FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kelley, E Naigles, L Fein, D AF Kelley, Elizabeth Naigles, Letitia Fein, Deborah TI An in-depth examination of optimal outcome children with a history of autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE High-functioning autism; Outcome; Adaptive behavior; Optimal outcome; Language ID PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE BEHAVIORAL TREATMENT; EARLY INTERVENTION; COMMUNICATION; IDENTIFICATION; PREDICTORS; CHILDHOOD; STABILITY; EFFICACY; DEFICITS AB Previous research has suggested that some children with autism spectrum disorders (ASD) may improve to such an extent that they lose their diagnosis, yet little research has examined these 'optimal outcome' children in depth. We examined multiple aspects of functioning in a group of 13 optimal outcome (OO) children, matched on age, gender, and non-verbal IQ to a group of typically developing children (N = 14) and a group of high-functioning children with ASD who still retained a diagnosis on the autism spectrum (N = 14). These children were tested on average about eight years after they had been diagnosed (OO = 93 months, HFA = 94 months). Unlike their high-functioning peers with ASD, the OO group's adaptive and problem behavior scores fell within the average range. They also showed average language and communication scores on all language measures. The HFA group, however, continued to show pragmatic, linguistic, social, and behavioral difficulties. The OO children tended to have been diagnosed at younger ages and were significantly more likely to have received intensive early intervention. Although the high-functioning children with ASD continued to show difficulties in the behavioral realm, the individuals in the OO group were functioning within the average range on all measures. Future research should address how this optimal outcome is achieved. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Kelley, Elizabeth; Naigles, Letitia; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. RP Kelley, E (reprint author), Queens Univ, Dept Psychol, 62 Arch St, Kingston, ON K7L 3N6, Canada. EM kelleyb@queensu.ca CR Beglinger L, 2005, J AUTISM DEV DISORD, V35, P295, DOI 10.1007/s10803-005-3292-3 Bibby Peter, 2002, Research in Developmental Disabilities, V23, P81, DOI 10.1016/S0891-4222(02)00095-1 Billstedt E, 2005, J AUTISM DEV DISORD, V35, P351, DOI 10.1007/s10803-005-3302-5 Charman T, 2003, AUTISM, V7, P217 Dawson G, 2008, DEV PSYCHOPATHOL, V20, P775, DOI 10.1017/S0954579408000370 Dunn L. 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R., 1992, BEHAV ASSESSMENT SYS Sallows GO, 2005, AM J MENT RETARD, V110, P417, DOI 10.1352/0895-8017(2005)110[417:IBTFCW]2.0.CO;2 SCHOPLER E, 1989, J CONSULT CLIN PSYCH, V57, P162 Semel E, 1995, CLIN EVALUATION LANG, V3rd SHONKOFF JP, 1988, TOP EARLY CHILD SPEC, V8, P81 Sigman M., 1999, MONOGRAPHS SOC RES C, P64 Sparrow S, 1984, VINELAND ADAPTIVE BE Starr E, 2003, J AUTISM DEV DISORD, V33, P15, DOI 10.1023/A:1022222202970 Stevens MC, 2000, J AM ACAD CHILD PSY, V39, P346, DOI 10.1097/00004583-200003000-00017 Sutera S, 2007, J AUTISM DEV DISORD, V37, P98, DOI 10.1007/s10803-006-0340-6 SZATMARI P, 1989, J AUTISM DEV DISORD, V19, P213, DOI 10.1007/BF02211842 Tsatsanis KD, 2004, TOP LANG DISORD, V24, P249 Wechsler D., 2003, WECHSLER INTELLIGENC Wiig EH, 1989, TEST LANGUAGE COMPET NR 41 TC 18 Z9 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUL-SEP PY 2010 VL 4 IS 3 BP 526 EP 538 DI 10.1016/j.rasd.2009.12.001 PG 13 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 587AS UT WOS:000276959200024 ER PT J AU Yang, PC Lung, FW Jong, YJ Hsu, HY Chen, CC AF Yang, Pinchen Lung, For-Wey Jong, Yuh-Jyh Hsu, Hsiu-Yi Chen, Cheng-Chung TI Stability and change of cognitive attributes in children with uneven/delayed cognitive development from preschool through childhood SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Cognitive stability; Intellectual disability; Autism; Preschool age child ID AUTISTIC SPECTRUM; YOUNG-CHILDREN; INTELLIGENCE; DISORDER; SCORES; AGE; RELIABILITY; PERFORMANCE; PARAMETERS; PROGRAMS AB As part of an ongoing clinical service program for children with developmental delay in an Asian developing country, we analyzed the cognitive attributes of 362 Taiwanese children (average age 48.5 +/- 12.9 month-old) with uneven/delayed cognitive development as they were assessed repeatedly with average duration of 39.7 +/- 22.6 months from preschool through early childhood. The objectives were to determine the stability and related factors in cognitive scores of these 362 children belonging to three diagnostic subgroups: 181 children with non-autistic mental retardation (MR), 95 children with autism spectrum disorder (ASD) and 64 children with mixed type developmental language disorder (DLD); and to contribute to the accumulation of data on cognitive outcome in preschool children with developmental delay. Analysis revealed that mean initial cognitive score (IQ1) was 64.9 +/- 16.9 while mean cognitive measure at follow-up (IQ2) was 72.2 +/- 19.7. Whole group analysis showed the correlation between IQ1 and IQ2 was moderate (r = 0.73, p < 0.001). Analysis by a general linear model showed only male gender (beta = 4.95, p = 0.02, C.I. = 0.8-9.1) and IQ1 (beta = 0.79, p < 0.001, C.I. = 0.68-0.90) to be significant predictors of IQ2. There were differences among three groups in IQ1 (p < 0.001), IQ2 (p < 0.001) and IQ change (p < 0.001). Correlation coefficients of IQ1 and IQ2 were 0.6 for ASD group, 0.7 for MR group and 0.4 for DLD group respectively. The greatest proportion of children remained within the same cognitive range for both assessment points, however, it is noted that a substantial minority of children changed IQ ranges drastically from preschool through early childhood. Our results suggest that measurements of cognitive function at preschool age for children With developmental delay were valid in the context of a developing country, and the observed change in cognitive scores during follow-up emphasized the need to interpret the initial results of cognitive tests with caution. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Yang, Pinchen] Kaohsiung Med Univ, Dept Psychiat, Kaohsiung, Taiwan. [Jong, Yuh-Jyh; Hsu, Hsiu-Yi] Kaohsiung Med Univ Hosp, Dept Pediat & Lab Med, Kaohsiung, Taiwan. [Lung, For-Wey] Kaohsiung Armed Forces Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan. [Lung, For-Wey] Kaohsiung Med Univ, Dept Neurol, Kaohsiung, Taiwan. [Lung, For-Wey] Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. [Jong, Yuh-Jyh] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung, Taiwan. [Chen, Cheng-Chung] Kaohsiung Kai Suan Psychiat Hosp, Kaohsiung 802, Taiwan. RP Chen, CC (reprint author), 130 Kai Suan 2nd RD, Kaohsiung 802, Taiwan. 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Dev. Disabil. PD JUL-AUG PY 2010 VL 31 IS 4 BP 895 EP 902 DI 10.1016/j.ridd.2010.02.011 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 601OR UT WOS:000278072200004 PM 20346615 ER PT J AU Gondalia, SV Palombo, EA Knowles, SR Austin, DW AF Gondalia, Shakuntla V. Palombo, Enzo A. Knowles, Simon R. Austin, David W. TI Gastrointestinal microbiology in autistic spectrum disorder: a review SO REVIEWS IN MEDICAL MICROBIOLOGY LA English DT Review ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; BLOOD-BRAIN-BARRIER; INFANTILE-AUTISM; ONSET AUTISM; CLOSTRIDIUM-DIFFICILE; EPIDEMIOLOGIC SURVEY; POSTNATAL FACTORS; MEASLES-VIRUS; IN-VITRO; CHILDREN AB Cases of autism have frequently been reported in association with gastrointestinal problems. These observations have stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. The objectives of this paper were to review the possible involvement and mechanisms of gastrointestinal microbiota in autistic spectrum disorder and explain the possible role of gastrointestinal microbiota in the condition. This review addresses the possible involvement of bacteria, viruses and fungi, and their products in autism. Direct viral damage of neurons or disruption of normal neurodevelopment by immune elements such as cytokines, nitric oxide and bacterial products, including lipopolysaccharides, toxins and metabolites, have been suggested to contribute to autistic pathology. Numerous intestinal microbial abnormalities have been reported in individuals with autism. Research to date exploring possible gastrointestinal problems and infection in autism has been limited by small and heterogeneous samples, study design flaws and conflicting results. Furthermore, interventions designed to modify the intestinal microbial population of autistic patients are few and limited in their generalisation. In order to bring clarity to this field, high-quality and targeted investigations are needed to explore the role of gastrointestinal microbiology in autism. To this end, several promising avenues for future research are suggested. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Gondalia, Shakuntla V.; Palombo, Enzo A.; Knowles, Simon R.; Austin, David W.] Swinburne Univ Technol, Fac Life & Social Sci, SABRI, Melbourne, Vic, Australia. [Palombo, Enzo A.] Swinburne Univ Technol, Fac Life & Social Sci, Environm & Biotechnol Ctr, Melbourne, Vic, Australia. [Knowles, Simon R.] Swinburne Univ Technol, Fac Life & Social Sci, Swin PSYCHE Unit, Melbourne, Vic, Australia. RP Gondalia, SV (reprint author), Swinburne Univ Technol, Fac Life & Social Sci, Mail H29,POB 218, Hawthorn, Vic 3122, Australia. 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Med. Microbiol. PD JUL PY 2010 VL 21 IS 3 BP 44 EP 50 DI 10.1097/MRM.0b013e32833a3dc9 PG 7 GA 622HC UT WOS:000279651000002 ER PT J AU Fatemi, SH Folsom, TD Reutiman, TJ Braun, NN Lavergne, LG AF Fatemi, S. Hossein Folsom, Timothy D. Reutiman, Teri J. Braun, Natalie N. Lavergne, Luke G. TI Levels of Phosphodiesterase 4A and 4B Are Altered by Chronic Treatment With Psychotropic Medications in Rat Frontal Cortex SO SYNAPSE LA English DT Article DE phosphodiesterase 4A; phosphodiesterase 4B; schizophrenia; rat; frontal cortex ID REPEATED ANTIDEPRESSANT TREATMENT; CAUSES DIFFERENTIAL EXPRESSION; CHRONIC OLANZAPINE TREATMENT; IN-SITU HYBRIDIZATION; CHRONIC HALOPERIDOL; BRAIN; SCHIZOPHRENIA; GENES; PDE4B; MORPHOGENESIS AB Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (FC) following chronic treatment with clozapine, fluoxetine, haloperidol, lithium, olanzapine, valproic acid (VPA), or sterile saline for 21 days. Western blotting experiments showed decreased expression of PDE4A subtypes in FC following treatment with clozapine, haloperidol, lithium, and VPA. PDE4B subtypes were similarly reduced in FC following treatment with clozapine, fluoxetine, and lithium. We also measured levels of nine PDE subtypes via qRT-PCR in FC and found significant upregulation of PDE1A and PDE8B following treatment with olanzapine, while treatment with lithium reduced expression of mRNA for PDE8B. Our results demonstrate altered expression of PDE4A and PDE4B in response to a variety of psychotropic medications suggesting potentially new therapeutic avenues for treatment of neuropsychiatric diseases. Synapse 64:550-555, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Fatemi, S. Hossein; Folsom, Timothy D.; Reutiman, Teri J.; Braun, Natalie N.; Lavergne, Luke G.] Univ Minnesota, Sch Med, Dept Psychiat, Div Neurosci Res, 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. RP Fatemi, SH (reprint author), 420 Delaware St SE,MMC 392, Minneapolis, MN 55455 USA. EM fatem002@umn.edu FU Stanley Medical Research Institute [06R-1406] FX Contract grant sponsor: Stanley Medical Research Institute; Contract grant number: 06R-1406. 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Limitations in the mirrored "understanding" of emotion SO SYNTHESE LA English DT Article DE Empathy; Mirroring; Mirror neurons; Mindreading ID SOCIAL COGNITION; PREMOTOR CORTEX; NEURON SYSTEM; ACTION RECOGNITION; MOTOR; IMITATION; MECHANISMS; OTHERS; AUTISM; HUMANS AB The recent discovery of so-called "mirror-neurons" in monkeys and a corresponding mirroring "system" in humans has provoked wide endorsement of the claim that humans understand a variety of observed actions, somatic sensations, and emotions via a kind of direct representation of those actions, sensations, and emotions. Philosophical efforts to assess the import of such "mirrored understanding" have typically focused on how that understanding might be brought to bear on theories of mindreading (how we represent other creatures as having mental states), and usually in cases of action. By contrast, this paper assesses mirrored understanding in cases of emotion and its import for theories of empathy and especially empathy in ethical contexts. In particular, this paper argues that the mirrored understanding claim is ambiguous and ultimately misleading when applied to emotion, partly because mirroring proponents fail to appreciate the way in which empathy might serve a distinct normative function in our judgments of what other people feel. The paper thus concludes with a call to revise the mirrored understanding claim, whether in neuroscience, psychology, or philosophy. C1 Univ Memphis, Memphis, TN 38152 USA. RP Debes, R (reprint author), Univ Memphis, Memphis, TN 38152 USA. 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Several studies demonstrate the effectiveness of parents as agents of intervention in the child's home environment. However, this approach requires intense one-on-one supervision by highly trained professionals. Consequently, there is a significant gap between the intensive service requirements for children with ASD and the available resources to provide these services. In the current pilot study, the use of remote technology, telepractice, is evaluated as a tool for coaching parents of two children found to have ASD. Two clinical models of intervention are compared: a traditional model of twice-weekly speech and language therapy sessions (traditional clinical model) and a model where a once-a-week clinical session is followed by a home-based session administered by the parents and remotely supervised and coached by the clinician (clinic/telepractice model). Results suggest that gains obtained in traditional therapy can be maintained and even exceeded in a treatment model that uses telepractice. Parents reported that they perceived telepractice sessions to be as valuable as those delivered directly by the clinician, felt comfortable using the technology, and were willing to continue intervention with their children at home. These preliminary results suggest that use of telepractice holds promise for reducing the demands on available resources of service for this population. A study with a larger population is currently underway including cost-benefit analyses to examine the implications for such a treatment model to its users and to the healthcare system. C1 [Baharav, Eva; Reiser, Carly] Western Washington Univ, Dept Commun Sci & Disorders, Speech Language Hearing Clin, Bellingham, WA 98225 USA. 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J. e-Health PD JUL-AUG PY 2010 VL 16 IS 6 BP 727 EP 731 DI 10.1089/tmj.2010.0029 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 635PV UT WOS:000280669500049 PM 20583950 ER PT J AU [Anonymous] AF [Anonymous] TI Urine test could predict autism earlier SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT News Item CR Yap IKS, 2010, J PROTEOME RES, V9, P2996, DOI 10.1021/pr901188e NR 1 TC 0 Z9 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0165-9936 J9 TRAC-TREND ANAL CHEM JI Trac-Trends Anal. Chem. PD JUL-AUG PY 2010 VL 29 IS 7 SI SI BP V EP VI PG 2 WC Chemistry, Analytical SC Chemistry GA 639UZ UT WOS:000281001600002 ER PT J AU Bozkurt, H Mukaddes, NM AF Bozkurt, Hasan Mukaddes, Nahit Motavalli TI Catatonia in a child with autistic disorder SO TURKISH JOURNAL OF PEDIATRICS LA English DT Article DE catatonia; children; autism; lorazepam ID ELECTROCONVULSIVE-THERAPY; ARIPIPRAZOLE; OLANZAPINE; SUBTYPE AB Bozkurt H, Mukaddes NM. Catatonia in a child with autistic disorder. Turk J Pediatr 2010; 52: 435-438. Catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses. It is being increasingly reported in individuals with autism, a disorder characterized by impaired reciprocal social interactions, aberrant language development and restricted behavioral repertoire. However, relatively little is known about the presentation and treatment of catatonia in children with autism. We describe herein an 11-year-old pediatric case with autism who developed catatonic symptoms and was treated effectively with lorazepam. The case reported here differs from previously reported cases in terms of age of onset and the display of all characteristics of catatonia as defined in the Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV). In addition, although it was stated that catatonia in autism is commonly associated with impaired language and social passivity, our case is an active verbal individual. C1 [Bozkurt, Hasan; Mukaddes, Nahit Motavalli] Istanbul Univ, Istanbul Fac Med, Dept Child & Adolescent Psychiat, Istanbul, Turkey. RP Bozkurt, H (reprint author), Istanbul Univ, Istanbul Fac Med, Dept Child & Adolescent Psychiat, Istanbul, Turkey. 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J. Pediatr. PD JUL-AUG PY 2010 VL 52 IS 4 BP 435 EP 438 PG 4 WC Pediatrics SC Pediatrics GA 671AB UT WOS:000283470400019 PM 21043395 ER PT J AU Chaudhuri, S Chakraborty, S Sengupta, PK AF Chaudhuri, Sudip Chakraborty, Sandipan Sengupta, Pradeep K. TI Encapsulation of serotonin in beta-cyclodextrin nano-cavities: Fluorescence spectroscopic and molecular modeling studies SO JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE Serotonin; SHP beta-cyclodextrin; Fluorescence intensity; Fluorescence anisotropy; Molecular docking; Semiempirical methods ID INTRAMOLECULAR CHARGE-TRANSFER; INCLUSION COMPLEXES; EXCITED-STATE; MECHANICS; ENVIRONMENTS; DERIVATIVES; ENERGY AB Serotonin is a physiologically important biogenic amine, deficiency of which leads to mental disorders such as Alzheimer's disease, schizophrenia, infantile autism, and depression. Both beta-cyclodextrin (beta-CD) and its chemically substituted synthetic varieties (often possessing enhanced aqueous solubility and improved drug complexing abilities) are finding wide applications as drug delivery vehicles. Here we have studied the encapsulation of serotonin in beta-CD and succinyl-2-hydroxypropyl p-cyclodextrin (SHP-beta-CD) by exploiting the intrinsic serotonin fluorescence. Enhanced fluorescence emission intensity (which increases by similar to 18% and 34% in beta-CD and SHP beta-CD respectively) and anisotropy (r) (r = 0.075 and 0.1 in beta-CD and SHP beta-CD respectively) are observed in presence of the cyclodextrins. From the fluorescence data host-guest interaction with 1:1 stoichiometry is evident, the association constants (K) being 126.06 M-1 and 461.62 M-1 for beta-CD and SHP beta-CD respectively. Additionally, molecular docking and semiempirical calculations have been carried out which provide, for the first time, detailed insights regarding the encapsulation process. In particular, it is evident that the indole ring is inserted within the beta-CD cavity with the aliphatic amine side chain protruding towards the primary rim of the beta-CD cavity. Docking calculations reveal that hydrogen bonding interactions are involved in the formation of the inclusion complex. Semiempirical calculations indicate that formation of the 1:1 inclusion complex is energetically favorable which is consistent with the fluorescence data. (C) 2010 Elsevier B.V. All rights reserved. C1 [Chaudhuri, Sudip; Chakraborty, Sandipan; Sengupta, Pradeep K.] Saha Inst Nucl Phys, Div Biophys, Kolkata 700064, India. [Chaudhuri, Sudip] Gandhi Centenary BT Coll, Habra, India. RP Sengupta, PK (reprint author), Saha Inst Nucl Phys, Div Biophys, 1-AF Bidhannagar, Kolkata 700064, India. 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Mol. Struct. PD JUN 30 PY 2010 VL 975 IS 1-3 BP 160 EP 165 DI 10.1016/j.molstruc.2010.04.014 PG 6 WC Chemistry, Physical SC Chemistry GA 627GX UT WOS:000280028600023 ER PT J AU Yoshida, W Dziobek, I Kliemann, D Heekeren, HR Friston, KJ Dolan, RJ AF Yoshida, Wako Dziobek, Isabel Kliemann, Dorit Heekeren, Hauke R. Friston, Karl J. Dolan, Ray J. TI Cooperation and Heterogeneity of the Autistic Mind SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HIGH-FUNCTIONING AUTISM; SOCIAL DECISION-MAKING; DIAGNOSTIC INTERVIEW; NEURAL BASIS; GAME-THEORY; NEUROSCIENCE; DISORDER; CORTEX; BRAIN; SELF AB Individuals with autism spectrum conditions (ASCs) have a core difficulty in recursively inferring the intentions of others. The precise cognitive dysfunctions that determine the heterogeneity at the heart of this spectrum, however, remains unclear. Furthermore, it remains possible that impairment in social interaction is not a fundamental deficit but a reflection of deficits in distinct cognitive processes. To better understand heterogeneity within ASCs, we employed a game-theoretic approach to characterize unobservable computational processes implicit in social interactions. Using a social hunting game with autistic adults, we found that a selective difficulty representing the level of strategic sophistication of others, namely inferring others' mindreading strategy, specifically predicts symptom severity. In contrast, a reduced ability in iterative planning was predicted by overall intellectual level. Our findings provide the first quantitative approach that can reveal the underlying computational dysfunctions that generate the autistic "spectrum." C1 [Yoshida, Wako; Friston, Karl J.; Dolan, Ray J.] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England. [Kliemann, Dorit; Heekeren, Hauke R.] Free Univ Berlin, Dept Educ Sci & Psychol, D-14195 Berlin, Germany. [Kliemann, Dorit; Heekeren, Hauke R.] Max Planck Inst Human Dev, D-14195 Berlin, Germany. RP Yoshida, W (reprint author), UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, 12 Queen Sq, London WC1N 3BG, England. EM w.yoshida@fil.ion.ucl.ac.uk RI Friston, Karl/D-9230-2011; Heekeren, Hauke/B-7739-2008 OI Friston, Karl/0000-0001-7984-8909; Heekeren, Hauke/0000-0001-7912-6826 FU Wellcome Trust FX This work was supported by Wellcome Trust Programme grants to R.J.D. and K.J.F. 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We compared digit ratios in two groups of psychometrically-identified schizotypes, namely, those characterized by positive schizotypy (perceptual aberrations and magical ideation; n = 76) and those characterized by negative schizotypy (social anhedonia; n = 64), to a control group (n = 110). The groups were also compared in terms of their performance on a measure of Theory of Mind, namely, the Reading the Mind in the Eyes Test (RMET) and trait affect, as measured by the PANAS. Our results indicate that neither negative schizotypy nor positive schizotypy is associated with altered digit ratios. Similarly, the groups showed no significant differences on the RMET. However, we observed a small but significant inverse association between Theory of Mind performance and negative affect. The findings are considered in light of the extant literature. 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PD JUN 30 PY 2010 VL 178 IS 1 BP 73 EP 78 DI 10.1016/j.psychres.2010.04.023 PG 6 WC Psychiatry SC Psychiatry GA 620HI UT WOS:000279489400013 PM 20471104 ER PT J AU Yang, SY Cho, SC Yoo, HJ Cho, IH Park, M Yoe, J Kim, SA AF Yang, So Young Cho, Soo-Churl Yoo, Hee Jeong Cho, In Hee Park, Mira Yoe, Jin Kim, Soon Ae TI Family-based association study of microsatellites in the 5 ' flanking region of AVPR1A with autism spectrum disorder in the Korean population SO PSYCHIATRY RESEARCH LA English DT Article DE Autism spectrum disorder (ASD); AVPR1A; Association ID VASOPRESSIN; GENE; BEHAVIOR AB This study evaluated the association between autism spectrum disorders (ASDs) and microsatellites (RS3 and RS1) in the 5' flanking region of AVPR1A in 148 Korean trios comprising children with ASDs. In the transmission equilibrium test and haplotype analysis, we found a statistically significant association between microsatellites and Korean ASDs. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved. C1 [Yang, So Young; Yoe, Jin; Kim, Soon Ae] Eulji Univ, Dept Pharmacol, Sch Med, Taejon 301746, South Korea. [Cho, Soo-Churl] Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul Natl Univ Hosp, Seoul, South Korea. [Yoo, Hee Jeong] Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Songnam, Kyeonggi, South Korea. [Cho, In Hee] Gachon Univ Med & Sci, Dept Psychiat, Gil Med Ctr, Inchon, South Korea. [Park, Mira] Eulji Univ, Dept Prevent Med, Sch Med, Taejon 301746, South Korea. [Kim, Soon Ae] Eulji Univ, Med Sci Res Inst, Taejon 301746, South Korea. RP Kim, SA (reprint author), Eulji Univ, Dept Pharmacol, Sch Med, 143-5 Yongdu Dong, Taejon 301746, South Korea. EM sakim@eulji.ac.kr RI Yoo, Hee Jeong/J-5555-2012 FU Ministry of Health and Welfare, Republic of Korea [A080651] FX This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A080651). 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PD JUN 30 PY 2010 VL 178 IS 1 BP 199 EP 201 DI 10.1016/j.psychres.2009.11.007 PG 3 WC Psychiatry SC Psychiatry GA 620HI UT WOS:000279489400037 PM 20452058 ER PT J AU Adler, N Nadler, B Eviatar, Z Shamay-Tsoory, SG AF Adler, Noga Nadler, Benny Eviatar, Zohar Shamay-Tsoory, Simone G. TI The relationship between theory of mind and autobiographical memory in high-functioning autism and Asperger syndrome SO PSYCHIATRY RESEARCH LA English DT Article DE Autism; Autobiographical memory; Theory of mind ID CHILDREN; ADULTS AB The relationship between theory of mind (ToM) and autobiographical memory (AM) in high-functioning autism (HFA) and Asperger syndrome (AS) has never been investigated. Here, we show that ToM abilities could be predicted by levels of AM in HFA and AS as compared to controls, suggesting that difficulties in AM are closely related to ToM impairments in HFA and AS. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Adler, Noga; Nadler, Benny; Eviatar, Zohar; Shamay-Tsoory, Simone G.] Univ Haifa, Dept Psychol, IL-31905 Haifa, Israel. RP Shamay-Tsoory, SG (reprint author), Univ Haifa, Dept Psychol, IL-31905 Haifa, Israel. 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PD JUN 30 PY 2010 VL 178 IS 1 BP 214 EP 216 DI 10.1016/j.psychres.2009.11.015 PG 3 WC Psychiatry SC Psychiatry GA 620HI UT WOS:000279489400042 PM 20452047 ER PT J AU Tanimura, Y Vaziri, S Lewis, MH AF Tanimura, Yoko Vaziri, Sasha Lewis, Mark H. TI Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Autism; Stereotypy; Subthalamic nucleus; Neurodevelopmental disorders; Deer mice; Animal models ID HIGH-FREQUENCY STIMULATION; DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; RAT STRIATUM; SPONTANEOUS STEREOTYPY; ENVIRONMENTAL ENRICHMENT; HUNTINGTONS-DISEASE; ANTAGONIST KW-6002; DOPAMINE RELEASE; GENE-EXPRESSION AB Repetitive behaviors are diagnostic for autism and common in related neurodevelopmental disorders. Despite their clinical importance, underlying mechanisms associated with the expression of these behaviors remain poorly understood. Our lab has previously shown that the rates of spontaneous stereotypy in deer mice (Peromyscus maniculatus) were negatively correlated with enkephalin content, a marker of striatopallidal but not striatonigral neurons. To investigate further the role of the indirect basal ganglia pathway, we examined neuronal activation of the subthalamic nucleus (STN) using cytochrome oxidase (CO) histochemistry in high- and low-stereotypy mice. CO activity in STN was significantly lower in high-stereotypy mice and negatively correlated with the frequency of stereotypy. In addition, exposure to environmental enrichment, which attenuated stereotypy, normalized the activity of STN. Co-administration of the adenosine A(2A) receptor agonist CGS21680 and the AI receptor agonist CPA attenuated stereotypy dose-dependently. The significant reduction associated with the lowest dose of the drug combination tested was due to its effects on mice with lower baseline levels of stereotypy. Higher doses of the drug combination were required to show robust behavioral effects, and presumably requisite activation of the indirect pathway, in high-stereotypy mice. These findings support that decreased indirect pathway activity is linked to the expression of high levels of stereotypy in deer mice and that striatal A(1) and A(2A) receptors may provide promising therapeutic targets for the treatment of repetitive behaviors in neurodevelopmental disorders. (C) 2010 Elsevier B.V. All rights reserved. C1 [Lewis, Mark H.] Univ Florida, McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32611 USA. Univ Florida, Dept Psychol, McKnight Brain Inst, Gainesville, FL 32611 USA. RP Lewis, MH (reprint author), Univ Florida, McKnight Brain Inst, Dept Psychiat, 100 S Newell Dr L4-116, Gainesville, FL 32611 USA. EM marklewis@ufl.edu RI Tanimura, Yoko/D-3141-2014 FU NIH [MH080055] FX This work was supported by NIH grant MH080055. 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Brain Res. PD JUN 26 PY 2010 VL 210 IS 1 BP 116 EP 122 DI 10.1016/j.bbr.2010.02.030 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 597YQ UT WOS:000277798900015 PM 20178817 ER PT J AU Puzzo, I Cooper, NR Vetter, P Russo, R AF Puzzo, Ignazio Cooper, Nicholas R. Vetter, Petra Russo, Riccardo TI EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism SO BRAIN RESEARCH LA English DT Article DE EEG; Social cognition; Mirror neuron ID LIGHT BIOLOGICAL MOTION; MIRROR NEURON ACTIVITY; PACED FINGER MOVEMENT; HIGH-RESOLUTION EEG; VOLUNTARY MOVEMENT; SPECTRUM DISORDER; MU-RHYTHMS; SYSTEM; IMITATION; ELECTROENCEPHALOGRAPHY AB The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12 Hz) and low beta band (12-20 Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. (C) 2010 Elsevier B.V. All rights reserved. C1 [Puzzo, Ignazio; Cooper, Nicholas R.; Russo, Riccardo] Univ Essex, Dept Psychol, Colchester CO4 3SQ, Essex, England. [Vetter, Petra] Univ Glasgow, Dept Psychol, Ctr Cognit Neuroimaging, Glasgow G12 8QB, Lanark, Scotland. RP Puzzo, I (reprint author), Univ Essex, Dept Psychol, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM ipuzzo@essex.ac.uk FU University of Essex FX This study was supported by a University of Essex studentship to Ignazio Puzzo and a University of Essex Research Promotion Fund grant to Nicholas Cooper. 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PD JUN 25 PY 2010 VL 1342 BP 104 EP 110 DI 10.1016/j.brainres.2010.04.060 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 623DF UT WOS:000279717500011 PM 20435023 ER PT J AU Stone, J AF Stone, John TI Autism SO TLS-THE TIMES LITERARY SUPPLEMENT LA English DT Letter RP Stone, J (reprint author), 34 Outram Rd, London N22, England. NR 0 TC 2 Z9 2 PU TIMES SUPPLEMENTS LIMITED PI MARKET HARBOROUGH PA TOWER HOUSE, SOVEREIGN PARK, MARKET HARBOROUGH LE87 4JJ, ENGLAND SN 0307-661X J9 TLS-TIMES LIT SUPPL JI TLS-Times Lit. Suppl. PD JUN 25 PY 2010 IS 5595 BP 6 EP 6 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 616WB UT WOS:000279240600007 ER PT J AU Falck-Ytter, T AF Falck-Ytter, Terje TI Young children with autism spectrum disorder use predictive eye movements in action observation SO BIOLOGY LETTERS LA English DT Article DE autism spectrum disorders; mirror neuron system; forward models; action prediction; eye movements ID MIRROR NEURON DYSFUNCTION; IMITATION; OTHERS; SYSTEM; GOALS AB Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others' actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand-object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS. C1 Uppsala Univ, Dept Psychol, S-75142 Uppsala, Sweden. RP Falck-Ytter, T (reprint author), Uppsala Univ, Dept Psychol, Box 1225, S-75142 Uppsala, Sweden. EM terje.falck-ytter@psyk.uu.se FU Bank of Sweden [J2004-0511]; European Union [EU15636: TACT] FX I am grateful to Claes von Hofsten, Therese Ljunghammar, Gunilla Bohlin and Ben Kenward for their comments on an earlier version of this paper. This research was supported by grants to Claes von Hofsten from the Tercentennial Fund of the Bank of Sweden (J2004-0511) and the European Union (EU15636: TACT). 