Elisabetta] Univ Bologna, Dept Agr & Food Sci, Bologna, Italy. [De Giacomo, Andrea] Univ Bari Aldo Moro, Child Neurol & Psychiat Unit, Dept Neurol & Psychiat Sci, Bari, Italy. [Cristofori, Fernanda; Francavilla, Ruggiero] Univ Bari Aldo Moro, Dept Interdisciplinary Med, Bari, Italy. RP De Angelis, M (reprint author), Univ Bari Aldo Moro, Dept Soil Plant & Food Sci, Bari, Italy. EM maria.deangelis@uniba.it FU Department of Soil, Plant and Food Science FX The work was funded by the Department of Soil, Plant and Food Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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We hypothesize that acute brain inflammation caused by neonatal infection reduces the bioavailability of iron required for oligodendrocyte maturation and white matter development. Here, we confirm that peripheral Escherichia coli infection in neonates at postnatal day 3 (P3) caused acute brain inflammation that was resolved within 72 h. Nonetheless, transient early life infection (ELI) profoundly influenced behavior, white matter development, and iron homeostasis in the brain. For instance, mice exposed to E. coli as neonates had increased locomotor activity and impaired motor coordination as juveniles (P35) and young adults (P60). In addition, these behavioral deficits were associated with marked hypomyelination and a reduction of oligodendrocytes in subcortical white matter and motor cortex. Moreover, ELI altered transcripts related to cellular sequestration of iron in the brain including hepcidin, ferroportin, and L-ferritin. For example, ELI increased hepcidin mRNA and decreased ferroportin mRNA and protein in the brain at P4, which preceded increased L-ferritin mRNA at P12. Consistent with the mRNA results, L-ferritin protein was robustly increased at P12 specifically in neurons of E. coli infected mice. We interpret these data to indicate that neonatal infection causes significant neuronal sequestration of iron at a time point before myelination. Together, these data indicate a possible role for aberrant neuronal iron storage in neonatal infection-induced disturbances in myelination and behavior. C1 [Lieblein-Boff, Jacqueline C.; Mckim, Daniel B.; Wei, Ping; Deng, Zhen; Sawicki, Caroline; McTigue, Dana M.; Godbout, Jonathan P.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. [Mckim, Daniel B.; Shea, Daniel T.; Sawicki, Caroline; Quan, Ning; Bailey, Michael T.] Ohio State Univ, Div Oral Biol, Columbus, OH 43210 USA. 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Aside from the physical and behavioural issues that need to be dealt with, there are significant emotional and financial costs associated with living with someone diagnosed with ASD. Understanding how autism occurs will assist in preparing families to deal with ASD, if not preventing or lessening its occurrence. Serotonin plays a vital role in the development of the brain during the prenatal and postnatal periods, yet very little is known about the serotonergic systems that affect children with ASD. This review seeks to provide an understanding of the biochemistry and physiological actions of serotonin and its termination of action through the serotonin reuptake transporter (SERT). Epidemiological studies investigating prenatal conditions that can increase the risk of ASD describe a number of factors which elevate plasma cortisol levels causing such symptoms during pregnancy such as hypertension, gestational diabetes and depression. Because cortisol plays an important role in driving dysregulation of serotonergic signalling through elevating SERT production in the developing brain, it is also necessary to investigate the physiological functions of cortisol, its action during gestation and metabolic syndromes. C1 Griffith Univ, Sch Med Sci, Southport, Qld 4222, Australia. RP Rose'Meyer, R (reprint author), Griffith Univ, Sch Med Sci, Gold Coast Campus,Parklands Dr, Southport, Qld 4222, Australia. 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Autism PD OCT 8 PY 2013 VL 4 AR 37 DI 10.1186/2040-2392-4-37 PG 16 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254YJ UT WOS:000327205700001 PM 24103554 ER PT J AU Yoshimura, Y Kikuchi, M Shitamichi, K Ueno, S Munesue, T Ono, Y Tsubokawa, T Haruta, Y Oi, M Niida, Y Remijn, GB Takahashi, T Suzuki, M Higashida, H Minabe, Y AF Yoshimura, Yuko Kikuchi, Mitsuru Shitamichi, Kiyomi Ueno, Sanae Munesue, Toshio Ono, Yasuki Tsubokawa, Tsunehisa Haruta, Yasuhiro Oi, Manabu Niida, Yo Remijn, Gerard B. Takahashi, Tsutomu Suzuki, Michio Higashida, Haruhiro Minabe, Yoshio TI Atypical brain lateralisation in the auditory cortex and language performance in 3-to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study SO MOLECULAR AUTISM LA English DT Article DE Autism spectrum disorder (ASD); Laterality index; Magnetoencephalography (MEG); P50m; Young children ID 2-TO 5-YEAR-OLD CHILDREN; HUMAN CEREBRAL-CORTEX; EVOKED FIELDS; DEVELOPMENTAL-CHANGES; MAGNETIC-FIELDS; YOUNG-CHILDREN; SPEECH; IMPAIRMENT; MATURATION; RESPONSES AB Background: Magnetoencephalography (MEG) is used to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. In young children, however, the simultaneous quantification of the bilateral auditory-evoked response during binaural hearing is difficult using conventional adult-sized MEG systems. Recently, a child-customised MEG device has facilitated the acquisition of bi-hemispheric recordings, even in young children. Using the child-customised MEG device, we previously reported that language-related performance was reflected in the strength of the early component (P50m) of the auditory evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5 years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to investigate how this neurophysiological index in each hemisphere is correlated with language performance in autism spectrum disorder (ASD) and TD children. Methods: We used magnetoencephalography (MEG) to measure the auditory evoked magnetic field (AEF), which reflects language-related performance. We investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33 young children (3 to 7 years old) with ASD and in 30 young children who were typically developing (TD). The children were matched according to their age (in months) and gender. Most of the children with ASD were high-functioning subjects. Results: The results showed that the children with ASD exhibited significantly less leftward lateralisation in their P50m intensity compared with the TD children. Furthermore, the results of a multiple regression analysis indicated that a shorter P50m latency in both hemispheres was specifically correlated with higher language-related performance in the TD children, whereas this latency was not correlated with non-verbal cognitive performance or chronological age. The children with ASD did not show any correlation between P50m latency and language-related performance; instead, increasing chronological age was a significant predictor of shorter P50m latency in the right hemisphere. Conclusions: Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development. C1 [Yoshimura, Yuko; Kikuchi, Mitsuru; Munesue, Toshio; Oi, Manabu; Niida, Yo; Higashida, Haruhiro; Minabe, Yoshio] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa, Japan. [Yoshimura, Yuko; Kikuchi, Mitsuru; Shitamichi, Kiyomi; Ueno, Sanae; Munesue, Toshio; Ono, Yasuki; Minabe, Yoshio] Kanazawa Univ, Grad Sch Med Sci, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa, Japan. [Kikuchi, Mitsuru; Munesue, Toshio; Oi, Manabu; Higashida, Haruhiro; Minabe, Yoshio] Kanazawa Univ, Osaka Univ, United Grad Sch Child Dev, Dept Child Dev, Osaka, Japan. [Kikuchi, Mitsuru; Munesue, Toshio; Oi, Manabu; Higashida, Haruhiro; Minabe, Yoshio] Osaka Univ, Hamamatsu Univ Sch Med, Osaka, Japan. [Remijn, Gerard B.] Kyushu Univ, Int Educ Ctr, Fukuoka 812, Japan. [Tsubokawa, Tsunehisa] Kanazawa Univ, Grad Sch Med Sci, Dept Anaesthesiol, Kanazawa, Ishikawa, Japan. [Haruta, Yasuhiro] Yokogawa Elect Corp, Dept MEG, Tokyo, Japan. [Takahashi, Tsutomu; Suzuki, Michio] Toyama Univ, Dept Neuropsychiat, Toyama 930, Japan. RP Kikuchi, M (reprint author), Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa, Japan. EM mitsuru@zc4.so-net.ne.jp FU MEXT, Japan [24000012] FX This study was supported by Grant-in-Aid for Specially Promoted (research no. 24000012), the Hokuriku Innovation Cluster for Health Science (MEXT Program for Fostering Regional Innovation) and the Strategic Research Program for Brain Sciences from MEXT, Japan. 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Autism PD OCT 8 PY 2013 VL 4 AR 38 DI 10.1186/2040-2392-4-38 PG 14 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 254YJ UT WOS:000327205700002 PM 24103585 ER PT J AU Sawa, T Kodaira, M Oiji, A Sasayama, D Iwadare, Y Ushijima, H Usami, M Watanabe, K Saito, K AF Sawa, Tetsuji Kodaira, Masaki Oiji, Arata Sasayama, Daimei Iwadare, Yoshitaka Ushijima, Hirokage Usami, Masahide Watanabe, Kyota Saito, Kazuhiko TI Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders SO ANNALS OF GENERAL PSYCHIATRY LA English DT Article DE Pervasive developmental disorders; Childhood; Adolescence; Iowa gambling task; Wisconsin card sorting test; Orbitofrontal cortex; Dorsolateral prefrontal cortex ID IOWA GAMBLING TASK; CARD SORTING TEST; DECISION-MAKING; AUTISM; CORTEX; PERFORMANCE; ACTIVATION AB Background: Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes to the pathophysiology of pervasive developmental disorders (PDD). The purpose of this study was to investigate neuropsychological dysfunctions in both the DLPFC and OFC of children and adolescents with high-functioning PDD. Methods: The Iowa gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting Test (WCST), which reflects DLPFC function, were assigned to 19 children and early adolescents with high-functioning PDD and 19 healthy controls matched for gender, age, and intelligence. Results: Compared to healthy controls, patients with high-functioning PDD displayed poorer performance on the IGT and the WCST. Conclusions: These results indicate that both the DLPFC and OFC could be impaired in children and early adolescents with high-functioning PDD. C1 [Sawa, Tetsuji; Oiji, Arata] Kitasato Univ, Grad Sch Med Sci, Dept Dev Psychiat, Minami Ku, Sagamihara, Kanagawa 2520374, Japan. [Kodaira, Masaki; Saito, Kazuhiko] Aiiku Hosp, Dept Child & Adolescent Mental Hlth, Minato Ku, Tokyo 1068580, Japan. [Sasayama, Daimei] Shinshu Univ, Sch Med, Dept Neuropsychiat, Matsumoto, Nagano 3908621, Japan. [Iwadare, Yoshitaka; Ushijima, Hirokage; Usami, Masahide; Watanabe, Kyota] Kohnodai Hosp, Natl Ctr Global Hlth & Med, Dept Child & Adolescent Psychiat, Ichikawa, Chiba 2720836, Japan. RP Oiji, A (reprint author), Kitasato Univ, Grad Sch Med Sci, Dept Dev Psychiat, Minami Ku, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520374, Japan. EM pah00652@gmail.com RI Usami, Masahide/G-1404-2015 OI Usami, Masahide/0000-0002-1145-9971 FU Japanese Ministry of Health, Labour, and Welfare [20B-6] FX This study was funded by a research grant for Nervous and Mental Disorders (20B-6) of the Japanese Ministry of Health, Labour, and Welfare. We would like to express our deep gratitude to Professor Katsutoshi Tanaka, Professor Hirokuni Tagaya, and Professor Yumi Iwamitsu for giving us good opinions and advice. Moreover, we feel deeply grateful for the children, caregivers, and staff members who participated in this study. 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Keown, Christopher L. Nair, Aarti Mueller, Ralph-Axel TI Approaches to local connectivity in autism using resting state functional connectivity MRI SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE autism; local connectivity; functional MRI; regional homogeneity; graphtheory; BOLD signal; intrinsic connectivity ID SPECTRUM DISORDERS; BRAIN CONNECTIVITY; DEFAULT MODE; REGIONAL HOMOGENEITY; NEURAL SYSTEMS; NETWORKS; MOTION; CORTEX; PERCEPTION; IMAGES AB While the literature on aberrant long-distance connectivity in autism spectrum disorder (ASD) has grown fast over the past decade, little is known about local connectivity. We used regional homogeneity and local density approaches at different spatial scales to examine local connectivity in 29 children and adolescents with ASD and 29 matched typically developing participants, using resting state functional magnetic resonance imaging data. Across a total of 12 anlysis pipelines the gross pattern of between-group findings was overall stable, with local overconnectivity in the ASD group in occipital and posterior tempporal regions and underconnectivity in middle/posterior cingulate, and medial prefrontal regions. This general patern was confirmed in secondary anlyses for low-mention subsamples (n= 20 per group), in which time series segments with >0.25 mm head motion were censored, as well as in an analysis including global signal regression. Local overconnectivity in visual regions appears in ASD, whereas cingulate and medial frontal underconnnectivity may relate to aberrant function within the defalut mode network. C1 [Maximo, Jose O.; Keown, Christopher L.; Nair, Aarti; Mueller, Ralph-Axel] San Diego State Univ, Dept Psychol, Brain Dev Imaging Lab, San Diego, CA 92120 USA. [Keown, Christopher L.] San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92120 USA. [Nair, Aarti] San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92120 USA. [Nair, Aarti] Univ Calif San Diego, San Diego, CA 92103 USA. RP Muller, RA (reprint author), San Diego State Univ, Dept Psychol, Brain Dev Imaging Lab, 6363 Alvarado Court,Suite 200, San Diego, CA 92120 USA. EM rmueller@mail.sdsu.edu FU National Institutes of Health [R01MH081023]; NIH/NIGMS IMSD [5R25GM058906-13]; Autism Speaks (Dennis Weatherstone Predoctoral Fellowship) [7850] FX This study was supported by the National Institutes of Health R01MH081023, with additional funding from NIH/NIGMS IMSD 5R25GM058906-13 (Jose O. Maximo) and Autism Speaks (Dennis Weatherstone Predoctoral Fellowship# 7850; to Aarti Nair). Special thanks to the participants and their families. 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Hum. Neurosci. PD OCT 8 PY 2013 VL 7 AR 605 DI 10.3389/fnhum.2013.00605 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 230GM UT WOS:000325325100001 PM 24155702 ER PT J AU Pearson, A Ropar, D Hamilton, AFD AF Pearson, Amy Ropar, Danielle Hamilton, Antonia F. de C. TI A review of visual perspective taking in autism spectrum disorder SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Review DE visual perspective taking; autism spectrum disorder; spatial transformations; social cognition; spatial cognition; theory of mind ID ASPERGER-SYNDROME; FUNCTIONING AUTISM; JOINT ATTENTION; MIND; CHILDREN; ADULTS; TRANSFORMATIONS; SKILLS; BRAIN; ATTRIBUTION AB Impairments in social cognition are a key symptom of autism spectrum disorder (ASD). People with autism have great difficulty with understanding the beliefs and desires of other people. In recent years literature has begun to examine the link between impairments in social cognition and abilities which demand the use of spatial and social skills, such as visual perspective taking (VPT). Flavell (1977) defined two levels of perspective taking: VPT level 1 is the ability to understand that other people have a different line of sight to ourselves, whereas VPT level 2 is the understanding that two people viewing the same item from different points in space may see different things. So far, literature on whether either level of VPT is impaired or intact in autism is inconsistent. Here we review studies which have examined VPT levels 1 and 2 in people with autism with a focus on their methods. We conclude the review with an evaluation of the findings into VPT in autism and give recommendations for future research which may give a clearer insight into whether perspective taking is truly impaired in autism. 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Hum. Neurosci. PD OCT 8 PY 2013 VL 7 AR 652 DI 10.3389/fnhum.2013.00652 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 230HS UT WOS:000325328900001 PM 24115930 ER PT J AU Chanda, S Marro, S Wernig, M Sudhof, TC AF Chanda, Soham Marro, Samuele Wernig, Marius Suedhof, Thomas C. TI Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cellular reprogramming; stem cells; postsynaptic density; neurexin; synapse ID PLURIPOTENT STEM-CELLS; FUNCTIONAL-NEURONS; NEUROLOGICAL DISEASE; DOPAMINERGIC-NEURONS; TRANSMISSION; INDUCTION; PROGRESS; BINDING; MODEL; IPSCS AB Recent studies suggest that induced neuronal (iN) cells that are directly transdifferentiated from nonneuronal cells provide a powerful opportunity to examine neuropsychiatric diseases. However, the validity of using this approach to examine disease-specific changes has not been demonstrated. Here, we analyze the phenotypes of iN cells that were derived from murine embryonic fibroblasts cultured from littermate wild-type and mutant mice carrying the autism-associated R704C substitution in neuroligin-3. We show that neuroligin-3 R704C-mutant iN cells exhibit a large and selective decrease in AMPA-type glutamate receptor-mediated synaptic transmission without changes in NMDA-type glutamate receptor-or in GABAA receptor-mediated synaptic transmission. Thus, the synaptic phenotype observed in R704C-mutant iN cells replicates the previously observed phenotype of R704C-mutant neurons. Our data show that the effect of the R704C mutation is applicable even to neurons transdifferentiated from fibroblasts and constitute a proof-of-concept demonstration that iN cells can be used for cellular disease modeling. C1 [Chanda, Soham; Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Chanda, Soham; Marro, Samuele; Wernig, Marius] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Chanda, Soham; Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Chanda, Soham; Marro, Samuele; Wernig, Marius] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. RP Wernig, M (reprint author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. EM wernig@stanford.edu; tcs1@stanford.edu RI Marro, Samuele/I-4493-2014 OI Marro, Samuele/0000-0002-9326-6945 FU National Institutes of Health [R01 MH092931, AG010770-18A1]; Dean's Postdoctoral Fellowship FX We thank all members of the T.C.S. and M.W. laboratories for helpful discussions. This study was supported by National Institutes of Health Grants R01 MH092931 and AG010770-18A1 (to T.C.S. and M.W.), and a Dean's Postdoctoral Fellowship (to S.M.). M.W. is a New York Stem Cell Foundation-Robertson Investigator. 