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Although the neural bases of these control mechanisms have been examined in many contexts, almost no attention has been paid to their role in resolving conflicts between competing social cues, which is surprising given that cognitive conflicts are part of many social interactions. Evidence about the neural processing of social information suggests that two systems-the mirror neuron system (MNS) and mental state attribution system (MSAS)-are specialized for processing nonverbal and contextual social cues, respectively. This could support a model of social cognitive conflict resolution in which competition between social cues would recruit domain-general cognitive control mechanisms, which in turn would bias processing toward the MNS or MSAS. Such biasing could also alter social behaviors, such as inferences made about the internal states of others. We tested this model by scanning participants using functional magnetic resonance imaging while they drew inferences about the social targets' emotional states based on congruent or incongruent nonverbal and contextual social cues. Conflicts between social cues recruited the anterior cingulate and lateral prefrontal cortex, brain areas associated with domain-general control processes. This activation was accompanied by biasing of neural activity toward areas in the MNS or MSAS, which tracked, respectively, with perceivers' behavioral reliance on nonverbal or contextual cues when drawing inferences about targets' emotions. Together, these data provide evidence about both domain-general and domain-specific mechanisms involved in resolving social cognitive conflicts. C1 [Zaki, Jamil; Weber, Jochen; Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Hennigan, Kelly] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Zaki, J (reprint author), Columbia Univ, Dept Psychol, 1190 Amsterdam Ave, New York, NY 10027 USA. EM jamil@psych.columbia.edu; ochsner@psych.columbia.edu FU Autism Speaks Grant [4787]; National Institute on Drug Abuse [DA022541]; National Institutes of Health [MH076137] FX This work was supported by Autism Speaks Grant 4787 (J.Z.), National Institute on Drug Abuse Grant DA022541 (K.N.O.), and National Institutes of Health Grant MH076137 (K.N.O.). We thank Marget Thomas and Annie Knickman for assistance in data collection. 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Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased paired-pulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework. C1 [Suvrathan, Aparna; Chattarji, Sumantra] Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India. [Hoeffer, Charles A.; Wong, Helen; Klann, Eric] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Chattarji, S (reprint author), Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India. EM shona@ncbs.res.in FU FRAXA Research Foundation; Pfizer Asia; National Centre for Biological Sciences, Bangalore FX We thank Candice Carr, Bridget Dolan, Kathleen Oram, and others at the Tonegawa and Bear laboratories (Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA) for genotyping and providing us the mice. This work was supported by funds from the FRAXA Research Foundation, a Pfizer Asia R and D collaborative grant, and the National Centre for Biological Sciences, Bangalore. 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PD JUN 22 PY 2010 VL 107 IS 25 BP 11591 EP 11596 DI 10.1073/pnas.1002262107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 614KS UT WOS:000279058000078 PM 20534533 ER PT J AU Delorme, R Moreno-De-Luca, D Gennetier, A Maier, W Chaste, P Mossner, R Grabe, HJ Ruhrmann, S Falkai, P Mouren, MC Leboyer, M Wagner, M Betancur, C AF Delorme, Richard Moreno-De-Luca, Daniel Gennetier, Aurelie Maier, Wolfgang Chaste, Pauline Moessner, Rainald Grabe, Hans Joergen Ruhrmann, Stephan Falkai, Peter Mouren, Marie-Christine Leboyer, Marion Wagner, Michael Betancur, Catalina TI Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder SO BMC MEDICAL GENETICS LA English DT Article ID PRADER-WILLI-SYNDROME; CARDIO-FACIAL SYNDROME; DEPENDENT PROBE AMPLIFICATION; AUTISM SPECTRUM DISORDERS; MENTAL-RETARDATION; DELETION SYNDROME; TOURETTE-SYNDROME; VELOCARDIOFACIAL SYNDROME; DUPLICATION SYNDROME; PROXIMAL 15Q AB Background: Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients. Methods: We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA). Results: No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients. Conclusions: Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD. C1 [Moreno-De-Luca, Daniel; Gennetier, Aurelie; Betancur, Catalina] INSERM, U952, Paris, France. [Delorme, Richard; Chaste, Pauline; Leboyer, Marion] Inst Mondor Rech Biomed, INSERM, Creteil, France. [Delorme, Richard; Chaste, Pauline; Mouren, Marie-Christine] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. [Moreno-De-Luca, Daniel; Gennetier, Aurelie; Betancur, Catalina] CNRS, UMR 7224, Paris, France. [Moreno-De-Luca, Daniel; Gennetier, Aurelie; Betancur, Catalina] Univ Paris 06, Paris, France. [Maier, Wolfgang; Moessner, Rainald; Wagner, Michael] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. [Grabe, Hans Joergen] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Ruhrmann, Stephan] Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany. [Falkai, Peter] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Leboyer, Marion] Henri Mondor Albert Chenevier Hosp, AP HP, Dept Psychiat, Creteil, France. [Leboyer, Marion] Univ Paris 12, Fac Med, Creteil, France. RP Betancur, C (reprint author), INSERM, U952, Paris, France. EM catalina.betancur@inserm.fr RI Wagner, Michael/E-2325-2011; Ruhrmann, Stephan/F-1461-2013 OI Ruhrmann, Stephan/0000-0002-6022-2364 FU INSERM; Fondation de France; FondaMental Foundation; German Research Foundation (DFG) FX We are grateful to the patients and their families who made this research possible. We thank the Centre d'Investigations Cliniques of the Robert Debre hospital (Prof. Jacz-Aigrain) and the cell bank of the Cochin hospital (Prof. Delpech) for their technical assistance in the blood sampling and cell line immortalization of the French families. Drs. F. Rampacher, S. Schulze-Rauschenbach, S. Ettelt, K. Meyer, S. Kraft, C. Reck, A. Vogeley are acknowledged for the clinical assessment of the German patients, and V. Guttenthaler and C. Hanses for expert technical assistance provided to the German research group. This research was supported by INSERM, Fondation de France, FondaMental Foundation, and the German Research Foundation (DFG). 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Genet. PD JUN 21 PY 2010 VL 11 AR 100 DI 10.1186/1471-2350-11-100 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 637ND UT WOS:000280824100001 PM 20565924 ER PT J AU Dorey, E AF Dorey, Emma TI Diagnostics Hope for genetic test for autism SO CHEMISTRY & INDUSTRY LA English DT News Item NR 0 TC 0 Z9 0 PU SOC CHEMICAL INDUSTRY PI LONDON PA 14 BELGRAVE SQUARE, LONDON SW1X 8PS, ENGLAND SN 0009-3068 J9 CHEM IND-LONDON JI Chem. Ind. PD JUN 21 PY 2010 IS 12 BP 9 EP 9 PG 1 WC Chemistry, Applied SC Chemistry GA 616LB UT WOS:000279209800012 ER PT J AU Spence, SJ Thurm, A AF Spence, Sarah J. Thurm, Audrey TI Testing autism interventions: trials and tribulations SO LANCET LA English DT Editorial Material ID SPECTRUM DISORDERS; CHILDREN C1 [Spence, Sarah J.; Thurm, Audrey] NIMH, Pediat & Behav Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Spence, SJ (reprint author), NIMH, Pediat & Behav Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM spences2@mail.nih.gov CR Geschwind DH, 2007, CURR OPIN NEUROBIOL, V17, P103, DOI 10.1016/j.conb.2007.01.009 Gotham K, 2009, J AUTISM DEV DISORD, V39, P693, DOI 10.1007/s10803-008-0674-3 Green J, 2010, LANCET, V375, P2152, DOI 10.1016/S0140-6736(10)60587-9 Kasari C, 2002, J AUTISM DEV DISORD, V32, P447, DOI 10.1023/A:1020546006971 Levy SE, 2009, LANCET, V374, P1627, DOI 10.1016/S0140-6736(09)61376-3 Lord C., 1999, AUTISM DIAGNOSTIC OB Lord C, 2005, J AUTISM DEV DISORD, V35, P695, DOI 10.1007/s10803-005-0017-6 Rogers SJ, 2008, J CLIN CHILD ADOLESC, V37, P8, DOI 10.1080/15374410701817808 Spreckley M, 2009, J PEDIATR-US, V154, P338, DOI 10.1016/j.jpeds.2008.09.012 Turner LM, 2007, J CHILD PSYCHOL PSYC, V48, P793, DOI 10.1111/j.1469-7610.2007.01744.x NR 10 TC 10 Z9 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 19 PY 2010 VL 375 IS 9732 BP 2124 EP 2125 DI 10.1016/S0140-6736(10)60757-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 617BF UT WOS:000279255100005 PM 20494435 ER PT J AU Green, J Charman, T McConachie, H Aldred, C Slonims, V Howlin, P Le Couteur, A Leadbitter, K Hudry, K Byford, S Barrett, B Temple, K Macdonald, W Pickles, A AF Green, Jonathan Charman, Tony McConachie, Helen Aldred, Catherine Slonims, Vicky Howlin, Pat Le Couteur, Ann Leadbitter, Kathy Hudry, Kristelle Byford, Sarah Barrett, Barbara Temple, Kathryn Macdonald, Wendy Pickles, Andrew CA PACT Consortium TI Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial SO LANCET LA English DT Article ID SPECTRUM DISORDERS; JOINT ATTENTION; YOUNG-CHILDREN; INTERVENTION; LANGUAGE; BEHAVIORS; EFFICACY; PLAY AB Background Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial. Methods Children with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (<= 42 months or >42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12-17 or 18-24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58133827. Results 152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3.9 points (SD 4.7) on the ADOS-G algorithm in the group assigned to PACT, and 2.9 (3.9) in the group assigned to treatment as usual, representing a between-group effect size of 0.24 (95% CI 0.59 to 0.11), after adjustment for centre, sex, socioeconomic status, age, and verbal and nonverbal abilities. Treatment effect was positive for parental synchronous response to child (1.22, 0.85 to 1.59), child initiations with parent (0.41, 0.08 to 0.74), and for parent-child shared attention (0.33, 0.02 to 0.68). Effects on directly assessed language and adaptive functioning in school were small. Interpretation On the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms; however, a clear benefit was noted for parent-child dyadic social communication. C1 [Green, Jonathan; Aldred, Catherine; Leadbitter, Kathy] Univ Manchester, Psychiat Res Grp, Manchester, Lancs, England. [Pickles, Andrew] Univ Manchester, Hlth Sci Res Grp, Manchester, Lancs, England. [Macdonald, Wendy] Univ Manchester, Natl Inst Hlth Res, Sch Primary Care Res, Manchester, Lancs, England. [Green, Jonathan] Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England. [Green, Jonathan] Manchester Biomed Res Ctr, Manchester, Lancs, England. [Charman, Tony; Hudry, Kristelle] Univ London, Inst Educ, Ctr Res Autism & Educ, London WC1N 1AZ, England. [McConachie, Helen; Le Couteur, Ann; Temple, Kathryn] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England. [Aldred, Catherine] Stockport Primary Care Trust, Childrens Therapy Serv, Stockport, Lancs, England. [Slonims, Vicky] Guys & St Thomas NHS Fdn Trust, Newcomen Ctr, London, England. [Howlin, Pat] Kings Coll London, Inst Psychiat, Dept Clin Psychol, London WC2R 2LS, England. [Byford, Sarah; Barrett, Barbara] Kings Coll London, Ctr Econ Mental Hlth, London WC2R 2LS, England. RP Green, J (reprint author), Room 4-319,Univ Pl,Oxford Rd, Manchester M13 9PL, Lancs, England. EM jonathan.green@manchester.ac.uk RI Howlin, Patricia/A-7622-2011; Pickles, Andrew/A-9625-2011; Barrett, Barbara/F-7606-2010; Byford, Sarah/D-1699-2010; Charman, Tony/A-2085-2014 OI Pickles, Andrew/0000-0003-1283-0346; Barrett, Barbara/0000-0002-0270-6256; Byford, Sarah/0000-0001-7084-1495; Charman, Tony/0000-0003-1993-6549 FU UK Medical Research Council; UK Department for Children, Schools and Families; University of Manchester; Medical Research Council [G0401546]; UK Department of Health; UK National Autistic Society; UK Mental Health Research Network FX This study was sponsored by the University of Manchester. PACT was funded by the Medical Research Council (G0401546), the UK Department for Children, Schools and Families; with a UK Department of Health award for excess treatment and support costs. We gratefully thank all families participating in the study and the referring professionals. We acknowledge invaluable support and guidance from our trial steering committee (Eric Taylor, Alan Emond, Francis Creed, Richard Mills, and Tina McClelland), and our data monitoring and ethics committee (Patrick Bolton, Paula Williamson, and Brain Neville). Other support for trial design and management was provided by Barbara Farrell, and Richard Mills. We are grateful for the support and collaboartion of the UK National Autistic Society throughout the trial. The study was adopted by the UK Mental Health Research Network, who provided valuable officer support clinical studies. UK Medical Research Council. 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PD JUN 18 PY 2010 VL 1338 SI SI BP 36 EP 47 DI 10.1016/j.brainres.2010.03.042 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 614YW UT WOS:000279096700005 PM 20307503 ER PT J AU Xu, B Karayiorgou, M Gogos, JA AF Xu, Bin Karayiorgou, Maria Gogos, Joseph A. TI MicroRNAs in psychiatric and neurodevelopmental disorders SO BRAIN RESEARCH LA English DT Review DE MicroRNA; Psychiatric disorder; Schizophrenia; Chromosome 22q11.2; Mental retardation; Autism; Neurodevelopment; Synaptic plasticity ID FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; 22Q11.2 DELETION SYNDROME; AUTISM SPECTRUM DISORDER; RETT-SYNDROME; TOURETTE-SYNDROME; DOWN-SYNDROME; POSTTRANSCRIPTIONAL REGULATION; NEURONAL DIFFERENTIATION; SYNAPTIC PLASTICITY AB Abnormalities in microRNA (miRNA)-mediated gene regulation have been observed in a variety of human diseases, especially in cancer. Here, we provide an account of newly emerging connections between miRNAs with various psychiatric and neurodevelopmental disorders, including recent findings of miRNA dysregulation in the 22q11.2 microdeletion syndrome, a well-established genetic risk factor for schizophrenia. miRNAs appear to be components of both the genetic architecture of these complex phenotypes as well as integral parts of the biological pathways that mediate the effects of primary genetic deficits. Therefore, they may contribute to both genetic heterogeneity and phenotypic variation of psychiatric and neurodevelopmental disorders and could serve as novel therapeutic targets. (C) 2010 Elsevier B.V. All rights reserved. C1 [Gogos, Joseph A.] Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Xu, Bin; Karayiorgou, Maria] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Gogos, Joseph A.] Columbia Univ, Dept Neurosci, New York, NY 10032 USA. RP Gogos, JA (reprint author), Columbia Univ, Med Ctr, Dept Physiol & Cellular Biophys, 630 W 168th St,P&S 11-519, New York, NY 10032 USA. EM jag90@columbia.edu FU NIMH; McKnight Foundation; March of Dimes; Lieber Center for Schizophrenia Research; Simons Foundation; NARSAD FX Work in the authors' laboratory is supported by grants from NIMH, McKnight Foundation, March of Dimes, Lieber Center for Schizophrenia Research, Simons Foundation and NARSAD. We thank P. A. Arguello and R. Levy for critical reading of the manuscript. 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PD JUN 18 PY 2010 VL 1338 SI SI BP 78 EP 88 DI 10.1016/j.brainres.2010.03.109 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 614YW UT WOS:000279096700009 PM 20388499 ER PT J AU Miller, BH Wahlestedt, C AF Miller, Brooke H. Wahlestedt, Claes TI MicroRNA dysregulation in psychiatric disease SO BRAIN RESEARCH LA English DT Review DE MicroRNA; Schizophrenia; Bipolar disorder; NMDA; miR-132 ID GENOME-WIDE ASSOCIATION; COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; BIPOLAR DISORDER; POSTTRANSCRIPTIONAL REGULATION; SYNAPTIC PLASTICITY; GENETIC ASSOCIATION; MENTAL-RETARDATION; PREFRONTAL CORTEX; PROTEIN-SYNTHESIS AB MicroRNAs (miRNAs) are small regulatory RNAs that individually regulate up to several hundred genes, and collectively may regulate as much as two-thirds of the transcriptome. Recent evidence supports a role for miRNA dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, and autism. 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PD JUN 18 PY 2010 VL 1338 SI SI BP 89 EP 99 DI 10.1016/j.brainres.2010.03.035 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 614YW UT WOS:000279096700010 PM 20303342 ER PT J AU De Smaele, E Ferretti, E Gulino, A AF De Smaele, Enrico Ferretti, Elisabetta Gulino, Alberto TI MicroRNAs as biomarkers for CNS cancer and other disorders SO BRAIN RESEARCH LA English DT Review DE miRNA; Neurodegeneration; Tumors; Medulloblastoma; Glioma ID CENTRAL-NERVOUS-SYSTEM; TUMOR STEM-CELLS; ALZHEIMERS-DISEASE; EXPRESSION PROFILES; HUNTINGTONS-DISEASE; HETEROGENEOUS DYSREGULATION; PLASMA MICRORNAS; AUTISM SPECTRUM; GENE-EXPRESSION; DOWN-REGULATION AB The use of miRNAs as biomarkers has gained growing interest in the last few years. Their role in regulating a great variety of targets and, as a consequence, multiple pathways, makes their use in diagnostics a powerful tool to be exploited for early detection of disease, risk assessment and prognosis and for the design of innovative therapeutic strategies. While still not fully validated, profiling of blood cells, exosomes or body fluid miRNAs would represent a tremendous and promising advance in non-invasive diagnostics of CNS disorders. A major challenge is represented by technological aspects of miRNA detection and discovery aiming to genome-wide high throughput, sensitive and accurate analysis. Although there is much to be learned in the field, this review will highlight the potential role of miRNA as a new class of biomarkers in several CNS disorders, including neurodegenerative diseases such as Alzheimer, Huntington and Parkinson diseases, schizophrenia and autism as well as different types of cancer (e.g. gliomas and medulloblastomas). (C) 2010 Elsevier B.V. All rights reserved. C1 [De Smaele, Enrico; Ferretti, Elisabetta; Gulino, Alberto] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. [Gulino, Alberto] Neuromed Inst, Pozzilli, Italy. RP Gulino, A (reprint author), Univ Roma La Sapienza, Dept Expt Med, 324 Viale Regina Elena, I-00161 Rome, Italy. EM alberto.gulino@uniroma1.it RI De Smaele, Enrico/C-1124-2013; ferretti, elisabetta/G-5413-2013 OI De Smaele, Enrico/0000-0003-4524-4423; ferretti, elisabetta/0000-0001-7265-6429 FU Telethon [GGP07118]; Associazione Italiana per la Ricerca sul Cancro; Italian Ministry of University and Research (FIRB, PRIN); Italian Ministry of Health; Mariani Foundation; Roma Foundation; Pasteur Institute, Cenci Bolognetti Foundation FX We apologize to all scientists whose work could not be cited due to space constraints. The authors are supported by Telethon Grant GGP07118, Associazione Italiana per la Ricerca sul Cancro, the Italian Ministry of University and Research (FIRB, PRIN), the Italian Ministry of Health, Mariani Foundation, Roma Foundation and the Pasteur Institute, Cenci Bolognetti Foundation. 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PD JUN 18 PY 2010 VL 1338 SI SI BP 100 EP 111 DI 10.1016/j.brainres.2010.03.103 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 614YW UT WOS:000279096700011 PM 20380821 ER PT J AU Apicella, CL Cesarini, D Johannesson, M Dawes, CT Lichtenstein, P Wallace, B Beauchamp, J Westberg, L AF Apicella, Coren L. Cesarini, David Johannesson, Magnus Dawes, Christopher T. Lichtenstein, Paul Wallace, Bjoern Beauchamp, Jonathan Westberg, Lars TI No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences SO PLOS ONE LA English DT Article ID GENOME-WIDE; AUTISM LOCI; HUMANS; BEHAVIOR; TRUST; REPLICATION; DISORDERS; DEFICITS; SEARCH; GAME AB Background: Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. Methodology/Principal Findings: We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games. Conclusion: We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant. C1 [Apicella, Coren L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Apicella, Coren L.] Harvard Univ, Dept Human Evolutionary Biol, Boston, MA 02115 USA. [Cesarini, David] MIT, Dept Econ, Cambridge, MA 02139 USA. [Dawes, Christopher T.] Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA. [Johannesson, Magnus; Wallace, Bjoern] Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Beauchamp, Jonathan] Harvard Univ, Dept Econ, Boston, MA 02115 USA. [Westberg, Lars] Univ Gothenburg, Dept Pharmacol, Inst Neurosci & Physiol, Gothenburg, Sweden. RP Apicella, CL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM apicella@fas.harvard.edu RI Johannesson, Magnus/E-9680-2011 OI Johannesson, Magnus/0000-0001-8759-6393 FU Swedish Resarch Council; Jan Wallander and Tom Hedelius Foundation; Swedish Research Council; Swedish Council; Ministry for Higher Education FX LW thanks Fredrik och Ingrid Thuringsstiftelse, Ake Wibergsstiftelse, Ahlen-Stiftelsen, Jeanssons-stiftelsen, Magnus Bergvalls stiftelse, Soderstrom-Konigska stiftelsen, Marta Lundqvist stiftelse and the Swedish Resarch Council for financial support. MJ thanks the Jan Wallander and Tom Hedelius Foundation, the Swedish Research Council, and the Swedish Council for Working Life and Social Research for financial support. The Swedish Twin Registry is supported by grants from the Swedish Research Council and the The Ministry for Higher Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Katrin Yang, Shi-Bing Jan, Yuh Nung Jan, Lily Yeh TI Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE USV; TSC; mTOR; maternal care; social communication ID KNOCKOUT MICE; BEHAVIOR; COMPLEX; COMMUNICATION; CHILDREN; DEFICITS; INFANT; RATS AB Tuberous sclerosis (TSC) is an autosomally dominant neurocutaneous disease notable for its high comorbidity with autism in human patients. Studies of murine models of tuberous sclerosis have found defects in cognition and learning, but thus far have not uncovered deficits in social behaviors relevant to autism. To explore social communication and interaction in TSC2 heterozygous mice, we recorded ultrasonic vocalizations (USV) and found that although both wild-type (WT) and heterozygous pups born to WT dams showed similar call rates and patterns, baseline vocalization rates were elevated in pups born to heterozygous dams. Further analysis revealed several robust features of maternal potentiation in all but WT pups born to heterozygous dams. This lack of potentiation is suggestive of defects in mother-pup social interaction during or before the reunion period between WT pups and heterozygous dams. Intriguingly, male pups of both genotypes born to heterozygous dams showed particularly heightened call rates and burst patterns. Because our maternal retrieval experiments revealed that TSC2(+/-) dams exhibited improved defensive reactions against intruders and highly efficient pup retrieval performance, the alterations in their pups' USVs and maternal potentiation do not appear to result from poor maternal care. These findings suggest that a pup's interaction with its mother strongly influences the pup's vocal communication, revealing an intriguing dependence of this social behavior on TSC2 gene dosage of both parties involved. Our study of this murine model thus uncovers social abnormalities that arise from TSC haploinsufficiency and are suggestive of autism. C1 [Young, David M.; Yang, Shi-Bing; Jan, Yuh Nung; Jan, Lily Yeh] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Young, David M.; Yang, Shi-Bing; Jan, Yuh Nung; Jan, Lily Yeh] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Schenk, A. Katrin] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Jan, LY (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. EM Lily.Jan@ucsf.edu FU National Institutes of Health [R37 MH 06334] FX We thank S. Bonasera, E. Storm, E. Goulding, R. Liu, J. Rubenstein, B. Cheyette, L. Tecott, and F. Huang for helpful conversations, code, and support; N. Shao and M. Wu for guidance in maternal care experiments; and A. Rowson-Baldwin and Y. Shu for excellent technical assistance. This study was supported by National Institutes of Health Grant R37 MH 06334 (to L. Y. J.). Y. N. Jan and L. Y. Jan are Howard Hughes Medical Institute investigators. 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Natl. Acad. Sci. U. S. A. PD JUN 15 PY 2010 VL 107 IS 24 BP 11074 EP 11079 DI 10.1073/pnas.1005620107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 611IC UT WOS:000278807400054 PM 20534473 ER PT J AU Chen, KY Gracheva, EO Yu, SC Sheng, Q Richmond, J Featherstone, DE AF Chen, Kaiyun Gracheva, Elena O. Yu, Szi-Chieh Sheng, Qi Richmond, Janet Featherstone, David E. TI Neurexin in Embryonic Drosophila Neuromuscular Junctions SO PLOS ONE LA English DT Article ID GLUTAMATE-RECEPTOR SUBUNIT; SYNAPTIC VESICLE EXOCYTOSIS; ALPHA-LATROTOXIN RECEPTOR; AUTISM SPECTRUM DISORDER; CENTRAL-NERVOUS-SYSTEM; CELL-SURFACE PROTEINS; CA2+ CHANNELS; NEUROLIGINS; RELEASE; CASK AB Background: Neurexin is a synaptic cell adhesion protein critical for synapse formation and function. Mutations in neurexin and neurexin-interacting proteins have been implicated in several neurological diseases. Previous studies have described Drosophila neurexin mutant phenotypes in third instar larvae and adults. However, the expression and function of Drosophila neurexin early in synapse development, when neurexin function is thought to be most important, has not been described. Methodology/Principal Findings: We use a variety of techniques, including immunohistochemistry, electron microscopy, in situ hybridization, and electrophysiology, to characterize neurexin expression and phenotypes in embryonic Drosophila neuromuscular junctions (NMJs). Our results surprisingly suggest that neurexin in embryos is present both pre and postsynaptically. Presynaptic neurexin promotes presynaptic active zone formation and neurotransmitter release, but along with postsynaptic neurexin, also suppresses formation of ectopic glutamate receptor clusters. Interestingly, we find that loss of neurexin only affects receptors containing the subunit GluRIIA. Conclusions/Significance: Our study extends previous results and provides important detail regarding the role of neurexin in Drosophila glutamate receptor abundance. The possibility that neurexin is present postsynaptically raises new hypotheses regarding neurexin function in synapses, and our results provide new insights into the role of neurexin in synapse development. C1 [Chen, Kaiyun; Gracheva, Elena O.; Yu, Szi-Chieh; Sheng, Qi; Richmond, Janet; Featherstone, David E.] Univ Illinois, Chicago, IL 60680 USA. RP Chen, KY (reprint author), Univ Illinois, Chicago, IL 60680 USA. EM def@uic.edu FU National Institutes of Health (NIH/NINDS) FX This work was funded by grants from the National Institutes of Health (NIH/NINDS) to D.E.F. and J.E.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Bakare, Muideen O. Agomoh, Ahamefule O. Onyeama, Gabriel M. Okonkwo, Kevin O. TI Factors influencing knowledge about childhood autism among final year undergraduate Medical, Nursing and Psychology students of University of Nigeria, Enugu State, Nigeria SO ITALIAN JOURNAL OF PEDIATRICS LA English DT Article ID EPIDEMIOLOGY; PERSPECTIVES; PREVALENCE; DISORDERS; CHILDREN AB Background: Knowledge and awareness about childhood autism is low among health care workers and the general populace in Nigeria. Poor knowledge about childhood autism among final year medical, nursing and psychology students who would form tomorrow's child health care professionals can compromise early recognition and interventions that are known to improve prognosis in childhood autism. Educational factors that could be influencing knowledge about childhood autism among these future health care professionals are unknown. This study assessed knowledge about childhood autism among final year undergraduate medical, nursing and psychology students in south-eastern Nigeria and determined the factors that could be influencing such knowledge. Methods: One hundred final year undergraduate students were randomly selected from each of the Departments of Medicine, Nursing Science and Psychology respectively of University of Nigeria, Enugu State, Nigeria making a sample size of three hundred. A socio-demographic questionnaire and knowledge about childhood autism among health workers (KCAHW) questionnaire were administered to the students. Results: The total mean score for the three groups of students on the KCAHW questionnaire was 10.67 +/- 3.73 out of a possible total score of 19, with medical, nursing and psychology students having total mean scores of 12.24 +/- 3.24, 10.76 +/- 3.50 and 9.01 +/- 3.76 respectively. The mean scores for the three groups showed statistically significant difference for domain 1 (p = 0.000), domain 3 (p = 0.029), domain 4 (p = 0.000) and total score (p = 0.000), with medical students more likely to recognise symptoms and signs of autism compared to nursing and psychology students. The mean score in domain 2 did not show statistically significant difference among the three groups (p = 0.769). The total score on the KCAHW questionnaire is positively correlated with the number of weeks of posting in psychiatry (r = 0.319, p = 0.000) and the number of weeks of posting in paediatrics (r = 0.372, p = 0.000). The total score is also positively correlated with the number of credit hours of lectures in psychiatry/abnormal psychology (r = 0.324, p = 0.000) and the number of credit hours of lectures in paediatrics (r = 0.372, p = 0.000). The field of study also influenced knowledge about childhood autism (p = 0.000). Conclusion: Peculiar situation in this environment as signified by inadequate human resources needed in the area of clinical psychology training often times necessitates employing first degree graduates in psychology into clinical positions. This calls for additional exposure of the undergraduate psychology students to training curriculum aimed at improving their early recognition of symptoms of autism spectrum disorders in this environment. C1 [Igwe, Monday N.; Onyeama, Gabriel M.; Okonkwo, Kevin O.] Univ Nigeria Teaching Hosp Enugu, Dept Psychol Med, Enugu, Nigeria. [Bakare, Muideen O.; Agomoh, Ahamefule O.] Fed Neuropsychiat Hosp, Child & Adolescent Unit, New Haven, Enugu, Nigeria. RP Igwe, MN (reprint author), Univ Nigeria Teaching Hosp Enugu, Dept Psychol Med, Enugu, Nigeria. 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Umemori, Hisashi TI Distinct FGFs promote differentiation of excitatory and inhibitory synapses SO NATURE LA English DT Article ID PRESYNAPTIC ORGANIZING MOLECULES; SYNAPTIC-TRANSMISSION; GROWTH-FACTOR; BRAIN; INTERNEURONS; LOCALIZATION; EPILEPSY; FAMILY AB The differential formation of excitatory (glutamate-mediated) and inhibitory(GABA-mediated) synapses is a critical step for the proper functioning of the brain. An imbalance in these synapses may lead to various neurological disorders such as autism, schizophrenia, Tourette's syndrome and epilepsy(1-4). Synapses are formed through communication between the appropriate synaptic partners(5-8). However, the molecular mechanisms that mediate the formation of specific synaptic types are not known. Here we show that two members of the fibroblast growth factor (FGF) family, FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. FGF22 and FGF7 are expressed by CA3 pyramidal neurons in the hippocampus. The differentiation of excitatory or inhibitory nerve terminals on dendrites of CA3 pyramidal neurons is specifically impaired in mutants lacking FGF22 or FGF7. These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. FGF22-deficientmice are resistant to epileptic seizures, and FGF7-deficient mice are prone to them, as expected from the alterations in excitatory/inhibitory balance. Differential effects of FGF22 and FGF7 involve both their distinct synaptic localizations and their use of different signalling pathways. These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain. C1 [Terauchi, Akiko; Johnson-Venkatesh, Erin M.; Toth, Anna B.; Javed, Danish; Sutton, Michael A.; Umemori, Hisashi] Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Sutton, Michael A.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Umemori, Hisashi] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. RP Umemori, H (reprint author), Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. EM umemoh@umich.edu RI Sutton, Michael/C-6264-2011 FU Ester A. & Joseph Klingenstein Fund; Edward Mallinckrodt Jr Foundation; March of Dimes Foundation; Whitehall Foundation FX We thank J. Sanes and M. Hortsch for critical comments on the manuscript; M. Webb and P. Woodhams for the antibody Py; D. Sorenson for help with electron microscopy; A. Murayama for plasmid construction; M. De Freitas for help with histology; and M. Zhang for technical assistance. This work was supported by the Ester A. & Joseph Klingenstein Fund, the Edward Mallinckrodt Jr Foundation, the March of Dimes Foundation and the Whitehall Foundation (H. U.). 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However, the relationship between seeing and information processing is seldom considered. In this study, we aimed to reveal this relationship using simultaneous eye-tracking measurements and near-infrared spectroscopy (NIRS) in face identification tasks. Methodology/Principal Findings: 22 healthy adult subjects (8 males and 14 females) were shown facial morphing movies in which an initial facial image gradually changed into another facial image (that is, the subject's own face was changed to a familiar face). The fixation patterns on facial features were recorded, along with changes in oxyhemoglobin (oxyHb) levels in the frontal lobe, while the subjects identified several faces. In the self-face condition (self-face as the initial image), hemodynamic activity around the right inferior frontal gyrus (IFG) was significantly greater than in the familiar-face condition. On the other hand, the scanning strategy was similar in almost all conditions with more fixations on the eyes and nose than on other areas. Fixation time on the eye area did not correlate with changes in oxyHb levels, and none of the scanning strategy indices could estimate the hemodynamic changes. Conclusions/Significance: We conclude that hemodynamic activity, i.e., the means of processing facial information, is not always modulated by the face-scanning strategy, i.e., the way of seeing, and that the right IFG plays important roles in both self-other facial discrimination and self-evaluation. C1 [Kita, Yosuke; Hosokawa, Toru] Tohoku Univ, Grad Sch Educ, Sendai, Miyagi 980, Japan. [Kita, Yosuke] Japan Soc Promot Sci, Tokyo, Japan. [Kita, Yosuke; Gunji, Atsuko; Sakihara, Kotoe; Inagaki, Masumi; Kaga, Makiko] Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Dept Dev Disorders, Tokyo, Japan. [Nakagawa, Eiji] Natl Ctr Hosp Neurol & Psychiat, Natl Ctr Neurol & Psychiat, Dept Child Neurol, Tokyo, Japan. RP Kita, Y (reprint author), Tohoku Univ, Grad Sch Educ, Sendai, Miyagi 980, Japan. EM kitay@ncnp.go.jp RI Gunji, Atsuko/O-6323-2014 OI Gunji, Atsuko/0000-0001-8908-8739 FU Japan Society for the Promotion of Science (JSPS) [20-8503]; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [4002] FX The study was supported in part by a Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for the JSPS research fellows (20-8503 to YK) and a Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Grant-in-Aid for Scientific Research on Innovative Areas (4002 to Ryusuke Kakigi and MI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Cortical pyramidal neurons in affected individuals and Fmr1 knock-out (KO) mice have an increased density of dendritic spines. The mutant mice also show defects in synaptic and experience dependent circuit plasticity, which are known to be mediated in part by dendritic spine dynamics. We used in vivo time-lapse imaging with two-photon microscopy through cranial windows in male and female neonatal mice to test the hypothesis that dynamics of dendritic protrusions are altered in KO mice during early postnatal development. We find that layer 2/3 neurons from wild-type mice exhibit a rapid decrease in dendritic spine dynamics during the first 2 postnatal weeks, as immature filopodia are replaced by mushroom spines. In contrast, KO mice show a developmental delay in the downregulation of spine turnover and in the transition from immature to mature spine subtypes. Blockade of metabotropic glutamate receptor (mGluR) signaling, which reverses some adult phenotypes of KO mice, accentuated this immature protrusion phenotype in KO mice. Thus, absence of FMRP delays spine stabilization and dysregulated mGluR signaling in FXS may partially normalize this early synaptic defect. C1 [Portera-Cailliau, Carlos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Reed Neurol Res Ctr A145, Los Angeles, CA 90095 USA. [Portera-Cailliau, Carlos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Portera-Cailliau, C (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Reed Neurol Res Ctr A145, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM cpcailliau@mednet.ucla.edu FU National Institute of Child Health and Human Development-National Institutes of Health (NIH) [5R01 HD054453]; Diversity Supplement; University of California; NIH-National Institute of General Medical Sciences; FRAXA; Dana Foundations; Fu-Hsing and Jyu-Yuan Chen Family Foundation FX This work was supported by National Institute of Child Health and Human Development-National Institutes of Health (NIH) Grant 5R01 HD054453 (C. P.-C.) and a Diversity Supplement (A. C.-M.), the University of California President's Postdoctoral Fellowship Program (A. C.-M.), Minority Access to Research Careers Undergraduate Student Training in Academic Research NIH-National Institute of General Medical Sciences (M. C.), and the FRAXA and Dana Foundations, as well as by the generous support of The Fu-Hsing and Jyu-Yuan Chen Family Foundation. We thank Tara Chowdhury and James Anstey for maintaining the Fmr1 KO colony and genotyping the mice, Adrian Cheng for help with MATLAB, Mike Tranfaglia (from FRAXA) for providing MPEP, Karel Svoboda and Tim O'Connor for the spine analysis software, and William Greenough for providing the Fmr1 KO mice. We are grateful to Felix Schweizer, Peyman Golshani, and members of the Portera-Cailliau Laboratory, especially Ricardo Mostany, for helpful discussions and feedback on this manuscript. 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Buxbaum, Joseph D. Gur, Raquel E. Hakonarson, Hakon TI Strong synaptic transmission impact by copy number variations in schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; genomics; neurobiology ID GENOME-WIDE ASSOCIATION; BIPOLAR AFFECTIVE-DISORDER; RARE STRUCTURAL VARIANTS; MITOCHONDRIAL DYSFUNCTION; EUROPEAN-ANCESTRY; AUTISM; GENES; BRAIN; MICRODELETIONS; IDENTIFICATION AB Schizophrenia is a psychiatric disorder with onset in late adolescence and unclear etiology characterized by both positive and negative symptoms, as well as cognitive deficits. To identify copy number variations (CNVs) that increase the risk of schizophrenia, we performed a whole-genome CNV analysis on a cohort of 977 schizophrenia cases and 2,000 healthy adults of European ancestry who were genotyped with 1.7 million probes. Positive findings were evaluated in an independent cohort of 758 schizophrenia cases and 1,485 controls. The Gene Ontology synaptic transmission family of genes was notably enriched for CNVs in the cases (P = 1.5 x 10(-7)). Among these, CACNA1B and DOC2A, both calcium-signaling genes responsible for neuronal excitation, were deleted in 16 cases and duplicated in 10 cases, respectively. In addition, RET and RIT2, both ras-related genes important for neural crest development, were significantly affected by CNVs. RET deletion was exclusive to seven cases, and RIT2 deletions were overrepresented common variant CNVs in the schizophrenia cases. Our results suggest that novel variations involving the processes of synaptic transmission contribute to the genetic susceptibility of schizophrenia. C1 [Glessner, Joseph T.; Kim, Cecilia E.; Albano, Anthony; Hou, Cuiping; Bradfield, Jonathan P.; Zhang, Haitao; Sleiman, Patrick M. A.; Flory, James H.; Imielinski, Marcin; Frackelton, Edward C.; Chiavacci, Rosetta; Thomas, Kelly A.; Garris, Maria; Otieno, Frederick G.; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Reilly, Muredach P.; Cappola, Thomas P.; Margulies, Kenneth B.; Rader, Daniel J.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Takahashi, Nagahide; Davis, Kenneth L.; Friedman, Joseph I.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Conte Ctr Neurosci Mental Disorders, New York, NY 10029 USA. [Takahashi, Nagahide; Davis, Kenneth L.; Friedman, Joseph I.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Davidson, Michael; Weiser, Mark] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Reichenberg, Abraham] Kings Coll London, Mt Sinai & Inst Psychiat, London SE5 8AF, England. [Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Grant, Struan F. A.; Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Div Neuropsychiat, Schizophrenia Ctr, Philadelphia, PA 19104 USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. EM hakonarson@chop.edu FU National Institute of Mental Health; National Alliance for Research on Schizophrenia and Depression; CHOP; Cotswold Foundation; National Institutes of Health [R21HL092379, R01HL0885775, R01AG17022]; National Institute of Mental Health, Conte Center for Neuroscience of Mental Disorders [MH066392]; [MH-64045]; [MH-60722] FX We gratefully thank all of the schizophrenia patients who participated in this study and all of the control subjects who donated blood samples to CHOP and the UPenn for genetic research purposes. We thank the technical staff at CHOP's Center for Applied Genomics for generating the genotypes used in this study and the medical assistants, nurses, and medical staff who recruited the study subjects. We thank Kai Wang for development of PennCNV-Affy. We also thank S. Kristinsson, L. A. Hermannsson, and A. Krisbjornsson for their software design and contributions; Pablo V. Gejman and Daniel B. Mirel for their oversight of the MGS project and for providing access to the data; and Jonathan Sebat and Deborah L. Levy for their collaborative contributions. We thank the MGS consortium investigators for making the genotype data available. Support for MGS case: control was provided by funding from the National Institute of Mental Health and the National Alliance for Research on Schizophrenia and Depression. Genotyping of part of the sample was supported by the Genetic Association Information Network, and the Paul Michael Donovan Charitable Foundation, The genotyping of samples was provided through the National Center for Research Resources and performed by the Center for Genotyping and Analysis at the Broad Institute of Harvard and MIT. The dataset used for the analyses described in this manuscript was obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap (dbGaP accession number phs000021.v2.p1). Data were accessed based on an authorized data access request by H. H. and S. F. A. G. The study was supported by an Institutional Development Award to the Center for Applied Genomics from CHOP (to H. H.) and a Research Development Award from the Cotswold Foundation (to H. H. and S. F. A. G.). The schizophrenia case recruitment at UPenn was supported by MH-64045 and MH-60722 (to R. E. G.). The sample collection and genotyping for the control population typed at CHOP was supported by the National Institutes of Health [Research Grants R21HL092379, R01HL0885775, and R01AG17022 (to T. P. C. and K. B. M.)]. The collection and genotyping of samples from Mount Sinai and Sheba Hospital was partially supported by the National Institute of Mental Health, Conte Center for Neuroscience of Mental Disorders (Grant MH066392 to J.D.B.). 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Natl. Acad. Sci. U. S. A. PD JUN 8 PY 2010 VL 107 IS 23 BP 10584 EP 10589 DI 10.1073/pnas.1000274107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608AH UT WOS:000278549300047 PM 20489179 ER PT J AU Takayanagi, Y Fujita, E Yu, ZL Yamagata, T Momoi, MY Momoi, T Onaka, T AF Takayanagi, Yuki Fujita, Eriko Yu, Zhiling Yamagata, Takanori Momoi, Mariko Y. Momoi, Takashi Onaka, Tatsushi TI Impairment of social and emotional behaviors in Cadm1-knockout mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Cell adhesion molecule 1 (CADM1); Social behavior; Anxiety-related behavior; Motor function; Autism ID AUTISM SPECTRUM DISORDER; CELL-ADHESION MOLECULE; IMMUNOGLOBULIN SUPERFAMILY; OXYTOCIN; CHILDREN; MOUSE; GENE; ADOLESCENTS; DEFICITS; LACKING AB Cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, mediates synaptic cell adhesion. Missense mutations in the CADM1 gene have been identified in autism spectrum disorder (ASD) patients. In the present study, we examined emotional behaviors, social behaviors and motor performances in Cadm1-knockout (KO) mice. Cadm1-KO mice showed increased anxiety-related behavior in open-field and light-dark transition tests. Social behaviors of Cadm1-KO mice were impaired in social interaction, resident-intruder and social memory/recognition tests. Furthermore, motor coordination and gait of Cadm1-MO mice were impaired in rotarod and footprint tests. Our study demonstrates that CADM1 plays roles in regulating emotional behaviors, social behaviors and motor performances, and that CADM1 has important implications for psychiatric disorders with disruptions in social behavior, such as autism. (C) 2010 Elsevier Inc. All rights reserved. C1 [Onaka, Tatsushi] Jichi Med Univ, Div Brain & Neurophysiol, Dept Physiol, Shimotsuke, Tochigi 3290498, Japan. [Fujita, Eriko; Momoi, Takashi] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Div Dev & Differentiat, Kodaira, Tokyo 1878502, Japan. [Fujita, Eriko; Yu, Zhiling; Yamagata, Takanori; Momoi, Mariko Y.] Jichi Med Univ, Dept Pediat, Shimotsuke, Tochigi 3290498, Japan. RP Onaka, T (reprint author), Jichi Med Univ, Div Brain & Neurophysiol, Dept Physiol, Shimotsuke, Tochigi 3290498, Japan. EM tonaka@jichi.ac.jp RI Onaka, Tatsushi/I-7115-2012 FU MEXT [20590237, 20020023, 20790194, 22120512, 22659050]; JSPS FX This work was supported by KAKENHI (20590237, 20020023, 20790194, 22120512, 22659050) from MEXT and JSPS. 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Biophys. Res. Commun. PD JUN 4 PY 2010 VL 396 IS 3 BP 703 EP 708 DI 10.1016/j.bbrc.2010.04.165 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 610DG UT WOS:000278710200022 PM 20450890 ER PT J AU Siddiqui, TJ Pancaroglu, R Kang, Y Rooyakkers, A Craig, AM AF Siddiqui, Tabrez J. Pancaroglu, Raika Kang, Yunhee Rooyakkers, Amanda Craig, Ann Marie TI LRRTMs and Neuroligins Bind Neurexins with a Differential Code to Cooperate in Glutamate Synapse Development SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INHIBITORY SYNAPSES; ALPHA-NEUREXINS; CELL-ADHESION; SYNAPTOGENIC PROTEINS; NERVOUS-SYSTEM; CA2+ CHANNELS; COMPLEX; AUTISM; PSD-95; SCHIZOPHRENIA AB Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) were recently found to instruct presynaptic and mediate postsynaptic glutamatergic differentiation. In a candidate screen, here we identify neurexin-1 beta lacking an insert at splice site 4 (-S4) as a ligand for LRRTM2. Neurexins bind LRRTM2 with a similar affinity but distinct code from the code for binding neuroligin-1 (the predominant form of neuroligin-1 at glutamate synapses, containing the B splice site insert). Whereas neuroligin-1 binds to neurexins 1, 2, and 3 beta but not alpha variants, regardless of insert at splice site 4, LRRTM2 binds to neurexins 1, 2, and 3 alpha and beta variants specifically lacking an insert at splice site 4. We further show that this binding code is conserved in LRRTM1, the family member linked to schizophrenia and handedness, and that the code is functional in a coculture hemisynapse formation assay. Mutagenesis of LRRTM2 to prevent binding to neurexins abolishes presynaptic inducing activity of LRRTM2. Remarkably, mutagenesis of neurexins shows that the binding face on neurexin-1 beta (-S4) is highly overlapping for the structurally distinct LRRTM2 and neuroligin-1 partners. Finally, we explore here the interplay of neuroligin-1 and LRRTM2 in synapse regulation. In neuron cultures, LRRTM2 is more potent than neuroligin-1 in promoting synaptic differentiation, and, most importantly, these two families of neurexin-binding partners cooperate in an additive or synergistic manner. Thus, we propose a synaptic code hypothesis suggesting that neurexins are master regulators of the cooperative activities of LRRTMs and neuroligins. C1 [Craig, Ann Marie] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 2B5, Canada. RP Craig, AM (reprint author), Univ British Columbia, Brain Res Ctr, Room F149,2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. EM amcraig@interchange.ubc.ca RI Craig, Ann Marie/M-2054-2014 FU Canadian Institutes of Health Research [MOP84241]; National Institutes of Health [MH70860]; Mind Foundation of British Columbia; Michael Smith Foundation for Health Research; Bluma Tischler Postdoctoral Fellowship; Canada Research Chair program FX This work was supported by Canadian Institutes of Health Research Grant MOP84241, National Institutes of Health Grant MH70860, the Mind Foundation of British Columbia, a Michael Smith Foundation for Health Research Postdoctoral Fellowship (T.J.S.), a Bluma Tischler Postdoctoral Fellowship (Y.K.), and the Canada Research Chair program (A.M.C.). We thank Xiling Zhou for excellent assistance with experiments, Dr. Filip Van Petegem for advice on LRRTM2 mutagenesis and generating a structural model, and Drs. Ethan R. Graf and Michael W. Linhoff for numerous constructs. 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Ted Wisniewski, Thomas TI The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes SO ACTA NEUROPATHOLOGICA LA English DT Article DE Autism; Developmental neuropathology; Subependymal nodular dysplasia; Heterotopia; Dysplasia ID TUBEROUS SCLEROSIS COMPLEX; FOCAL CORTICAL DYSPLASIA; UNIPOLAR BRUSH CELLS; MICROTUBULE-ASSOCIATED PROTEIN; ANTIDEPRESSANT TREATMENT; REPETITIVE BEHAVIORS; CLINICAL-FEATURES; ENTORHINAL CORTEX; CEREBELLAR CORTEX; INFANTILE-AUTISM AB Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4-60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-mu m-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype. C1 [Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Imaki, Humi; Wegiel, Jarek; Marchi, Elaine; Ma, Shuang Yong; Wisniewski, Thomas] NYS Inst Basic Res Dev Disabil IBR, Dept Dev Neurobiol, Staten Isl, NY 10314 USA. [de Leon, Mony; Saint Louis, Leslie A.; Wisniewski, Thomas] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. [de Leon, Mony; Saint Louis, Leslie A.; Wisniewski, Thomas] NYU, Dept Pathol, Sch Med, New York, NY 10016 USA. [de Leon, Mony; Saint Louis, Leslie A.; Wisniewski, Thomas] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Chauhan, Abha; Chauhan, Ved] IBR, Dept Neurochem, Staten Isl, NY USA. [Bobrowicz, Teresa Wierzba] Inst Psychiat & Neurol, Dept Neuropathol, Warsaw, Poland. [Cohen, Ira L.; London, Eric] IBR, Dept Psychol, Staten Isl, NY USA. [Brown, W. Ted] IBR, Dept Human Genet, Staten Isl, NY USA. [Saint Louis, Leslie A.] Corinthian Diagnost Radiol, New York, NY USA. [de Leon, Mony] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Wegiel, J (reprint author), NYS Inst Basic Res Dev Disabil IBR, Dept Dev Neurobiol, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM jerzy.wegiel@omr.state.ny.us FU New York State Office of Mental Retardation and Developmental Disabilities; Department of Defense [AS073234]; Autism Speaks (Princeton, NJ); National Institutes of Health, National Institute of Child Health and Human Development [R01 HD43960]; PHS [R24-MH 068855]; National Institute of Child Health; Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore; Brain Bank for Developmental Disabilities and Aging of the New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY FX This study was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities, a grant from the Department of Defense Autism Spectrum Disorders Research Program (AS073234, Program Project; J.W., T. W., A. C.), a grant from Autism Speaks (Princeton, NJ), and grant R01 HD43960 (J.W.) from the National Institutes of Health, National Institute of Child Health and Human Development. Tissue and clinical records' acquisition was coordinated by the Autism Tissue Program ( Princeton, NJ; Directors: Jane Pickett, Ph.D. and Daniel Lightfoot, Ph.D.). The tissue was obtained from the Harvard Brain Tissue Resource Center, Belmont, MA, supported in part by PHS grant number R24-MH 068855; the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore; and the Brain Bank for Developmental Disabilities and Aging of the New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY. We thank Drs. Helmut Hainsen and Christoph Schmitz for help in implementation of the celloidin protocol, and Mrs. Jadwiga Wegiel, Cathy Wang and En Wu Zhang for histology. We are deeply indebted to the families of the tissue donors who have made this study possible. 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PD JUN PY 2010 VL 119 IS 6 BP 755 EP 770 DI 10.1007/s00401-010-0655-4 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 592VS UT WOS:000277410300009 PM 20198484 ER PT J AU Calhoun, VD Wu, L Kiehl, KA Eichele, T Pearlson, GD AF Calhoun, Vince D. Wu, Lei Kiehl, Kent A. Eichele, Tom Pearlson, Godfrey D. TI Aberrant processing of deviant stimuli in schizophrenia revealed by fusion of fMRI and EEG data SO ACTA NEUROPSYCHIATRICA LA English DT Article DE data fusion; event-related potential; functional magnetic resonance imaging; independent component analysis; N2; schizophrenia ID INDEPENDENT COMPONENT ANALYSIS; EVENT-RELATED POTENTIALS; AUDITORY ODDBALL TASK; MISMATCH NEGATIVITY MMN; FUNCTIONAL MRI; TEMPORAL-LOBE; GRAY-MATTER; 1ST-EPISODE SCHIZOPHRENIA; P300 ABNORMALITIES; BLIND SEPARATION AB Background: Aberrant electrophysiological and haemodynamic processing of auditory oddball stimuli is among the most robustly documented findings in patients with schizophrenia. However, no study to date has directly examined linked patterns of electrical and haemodynamic differences in patients and controls. Methods: In a recent paper we demonstrated a data-driven approach, joint independent component analysis (jICA) to fuse together functional magnetic resonance imaging (fMRI) and event-related potential (ERP) data and elucidated the chronometry of auditory oddball target detection in healthy control subjects. In this paper we extend our fusion method to identify specific differences in the neuronal chronometry of target detection for chronic schizophrenia patients compared to healthy controls. Results: We found one linked source, consistent with the N2 response, known to be related to cognitive processing of deviant stimuli, spatially localized to bilateral fronto-temporal regions. This source showed significant between-group differences both in amplitude response and in the fMRI/ERP distribution pattern. These findings are consistent with previous work showing N2 amplitude and latency abnormalities in schizophrenia, and provide new information about the linkage between the two. Conclusions: In summary, we use a novel approach to isolate and identify a linked fMRI/ERP component which shows marked differences in chronic schizophrenia patients. We also show that jointly using both fMRI and ERP measures provides a fully picture of the underlying haemodynamic and electrical changes which are present in patients. Our approach also has broad applicability to other diseases such as autism, Alzheimer's disease, or bipolar disorder. C1 [Calhoun, Vince D.; Wu, Lei; Kiehl, Kent A.] Mind Res Network, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Wu, Lei] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Kiehl, Kent A.; Pearlson, Godfrey D.] Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06106 USA. [Calhoun, Vince D.; Kiehl, Kent A.; Pearlson, Godfrey D.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. [Kiehl, Kent A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Eichele, Tom] Univ Bergen, Dept Biol & Med Psychol, N-5009 Bergen, Norway. RP Calhoun, VD (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM vcalhoun@unm.edu FU National Institutes of Health [1 R01 EB 006841, 1 R01 EB 005846, 1 R01 MH 0705539, 5 R37 MH 43775, 1 RO1 MH 074797, 1 R01 MH 077945]; two Hartford Hospital Open Grant; two National Alliance for Research on Schizophrenia and Depression Young Investigator; Distinguished Investigator; L. Meltzer university fund [801616] FX This research was supported in part by the National Institutes of Health, under grants 1 R01 EB 006841, 1 R01 EB 005846 (V. D. C), 1 R01 MH 0705539 (K. A. K), 5 R37 MH 43775, 1 RO1 MH 074797, 1 R01 MH 077945 (G. D. P) and by two Hartford Hospital Open Grant Competition Awards (V. D. C and K. A. K), two National Alliance for Research on Schizophrenia and Depression Young Investigator Awards (V. D. C and K. A. K) and a Distinguished Investigator Award (G. D. P) and a grant from the L. Meltzer university fund 801616 (T. E.). We thank the research staff at the Olin Neuropsychiatry Research Center and the Mind Research Network who helped collect and process the data.All authors have contributed substantially to the manuscript and none have financial interests to disclose. 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Thomas, Philip O'Doherty, Catherine E. Fenech, Michael TI Folate and methionine metabolism in autism: a systematic review SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review ID OXIDATIVE STRESS; AMINO-ACIDS; DEVELOPMENTAL NEUROTOXICITY; SCHIZOPHRENIC-PATIENTS; ALZHEIMERS-DISEASE; SPECTRUM DISORDER; INFANTILE-AUTISM; FOLIC-ACID; CHILDREN; HOMOCYSTEINE AB Background: Autism is a complex neurodevelopmental disorder that is increasingly being recognized as a public health issue. Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folate-methionine cycle may play a key role in the etiology of autism. Objective: The objective was to conduct a systematic review to examine the evidence for the involvement of alterations in folate-methionine metabolism in the etiology of autism. Design: A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folate-methionine pathway in autism. Eighteen studies met the inclusion criteria, 17 of which provided data on metabolites, 5 on interventions, and 6 on genes and their related polymorphisms. Results: The findings of the review were conflicting. The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used. Most genetic studies were inadequately powered to provide more than an indication of likely genetic relations. Conclusions: The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism. There is also a need to determine whether functional benefits occur when correcting apparent deficits in folate-methionine metabolism in children with autism. Am J Clin Nutr 2010;91:1598-620. C1 [Main, Penelope A. E.; Thomas, Philip; Fenech, Michael] CSIRO, Adelaide, SA 5000, Australia. [Main, Penelope A. E.; Angley, Manya T.; O'Doherty, Catherine E.] Univ S Australia, Sansom Inst, Autism Res Grp, Adelaide, SA 5001, Australia. RP Main, PAE (reprint author), CSIRO, Gate 13 Kintore St, Adelaide, SA 5000, Australia. 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TI PRENATAL AND NEONATAL PERIPHERAL BLOOD MERCURY LEVELS AND AUTISM SPECTRUM DISORDERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Lutsky, M.; Yoshida, C.; Green, P.; Kharrazi, M.; Croen, L. A.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S110 EP S110 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300440 ER PT J AU Lyall, K Pauls, D Spiegelman, D Ascherio, A Santangelo, S AF Lyall, K. Pauls, D. Spiegelman, D. Ascherio, A. Santangelo, S. 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TI ASSOCIATION BETWEEN OVULATION INDUCING DRUG USE, INFERTILITY, AND AUTISM SPECTRUM DISORDERS IN THE NURSES' HEALTH STUDY II SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, CA SP Soc Epidemiol Res C1 [Lyall, K.; Pauls, D.; Santangelo, S.; Spiegelman, D.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S89 EP S89 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300356 ER PT J AU Bedoyan, JK Kumar, RA Sudi, J Silverstein, F Ackley, T Iyer, RK Christian, SL Martin, DM AF Bedoyan, Jirair K. Kumar, Ravinesh A. Sudi, Jyotsna Silverstein, Faye Ackley, Todd Iyer, Ramaswamy K. Christian, Susan L. Martin, Donna M. TI Duplication 16p11.2 in a Child With Infantile Seizure Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autism; seizure; 16p11.2; microarrays; DOC2A; QPRT; SEZ6L2 ID MIGRATING PARTIAL SEIZURES; GENOMIC DISORDERS; CANDIDATE GENES; AUTISM; PROTEIN; INFANCY; MICRODELETIONS; REARRANGEMENTS; ASSOCIATION; PHENOTYPE AB Submicroscopic recurrent 16p11.2 rearrangements are associated with several neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. The common 16p11.2 region includes 24 known genes, of which 22 are expressed in the developing human fetal nervous system. As yet, the mechanisms leading to neurodevelopmental abnormalities and the broader phenotypes associated with deletion or duplication of 16p11.2 have not been clarified. Here we report a child with spastic quadriparesis, refractory infantile seizures, severe global developmental delay, hypotonia, and microcephaly, and a de novo 598 kb 16p11.2 microduplication. Family history is negative for any of these features in parents and immediate family members. Sequencing analyses showed no mutations in DOC2A, QPRT, and SEZ6L2, genes within the duplicated 16p11.2 region that have been implicated in neuronal function and/or seizure related phenotypes. The child's clinical course is consistent with a rare seizure disorder called malignant migrating partial seizure disorder of infancy, raising the possibility that duplication or disruption of genes in the 16p11.2 interval may contribute to this severe disorder. (C) 2010 Wiley-Liss, Inc. C1 [Bedoyan, Jirair K.; Silverstein, Faye; Ackley, Todd; Iyer, Ramaswamy K.; Martin, Donna M.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Martin, Donna M.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Iyer, Ramaswamy K.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Kumar, Ravinesh A.; Sudi, Jyotsna; Christian, Susan L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. RP Martin, DM (reprint author), Univ Michigan, Dept Pediat, 3520A MSRB 1,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM donnamm@umich.edu FU NIH [DC009410, NS054784]; MMGL; Department of Pediatrics; Department of Human Genetics; University of Michigan [UL1RR024986]; Autism Speaks FX Grant sponsor: NIH; Grant numbers: DC009410, NS054784.We thank Dr. Jeffrey W. Innis for critical review of this manuscript and for support through MMGL. This study was also supported by funds from MMGL, the Department of Pediatrics, the Department of Human Genetics, and a CTSA pilot award (UL1RR024986) from the University of Michigan. RAK is supported by a postdoctoral fellowship award from Autism Speaks. DMM is supported by NIH grants DC009410 and NS054784. 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Stoler, Joan M. Walsh, Christopher A. Wolff, Robert R. Zhang, Ting Nasir, Ramzi H. Wu, Bai-Lin CA Childrens Hosp Boston Genotype Phe TI Deletions of NRXN1 (Neurexin-1) Predispose to a Wide Spectrum of Developmental Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE NRXN1 (neurexin-1); developmental disorders; array CGH; NRXN1 exonic deletions; CNV ID ALPHA-NEUREXINS; STRUCTURAL VARIANTS; NICOTINE DEPENDENCE; CA2+ CHANNELS; AUTISM; GENES; SCHIZOPHRENIA; ASSOCIATION; NEUROLIGINS; COMPLEX AB Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P=8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders. (C) 2010 Wiley-Liss, Inc. C1 [Nasir, Ramzi H.] Harvard Univ, Sch Med, Div Dev Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Tan, Wen-Hann; Yoo, Seung-Yun; Austin, Christina; Berry, Gerard T.; Hisama, Fuki M.; Irons, Mira B.; Miller, David T.; Picker, Jonathan D.; Stoler, Joan M.; Walsh, Christopher A.] Childrens Hosp Boston, Div Genet, Boston, MA USA. [Jeste, Shafali S.; Engle, Elizabeth C.; Rooney, Cynthia M.; Sarco, Dean P.; Wolff, Robert R.