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Fernandez, Bridget Szatmari, Peter TI A molecular genetic study of autism and related phenotypes in extended pedigrees SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Genetics; Linkage; Pedigree; Phenotype; Posterior probability of linkage ID PERVASIVE DEVELOPMENTAL DISORDERS; GENOME-WIDE LINKAGE; SPECTRUM DISORDERS; BROAD AUTISM; MULTIPLE-INCIDENCE; FAMILY-HISTORY; REPETITIVE BEHAVIOR; RECURRENCE RISK; INDIVIDUALS; SIBLINGS AB Background: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e. g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. C1 [Piven, Joseph; Parlier, Morgan] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Vieland, Veronica J.; Huang, Yungui; Walters, Kimberly A.] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH 43215 USA. [Vieland, Veronica J.] Ohio State Univ, Dept Pediat, Columbus, OH 43215 USA. [Vieland, Veronica J.] Ohio State Univ, Dept Stat, Columbus, OH 43215 USA. [Thompson, Ann; O'Conner, Irene; Woodbury-Smith, Mark; Szatmari, Peter] McMaster Dept Psychiat & Behav Neurosci, Hamilton, ON L9H 3Z5, Canada. [Fernandez, Bridget] Hlth Sci Ctr, Prov Med Genet Program, St John, NF A1B 3V6, Canada. [Szatmari, Peter] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. RP Piven, J (reprint author), Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, CB 3367, Chapel Hill, NC 27599 USA. EM jpiven@med.unc.edu FU NIH [MH076028, HD003110, R01 MH086117, U24 MH068457] FX This project was supported by the following grants: NIH MH076028, HD003110 (JP), R01 MH086117 (VJV); U24 MH068457 (J Tischfield, PI). We also acknowledge the contributions of Molly Losh, Ph.D. to the design of this study. Finally, we would like to thank all the families who participated in this research. 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The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries. Case presentation: The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation. Conclusions: Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability. 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Middelman, Anthonieke van Hulten, Josephus A. Martens, Gerard J. M. Homberg, Judith R. Kolk, Sharon M. TI Lack of serotonin reuptake during brain development alters rostral raphe-prefrontal network formation SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE explant assays; prefrontal cortex; serotonin transporter; microdissection; axon guidance; depression; SERT; autism ID DEVELOPING RAT-BRAIN; KNOCK-OUT MICE; CEREBRAL-CORTEX; TRANSIENT EXPRESSION; CORTICAL DEVELOPMENT; AXON GUIDANCE; SSRI ANTIDEPRESSANTS; NEUROTROPHIC FACTOR; PRENATAL EXPOSURE; GENETIC-VARIATION AB Besides its classical neurotransmitter function, serotonin (5-HT) has been found to also act as a neurodevelopmental signal. During development, the 5-HT projection system, besides an external placental source, represents one of the earliest neurotransmitter systems to innervate the brain. One of the targets of the 5-HT projection system, originating in the brainstem raphe nuclei, is the medial prefrontal cortex (mPFC), an area involved in higher cognitive functions and important in the etiology of many neurodevelopmental disorders. Little is known, however, about the exact role of 5-HT and its signaling molecules in the formation of the raphe-prefrontal network. Using explant essays, we here studied the role of the 5-HT transporter (5-HTT), an important modulator of the 5-HT signal, in rostral raphe-prefrontal network formation. We found that the chemotrophic nature of the interaction between the origin (rostral raphe cluster) and a target (mPFC) of the 5-HT projection system was affected in rats lacking the 5-HTT (5-HTT-/-). While 5-HTT deficiency did not affect the dorsal raphe 5-HT-positive outgrowing neurites, the median raphe 5-HT neurites switched from a strong repulsive to an attractive interaction when co-cultured with the mPFC. Furthermore, the fasciculation of the mPFC outgrowing neurites was dependent on the amount of 5-HTT. In the mPFC of 5-HTT-/- pups, we observed clear differences in 5-HT innervation and the identity of a class of projection neurons of the mPFC. In the absence of the 5-HTT, the 5-HT innervation in all subareas of the early postnatal mPFC increased dramatically and the number of Satb2-positive callosal projection neurons was decreased. Together, these results suggest a 5-HTT dependency during early development of these brain areas and in the formation of the raphe-prefrontal network. The tremendous complexity of the 5-HT projection system and its role in several neurodevelopmental disorders highlights the need for further research in this largely unexplored area. C1 [Witteveen, Josefine S.; van Hulten, Josephus A.; Martens, Gerard J. M.; Kolk, Sharon M.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Mol Anim Physiol, NL-6525 GA Nijmegen, Netherlands. [Middelman, Anthonieke; Homberg, Judith R.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Med Ctr, Dept Cognit Neurosci, NL-6525 GA Nijmegen, Netherlands. RP Kolk, SM (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen Ctr Mol Life Sci, Dept Mol Anim Physiol, Geert Grootepl Zuid 28, NL-6525 GA Nijmegen, Netherlands. EM s.kolk@ncmls.ru.nl RI Homberg, Judith/D-2473-2010; Kolk, Sharon/A-9055-2011; Martens, Gerard/D-1925-2010 OI Kolk, Sharon/0000-0003-2116-5456; FU Dutch Organization of Scientific Research (NWO) [433-09-311] FX This work was supported by the Dutch Organization of Scientific Research (NWO grant # 433-09-311) awarded to J. Homberg. We thank Stephanie Miceli and the reviewers for critically reading this manuscript and members of the Martens, Kolk, and Homber labs for helpful editing and discussions. We thank the NCMLS microscopy platform (http://ncmls.nl/technology-platform/microscope-imaging-centre/) for excellent support and maintenance of the equipment. 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Cell. Neurosci. PD OCT 4 PY 2013 VL 7 AR 143 DI 10.3389/fncel.2013.00143 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 228FP UT WOS:000325171500001 PM 24109430 ER PT J AU Abrahams, BS Arking, DE Campbell, DB Mefford, HC Morrow, EM Weiss, LA Menashe, I Wadkins, T Banerjee-Basu, S Packer, A AF Abrahams, Brett S. Arking, Dan E. Campbell, Daniel B. Mefford, Heather C. Morrow, Eric M. Weiss, Lauren A. Menashe, Idan Wadkins, Tim Banerjee-Basu, Sharmila Packer, Alan TI SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs) SO MOLECULAR AUTISM LA English DT Letter AB New technologies enabling genome-wide interrogation have led to a large and rapidly growing number of autism spectrum disorder (ASD) candidate genes. Although encouraging, the volume and complexity of these data make it challenging for scientists, particularly non-geneticists, to comprehensively evaluate available evidence for individual genes. Described here is the Gene Scoring module within SFARI Gene 2.0 (https://gene.sfari.org/autdb/GS_Home.do), a platform developed to enable systematic community driven assessment of genetic evidence for individual genes with regard to ASD. C1 [Abrahams, Brett S.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Abrahams, Brett S.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Campbell, Daniel B.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Campbell, Daniel B.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Mefford, Heather C.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 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. [Weiss, Lauren A.] UCSF, Ctr Neurobiol & Psychiat, Inst Human Genet, Dept Psychiat, San Francisco, CA USA. [Menashe, Idan; Wadkins, Tim; Banerjee-Basu, Sharmila] MindSpec Inc, Mclean, VA USA. [Menashe, Idan] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Publ Hlth, IL-84105 Beer Sheva, Israel. [Packer, Alan] Simons Fdn Autism Res Initiat, New York, NY USA. RP Banerjee-Basu, S (reprint author), MindSpec Inc, 8280 Greensboro Dr,Suite 150, Mclean, VA USA. 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Pawlikowska, Ludmila TI A Genome-Wide Investigation of Copy Number Variation in Patients with Sporadic Brain Arteriovenous Malformation SO PLOS ONE LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; AUTISM SPECTRUM DISORDERS; RISK; POLYMORPHISMS; ASSOCIATION; GENE; SUSCEPTIBILITY; SCHIZOPHRENIA; PATHOGENESIS; MUTATIONS AB Background: Brain arteriovenous malformations (BAVM) are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGF beta) signaling pathway. Methods: To investigate whether copy number variations (CNVs) contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs were called using the PennCNV and Birdsuite algorithms and analyzed via segment-based and gene-based approaches. Common and rare CNVs were evaluated for association with BAVM. Results: A CNV region on 1p36.13, containing the neuroblastoma breakpoint family, member 1 gene (NBPF1), was significantly enriched with duplications in BAVM cases compared to controls (P = 2.2x10(-9)); NBPF1 was also significantly associated with BAVM in gene-based analysis using both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication; however, the association did not replicate in an independent cohort of 184 sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8). Rare CNV analysis did not identify genes significantly associated with BAVM. Conclusion: We did not identify common CNVs associated with sporadic BAVM that replicated in an independent cohort. Replication in larger cohorts is required to elucidate the possible role of common or rare CNVs in BAVM pathogenesis. C1 [Bendjilali, Nasrine; Kim, Helen; Weinsheimer, Shantel; Guo, Diana E.; Young, William L.; Pawlikowska, Ludmila] Univ Calif San Francisco, Cerebrovasc Res Ctr, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Kim, Helen; Kwok, Pui-Yan; Pawlikowska, Ludmila] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Kim, Helen; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kwok, Pui-Yan] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Zaroff, Jonathan G.; Sidney, Stephen] Kaiser Northern Calif Div Res, San Francisco, CA USA. [Lawton, Michael T.; Young, William L.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Koeleman, Bobby P. C.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands. [Klijn, Catharina J. M.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Young, William L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Pawlikowska, L (reprint author), Univ Calif San Francisco, Cerebrovasc Res Ctr, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. EM pawlikowskal@anesthesia.ucsf.edu RI Kwok, Pui-Yan/F-7725-2014 OI Kwok, Pui-Yan/0000-0002-5087-3059 FU National Institutes of Health (NIH) [P01 NS044155, R01 NS034949, K23 NS058357]; private Dutch foundation; NIH [P50 NS2372, U19 AI063603] FX This work was supported by National Institutes of Health (NIH) grants: P01 NS044155 (WLY), R01 NS034949 (WLY), and K23 NS058357 (HK). Additional support was provided by "Running for Nona,'' a private Dutch foundation (CJMK). Control cohorts were supported by NIH grants P50 NS2372 (to E. Mignot) and U19 AI063603 (to D. Salomon). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Pedrosa, Erika Hrabovsky, Anastasia Carroll, Reed Zheng, Deyou Lachman, Herbert M. TI Transcriptome Comparison of Human Neurons Generated Using Induced Pluripotent Stem Cells Derived from Dental Pulp and Skin Fibroblasts SO PLOS ONE LA English DT Article ID AUTISM SPECTRUM DISORDER; BIPOLAR DISORDER; DEFINED FACTORS; IPS CELLS; ASSOCIATION; INDUCTION; GENES; MODEL AB Induced pluripotent stem cell (iPSC) technology is providing an opportunity to study neuropsychiatric disorders through the capacity to grow patient-specific neurons in vitro. Skin fibroblasts obtained by biopsy have been the most reliable source of cells for reprogramming. However, using other somatic cells obtained by less invasive means would be ideal, especially in children with autism spectrum disorders (ASD) and other neurodevelopmental conditions. In addition to fibroblasts, iPSCs have been developed from cord blood, lymphocytes, hair keratinocytes, and dental pulp from deciduous teeth. Of these, dental pulp would be a good source for neurodevelopmental disorders in children because obtaining material is non-invasive. We investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on differentiated neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs). This is the first RNA-seq analysis comparing gene expression profiles in neurons derived from iPSCs made from different somatic cells. For the most part, gene expression profiles were quite similar with only 329 genes showing differential expression at a nominally significant p-value (p<0.05), of which 63 remained significant after correcting for genome-wide analysis (FDR <0.05). The most striking difference was the lower level of expression detected for numerous members of the all four HOX gene families in neurons derived from T-iPSCs. In addition, an increased level of expression was seen for several transcription factors expressed in the developing forebrain (FOXP2, OTX1, and LHX2, for example). Overall, pathway analysis revealed that differentially expressed genes that showed higher levels of expression in neurons derived from T-iPSCs were enriched for genes implicated in schizophrenia (SZ). The findings suggest that neurons derived from T-iPSCs are suitable for disease-modeling neuropsychiatric disorder and may have some advantages over those derived from F-iPSCs. C1 [Chen, Jian; Pedrosa, Erika; Hrabovsky, Anastasia; 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. [Foxe, John J.; Carroll, Reed; Zheng, Deyou; Lachman, Herbert M.] Albert Einstein Coll Med, Dominick Purpura Dept Neurosci, Bronx, NY 10467 USA. [Foxe, John J.] Albert Einstein Coll Med, Dept Pediat, 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 Lachman, HM (reprint author), Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. EM Herb.Lachman@einstein.yu.edu FU National Institutes of Health [MH087840, MH073164]; CTSA from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1RR025750, KL2RR025749, TL1RR025748]; NIH roadmap for Medical Research; Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) at the NIH [1P30HD071593-01] FX This work was supported by the National Institutes of Health (MH087840 and MH073164 to HML). This publication was also supported in part by the CTSA Grant UL1RR025750, KL2RR025749 and TL1RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research, and a grant to The Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK-IDDRC) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) at the NIH (1P30HD071593-01). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NICHD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Karakoc, Emre Mohajeri, Kiana Nelson, Ben Vives, Laura Jacquemont, Sebastien Munson, Jeff Bernier, Raphe Eichler, Evan E. TI Transmission Disequilibrium of Small CNVs in Simplex Autism SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; SPECTRUM DISORDERS; GENE; ALGORITHM; UBIQUITIN; VARIANTS; RESOURCE; DELETION; ORIGIN AB We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded similar to 2x more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p < 0.0002, measured by Social Responsiveness Scale [SRS] score), which contrasts with families where the phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p < 0.05). Taken together, these results suggest that small transmitted rare CNVs play a role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD. C1 [Krumm, Niklas; O'Roak, Brian J.; Karakoc, Emre; Mohajeri, Kiana; Nelson, Ben; Vives, Laura; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Jacquemont, Sebastien] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Vaud, Switzerland. [Munson, Jeff; Bernier, Raphe] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM eee@gs.washington.edu FU National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [HL-102923, HL-102924, HL-102925, HL-102926, HL-103010]; Simons Foundation Autism Research Initiative [SFARI 137578, 191889]; NIH [HD065285] FX We thank the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute Grand Opportunity (GO) Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the Women's Health Initiative Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010). We thank all the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R.B., J. Constantino, E. Cook, E. Fombonne, D. Geschwind, E. Hanson, D. Grice, A. Klin, R. Kochel, D. Ledbetter, C. Lord, C. Martin, D. 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TI Identification of Small Exonic CNV from Whole-Exome Sequence Data and Application to Autism Spectrum Disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; HUMAN GENOME; GENE; TOOL; REVEALS; DISCOVERY; NETWORK; 17P13.1; MAP AB Copy number variation (CNV) is an important determinant of human diversity and plays important roles in susceptibility to disease. Most studies of CNV carried out to date have made use of chromosome microarray and have had a lower size limit for detection of about 30 kilobases (kb). With the emergence of whole-exome sequencing studies, we asked whether such data could be used to reliably call rare exonic CNV in the size range of 1-30 kilobases (kb), making use of the eXome Hidden Markov Model (XHMM) program. By using both transmission information and validation by molecular methods, we confirmed that small CNV encompassing as few as three exons can be reliably called from whole-exome data. We applied this approach to an autism case-control sample (n = 811, mean per-target read depth = 161) and observed a significant increase in the burden of rare (MAF <= 1%) 1-30 kb CNV, 1-30 kb deletions, and 1-10 kb deletions in ASD. CNV in the 1-30 kb range frequently hit just a single gene, and we were therefore able to carry out enrichment and pathway analyses, where we observed enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. In summary, our results showed that XHMM provided an effective means to assess small exonic CNV from whole-exome data, indicated that rare 1-30 kb exonic deletions could contribute to risk in up to 7% of individuals with ASD, and implicated a candidate pathway in developmental delay syndromes. C1 [Poultney, Christopher S.; Goldberg, Arthur P.; Drapeau, Elodie; Kou, Yan; Harony-Nicolas, Hala; Kajiwara, Yuji; De Rubeis, Silvia; Durand, Simon; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Poultney, Christopher S.; Goldberg, Arthur P.; Drapeau, Elodie; Harony-Nicolas, Hala; Kajiwara, Yuji; De Rubeis, Silvia; Durand, Simon; Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Goldberg, Arthur P.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Kou, Yan; Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Syst Biol Ctr New York, New York, NY 10029 USA. [Stevens, Christine; Palotie, Aarno; Daly, Mark J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Rehnstroem, Karola; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland. [Rehnstroem, Karola] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, Dept Genet & Genom Sci, New York, NY 10029 USA. [Fromer, Menachem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu FU National Institute of Mental Health, National Institutes of Health [MH089025, MH097849, MH100233]; Seaver Foundation FX This work was supported by the National Institute of Mental Health, National Institutes of Health (grants MH089025, MH097849, and MH100233 to J.D.B.) and the Seaver Foundation. C.S.P. is a Seaver Fellow and A.P.G. is a Seaver Fellow. 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TI The Sacred Disease: The Puzzling Genetics of Epileptic Disorders SO NEURON LA English DT Editorial Material ID DE-NOVO MUTATIONS; INTELLECTUAL DISABILITY; AUTISM AB In the September 12, 2013 issue of Nature, the Epi4K Consortium (Allen et al., 2013) reported sequencing 264 patient trios with epileptic encephalopathies. The Consortium focused on genes exceptionally intolerant to sequence variations and found substantial interconnections with autism and intellectual disability gene networks. C1 [Novarino, Gaia; Baek, Seung Tae; Gleeson, Joseph G.] Univ Calif San Diego, Dept Neurosci, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Gleeson, JG (reprint author), Univ Calif San Diego, Dept Neurosci, Howard Hughes Med Inst, La Jolla, CA 92093 USA. 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Schmidt, Michael Yang, Unikora Gong, Jingyi Ellisor, Debra Kauer, Julie A. Morrow, Eric M. TI Christianson Syndrome Protein NHE6 Modulates TrkB Endosomal Signaling Required for Neuronal Circuit Development SO NEURON LA English DT Article ID NA+/H+ EXCHANGER ISOFORM-6; MENTAL-RETARDATION; SODIUM/PROTON EXCHANGER; NEUROTROPHIC FACTOR; ANGELMAN-SYNDROME; AUTISM; MECHANISMS; CELLS; YEAST; PH AB Neuronal arborization is regulated by cell-autonomous and nonautonomous mechanisms including endosomal signaling via BDNF/TrkB. The endosomal Na+/H+ exchanger 6 (NHE6) is mutated in a new autism-related disorder. NHE6 functions to permit proton leak from endosomes, yet the mechanisms causing disease are unknown. We demonstrate that loss of NHE6 results in overacidification of the endosomal compartment and attenuated TrkB signaling. Mouse brains with disrupted NHE6 display reduced axonal and dendritic branching, synapse number, and circuit strength. Site-directed mutagenesis shows that the proton leak function of NHE6 is required for neuronal arborization. We find that TrkB receptor colocalizes to NHE6-associated endosomes. TrkB protein and phosphorylation are reduced in NHE6 mutant neurons in response to BDNF signaling. Finally, exogenous BDNF rescues defects in neuronal arborization. We propose that NHE6 mutation leads to circuit defects that are in part due to impoverished neuronal arborization that may be treatable by enhanced TrkB signaling. C1 [Ouyang, Qing; Lizarraga, Sofia B.; Schmidt, Michael; Yang, Unikora; Gong, Jingyi; Ellisor, Debra; Morrow, Eric M.] Brown Univ, Dept Mol Biol, Mol Med Lab, Providence, RI 02903 USA. [Ouyang, Qing; Lizarraga, Sofia B.; Schmidt, Michael; Yang, Unikora; Gong, Jingyi; Ellisor, Debra; Morrow, Eric M.] Brown Univ, Dept Cell Biol, Mol Med Lab, Providence, RI 02903 USA. [Ouyang, Qing; Lizarraga, Sofia B.; Schmidt, Michael; Yang, Unikora; Gong, Jingyi; Ellisor, Debra; Morrow, Eric M.] Brown Univ, Dept Biochem, Mol Med Lab, Providence, RI 02903 USA. [Ouyang, Qing; Lizarraga, Sofia B.; Schmidt, Michael; Yang, Unikora; Gong, Jingyi; Ellisor, Debra; Morrow, Eric M.] Brown Univ, Inst Brain Sci, Mol Med Lab, Providence, RI 02903 USA. [Kauer, Julie A.] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA. [Kauer, Julie A.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Sch Med, Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, East Providence, RI 02915 USA. [Morrow, Eric M.] Brown Univ, Sch Med, Dept Psychiat & Human Behav, East Providence, RI 02915 USA. RP Morrow, EM (reprint author), Brown Univ, Dept Mol Biol, Mol Med Lab, 70 Ship St, Providence, RI 02903 USA. EM eric_morrow@brown.edu FU Career Award in Medical Science; Burroughs Wellcome Fund; NIH NIGMS COBRE [8P20GM103537-10]; NIH [5T32MH019118-21]; Simons Foundation [SFARI 239834]; Nancy Lurie Marks Foundation FX We thank Dr. Robbed Creton at Brown University Leduc Bioimaging Facility for advice regarding microscopy and Dr. Peter Davies for the kind gift of Phospho-Tau1 antibody. E.M.M. has received support from Career Award in Medical Science, Burroughs Wellcome Fund, and NIH NIGMS COBRE 8P20GM103537-10. S.B.L. has received support from NIH 5T32MH019118-21. This work was supported by a grant from the Simons Foundation (SFARI 239834 to E.M.M.) and also generous support to E.M.M. from the Nancy Lurie Marks Foundation. 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The transmembrane form of calsyntenin-3 can trigger excitatory and inhibitory presynapse differentiation in contacting axons. However, calsyntenin-3-shed ectodomain, which represents about half the calsyntenin-3 pool in brain, suppresses the ability of multiple alpha-neurexin partners including neuroligin 2 and LRRTM2 to induce presynapse differentiation. Cistn3(-/-) mice show reductions in excitatory and inhibitory synapse density by confocal and electron microscopy and corresponding deficits in synaptic transmission. These results identify calsyntenin-3 as an alpha-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development. C1 [Pettem, Katherine L.; Yokomaku, Daisaku; Luo, Lin; Linhoff, Michael W.; Prasad, Tuhina; Connor, Steven A.; Siddiqui, Tabrez J.; Zhang, Ling; Wang, Yu Tian; Craig, Ann Marie] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada. [Pettem, Katherine L.; Yokomaku, Daisaku; Luo, Lin; Linhoff, Michael W.; Prasad, Tuhina; Connor, Steven A.; Siddiqui, Tabrez J.; Craig, Ann Marie] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 2B5, Canada. [Connor, Steven A.; Zhang, Ling; Wang, Yu Tian] Univ British Columbia, Dept Med, Vancouver, BC V6T 2B5, Canada. [Kawabe, Hiroshi; Brose, Nils] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075 Gottingen, Germany. [Chen, Fang; Rudenko, Gabby] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA. [Chen, Fang; Rudenko, Gabby] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Craig, AM (reprint author), Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada. EM acraig@mail.ubc.ca RI Craig, Ann Marie/M-2054-2014 FU National Institutes of Health [MH070860, MH077303]; Canada Research Chair salary award; Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship; Michael Smith Foundation for Health Research Fellowships; German Research Foundation [SPP1365/KA3423/1-1]; Fritz Thyssen Foundation FX We thank Xiling Zhou and Nazarine Fernandes for excellent technical assistance, Vivian Lam and Sarah Au-Yeung for contributions for the western blot analysis, Fergil Mills and Dr. Shernaz Bamji for experimental advice and Derrick Home and Bradford Ross of the Bioimaging Facility for technical assistance with electron microscopy, Michiko Takeda for contributions to mouse colony management, Mika Kishimoto-Suga for experimental advice with antibody generation, and Dr. Robert Holt and team at the Michael Smith Genome Sciances Centre for arraying the cDNA subpool and preparing DNA in 384-well format. This work was supported by the National Institutes of Health (MH070860) and Canada Research Chair salary award to A.M.C., a Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship to K.L.P., Michael Smith Foundation for Health Research Fellowships to K.L.P. and T.J.S., the German Research Foundation (SPP1365/KA3423/1-1) to H.K, and N.B., the Fritz Thyssen Foundation to H.K., and the National Institutes of Health (MH077303) to G.R. 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Taylor, Margot J. Soorya, Latha V. Wang, Ting Fan, Jin Anagnostou, Evdokia TI Neural correlates of inhibition of socially relevant stimuli in adults with autism spectrum disorder SO BRAIN RESEARCH LA English DT Article DE Autism; Emotion; Executive functioning; Brain; MRI; Human ID HIGH-FUNCTIONING AUTISM; DORSOLATERAL PREFRONTAL CORTEX; INFERIOR FRONTAL-CORTEX; RESPONSE-INHIBITION; EXECUTIVE FUNCTION; DELAYED ALTERNATION; FACIAL EXPRESSIONS; ASPERGERS-DISORDER; BEHAVIORAL-CONTROL; COGNITIVE CONTROL AB Adults with autism spectrum disorder (ASD) can demonstrate difficulties with inhibiting inappropriate social responses. Presently, little research has utilized socially relevant stimuli to explore the modulatory effects of emotion on cognitive control in this population. 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EM emma.duerden@sickkids.ca FU Seaver Foundation; Research Training Competition Fellowship from the Hospital for Sick Children; Reva Gerstein Fellowship in Pediatric Psychology; Holland Bloorview Kids Rehabilitation Foundation FX The authors would like to acknowledge the Seaver Foundation (EA), for providing primary funding for this study. Additionally, support during the data analysis and manuscript preparation process was provided by Research Training Competition Fellowship from the Hospital for Sick Children (ED), a Reva Gerstein Fellowship in Pediatric Psychology (ED) and the Holland Bloorview Kids Rehabilitation Foundation (EA). 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PD OCT 2 PY 2013 VL 1533 BP 80 EP 90 DI 10.1016/j.brainres.2013.08.021 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 233UL UT WOS:000325594900009 PM 23962468 ER PT J AU Duffney, LJ Wei, J Cheng, J Liu, WH Smith, KR Kittler, JT Yan, Z AF Duffney, Lara J. Wei, Jing Cheng, Jia Liu, Wenhua Smith, Katharine R. Kittler, Josef T. Yan, Zhen TI Shank3 Deficiency Induces NMDA Receptor Hypofunction via an Actin-Dependent Mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article ID RHO FAMILY GTPASES; POSTSYNAPTIC DENSITY PROTEINS; SMALL-MOLECULE INHIBITOR; AUTISTIC-LIKE BEHAVIORS; DENDRITIC SPINES; P21-ACTIVATED KINASE; MENTAL-RETARDATION; PREFRONTAL CORTEX; ALPHA-ACTININ; GLUTAMATERGIC TRANSMISSION AB Shank3, which encodes a scaffolding protein at glutamatergic synapses, is a genetic risk factor for autism. In this study, we examined the impact of Shank3 deficiency on the NMDA-type glutamate receptor, a key player in cognition and mental illnesses. We found that knockdown of Shank3 with a small interfering RNA (siRNA) caused a significant reduction of NMDAR-mediated ionic or synaptic current, as well as the surface expression of NR1 subunits, in rat cortical cultures. The effect of Shank3 siRNA on NMDAR currents was blocked by an actin stabilizer, and was occluded by an actin destabilizer, suggesting the involvement of actin cytoskeleton. Since actin dynamics is regulated by the GTPase Rac1 and downstream effector p21-activated kinase (PAK), we further examined Shank3 regulation of NMDARs when Rac1 or PAK was manipulated. We found that the reducing effect of Shank3 siRNA on NMDAR currents was mimicked and occluded by specific inhibitors for Rac1 or PAK, and was blocked by constitutively active Rac1 or PAK. Immunocytochemical data showed a strong reduction of F-actin clusters after Shank3 knockdown, which was occluded by a PAK inhibitor. Inhibiting cofilin, the primary downstream target of PAK and a major actin depolymerizing factor, prevented Shank3 siRNA from reducing NMDAR currents and F-actin clusters. Together, these results suggest that Shank3 deficiency induces NMDAR hypofunction by interfering with the Rac1/PAK/cofilin/actin signaling, leading to the loss of NMDAR membrane delivery or stability. It provides a potential mechanism for the role of Shank3 in cognitive deficit in autism. C1 [Duffney, Lara J.; Wei, Jing; Cheng, Jia; Liu, Wenhua; Yan, Zhen] SUNY Buffalo, Sch Med & Biomed Sci, Dept Physiol & Biophys, Buffalo, NY 14214 USA. [Smith, Katharine R.; Kittler, Josef T.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England. RP Yan, Z (reprint author), SUNY Buffalo, Dept Physiol & Biophys, 124 Sherman Hall, Buffalo, NY 14214 USA. EM zhenyan@buffalo.edu RI Kittler, Josef/E-9113-2010 FU NIH [R01-MH085774, R21-MH101690] FX This work was supported by NIH Grants (R01-MH085774 and R21-MH101690) to Z.Y. We thank Xiaoqing Chen for her excellent technical support. We thank Drs. Carlo Sala and Eunjoon Kim for providing Shank3 plasmids. 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This problem is common to a number of areas in biology and medicine, for example, obstetrics, neurology/psychiatry, parasitology, virology, oncology, and teratology. It is established that there are significantly biased, but unexplained, sex ratios in each of these fields. Yet workers in them (with the possible exception of virology) have regarded the problem as a minor loose end, irrelevant to the field's major problems. However, as far as I know, no one has previously noted that unexplained biased sex ratios occur, and thus pose (perhaps similar) problems, in all these fields. Here it is suggested that similar sorts of solutions apply in each. Further research is proposed for testing each solution. If the argument here is substantially correct across this range of topics, it may lead to an improved understanding not only of sex ratio but also of some of the pathologies in these specialties. C1 UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England. 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PD OCT PY 2013 VL 85 IS 5 BP 769 EP 787 PG 19 WC Anthropology; Biology; Genetics & Heredity SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA AJ2QO UT WOS:000337504300008 PM 25078960 ER PT J AU Berard, A Sheehy, O Boukris, T AF Berard, Anick Sheehy, Odile Boukris, Takoua TI Relation between the Prevalence of Attention Deficit and Hyperactivity Disorders (ADHD) and Autism Spectrum Disorders (ASD), and Maternal Depression and Antidepressant Use during Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Berard, Anick; Boukris, Takoua] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada. [Berard, Anick; Boukris, Takoua] Univ Montreal, CHU Ste Justine, Montreal, PQ H3C 3J7, Canada. [Sheehy, Odile] CHU Ste 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 345 BP 167 EP 167 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876100322 ER PT J AU Sirois, C Gascon, H Faubert, M Gagnon, ME AF Sirois, Caroline Gascon, Hubert Faubert, Mirella Gagnon, Marie-Eve TI Use of Medication by Young People with Autism-Spectrum Disorders in Quebec SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Sirois, Caroline; Faubert, Mirella; Gagnon, Marie-Eve] Univ Quebec Rimouski, Dept Nursing, Levis, PQ, Canada. [Gascon, Hubert] Univ Quebec Rimouski, Dept Educ, Levis, PQ, Canada. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2013 VL 22 SU 1 SI SI MA 1036 BP 516 EP 516 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF7EJ UT WOS:000334876102141 ER PT J AU Egiebor, E Tulu, A Abou-Zeid, N Aighewi, IT Ishaque, A AF Egiebor, Egbe Tulu, Adam Abou-Zeid, Nadia Aighewi, Isoken Tito Ishaque, Ali TI The Kinetic Signature of Toxicity of Four Heavy Metals and Their Mixtures on MCF7 Breast Cancer Cell Line SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE heavy metals; real time electronic cell sensing; glutathione; L-buthionine sulphoximine ID MITOCHONDRIAL DYSFUNCTION; CARCINOMA-CELLS; GLUTATHIONE; CYTOTOXICITY; MECHANISMS; CADMIUM; APOPTOSIS; STRESS; LEAD AB This study evaluated the kinetic signature of toxicity of four heavy metals known to cause severe health and environmental issues-cadmium (Cd), mercury (Hg) lead (Pb) arsenic (As)-and the mixture of all four metals (Mix) on MCF7 cancer cells, in the presence and absence of the antioxidant glutathione (GSH). The study was carried out using real time cell electronic sensing (RT-CES). RT-CES monitors in real time the electrical impedance changes at the electrode/culture medium interface due to the number of adhered cells, which is used as an index of cell viability. Cells were seeded for 24 h before exposure to the metals and their mixtures. The results showed that in the presence and absence of cellular glutathione, arsenic was the most cytotoxic of all five treatments, inducing cell death after 5 h of exposure. Lead was the least cytotoxic in both scenarios. In the presence of cellular GSH, the cytotoxic trend was As > Cd > MIX > Hg > Pb, while in the absence of GSH, the cytotoxic trend was As > Hg > MIX > Cd > Pb. 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Public Health PD OCT PY 2013 VL 10 IS 10 BP 5209 EP 5220 DI 10.3390/ijerph10105209 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 301GJ UT WOS:000330520500041 PM 24157516 ER PT J AU Addae, C Cheng, H Martinez-Ceballos, E AF Addae, Cynthia Cheng, Henrique Martinez-Ceballos, Eduardo TI Effect of the Environmental Pollutant Hexachlorobenzene (HCB) on the Neuronal Differentiation of Mouse Embryonic Stem Cells SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE hexachlorobenzene; retinoid acid; reactive oxygen species; antioxidant; environmental pollutant; GABAergic; encapsulation; embryonic stem cells; autism; ADD ID OXIDATIVE STRESS; GROWTH-FACTORS; RAT; EXPOSURE; GENOTOXICITY; ACTIVATION; APOPTOSIS; PATHWAYS; THERAPY; DISEASE AB Exposure to persistent environmental pollutants may constitute an important factor on the onset of a number of neurological disorders such as autism, Parkinson's disease, and Attention Deficit Disorder (ADD), which have also been linked to reduced GABAergic neuronal function. GABAergic neurons produce gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. However, the lack of appropriate models has hindered the study of suspected environmental pollutants on GABAergic function. In this work, we have examined the effect of hexachlorobenzene (HCB), a persistent and bioaccumulative environmental pollutant, on the function and morphology of GABAergic neurons generated in vitro from mouse embryonic stem (ES) cells. We observed that: (1) treatment with 0.5 nM HCB did not affect cell viability, but affected the neuronal differentiation of ES cells; (2) HCB induced the production of reactive oxygen species (ROS); and (3) HCB repressed neurite outgrowth in GABAergic neurons, but this effect was reversed by the ROS scavenger N-acetylcysteine (NAC). Our study also revealed that HCB did not significantly interfere with the function of K+ ion channels in the neuronal soma, which indicates that this pollutant does not affect the maturation of the GABAergic neuronal soma. Our results suggest a mechanism by which environmental pollutants interfere with normal GABAergic neuronal function and may promote the onset of a number of neurological disorders such as autism and ADD. C1 [Addae, Cynthia; Martinez-Ceballos, Eduardo] Southern Univ, Dept Biol Sci, Baton Rouge, LA 70813 USA. [Addae, Cynthia; Martinez-Ceballos, Eduardo] Southern Univ, Environm Toxicol Program, Baton Rouge, LA 70813 USA. [Addae, Cynthia; Martinez-Ceballos, Eduardo] A&M Coll, Baton Rouge, LA 70813 USA. [Cheng, Henrique] Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA. RP Martinez-Ceballos, E (reprint author), Southern Univ, Dept Biol Sci, Baton Rouge, LA 70813 USA. 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NR 0 TC 0 Z9 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2013 VL 108 SU 1 MA 2052 BP S623 EP S623 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296II UT WOS:000330178102379 ER PT J AU Bauer, NS Sturm, LA Carroll, AE Downs, SM AF Bauer, Nerissa S. Sturm, Lynne A. Carroll, Aaron E. Downs, Stephen M. TI Computer Decision Support to Improve Autism Screening and Care in Community Pediatric Clinics SO INFANTS & YOUNG CHILDREN LA English DT Article DE access and evaluation; autism; computerized; health care quality; medical informatics; medical record systems; primary health care ID SPECTRUM DISORDER; AMERICAN-ACADEMY; CHICA SYSTEM; CHILDREN; QUALITY; IMPLEMENTATION; IDENTIFICATION; GUIDELINES; MANAGEMENT; TODDLERS AB An autism module was added to an existing computer decision support system (CDSS) to facilitate adherence to recommended guidelines for screening for autism spectrum disorders in primary care pediatric clinics. User satisfaction was assessed by survey and informal feedback at monthly meetings between clinical staff and the software team. To assess outcomes, such as changes in identification and referrals, we reviewed data captured from the CDSS. Between November 15, 2010 and July 26, 2012, 857 patients were eligible for screening. Of these, 66% (567/857) were screened as determined by the number of forms scanned into the system, of which 30% (171/567) had concerning Modified Checklist for Autism in Toddlers. However, pediatricians failed to respond to alerts for 73 children. Of the remaining 98 children, pediatricians felt 50 (68%) did not have an Autism spectrum disorder, 23 (32%) were referred for autism evaluation, eight (11%) were suspected but not referred and two (3%) were referred for audiology. Seventy percent of all users agreed that automation of the screening process helped them to adhere to recommended guidelines. Automating autism care into a CDSS resulted in moderate adherence to guidelines. Health information technology can facilitate the implementation of autism guidelines in busy pediatric clinics. C1 [Bauer, Nerissa S.; Sturm, Lynne A.; Carroll, Aaron E.; Downs, Stephen M.] Indiana Univ Sch Med, Dept Gen & Community Pediat, Indianapolis, IN 46202 USA. 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M., 2008, SCREENING AUTISM SPE NR 38 TC 1 Z9 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0896-3746 EI 1550-5081 J9 INFANT YOUNG CHILD JI Infants Young Child. PD OCT-DEC PY 2013 VL 26 IS 4 BP 306 EP 317 DI 10.1097/IYC.0b013e3182a4ec5e PG 12 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 299CK UT WOS:000330372400004 ER PT J AU Lee, TY Lin, FY AF Lee, Tzu-Ying Lin, Fang-Yi TI Taiwanese Parents' Perceptions of Their Very Low-Birth-Weight Infant With Developmental Disabilities SO JOURNAL OF PERINATAL & NEONATAL NURSING LA English DT Article DE developmental disability; infant; parent; Taiwan; very low-birth-weight ID QUALITATIVE CONTENT-ANALYSIS; PREMATURE-INFANTS; YOUNG-CHILDREN; MOTHERS; FAMILIES; CARE; EXPERIENCES; SERVICES; AUTISM; HEALTH AB This study explores the perceptions and experiences of Taiwanese parents in coping with the unfolding evidence of a disability, their response to the official diagnosis, and their views about their child's developmental disability. This descriptive qualitative study is a partial analysis of data from a larger study including 19 Taiwanese parents of very low-birth-weight infants with developmental disability at 6 and 12 months of corrected age. Four themes were generated: uncertainty and worry about developmental progress, search for meaning and supernatural will, desire for normality and attitude toward services, and finding a balance point in family life and relationships. The parents of very low-birth-weight infants face uncertainty about developmental and other potential problems in the infant's early age. Adequate information related to infant development needs to be integrated into follow-up clinic and early intervention services. Early intervention programs should not only focus on the needs of these infants but also provide support and care to the whole family. Understanding parental beliefs and values toward developmental disabilities can help neonatal and pediatric professionals to provide optimal early intervention to these families. C1 [Lee, Tzu-Ying; Lin, Fang-Yi] Natl Taipei Univ Nursing & Hlth Sci, Sch Nursing, Taipei 11219, Taiwan. RP Lee, TY (reprint author), Natl Taipei Univ Nursing & Hlth Sci, Sch Nursing, 365 Ming Te Rd, Taipei 11219, Taiwan. EM tzuying@ntunhs.edu.tw FU National Science Council in Taiwan [NSC 94-2516-S-227-002] FX Funded by the National Science Council in Taiwan (NSC 94-2516-S-227-002). CR Allen EC, 2004, PEDIATRICS, V113, P267, DOI 10.1542/peds.113.2.267 Al-Yagon M, 2010, FAM RELAT, V59, P152, DOI 10.1111/j.1741-3729.2010.00592.x Amess P, 2010, EUR J PAEDIATR NEURO, V14, P219, DOI 10.1016/j.ejpn.2009.06.005 Andrews MM, 2008, TRANSCULTURAL CONCEP Chao R. 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Perinat. Neonatal Nurs. PD OCT-DEC PY 2013 VL 27 IS 4 BP 345 EP 352 DI 10.1097/JPN.0b013e3182a98408 PG 8 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 300HG UT WOS:000330454400011 PM 24164817 ER PT J AU Kutchko, KM Frohlich, F AF Kutchko, Katrina M. Froehlich, Flavio TI Emergence of Metastable State Dynamics in Interconnected Cortical Networks with Propagation Delays SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID TRANSCRANIAL ELECTRICAL-STIMULATION; ALTERNATING-CURRENT STIMULATION; HIGH-FREQUENCY OSCILLATIONS; FUNCTIONAL CONNECTIVITY; BRAIN-STIMULATION; CORPUS-CALLOSUM; SPIKING NEURONS; VISUAL-CORTEX; SCHIZOPHRENIA; SYNCHRONY AB The importance of the large number of thin-diameter and unmyelinated axons that connect different cortical areas is unknown. The pronounced propagation delays in these axons may prevent synchronization of cortical networks and therefore hinder efficient information integration and processing. Yet, such global information integration across cortical areas is vital for higher cognitive function. We hypothesized that delays in communication between cortical areas can disrupt synchronization and therefore enhance the set of activity trajectories and computations interconnected networks can perform. To evaluate this hypothesis, we studied the effect of long-range cortical projections with propagation delays in interconnected large-scale cortical networks that exhibited spontaneous rhythmic activity. Long-range connections with delays caused the emergence of metastable, spatio-temporally distinct activity states between which the networks spontaneously transitioned. Interestingly, the observed activity patterns correspond to macroscopic network dynamics such as globally synchronized activity, propagating wave fronts, and spiral waves that have been previously observed in neurophysiological recordings from humans and animal models. Transient perturbations with simulated transcranial alternating current stimulation (tACS) confirmed the multistability of the interconnected networks by switching the networks between these metastable states. Our model thus proposes that slower long-range connections enrich the landscape of activity states and represent a parsimonious mechanism for the emergence of multistability in cortical networks. These results further provide a mechanistic link between the known deficits in connectivity and cortical state dynamics in neuropsychiatric illnesses such as schizophrenia and autism, as well as suggest non-invasive brain stimulation as an effective treatment for these illnesses. C1 [Kutchko, Katrina M.; Froehlich, Flavio] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. [Kutchko, Katrina M.; Froehlich, Flavio] Univ N Carolina, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC USA. [Froehlich, Flavio] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA. [Froehlich, Flavio] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. [Froehlich, Flavio] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC USA. RP Kutchko, KM (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. EM flavio_frohlich@med.unc.edu FU UNC Department of Psychiatry; UNC School of Medicine; Foundation of Hope FX This work was supported by the UNC Department of Psychiatry, UNC School of Medicine, and the Foundation of Hope. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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However, such herd behavior can also be pathologically misleading by coaxing individuals into behaviors that are otherwise irrational and it may be one source of the irrational behaviors underlying market bubbles and crashes. Using a two-person tandem investment game, we sought to examine the neural and behavioral responses of herd instincts in situations stripped of the incentive to be influenced by the choices of one's partner. We show that the investments of the two subjects correlate over time if they are made aware of their partner's choices even though these choices have no impact on either player's earnings. We computed an "interpersonal prediction error", the difference between the investment decisions of the two subjects after each choice. BOLD responses in the striatum, implicated in valuation and action selection, were highly correlated with this interpersonal prediction error. The revelation of the partner's investment occurred after all useful information about the market had already been revealed. This effect was confirmed in two separate experiments where the impact of the time of revelation of the partner's choice was tested at 2 seconds and 6 seconds after a subject's choice; however, the effect was absent in a control condition with a computer partner. These findings strongly support the existence of mechanisms that drive correlated behavior even in contexts where there is no explicit advantage to do so. C1 [Lohrenz, Terry; Bhatt, Meghana; Apple, Nathan; Montague, P. Read] Virginia Tech Carilion Res Inst, Roanoke, VA 24016 USA. [Montague, P. Read] UCL, Wellcome Trust Ctr Neuroimaging, London, England. RP Lohrenz, T (reprint author), Virginia Tech Carilion Res Inst, Roanoke, VA 24016 USA. EM read@vt.edu FU National Institutes of Health [1 RC4 AG039067, R01 DA11723, R01 MH085496, R01 DA030241]; Kane Foundation Fellowship; Wellcome Trust FX This research was funded by the following grants: National Institutes of Health grant # 1 RC4 AG039067, National Institutes of Health grant # R01 DA11723, National Institutes of Health grant # R01 MH085496, National Institutes of Health grant # R01 DA030241, The Kane Foundation Fellowship, and the Wellcome Trust. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. 