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. [Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Shen, Yiping; Chen, Xiaoli; Miller, David T.; Wu, Bai-Lin] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Chen, Xiaoli; Zhang, Ting] Capital Inst Pediat, Dept Mol Immunol, Beijing, Peoples R China. [Mukaddes, Nahit M.] Istanbul Univ, Istanbul Fac Med, Dept Child Psychiat, Istanbul, Turkey. [Engle, Elizabeth C.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA. [Engle, Elizabeth C.; Walsh, Christopher A.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. [Engle, Elizabeth C.] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA USA. [Walsh, Christopher A.] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. [Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 200433, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. RP Nasir, RH (reprint author), Harvard Univ, Sch Med, Div Dev Med, Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM ramzi.nasir@childrens.harvard.edu; bai-lin.wu@childrens.harvard.edu RI Morrow, Eric/J-2767-2013 FU Nancy Lurie Marks Family Foundation; Simons Foundation; Autism Speaks; NIH [5K23MH080954-02, 1R01MH083565]; Children's Tumor Foundation; Harvard Medical School; Burroughs Wellcome Fund; Fudan University FX The authors gratefully acknowledge the assistance by our colleagues from the DNA Diagnostics Lab: Va Lip, Xiaoming Sheng, Ann Reinhard, Hong Fang, Sly Tang, Hong Shao, Haitao Zhu, Sam Tang, and Andrew Cheng for technical support of array CGH; Christopher A. Walsh Lab: Danielle Gleason and Daniel Rakiec for technical support and Robert Sean Hill for bioinformatics support. We are further grateful for the support from the Nancy Lurie Marks Family Foundation (C.A.W.), the Simons Foundation (C.A.W. and J.F.G.), Autism Speaks (J.F.G.), and the NIH (5K23MH080954-02 to E.M.M. and 1R01MH083565 to C.A.W). E.C.E. and C.A.W. are Investigators of the Howard Hughes Medical Institute. Y.S. holds a Young Investigator Award from the Children's Tumor Foundation and Catalyst Award from Harvard Medical School, E.M.M. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund, B.L.W. holds a Fudan Scholar Research Award from Fudan University. 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TI A Co-segregating Microduplication of Chromosome 15q11.2 Pinpoints Two Risk Genes for Autism Spectrum Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE autism spectrum disorder; genetics; copy-number; gene-dosage; gene expression ID PRADER-WILLI; NEURONAL CONNECTIVITY; CRITICAL REGION; DROSOPHILA; PROTEIN AB High resolution genomic copy-number analysis has shown that inherited and de novo copy-number variations contribute significantly to autism pathology, and that identification of small chromosomal aberrations related to autism will expedite the discovery of risk genes involved. Here, we report a microduplication of chromosome 15q11.2, spanning only four genes, co-segregating with autism in a Dutch pedigree, identified by SNP microarray analysis, and independently confirmed by FISH and MLPA analysis. Quantitative RT-PCR analysis revealed over 70% increase in peripheral blood mRNA levels for the four genes present in the duplicated region in patients, and RNA in situ hybridization on mouse embryonic and adult brain sections revealed that two of the four genes, CYFIP1 and NIPA1, were highly expressed in the developing mouse brain. These findings point towards a contribution of microduplications at chromosome 15q11.2 to autism, and highlight CYFIP1 and NIPA1 as autism risk genes functioning in axonogenesis and synapto-genesis. Thereby, these findings further implicate defects in dosage-sensitive molecular control of neuronal connectivity in autism. However, the prevalence of this microduplication in patient samples was statistically not significantly different from control samples (0.94% in patients vs. 0.42% controls, P= 0.247), which suggests that our findings should be interpreted with caution and indicates the need for studies that include large numbers of control subjects to ascertain the impact of these changes on a population scale. (C) 2009 Wiley-Liss, Inc. C1 [van der Zwaag, Bert; Spierenburg, Henk A.; Burbach, J. Peter H.] UMC Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, Utrecht, Netherlands. [Staal, Wouter G.; de Jonge, Maretha V.; van Engeland, Herman] UMC Utrecht, Rudolf Magnus Inst Neurosci, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. [Hochstenbach, Ron; Poot, Martin; Verbeek, Nienke E.; Nelen, Marcel R.; van Amstel, Hans K. Ploos] UMC Utrecht, Dept Med Genet, Utrecht, Netherlands. [van't Slot, Ruben; Buizer-Voskamp, Jacobine E.] UMC Utrecht, Dept Biomed Genet, Complex Genet Sect, Utrecht, Netherlands. [van Es, Michael A.; van den Berg, Leonard H.] UMC Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Staal, Frank J.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Freitag, Christine M.] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Germany. [Buizer-Voskamp, Jacobine E.] Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. RP Burbach, JPH (reprint author), Univ Weg 100, NL-3584 CG Utrecht, Netherlands. EM j.p.h.burbach@umcutrecht.nl RI Poot, Martin/F-9427-2010; Staal, Wouter/A-3099-2013 FU Breedtestrategie program; Utrecht University; Hersenstichting (Netherlands Foundation) [2008(1).43]; Autism Genetic Resource Exchange (AGRE); Autism Speaks; National Institute of Mental Health [1U24MH081810] FX We thank the ASD family and healthy control individuals for their participation in this study. B. van der Zwaag was supported by the "Breedtestrategie" program and the Prestigous Master Neuroscience and Cognition of the Utrecht University. Part of this research was funded by the Hersenstichting (Netherlands Foundation for Brain Research), grant #2008(1).43 to M. Poot. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. 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TI Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Article DE Event-related potentials; Autism; Novelty; Transcranial Magnetic Stimulation; Cortical excitation/inhibition balance; Minicolumns ID DEVELOPMENTAL LANGUAGE DISORDER; AUDITORY-EVOKED POTENTIALS; MINICOLUMNAR ORGANIZATION; BRAIN POTENTIALS; SELECTIVE ATTENTION; MISMATCH NEGATIVITY; CHILDREN; ABNORMALITIES; DEPRESSION; CORTEX AB In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders. C1 [Sokhadze, Estate; Baruth, Joshua; Tasman, Allan; Mansoor, Mehreen; Ramaswamy, Rajesh; El-Baz, Ayman; Casanova, Manuel F.] Univ Louisville, Dept Psychiat & Behav Sci, Sch Med, Louisville, KY 40292 USA. 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RP Assouline, B (reprint author), Ctr Hosp St Egreve, CADIPA Ctr Ressources Autisme Rhone Alpes, Grenoble, France. EM bassouline@ch-saint-egreve.fr CR BAGDHADLI A, 2005, RECOMMANDATIONS PRAT BURSZTEJN C, 2006, DIAGNOSTIC PSYCHIAT, P81 DANONGRILLIAT A, 2006, DIAGNOSTIC PSYCHIAT, P65 *HAUT AUT SANT FED, 2008, DEP DIAGN AUT REC PR Poirier Annie, 2008, J DEV DISAB, V14, P19 NR 5 TC 0 Z9 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0929-693X J9 ARCH PEDIATRIE JI Arch. Pediatr. PD JUN PY 2010 VL 17 IS 6 BP 647 EP 648 PG 2 WC Pediatrics SC Pediatrics GA 619GM UT WOS:000279417200028 PM 20654823 ER PT J AU Amiet, C Gourfinkel-An, I Consoli, A Perisse, D Cohen, D AF Amiet, C. Gourfinkel-An, I. Consoli, A. Perisse, D. Cohen, D. TI Epilepsy and autism: a complex issue SO ARCHIVES DE PEDIATRIE LA French DT Article ID SPECTRUM DISORDERS C1 [Amiet, C.; Gourfinkel-An, I.; Consoli, A.; Perisse, D.; Cohen, D.] Univ Paris 06, Grp Hosp Pitie Salpetriere, Serv Psychiat Enfant & Adolescent, Lab Psychol & Neurosci Cognit,CNRS,UMR 8189, F-75252 Paris 05, France. RP Amiet, C (reprint author), Univ Paris 06, Grp Hosp Pitie Salpetriere, Serv Psychiat Enfant & Adolescent, Lab Psychol & Neurosci Cognit,CNRS,UMR 8189, F-75252 Paris 05, France. EM claire.amiet@pst.aphp.fr CR Amiet C, 2008, BIOL PSYCHIAT, V64, P577, DOI 10.1016/j.biopsych.2008.04.030 Canitano R, 2007, EUR CHILD ADOLES PSY, V16, P61, DOI 10.1007/s00787-006-0563-2 Casanova MF, 2003, NEUROSCIENTIST, V9, P496, DOI 10.1177/1073858403253552 Federation francaise de psychiatric, 2005, Recupere de Jambaque I, 1998, J NEUROL NEUROSUR PS, V65, P555, DOI 10.1136/jnnp.65.4.555 Nass R, 1999, PEDIATR NEUROL, V21, P464, DOI 10.1016/S0887-8994(99)00029-6 Saemundsen E, 2007, EPILEPSIA, V48, P1724, DOI 10.1111/j.1528-1167.2007.01150.x Tuchman R, 2002, LANCET NEUROL, V1, P352, DOI 10.1016/S1474-4422(02)00160-6 VOLKMAR FR, 1990, J AM ACAD CHILD PSY, V29, P127, DOI 10.1097/00004583-199001000-00020 NR 9 TC 0 Z9 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0929-693X J9 ARCH PEDIATRIE JI Arch. Pediatr. PD JUN PY 2010 VL 17 IS 6 BP 650 EP 651 PG 2 WC Pediatrics SC Pediatrics GA 619GM UT WOS:000279417200030 PM 20654825 ER PT J AU Schiff, M Delorme, R Benoist, JF de Baulny, HO AF Schiff, M. Delorme, R. Benoist, J. -F. de Baulny, H. Ogier TI Should a metabolic work-up be performed in autism? SO ARCHIVES DE PEDIATRIE LA French DT Article ID SPECTRUM DISORDERS; YIELD C1 [Schiff, M.; Benoist, J. -F.; de Baulny, H. Ogier] Hop Robert Debre, AP HP, Ctr Reference Malad Metab, F-75019 Paris, France. [Schiff, M.; de Baulny, H. Ogier] Hop Robert Debre, AP HP, Serv Neuropediat, F-75019 Paris, France. [Delorme, R.] Hop Robert Debre, AP HP, Serv Psychopathol Enfant & Adolescent, F-75019 Paris, France. [Benoist, J. -F.] Hop Robert Debre, AP HP, Serv Biochim, F-75019 Paris, France. RP Schiff, M (reprint author), Hop Robert Debre, AP HP, Ctr Reference Malad Metab, F-75019 Paris, France. EM manuel.schiff@rdb.aphp.fr CR Cohen D, 2005, J AUTISM DEV DISORD, V35, P103, DOI 10.1007/s10803-004-1038-2 KAYSER MA, 2008, PEDIATR NEUROL, V15, P127 Kosinovsky B, 2005, J NEURAL TRANSM, V112, P587, DOI 10.1007/s00702-004-0198-8 Levy SE, 2009, LANCET, V374, P1627, DOI 10.1016/S0140-6736(09)61376-3 Muhle R., 2004, PEDIATRICS, V113, P472 Schaefer GB, 2006, GENET MED, V8, P549, DOI 10.1097/01.gim.0000237789.98842.fi Weissman JR, 2008, PLOS ONE, V3, DOI 10.1371/journal.pone.0003815 Zecavati N, 2009, CURR NEUROL NEUROSCI, V9, P129, DOI 10.1007/s11910-009-0021-x NR 8 TC 4 Z9 4 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0929-693X J9 ARCH PEDIATRIE JI Arch. Pediatr. PD JUN PY 2010 VL 17 IS 6 BP 802 EP 803 PG 2 WC Pediatrics SC Pediatrics GA 619GM UT WOS:000279417200106 PM 20654901 ER PT J AU Dawes, P Bishop, DVM AF Dawes, Piers Bishop, Dorothy V. M. TI Psychometric profile of children with auditory processing disorder and children with dyslexia SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID LANGUAGE IMPAIRMENT; COMMUNICATION; AUTISM AB Objective The aim was to address the controversy that exists over the extent to which auditory processing disorder (APD) is a separate diagnostic category with a distinctive psychometric profile, rather than a reflection of a more general learning disability. Methods Children with an APD diagnosis (N=25) were compared with children with dyslexia (N=19) on a battery of standardised auditory processing, language, literacy and non-verbal intelligence quotient measures as well as parental report measures of communicative skill and listening behaviour. A follow-up of a subset of children included a parent report screening questionnaire for Asperger syndrome (Childhood Asperger Syndrome Test). Results There were similarly high levels of attentional, reading and language problems in both groups. One peculiarity of the APD group was a discrepancy between parental report of poor communication and listening skill disproportionate to expectations based on standardised test performance. Follow-up assessment suggested high levels of previously unrecognised autistic features within the APD group. Conclusions Children diagnosed by audiological experts as having APD are likely to have broader neurodevelopmental disorders and would benefit from evaluation by a multidisciplinary team. C1 [Dawes, Piers] Univ Manchester, Dept Psychol, Audiol & Deafness Res Grp, Manchester M13 9PL, Lancs, England. [Bishop, Dorothy V. M.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. RP Dawes, P (reprint author), Univ Manchester, Dept Psychol, Audiol & Deafness Res Grp, Manchester M13 9PL, Lancs, England. EM piers.dawes@manchester.ac.uk FU Deafness Research UK FX This study was funded by Deafness Research UK. Thank you to T Sirimanna (Great Ormond Street Hospital), F Tweedy (Manchester Royal Infirmary), M Burton (John Radcliffe Hospital) and I Vanniasegaram (St Georges Hospital) for help with recruitment of subjects. CR Alcantara JI, 2004, J CHILD PSYCHOL PSYC, V45, P1107, DOI 10.1111/j.1469-7610.2004.t01-1-00303.x American Speech-Language-Hearing Association, 2005, COSM SURG NAT DAT BA, P1 Bishop D. V. M., 2003, CHILDRENS COMMUNICAT Bishop D. V. 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PD JUN PY 2010 VL 95 IS 6 BP 432 EP 436 DI 10.1136/adc.2009.170118 PG 5 WC Pediatrics SC Pediatrics GA 600QL UT WOS:000278002000007 PM 20501538 ER PT J AU Bauminger, N Solomon, M Rogers, SJ AF Bauminger, Nirit Solomon, Marjorie Rogers, Sally J. TI Externalizing and Internalizing Behaviors in ASD SO AUTISM RESEARCH LA English DT Article DE psychopathology; adaptive behavior; high-functioning ASD; parental stress ID PERVASIVE DEVELOPMENTAL DISORDERS; SCHOOL-AGE-CHILDREN; ASPERGER-SYNDROME; CONSCIENCE DEVELOPMENT; PSYCHIATRIC-DISORDERS; ATTACHMENT SECURITY; PEER RELATIONSHIPS; AUTISTIC-CHILDREN; POSITIVE AFFECT; YOUNG-CHILDREN AB The current study investigated the relationships between internalizing and externalizing (I-E) behaviors and family variables, including both parenting stress and quality of attachment relations, in children aged 8-12 with high-functioning autism spectrum disorder (ASD) or with typical development. Compared to the group with typical development, children with ASD exhibited significantly greater levels of psychopathology as assessed by the Child Behavior Checklist [Achenbach, 1991], and parents of children with ASD exhibited higher parenting stress as assessed by the Parenting Stress Index [Abidin, 1995]. In a hierarchical multiple regression analysis, parenting stress emerged as the most important predictor of children's I-E problems. Results are discussed in light of the two groups' similar relationships between parenting stress and child psychopathology. C1 [Bauminger, Nirit] Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. [Solomon, Marjorie; Rogers, Sally J.] UC Davis, Mind Inst, Dept Psychiat, Sacramento, CA USA. RP Bauminger, N (reprint author), Bar Ilan Univ, Sch Educ, IL-52900 Ramat Gan, Israel. EM bauminn@mail.biu.ac.il FU United States-Israel Binational Science Foundation (BSF) FX This study was supported by the United States-Israel Binational Science Foundation (BSF) to Drs. Rogers and Bauminger. 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PD JUN PY 2010 VL 3 IS 3 BP 101 EP 112 DI 10.1002/aur.131 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 620NV UT WOS:000279507500001 PM 20575109 ER PT J AU Mitchell, P Mottron, L Soulieres, I Ropar, D AF Mitchell, Peter Mottron, Laurent Soulieres, Isabelle Ropar, Danielle TI Susceptibility to the Shepard Illusion in Participants with Autism: Reduced Top-Down Influences Within Perception? SO AUTISM RESEARCH LA English DT Article DE low-level perception; visual illusion; 3D perception ID PRIOR KNOWLEDGE; LOCAL BIAS; INDIVIDUALS; CHILDREN; PERFORMANCE; ABILITIES; DEFICIT; TASKS AB Previous research [Ropar & Mitchell, 2002] has shown that autistic individuals are somewhat immune to biases induced by top-down processes, particularly the influence of previous knowledge on perception. In order to test this hypothesis within perception, 18 participants with autism who had measured intelligence in the normal range were compared against 18 matched controls in their susceptibility to the Shepard illusion. The illusion consists in misperceiving the shape of a parallelogram in the presence of depth cues. It is attributed [Mitchell, Ropar, Ackroyd, & Rajendran, 2005] to the effect of top-down constraints within perception. The task involved adjusting a stimulus to the dimensions of a template on a computer screen. Both groups were susceptible to the illusion and the illusion effect was stronger when three-dimensional perspective cues were prominent. Notably, participants with autism were less susceptible to the illusion than typically developing individuals. The findings raise the possibility that in some instances top-down influences are attenuated in individuals with autism. C1 [Mitchell, Peter; Ropar, Danielle] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England. [Mottron, Laurent; Soulieres, Isabelle] CETEDUM, Montreal, PQ, Canada. [Mottron, Laurent; Soulieres, Isabelle] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. RP Mitchell, P (reprint author), Univ Nottingham, Sch Psychol, Univ Pk, Nottingham NG7 2RD, England. EM peter.mitchell@nottingham.edu.my FU Canadian Institutes for Health Research [MOP-84243] FX Grant sponsor: Canadian Institutes for Health Research; Grant number: MOP-84243. 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PD JUN PY 2010 VL 3 IS 3 BP 113 EP 119 DI 10.1002/aur.130 PG 7 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 620NV UT WOS:000279507500002 PM 20575110 ER PT J AU Mazefsky, CA Conner, CM Oswald, DP AF Mazefsky, Carla A. Conner, Caitlin M. Oswald, Donald P. TI Association Between Depression and Anxiety in High-Functioning Children with Autism Spectrum Disorders and Maternal Mood Symptoms SO AUTISM RESEARCH LA English DT Article DE autism; Asperger's disorder; psychiatric comorbidity; anxiety; depression; mood disorders; familial aggregation; maternal symptoms ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; FAMILY-HISTORY; GENETIC EPIDEMIOLOGY; ASPERGER-SYNDROME; INDIVIDUALS; SCL-90-R; ADULTS; METAANALYSIS; INTERVIEW AB Research suggests that children with autism spectrum disorders (ASDs) and their relatives have high rates of depression and anxiety. However, relatively few studies have looked at both factors concurrently. This study examined the potential relationship between maternal mood symptoms and depression and anxiety in their children with ASD. Participants were 31 10- to 17-year-old children with an ASD diagnosis that was supported by gold-standard measures and their biological mothers. Mothers completed the Autism Comorbidity Interview to determine whether the child with ASD met criteria for any depressive or anxiety diagnoses and a questionnaire of their own current mood symptoms. As expected, many children with ASD met criteria for lifetime diagnoses of depressive (32%) and anxiety disorders (39%). Mothers' report of their own current mood symptoms revealed averages within the normal range, though there was significant variability. Approximately 75% of children with ASD could be correctly classified as having a depressive or anxiety disorder history or not based on maternal symptoms of interpersonal sensitivity, hostility, phobic anxiety, depression, and anxiety. The results provide preliminary evidence that maternal mood symptoms may be related to depression and anxiety in their children with ASD. Although the design did not allow for testing of heritability per se, the familial transmission patterns were generally consistent with research in typical populations. While larger follow-up studies are needed, this research has implications for prevention and intervention efforts. C1 [Mazefsky, Carla A.; Conner, Caitlin M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Oswald, Donald P.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. RP Mazefsky, CA (reprint author), Univ Pittsburgh, Dept Psychiat, Webster Hall Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. EM mazefskyca@upmc.edu FU Organization for Autism Research FX Grant sponsor: Organization for Autism Research. 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Plaisted Davis, Greg TI Object-Based Attention Benefits Reveal Selective Abnormalities of Visual Integration in Autism SO AUTISM RESEARCH LA English DT Article DE autism; Gestalt; grouping; top-down ID GLOBAL PRECEDENCE; LOCAL PRECEDENCE; CHILDREN; INDIVIDUALS; PERCEPTION; DISORDERS; TASK AB A pervasive integration deficit could provide a powerful and elegant account of cognitive processing in autism spectrum disorders (ASD). However, in the case of visual Gestalt grouping, typically assessed by tasks that require participants explicitly to introspect on their own grouping perception, clear evidence for such a deficit remains elusive. To resolve this issue, we adopt an index of Gestalt grouping from the object-based attention literature that does not require participants to assess their own grouping perception. Children with ASD and mental- and chronological-age matched typically developing children (TD) performed speeded orientation discriminations of two diagonal lines. The lines were superimposed on circles that were either grouped together or segmented on the basis of color, proximity or these two dimensions in competition. The magnitude of performance benefits evident for grouped circles, relative to ungrouped circles, provided an index of grouping under various conditions. Children with ASD showed comparable grouping by proximity to the TO group, but reduced grouping by similarity. ASD seems characterized by a selective bias away from grouping by similarity combined with typical levels of grouping by proximity, rather than by a pervasive integration deficit. C1 [Falter, Christine M.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. [Grant, Kate C. Plaisted; Davis, Greg] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. RP Falter, CM (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM christine.falter@psych.ox.ac.uk; gjd1000@cam.ac.uk RI Davis, Gregory/G-9954-2012 FU German National Academic Foundation FX Grant sponsor: German National Academic Foundation. 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TI Confirmation Study of PTEN Mutations Among Individuals with Autism or Developmental Delays/Mental Retardation and Macrocephaly SO AUTISM RESEARCH LA English DT Article DE genetic; Cowden syndrome; molecular genetics; PTEN; cancer; autism; developmental delay ID RILEY-RUVALCABA-SYNDROME; SPECTRUM DISORDERS; TUMOR-SUPPRESSOR; COWDEN-SYNDROME; PREVALENCE; GENETICS; PHOSPHATASE; PROTEIN; FAMILY AB There is a strong genetic component to autism spectrum disorders (ASD), but due to significant genetic heterogeneity, individual genetic abnormalities contribute a small percentage to the overall total. Previous studies have demonstrated PTEN mutations in a sizable proportion of individuals with ASD or mental retardation/developmental delays (MR/DD) and macrocephaly that do not have features of Cowden or Bannayan-Riley-Ruvalcaba syndrome. This study was performed to confirm our previous results. We reviewed the charts of individuals who had PTEN clinical sequencing performed at our institution from January 2008 to July 2009. There were 93 subjects tested from our institution during that period. PTEN mutations were found in 2/39 (5.1%) ASD patients and 2/51 (3.9%) MR/DD patients. Three additional patients without mutations had no diagnostic information. Multiple relatives of individuals with a PTEN mutation had macrocephaly, MR, or early onset cancer (breast, renal, and prostate). Of those relatives tested, all had the familial PTEN mutation. None of the affected relatives had previously been diagnosed with Cowden or Bannayan-Riley-Ruvalcaba syndrome. We noted in our previous study several adult relatives without any findings who puled a mutation. Combined with data from our previous cohort, we have found PTEN mutations in 7/99 (7.1%) of individuals with ASD and 8/100 (8.0%) of individuals with MR/DD, all of whom had macrocephaly. We recommend testing for mutations in PTEN for individuals with ASD or MR/DD and macrocephaly. If mutations are found, other family Members should be offered testing and the adults offered cancer screening if they have a PTEN mutation. C1 [McBride, Kim L.; Varga, Elizabeth A.; Herman, Gail E.] Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet, Columbus, OH 43205 USA. [McBride, Kim L.; Varga, Elizabeth A.; Pastore, Matthew T.; Manickam, Kandamurugu; Atkin, Joan F.; Herman, Gail E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Prior, Thomas W.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA. RP McBride, KL (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet, 700 Childrens Dr, Columbus, OH 43205 USA. 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PD JUN PY 2010 VL 3 IS 3 BP 137 EP 141 DI 10.1002/aur.132 PG 5 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 620NV UT WOS:000279507500005 PM 20533527 ER PT J AU Cook, EH AF Cook, Edwin H., Jr. TI Clinical Genetic Microarray Testing; ASD Neuropathology SO AUTISM RESEARCH LA English DT Review ID AUTISM SPECTRUM DISORDERS C1 Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. RP Cook, EH (reprint author), Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. 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SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT 16th European Bioenergetics Conference CY JUL 17-22, 2010 CL Warsaw, POLAND DE Autism; Mitochondria; Aspartate-glutamate carrier; Calcium signalling; Oxidative stress; Immune dysfunction ID PROTEIN-KINASE-C; INCREASED OXIDATIVE STRESS; CARRIER SLC25A12 GENE; METABOLIC BIOMARKERS; DIETARY INTERVENTION; GLUTAMATE CARRIER; ENERGY-METABOLISM; DIABETIC-RATS; CHILDREN; EXPRESSION AB Autism Spectrum Disorders encompass severe developmental disorders characterized by variable degrees of impairment in language, communication and social skills, as well as by repetitive and stereotypic patterns of behaviour. Substantial percentages of autistic patients display peripheral markers of mitochondrial energy metabolism dysfunction, such as (a) elevated lactate, pyruvate, and alanine levels in blood, urine and/or cerebrospinal fluid, (b) serum carnitine deficiency, and/or (c) enhanced oxidative stress. These biochemical abnormalities are accompanied by highly heterogeneous clinical presentations, which generally (but by no means always) encompass neurological and systemic symptoms relatively unusual in idiopathic autistic disorder. In some patients, these abnormalities have been successfully explained by the presence of specific mutations or rearrangements in their mitochondrial or nuclear DNA. However, in the majority of cases, abnormal energy metabolism cannot be immediately linked to specific genetic or genomic defects. Recent evidence from post-mortem studies of autistic brains points toward abnormalities in mitochondrial function as possible downstream consequences of dysreactive immunity and altered calcium (Ca(2+)) signalling. (C) 2010 Elsevier B.V. All rights reserved. C1 [Palmieri, Luigi] Univ Bari, Dept Pharmacobiol, Biochem & Mol Biol Lab, I-70125 Bari, Italy. [Palmieri, Luigi] Inst Biomembranes & Bioenerget, CNR, Bari, Italy. 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Biophys. Acta-Bioenerg. PD JUN-JUL PY 2010 VL 1797 IS 6-7 BP 1130 EP 1137 DI 10.1016/j.bbabio.2010.04.018 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 622KV UT WOS:000279663200064 PM 20441769 ER PT J AU Yorbik, O Kurt, I Hasimi, A Ozturk, O AF Yorbik, Oezguer Kurt, Ismail Hasimi, Adnan Ozturk, Ozlem TI Chromium, Cadmium, and Lead Levels in Urine of Children with Autism and Typically Developing Controls SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE Autism; Chromium; Cadmium; Lead; Heavy metals; Trace elements ID OXIDATIVE STRESS; LIPID-PEROXIDATION; TOXIC METALS; HAIR; TRANSSULFURATION; GLUTATHIONE; BIOMARKERS; DISORDERS; EXCRETION; APOPTOSIS AB Although potentially harmful effects of heavy metals are well known, limited numbers of studies exist regarding their relationship with autism. The aim of this study was to investigate urine levels of some heavy metals such as of chromium (Cr), cadmium (Cd), and lead (Pb) in children with autism and healthy subjects. Urine levels of Cr, Cd, and Pb were measured by atomic absorption spectrometry in 30 children with autism and compared with 20 healthy controls. Urine Cd and Pb levels were found as significantly decreased in children with autism compared to healthy subjects (p < 0.05). On the other hand, urine Cr levels were significantly higher in children with autism than healthy subjects (p < 0.05). This study suggested that autism may be associated with significant decrease in excretion rate of Cd and Pb and a significant increase excretion rate in the levels of Cr in the urine. These results have indicated that further studies are warranted for investigation of possible roles of heavy metals in autism. C1 [Yorbik, Oezguer] Gulhane Mil Med Fac, Child Psychiat Dept, TR-06018 Ankara, Turkey. 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The present study aimed to examine the possibility that in addition to their pragmatic deficits, the difficulties in the comprehension of metaphors in AS may be explained by deficient linguistic information processing. Specifically, we aimed to examine whether a deficient semantic integration process underlies the difficulties in metaphor comprehension frequently experienced by persons with AS. The semantic integration process of sixteen AS participants and sixteen matched controls was examined using event related potentials (ERPs). N400 amplitude served as an index for degree of effort invested in the semantic integration process of two-word expressions denoting literal, conventional metaphoric, and novel metaphoric meaning, as well as unrelated word pairs. Large N400 amplitudes for both novel and conventional metaphors demonstrated the greater difficulties in metaphor comprehension in the AS participants as compared to controls. Findings suggest that differences in linguistic information processing cause difficulties in metaphor comprehension in AS. (C) 2010 Elsevier Inc. All rights reserved. C1 [Faust, Miriam] Bar Ilan Univ, Dept Psychol, IL-52900 Ramat Gan, Israel. [Gold, Rinat; Faust, Miriam; Goldstein, Abraham] Bar Ilan Univ, Leslie & Susan Gonda Goldschmied Multidisciplinar, IL-52900 Ramat Gan, Israel. RP Faust, M (reprint author), Bar Ilan Univ, Dept Psychol, IL-52900 Ramat Gan, Israel. EM faustm@mail.biu.ac.il FU Israel Science Foundation (ISF) [724/09] FX The authors thank the Asperger syndrome research participants and their families for their cooperation and interest in this study. The authors thank the Israel Asperger Syndrome Association and Beit Ekstein organization for their assistance in recruiting the Asperger syndrome participants. The authors thank Chen Kleiman for his useful assistance in conducting the experiments.This study was performed in partial fulfillment of the requirements for the first author's doctoral dissertation at Bar-Ilan University.This research was supported by the Israel Science Foundation (ISF) grant (number 724/09) to Miriam Faust. 