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PD OCT PY 2013 VL 9 IS 10 AR e1003275 DI 10.1371/journal.pcbi.1003275 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 298WN UT WOS:000330355300035 PM 24204226 ER PT J AU Davis, LK Yu, DM Keenan, CL Gamazon, ER Konkashbaev, AI Derks, EM Neale, BM Yang, J Lee, SH Evans, P Barr, CL Bellodi, L Benarroch, F Berrio, GB Bienvenu, OJ Bloch, MH Blom, RM Bruun, RD Budman, CL Camarena, B Campbell, D Cappi, C Silgado, JCC Cath, DC Cavallini, MC Chavira, DA Chouinard, S Conti, DV Cook, EH Coric, V Cullen, BA Deforce, D Delorme, R Dion, Y Edlund, CK Egberts, K Falkai, P Fernandez, TV Gallagher, PJ Garrido, H Geller, D Girard, SL Grabe, HJ Grados, MA Greenberg, BD Gross-Tsur, V Haddad, S Heiman, GA Hemmings, SMJ Hounie, AG Illmann, C Jankovic, J Jenike, MA Kennedy, JL King, RA Kremeyer, B Kurlan, R Lanzagorta, N Leboyer, M Leckman, JF Lennertz, L Liu, C Lochner, C Lowe, TL Macciardi, F McCracken, JT McGrath, LM Restrepo, SCM Moessner, R Morgan, J Muller, H Murphy, DL Naarden, AL Ochoa, WC Ophoff, RA Osiecki, L Pakstis, AJ Pato, MT Pato, CN Piacentini, J Pittenger, C Pollak, Y Rauch, SL Renner, TJ Reus, VI Richter, MA Riddle, MA Robertson, MM Romero, R Rosario, MC Rosenberg, D Rouleau, GA Ruhrmann, S Ruiz-Linares, A Sampaio, AS Samuels, J Sandor, P Sheppard, B Singer, HS Smit, JH Stein, DJ Strengman, E Tischfield, JA Duarte, AVV Vallada, H Van Nieuwerburgh, F Veenstra-VanderWeele, J Walitza, S Wang, Y Wendland, JR Westenberg, HGM Shugart, YY Miguel, EC McMahon, W Wagner, M Nicolini, H Posthuma, D Hanna, GL Heutink, P Denys, D Arnold, PD Oostra, BA Nestadt, G Freimer, NB Pauls, DL Wray, NR Stewart, SE Mathews, CA Knowles, JA Cox, NJ Scharf, JM AF Davis, Lea K. Yu, Dongmei Keenan, Clare L. Gamazon, Eric R. Konkashbaev, Anuar I. Derks, Eske M. Neale, Benjamin M. Yang, Jian Lee, S. Hong Evans, Patrick Barr, Cathy L. Bellodi, Laura Benarroch, Fortu Berrio, Gabriel Bedoya Bienvenu, Oscar J. Bloch, Michael H. Blom, Rianne M. Bruun, Ruth D. Budman, Cathy L. Camarena, Beatriz Campbell, Desmond Cappi, Carolina Silgado, Julio C. Cardona Cath, Danielle C. Cavallini, Maria C. Chavira, Denise A. Chouinard, Sylvain Conti, David V. Cook, Edwin H. Coric, Vladimir Cullen, Bernadette A. Deforce, Dieter Delorme, Richard Dion, Yves Edlund, Christopher K. Egberts, Karin Falkai, Peter Fernandez, Thomas V. Gallagher, Patience J. Garrido, Helena Geller, Daniel Girard, Simon L. Grabe, Hans J. Grados, Marco A. Greenberg, Benjamin D. Gross-Tsur, Varda Haddad, Stephen Heiman, Gary A. Hemmings, Sian M. J. Hounie, Ana G. Illmann, Cornelia Jankovic, Joseph Jenike, Michael A. Kennedy, James L. King, Robert A. Kremeyer, Barbara Kurlan, Roger Lanzagorta, Nuria Leboyer, Marion Leckman, James F. Lennertz, Leonhard Liu, Chunyu Lochner, Christine Lowe, Thomas L. Macciardi, Fabio McCracken, James T. McGrath, Lauren M. Restrepo, Sandra C. Mesa Moessner, Rainald Morgan, Jubel Muller, Heike Murphy, Dennis L. Naarden, Allan L. Ochoa, William Cornejo Ophoff, Roel A. Osiecki, Lisa Pakstis, Andrew J. Pato, Michele T. Pato, Carlos N. Piacentini, John Pittenger, Christopher Pollak, Yehuda Rauch, Scott L. Renner, Tobias J. Reus, Victor I. Richter, Margaret A. Riddle, Mark A. Robertson, Mary M. Romero, Roxana Rosario, Maria C. Rosenberg, David Rouleau, Guy A. Ruhrmann, Stephan Ruiz-Linares, Andres Sampaio, Aline S. Samuels, Jack Sandor, Paul Sheppard, Brooke Singer, Harvey S. Smit, Jan H. Stein, Dan J. Strengman, E. Tischfield, Jay A. Duarte, Ana V. Valencia Vallada, Homero Van Nieuwerburgh, Filip Veenstra-VanderWeele, Jeremy Walitza, Susanne Wang, Ying Wendland, Jens R. Westenberg, Herman G. M. Shugart, Yin Yao Miguel, Euripedes C. McMahon, William Wagner, Michael Nicolini, Humberto Posthuma, Danielle Hanna, Gregory L. Heutink, Peter Denys, Damiaan Arnold, Paul D. Oostra, Ben A. Nestadt, Gerald Freimer, Nelson B. Pauls, David L. Wray, Naomi R. Stewart, S. Evelyn Mathews, Carol A. Knowles, James A. Cox, Nancy J. Scharf, Jeremiah M. TI Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture SO PLOS GENETICS LA English DT Article ID MISSING HERITABILITY; TIC DISORDERS; NEUROPSYCHIATRIC DISORDERS; COMPLEX DISEASES; COMMON SNPS; GILLES; FAMILY; BRAIN; EXPRESSION; AUTISM AB The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures. C1 [Davis, Lea K.; Gamazon, Eric R.; Konkashbaev, Anuar I.; Evans, Patrick; Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Yu, Dongmei; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Osiecki, Lisa; Pauls, David L.; Scharf, Jeremiah M.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat,Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA. [Yu, Dongmei; Neale, Benjamin M.; Scharf, Jeremiah M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Keenan, Clare L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Keenan, Clare L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Derks, Eske M.; Blom, Rianne M.; Denys, Damiaan] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Yang, Jian] Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia. [Yang, Jian; Lee, S. Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Barr, Cathy L.] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Barr, Cathy L.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bellodi, Laura] Univ Vita Salute San Raffaele, Milan, Italy. [Benarroch, Fortu] Hadassah Hebrew Univ Med Ctr, Herman Dana Div Child & Adolescent Psychiat, Jerusalem, Israel. [Berrio, Gabriel Bedoya; Silgado, Julio C. Cardona; Restrepo, Sandra C. Mesa; Ochoa, William Cornejo; Duarte, Ana V. Valencia] Univ Pontificia Bolivariana, Univ Antioquia, Medellin, Colombia. [Bienvenu, Oscar J.; Cullen, Bernadette A.; Gallagher, Patience J.; Grados, Marco A.; Riddle, Mark A.; Samuels, Jack; Wang, Ying; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Bloch, Michael H.; Coric, Vladimir] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Bloch, Michael H.; Fernandez, Thomas V.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Bruun, Ruth D.] North Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. [Bruun, Ruth D.] NYU Med Ctr, New York, NY 10016 USA. [Budman, Cathy L.] North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. [Budman, Cathy L.] Hofstra Univ, Sch Med, Hempstead, NY 11550 USA. [Camarena, Beatriz] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Mexico City, DF, Mexico. [Campbell, Desmond; Kremeyer, Barbara; Muller, Heike; Robertson, Mary M.; Ruiz-Linares, Andres] UCL, London, England. [Campbell, Desmond] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Cappi, Carolina; Vallada, Homero; Miguel, Euripedes C.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Cath, Danielle C.; Smit, Jan H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Cath, Danielle C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [Cath, Danielle C.] Altrecht Acad Anxiety Ctr, Utrecht, Netherlands. [Cavallini, Maria C.] Univ Milan, Osped San Raffaele, I-20127 Milan, Italy. [Chavira, Denise A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Chavira, Denise A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Chouinard, Sylvain; Girard, Simon L.] Univ Montreal, Montreal, PQ, Canada. [Conti, David V.; Edlund, Christopher K.] Univ Calif Los Angeles, Keck Sch Med, Div Biostat, Dept Preventat Med, Los Angeles, CA USA. [Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. [Deforce, Dieter; Van Nieuwerburgh, Filip] Univ Ghent, Lab Pharmaceut Biotechnol, B-9000 Ghent, Belgium. [Delorme, Richard] Inst Pasteur, Paris, France. [Delorme, Richard; Leboyer, Marion] French Natl Sci Fdn, Fondat Fondamental, Creteil, France. [Delorme, Richard; Leboyer, Marion] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. [Dion, Yves] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Egberts, Karin; Renner, Tobias J.] Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-97070 Wurzburg, Germany. [Falkai, Peter] Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. [Fernandez, Thomas V.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,OCD Program, Boston, MA 02115 USA. [Grabe, Hans J.] Univ Med Greifswald, Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Garrido, Helena; Greenberg, Benjamin D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Geller, Daniel; Gross-Tsur, Varda; Pollak, Yehuda] Shaare Zedek Med Ctr, Neuropediatr Unit, Jerusalem, Israel. [Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Dept Genet, Human Genet Inst New Jersey, Piscataway, NJ USA. [Hemmings, Sian M. J.] Univ Stellenbosch, Dept Psychiat, ZA-7600 Stellenbosch, South Africa. [Hounie, Ana G.; Sampaio, Aline S.] Univ Sao Paulo, Fac Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. [Jenike, Michael A.; Stewart, S. Evelyn] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kennedy, James L.] Ctr Addict & Mental Hlth, Neurogenet Sect, Toronto, ON, Canada. [Kennedy, James L.; Richter, Margaret A.; Arnold, Paul D.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [King, Robert A.] Yale Univ, Sch Med, Dept Genet, Yale Child Study Ctr, New Haven, CT 06510 USA. [Kurlan, Roger] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA. [Lanzagorta, Nuria] Carracci Med Grp, Mexico City, DF, Mexico. [Leboyer, Marion] Inst Mondor Rech Biomed, Creteil, France. [Leckman, James F.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Lennertz, Leonhard; Moessner, Rainald; Wagner, Michael] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Liu, Chunyu] Univ Illinois, Dept Psychiat, Inst Human Genet, Chicago, IL 60612 USA. [Lochner, Christine] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. [Lowe, Thomas L.; Reus, Victor I.; Sheppard, Brooke; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Macciardi, Fabio; McCracken, James T.] UCI, Sch Med, Dept Psychiat & Human Behav, Irvine, CA USA. [Morgan, Jubel] Univ Utah, Salt Lake City, UT USA. [Murphy, Dennis L.; Wendland, Jens R.] NIMH Intramural Res Program, Clin Sci Lab, Bethesda, MD USA. [Naarden, Allan L.] Med City Dallas Hosp, Dept Clin Res, Dallas, TX USA. [Ophoff, Roel A.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Ophoff, Roel A.; Freimer, Nelson B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Pakstis, Andrew J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Pato, Michele T.; Pato, Carlos N.; Knowles, James A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Piacentini, John] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Pittenger, Christopher] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Pittenger, Christopher] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Pittenger, Christopher] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Rauch, Scott L.] Partners Psychiat & McLean Hosp, Boston, MA USA. [Richter, Margaret A.] Sunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, Canada. [Robertson, Mary M.] St George Hosp, London, England. [Robertson, Mary M.] Sch Med, London, England. [Romero, Roxana] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Rosario, Maria C.] Univ Fed Sao Paulo, Dept Psychiat, Child & Adolescent Psychiat Unit UPIA, Sao Paulo, Brazil. [Rosenberg, David] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Rosenberg, David] Detroit Med Ctr, Detroit, MI USA. [Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Ruhrmann, Stephan] Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Sampaio, Aline S.] Univ Fed Bahia, Univ Hlth Care Serv SMURB, Salvador, BA, Brazil. [Sandor, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Sandor, Paul] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Sandor, Paul] Youthdale Treatment Ctr, Toronto, ON, Canada. [Singer, Harvey S.] Johns Hopkins Univ Sch Med, Baltimore, MD USA. [Stein, Dan J.] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Strengman, E.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN 37235 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Dept Pediat & Pharmacol, Nashville, TN 37235 USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Inst Brain, Nashville, TN 37235 USA. [Walitza, Susanne] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [Walitza, Susanne] Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97070 Wurzburg, Germany. [Westenberg, Herman G. M.] Univ Amsterdam, Acad Med Ctr, Ctr Psychiat, NL-1105 BC Amsterdam, Netherlands. [Westenberg, Herman G. M.; Denys, Damiaan] Inst Royal Netherlands Acad Arts & Sci NIN KNAW, Netherlands Inst Neurosci, Amsterdam, Netherlands. [Shugart, Yin Yao] NIMH Intramural Res Program, Unit Stat Genom, Bethesda, MD USA. [McMahon, William] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Nicolini, Humberto] Natl Inst Genom Med SAP, Carracci Med Grp, Mexico City, DF, Mexico. [Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Hanna, Gregory L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. [Heutink, Peter] German Ctr Neurodegenerat Dis, Tubingen, Germany. [Arnold, Paul D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Stewart, S. Evelyn] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Davis, LK (reprint author), Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM lea.k.davis@gmail.com; jscharf@partners.org RI Vallada, Homero/D-1333-2014; Yang, Jian/A-5852-2010; Fernandez, Thomas/D-4295-2009; Stein, Dan/A-1752-2008; Renner, Tobias/I-2120-2013; Lee, Sang Hong/A-2569-2011; Wray, Naomi/C-8639-2015 OI Vallada, Homero/0000-0001-5123-8295; Yang, Jian/0000-0003-2001-2474; Fernandez, Thomas/0000-0003-0830-022X; Stein, Dan/0000-0001-7218-7810; Lee, Sang Hong/0000-0001-9701-2718; Wray, Naomi/0000-0001-7421-3357 FU Judah Foundation; NIH [NS40024, NS16648, MH079489, MH073250, NS037484, 1R01MH079487-01A1, K20 MH01065, R01 MH58376, MH085057, MH079494, HHSN268200782096C]; Tourette Syndrome Association International Consortium for Genetics (TSAICG); New Jersey Center for Tourette Syndrome and Associated Disorders; NIMH [R01MH092293]; Obsessive Compulsive Foundation; Ontario Mental Health Foundation; Tourette Syndrome Association; American Academy of Child and Adolescent Psychiatry (AACAP); Anxiety Disorders Association of America (ADAA); University of British Columbia; Michael Smith Foundation; American Recovery and Re-investment Act (ARRA) [NS40024-07S1, NS16648-29S1]; Australian Research Council [FT0991360, DE130100614]; Australian National Health and Medical Research Council [1047956, 1052684]; German Research Foundation [DFG GR 1912/1-1]; NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; [R01 MH090937]; [P50MH094267] FX This work was supported by a grant from the Judah Foundation, NIH grant NS40024 to DLP/JMS and the Tourette Syndrome Association International Consortium for Genetics (TSAICG), NIH grant NS16648, MH079489, and MH073250 to DLP, NIH grant NS037484 to NBF, NIH grant 1R01MH079487-01A1 to JTM, New Jersey Center for Tourette Syndrome and Associated Disorders and NIMH (R01MH092293) to GAH/RAK/JAT, NIH grant K20 MH01065 and R01 MH58376 and a grant from the Obsessive Compulsive Foundation to GLH, Ontario Mental Health Foundation grant to PR and JLK, and a grant from the Tourette Syndrome Association and NIH grant MH085057 to JMS, MH079494 to JAK and the OCD Collaborative Genetics Association Study which supported the imputation, by an American Academy of Child and Adolescent Psychiatry (AACAP) Early Investigator Research Grant, an Anxiety Disorders Association of America (ADAA) Junior Investigator Research Grant, the University of British Columbia and a Michael Smith Foundation Clinical Research Scholar Award to SES, and American Recovery and Re-investment Act (ARRA) awards NS40024-07S1 to DLP/JMS and NS16648-29S1 to DLP. Additional support for analysis was provided by R01 MH090937 and P50MH094267 awarded to NJC. Support was also provided by the Australian Research Council FT0991360 (NRW), DE130100614 (SHL) and the Australian National Health and Medical Research Council: 1047956 (NRW), 1052684 (JY), and the German Research Foundation (DFG GR 1912/1-1) to HJG and to PF, SR, MW. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423), and R01-MH-50214 (GN). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs00 0092.v1.p1 through dbGaP accession number phs000092.v1.p. None of the funding agencies for this project (NINDS, NIMH, the Tourette Syndrome Association and the Judah Foundation) had any influence or played any role in a) the design or conduct of the study; b) management, analysis or interpretation of the data; c) preparation, review or approval of the manuscript. 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Here we show that Atg7, an essential macroautophagy component, regulates dopaminergic axon terminal morphology. Mature Atg7-deficient midbrain dopamine (DA) neurons harbored selectively enlarged axonal terminals. This contrasted with the phenotype of DA neurons deficient in Pten - a key negative regulator of the mTOR kinase signaling pathway and neuron size - that displayed enlarged soma but unaltered axon terminals. Surprisingly, concomitant deficiency of both Atg7 and Pten led to a dramatic enhancement of axon terminal enlargement relative to Atg7 deletion alone. Similar genetic interactions between Atg7 and Pten were observed in the context of DA turnover and DA-dependent locomotor behaviors. These data suggest a model for morphological regulation of mature dopaminergic axon terminals whereby the impact of mTOR pathway is suppressed by macroautophagy. C1 [Inoue, Keiichi; Rispoli, Joanne; MacLeod, David; Abeliovich, Asa] Columbia Univ, Dept Pathol, Taub Inst, Med Ctr, New York, NY 10027 USA. [Inoue, Keiichi; Rispoli, Joanne; MacLeod, David; Abeliovich, Asa] Columbia Univ, Dept Neurol, Taub Inst, Med Ctr, New York, NY USA. [Yang, Lichuan; Beal, M. Flint] Cornell Univ, Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. [Klann, Eric] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Inoue, K (reprint author), Columbia Univ, Dept Pathol, Taub Inst, Med Ctr, New York, NY 10027 USA. EM aa900@columbia.edu FU NIH [NS064433-01, NS060876, NS082068-01]; Michael J. Fox Foundation; Kanae Foundation for the Promotion of Medical Science and Research Foundation ITSUU Laboratory FX This work was supported by NIH grants NS064433-01, NS060876, and NS082068-01 to AA; Michael J. Fox Foundation to AA; and the Kanae Foundation for the Promotion of Medical Science and Research Foundation ITSUU Laboratory to KI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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TI Both Rare and De Novo Copy Number Variants Are Prevalent in Agenesis of the Corpus Callosum but Not in Cerebellar Hypoplasia or Polymicrogyria SO PLOS GENETICS LA English DT Article ID 17Q21.31 MICRODELETION SYNDROME; DANDY-WALKER MALFORMATION; WHITE-MATTER; MENTAL-RETARDATION; DEVELOPMENTAL DELAY; SPECTRUM DISORDERS; KANSL1 CAUSE; AUTISM; DELETION; MUTATIONS AB Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and polymicrogyria (PMG) are severe congenital brain malformations with largely undiscovered causes. We conducted a large-scale chromosomal copy number variation (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349 controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH or PMG patients, had rare genic CNVs over one megabase (p = 1.48x10(-3); odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.89-5.39). Rare genic CNVs were those that impacted at least one gene in less than 1% of the combined population of patients and controls. Compared to controls, significantly more ACC but not CBLH or PMG patients had rare CNVs impacting over 20 genes (p = 0.01; OR = 2.95; 95% CI = 1.69-5.18). Independent qPCR confirmation showed that 9.4% of ACC patients had de novo CNVs. These, in comparison to inherited CNVs, preferentially overlapped de novo CNVs previously observed in patients with autism spectrum disorders (p = 3.06x10(-4); OR = 7.55; 95% CI = 2.40-23.72). Interestingly, numerous reports have shown a reduced corpus callosum area in autistic patients, and diminished social and executive function in many ACC patients. We also confirmed and refined previously known CNVs, including significantly narrowing the 8p23.1-p11.1 duplication present in 2% of our current ACC cohort. We found six novel CNVs, each in a single patient, that are likely deleterious: deletions of 1p31.3-p31.1, 1q31.2-q31.3, 5q23.1, and 15q11.2-q13.1; and duplications of 2q11.2-q13 and 11p14.3-p14.2. One ACC patient with microcephaly had a paternally inherited deletion of 16p13.11 that included NDE1. Exome sequencing identified a recessive maternally inherited nonsense mutation in the non-deleted allele of NDE1, revealing the complexity of ACC genetics. This is the first systematic study of CNVs in congenital brain malformations, and shows a much higher prevalence of large gene-rich CNVs in ACC than in CBLH and PMG. C1 [Sajan, Samin A.] Baylor Coll Med, Dept Pediat, Neurol Sect, Houston, TX 77030 USA. [Fernandez, Liliana; Nieh, Sahar Esmaeeli; Rider, Eric; Bukshpun, Polina; Wakahiro, Mari; Sherr, Elliott H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Christian, Susan L.; Sullivan, Christopher T.; Millen, Kathleen J.; Dobyns, William B.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA. [Riviere, Jean-Baptiste] Univ Bourgogne, Equipe Genet Anomalies Dev, Dijon, France. [Sudi, Jyotsna] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Herriges, Michael J.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Paciorkowski, Alexander R.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Paciorkowski, Alexander R.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. [Paciorkowski, Alexander R.] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Div Neuroradiol, San Francisco, CA 94143 USA. [Glessner, Joseph T.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Millen, Kathleen J.; Dobyns, William B.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Hakonarson, Hakon] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dobyns, William B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Sajan, SA (reprint author), Baylor Coll Med, Dept Pediat, Neurol Sect, Houston, TX 77030 USA. EM SherrE@neuropeds.ucsf.edu FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health [R01NS058721] FX The research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health under award number R01NS058721 (to WBD, EHS, and KJM), and by a donation from Eric, Marnie, Alan and Patricia Baer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2013 VL 9 IS 10 AR e1003823 DI 10.1371/journal.pgen.1003823 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 299AR UT WOS:000330367200014 PM 24098143 ER PT J AU Botting, N Psarou, P Caplin, T Nevin, L AF Botting, Nicola Psarou, Popi Caplin, Tamara Nevin, Laura TI Short-Term Memory Skills in Children With Specific Language Impairment The Effect of Verbal and Nonverbal Task Content SO TOPICS IN LANGUAGE DISORDERS LA English DT Article DE children; language impairment; nonverbal; short-term memory ID NON-WORD REPETITION; WORKING-MEMORY; PSYCHOLINGUISTIC MARKERS; DYNAMIC ASSESSMENT; SLI; VOCABULARY; CAPACITY; AUTISM AB Background and Design: In recent years, evidence has emerged that suggests specific language impairment (SLI) does not exclusively affect linguistic skill. Studies have revealed memory difficulties, including those measured using nonverbal tasks. However, there has been relatively little research into the nature of the verbal/nonverbal boundaries either at a conceptual level or at a task-related level. This study explores the short-term memory performance of children with and without SLI on a series of tasks that involve varying degrees of verbal content, implied or explicit. In total, 14 children with SLI and 20 comparison peers participated. Results: Findings show that children with SLI performed more poorly than peers on all tasks except the purely nonverbal block recall task. Interestingly, a task that required no verbal processing or output was as problematic for the SLI group as a traditional nonword memory span task, suggesting that verbal encoding was used by the typical peers but less so by those with SLI. Furthermore, a verbal input picture span task (involving hearing a list of words but requiring a nonverbal response) correlated strongly with the block recall task for children with SLI. This may provide preliminary evidence that visual encoding was being used as a central strategy by the SLI group to aid performance. Discussion: The findings have implications for our understanding of the nature of SLI and also for the use of verbal and visual content in the classroom and other real-life settings. C1 [Botting, Nicola; Psarou, Popi; Caplin, Tamara; Nevin, Laura] City Univ London, London EC1V 0HB, England. RP Botting, N (reprint author), City Univ London, Northampton Sq, London EC1V 0HB, England. EM nicola.botting.1@city.ac.uk CR Baddeley A, 2003, NAT REV NEUROSCI, V4, P829, DOI 10.1038/nrn1201 Baddeley A. D., 1974, PSYCHOL LEARN MOTIV, V8, P47, DOI DOI 10.1016/S0079-7421(08)60452-1 Bavin EL, 2005, INT J LANG COMM DIS, V40, P319, DOI 10.1080/13682820400027750 Bishop D. V. 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Lang. Disord. PD OCT-DEC PY 2013 VL 33 IS 4 BP 313 EP 327 DI 10.1097/01.TLD.0000437940.01237.51 PG 15 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 299DY UT WOS:000330376700005 ER PT J AU Ameis, SH Fan, J Rockel, C Soorya, L Wang, AT Anagnostou, E AF Ameis, Stephanie H. Fan, Jin Rockel, Conrad Soorya, Latha Wang, A. Ting Anagnostou, Evdokia TI Altered cingulum bundle microstructure in autism spectrum disorder SO ACTA NEUROPSYCHIATRICA LA English DT Article DE autism spectrum disorder; diffusion tensor imaging; limbic system ID PERVASIVE DEVELOPMENTAL DISORDERS; WHITE-MATTER; IMAGING TRACTOGRAPHY; DIFFUSION; BRAIN; CONNECTIVITY; CHILDREN; ADOLESCENTS; PATHOLOGY; ATLAS AB Objective Here, we examined the cingulum bundle, a long-range white matter tract mediating dorsal limbic connectivity, using diffusion tensor imaging (DTI) tractography, in children and adolescents with autism spectrum disorder (ASD) versus controls. We hypothesised that cingulum bundle microstructure would be altered in ASD, based on evidence implicating abnormal white matter connectivity in this disorder. Methods DTI data were acquired for 19 ASD participants (IQ 70; 7-18 years; mean = 12.4 3.1) and 16 age-matched controls (7-18 years; mean = 12.3 3.6) on a 3 T magnetic resonance imaging system. Deterministic tractography was used to isolate the cingulum bundle. Left and right cingulum bundles were examined for differences in several DTI metrics in ASD children/adolescents versus controls, including: fractional anisotropy (FA), mean, axial, and radial diffusivity. Results Significant age x group interaction effects were found for all DTI metrics (mean diffusivity: F-1,F-28 = 9.5, p = 0.005, radial diffusivity: F-1,F-28 = 7.8, p = 0.009, axial diffusivity: F-1,F-28 = 5.2, p = 0.03, FA: F-1,F-28 = 4.4, p = 0.04). Interaction effects were driven by increases in cingulum bundle diffusivity (mean, radial, and axial diffusivity), and decreased FA, in younger ASD participants within our sample versus controls. Conclusion Our results point to immature microstructural organisation of the cingulum bundle in ASD, particularly during the early years of life, with implications for limbic network synchronisation and complex socio-emotional performance. C1 [Ameis, Stephanie H.; Rockel, Conrad] Univ Toronto, Hosp Sick Children, Dept Psychiat, Toronto, ON M4G 1R8, Canada. [Fan, Jin] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Fan, Jin; Soorya, Latha; Wang, A. Ting; Anagnostou, Evdokia] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Anagnostou, Evdokia] Univ Toronto, Bloorview Res Inst, Holland Bloorview Kids Rehabil Hosp, Dept Pediat, Toronto, ON M4G 1R8, Canada. RP Anagnostou, E (reprint author), Univ Toronto, Bloorview Res Inst, Holland Bloorview Kids Rehabil Hosp, Dept Pediat, 150 Kilgour Rd, Toronto, ON M4G 1R8, Canada. EM eanagnostou@hollandbloorview.ca RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 FU NARSAD; Autism Speaks; NIMH [MH083164]; Autism Research Training Program; Canadian Institutes of Health Research (CIHR) Strategic Training Initiative in Health Research (STIHR); Sinneave Family Foundation FX The research work presented here was carried out at: The Mount Sinai School of Medicine (Department of Psychiatry), The Hospital for Sick Children (Department of Psychiatry), and Holland Bloorview Kids Rehabilitation Hospital. The authors would like to thank Ms. Nadia Tanel (Holland Bloorview Kids Rehabilitation Hospital) for assistance with data organisation. This work was supported by NARSAD (PI: Anagnostou), Autism Speaks (PI: Anagnostou), NIMH MH083164 (PI: Fan), and the Autism Research Training Program (salary support to S.H.A.), funded by the Canadian Institutes of Health Research (CIHR) Strategic Training Initiative in Health Research (STIHR), with supplemental funding from the Sinneave Family Foundation. 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Oxytocin is one element in a complex network of interactions observed in natural phenomena ranging from molecular biology, etology, social behavior and human psychology. C1 [Orsucci, F.] UCL, Div Psychol & Language Sci, London WC1E 6BT, England. [Paoloni, G.; Conti, C. M.; Fulcheri, M.] Univ G dAnnunzio, Dept Psychol Humanist & Territorial Sci, Pescara, Italy. [Reda, M.] Univ Siena, Dept Neurol & Behav Sci, I-53100 Siena, Italy. RP Orsucci, F (reprint author), UCL, Div Psychol & Language Sci, Gower St, London WC1E 6BT, England. 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W., 1958, COLLECTED PAPERS PAE Young LJ, 2005, J COMP NEUROL, V493, P51, DOI 10.1002/cne.20771 Zak PJ, 2007, PLOS ONE, V2, P1128 Zanette DH, 2004, PHYSICA D, V194, P203, DOI 10.1016/j.physd.2004.03.002 NR 40 TC 0 Z9 0 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0393-974X EI 1724-6083 J9 J BIOL REG HOMEOS AG JI J. Biol. Regul. Homeost. Agents PD OCT-DEC PY 2013 VL 27 IS 4 BP 947 EP 954 PG 8 WC Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology SC Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology GA 292HO UT WOS:000329893000003 PM 24382175 ER PT J AU Matsui, G Ohtoshi, T Takada, S AF Matsui, Gakuyo Ohtoshi, Taro Takada, Satoshi TI Imitation of 'bye-bye' in very low-birthweight infants SO PEDIATRICS INTERNATIONAL LA English DT Article DE bye-bye; development; imitation ability; very low-birthweight infant ID MIRROR-NEURON SYSTEM; PRETERM INFANTS; AGE; MOVEMENTS; GESTURES; AUTISM AB BackgroundThe aim of this study was to clarify the development of imitation skills in very low-birthweight (VLBW) infants compared with full-term infants with regard to the onset of bye-bye'. MethodsA total of 597 full-term infants (age, 6-21 months) and 95 VLBW infants (corrected age, 6-21 months) participated in this study. The time at which the infants began to imitate bye-bye and how they moved their hands were investigated by direct observations of their behaviors. ResultSome full-term infants began to imitate bye-bye at 9 months, and all full-term infants could imitate bye-bye by 16 months old. The imitation of bye-bye was delayed in VLBW infants, but all of them could imitate it at 17 months old. Bye-bye motions were divided into five types. The moving wrist up and down' motion was observed most frequently at the initial bye-bye in both groups, but it was more frequent in VLBW infants at the early stage. The motion types changed with age, with the palm facing others' motion observed exclusively at 16 months in full-term infants. All infants of both groups could imitate this type at 17 months old. ConclusionThe development of the ability to imitate bye-bye was delayed in VLBW infants even after correction for gestational age. It was suspected that the fine motor development delay might contribute to the late appearance of bye-bye in VLBW infants. Further follow-up study is required to clarify the clinical significance. C1 [Matsui, Gakuyo; Takada, Satoshi] Kobe Univ, Grad Sch Hlth Sci, Kobe, Hyogo 6540142, Japan. [Ohtoshi, Taro] Kansai Univ Welf Sci, Osaka, Japan. Kobe Univ, Grad Sch Hlth Sci, Suma Ku, Kobe, Hyogo 6540142, Japan. RP Matsui, G (reprint author), Kobe Univ, Grad Sch Hlth Sci, Suma Ku, 7-10-2 Tomogaoka, Kobe, Hyogo 6540142, Japan. 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Int. PD OCT PY 2013 VL 55 IS 5 BP 561 EP 565 DI 10.1111/ped.12160 PG 5 WC Pediatrics SC Pediatrics GA 286ZL UT WOS:000329507700014 PM 23773446 ER PT J AU Benson, AD Burket, JA Deutsch, SI AF Benson, Andrew D. Burket, Jessica A. Deutsch, Stephen I. TI Balb/c mice treated with D-cycloserine arouse increased social interest in conspecifics SO BRAIN RESEARCH BULLETIN LA English DT Article DE D-Cycloserine; NMDA receptor; Sociability; Social preference; Balb/c mouse ID AUTISM SPECTRUM DISORDERS; INBRED MOUSE STRAINS; NMDA RECEPTOR ANTAGONIST; STEREOTYPIC BEHAVIORS; IMPROVES SOCIABILITY; MK-801; MODEL; SCHIZOPHRENIA; SENSITIVITY; DIFFER AB The genetically inbred Balb/cJ (Balb/c) mouse with functional alteration of its endogenous tone of NMDA receptor-mediated neurotransmission displays impaired sociability in a standard paradigm; this mouse strain has been proposed as a model of autism spectrum disorders (ASDs). Prior work showed that treatment of the Balb/c mouse with a centrally effective dose of D-cycloserine, a partial glycine(B) NMDA receptor agonist, improved several measures of its sociability. Additionally, D-cycloserine-treated Balb/c mice show greater preference for a social stimulus mouse than an inanimate object. We wondered if treatment with D-cycloserine also improved the social salience of the Balb/c mouse for "normally" sociable comparator strains. The current experiments explored whether C578I/6J (B6) and ICR mouse strains prefer D-cycloserine-treated to vehicle-treated Balb/c stimulus mice in a paradigm that evaluated social preference. The results showed that B6 mice prefer D-cycloserine-treated Balb/c mice to vehicle-treated Balb/c mice, suggesting that treatment could have resulted in normalization of "emitted" social cues. (C) 2013 Elsevier Inc. All rights reserved. C1 [Benson, Andrew D.; Burket, Jessica A.; Deutsch, Stephen I.] Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, Norfolk, VA 23507 USA. RP Deutsch, SI (reprint author), Eastern Virginia Med Sch, Dept Psychiat & Behav Sci, 825 Fairfax Ave,Suite 710, Norfolk, VA 23507 USA. EM deutscsi@evms.edu FU Eastern Virginia Medical School; Commonwealth Health Research Board of the Commonwealth of Virginia; Office of the Dean of Eastern Virginia Medical School FX The authors acknowledge the support they received from the Office of the Dean of Eastern Virginia Medical School, a Research Enhancement Grant from Eastern Virginia Medical School, and a grant from the Commonwealth Health Research Board of the Commonwealth of Virginia. 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TI USEFULNESS OF NEEDLE ELECTROMYOGRAPHY IN CHILDREN WITH AUTISM SO MUSCLE & NERVE LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-of-Neuromuscular-and-Electrodiagnostic-Medicine (AANEM) CY OCT 16-19, 2013 CL San Antonio, TX SP Amer Assoc Neuromuscular & Electrodiagnost Med NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2013 VL 48 IS 4 BP 634 EP 634 DI 10.1002/mus.24071 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264NF UT WOS:000327884200030 ER PT J AU Catassi, C Bai, JC Bonaz, B Bouma, G Calabro, A Carroccio, A Castillejo, G Ciacci, C Cristofori, F Dolinsek, J Francavilla, R Elli, L Green, P Holtmeier, W Koehler, P Koletzko, S Meinhold, C Sanders, D Schumann, M Schuppan, D Ullrich, R Vecsei, A Volta, U Zevallos, V Sapone, A Fasano, A AF Catassi, Carlo Bai, Julio C. Bonaz, Bruno Bouma, Gerd Calabro, Antonio Carroccio, Antonio Castillejo, Gemma Ciacci, Carolina Cristofori, Fernanda Dolinsek, Jernej Francavilla, Ruggiero Elli, Luca Green, Peter Holtmeier, Wolfgang Koehler, Peter Koletzko, Sibylle Meinhold, Christof Sanders, David Schumann, Michael Schuppan, Detlef Ullrich, Reiner Vecsei, Andreas Volta, Umberto Zevallos, Victor Sapone, Anna Fasano, Alessio TI Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders SO NUTRIENTS LA English DT Review DE gluten sensitivity; celiac disease; wheat allergy; gluten-related disorders; gluten-free diet ID AUTISM SPECTRUM DISORDERS; CONTROLLED-TRIAL; FREE DIET; DISEASE; CHILDREN; BLIND; WHEAT; PREVALENCE; CHALLENGE; SYMPTOMS AB Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a re-discovered disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS. C1 [Catassi, Carlo] Univ Politecn Marche, Dept Pediat, I-60121 Ancona, Italy. [Bai, Julio C.] Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Dept Med, RA-1264 Buenos Aires, DF, Argentina. [Bonaz, Bruno] CHU Grenoble, Dept Gastroenterol & Liver Dis, F-38043 Grenoble, France. [Bouma, Gerd] Vrije Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-1081 HV Amsterdam, Netherlands. [Calabro, Antonio] Univ Florence, Dept Expt & Clin Biomed Sci, Gastroenterol Unit, I-50134 Florence, Italy. [Carroccio, Antonio] Giovanni Paolo II Hosp, Dept Internal Med, Sciacca, AG, Italy. [Carroccio, Antonio] Univ Palermo, I-92019 Sciacca, Italy. [Castillejo, Gemma] Univ Rovira & Virgili, Hosp Univ St Joan de Reus, Pediat Gastroenterol Unit, Tarragona 43204, Spain. [Ciacci, Carolina] Univ Salerno, Dept Med & Surg, I-84081 Salerno, Italy. [Cristofori, Fernanda; Francavilla, Ruggiero] Univ Bari, Interdisciplinary Dept Med, I-70124 Bari, Italy. [Dolinsek, Jernej] Univ Med Ctr Maribor, Dept Pediat, Gastroenterol Unit, Maribor 2000, Slovenia. [Elli, Luca] Ctr Prevenz & Diagnosi Malattia Celiaca Fdn IRCCS, I-20122 Milan, Italy. [Green, Peter] Columbia Univ Med Ctr, Dept Med, Celiac Dis Ctr, New York, NY 10032 USA. [Holtmeier, Wolfgang] Hosp Porz Rhein, Div Gastroenterol & Internal Med, D-51149 Cologne, Germany. [Koehler, Peter] Leibniz Inst, German Res Ctr Food Chem, D-85354 Freising Weihenstephan, Germany. [Koletzko, Sibylle] Univ Munich Med Ctr, Dr von Hauner Childrens Hosp, Div Pediat Gastroenterol & Hepatol, D-80337 Munich, Germany. [Meinhold, Christof] Practice Nutr Therapy Meinhold & Team, D-50674 Cologne, Germany. [Sanders, David] Royal Hallamshire Hosp, Dept Gastroenterol & Hepatol, Sheffield S10 2JF, S Yorkshire, England. [Sanders, David] Univ Sheffield Med Sch, Sheffield S10 2JF, S Yorkshire, England. [Schumann, Michael; Ullrich, Reiner] Charite, Dept Gastroenterol Rheumatol & Infectiol, D-10203 Berlin, Germany. [Schuppan, Detlef; Zevallos, Victor] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, D-55131 Mainz, Germany. [Schuppan, Detlef] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Schuppan, Detlef] Beth Israel Deaconess Med Ctr, Celiac Ctr, Boston, MA 02215 USA. [Schuppan, Detlef] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Vecsei, Andreas] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Volta, Umberto] Univ Bologna, Dept Med & Surg Sci, I-40138 Bologna, Italy. [Sapone, Anna] Univ Naples 2, Dept Gastroenterol, I-80136 Naples, Italy. [Fasano, Alessio] MassGen Hosp Children, Boston, MA 02129 USA. RP Fasano, A (reprint author), MassGen Hosp Children, Boston, MA 02129 USA. EM catassi@tin.it; jbai@intramed.net; bbonaz@chu-grenoble.fr; g.bouma@vumc.nl; a.calabro@dfc.unifi.it; acarroccio@hotmail.com; gcv@tinet.cat; cciacci@unisa.it; fernandacristofori@gmail.com; jernej.dolinsek@ukc-mb.si; rfrancavilla@gmail.com; lucelli@yahoo.com; pg11@columbia.edu; w.holtmeier@khporz.de; peter.koehler@tum.de; sybille.koletzko@med.uni-muenchen.de; praxis@christof-meinhold.de; david.sanders@sth.nhs.uk; michael.schumann@charite.de; dschuppa@bidmc.harvard.edu; reiner.ullrich@charite.de; andreas.vecsei@stanna.at; uvolt@yahoo.com; zevallos@uni-mainz.de; annasapone@yahoo.it; afasano@partners.org RI bouma, gerd/E-2520-2013 FU Schar; Menarini Diagnostics FX Carlo Catassi received consulting fees from Schar and Menarini Diagnostics. Luca Elli and Anna Sapone received consulting fees from Schar. Peter Green is a member of the scientific advisory board of Alvine Pharmaceuticals and Alba Therapeutics. Alessio Fasano owns stock in Alba Therapeutics. The other authors declared no conflict of interest. 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Y. Conley, Sandra K. Gropman, Andrea Porter, Forbes D. Baker, Eva H. TI Brain Magnetic Resonance Imaging Findings in Smith-Lemli-Opitz Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Smith-Lemli-Opitz syndrome (SLOS); magnetic resonance imaging (MRI); brain ID DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; MULTIPLE CONGENITAL-ANOMALIES; AUTISM SPECTRUM DISORDERS; SONIC-HEDGEHOG; LIPID RAFTS; SEPTI PELLUCIDI; OPTIZ-SYNDROME; METABOLISM; FOREBRAIN; PHENOTYPE AB Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27 M, 28 F) between age 0.17 years and 25.4 years (mean=6.2, SD=5.8) received a total of 173 brain MRI scans (mean=3.1 per subject) on a 1.5T GE scanner between September 1998 and December 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS. (c) 2013 Wiley Periodicals, Inc. C1 [Lee, Ryan W. Y.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA. [Lee, Ryan W. Y.; Conley, Sandra K.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Gropman, Andrea] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Lee, RWY (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, 716 North Broadway St, Baltimore, MD 21205 USA. EM leer@kennedykrieger.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH Clinical Center; NIH Office of Rare Diseases; RSH/Smith-Lemli-Opitz Foundation FX Grant sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development; Grant sponsor: NIH Clinical Center; Grant sponsor: NIH Office of Rare Diseases; Grant sponsor: RSH/Smith-Lemli-Opitz Foundation. 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J. Med. Genet. A PD OCT PY 2013 VL 161 IS 10 BP 2407 EP 2419 DI 10.1002/ajmg.a.36096 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 264FP UT WOS:000327862700002 PM 23918729 ER PT J AU Fisch, GS AF Fisch, Gene S. TI Autism and Epistemology IV: Does Autism Need a Theory of Mind? SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material DE theory of mind; autism; cognition; mirror neurons; mental states; validity ID FRAGILE-X-SYNDROME; MIRROR NEURON SYSTEM; THEORY-OF-MIND; FALSE-BELIEF; SPECTRUM DISORDERS; EMOTION RECOGNITION; DEVELOPMENTAL DISORDERS; CHILDRENS KNOWLEDGE; TYPICAL DEVELOPMENT; MENTAL-RETARDATION AB In their article, Does the autistic child have a theory of mind'?, Baron-Cohen et al. [1985] proposed a novel paradigm to explain social impairment in children diagnosed as autistic (AD). Much research has been undertaken since their article went to print. The purpose of this commentary is to gauge whether Theory of Mind (ToM)or lack thereofis a valid model for explaining abnormal social behavior in children with AD. ToM is defined as the ability to impute mental states to oneself and to others and the ability to make inferences about what other people believe to be the case. The source for their model was provided by an article published earlier by Premack and Woodruff, Does the chimpanzee have a theory of mind? Later research in chimpanzees did not support a ToM in primates. From the outset, ToM as a neurocognitive model of autism has had many shortcomingsmethodological, logical, and empirical. Other ToM assumptions, for example, its universality in all children in all cultures and socioeconomic conditions, are not supported by data. The age at which a ToM emerges, or events that presage a ToM, are too often not corroborated. Recent studies of mirror neurons, their location and interconnections in brain, their relationship to social behavior and language, and the effect of lesions there on speech, language and social behavior, strongly suggests that a neurobiological as opposed to neurocognitive model of autism is a more parsimonious explanation for the social and behavioral phenotypes observed in autism. (c) 2013 Wiley Periodicals, Inc. C1 [Fisch, Gene S.] NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY 10003 USA. [Fisch, Gene S.] NYU, Coll Nursing, Dept Epidemiol & Hlth Promot, New York, NY 10003 USA. RP Fisch, GS (reprint author), NYU, Coll Dent, Dept Epidemiol & Hlth Promot, 250 Pk Ave S,6th Fl, New York, NY 10003 USA. 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J. Med. Genet. A PD OCT PY 2013 VL 161 IS 10 BP 2464 EP 2480 DI 10.1002/ajmg.a.36135 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 264FP UT WOS:000327862700007 PM 23956150 ER PT J AU Dimassi, S Andrieux, J Labalme, A Lesca, G Cordier, MP Boute, O Neut, D Edery, P Sanlaville, D Schluth-Bolard, C AF Dimassi, Sarra Andrieux, Joris Labalme, Audrey Lesca, Gaetan Cordier, Marie-Pierre Boute, Odile Neut, Dorothee Edery, Patrick Sanlaville, Damien Schluth-Bolard, Caroline TI Interstitial 12p13.1 Deletion Involving GRIN2B in Three Patients With Intellectual Disability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE aCGH; 12p13; 1 deletion; GRIN2B; intellectual disability; NMDA receptor ID AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; NMDA RECEPTORS; SCHIZOPHRENIA; SUBUNIT; MEMORY; PERFORMANCE; EXPRESSION; DIVERSITY; CHANNEL AB We report on three patients presenting moderate intellectual disability, delayed language acquisition, and mild facial dysmorphia. Array-CGH studies revealed overlapping interstitial 12p13.1 microdeletions encompassing all or part of GRIN2B. GRIN2B encodes the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor. This receptor is a heteromeric glutamate-activated ion channel, present throughout the central nervous system. It plays a critical role in corticogenesis, neuronal migration, and synaptogenesis during brain development. GRIN2B alterations, including mutation and gene disruption by apparently balanced chromosomal rearrangements, have been described in patients with intellectual disability and autism spectrum disorder. We report here on the first cases of GRIN2B deletion, enlarging the spectrum of GRIN2B abnormalities. Our findings confirm the involvement of this gene in neurodevelopmental disorders. (c) 2013 Wiley Periodicals, Inc. C1 [Dimassi, Sarra; Labalme, Audrey; Lesca, Gaetan; Cordier, Marie-Pierre; Edery, Patrick; Sanlaville, Damien; Schluth-Bolard, Caroline] Hosp Civils Lyon, Serv Genet, Lab Cytogenet Constitut, Ctr Biol & Pathol Est, Lyon, France. [Andrieux, Joris] Hop Jeanne de Flandre, Lab Genet Med, CHRU Lille, Lille, France. [Lesca, Gaetan; Edery, Patrick; Sanlaville, Damien; Schluth-Bolard, Caroline] Univ Lyon 1, CNRL, INSERM U1028, CNRS UMR5292,Equipe TIGER, F-69365 Lyon, France. [Boute, Odile] Hop Jeanne de Flandre, Serv Genet Clin, CHRU Lille, Lille, France. RP Schluth-Bolard, C (reprint author), Ctr Biol & Pathol EST, Serv Genet, Lab Cytogenet Constitut, 59 Blvd Pinel, F-69677 Bron, France. EM caroline.schluth-bolard@chu-lyon.fr RI sanlaville, damien/M-4716-2014 OI sanlaville, damien/0000-0001-9939-2849 FU French Ministry of Health FX Grant sponsor: French Ministry of Health. 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A PD OCT PY 2013 VL 161 IS 10 BP 2564 EP 2569 DI 10.1002/ajmg.a.36079 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 264FP UT WOS:000327862700020 PM 23918416 ER PT J AU Lacaze, E Gruchy, N Penniello-Valette, MJ Plessis, G Richard, N Decamp, M Mittre, H Leporrier, N Andrieux, J Kottler, ML Gerard, M AF Lacaze, Elodie Gruchy, Nicolas Penniello-Valette, Marie-Jose Plessis, Ghislaine Richard, Nicolas Decamp, Mathieu Mittre, Herve Leporrier, Nathalie Andrieux, Joris Kottler, Marie-Laure Gerard, Marion TI De Novo 15q13.3 Microdeletion With Cryptogenic West Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE West syndrome; epilepsy; CHRNA7; array-CGH; 15q13; 3 microdeletion ID FRONTAL-LOBE EPILEPSY; AUTISM SPECTRUM DISORDERS; INFANTILE SPASMS; MENTAL-RETARDATION; DEVELOPMENTAL DISORDER; GENE; MUTATIONS; DELETION; ASSOCIATION; PHENOTYPES AB West syndrome is a well-recognized form of epilepsy, defined by a triad of infantile spasms, hypsarrhythmia and developmental arrest. West syndrome is heterogenous, caused by mutations of genes ARX, STXBP1, KCNT1 among others; 16p13.11 and 17q21.31 microdeletions are less frequent, usually associated with intellectual disability and facial dysmorphism. So-called idiopathic West syndrome is of better prognostic, without prior intellectual deficiency and usually responsive to anti-epileptic treatment. We report on a boy falling within the scope of idiopathic West syndrome, with no dysmorphic features and normal development before the beginning of West syndrome, with a good resolution after treatment, bearing a de novo 15q13.3 microdeletion. Six genes are located in the deleted region, including CHRNA7, which encodes a subunit of a nicotinic acetylcholine receptor, and is frequently associated with epilepsy. Exploration of the 15q13.3 region should be proposed in idiopathic West syndrome. (c) 2013 Wiley Periodicals, Inc. C1 [Lacaze, Elodie; Gruchy, Nicolas; Plessis, Ghislaine; Richard, Nicolas; Decamp, Mathieu; Mittre, Herve; Leporrier, Nathalie; Kottler, Marie-Laure; Gerard, Marion] Hop Cote Nacre, Dept Genet, Caen, France. [Penniello-Valette, Marie-Jose] Hop Cote Nacre, Dept Neuropediat, Caen, France. [Andrieux, Joris] CHRU Lille, Lab Genet Med, F-59037 Lille, France. RP Gerard, M (reprint author), CHR Clemenceau, Caen, France. 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A PD OCT PY 2013 VL 161 IS 10 BP 2582 EP 2587 DI 10.1002/ajmg.a.36085 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 264FP UT WOS:000327862700023 PM 23929658 ER PT J AU Schwaibold, EMC Zoll, B Burfeind, P Hobbiebrunken, E Wilken, B Funke, R Shoukier, M AF Schwaibold, Eva Maria Christina Zoll, Barbara Burfeind, Peter Hobbiebrunken, Elke Wilken, Bernd Funke, Rudolf Shoukier, Moneef TI A 3p Interstitial Deletion in Two Monozygotic Twin Brothers and an 18-Year-Old Man: Further Characterization and Review SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 3p interstitial deletion; intellectual disability; autistic features; 3p proximal deletion ID SEVERE SPEECH DELAY; PROXIMAL 3P; FOXP1 GENE; TUMOR; EXPRESSION; PATIENT; PROTEIN; AUTISM AB An increasing number of patients with 3p proximal deletions were reported in the previous decade, but the region responsible for the main features such as intellectual disability (ID) and developmental delay is not yet characterized. Here we report on two monozygotic twin brothers of 2 10/12 years and an 18-year-old man, all three of them displaying severe ID, psychomotoric delay, autistic features, and only mild facial dysmorphisms. Array CGH (aCGH), revealed a 6.55Mb de novo interstitial deletion of 3p14.1p14.3 in the twin brothers and a 4.76Mb interstitial deletion of 3p14.1p14.2 in the 18-year-old patient, respectively. We compared the malformation spectrum with previous molecularly well-defined patients in the literature and in the DECIPHER database (Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources; http://decipher.sanger.ac.uk/). In conclusion, the deletion of a region containing 3p14.2 seems to be associated with a relative concise phenotype including ID and developmental delay. Thus, we hypothesize that 3p14.2 is the potential core region in 3p proximal deletions. The knowledge of this potential core region could be helpful in the genetic counselling of patients with 3p proximal deletions, especially concerning their phenotype. (c) 2013 Wiley Periodicals, Inc. C1 [Schwaibold, Eva Maria Christina; Zoll, Barbara; Burfeind, Peter] Univ Gottingen, Inst Human Genet, D-37073 Gottingen, Germany. [Hobbiebrunken, Elke] Univ Gottingen, Dept Pediat & Pediat Neurol, D-37073 Gottingen, Germany. [Wilken, Bernd; Funke, Rudolf] Sozialpadiatr Zentrum, Dept Neuropediat, Kassel, Germany. [Shoukier, Moneef] Univ Gottingen, Dept Gynecol & Obstet, D-37073 Gottingen, Germany. RP Schwaibold, EMC (reprint author), Inst Human Genet, Heinrich Duker Weg 12, D-37073 Gottingen, Germany. 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J. Med. Genet. A PD OCT PY 2013 VL 161 IS 10 BP 2634 EP 2640 DI 10.1002/ajmg.a.36129 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 264FP UT WOS:000327862700032 PM 23949945 ER PT J AU Emerson, E Felce, D Stancliffe, RJ AF Emerson, Eric Felce, David Stancliffe, Roger J. TI Issues Concerning Self-Report Data and Population-Based Data Sets Involving People With Intellectual Disabilities SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE intellectual disabilities; self-report; proxy; response bias; population-based data; secondary analysis ID QUALITY-OF-LIFE; MATERNAL MENTAL-HEALTH; DEVELOPMENTAL-DISABILITIES; WESTERN-AUSTRALIA; COGNITIVE DELAY; CHILDREN; PREVALENCE; RETARDATION; AUTISM; SCALE AB This article examines two methodological issues regarding ways of obtaining and analyzing outcome data for people with intellectual disabilities: (a) self-report and proxy-report data and (b) analysis of population-based data sets. Some people with intellectual disabilities have difficulties with self-reporting due to problems of understanding and communication. However, there are serious doubts about the validity of proxy data for subjective issues. One important challenge with secondary analysis of population-based data sets is the difficulty of accurately identifying survey participants with intellectual disabilities. In both areas examined, it is important to recognize these constraints when interpreting research based on such data. C1 [Emerson, Eric; Stancliffe, Roger J.] Univ Sydney, Ctr Disabil Res & Policy, Lidcombe, NSW 1825, Australia. [Emerson, Eric] Univ Lancaster, Ctr Disabil Res, Lancaster LA1 4YW, England. [Felce, David] Cardiff Univ, Sch Med, Welsh Ctr Learning Disabil, Cardiff CF10 3AX, S Glam, Wales. RP Emerson, E (reprint author), Univ Lancaster, Ctr Disabil Res, Lancaster LA1 4YW, England. 