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PD JUN PY 2010 VL 113 IS 3 BP 124 EP 134 DI 10.1016/j.band1.2010.03.002 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 594PC UT WOS:000277548600003 PM 20359737 ER PT J AU Rahko, J Paakki, JJ Starck, T Nikkinen, J Remes, J Hurtig, T Kuusikko-Gauffin, S Mattila, ML Jussila, K Jansson-Verkasalo, E Katsyri, J Sams, M Pauls, D Ebeling, H Moilanen, I Tervonen, O Kiviniemi, V AF Rahko, Jukka Paakki, Jyri-Johan Starck, Tuomo Nikkinen, Juha Remes, Jukka Hurtig, Tuula Kuusikko-Gauffin, Sanna Mattila, Marja-Leena Jussila, Katja Jansson-Verkasalo, Eira Katsyri, Jari Sams, Mikko Pauls, David Ebeling, Hanna Moilanen, Irma Tervonen, Osmo Kiviniemi, Vesa TI Functional Mapping of Dynamic Happy and Fearful Facial Expression Processing in Adolescents SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Adolescent; Arousal; Basic emotion; Emotional facial expressions; Emotion recognition; Emotional and social interaction; Face processing; Mirror neuron system; Theory of mind; Typical development; Valence; Visual perception ID MIRROR-NEURON SYSTEM; AUTISM SPECTRUM DISORDERS; SCHOOL-AGE-CHILDREN; ASPERGER-SYNDROME; HUMAN BRAIN; EMOTION PERCEPTION; FACE PERCEPTION; FMRI; RECOGNITION; AMYGDALA AB This paper assessed the neural systems involved in processing of dynamic facial expressions in adolescents. The processing of facial expressions changes as a function of age, and it is thus important to understand how healthy adolescent subjects process dynamic facial expressions prior to analyzing disease-related changes. We hypothesized that viewing of dynamic facial expressions with opposing valences (happy vs. fearful) induces differential activations and deactivations in the brain. 27 healthy adolescents (9 a (TM) Euro, 18 a (TM),, mean age = 14.5 years; age range 11.6-17.3 years) were examined by using the ASSQ and K-SADS-PL and scanned with 1.5-T fMRI during viewing of dynamic facial expressions and mosaic control images. The stimuli activated the same areas as previously seen in dynamic facial expression in adults. Our results indicated that opposing-valence dynamic facial expressions had differential effects on many cortical structures but not on subcortical limbic structures. The mirror neuron system is activated more during viewing of fearful compared to happy expressions in bilateral inferior frontal gyrus (IFG) and superior temporal sulcus (STS) left dominantly. We also detected more deactivation in the ventral anterior cingulate gyrus (ACG), showing more automated attentional processing of fearful expressions during passive viewing. Females were found to deactivate the right frontal pole more than male adolescents during happy facial expressions, while there were no differences in fear processing between genders. No clear gender or age effects were detected. In conclusion fear induces stronger responses in attention and mirror neurons probably related to fear contagion. C1 [Rahko, Jukka; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jussila, Katja; Ebeling, Hanna; Moilanen, Irma] Univ Oulu, Dept Child Psychiat, Oulu 90029, Finland. [Rahko, Jukka; Paakki, Jyri-Johan; Starck, Tuomo; Nikkinen, Juha; Remes, Jukka; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jussila, Katja; Ebeling, Hanna; Moilanen, Irma; Tervonen, Osmo; Kiviniemi, Vesa] Univ Hosp Oulu, Oulu 90029, Finland. [Paakki, Jyri-Johan; Starck, Tuomo; Nikkinen, Juha; Remes, Jukka; Tervonen, Osmo; Kiviniemi, Vesa] Univ Oulu, Dept Diagnost Radiol, Oulu 90029, Finland. [Hurtig, Tuula] Univ Oulu, Inst Hlth Sci, Oulu 90029, Finland. [Hurtig, Tuula] Univ Oulu, Clin Child Psychiat, Oulu 90029, Finland. [Jansson-Verkasalo, Eira] Univ Hosp Oulu, Dept Clin Neurophysiol, Oulu, Finland. [Katsyri, Jari; Sams, Mikko] Aalto Univ, Sch Sci & Technol, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Pauls, David] Massachusetts Gen Hosp Harvard Med Sch, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Oulu, Finland. RP Rahko, J (reprint author), Univ Oulu, Dept Child Psychiat, POB 26, Oulu 90029, Finland. EM Jukka.Rahko@oulu.fi; jpaakki@mail.student.oulu.fi; tstarck@paju.oulu.fi; juha.nikkinen@oulu.fi; jjremes@ee.oulu.fi; tuula.hurtig@oulu.fi; sanna.kuusikkogauffin@gmail.com; marja-leena.mattila@fimnet.fi; katja.jussila@oulu.fi; Hanna.Ebeling@ppshp.fi; Irma.Moilanen@oulu.fi; Osmo.Tervonen@ppshp.fi; Vesa.Kiviniemi@oulu.fi RI Sams, Mikko/G-7060-2012; Frank, David/E-8213-2012; Remes, Jukka/E-4217-2015 OI Remes, Jukka/0000-0003-1685-8346 FU Alma and K.A. Snellman Foundation, Oulu, Finland; Emil Aaltonen Foundation, Finland; Sigrid Juselius Foundation, Finland; Thule Institute, Oulu, Finland; Finnish Academy [117111]; Finnish Medical Foundation; Graduate School of Circumpolar Wellbeing Health and Adaptation FX We wish to thank the adolescents and their families for participating. This study received financial support from the Alma and K.A. 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TI Effect of Propranolol on Functional Connectivity in Autism Spectrum Disorder-A Pilot Study SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Autism; Functional connectivity; Noradrenergic; Language; Propranolol; Asperger syndrome ID WORKING-MEMORY PERFORMANCE; BETA-ADRENERGIC MODULATION; COGNITIVE FLEXIBILITY; NORADRENERGIC MODULATION; INFANTILE-AUTISM; CHILDREN; LANGUAGE; ADULTS; MIND; INDIVIDUALS AB A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol. Ten ASD subjects underwent fMRI scans after administration of placebo, propranolol or nadolol, while performing a phonological decision making task. Comparison of functional connectivity between pre-defined ROI-pairs revealed a significant increase with propranolol compared to nadolol, suggesting a potential imaging marker for the cognitive effects of propranolol in ASD. C1 [Narayanan, Ananth; Saklayen, Sanjida; Beversdorf, David Q.] Univ Missouri, Dept Radiol, Thompson Ctr, Columbia, MO 65211 USA. [White, Catherine A.] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [White, Catherine A.] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. [Saklayen, Sanjida; Scaduto, Mary J.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Carpenter, Allen L.] Ohio State Univ, Neurosci Grad Studies Program, Columbus, OH 43210 USA. [Abduljalil, Amir; Schmalbrock, Petra] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Beversdorf, David Q.] Univ Missouri, Dept Neurol, Columbia, MO USA. [Beversdorf, David Q.] Univ Missouri, Dept Psychol, Columbia, MO USA. RP Beversdorf, DQ (reprint author), Univ Missouri, Dept Radiol, Thompson Ctr, 300 Portland St,Suite 122, Columbia, MO 65211 USA. EM beversdorfd@health.missouri.edu FU National Alliance for Autism Research [1033/DB//01-201-005-00-00]; NINDS [K23 NS43222]; The Ohio State University Medical Center Research Investment Fund; Wright Center for Innovation; University of Missouri Department of Radiology Research Investment Fund FX This research is funded through a pilot grant from National Alliance for Autism Research (now Autism Speaks) (1033/DB//01-201-005-00-00), grants from NINDS (K23 NS43222), The Ohio State University Medical Center Research Investment Fund and the Wright Center for Innovation, and by the University of Missouri Department of Radiology Research Investment Fund. We would like to thank Bradley Ferguson for his help with the manuscript. 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TI Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1 SO CELL DEATH & DISEASE LA English DT Article DE autism; Cadm1; ER stress ID QUALITY-CONTROL; PROTEIN; NEUROLIGINS; MICE; EXPRESSION; PLASTICITY; MEMORY; MODEL; GENE; CHOP AB Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown molecular pathogenesis. A recent molecular focus has been the mutated neuroligin 3, neuroligin 3(R451C), in gain-of-function studies and for its role in induced impairment of synaptic function, but endoplasmic reticulum (ER) stress induced by mutated molecules also deserves investigation. We previously found two missense mutations, H246N and Y251S, in the gene-encoding synaptic cell adhesion molecule-1 (CADM1) in ASD patients, including cleavage of the mutated CADM1 and its intracellular accumulation. In this study, we found that the mutated CADM1 showed slightly reduced homophilic interactions in vitro but that most of its interactions persist. The mutated CADM1 also showed morphological abnormalities, including shorter dendrites, and impaired synaptogenesis in neurons. Wild-type CADM1 was partly localized to the ER of C2C5 cells, whereas mutated CADM1 mainly accumulated in the ER despite different sensitivities toward 4-phenyl butyric acid with chemical chaperone activity and rapamycin with promotion activity for degradation of the aggregated protein. Modeling analysis suggested a direct relationship between the mutations and the conformation alteration. Both mutated CADM1 and neuroligin 3(R451C) induced upregulation of C/EBP-homologous protein (CHOP), an ER stress marker, suggesting that in addition to the trafficking impairment, this CHOP upregulation may also be involved in ASD pathogenesis. Cell Death and Disease (2010) 1, e47; doi:10.1038/cddis.2010.23; published online 3 June 2010 C1 [Fujita, E.; Dai, H.; Tanabe, Y.; Momoi, T.] Natl Inst Neurosci, Div Differentiat & Dev, NCNP, Kodaira, Tokyo 1878502, Japan. [Fujita, E.; Zhiling, Y.; Yamagata, T.; Momoi, M. Y.] Jichi Med Univ, Dept Pediat, Shimotsukeshi, Tochigi 3290498, Japan. [Dai, H.; Tanabe, Y.; Momoi, T.] Int Univ Hlth & Welf, Ctr Med Sci, Ohtawara, Tochigi 3248501, Japan. [Miyakawa, T.; Tanokura, M.] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan. RP Momoi, T (reprint author), Natl Inst Neurosci, Div Differentiat & Dev, NCNP, 4-1-1 Ogawahigashi Machi, Kodaira, Tokyo 1878502, Japan. EM momoi@ncnp.go.jp FU Autism Genetic Resource Exchange (AGRE) Consortium; National Institute of Mental Health [1U24MH081810]; Japanese Ministry of Education, Culture, Sports, Science and Technology [21200011, 21500334, 21700377]; Ministry of Health, Labor and Welfare [20B-13]; Japan Health Science Foundation FX We express our deepest sympathy at the untimely passing of an excellent neuroscientist, Dr. Alaa El-Husseini. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. 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). This work was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (21200011, 21500334, 21700377), for research into nervous and mental disorders from the Ministry of Health, Labor and Welfare (20B-13), for research on Publicly Essential Drugs and Medical Devices from the Japan Health Science Foundation. 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PD JUN PY 2010 VL 1 AR e47 DI 10.1038/cddis.2010.23 PG 7 WC Cell Biology SC Cell Biology GA 624LB UT WOS:000279819000001 PM 21364653 ER PT J AU Juranek, J Dennis, M Cirino, PT El-Messidi, L Fletcher, JM AF Juranek, Jenifer Dennis, Maureen Cirino, Paul T. El-Messidi, Lyla Fletcher, Jack M. TI The Cerebellum in Children with Spina Bifida and Chiari II Malformation: Quantitative Volumetrics by Region SO CEREBELLUM LA English DT Article DE Cerebellum; Volumetrics; Parcellation; Spina bifida; Chiari II ID COGNITIVE-AFFECTIVE SYNDROME; VELOCARDIOFACIAL SYNDROME; WILLIAMS-SYNDROME; MOTOR CORTEX; BRAIN IMAGES; NEURAL-TUBE; MR-IMAGES; HYDROCEPHALUS; MYELOMENINGOCELE; AUTISM AB Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction. C1 [Juranek, Jenifer] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Childrens Learning Inst, Houston, TX 77030 USA. 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Paus, Tomas Murphy, Declan G. M. TI Cortical Anatomy in Autism Spectrum Disorder: An In Vivo MRI Study on the Effect of Age SO CEREBRAL CORTEX LA English DT Article DE age; autism; brain; cortical thickness; MRI ID HUMAN CEREBRAL-CORTEX; BRAIN SIZE; HEAD CIRCUMFERENCE; ASPERGERS-SYNDROME; LONGITUDINAL MRI; NEURAL CIRCUITRY; GRAY-MATTER; CHILDREN; THICKNESS; GROWTH AB There is increasing evidence that children with autism spectrum disorder (ASD) have age-related differences from controls in cortical volume (CV). It is less clear, however, if these persist in adulthood and whether these reflect alterations in cortical thickness (CT) or cortical surface area (SA). Hence, we used magnetic resonance imaging to investigate the relationship between age and CV, CT, and SA in 127 males aged 10 through 60 years (76 with ASD and 51 healthy controls). "Regional" analyses (using cortical parcellation) identified significant age-by-group interactions in both CV and CT (but not SA) in the temporal lobes and within these the fusiform and middle temporal gyri. Spatially nonbiased "vertex-based" analysis replicated these results and identified additional "age-by-group" interactions for CT within superior temporal, inferior and medial frontal, and inferior parietal cortices. Here, CV and CT were 1) significantly negatively correlated with age in controls, but not in ASD, and 2) smaller in ASD than controls in childhood but vice versa in adulthood. Our findings suggest that CV dysmaturation in ASD extends beyond childhood, affects brain regions crucial to social cognition and language, and is driven by CT dysmaturation. This may reflect primary abnormalities in cortical plasticity and/or be secondary to disturbed interactions between individuals with ASD and their environment. C1 [Raznahan, Armin] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England. [Toro, Roberto; Paus, Tomas] Univ Nottingham, Brain & Body Ctr, Nottingham NG7 2RD, England. [Daly, Eileen; Robertson, Dene; Murphy, Clodagh; Deeley, Quinton; Murphy, Declan G. M.] Kings Coll London, Inst Psychiat, Sect Brain Maturat, Dept Psychol Med, London SE5 8AF, England. [Bolton, Patrick F.] Kings Coll London, Inst Psychiat, MRC Ctr Social Genet & Dev Psychiat, London SE5 8AF, England. [Paus, Tomas] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. RP Raznahan, A (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England. EM armin.raznahan@iop.kcl.ac.uk RI daly, eileen/B-6716-2011; Raznahan, Armin/F-4534-2012; Bolton, Patrick/E-8501-2010 OI Bolton, Patrick/0000-0002-5270-6262 FU UK Medical Research Council [G0701370] FX UK Medical Research Council Clinical Research Training Fellowship (A. R. to G0701370). 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Cortex PD JUN PY 2010 VL 20 IS 6 BP 1332 EP 1340 DI 10.1093/cercor/bhp198 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 600KW UT WOS:000277985800008 PM 19819933 ER PT J AU Virues-Ortega, J AF Virues-Ortega, Javier TI Applied behavior analytic intervention for autism in early childhood: Meta-analysis, meta-regression and dose-response meta-analysis of multiple outcomes SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Autism spectrum disorders; Applied behavior analysis; Language; Meta-analysis ID PERVASIVE DEVELOPMENTAL DISORDER; YOUNG-CHILDREN; SPECTRUM DISORDERS; MENTAL-RETARDATION; FOLLOW-UP; HETEROGENEITY; PRESCHOOLERS; FEASIBILITY; INDIVIDUALS; PREDICTORS AB A number of clinical trials and single-subject studies have been published measuring the effectiveness of long-term, comprehensive applied behavior analytic (ABA) intervention for young children with autism. However, the overall appreciation of this literature through standardized measures has been hampered by the varying methods, designs, treatment features and quality standards of published studies. In an attempt to fill this gap in the literature, state-of-the-art meta-analytical methods were implemented, including quality assessment, sensitivity analysis, meta-regression, dose-response meta-analysis and meta-analysis of studies of different metrics. Results suggested that long-term, comprehensive ABA intervention leads to (positive) medium to large effects in terms of intellectual functioning, language development, acquisition of daily living skills and social functioning in children with autism. Although favorable effects were apparent across all outcomes, language-related outcomes (IQ receptive and expressive language, communication) were superior to non-verbal IQ social functioning and daily living skills, with effect sizes approaching 1.5 for receptive and expressive language and communication skills. Dose-dependant effect sizes were apparent by levels of total treatment hours for language and adaptation composite scores. Methodological issues relating ABA clinical trials for autism are discussed. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Virues-Ortega, Javier] Inst Salud Carlos III, Ctr Nacl Epidemiol, CIBERNED, Madrid 28029, Spain. [Virues-Ortega, Javier] ABA Espana, Madrid, Spain. RP Virues-Ortega, J (reprint author), Inst Salud Carlos III, Ctr Nacl Epidemiol, CIBERNED, Sinesio Delgado 6, Madrid 28029, Spain. 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J., 2006, FOCUS AUTISM OTHER D, V21, P45, DOI 10.1177/10883576060210010601 Whitehead A, 2002, METAANALYSIS CONTROL Zachor DA, 2007, RES AUTISM SPECT DIS, V1, P304, DOI 10.1016/j.rasd.2006.12.001 NR 67 TC 65 Z9 66 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUN PY 2010 VL 30 IS 4 BP 387 EP 399 DI 10.1016/j.cpr.2010.01.008 PG 13 WC Psychology, Clinical SC Psychology GA 592ZU UT WOS:000277421600002 PM 20223569 ER PT J AU Silverman, LB Bennetto, L Campana, E Tanenhaus, MK AF Silverman, Laura B. Bennetto, Loisa Campana, Ellen Tanenhaus, Michael K. TI Speech-and-gesture integration in high functioning autism SO COGNITION LA English DT Article DE Autism; Cross-modal integration; Eye movements; Gesture; Semantic processing ID SPOKEN LANGUAGE COMPREHENSION; CONVERSATIONAL HAND GESTURES; VISUAL-SEARCH; SEMANTIC INFORMATION; SPECTRUM DISORDER; TALKING TODDLERS; ICONIC GESTURES; NORMAL INFANTS; EYE-MOVEMENTS; CHILDREN AB This study examined iconic gesture comprehension in autism, with the goal of assessing whether cross-modal processing difficulties impede speech-and-gesture integration. Participants were 19 adolescents with high functioning autism (HFA) and 20 typical controls matched on age, gender, verbal IQ and socio-economic status (SES). Gesture comprehension was assessed via quantitative analyses of visual fixations during a video-based task, using the visual world paradigm. Participants' eye movements were recorded while they watched videos of a person describing one of four shapes shown on a computer screen, using speech-and-gesture or speech-only descriptions. Participants clicked on the shape that the speaker described. Since gesture naturally precedes speech, earlier visual fixations to the target shape during speech-and-gesture compared to speech-only trials, would suggest immediate integration of auditory and visual information. Analyses of eye movements supported this pattern in control participants but not in individuals with autism: iconic gestures facilitated comprehension in typical individuals, while it hindered comprehension in those with autism. Cross-modal processing difficulties in autism were not accounted for by impaired unimodal speech or gesture processing. The results have important implications for the treatment of children and adults with this disorder. (C) 2010 Elsevier B.V. All rights reserved. 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German, Tamsin C. TI A reaction time advantage for calculating beliefs over public representations signals domain specificity for 'theory of mind' SO COGNITION LA English DT Article DE Theory of mind; Domain specificity ID TEMPORO-PARIETAL JUNCTION; THEORY-OF-MIND; FALSE-BELIEF; NEUROPSYCHOLOGICAL EVIDENCE; INTENTIONAL STANCE; LOBE CONTRIBUTIONS; AUTISM; BRAIN; PERFORMANCE; PRESCHOOLERS AB In a task where participants' overt task was to track the location of an object across a sequence of events, reaction times to unpredictable probes requiring an inference about a social agent's beliefs about the location of that object were obtained. Reaction times to false belief situations were faster than responses about the (false) contents of a map showing the location of the object (Experiment 1) and about the (false) direction of an arrow signaling the location of the object (Experiment 2). 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Aharon-Peretz, Judith Adler, Noga TI Brain Asymmetry in Emotional Processing in Asperger Syndrome SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE brain asymmetry; Asperger syndrome; emotional processing ID AUTISM SPECTRUM DISORDERS; HIGH-FUNCTIONING AUTISM; RIGHT-HEMISPHERE; IMPAIRED RECOGNITION; FACIAL EXPRESSIONS; INFANTILE-AUTISM; COMPLEX EMOTIONS; AMYGDALA DAMAGE; SOCIAL EMOTIONS; NORMAL ADULTS AB The role of brain asymmetry in emotional processing in Asperger syndrome (AS) is still largely unknown. Although the valence hypothesis predicts that positive emotions are processed preferentially by the left hemisphere and negative emotions by the right hemisphere, reports concerning laterality of emotion point to a left hemisphere advantage for complex emotion versus a right hemisphere advantage for basic emotions (the "type hypothesis''). In this study, we investigated the lateralization of basic versus complex (negative and positive) eye expressions in adults with AS in 2 consecutive experiments: in the first experiment, the performance of AS and healthy controls were compared in a divided visual field task. In the second experiment, the ability of participants with AS to identify eye expressions varying in valence and type was compared with that of patients with localized lesions in either the right or the left hemispheres. Controls were better in recognizing negative emotions presented to the left visual field and positive emotions presented to the right visual field, whereas individuals with AS failed to show this interaction effect. Lateralization of basic versus complex emotions was less evident although indeed controls identified better basic emotions presented to the right visual field. 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Behav. Neurol. PD JUN PY 2010 VL 23 IS 2 BP 74 EP 84 DI 10.1097/WNN.0b013e3181d748ec PG 11 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 608GD UT WOS:000278570500002 PM 20535055 ER PT J AU Kalbe, E Schlegel, M Sack, AT Nowak, DA Dafotakis, M Bangard, C Brand, M Shamay-Tsoory, S Onur, OA Kessler, J AF Kalbe, Elke Schlegel, Marius Sack, Alexander T. Nowak, Dennis A. Dafotakis, Manuel Bangard, Christopher Brand, Matthias Shamay-Tsoory, Simone Onur, Oezguer A. Kessler, Josef TI Dissociating cognitive from affective theory of mind: A TMS study SO CORTEX LA English DT Article DE Theory of Mind; Transcranial magnetic stimulation; Dorsolateral prefrontal cortex; 5 cm rule ID TRANSCRANIAL MAGNETIC STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; HIGH-FUNCTIONING AUTISM; SPATIAL WORKING-MEMORY; SOCIAL COGNITION; FRONTOTEMPORAL DEMENTIA; ASPERGER-SYNDROME; FRONTAL-LOBE; STORY COMPREHENSION; EXECUTIVE FUNCTION AB Introduction: "Theory of Mind" (TOM), i.e., the ability to infer other persons' mental states, is a key function of social cognition. It is increasingly recognized to form a multidimensional construct. One differentiation that has been proposed is that between cognitive and affective ToM, whose neural correlates remain to be identified. We aimed to ascertain the possible role of the right dorsolateral prefrontal cortex (DLPFC) for cognitive ToM as opposed to affective ToM processes. Methods: 1 Hz repetitive transcranial magnetic stimulation (rTMS) was used to interfere offline with cortical function of the right DLPFC in healthy male subjects who subsequently had to perform a computerized task assessing cognitive and affective ToM. Results: RTMS over the right DLPFC induced a selective effect on cognitive but not affective ToM. More specifically, a significant acceleration of reaction times in cognitive ToM compared to affective ToM and control items was observed in the experimental (right DLPFC) compared to the control (vertex) rTMS stimulation condition. Conclusions: Our findings provide evidence for the functional independence of cognitive from affective ToM. Furthermore, they point to an important role of the right DLPFC within neural networks mediating cognitive ToM. Possible underlying mechanisms of the acceleration of cognitive ToM processing under rTMS are discussed. (C) 2009 Elsevier Srl. All rights reserved. C1 [Kalbe, Elke; Nowak, Dennis A.; Dafotakis, Manuel; Onur, Oezguer A.] Res Ctr Julich, Inst Neurosci & Med INM 3, Cognit Neurol Sect, D-52425 Julich, Germany. [Schlegel, Marius; Dafotakis, Manuel; Onur, Oezguer A.; Kessler, Josef] Univ Hosp Cologne, Dept Neurol, Cologne, Germany. [Sack, Alexander T.] Maastricht Univ, Fac Psychol, Dept Cognit Neurosci, Maastricht, Netherlands. [Bangard, Christopher] Univ Hosp Cologne, Dept Radiol, Cologne, Germany. [Brand, Matthias] Univ Duisburg Essen, Dept Gen Psychol, Essen, Germany. [Brand, Matthias] Erwin L Hahn Inst Magnet Resonance Imaging, Essen, Germany. [Shamay-Tsoory, Simone] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. [Shamay-Tsoory, Simone] Univ Haifa, Brain & Behav Ctr, IL-31999 Haifa, Israel. RP Kalbe, E (reprint author), Res Ctr Julich, Inst Neurosci & Med INM 3, Cognit Neurol Sect, Leo Brandt Str 5, D-52425 Julich, Germany. EM e.kalbe@fz-juelich.de FU Faculty of Psychology, Maastricht University; EC-FP6-project DiMI [LSHBCT-2005-512146] FX We thank Michelle Moerel, Faculty of Psychology, Maastricht University, for support in graphical image processing, and Ingo Meister and Mitra Ameli, Department of Neurology, University of Cologne, for assistance in MRI and rTMS. Furthermore, the work of the first author was funded in part by the EC-FP6-project DiMI, LSHBCT-2005-512146. 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Grant, Jon E. Franklin, Martin E. Keuthen, Nancy Lochner, Christine Singer, Harvey S. Woods, Douglas W. TI TRICHOTILLOMANIA (HAIR PULLING DISORDER), SKIN PICKING DISORDER, AND STEREOTYPIC MOVEMENT DISORDER: TOWARD DSM-V SO DEPRESSION AND ANXIETY LA English DT Review DE trichotillontania; hair pulling; skin picking; stereotypic movement disorder; stereotypy ID OBSESSIVE-COMPULSIVE DISORDER; SELF-INJURIOUS-BEHAVIOR; PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDERS; IMPULSE-CONTROL DISORDERS; BODY DYSMORPHIC DISORDER; HIGH-FUNCTIONING AUTISM; LONGITUDINAL FOLLOW-UP; REPETITIVE BEHAVIOR; CLINICAL CHARACTERISTICS AB In DSM-IV-TR, trichotillomania (TTM) is classified as an impulse control disorder (not classified elsewhere), skin picking lacks its own diagnostic category (but might be diagnosed as an impulse control disorder not otherwise specified), and stereotypic movement disorder is classified as a disorder usually first diagnosed in infancy, childhood, or adolescence. ICD-10 classifies TTM as a habit and impulse disorder; and includes stereotyped movement disorders in a section on other behavioral and emotional disorders with onset usually occurring in childhood and adolescence. This article provides a focused review of nosological issues relevant to DSM-V; given recent empirical findings. This review presents a number of options and preliminary recommendations to be considered for DSM-V (1) Although TTM fits optimally into a category of body-focused repetitive behavioral disorders, in a nosology comprised of relatively few major categories it fits best within a category of motoric obsessive-compulsive spectrum disorders, (2) available evidence does not support continuing to include (current) diagnostic criteria B and C for TTM in DSM-V (3) the text for TTM should be updated to describe subtypes and forms of hair pulling, (4) there are persuasive reasons for referring to rim as "hair pulling disorder (trichotillomania)," (5) diagnostic criteria for skin picking disorder should be included in DSM-V or in DSM-Vs Appendix of Criteria Sets Provided for Further Study, and (6) the diagnostic criteria for stereotypic movement disorder should be clarified and simplified, bringing them in line with those for hair pulling and skin picking disorder. Depression and Anxiety 27:611-626, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. [Grant, Jon E.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Franklin, Martin E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Keuthen, Nancy] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lochner, Christine] Univ Stellenbosch, Dept Psychiat, Matieland, South Africa. [Singer, Harvey S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Woods, Douglas W.] Univ Wisconsin, Dept Psychiat, Milwaukee, WI 53201 USA. RP Stein, DJ (reprint author), Groote Schuur Hosp, Dept Psychiat, J2 Anzio Rd, ZA-7925 Cape Town, South Africa. EM dan.stein@uct.ac.za RI Citations, TLC SAB/C-4006-2011; Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 FU Astrozeneca; Eli-Lilly; GlaxoSmithKline; Jazz Pharmaceuticals; Johnson Johnson; Lundbeck; Orion; Pfizer; Pharmacia; Roche; Servier; Solvay; Sumitomo; Takeda; Tikvah; Wyeth FX Dr. Stein has received research grants and/or consultancy honoraria from Astrozeneca, Eli-Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Takeda, Tikvah, and Wyeth. 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DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2010 VL 27 IS 6 BP 611 EP 626 DI 10.1002/da.20700 PG 16 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 608GY UT WOS:000278572700008 PM 20533371 ER PT J AU Roehl, HH Pacifici, M AF Roehl, Henry H. Pacifici, Maurizio TI Shop Talk: Sugars, Bones, and a Disease Called Multiple Hereditary Exostoses SO DEVELOPMENTAL DYNAMICS LA English DT Editorial Material DE cartilage; bone; tumor; exostoses; osteochondroma; heparan sulfate ID HEPARAN-SULFATE; GROWTH-PLATE; GENE; OSTEOCHONDROMAS; CLONING; AUTISM; EXT1 AB October 29, 2009, researchers and physicians gathered at the Sheraton Four Points Hotel in Boston for 4 days to discuss a disease called multiple hereditary exostoses (MHE). MHE is an autosomal dominant disease that is associated with mutations in two enzymes that are required for heparan sulfate (HS) synthesis. Children with the disease form numerous benign bone tumors (osteochondromas) and have >2% chance of developing chondrosarcoma. The aim of the meeting was to generate new ideas for the diagnoses, treatment, and cure of this disease. Discussions ranged from orthopedic surgical treatment and patients' personal experiences to fundamental questions in skeletal biology and the precise molecular role that HS plays in developmental signaling pathways. Developmental Dynamics 239:1901 1904, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Roehl, Henry H.] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Sheffield S10 2TN, S Yorkshire, England. [Pacifici, Maurizio] Thomas Jefferson Univ, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Roehl, HH (reprint author), Univ Sheffield, MRC Ctr Dev & Biomed Genet, Firth Court,Western Bank, Sheffield S10 2TN, S Yorkshire, England. 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Dyn. PD JUN PY 2010 VL 239 IS 6 BP 1901 EP 1904 DI 10.1002/dvdy.22290 PG 4 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 610UB UT WOS:000278761700031 PM 20503385 ER PT J AU Patel, DR Greydanus, DE Calles, JL Pratt, HD AF Patel, Dilip R. Greydanus, Donald E. Calles, Joseph L., Jr. Pratt, Helen D. TI Developmental Disabilities Across the Lifespan SO DM DISEASE-A-MONTH LA English DT Article ID AUTISM SPECTRUM DISORDERS; SELF-INJURIOUS-BEHAVIOR; DEFICIT HYPERACTIVITY DISORDER; HEALTH-CARE NEEDS; QUALITY-STANDARDS-SUBCOMMITTEE; RECEPTIVE LANGUAGE DISORDER; CHILD-NEUROLOGY-SOCIETY; ACADEMY-OF-NEUROLOGY; EARLY ADULT LIFE; CEREBRAL-PALSY C1 [Patel, Dilip R.] Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. [Patel, Dilip R.] Western Michigan Univ, Dept Speech Pathol & Audiol, Kalamazoo Ctr Med Studies, Div Neurodev Disabil,Pediat Residency Program, Kalamazoo, MI 49008 USA. [Greydanus, Donald E.] Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, Pediat Residency Program,Kalamazoo Ctr Med Studie, Kalamazoo, MI USA. [Calles, Joseph L., Jr.] Michigan State Univ, Coll Human Med Child & Adolescent Psychiat, Dept Psychiat, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA. [Pratt, Helen D.] Michigan State Univ, Coll Human Med, Kalamazoo Ctr Med Studies, Dept Pediat & Human Dev,Div Dev Behav Pediat, Kalamazoo, MI USA. RP Patel, DR (reprint author), Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. 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PD JUN PY 2010 VL 56 IS 6 BP 305 EP 397 DI 10.1016/j.disamonth.2010.02.001 PG 93 WC Medicine, General & Internal SC General & Internal Medicine GA 609VX UT WOS:000278687200002 ER PT J AU Skoe, E Kraus, N AF Skoe, Erika Kraus, Nina TI Auditory Brain Stem Response to Complex Sounds: A Tutorial SO EAR AND HEARING LA English DT Review ID FREQUENCY-FOLLOWING RESPONSES; MISSING FUNDAMENTAL STIMULI; LANGUAGE-IMPAIRED CHILDREN; AUTISM SPECTRUM DISORDERS; NORMAL-HEARING ADULTS; SPEECH-IN-NOISE; LEARNING-PROBLEMS; SELECTIVE ATTENTION; EVOKED-POTENTIALS; MUSICAL EXPERIENCE AB This tutorial provides a comprehensive overview of the methodological approach to collecting and analyzing auditory brain stem responses to complex sounds (cABRs). cABRs provide a window into how behaviorally relevant sounds such as speech and music are processed in the brain. Because temporal and spectral characteristics of sounds are preserved in this subcortical response, cABRs can be used to assess specific impairments and enhancements in auditory processing. Notably, subcortical auditory function is neither passive nor hardwired but dynamically interacts with higher-level cognitive processes to refine how sounds are transcribed into neural code. This experience-dependent plasticity, which can occur on a number of time scales (e.g., life-long experience with speech or music, short-term auditory training, on-line auditory processing), helps shape sensory perception. Thus, by being an objective and noninvasive means for examining cognitive function and experience-dependent processes in sensory activity, cABRs have considerable utility in the study of populations where auditory function is of interest (e.g., auditory experts such as musicians, and persons with hearing loss, auditory processing, and language disorders). This tutorial is intended for clinicians and researchers seeking to integrate cABRs into their clinical or research programs. C1 [Skoe, Erika; Kraus, Nina] Northwestern Univ, Dept Commun Sci, Evanston, IL 60208 USA. [Kraus, Nina] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. RP Skoe, E (reprint author), Northwestern Univ, Dept Commun Sci, 2240 Campus Dr, Evanston, IL 60208 USA. EM eeskoe@northwestern.edu FU NSF [0842376]; NIH [R01 DC01510, F32 DC008052] FX This work was supported by NSF 0842376 and NIH R01 DC01510, F32 DC008052. 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A university supervisor used VTC equipment (i.e., computers equipped with web cameras and Internet) to provide feedback to teachers learning to implement functional analysis conditions (i.e., escape, attention, and play) with students with autism. Multiple baseline designs across teacher-student dyads with embedded multi-element designs were used to evaluate the effects of performance feedback delivered via VTC on the percentage of functional analysis procedures implemented correctly. Results indicated that teachers learned to implement functional analysis conditions following training (M duration of training = 75 minutes; range = 60-95 minutes). Rice tilts were maintained fir a number of weeks following the termination of performance feedback (M = 5 weeks; range = 4-9 weeks), but leacher performance declined thereafter. Video conferencing technology may provide supervisors an efficacious way to deliver performance feedback to teachers learning research-based strategies. C1 [Machalicek, Wendy] Univ Wisconsin, Dept Rehabil Psychol & Special Educ, Madison, WI 53706 USA. [O'Reilly, Mark F.] Univ Texas Austin, Austin, TX 78712 USA. [Rispoli, Mandy] Texas A&M, College Stn, TX USA. [Davis, Tonya] Baylor Univ, Waco, TX 76798 USA. [Lang, Russell] Texas State Univ San Marcos, San Marcos, TX USA. [Franco, Jessica Hetlinger] Autism Community Network, San Antonio, TX USA. [Chan, Jeffrey M.] No Illinois Univ, De Kalb, IL 60115 USA. RP Machalicek, W (reprint author), Univ Wisconsin, Dept Rehabil Psychol & Special Educ, 432 E Campus Mall,Rm 310, Madison, WI 53706 USA. 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Train. Autism Dev. Disabil. PD JUN PY 2010 VL 45 IS 2 BP 203 EP 215 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 596LU UT WOS:000277687300004 ER PT J AU Dogoe, MS Banda, DR Lock, RH AF Dogoe, Maud S. Banda, Devender R. Lock, Robin H. TI Acquisition and Generalization of the Picture Exchange Communication System Behaviors across Settings, Persons, and Stimulus Classes with Three Students with Autism SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID ALTERNATIVE COMMUNICATION; FUNCTIONAL COMMUNICATION; SPEECH DEVELOPMENT; CHILDREN; PECS; INTERVENTION; DISABILITIES; ADULTS; SKILLS; HOME AB This study examined the acquisition and generalization of requesting behaviors learned through PEGS with three children with autism. A single-subject multiple baseline across participants design was used to determine the effects of PECS. 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L, 2001, J POSIT BEHAV INTERV, V3, P194, DOI 10.1177/109830070100300401 Warren SF, 2007, MENT RETARD DEV D R, V13, P1, DOI 10.1002/mrdd.20153 YAMAMOTO J., 2006, JAPANESE J SPECIAL E, V43, P485 NR 45 TC 0 Z9 0 PU COUNCIL EXCEPTIONAL CHILDREN PI ARLINGTON PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA SN 2154-1647 J9 EDUC TRAIN AUTISM DE JI Educ. Train. Autism Dev. Disabil. PD JUN PY 2010 VL 45 IS 2 BP 216 EP 229 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 596LU UT WOS:000277687300005 ER PT J AU Lang, R O'Reilly, MF Sigafoos, J Machalicek, W Rispoli, M Shogren, K Chan, JM Davis, T Lancioni, G Hopkins, S AF Lang, Russell O'Reilly, Mark F. Sigafoos, Jeff Machalicek, Wendy Rispoli, Mandy Shogren, Karrie Chan, Jeffrey M. Davis, Tonya Lancioni, Giulio Hopkins, Shannon TI Review of Teacher Involvement in the Applied Intervention Research for Children with Autism Spectrum Disorders SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Review ID SOCIAL STORIES; DEVELOPMENTAL-DISABILITIES; SPECIAL-EDUCATION; FUNCTIONAL COMMUNICATION; CHALLENGING BEHAVIORS; ACTIVITY SCHEDULES; GENERAL-EDUCATION; VOCAL STEREOTYPY; SELF-MANAGEMENT; YOUNG-CHILDREN AB This review examined the involvement of teachers in the intervention research for children with autism spectrum disorders (ASD) from 1996 through February 2008. Forty-nine studies involving teachers of children with ASD were coded for different types of involvement. Findings are discussed in regards to three issues: (a) the manner in which teachers have been involved in autism research, (b) how teachers were trained to implement research based practices, and (c) teachers' perceptions of interventions (i.e. social validity). Results showed that teachers have been included in a variety of meaningful ways in recent research. However, our review also highlights the need for additional research. regarding teachers' perceptions and training teachers to effectively implement research-based interventions. C1 [Lang, Russell] Texas State Univ San Marcos, San Marcos, TX 78666 USA. [O'Reilly, Mark F.] Univ Texas Austin, Austin, TX 78712 USA. [Sigafoos, Jeff] Victoria Univ, Wellington, New Zealand. [Machalicek, Wendy] Univ Wisconsin, Madison, WI 53706 USA. [Rispoli, Mandy] Texas A&M, College Stn, TX USA. [Shogren, Karrie] Univ Illinois Urban Champaign, Urbana, IL USA. [Chan, Jeffrey M.] No Illinois Univ, De Kalb, IL 60115 USA. [Davis, Tonya] Baylor Univ, Waco, TX 76798 USA. [Lancioni, Giulio] Univ Bari, I-70121 Bari, Italy. [Hopkins, Shannon] Autism Treatment Ctr, Dallas, TX USA. RP Lang, R (reprint author), Texas State Univ San Marcos, 601 Univ Dr, San Marcos, TX 78666 USA. 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Autism Dev. Disabil. PD JUN PY 2010 VL 45 IS 2 BP 268 EP 283 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 596LU UT WOS:000277687300008 ER PT J AU Travers, J Tincani, M AF Travers, Jason Tincani, Matt TI Sexuality Education for Individuals with Autism Spectrum Disorders: Critical Issues and Decision Making Guidelines SO EDUCATION AND TRAINING IN AUTISM AND DEVELOPMENTAL DISABILITIES LA English DT Article ID SEVERE INTELLECTUAL DISABILITIES; DEVELOPMENTAL-DISABILITIES; PARENTAL PERSPECTIVE; ADOLESCENTS; PEOPLE; ADULTS; MANAGEMENT; BEHAVIORS; KNOWLEDGE; ATTITUDES AB Individuals with autism spectrum disorders (ASD) present unique needs regarding sexuality education. While the topic of sexuality has received increased attention in the fields of intellectual and developmental disabilities generally, less consideration has focused on the unique needs of individuals with ASD specifically. This paper presents one position in support of sexuality education for children and adolescents with ASD. The nature of human sexuality is discussed to provide a context for the rights of individuals with ASD to learn about their sexuality. Further justification far providing sexuality education in terms of the unique characteristics of this population is offered in conjunction with potential consequences of failing to provide sexuality education. Lastly, information regarding a decision-making process for sexuality education curriculum is presented, including the responsibilities of families and professionals providing sexuality education. C1 [Tincani, Matt] Temple Univ, Philadelphia, PA 19122 USA. [Travers, Jason] Univ Nevada, Las Vegas, NV 89154 USA. RP Tincani, M (reprint author), Temple Univ, 1301 Cecil B Moore Ave,Ritter Hall 367, Philadelphia, PA 19122 USA. 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TI Autism, information, deontology SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Editorial Material RP Sauvage, D (reprint author), 6 Rue Racine, F-37000 Tours, France. EM domsauvage@wanadoo.fr NR 0 TC 0 Z9 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0013-7006 J9 ENCEPHALE JI Enceph.-Rev. Psychiatr. Clin. Biol. Ther. PD JUN PY 2010 VL 36 IS 3 BP 187 EP 188 DI 10.1016/j.encep.2009.10.002 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 629SX UT WOS:000280221100001 PM 20620260 ER PT J AU [Anonymous] AF [Anonymous] TI Epigenetic contribution to autism spectrum disorders investigated SO EPIGENOMICS LA English DT News Item CR Nguyen A, 2010, FASEB J, V24, P3036, DOI [10.1096/fj.10-154484, 10.1096/fj.09-154484] NR 1 TC 0 Z9 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 J9 EPIGENOMICS-UK JI Epigenomics PD JUN PY 2010 VL 2 IS 3 BP 355 EP 355 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 607US UT WOS:000278533000004 ER PT J AU Wynder, C Stalker, L Doughty, ML AF Wynder, Christopher Stalker, Leanne Doughty, Martin L. TI Role of H3K4 demethylases in complex neurodevelopmental diseases SO EPIGENOMICS LA English DT Review DE autism; brain development; gene regulation; histone demethylation ID HISTONE LYSINE METHYLATION; EMBRYONIC STEM-CELLS; LINKED MENTAL-RETARDATION; AUTISM-SPECTRUM-DISORDER; TRANSLATIONAL PROFILING APPROACH; DOMAIN-CONTAINING PROTEINS; ESCAPES X-INACTIVATION; RETT-SYNDROME; GENE-EXPRESSION; BREAST-CANCER AB Significant neurological disorders can result from subtle perturbations of gene regulation that are often linked to epigenetic regulation. Proteins that regulate the methylation of lysine 4 of histone H3 (H3K4) and play a central role in epigenetic regulation, and mutations in genes encoding these enzymes have been identified in both autism and Rett syndrome. The H3K4 demethylases remove methyl groups from lysine 4 leading to loss of RNA polymerase binding and transcriptional repression. When these proteins are mutated, brain development is altered. 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PD JUN PY 2010 VL 31 IS 2 BP 133 EP 143 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 604RV UT WOS:000278297100002 ER PT J AU Noterdaeme, M Wriedt, E Hohne, C AF Noterdaeme, Michele Wriedt, Elke Hoehne, Christian TI Asperger's syndrome and high-functioning autism: language, motor and cognitive profiles SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Asperger syndrome; High-functioning autism; Intelligence; Language impairment; Motor disorder ID PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; INDIVIDUALS; SPECTRUM; DEFICITS; CHILDREN AB The objective of this study is to compare the cognitive profile, the motor and language functioning and the psychosocial adaptation of children with Asperger syndrome (AS) and with high-functioning autism (HFA). Subjects were recruited through the department Autism and Developmental Disorders of the Heckscher-Klinikum. To be included in the study, the full-scale-IQ had to be at least 80. Subjects with AS had to have a normal early language development and subjects with HFA a clear delay in language development, as reported by their parents. The sample consisted of 57 children with Asperger syndrome and 55 children with high-functioning autism. The mean age of the children was 10 years. All subjects were examined with a standardised test battery. Children with AS had a higher full-scale-IQ than children with HFA. This was due to a higher verbal-IQ. There were no significant differences in the performance-IQ. At a mean age of 10 years, subjects with AS had better language skills than subjects with HFA, but at least 30% showed clear receptive language problems. Motor problems were present in about 50% of the children with AS and HFA. The level of psychosocial adaptation was clearly reduced, but was comparable for the two groups. The differences in verbal-IQ and language skills between the two groups could be explained through the definition of the syndromes. The presence of language problems in the subjects with AS at age 10, the comparable degree of motor impairment and level of psychosocial adaptation question the validity of the distinction between AS and HFA within the category of pervasive developmental disorders. C1 [Noterdaeme, Michele] Klin Kinder & Jugendpsychiat & Psychotherapie, D-86154 Augsburg, Germany. [Wriedt, Elke; Hoehne, Christian] Heckscher Klinikum Kinder & Jugendpsychiat Psycho, D-81539 Munich, Germany. RP Noterdaeme, M (reprint author), Klin Kinder & Jugendpsychiat & Psychotherapie, Kapellenstr 30, D-86154 Augsburg, Germany. EM noterdaeme.michele@josefinum.de CR Asperger H, 1944, ARCH PSYCHIAT NERVEN, V117, P76, DOI 10.1007/BF01837709 EHLERS S, 1993, J CHILD PSYCHOL PSYC, V34, P1327, DOI 10.1111/j.1469-7610.1993.tb02094.x Eisenmajer R, 1998, J AUTISM DEV DISORD, V28, P527, DOI 10.1023/A:1026004212375 Elben C. 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Child Adolesc. Psych. PD JUN PY 2010 VL 19 IS 6 BP 475 EP 481 DI 10.1007/s00787-009-0057-0 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 602QH UT WOS:000278153400002 PM 19813070 ER PT J AU Foss-Feig, JH Kwakye, LD Cascio, CJ Burnette, CP Kadivar, H Stone, WL Wallace, MT AF Foss-Feig, Jennifer H. Kwakye, Leslie D. Cascio, Carissa J. Burnette, Courtney P. Kadivar, Haleh Stone, Wendy L. Wallace, Mark T. TI An extended multisensory temporal binding window in autism spectrum disorders SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Autism; Multisensory; Temporal binding; Audiovisual; Sensory processing; Cross-modal integration ID AUDIOVISUAL SPEECH INTEGRATION; DEVELOPMENTAL DISORDERS; SENSORY PROFILE; YOUNG-CHILDREN; INDIVIDUALS; PERCEPTION; ADULTS; DISCRIMINATION; ABNORMALITIES; INFORMATION AB Autism spectrum disorders (ASD) form a continuum of neurodevelopmental disorders, characterized by deficits in communication and reciprocal social interaction, as well as by repetitive behaviors and restricted interests. Sensory disturbances are also frequently reported in clinical and autobiographical accounts. However, surprisingly few empirical studies have characterized the fundamental features of sensory and multisensory processing in ASD. The current study is structured to test for potential differences in multisensory temporal function in ASD by making use of a temporally dependent, low-level multisensory illusion. In this illusion, the presentation of a single flash of light accompanied by multiple sounds often results in the illusory perception of multiple flashes. By systematically varying the temporal structure of the audiovisual stimuli, a "temporal window" within which these stimuli are likely to be bound into a single perceptual entity can be defined. The results of this study revealed that children with ASD report the flash-beep illusion over an extended range of stimulus onset asynchronies relative to children with typical development, suggesting that children with ASD have altered multisensory temporal function. These findings provide valuable new insights into our understanding of sensory processing in ASD and may hold promise for the development of more sensitive diagnostic measures and improved remediation strategies. C1 [Wallace, Mark T.] Vanderbilt Univ, Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [Foss-Feig, Jennifer H.; Cascio, Carissa J.; Stone, Wendy L.] Vanderbilt Univ, Dept Psychol & Human Dev, Nashville, TN 37232 USA. [Kwakye, Leslie D.] Vanderbilt Univ, Grad Program Neurosci, Nashville, TN 37232 USA. [Cascio, Carissa J.; Wallace, Mark T.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37232 USA. [Cascio, Carissa J.; Burnette, Courtney P.; Kadivar, Haleh; Stone, Wendy L.; Wallace, Mark T.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. [Burnette, Courtney P.; Stone, Wendy L.] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. [Wallace, Mark T.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37232 USA. [Cascio, Carissa J.; Wallace, Mark T.] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37232 USA. RP Wallace, MT (reprint author), Vanderbilt Univ, Dept Hearing & Speech Sci, 7110 MRB 3,BioSci Bldg,465 21st Ave S, Nashville, TN 37232 USA. EM mark.wallace@vanderbilt.edu FU Marino Autism Research Institute; National Institute of Child Health and Development [T32 HD07226]; Meharry-Vanderbilt Alliance; Vanderbilt Kennedy Center FX This work was supported by a Marino Autism Research Institute Discovery Grant (PI: MTW); National Institute of Child Health and Development T32 HD07226 predoctoral fellowship for JHF; Meharry-Vanderbilt Alliance Training Grant for LDK; Vanderbilt Kennedy Center. 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W., 2001, WOODCOCKJOHNSON TEST NR 49 TC 66 Z9 66 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2010 VL 203 IS 2 BP 381 EP 389 DI 10.1007/s00221-010-2240-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 596VB UT WOS:000277712500014 PM 20390256 ER PT J AU Stiegler, LN Davis, R AF Stiegler, Lillian N. Davis, Rebecca TI Understanding Sound Sensitivity in Individuals with Autism Spectrum Disorders SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism spectrum disorders (ASD); sound sensitivity; hyperacusis; auditory; [one phrase] hyperreactivity ID CHILDREN; HYPERSENSITIVITY; HYPERACUSIS; COMMUNICATION; PHOBIAS; NOISE; MODEL AB Literature on sound sensitivity in individuals with and without autism spectrum disorders (ASD) is reviewed in this article. Empirical evidence is examined, and physiologic and psychoemotional-behavioral perspectives are described. There is virtually no evidence of true physiological differences in auditory systems of individuals with ASD. It is evident, however, that many people with ASD (a) feel fearful and anxious about sound, and (b) may experience unpleasant physiological sensations because of autonomic and/or behavioral responses to nonpreferred sounds, but (c) can learn to react in less stigmatizing, more effectively self-regulating ways. Current assessment and intervention practices are discussed, and a case is presented. Heightened understanding of this issue among caregivers and interventionists may ultimately improve life participation for individuals with ASD. C1 [Stiegler, Lillian N.; Davis, Rebecca] SE Louisiana Univ, Hammond, LA 70402 USA. RP Stiegler, LN (reprint author), Dept Commun Sci & Disorders, Box 10879SLU, Hammond, LA 70402 USA. 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TI Video Preference Assessment of Students with Autism for Watching Self, Adults, or Peers SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; video technology; self-modeling; other modeling; preference assessment ID TEACH PERSPECTIVE-TAKING; DAILY LIVING SKILLS; STIMULUS PREFERENCE; IDENTIFYING REINFORCERS; MODELING INTERVENTIONS; CHILDREN; DISABILITIES; PLAY; INDIVIDUALS; INSTRUCTION AB The preferences of students with autism for watching themselves, a familiar adult, or a familiar peer in video recordings were examined. A multi-stimulus video preference assessment was used to evaluate the preferences of five students with autism. Three video options of a preferred activity (e. g., vacuuming) or daily/routine activity (e. g., snack time) were available to students via a computer-based program. Results showed that collectively there was minimal difference between the three video choices across the five students. However, in their individual scores, preferences varied among the students and activities, providing a framework for discussion of individual preference assessments when using video for instructional programs and reinforcement of task performance and behavior. C1 [Mechling, Linda C.] Univ N Carolina, Wilmington, NC 28403 USA. [Moser, Sara V.] Adams Elementary, Cary, NC USA. RP Mechling, LC (reprint author), Univ N Carolina, 601 S Coll Rd, Wilmington, NC 28403 USA. EM mechlingl@uncw.edu CR 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 Buggey T., 2005, FOCUS AUTISM OTHER D, V20, P52, DOI DOI 10.1177/10883576050200010501 Buggey T., 1999, J POSIT BEHAV INTERV, V1, P205, DOI 10.1177/109830079900100403 Cannella-Malone H, 2006, EDUC TRAIN DEV DISAB, V41, P344 Carr JE, 2000, J APPL BEHAV ANAL, V33, P353, DOI 10.1901/jaba.2000.33-353 CHARLOP MH, 1989, J APPL BEHAV ANAL, V22, P275, DOI 10.1901/jaba.1989.22-275 Charlop-Christy MH, 2000, J AUTISM DEV DISORD, V30, P537, DOI 10.1023/A:1005635326276 Charlop-Christy MH, 2003, J POSIT BEHAV INTERV, V5, P12, DOI 10.1177/10983007030050010101 Coyle C, 2004, J INTELLECT DEV DIS, V29, P3, DOI 10.1080/08927020410001662642 D'Ateno P, 2003, J POSIT BEHAV INTERV, V5, P5, DOI 10.1177/10983007030050010801 DATTILO J, 1987, J ASSOC PERS SEVERE, V12, P306 Delano ME, 2007, REM SPEC EDUC, V28, P33, DOI 10.1177/07419325070280010401 DeLeon IG, 1996, J APPL BEHAV ANAL, V29, P519, DOI 10.1901/jaba.1996.29-519 Dowrick PW, 1999, APPL PREV PSYCHOL, V8, P23, DOI 10.1016/S0962-1849(99)80009-2 FISHER W, 1992, J APPL BEHAV ANAL, V25, P491, DOI 10.1901/jaba.1992.25-491 GREEN CW, 1988, J APPL BEHAV ANAL, V21, P31, DOI 10.1901/jaba.1988.21-31 Hanley GP, 1999, J APPL BEHAV ANAL, V32, P419, DOI 10.1901/jaba.1999.32-419 Hermansen E, 2007, ED TREATMENT CHILDRE, V30, P183, DOI DOI 10.1353/ETC.2007.0029 LeBlanc LA, 2003, J APPL BEHAV ANAL, V36, P253, DOI 10.1901/jaba.2003.36-253 Logan KR, 2001, J DEV PHYS DISABIL, V13, P97, DOI 10.1023/A:1016624923479 MASON SA, 1989, J APPL BEHAV ANAL, V22, P171, DOI 10.1901/jaba.1989.22-171 Mechling L., 2005, Journal of Special Education Technology, V20 Mechling L.C., 2006, FOCUS AUTISM OTHER D, V21, P7, DOI DOI 10.1177/10883576060210010201 MEHARG SS, 1990, ADV BEHAV RES THER, V12, P85, DOI 10.1016/0146-6402(90)90008-E Nikopoulos CK, 2003, BEHAV INTERVENT, V18, P87, DOI 10.1002/bin.129 Nikopoulos CK, 2004, J APPL BEHAV ANAL, V37, P93, DOI 10.1901/jaba.2004.37-93 Norman J. 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A., 2006, EDUC TREAT CHILD, V29, P517 Roane HS, 1998, J APPL BEHAV ANAL, V31, P605, DOI 10.1901/jaba.1998.31-605 Schreibman L., 2000, J POSIT BEHAV INTERV, V2, P3, DOI 10.1177/109830070000200102 Sherer M, 2001, BEHAV MODIF, V25, P140, DOI 10.1177/0145445501251008 Shipley-Benamou R, 2002, J POSIT BEHAV INTERV, V4, P165 Taylor BA, 1999, J DEV PHYS DISABIL, V11, P253, DOI 10.1023/A:1021800716392 Wert BY, 2003, J POSIT BEHAV INTERV, V5, P30, DOI 10.1177/10983007030050010501 WINDSOR J, 1994, RES DEV DISABIL, V15, P439, DOI 10.1016/0891-4222(94)90028-0 NR 43 TC 6 Z9 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD JUN PY 2010 VL 25 IS 2 BP 76 EP 84 DI 10.1177/1088357610364392 PG 9 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 598JX UT WOS:000277833500002 ER PT J AU Hartley, SL Sikora, DM AF Hartley, Sigan L. Sikora, Darryn M. TI Detecting Autism Spectrum Disorder in Children With Intellectual Disability: Which DSM-IV-TR Criteria Are Most Useful? SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE autism; intellectual disability; evaluation; diagnosis; parent interview ID MENTAL-RETARDATION; DIAGNOSTIC INTERVIEW; YOUNG-CHILDREN; ADI-R; EARLY INTERVENTION; CHILDHOOD AUTISM; PARENT INTERVIEW; ADOLESCENTS; LANGUAGE; CLASSIFICATION AB The diagnosis of autism spectrum disorders (ASDs) in older children with intellectual disabilities (IDs) is challenging because of overlap in symptomatology and the high comorbidity of these disorders. On the basis of a sample of 89 older children with IDs (aged 6-15 years) referred to an ASD clinic, semistructured parent interviews were used to investigate the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnostic criteria that differentiated children with ASDs from those without ASDs. Diagnostic criteria related to impaired social interactions, stereotyped or idiosyncratic language, poor conversational skills, lack of pretend and imitative play, and restricted or narrowed interests were related to ASD diagnoses. The findings of this study have implications for improving ASD diagnostic evaluations in children with IDs. C1 [Hartley, Sigan L.] Univ Wisconsin, Waisman Ctr, Lifespan Dev Lab, Madison, WI 53705 USA. [Sikora, Darryn M.] Oregon Hlth & Sci Univ, Child Dev & Rehabil Ctr, Autism Clin, Portland, OR 97201 USA. RP Hartley, SL (reprint author), Univ Wisconsin, Waisman Ctr, Lifespan Dev Lab, 1500 Highland Ave, Madison, WI 53705 USA. EM hartley@waisman.wisc.edu CR *AM AC CHILD AD PS, 1999, J AM ACAD CHILD ADOL, V38, P32 American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 1987, DIAGN STAT MAN MENT American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th BallabanGil K, 1996, PEDIATR NEUROL, V15, P217, DOI 10.1016/S0887-8994(96)00219-6 Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Carcani-Rathwell I, 2006, J CHILD PSYCHOL PSYC, V47, P573, DOI 10.1111/j.1469-7610.2005.01565.x Carrow-Woolfolk E., 1995, ORAL WRITTEN LANGUAG Charman T, 2003, AUTISM, V7, P217 Cox A, 1999, J CHILD PSYCHOL PSYC, V40, P719, DOI 10.1111/1469-7610.00488 Croen LA, 2002, J AUTISM DEV DISORD, V32, P207, DOI 10.1023/A:1015453830880 *CUR AUT NOW FDN C, 1998, CNS SPECTRUM J, V3, P40 DEB S, 1994, BRIT J PSYCHIAT, V165, P395, DOI 10.1192/bjp.165.3.395 de Bildt A, 2004, J AUTISM DEV DISORD, V34, P129 Edelson M. G., 2006, FOCUS AUTISM OTHER D, V21, P66, DOI DOI 10.1177/10883576060210020301 Filipek PA, 2000, NEUROLOGY, V55, P468 FOMBONNE E, 1992, J AUTISM DEV DISORD, V22, P563, DOI 10.1007/BF01046328 Fombonne E, 2005, J APPL RES INTELLECT, V18, P281, DOI 10.1111/j.1468-3148.2005.00266.x FREEMAN BJ, 1981, AM J PSYCHIAT, V138, P25 Goin-Kochel RP, 2006, AUTISM, V10, P439, DOI 10.1177/1362361306066601 Harrison P., 2006, ADAPTIVE BEHAV ASSES Howlin P, 1999, DEV MED CHILD NEUROL, V41, P834, DOI 10.1017/S0012162299001656 Howlin P, 1997, AUTISM, V1, P135, DOI DOI 10.1177/1362361397012003 JICK H, 2003, PHARMACOTHERAPY, V23, P272 Johnson CP, 2007, PEDIATRICS, V120, P1183, DOI 10.1542/peds.2007-2361 KAMINER RK, 1984, PERSPECTIVES PROGR M, V2, P289 Kraijer D, 2005, J AUTISM DEV DISORD, V35, P499, DOI 10.1007/s10803-005-5040-0 KRAIJER D, 1997, AUTISM AUTISM CONDIT Lord C, 1997, J AUTISM DEV DISORD, V27, P501, DOI 10.1023/A:1025873925661 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Lord C, 1995, J CHILD PSYCHOL PSYC, V36, P1365, DOI 10.1111/j.1469-7610.1995.tb01669.x LORD C, 1993, INF MENTAL HLTH J, V14, P234, DOI 10.1002/1097-0355(199323)14:3<234::AID-IMHJ2280140308>3.0.CO;2-F Mandell DS, 2002, J AM ACAD CHILD PSY, V41, P1447, DOI 10.1097/01.CHI.0000024863.60748.53 Matson JL, 2008, J INTELLECT DEV DIS, V33, P36, DOI 10.1080/13668250701829837 MUNDY P, 1994, DEV PSYCHOPATHOL, V6, P387 Osterling JA, 2002, DEV PSYCHOPATHOL, V14, P239 Roid G., 2003, STANFORDBINET INTELL, VFifth Rutter M., 2003, ADI R AUTISM DIAGNOS Schalock RL, 2007, INTELLECT DEV DISAB, V45, P116, DOI 10.1352/1934-9556(2007)45[116:TROMRU]2.0.CO;2 SCHOPLER E, 1980, J AUTISM DEV DISORD, V10, P91, DOI 10.1007/BF02408436 SIGMAN M, 1984, DEV PSYCHOL, V20, P293, DOI 10.1037/0012-1649.20.2.293 Skellern C, 2005, J PAEDIATR CHILD H, V41, P407, DOI 10.1111/j.1440-1754.2005.00634.x Skuse D, 2004, J AM ACAD CHILD PSY, V43, P548, DOI 10.1097/00004583-200405000-00008 Smith T, 2000, AM J MENT RETARD, V105, P269, DOI 10.1352/0895-8017(2000)105<0269:RTOIEI>2.0.CO;2 Sparrow SS, 2005, VINELAND ADAPTIVE BE STONE WL, 1993, J AUTISM DEV DISORD, V23, P639, DOI 10.1007/BF01046106 Stone WL, 2003, AUTISM, V7, P9, DOI 10.1177/1362361303007001003 VANBOURGONDIEN ME, 1992, J AUTISM DEV DISORD, V22, P493 Vig S, 1999, J AUTISM DEV DISORD, V29, P235, DOI 10.1023/A:1023084106559 Wechsler D., 2003, WECHSLER INTELLIGENC Wechsler D., 2002, WECHSLER PRESCHOOL P, V3rd WING L, 1981, J AUTISM DEV DISORD, V11, P31, DOI 10.1007/BF01531339 NR 52 TC 3 Z9 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD JUN PY 2010 VL 25 IS 2 BP 85 EP 97 DI 10.1177/1088357609356094 PG 13 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 598JX UT WOS:000277833500003 ER PT J AU Jegatheesan, B Miller, PJ Fowler, SA AF Jegatheesan, Brinda Miller, Peggy J. Fowler, Susan A. TI Autism From a Religious Perspective: A Study of Parental Beliefs in South Asian Muslim Immigrant Families SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE Muslim families; religion; autism ID EARLY INTERVENTION; CONSTRUCTION; CHILDREN; ISRAEL AB Three multilingual immigrant South Asian Muslim families who have children with autism were interviewed to ascertain their beliefs about autism. Data were drawn from interviews and conversations recorded during 17 months of ethnographic fieldwork in homes and community. Results indicate that families understood the task of raising a child with autism in religious terms. In keeping with the precepts of Islam, their overarching goal was to raise their children as normally as possible, incorporating them into ordinary social, linguistic, and religious practices at home and in the community. Parents strongly contested experts' understandings of autism, which they believed undermined rather than promoted their children's development. Findings have implications for multicultural teacher education and enhancing home, community, and school collaboration. C1 [Jegatheesan, Brinda] Univ Washington, Seattle, WA 98195 USA. [Miller, Peggy J.; Fowler, Susan A.] Univ Illinois, Urbana, IL 61801 USA. RP Jegatheesan, B (reprint author), Univ Washington, 322 J Miller Hall,Box 353600, Seattle, WA 98195 USA. EM brinda@u.washington.edu CR AZMI S, 1997, J MUSLIM MINORITY AF, V17, P153, DOI 10.1080/13602009708716365 Battle D. 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B., 1990, GIVE TAKE EVERYDAY L Shaked M, 2005, SOC SCI MED, V61, P2190, DOI 10.1016/j.socscimed.2005.04.022 Skinner D, 1999, EXCEPT CHILDREN, V65, P481 Skinner DG, 2001, AM J MENT RETARD, V106, P297, DOI 10.1352/0895-8017(2001)106<0297:RORITL>2.0.CO;2 STEVENSON I, 1987, CHILDREN WHO REMEMBE STEVENSON I, 1980, CASES REINCARNATION Suleiman M. W., 1999, J MUSLIM MINORITY AF, V19, P33, DOI 10.1080/13602009908716423 TIVETTE CM, 2005, DEC RECOMMENDED PRAC, P107 Turnbull AP, 2007, J EARLY INTERVENTION, V29, P187, DOI 10.1177/105381510702900301 Zhang C., 2003, FOCUS AUTISM OTHER D, V18, P51, DOI 10.1177/108835760301800107 Zionts L. T., 2003, FOCUS AUTISM OTHER D, V18, P2, DOI 10.1177/108835760301800101 NR 44 TC 9 Z9 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1088-3576 J9 FOCUS AUTISM DEV DIS JI Focus Autism Dev. Disabil. PD JUN PY 2010 VL 25 IS 2 BP 98 EP 109 DI 10.1177/1088357610361344 PG 12 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 598JX UT WOS:000277833500004 ER PT J AU Carbone, VJ Morgenstern, B Zecchin-Tirri, G Kolberg, L AF Carbone, Vincent J. Morgenstern, Barry Zecchin-Tirri, Gina Kolberg, Laura TI The Role of the Reflexive-Conditioned Motivating Operation (CMO-R) During Discrete Trial Instruction of Children With Autism SO FOCUS ON AUTISM AND OTHER DEVELOPMENTAL DISABILITIES LA English DT Article DE motivating operations; establishing operations; autism; escape and avoidance behavior; discrete trial instruction ID INJURIOUS ESCAPE BEHAVIOR; ESTABLISHING OPERATIONS; FUNCTIONAL-ANALYSIS; NEGATIVE REINFORCEMENT; SELF-INJURY; INTERSPERSED REQUESTS; DESTRUCTIVE BEHAVIOR; RESPONSE EFFICIENCY; MAINTAINED BEHAVIOR; SLEEP-DEPRIVATION AB The principle of motivation has resurfaced as an independent variable in the field of behavior analysis over the past 20 years. The increased interest is the result of refinements of the concept of the motivating operation and its application to the learning needs of persons with developmental disabilities. Notwithstanding the increased emphasis upon modification of motivating operations to reduce problem behavior, there is limited recognition of this important behavioral variable in autism treatment literature. An overview of antecedent-based instructional modifications that lead to a reduction of escape and avoidance behavior of children with autism during instruction is provided. An analysis of these instructional methods as motivating operations is proposed. A conceptually systematic analysis of the influence of instructional methods is offered as a tool for improving the selection and implementation of effective teaching procedures. C1 [Carbone, Vincent J.; Zecchin-Tirri, Gina; Kolberg, Laura] Carbone Clin, Valley Cottage, NY 10989 USA. [Morgenstern, Barry] Inst Profess Practice Inc, Woodbridge, CT USA. RP Carbone, VJ (reprint author), Carbone Clin, 614 Corp Way,Suite 1, Valley Cottage, NY 10989 USA. EM drvjc@aol.com RI Carbone, Virginia/H-7750-2013 CR Anderson S. 