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PD OCT PY 2013 VL 51 IS 5 SI SI BP 333 EP 348 DI 10.1352/1934-9556-51.5.333 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 272IO UT WOS:000328453900004 PM 24303821 ER PT J AU Anderson, LL Humphries, K McDermott, S Marks, B Sisarak, J Larson, S AF Anderson, Lynda Lahti Humphries, Kathy McDermott, Suzanne Marks, Beth Sisarak, Jasmina Larson, Sheryl TI The State of the Science of Health and Wellness for Adults With Intellectual and Developmental Disabilities SO INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article DE health; health care; wellness; IDD ID AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION; DOWN-SYNDROME; NUTRITIONAL-STATUS; PHYSICAL-ACTIVITY; UNITED-STATES; PROMOTION PROGRAM; PRIMARY-CARE; RISK-FACTORS; PEOPLE AB Historically, people with intellectual and developmental disabilities (IDD) have experienced health disparities related to several factors including: a lack of access to high quality medical care, inadequate preparation of health care providers to meet their needs, the social determinants of health (e.g., poverty, race and gender), and the failure to include people with IDD in public health efforts and other prevention activities. Over the past decade, a greater effort has been made to both identify and begin to address myriad health disparities experienced by people with IDD through a variety of activities including programs that address health lifestyles and greater attention to the training of health care providers. Gaps in the literature include the lack of intervention trials, replications of successful approaches, and data that allow for better comparisons between people with IDD and without IDD living in the same communities. Implications for future research needed to reduce health disparities for people with IDD include: better monitoring and treatment for chronic conditions common in the general population that are also experienced by people with IDD, an enhanced understanding of how to promote health among those in the IDD population who are aging, addressing the health needs of people with IDD who are not part of the disability service system, developing a better understanding of how to include people with IDD in health and wellness programs, and improving methods for addressing the health care needs of members of this group in an efficient and cost-effective manner, either through better access to general medical care or specialized programs. C1 [Anderson, Lynda Lahti; Larson, Sheryl] Univ Minnesota, Res & Training Ctr Community Living, Minneapolis, MN 55455 USA. [Humphries, Kathy] Univ Montana, Montana Disabil & Hlth Program, Rural Inst, Missoula, MT 59812 USA. 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Dev. Disabil. PD OCT PY 2013 VL 51 IS 5 SI SI BP 385 EP 398 DI 10.1352/1934-9556-51.5.385 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 272IO UT WOS:000328453900008 PM 24303825 ER PT J AU Tordjman, S Najjar, I Bellissant, E Anderson, GM Barburoth, M Cohen, D Jaafari, N Schischmanoff, O Fagard, R Lagdas, E Kermarrec, S Ribardiere, S Botbol, M Fougerou, C Bronsard, G Vernay-Leconte, J AF Tordjman, Sylvie Najjar, Imen Bellissant, Eric Anderson, George M. Barburoth, Marianne Cohen, David Jaafari, Nemat Schischmanoff, Olivier Fagard, Remi Lagdas, Enas Kermarrec, Solenn Ribardiere, Sophie Botbol, Michel Fougerou, Claire Bronsard, Guillaume Vernay-Leconte, Julie TI Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE melatonin; biological clocks; circadian rhythm; synchrony; autism spectrum disorders; social communication; stereotyped behaviors ID CONTROLLED-RELEASE MELATONIN; PARENT-INFANT SYNCHRONY; CIRCADIAN ACTIVITY RHYTHMS; PLACEBO-CONTROLLED TRIAL; FRAGILE-X-SYNDROME; SLEEP-WAKE RHYTHM; RETT-SYNDROME; NEURODEVELOPMENTAL DISABILITIES; INTELLECTUAL DISABILITY; DEVELOPMENTAL OUTCOMES AB Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. C1 [Tordjman, Sylvie; Najjar, Imen; Lagdas, Enas; Kermarrec, Solenn; Ribardiere, Sophie; Vernay-Leconte, Julie] Univ Rennes 1, Hosp Univ Dept Child & Adolescent Psychiat, Guillaume Regnier Hosp, F-35000 Rennes, France. [Tordjman, Sylvie; Barburoth, Marianne] CNRS UMR 8158, Lab Psychol Percept, F-75270 Paris, France. [Bellissant, Eric; Fougerou, Claire] Univ Rennes 1, Univ Hosp, Inserm CIC Clin Invest Ctr 0203, F-35033 Rennes, France. [Bellissant, Eric; Fougerou, Claire] Univ Rennes 1, Univ Hosp, Dept Clin Pharmacol, F-35033 Rennes, France. [Anderson, George M.] Yale Child Study Ctr, Lab Dev Neurochem, New Haven, CT 06519 USA. [Anderson, George M.] Yale Univ, Dept Lab Med, Sch Med, New Haven, CT 06519 USA. [Cohen, David] Univ Paris 06, Hosp Univ Dept Child & Adolescent Psychiat, Pitie Salpetriere Hosp, F-75013 Paris, France. [Jaafari, Nemat] Ctr Hosp Henri Laborit, Unite Rech Clin Intersectorielle Psychiat, CHU Poitiers, CIC INSERM U802, F-86022 Poitiers, France. [Schischmanoff, Olivier; Fagard, Remi] Univ Paris 13, INSERM UMR U978, F-93009 Bobigny, France. [Schischmanoff, Olivier; Fagard, Remi] Hop Avicenne, APHP, Lab Biochim & Biol Mol, F-93009 Bobigny, France. [Botbol, Michel] UBO, Serv Hosp Univ Psychiat Enfant & Adolescent Brest, F-29238 Brest, France. [Bronsard, Guillaume] Conseil Gen Bouches Du Rhone, Maison Dept Adolescent, F-13256 Marseille, France. [Bronsard, Guillaume] Conseil Gen Bouches Du Rhone, Ctr Medicopsychopedagog, F-13256 Marseille, France. [Bronsard, Guillaume] Fac Med Timone, Lab Sante Publ EA3279, F-13256 Marseille, France. RP Tordjman, S (reprint author), Univ Rennes 1, Hosp Univ Dept Child & Adolescent Psychiat, Guillaume Regnier Hosp, F-35000 Rennes, France. 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TI The BOLD signal and neurovascular coupling in autism SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE BOLD fMRI; Autism; Blood flow; Neurovascular coupling; Energy; Glutamate ID MENTAL-RETARDATION PROTEIN; CEREBRAL O-2 CONSUMPTION; GLUTAMATE-RECEPTOR 5; DEVELOPMENTAL-CHANGES; SPECTRUM DISORDERS; IMAGING SIGNALS; BLOOD-FLOW; EKER RATS; BRAIN; CHILDREN AB BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging) is commonly used to study differences in neuronal activity between human populations. As the BOLD response is an indirect measure of neuronal activity, meaningful interpretation of differences in BOLD responses between groups relies upon a stable relationship existing between neuronal activity and the BOLD response across these groups. However, this relationship can be altered by changes in neurovascular coupling or energy consumption, which would lead to problems in identifying differences in neuronal activity. In this review, we focus on fMRI studies of people with autism, and comparisons that are made of their BOLD responses with-those of-control groups. We examine neurophysiological-differences in autism that may alter neurovascular coupling or energy use, discuss recent studies that have used fMRI to identify differences between participants with autism and control participants, and explore experimental approaches that could help attribute between-group differences in BOLD signals to either neuronal or neurovascular factors. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Reynell, Clare; Harris, Julia J.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England. RP Reynell, C (reprint author), UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England. EM c.reynell@ucl.ac.uk FU MRC; Wellcome Trust; Fondation Leducq; ERC FX Supported by the MRC, Wellcome Trust, Fondation Leducq and ERC. 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Cogn. Neurosci. PD OCT PY 2013 VL 6 BP 72 EP 79 DI 10.1016/j.dcn.2013.07.003 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 270DI UT WOS:000328298700008 PM 23917518 ER PT J AU O'Reilly, H Thiebaut, FI White, SJ AF O'Reilly, Helen Thiebaut, Flora I. White, Sarah J. TI Is macrocephaly a neural marker of a local bias in autism? SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Macrocephaly; Local bias; Central coherence; Connectivity; Autism ID WEAK CENTRAL COHERENCE; EMBEDDED FIGURES TASK; SPECTRUM DISORDERS; CORTICAL UNDERCONNECTIVITY; SELECTIVE ATTENTION; HEAD CIRCUMFERENCE; ASPERGER-SYNDROME; COGNITIVE-STYLE; CHILDREN; PERFORMANCE AB Previous research has suggested that the local processing bias often reported in studies of Autism Spectrum Condition may only be typical of a subgroup of individuals with autism also presenting with macrocephaly. The current study examined a group of children with autism, with and without macrocephaly, on the Children's Embedded Figures Test (CEFT), a well-established measure of local processing bias. The results demonstrated that the children with autism and macrocephaly performed significantly better on the CEFT than children with autism without macrocephaly, indicative of a local bias. These results lend support to the proposal that both macrocephaly in autism and a local processing bias may arise from the same underlying neural processes and these characteristics represent an endophenotype in a subgroup of individuals with ASC worthy of further investigation. (C) 2013 Elsevier Ltd. All rights reserved. C1 [O'Reilly, Helen] Univ Cambridge, Autism Res Ctr, Cambridge CB2 1TN, England. [Thiebaut, Flora I.; White, Sarah J.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. RP White, SJ (reprint author), UCL, Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. 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Cogn. Neurosci. PD OCT PY 2013 VL 6 BP 149 EP 154 DI 10.1016/j.dcn.2013.09.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 270DI UT WOS:000328298700015 PM 24161549 ER PT J AU Naushad, SM Jain, JMN Prasad, CK Naik, U Akella, RRD AF Naushad, Shaik Mohammad Jain, Jamal Md Nurul Prasad, Chintakindi Krishna Naik, Usha Akella, Radha Rama Devi TI Autistic children exhibit distinct plasma amino acid profile SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article DE Autism; Glutamate; Asparagine; Tryptophan; Methionine ID BACTERIAL OVERGROWTH; SEROTONIN SYNTHESIS; GLUTAMATE; DISORDER; SUSCEPTIBILITY; VITAMIN-B12; CAPACITY; FAMILIES; PATHWAY; MICE AB In order to ascertain whether autistic children display characteristic metabolic signatures that are of diagnostic value, plasma amino acid analyses were carried out on a cohort Of 138 autistic children and 138 normal controls using reverse-phase HPLC. Pre-column derivatization of amino acids with phenyl isothiocyanate forms phenyl thio-carbamate derivates that have a lambda(max) of 254 nm, enabling their detection using photodiode array. Autistic children showed elevated levels of glutamic acid (120 +/- 89 vs. 83 +/- 35 mu mol/L) and asparagine (85 +/- 37 vs. 47 +/- 19 union); lower levels of phenylalanine (45 +/- 20 vs. 59 +/- 18 mu mol/L), tryptophan (24 +/- 11 vs. 41 +/- 16 mu mol/L), methionine (22 +/- 9 vs. 28 +/- 9 won) and histidine (45 +/- 21 vs. 58 +/- 15 mu mol/L). A low molar ratio of (tryptophan/large neutral amino acids) x 100 was observed in autism (5.4 vs 9.2), indicating lesser availability of tryptophan for neurotransmitter serotonin synthesis. To conclude, elevated levels of excitatory amino acids (glutamate and asparagine), decreased essential amino acids (phenylalanine, tryptophan and methionine) and decreased precursors of neurotransmitters (tyrosine and tryptophan) are the distinct characteristics of plasma amino acid profile of autistic children. Thus, such metabolic signatures might be useful tools for early diagnosis of autism. C1 [Naushad, Shaik Mohammad] SASTRA Univ, Sch Chem & Biotechnol, Thanjavur, TN, India. [Jain, Jamal Md Nurul; Prasad, Chintakindi Krishna] Ctr DNA Fingerprinting & Diagnost, Hyderabad, Andhra Pradesh, India. [Naik, Usha] Niloufer Hosp, Inst Child Hlth, Hyderabad, Andhra Pradesh, India. [Akella, Radha Rama Devi] Rainbow Childrens Hosp, Hyderabad, Andhra Pradesh, India. RP Naushad, SM (reprint author), SASTRA Univ, Sch Chem & Biotechnol, Thanjavur, TN, India. EM naushadsm@gmail.com FU Department of Biotechnology (DBT), India FX The research was supported by the core grant provided by Department of Biotechnology (DBT), India. We thank all the families who participated in this study. 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Biochem. Biophys. PD OCT PY 2013 VL 50 IS 5 SI SI BP 474 EP 478 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 270FR UT WOS:000328304800018 PM 24772971 ER PT J AU Brady, NC Thiemann-Bourque, K Fleming, K Matthews, K AF Brady, Nancy C. Thiemann-Bourque, Kathy Fleming, Kandace Matthews, Kris TI Predicting Language Outcomes for Children Learning Augmentative and Alternative Communication: Child and Environmental Factors SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE children; augmentative and alternative communication; assessment; outcomes; intellectual disabilities ID AUTISM SPECTRUM DISORDERS; SYMBOLIC PLAY; DEVELOPMENTAL DELAYS; YOUNG-CHILDREN; PRELINGUISTIC PREDICTORS; PRESCHOOL-CHILDREN; MENTAL-RETARDATION; VOCABULARY GROWTH; JOINT ATTENTION; DOWN-SYNDROME AB Purpose: To investigate a model of language development for nonverbal preschool-age children learning to communicate with augmentative or alternative communication. Method: Ninety-three preschool children with intellectual disabilities were assessed at Time 1, and 82 of these children were assessed 1 year later, at Time 2. The outcome variable was the number of different words the children produced (with speech, sign, or speech-generating devices). Children's intrinsic predictor for language was modeled as a latent variable consisting of cognitive development, comprehension, play, and nonverbal communication complexity. Adult input at school and home, and amount of augmentative or alternative communication instruction, were proposed mediators of vocabulary acquisition. Results: A confirmatory factor analysis revealed that measures converged as a coherent construct, and a structural equation model indicated that the intrinsic child predictor construct predicted different words children produced. The amount of input received at home, but not at school, was a significant mediator. Conclusions: The hypothesized model accurately reflects a latent construct of Intrinsic Symbolic Factor (ISF). Children who evidenced higher initial levels of ISF and more adult input at home produced more words 1 year later. 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Speech Lang. Hear. Res. PD OCT 1 PY 2013 VL 56 IS 5 BP 1595 EP 1612 DI 10.1044/1092-4388(2013/12-0102) PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 269UJ UT WOS:000328267300021 PM 23785187 ER PT J AU Bay, MJ Talisa, VB Vaurio, RG Kaufmann, WE Capone, GT AF Bay, M. J. Talisa, V. B. Vaurio, R. G. Kaufmann, W. E. Capone, G. T. TI Using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in Diagnosing Autism Spectrum Disorder (ASD) in Children with Down Syndrome (DS) SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Case studies/case series; Genetics NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S145 EP S145 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200425 ER PT J AU Brumback, AC Sohal, VS AF Brumback, A. C. Sohal, V. S. TI Mechanisms of Prefrontal Microcircuit Dysfunction in Animal Models of Autism SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Translational/experimental therapeutics NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S186 EP S187 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200551 ER PT J AU Dy, ME Ballantyne, AO Trauner, DA AF Dy, M. E. Ballantyne, A. O. Trauner, D. A. TI Behavioral Profiles of Children and Adolescents with Specific Language Impairment and High Functioning Autism SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Case studies/case series NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S138 EP S139 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200406 ER PT J AU Jeste, SS Freeman, SN Paparella, T Senturak, D Kupelian, C Kirkham, N Johnson, SP AF Jeste, S. S. Freeman, S. N. Paparella, T. Senturak, D. Kupelian, C. Kirkham, N. Johnson, S. P. TI Neural Correlates of Visual Statistical Learning in Young Children with Autism Spectrum Disorder (ASD) SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Neuroimaging NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S178 EP S179 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200527 ER PT J AU Johnson, WG Stenroos, ES Buyske, S AF Johnson, W. G. Stenroos, E. S. Buyske, S. TI Maternally Acting Gene Alleles (MAGAs) in Autism, a GWAS Study with Meta-analysis SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Genetics NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S165 EP S166 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200487 ER PT J AU Kaufmann, WE Walton-Bowen, KL Kuriyama, N Cherubini, M Carpenter, RL Bear, MF Wang, P AF Kaufmann, W. E. Walton-Bowen, K. L. Kuriyama, N. Cherubini, M. Carpenter, R. L. Bear, M. F. Wang, P. TI Randomized, Controlled, Phase2 Trial of STX209 (Arbaclofen) for Social Function in Autism Spectrum Disorder SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Case studies/case series; Translational/experimental therapeutics NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S129 EP S130 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200378 ER PT J AU Letovsky, SI Causey, ME Aryee, M Skoletsky, J Proulx, C Sharp, FR Pessah, IN Hansen, R Gregg, J Hertz-Picciotto, I AF Letovsky, S., I Causey, M. E. Aryee, M. Skoletsky, J. Proulx, C. Sharp, F. R. Pessah, I. N. Hansen, R. Gregg, J. Hertz-Picciotto, I TI Distinguishing Autism Spectrum Disorders from Other Developmental Delays Using Blood RNASeq SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the Child-Neurology-Society CY OCT 30-NOV 02, 2013 CL Austin, TX SP Child Neurol Soc DE Genetics NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2013 VL 74 SU 17 SI SI BP S166 EP S166 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 264XL UT WOS:000327914200488 ER EF