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PD JUN PY 2010 VL 25 IS 2 BP 110 EP 124 DI 10.1177/1088357610364393 PG 15 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 598JX UT WOS:000277833500005 ER PT J AU Silverman, C AF Silverman, Chloe TI 'Birdwatching and baby-watching': Niko and Elisabeth Tinbergen's ethological approach to autism SO HISTORY OF PSYCHIATRY LA English DT Article DE autism spectrum disorders; autistic; childhood schizophrenia; Elisabeth Tinbergen; ethology; holding therapy; motivational conflict; Niko Tinbergen; psychoanalysis ID BOWLBY,JOHN; MONKEYS; STRESS AB Biographers have largely dismissed Nikolaas 'Niko' Tinbergen's late research into the causes and treatment of autism, describing it as a deviation from his previous work, influenced by his personal desires. They have pointed to the incoherence of Tinbergen's assertions about best practices for treating autism, his lack of experience with children with autism, and his apparent embracing of psychogenic theories that the medical research community had largely abandoned. While these critiques have value, it is significant that Tinbergen himself saw his research as a logical extension of his seminal findings in the field of ethology, the science of animal behaviour. The reception of his theories, both positive and negative, was due less to their strengths or faults than to the fact that Tinbergen had inserted himself into a pre-existing and acrimonious debate in the autism research community. Debates about the relative role of environmental and hereditary factors in the aetiology of autism, and the implications of both for the efficacy of different treatments, had political and material significance for the success of parent organizations' lobbying efforts and financial support for research programmes. Tinbergen's approach was welcomed and even championed by a significant minority, who saw no problem with his ideas or methods. C1 Penn State Univ, STS Program, University Pk, PA 16803 USA. RP Silverman, C (reprint author), Penn State Univ, STS Program, 102 Old Bot, University Pk, PA 16803 USA. 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TI 5-HTTLPR Polymorphism: Analysis in South African Autistic Individuals SO HUMAN BIOLOGY LA English DT Article DE SEROTONIN TRANSPORTER; 5-HTTLPR POLYMORPHISM; AUTISM; SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS); SOUTH AFRICAN POPULATIONS ID SEROTONIN TRANSPORTER GENE; PROMOTER REGION POLYMORPHISM; SPECTRUM DISORDERS; ASSOCIATION; VARIANTS; POPULATION; CHILDREN; SLC6A4; HYPERSEROTONEMIA; GENOTYPE AB The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism; 5-HTTLPR) has long been implicated in autism and other psychiatric disorders. The use of selective serotonin reuptake inhibitors (SSRIs) has a positive effect on treating some symptoms of autism. The effects of these drugs vary in individuals because of the presence of the S or L allele of 5-HTTLPR. Studies performed on various autistic populations have found different allele frequencies for the L and S alleles. Allele frequencies and genotypes of the South African autistic populations (African, mixed, and Caucasian) were compared with matching South African ethnic control populations. The *S/*S genotype was found to be highly significantly associated with all the South African autistic ethnic populations. In the South African African population the *S/*S genotype was present in 7 (33%) of the autistic individuals but in none of the control subjects, yielding infinitely large odds of developing autism. The odds of developing autism with the *S/*S genotype compared to the *L/*L genotype increased 10.15-fold in the South African mixed group and 2.74-fold in the South African Caucasian population. The allele frequency of the South African autistic population was also compared with studies of other autistic populations around the world, and highly significant differences were found with the Japanese, Korean, and Indian population groups. The difference was not significant for the French, German, Israeli, Portuguese, and American groups. This is the first South African study of autistic individuals of different ethnic backgrounds that shows significant differences in allele and genotype frequencies of 5-HTTLPR. The results of this study open new avenues for investigating the role of transmission of the L and S alleles in families with autism in South Africa. C1 [Arieff, Zainunisha; Gameeldien, Hajirah] Univ Western Cape, Dept Biotechnol, ZA-7535 Cape Town, South Africa. [Kaur, Mandeep; Bajic, Vladimir B.] King Abdullah Univ Sci & Technol, Computat Biosci Res Ctr, Thuwal 239556900, Saudi Arabia. [van der Merwe, Lize] MRC, Biostat Unit, ZA-7505 Tygerberg, South Africa. [van der Merwe, Lize] Univ Western Cape, Dept Stat, ZA-7535 Cape Town, South Africa. RP Arieff, Z (reprint author), Univ Western Cape, Dept Biotechnol, Private Bag X17, ZA-7535 Cape Town, South Africa. RI Bajic, Vladimir/D-2810-2009 OI Bajic, Vladimir/0000-0001-5435-4750 FU National Research Foundation, South Africa [TTK2008050600011]; Autism South Africa; University of the Western Cape FX We would like to thank the National Research Foundation, South Africa (Thuthuka grant TTK2008050600011), Autism South Africa, and the University of the Western Cape for funds provided for this study. We also want to thank the children, their parents, the school staff, and volunteers of the Western Cape Education Department for their support and involvement during the sample collection. We thank Luke Esau, Lucinda Adonis, Muneera Davids, Zaida Dalvie, Cleo Williams, and all the final-year biotechnology student volunteers who so willingly helped us with the sample collection from the different schools. 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Biol. PD JUN PY 2010 VL 82 IS 3 BP 291 EP 300 PG 10 WC Anthropology; Biology; Genetics & Heredity SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 734LK UT WOS:000288335400003 PM 20649385 ER PT J AU Konrad, K Eickhoff, SB AF Konrad, Kerstin Eickhoff, Simon B. TI Is the ADHD Brain Wired Differently? A Review on Structural and Functional Connectivity in Attention Deficit Hyperactivity Disorder SO HUMAN BRAIN MAPPING LA English DT Article DE connectivity; ADHD; fMRI; DTI ID DEFAULT-MODE NETWORK; WHITE-MATTER ABNORMALITIES; ANTERIOR CINGULATE CORTEX; LOW-BIRTH-WEIGHT; DEFICIT/HYPERACTIVITY DISORDER; MAGNETIC-RESONANCE; INTERFERENCE CONTROL; DIFFUSION; CHILDREN; ACTIVATION AB In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. 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Brain Mapp. PD JUN PY 2010 VL 31 IS 6 SI SI BP 904 EP 916 DI 10.1002/hbm.21058 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 605IM UT WOS:000278341200008 PM 20496381 ER PT J AU Shaw, P Gogtay, N Rapoport, J AF Shaw, Philip Gogtay, Nitin Rapoport, Judith TI Childhood Psychiatric Disorders as Anomalies in Neurodevelopmental Trajectories SO HUMAN BRAIN MAPPING LA English DT Article DE magnetic resonance imaging; child development; childhood psychiatric disorders; modeling ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; CORTICAL BRAIN-DEVELOPMENT; ONSET SCHIZOPHRENIA; DOWNS-SYNDROME; UNAFFECTED SIBLINGS; ADHD; AUTISM; METAANALYSIS; CHILDREN AB Childhood psychiatric disorders are rarely static; rather they change over time and longitudinal studies are ideally suited to capture such dynamic processes. 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TI Early-life treatment of antiserotonin antibodies alters sensitivity to serotonin receptors, nociceptive stimulus and serotonin metabolism in adult rats SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Tremor; Pain; Dopamine; Nucleus raphe; Immunization against autism spectrum disorders Hyperserotoninemia; CNS 5-HT development ID CENTRAL-NERVOUS-SYSTEM; BRAIN-DEVELOPMENT; BALB/C MICE; BLOOD SEROTONIN; INDUCED TREMOR; AUTISM; SCHIZOPHRENIA; PHYSOSTIGMINE; INVOLVEMENT; CHILDREN AB A single systemic administration of serotonin (5-HT) antibodies on day-1 of the life of rat has been investigated for neurotransmitter contents in nucleus raphe, and several discrete brain regions, as well as for serotoninergic syndromes and nociceptive responses in adult animals. 5-HT antiserum raised in rabbits were purified and characterized prior to subcutaneous administration in neonatal rats. Control animals received normal rabbit serum. Antibodies tagged with radioactive iodine were traced in the brains of rat pups treated subcutaneously.These animals at adulthood, exhibited an increase in body weight, increased sensitivity to serotonin agonist 5-methoxy-N-N-dimethyl tryptamine, and to nociceptive stimulus to subcutaneously administered formalin. Animals neonatally treated with 5-HT antiserum once on day 1 of life, exhibited significant decrease in the contents of serotonin and its metabolite as compared to normal serum treated animals specifically in nucleus raphe dorsalis, but not in substantia gresia centralis, nucleus accumbens, nucleus caudatus putamen, substantia nigra or tuberculum olfactorium during the study period of seven days to four months. The contents of dopamine or norepinephrine were not consistently altered in any of the nuclei studied. Since 5-HT is known to act as a trophic factor for its own development and its target areas, exposure to 5-HT antibodies during birth might have adversely affected the development of the serotoninergic system and resulted in long-lasting changes in behavior and 5-HT levels in the brain. These results have strong implications for the treatment of childhood developmental disorders such as autism where hyperserotoninemia is associated with the disease syndromes. (C) 2010 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Mohanakumar, Kochupurackal P.] Indian Inst Chem Biol, Div Cell Biol & Physiol, Lab Clin & Expt Neurosci, CSIR, Kolkata 700032, W Bengal, India. RP Mohanakumar, KP (reprint author), Indian Inst Chem Biol, Div Cell Biol & Physiol, Lab Clin & Expt Neurosci, CSIR, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India. EM mohankumar@iicb.res.in FU Department of Science and Technology, Govt. of India; CSIR, Govt. of India FX The study was funded by a project grant (to KPM) from Department of Science and Technology, Govt. of India. S. Bhanja (nee Mohanty) received junior and senior research fellowships from CSIR, Govt. of India. 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Dimoska, Aneta TI Varying required effort during interference control in children with AD/HD: Task performance and ERPs SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Attention-deficit hyperactivity disorder; Children; Inhibition; Interference control; ERPs; Effort; N200; Arousal ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; EVENT-RELATED POTENTIALS; AUTISM SPECTRUM DISORDERS; COGNITIVE-ENERGETIC MODEL; RESPONSE-INHIBITION; SUSTAINED ATTENTION; SELECTIVE ATTENTION; STATE-REGULATION; ERROR-DETECTION AB Prominent models of attention-deficit/hyperactivity disorder (AD/HD) contend that disinhibition is the core deficit, or that any inhibition deficits that exist are secondary to dysfunctional energetic regulation (i.e. effort and arousal). This study tested these models by investigating the influence of task-directed effort, as manipulated by stimulus degradation, on interference control deficits in children with AD/HD. Twenty children with AD/HD aged between 7 and 14 years were matched in age to 20 controls and performed a modified visual Eriksen flanker task, while EEG and skin conductance level (SCL) were recorded. Participants completed the task under three conditions varying in stimulus degradation: none, 30% or 60%. Results revealed a quadratic effect with improved task performance in the 30% degradation condition, relative to the other conditions. Overall, children with AD/HD showed a tendency towards increased errors and more variable responding, although this did not differ between conditions. Importantly, children with AD/HD showed no deficits in interference control at a behavioural level. SCL revealed reduced activity in the AD/HD group during the non-degraded condition which normalised to control levels in the highest degradation condition. ERPs revealed two functionally distinct N2 components, one of which, along with the P3, was larger to incongruent stimuli, consistent with previous studies linking this component to inhibitory processing. Atypical activation of these components was evident in children with AD/HD and occurred as a function of degradation condition. Taken together these findings suggest the role of other factors such as state regulation as underlying deficits in AD/HD. (C) 2010 Elsevier B.V. All rights reserved. C1 [Johnstone, Stuart J.; Watt, Annele J.; Dimoska, Aneta] Univ Wollongong, Sch Psychol, Brain & Behav Res Inst, Wollongong, NSW 2522, Australia. RP Johnstone, SJ (reprint author), Univ Wollongong, Sch Psychol, Brain & Behav Res Inst, Wollongong, NSW 2522, Australia. EM sjohnsto@uow.edu.au FU Australian Research Council [DP0559048] FX This study was supported by a grant to SJJ from the Australian Research Council Discovery funding scheme (DP0559048). 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SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Letter RP Wiwanitkit, V (reprint author), Wiwanitkit House, Bangkok 10160, Thailand. EM wviroj@yahoo.com CR Piravej K, 2009, J ALTERN COMPLEM MED, V15, P1355, DOI 10.1089/acm.2009.0258 NR 1 TC 0 Z9 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUN PY 2010 VL 16 IS 6 BP 613 EP 613 DI 10.1089/acm.2010.0024 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 614CR UT WOS:000279033300003 PM 20569025 ER PT J AU Piravej, K AF Piravej, Krisna TI Reply to "Thai Massage and Autism: Correlation?'' SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Letter C1 Chulalongkorn Univ, Dept Rehabil Med, Fac Med, Bangkok 10330, Thailand. RP Piravej, K (reprint author), Chulalongkorn Univ, Dept Rehabil Med, Fac Med, Bangkok 10330, Thailand. 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Anwar, Mona Sidhom, Gloria TI Reduced Serum Levels of 25-Hydroxy and 1,25-Dihydroxy Vitamin D in Egyptian Children with Autism SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID D DEFICIENCY; CHRONIC DISEASES; OLDER-ADULTS; BRAIN; DISORDERS; SYSTEM; HEALTH; RATS; PREVALENCE; EXPRESSION AB Objective: The aim of this study was to investigate the potential role of vitamin D in autism through serum level assessment. Design: This was a case-controlled cross-sectional study. Setting: The study was conducted at the Out-patient Clinic for "Children with Special Needs'' at the Medical Services Unit of the National Research Centre in Cairo, Egypt. Subjects: Seventy (70) children with autism diagnosed according to the DSM-IV criteria of the American Psychiatric Association were recruited for this study. The mean age +/- standard deviation (SD) of the patients was 5.3 +/- 2.8 years. Controls included 42 age-matched randomly selected healthy children of the same socioeconomic status (mean age +/- SD, 6.1 +/- 1.8 years). Methods: Circulating levels of both forms of vitamin D (25(OH)D and 1,25(OH)(2)D) and serum calcium were measured for all subjects. Associations between vitamin D status, birth season, and clinical characteristics of autism were examined. Results: Children with autism had significantly lower 25(OH)D (p< 0.00001) and 1,25(OH)(2)D (p< 0.005) as well as lower calcium (p< 0.0001) serum values than the controls. A significant positive correlation was obtained between 25(OH)D and calcium (correlation coefficient r- 0.309, p< 0.01) within the children with autism. No significant difference was found on comparison of birth month and season of birth between children with autism and healthy controls. Furthermore, associations linking parental consanguinity or convulsions with vitamin D could not be established. Conclusions: Serum values of 25(OH)D in the children with autism of this study could classify them as being "vitamin D inadequate,'' which lends support to the hypothesis that autism is a vitamin D deficiency disorder. C1 [Sidhom, Gloria] Natl Res Ctr, Dept Clin & Chem Pathol, Cairo 11771, Egypt. [Meguid, Nagwa A.; Hashish, Adel F.; Anwar, Mona] Natl Res Ctr, Dept Res Children Special Needs, Cairo 11771, Egypt. RP Sidhom, G (reprint author), Natl Res Ctr, Dept Clin & Chem Pathol, POB 5216,Heliopolis W, Cairo 11771, Egypt. EM gloriasidhom@yahoo.com FU National Research Centre in Cairo, Egypt FX The authors would like to thank the National Research Centre in Cairo, Egypt for their financial support. 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TI INCREASING RESPONSE DIVERSITY IN CHILDREN WITH AUTISM SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; behavioral variability; lag reinforcement; stereotypy; response variability; stimulus variability ID REPETITIVE BEHAVIOR; SCHEDULES AB Repetitive and invariant behavior is a diagnostic feature of autism. We implemented a lag reinforcement schedule to increase response diversity for 6 participants with autism aged 6 to 10 years, 4 of whom also received prompting plus additional training. These procedures appeared to increase the variety of building-block structures, demonstrating that an intervention that includes differential reinforcement can increase response diversity for children with an autism spectrum disorder. C1 [Napolitano, Deborah A.] Univ Rochester, Sch Med, Div Neurodev & Behav Pediat, Rochester, NY 14642 USA. RP Napolitano, DA (reprint author), Univ Rochester, Sch Med, Div Neurodev & Behav Pediat, 601 Elmwood Ave,Box 671, Rochester, NY 14642 USA. EM deborah_napolitano@urmc.rochester.edu CR Bodfish JW, 2004, MENT RETARD DEV D R, V10, P318, DOI 10.1002/mrdd.20045 Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Cammilleri AP, 2005, J APPL BEHAV ANAL, V38, P111, DOI 10.1901/jaba.2005.34-04 GOETZ EM, 1973, J APPL BEHAV ANAL, V6, P209, DOI 10.1901/jaba.1973.6-209 Lang R, 2009, J APPL BEHAV ANAL, V42, P889, DOI 10.1901/jaba.2009.42-889 Lee R, 2006, J AUTISM DEV DISORD, V36, P421, DOI 10.1007/s10803-006-0080-7 Lee R, 2002, J APPL BEHAV ANAL, V35, P391, DOI 10.1901/jaba.2002.35-391 Napolitano DA, 2006, J DEV PHYS DISABIL, V18, P295, DOI 10.1007/s10882-006-9017-5 Neuringer A, 2004, AM PSYCHOL, V59, P891, DOI 10.1037/0003-066X.59.9.891 Pierce K, 2001, BIOL PSYCHIAT, V49, P655, DOI 10.1016/S0006-3223(00)01008-8 Sparrow SS, 2005, VINELAND ADAPTIVE BE Turner M, 1999, J CHILD PSYCHOL PSYC, V40, P839, DOI 10.1017/S0021963099004278 NR 12 TC 13 Z9 13 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2010 VL 43 IS 2 BP 265 EP 271 DI 10.1901/jaba.2010.43-265 PG 7 WC Psychology, Clinical SC Psychology GA 610YI UT WOS:000278776300006 PM 21119899 ER PT J AU Geiger, KB LeBlanc, LA Dillon, CM Bates, SL AF Geiger, Kaneen B. LeBlanc, Linda A. Dillon, Courtney M. Bates, Stephanie L. TI AN EVALUATION OF PREFERENCE FOR VIDEO AND IN VIVO MODELING SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; concurrent-chains schedules; modeling; preference assessment; video modeling ID AUTISM; CHILDREN; INTERVENTIONS; SPECTRUM AB We assessed preference for video or in vivo modeling using a concurrent-chains arrangement with 3 children with autism. The two modeling conditions produced similar acquisition rates and no differential selection (i.e., preference) for all 3 participants. C1 [LeBlanc, Linda A.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Dillon, Courtney M.; Bates, Stephanie L.] Western Michigan Univ, Kalamazoo, MI 49008 USA. RP LeBlanc, LA (reprint author), Auburn Univ, Dept Psychol, 226 Thach Hall, Auburn, AL 36849 USA. EM leblanc@auburn.edu CR Bellini S, 2007, EXCEPT CHILDREN, V73, P264 Charlop-Christy MH, 2000, J AUTISM DEV DISORD, V30, P537, DOI 10.1023/A:1005635326276 Corbett B. A., 2005, J EARLY INTENSIVE BE, V2, P2 Delano ME, 2007, REM SPEC EDUC, V28, P33, DOI 10.1177/07419325070280010401 Dowrick P. W., 1986, SOCIAL SURVIVAL CHIL Gilliam JE, 2006, GILLIAM AUTISM RATIN Hanley GP, 2005, J APPL BEHAV ANAL, V38, P51, DOI 10.1901/jaba.2005.6-04 LeBlanc LA, 2003, J APPL BEHAV ANAL, V36, P253, DOI 10.1901/jaba.2003.36-253 Lord C, 2000, J AUTISM DEV DISORD, V30, P205, DOI 10.1023/A:1005592401947 Marcus A, 2009, J APPL BEHAV ANAL, V42, P335, DOI 10.1901/jaba.2009.42-335 Sundberg M. L., 2008, VERBAL BEHAV MILESTO NR 11 TC 4 Z9 4 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2010 VL 43 IS 2 BP 279 EP 283 DI 10.1901/jaba.2010.43-279 PG 5 WC Psychology, Clinical SC Psychology GA 610YI UT WOS:000278776300008 PM 21119901 ER PT J AU Plavnick, JB Ferreri, SJ Maupin, AN AF Plavnick, Joshua B. Ferreri, Summer J. Maupin, Angela N. TI THE EFFECTS OF SELF-MONITORING ON THE PROCEDURAL INTEGRITY OF A BEHAVIORAL INTERVENTION FOR YOUNG CHILDREN WITH DEVELOPMENTAL DISABILITIES SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE autism; developmental disabilities; early childhood special education; procedural integrity; self-monitoring; token economy ID STUDENT BEHAVIOR; PERFORMANCE; FEEDBACK; TEACHERS AB The effects of self-monitoring on the procedural integrity of token economy implementation by 3 staff in a special education classroom were evaluated. The subsequent changes in academic readiness behaviors of 2 students with low-incidence disabilities were measured. Multiple baselines across staff and students showed that procedural integrity increased when staff used monitoring checklists, and students' academic readiness behavior also increased. Results are discussed with respect to the use of self-monitoring and the importance of procedural integrity in public school settings. C1 [Ferreri, Summer J.] Michigan State Univ, Coll Educ, E Lansing, MI 48824 USA. RP Ferreri, SJ (reprint author), Michigan State Univ, Coll Educ, 340 Erickson, E Lansing, MI 48824 USA. EM sferreri@msu.edu CR Allen SJ, 2003, SCHOOL PSYCHOL QUART, V18, P22, DOI 10.1521/scpq.18.1.22.20878 DiGennaro FD, 2005, SCHOOL PSYCHOL REV, V34, P220 Digennaro FD, 2007, J APPL BEHAV ANAL, V40, P447, DOI 10.1901/jaba.2007.40-447 HAGERMOSERSANET.LM, 2008, INT J BEHAV CONSULTA, V4, P95 Kazdin A. E., 1982, SINGLE CASE RES DESI Najdowski AC, 2008, J APPL BEHAV ANAL, V41, P459, DOI 10.1901/jaba.2008.41-459 RICHMAN GS, 1988, J APPL BEHAV ANAL, V21, P401, DOI 10.1901/jaba.1988.21-401 SELIGSONPETSCHE.E, 2006, J APPL BEHAV ANAL, V39, P215 NR 8 TC 7 Z9 7 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2010 VL 43 IS 2 BP 315 EP 320 DI 10.1901/jaba.2010.43-315 PG 6 WC Psychology, Clinical SC Psychology GA 610YI UT WOS:000278776300014 PM 21119907 ER PT J AU Vladescu, JC Kodak, T AF Vladescu, Jason C. Kodak, Tiffany TI A REVIEW OF RECENT STUDIES ON DIFFERENTIAL REINFORCEMENT DURING SKILL ACQUISITION IN EARLY INTERVENTION SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Review DE acquisition; differential reinforcement; early intervention; reinforcement quality; reinforcement schedules ID AUTISM; CHILDREN AB Although the use of differential reinforcement has been recommended in previous investigations and in early intervention curriculum manuals, few studies have evaluated the best method for providing differential reinforcement to maximize independent responding. This paper reviews previous research on the effectiveness of differential reinforcement as treatment and describes important areas of future research. C1 [Kodak, Tiffany] Univ Nebraska Med Ctr, Munroe Meyer Inst, Ctr Autism Spectrum Disorders, Omaha, NE 68198 USA. RP Kodak, T (reprint author), Univ Nebraska Med Ctr, Munroe Meyer Inst, Ctr Autism Spectrum Disorders, 985450 Nebraska Med Ctr, Omaha, NE 68198 USA. EM tkodak@unmc.edu CR Clark KM, 2004, J APPL BEHAV ANAL, V37, P503, DOI 10.1901/jaba.2004.37-503 Fisher WW, 2007, J APPL BEHAV ANAL, V40, P489, DOI 10.1901/jaba.2007.40-489 HAUSMAN NL, J APPL BEHA IN PRESS Karsten AM, 2009, J APPL BEHAV ANAL, V42, P327, DOI 10.1901/jaba.2009.42-327 Leaf R., 1999, WORK PROGR BEHAV MAN Lovaas O. I., 2003, TEACHING INDIVIDUALS Love JR, 2009, RES AUTISM SPECT DIS, V3, P421, DOI 10.1016/j.rasd.2008.08.008 OLENICK DL, 1980, J APPL BEHAV ANAL, V13, P77, DOI 10.1901/jaba.1980.13-77 TOUCHETTE PE, 1984, J APPL BEHAV ANAL, V17, P175, DOI 10.1901/jaba.1984.17-175 Walker G, 2008, J AUTISM DEV DISORD, V38, P261, DOI 10.1007/s10803-007-0390-4 NR 10 TC 2 Z9 2 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD SUM PY 2010 VL 43 IS 2 BP 351 EP 355 DI 10.1901/jaba.2010.43-351 PG 5 WC Psychology, Clinical SC Psychology GA 610YI UT WOS:000278776300020 PM 21119913 ER PT J AU Hobson, RP Lee, A Hobson, JA AF Hobson, R. Peter Lee, Anthony Hobson, Jessica A. TI Personal Pronouns and Communicative Engagement in Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Personal pronouns; Deixis; Eye gaze; Social interaction ID JOINT ATTENTION; CHILDREN; IDENTIFICATION; LANGUAGE; ACQUISITION; IMITATION; ENGLISH; SELF; ME AB In three experimental conditions, we tested matched children with and without autism (n = 15 per group) for their comprehension and use of first person plural ('we') and third person singular ('he') pronouns, and examined whether such linguistic functioning related to their social interaction. The groups were indistinguishable in their comprehension and use of 'we' pronouns, although within each group, such usage was correlated with ratings of interpersonal connectedness with the collaborator. On the other hand, participants with autism were less likely to use third person pronouns or to show patterns of eye gaze reflecting engagement with an interlocutor's stance vis-A -vis a third person. In these settings, atypical third person pronoun usage seemed to reflect limited communicative engagement, but first person pronouns were relatively spared. C1 [Hobson, R. Peter; Lee, Anthony; Hobson, Jessica A.] Tavistock Clin, London NW3 5BA, England. [Hobson, R. Peter; Hobson, Jessica A.] UCL, Inst Child Hlth, London, England. RP Hobson, RP (reprint author), Tavistock Clin, 120 Belsize Lane, London NW3 5BA, England. 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Bakeman, Roger TI Early Interests and Joint Engagement in Typical Development, Autism, and Down Syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Interests; Parent-child interaction; Autism; Down syndrome; Joint attention; Communication development ID YOUNG-CHILDREN; SPECTRUM DISORDER; ATTENTION; INFANTS; PLAY; RESPONSES; LANGUAGE; BEHAVIOR; STIMULI; PEOPLE AB This study examines how spontaneous interests in people and in objects relate to joint engagement in typically developing toddlers and young children with autism or Down syndrome. Ratings of interests were made repeatedly during intermissions in a laboratory-based protocol focused on caregiver-child interactions. Interests were moderated by diagnosis and relatively stable across intermissions. In autism, interest in people tended to be low and to decline rapidly, and the balance of interests favored familiar objects over people. 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TI Randomized Controlled Trial for Early Intervention for Autism: A Pilot Study of the Autism 1-2-3 Project SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Autism spectrum disorder (ASD); Early intervention; Social interaction; Communication; Autism diagnostic observation schedule (ADOS) ID SPECTRUM DISORDERS; YOUNG-CHILDREN; SYMBOLIC PLAY; STRESS; COMMUNICATION; PARENTS; SETTINGS; SERVICES; SKILLS; AGE AB We piloted a 2-week "Autism-1-2-3" early intervention for children with autism and their parents immediately after diagnosis that targeted at (1) eye contact, (2) gesture and (3) vocalization/words. Seventeen children were randomized into the Intervention (n = 9) and Control (n = 8) groups. Outcome measures included the Autism Diagnostic Observation Schedule, Ritvo-Freeman Real Life Rating Scale, Symbolic Play Test, and Parenting Stress Index. Children with autism improved in language/communication, reciprocal social interaction, and symbolic play. Parents perceived significant improvement in their children's language, social interaction, and their own stress level. This intervention can serve as short-term training on communication and social interaction for children with autism, and reduce the stress of their parents during the long waiting time for public health services. C1 [Wong, Virginia C. N.; Kwan, Queenie K.] Univ Hong Kong, Div Child Neurol Dev Paediat Neurohabilitat, Dept Paediat & Adolescent Med, Hong Kong, Peoples R China. RP Wong, VCN (reprint author), Univ Hong Kong, Div Child Neurol Dev Paediat Neurohabilitat, Dept Paediat & Adolescent Med, Pokfulam Rd, Hong Kong, Peoples R China. EM vcnwong@hku.hk CR Abidin RR, 1995, PARENTING STRESS IND Aldred C, 2004, J CHILD PSYCHOL PSYC, V45, P1420, DOI 10.1111/j1469-7610.2004.00338.x American Psychiatric Association, 2000, DIAGN STAT MAN MENT American Psychiatric Association, 2002, DIAGN STAT MAN MENT Anderson S. 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Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 677 EP 688 DI 10.1007/s10803-009-0916-z PG 12 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000003 PM 20020319 ER PT J AU Oosterling, I Roos, S de Bildt, A Rommelse, N de Jonge, M Visser, J Lappenschaar, M Swinkels, S van der Gaag, RJ Buitelaar, J AF Oosterling, Iris Roos, Sascha de Bildt, Annelies Rommelse, Nanda de Jonge, Maretha Visser, Janne Lappenschaar, Martijn Swinkels, Sophie van der Gaag, Rutger Jan Buitelaar, Jan TI Improved Diagnostic Validity of the ADOS Revised Algorithms: A Replication Study in an Independent Sample SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; ADOS; Algorithm; Sensitivity; Specificity; Diagnosis ID AUTISM SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; OBSERVATION-SCHEDULE; CHILDREN; ADOLESCENTS; INTERVIEW; CRITERIA AB Recently, Gotham et al. (2007) proposed revised algorithms for the Autism Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim of the current study was to replicate predictive validity, factor structure, and correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms for Modules 1 and 2 in a large independent Dutch sample (N = 532). Results showed that the improvement of diagnostic validity was most apparent for autism, except in very young or low functioning children. Results for other autism spectrum disorders were less consistent. Overall, these findings support the use of the more homogeneous revised algorithms, with the use of similar items across developmental cells making it easier to compare ADOS scores within and between individuals. C1 [Oosterling, Iris; Roos, Sascha; Rommelse, Nanda; Visser, Janne; Swinkels, Sophie; van der Gaag, Rutger Jan; Buitelaar, Jan] Karakter Child & Adolescent Psychiat Univ Ctr, NL-6525 GC Nijmegen, Netherlands. [Rommelse, Nanda; Lappenschaar, Martijn; Swinkels, Sophie; van der Gaag, Rutger Jan; Buitelaar, Jan] Radboud Univ Nijmegen Med Ctr, Dept Psychiat, Nijmegen, Netherlands. [de Bildt, Annelies] Univ Groningen, Univ Med Ctr Groningen, Child & Adolescent Psychiat Unit, NL-9713 AV Groningen, Netherlands. [de Jonge, Maretha] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. [Rommelse, Nanda; Swinkels, Sophie; van der Gaag, Rutger Jan; Buitelaar, Jan] NCEBP, Nijmegen, Netherlands. RP Oosterling, I (reprint author), Karakter Child & Adolescent Psychiat Univ Ctr, Reinier Postlaan 12, NL-6525 GC Nijmegen, Netherlands. EM i.oosterling@karakter.com RI Buitelaar, Jan/E-4584-2012; Rommelse, Nanda/D-4872-2009; Gaag, R.J./H-8030-2014 OI Buitelaar, Jan/0000-0001-8288-7757; Rommelse, Nanda/0000-0002-1711-0359; CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT BENTLER PM, 1990, PSYCHOL BULL, V107, P238, DOI 10.1037//0033-2909.107.2.238 Browne MW, 1993, TESTING STRUCTURAL E, P136, DOI DOI 10.1177/0049124192021002001 Chen P. 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TI Evaluation of the Efficacy of a Dental Plaque Control Program in Autistic Patients SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; OHI-S; Oral hygiene; Oral health; Dental plaque AB The aim of this study was to verify the efficacy of a programme for dental plaque control in autistics. Patients were evaluated on five occasions over a period of 180 days using the following instruments: OHI-S, DMF-T, the Fonnes brushing technique and diet questionnaire. Participants were divided into two groups according to level of co-operation on the programme: Group A (co-operative) and Group B (non-cooperative). A statistically significant improvement (p < 0.001) in Oral Hygiene was attained, with 84.2% showing regular or satisfactory hygiene at study end-point. Conclusion: Groups A and B both showed improvement in hygiene (p < 0.001 and p = 0.004), but improvement was significantly higher among co-operative patients (p < 0.001 at 180 days), who also had a higher mean age (p = 0.02). C1 [Dias, Guilherme G.; Prado, Eliane F. G. B.; Vadasz, Estevao] Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo, Brazil. [Dias, Guilherme G.; Prado, Eliane F. G. B.; Vadasz, Estevao] Univ Sao Paulo, Fac Med, Inst Psychiat, Sao Paulo, Brazil. [Siqueira, Jose Tadeu T.] Univ Sao Paulo, Fac Med, Hosp Clin, Dent Div, Sao Paulo, Brazil. RP Siqueira, JTT (reprint author), Rua Maria Candida 135,Vila Guilherme, BR-02071010 Sao Paulo, Brazil. EM guilhermegdias@yahoo.com.br; jtts@uol.com.br CR ASSUMPCAO FB, 1997, TRANSTORNOS INVASIVO ASSUNCAO WG, 2002, REV ODONTOLOGICA ARA, V23, P28 BASTING RT, 2000, REV ABO NACL, V8, P111 Fahlvik-Planefeldt C, 2001, SWED DENT J, V25, P113 Friedlander Arthur H, 2003, J Calif Dent Assoc, V31, P681 GREENE JC, 1964, J AM DENT ASSOC, V68, P7 GUEDESPINTO AC, 1999, REABILITACAO BUCAL O Hulland S, 2000, Spec Care Dentist, V20, P131, DOI 10.1111/j.1754-4505.2000.tb01149.x Kamen S, 1985, Spec Care Dentist, V5, P20, DOI 10.1111/j.1754-4505.1985.tb00928.x Klein U, 1999, Spec Care Dentist, V19, P200, DOI 10.1111/j.1754-4505.1999.tb01386.x Klein Ulrich, 1998, Pediatric Dentistry, V20, P312 Lowe O, 1985, ASDC J DENT CHILD, V3, P29 MAGALHAES MHC, 1997, RPG, V4, P109 Munro CL, 2006, BIOL RES NURS, V8, P35, DOI 10.1177/1099800406289343 Nomura Lincon Hideo, 2004, Braz Oral Res, V18, P134, DOI 10.1590/S1806-83242004000200008 Polyzois G L, 1989, Quintessence Int, V20, P775 QUIGLEY GA, 1962, J AM DENT ASSOC, V65, P26 *SECR EST SAUD SAO, 2002, COND SAUD BUC EST SA Shapira J, 1989, Spec Care Dentist, V9, P38, DOI 10.1111/j.1754-4505.1989.tb01022.x Surabian S R, 2001, J Calif Dent Assoc, V29, P424 TURESKY S, 1970, J PERIODONTOL, V41, P41, DOI 10.1902/jop.1970.41.1.41 VANGRUNSVEN MF, 1995, REV APCD, V49, P364 NR 22 TC 2 Z9 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 704 EP 708 DI 10.1007/s10803-009-0918-x PG 5 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000005 PM 20052608 ER PT J AU Reichle, J Johnson, L Monn, E Harris, M AF Reichle, Joe Johnson, LeAnne Monn, Emily Harris, Michael TI Task Engagement and Escape Maintained Challenging Behavior: Differential Effects of General and Explicit Cues When Implementing a Signaled Delay in the Delivery of Reinforcement SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Tolerance for delay; Signaled delay; Intervention; Self-regulation ID NEGATIVE REINFORCEMENT; DISRUPTIVE BEHAVIOR; EXTINCTION; CHILDREN; AUTISM; INTERVENTION; TOPOGRAPHIES; MANAGEMENT; REDUCTION; TOLERANCE AB This study was designed to evaluate the effects of explicit and general delay cues when implementing a tolerance for a delay in the delivery of a reinforcement procedure to increase task engagement and decrease escape maintained challenging behavior. Two preschool children with autism participated in an alternating treatments design with changing criterions for task engagement. For both children, descriptive and experimental analyses verified that the challenging behavior functioned to escape instructional task demands. Subsequently, two types of tasks were identified for each participant with assignment to either the explicit or general cue procedures. Both participants demonstrated increased task engagement with concurrent decreases in challenging behavior with both types of delay cues, though rate of successful work unit completion advanced more quickly with explicit delay cues. C1 [Reichle, Joe] Univ Minnesota, Dept Educ Psychol, Dept Speech Language Hearing Sci, Minneapolis, MN 55455 USA. [Harris, Michael] Univ Wisconsin, River Falls, WI 54022 USA. RP Reichle, J (reprint author), Univ Minnesota, Dept Educ Psychol, Dept Speech Language Hearing Sci, 250 Educ Sci Bldg,56 E River Rd, Minneapolis, MN 55455 USA. 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Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 709 EP 720 DI 10.1007/s10803-010-0946-6 PG 12 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000006 PM 20162345 ER PT J AU Kuhlthau, K Orlich, F Hall, TA Sikora, D Kovacs, EA Delahaye, J Clemons, TE AF Kuhlthau, Karen Orlich, Felice Hall, Trevor A. Sikora, Darryn Kovacs, Erica A. Delahaye, Jennifer Clemons, Traci E. TI Health-Related Quality of Life in Children with Autism Spectrum Disorders: Results from the Autism Treatment Network SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Quality of life; Behavior; Adaptive behavior ID HIGH-FUNCTIONING CHILDREN; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GENERIC CORE SCALES; INTELLECTUAL DISABILITY; PSYCHOMETRIC PROPERTIES; MATERNAL PERCEPTIONS; SLEEP PROBLEMS; ADOLESCENTS; POPULATION; PEDSQL(TM)-4.0 AB We examined data collected as a part of the Autism Treatment Network, a group of 15 autism centers across the United States and Canada. Mean Health-Related Quality of Life (HRQoL) scores of the 286 children assessed were significantly lower than those of healthy populations (according to published norms). When compared to normative data from children with chronic conditions, children with ASD demonstrated worse HRQoL for total, psychosocial, emotional and social functioning, but did not demonstrate differing scores for physical and school functioning. HRQoL was not consistently related to ASD diagnosis or intellectual ability. However, it was consistently related to internalizing and externalizing problems as well as repetitive behaviors, social responsiveness, and adaptive behaviors. Associations among HRQoL and behavioral characteristics suggest that treatments aimed at improvements in these behaviors may improve HRQoL. C1 [Kuhlthau, Karen; Delahaye, Jennifer] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Kuhlthau, Karen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Orlich, Felice] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Orlich, Felice] Seattle Childrens Hosp, Autism Program, Seattle, WA USA. [Hall, Trevor A.] Warm Springs Autism Diagnost & Treatment Ctr, Portland, OR USA. [Hall, Trevor A.; Sikora, Darryn] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kovacs, Erica A.] Columbia Univ, Med Ctr, Columbia Dev Neuropsychiat Program, Div Child & Adolescent Psychiat, New York, NY USA. [Clemons, Traci E.] EMMES Corp, Potomac, MD USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. EM kkuhlthau@partners.org CR Achenbach T. 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PD JUN PY 2010 VL 40 IS 6 BP 721 EP 729 DI 10.1007/s10803-009-0921-2 PG 9 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000007 PM 20033762 ER PT J AU Loth, E Happe, F Gomez, JC AF Loth, Eva Happe, Francesca Gomez, Juan Carlos TI Variety is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-life Events SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Theory of mind; Weak central coherence; Event schemas; Repetitive behaviours ID HIGH-FUNCTIONING AUTISM; WEAK CENTRAL COHERENCE; ASPERGER-SYNDROME; DOWN-SYNDROME; CHILDREN; MIND; INDIVIDUALS; PERFORMANCE; IMITATION; TASK AB This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in this type of situation. The ASD boys made significantly more errors than the typically developing boys in rating the occurrences of variable aspects. In both groups, ratings of variable aspects were age-related, but in the ASD boys, they were also related to theory of mind and weak coherence test scores, and to severity of autistic symptoms. Implications for the understanding of some repetitive behaviours, such as the tendency to adhere to inflexible routines, are discussed. C1 [Loth, Eva; Happe, Francesca] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Gomez, Juan Carlos] Univ St Andrews, Sch Psychol, St Andrews, Fife, Scotland. RP Loth, E (reprint author), Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, Crespigny Pk, London SE5 8AF, England. 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Folsom, Timothy D. Rooney, Robert J. Patel, Diven H. Thuras, Paul D. TI mRNA and Protein Levels for GABA(A)alpha 4, alpha 5, beta 1 and GABA(B)R1 Receptors are Altered in Brains from Subjects with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE GABBR1; GABR alpha 4; GABR alpha 5; GABR beta 1; Autism; Brain ID ACID DECARBOXYLASE 65; SUBUNIT GENES; NEURODEVELOPMENTAL DISORDERS; SIGNIFICANT ASSOCIATION; SPECTRUM DISORDERS; GABBR1 GENE; 67 KDA; EXPRESSION; SCHIZOPHRENIA; MOUSE AB We have shown altered expression of gamma-aminobutyric acid A (GABA(A)) and gamma-aminobutyric acid B (GABA(B)) receptors in the brains of subjects with autism. In the current study, we sought to verify our western blotting data for GABBR1 via qRT-PCR and to expand our previous work to measure mRNA and protein levels of 3 GABA(A) subunits previously associated with autism (GABR alpha 4; GABR alpha 5; GABR beta 1). Three GABA receptor subunits demonstrated mRNA and protein level concordance in superior frontal cortex (GABR alpha 4, GABR alpha 5, GABR beta 1) and one demonstrated concordance in cerebellum (GABI'R1). These results provide further evidence of impairment of GABAergic signaling in autism. C1 [Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Thuras, Paul D.] Univ Minnesota, Dept Psychiat, Sch Med, Div Neurosci Res, Minneapolis, MN 55455 USA. [Fatemi, S. Hossein] Univ Minnesota, Dept Pharmacol, Sch Med, Minneapolis, MN 55455 USA. [Fatemi, S. Hossein] Univ Minnesota, Dept Neurosci, Sch Med, Minneapolis, MN 55455 USA. [Rooney, Robert J.; Patel, Diven H.] Genome Explorat Inc, Memphis, TN USA. [Thuras, Paul D.] VA Med Ctr, Minneapolis, MN USA. RP Fatemi, SH (reprint author), Univ Minnesota, Dept Psychiat, Sch Med, Div Neurosci Res, 420 Delaware St SE MMC 392, Minneapolis, MN 55455 USA. 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Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 743 EP 750 DI 10.1007/s10803-009-0924-z PG 8 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000009 PM 20066485 ER PT J AU Bauminger, N Solomon, M Rogers, SJ AF Bauminger, Nirit Solomon, Marjorie Rogers, Sally J. TI Predicting Friendship Quality in Autism Spectrum Disorders and Typical Development SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE HFASD; Asperger syndrome; Friendship; Attachment; Theory of mind ID INDIVIDUAL-DIFFERENCES; ATTACHMENT; CHILDREN; SECURITY; ADOLESCENCE; BEHAVIOR; SCALE AB The role played by social relationship variables (attachment security; mother-child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children's descriptions of friendships (age 8-12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). 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Redash, Amanda Coleman, Katelyn Haimson, Jennifer Winner, Ellen TI 'Autistic' Local Processing Bias also Found in Children Gifted in Realistic Drawing SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Perceptual cohesiveness; Giftedness; Drawing ID HIGH-FUNCTIONING AUTISM; BLOCK DESIGN; TRAITS; SPECTRUM; INDIVIDUALS; PERFORMANCE; POPULATION; PERCEPTION; ABILITIES; ATTENTION AB We investigated whether typically-developing children with a gift for drawing realistically show the local processing bias seen in individuals with autism spectrum disorder (ASD). Twenty-seven 6-12 year-olds made an observational drawing (scored for level of realism) and completed three local processing tasks, and parents completed the Childhood Asperger Syndrome Test (CAST). Drawing score predicted local processing performance on all tasks independently of verbal IQ, age, and years of art lessons. 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Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 762 EP 773 DI 10.1007/s10803-009-0923-0 PG 12 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000011 PM 20049633 ER PT J AU Hippler, K Viding, E Klicpera, C Happe, F AF Hippler, Kathrin Viding, Essi Klicpera, Christian Happe, Francesca TI Brief Report: No Increase in Criminal Convictions in Hans Asperger's Original Cohort SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger syndrome; Autistic psychopathy; Convictions; Offending ID AUTISM SPECTRUM DISORDER; BEHAVIOR; PSYCHOPATHY; VIOLENCE AB Hans Asperger originally used the term "autistic psychopathy" to describe his patients on the autism spectrum, leading to a possible confusion with psychopathic disorder and delinquent behaviour. We conducted a penal register search for 177 former patients of Asperger's clinic with a childhood diagnosis of "autistic psychopathy" or features of the disorder in Austria. The mean percentage of registered convictions was similar to that in the general male population of Austria over the studied time period. A qualitative assessment of offence types in Asperger's former patients suggests that the nature of offences does not differ from that in the general population. In this original cohort of Asperger's patients, convictions were no more common than in the general male population. C1 [Hippler, Kathrin] Univ Klin Kinder & Jugendheilkunde, Tagesklin Stn Psychosomat, A-1090 Vienna, Austria. [Hippler, Kathrin; Klicpera, Christian] Univ Vienna, Dept Clin & Appl Psychol, Vienna, Austria. [Viding, Essi] UCL, Res Dept Clin Educ & Hlth Psychol, Div Psychol & Language Sci, London, England. [Happe, Francesca] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Hippler, K (reprint author), Med Univ Vienna, Dept Paediat & Adolescent Med, Vienna, Austria. EM kathrin.hippler@meduniwien.ac.at RI Happe, Francesca/D-5544-2012 CR Allen D, 2008, J AUTISM DEV DISORD, V38, P748, DOI 10.1007/s10803-007-0442-9 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Asperger H, 1944, ARCH PSYCHIAT NERVEN, V117, P76, DOI 10.1007/BF01837709 BARONCOHEN S, 1988, J CHILD PSYCHOL PSYC, V29, P351, DOI 10.1111/j.1469-7610.1988.tb00723.x Barry-Walsh JB, 2004, J FORENSIC PSYCHI PS, V15, P96, DOI 10.1080/14789940310001638628 Berney T, 2004, ADV PSYCHIAT TREATME, P341, DOI DOI 10.1192/APT.10.5.341 Blair RJR, 2005, CONSCIOUS COGN, V14, P698, DOI 10.1016/j.concog.2005.06.004 Chen PS, 2003, ACTA PSYCHIAT SCAND, V107, P73, DOI 10.1034/j.1600-0447.2003.01354.x Frith U., 1991, AUTISM ASPERGER SYND, P1, DOI 10.1017/CBO9780511526770.001 GHAZIUDDIN M, 1991, J AUTISM DEV DISORD, V21, P349, DOI 10.1007/BF02207331 GUTIERREZ-LOBOS K, 2006, BENACHTEILIGUNG MENS Hare D. 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PD JUN PY 2010 VL 40 IS 6 BP 774 EP 780 DI 10.1007/s10803-009-0917-y PG 7 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000012 PM 20024608 ER PT J AU Brown, JT AF Brown, Jane Thierfeld TI Realizing the College Dream with Autism or Asperger Syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Book Review C1 [Brown, Jane Thierfeld] Univ Connecticut, Sch Law, Coll Autism Spectrum LLC, Hartford, CT 06112 USA. RP Brown, JT (reprint author), Univ Connecticut, Sch Law, Coll Autism Spectrum LLC, Hartford, CT 06112 USA. EM jane.brown@law.uconn.edu CR BROWN JT, 2006, ANN PALMER REALIZING NR 1 TC 1 Z9 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JUN PY 2010 VL 40 IS 6 BP 782 EP 782 DI 10.1007/s10803-009-0846-9 PG 1 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000014 ER PT J AU Frazier, TW Youngstrom, EA Haycook, T Sinoff, A Dimitriou, F Knapp, J Sinclair, L AF Frazier, Thomas W. Youngstrom, Eric A. Haycook, Travis Sinoff, Aletta Dimitriou, Francine Knapp, Julie Sinclair, Leslie TI Effectiveness of Medication Combined with Intensive Behavioral Intervention for Reducing Aggression in Youth with Autism Spectrum Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; HIGH-FUNCTIONING AUTISM; BIPOLAR DISORDER; MENTAL-RETARDATION; CHILDREN; ADOLESCENTS; RISPERIDONE; EFFICACY; THERAPY AB Background: The use of antipsychotic medications to treat aggression in youths with autism spectrum disorders (ASD) is based on open-label trials and efficacy studies. There are no studies examining the combined effectiveness of antipsychotic medications and intensive behavioral intervention (IBI) to treat aggression in ASD. Methods: Youths with ASD and aggressive behavior received IBI. Medication use remained stable during the study period and was coded into antipsychotic, mood-stabilizing, and nonstimulant attention-deficit/hyperactivity disorder (ADHD)/sleep medication classes. Analysis of covariance (ANCOVA) and survival analyses examined the effects of medication classes on the average number of aggressive behaviors and time to behavior plan success. Results: Thirty-two youths (mean age = 11.16, standard deviation [SD] = 3.31, range =4-16 years, 75% male) with ASD received aggression reduction plans. Of these, 25 youths were taking at least one psychiatric medication (antipsychotic n = 18, mood stabilizing n = 10, and nonstimulant ADHD/sleep n = 12). Aggression dropped substantially following implementation of IBI (p< 0.001; d = 1.70). Antipsychotic medication use predicted significantly fewer sessions to achieve behavior plan success (x(2)(1) = 5.67, p = 0.017; d = 0.93). No other medication classes influenced aggressive behavior (largest x(2)(1) = 0.16, p = 0.694). Conclusions: Behavioral treatment combined with antipsychotic medication was the most effective approach to reducing aggressive behaviors in youths with ASD. Mood-stabilizing and nonstimulant ADHD/sleep medications did not contribute to aggression reduction. C1 [Frazier, Thomas W.; Haycook, Travis; Sinoff, Aletta; Dimitriou, Francine; Knapp, Julie; Sinclair, Leslie] Cleveland Clin, Ctr Autism, Cleveland, OH 44195 USA. [Frazier, Thomas W.] Cleveland Clin, Ctr Pediat Behav Hlth, Cleveland, OH 44195 USA. [Youngstrom, Eric A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Youngstrom, Eric A.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Frazier, TW (reprint author), Cleveland Clin, Ctr Autism CR11, 9500 Euclid Ave, Cleveland, OH 44195 USA. 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Child Adolesc. Psychopharmacol. PD JUN PY 2010 VL 20 IS 3 BP 167 EP 177 DI 10.1089/cap.2009.0048 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 615WA UT WOS:000279167600001 PM 20578929 ER PT J AU Russell, G Ford, T Steer, C Golding, J AF Russell, Ginny Ford, Tamsin Steer, Colin Golding, Jean TI Identification of children with the same level of impairment as children on the autistic spectrum, and analysis of their service use SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism; pervasive developmental disorders; Asperger's syndrome; epidemiology; prevalence; child mental health ID PREVALENCE; DISORDERS; COHORT AB Background: Data from epidemiology have consistently highlighted a disparity between the true prevalence of childhood psychiatric disorders and their recognition as defined by receiving a clinical diagnosis. Few studies have looked specifically at the level of unidentified autistic spectrum disorder (ASD) in the population. Method: Logistic regression was used to determine the behavioural traits associated with receiving a diagnosis of ASD using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). A composite score was derived to measure levels of autistic traits; undiagnosed children with scores matching those diagnosed with ASD were identified. Levels of educational provision beyond that provided by standard schooling were examined. Results: Fifty-five percent of children with autistic traits at the same levels as those who had an autism diagnosis had not been identified as needing extra support from education or specialised health services. Of those who were identified as having special needs, 37.5% had been formally diagnosed with an ASD. For children with impairment at the same level as that associated with Asperger's syndrome, 57% had no special provision at school, and were not accessing specialised health services. Twenty-six percent of those who did have special provision at school had an ASD diagnosis. Conclusions: The results suggest that there may be a substantial proportion of children on the autistic spectrum who are never identified by services. C1 [Russell, Ginny] Univ Exeter, ESRC Ctr Genom Soc, Exeter EX4 4PJ, Devon, England. [Ford, Tamsin] Peninsula Coll Med & Dent, Inst Hlth Serv Res, Exeter, Devon, England. [Steer, Colin; Golding, Jean] Univ Bristol, Dept Community Based Med, Bristol BS8 1TH, Avon, England. RP Russell, G (reprint author), Univ Exeter, ESRC Ctr Genom Soc, Byrne House,St Germans Rd, Exeter EX4 4PJ, Devon, England. EM g.russell@ex.ac.uk FU Medical Research Council; Economic and Social Research Council FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. The work of the first author was specifically funded by the Medical Research Council and Economic and Social Research Council. We would also like to thank Brahm Norwich for his helpful comments. 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Child Psychol. Psychiatry PD JUN PY 2010 VL 51 IS 6 BP 643 EP 651 DI 10.1111/j.1469-7610.2010.02233.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 594HI UT WOS:000277526700002 PM 20345841 ER PT J AU Tadic, V Pring, L Dale, N AF Tadic, Valerie Pring, Linda Dale, Naomi TI Are language and social communication intact in children with congenital visual impairment at school age? SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Visual impairment; language; social communication; autism ID BLIND-CHILDREN; YOUNG-CHILDREN; AUTISM; MIND; EMOTION; SETBACK AB Background: Development of children with congenital visual impairment (VI) has been associated with vulnerable socio-communicative outcomes often bearing striking similarities to those of sighted children with autism.1 To date, very little is known about language and social communication in children with VI of normal intelligence. Methods: We examined the presentation of language and social communication of 15 children with VI and normal-range verbal intelligence, age 6-12 years, using a standardised language assessment and parental reports of everyday social and communicative behaviours. Their profiles were compared to those of typically developing sighted children of similar age and verbal ability. Results: Compared to their sighted peers, and relative to their own good and potentially superior structural language skills, children with VI showed significantly poorer use of language for social purposes. Pragmatic language weaknesses were a part of a broader socio-communicative profile of difficulties, present in a substantial proportion of these children and consistent with the pattern found in sighted children with autism. Conclusions: There are ongoing socio-communicative and pragmatic language difficulties in children with congenital VI at school age, despite their good intellectual abilities and advanced linguistic skills. Further research is required to unpack the underlying causes and factors maintaining this vulnerability in such children. C1 [Tadic, Valerie] UCL Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, London WC1E 2EH, England. [Tadic, Valerie; Pring, Linda] Univ London, London WC1E 7HU, England. [Dale, Naomi] Great Ormond St Hosp NHS Trust, London, England. RP Tadic, V (reprint author), UCL Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, 30 Guildford St, London WC1E 2EH, England. EM v.tadic@ich.ucl.ac.uk FU ESRC [PTA-031-2004-00211] FX The authors thank the children and their families who participated in this research. The research was supported by a 1 + 3 ESRC studentship (PTA-031-2004-00211) awarded to the first author while completing a PhD at Goldsmiths, University of London. 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TI Perception of shapes targeting local and global processes in autism spectrum disorders SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism; local processing; global processing; ventral visual pathway; radial frequency patterns ID DEVELOPMENTAL DISORDERS; VISUAL-PERCEPTION; COGNITIVE-STYLE; WEAK COHERENCE; FORM VISION; MOTION; CHILDREN; INFORMATION; CONTOURS; RECOGNITION AB Background: Several researchers have found evidence for impaired global processing in the dorsal visual stream in individuals with autism spectrum disorders (ASDs). However, support for a similar pattern of visual processing in the ventral visual stream is less consistent. Critical to resolving the inconsistency is the assessment of local and global form processing ability. Methods: Within the visual domain, radial frequency (RF) patterns - shapes formed by sinusoidally varying the radius of a circle to add 'bumps' of a certain number to a circle - can be used to examine local and global form perception. Typically developing children and children with an ASD discriminated between circles and RF patterns that are processed either locally (RF24) or globally (RF3). Results: Children with an ASD required greater shape deformation to identify RF3 shapes compared to typically developing children, consistent with difficulty in global processing in the ventral stream. No group difference was observed for RF24 shapes, suggesting intact local ventral-stream processing. Conclusions: These outcomes support the position that a deficit in global visual processing is present in ASDs, consistent with the notion of Weak Central Coherence. C1 [Grinter, Emma J.; Maybery, Murray T.; Pellicano, Elizabeth; Badcock, David R.] Univ Western Australia, Sch Psychol, Perth, WA 6009, Australia. [Badcock, Johanna C.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Graylands Hosp, Ctr Clin Res Neuropsychiat, Perth, WA 6009, Australia. [Pellicano, Elizabeth] Univ Bristol, Dept Expt Psychol, Bristol BS8 1TH, Avon, England. RP Grinter, EJ (reprint author), Univ Western Australia, Sch Psychol, 35 Stirling Highway, Perth, WA 6009, Australia. EM emmagrinter@graduate.uwa.edu.au RI Badcock, David/A-4913-2008; Badcock, Johanna/C-3682-2013; Maybery, Murray/H-5390-2014 OI Badcock, David/0000-0002-4517-435X; Badcock, Johanna/0000-0003-4629-2929; FU NHMRC [403942] FX This research was supported by NH&MRC Project Grant 403942 awarded to M. T. Maybery, D. R. Badcock, J. C. Badcock and E. Pellicano. 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TI Language-related Cntnap2 Gene is Differentially Expressed in Sexually Dimorphic Song Nuclei Essential for Vocal Learning in Songbirds SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE autism; avian; birdsong; CASPR2; contactin; neurexin; zebra finch ID ZEBRA FINCH SONG; AUTISM-SPECTRUM DISORDERS; GANGLIA-FOREBRAIN CIRCUIT; RECEPTOR MESSENGER-RNA; AXONAL CONNECTIONS; MYELINATED AXONS; TELENCEPHALIC NUCLEUS; NEUREXIN SUPERFAMILY; HUMAN SPEECH; K+ CHANNELS AB Multiple studies, involving distinct clinical populations, implicate contactin associated protein-like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language. J. Comp. Neurol. 518:1995-2018,2010. (C) 2010 Wiley-Liss, Inc. C1 [Panaitof, S. Carmen; White, Stephanie A.] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. [Abrahams, Brett S.; Dong, Hongmei; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurobehav Genet, Los Angeles, CA 90095 USA. [Abrahams, Brett S.; Dong, Hongmei; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP White, SA (reprint author), Univ Calif Los Angeles, Dept Physiol Sci, 621 Charles E Young Dr, Los Angeles, CA 90095 USA. EM sawhite@ucla.edu FU National Institutes of Health [RO1 MH070712, R21 HD06527, RO1 MH64547, U54 MH68172, P50 HD055784]; Autism Speaks; Foundation for Psychocultural Research FX Grant sponsor: National Institutes of Health; Grant numbers: RO1 MH070712, R21 HD06527, RO1 MH64547, U54 MH68172, P50 HD055784; Grant sponsor: Autism Speaks; Grant sponsor: Foundation for Psychocultural Research. 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PD JUN 1 PY 2010 VL 518 IS 11 BP 1995 EP 2018 DI 10.1002/cne.22318 PG 24 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 591ID UT WOS:000277292700008 PM 20394055 ER PT J AU Barbaro, J Dissanayake, C AF Barbaro, Josephine Dissanayake, Cheryl TI Prospective Identification of Autism Spectrum Disorders in Infancy and Toddlerhood Using Developmental Surveillance: The Social Attention and Communication Study SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism spectrum disorders; developmental surveillance; screening; infants; toddlers; prospective identification; community-based ID TRAITS QUESTIONNAIRE ESAT; FOLLOW-UP; DIAGNOSTIC INTERVIEW; PRESCHOOL-CHILDREN; MENTAL-RETARDATION; MODIFIED CHECKLIST; HOME VIDEOTAPES; YOUNG-CHILDREN; ADI-R; AGE AB Objective: Despite behavioral markers of autism spectrum disorders (ASDs) being evident within the first year of life, there remains little research on the prospective identification of these children in a community-based setting before 18 months. The aim in the Social Attention and Communication Study was to identify infants and toddlers at risk of an ASD during their first 2 years. Methods: A total of 241 Maternal and Child Health nurses were trained on the early signs of ASDs at 8, 12, 18 and 24 months. Using a developmental surveillance approach with a community-based sample, a cohort of 20,770 children was monitored on early social attention and communication behaviors. Those infants/toddlers identified as "at risk" were referred to the Social Attention and Communication Study team from 12 months for developmental and diagnostic assessments at 6 monthly intervals, until 24 months. Results: A total of 216 children were referred, with 110 being further assessed. Of these, 89 children were classified with an ASD at 24 months, and 20 children had developmental and/or language delays, resulting in a Positive Predictive value of 81%. The estimated rate of ASDs in the Social Attention and Communication Study cohort ranged from 1: 119 to 1: 233 children. Estimated sensitivity ranged from 69% to 83.8%, and estimated specificity ranged from 99.8% to 99.9%. Conclusion: Developmental surveillance of social and communication behaviors, which differ according to the age at which the child is monitored, enables the accurate identification of children at risk for ASDs between 12 and 24 months. Education on the early signs is recommended for all primary health care professionals to facilitate early identification of ASDs. C1 [Barbaro, Josephine; Dissanayake, Cheryl] La Trobe Univ, Olga Tennison Autism Res Ctr, Sch Psychol Sci, Bundoora, Vic 3086, Australia. RP Dissanayake, C (reprint author), La Trobe Univ, Olga Tennison Autism Res Ctr, Sch Psychol Sci, Bundoora, Vic 3086, Australia. 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TI Examining Issues of Aided Communication Display and Navigational Strategies for Young Children with Developmental Disabilities SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE Augmentative and alternative communication; Aided communication; Young children; Navigation; Display ID AAC TECHNOLOGIES; MENTAL-RETARDATION; AUTISM; INDIVIDUALS; PERFORMANCE; ATTENTION; LAYOUTS; DEFICIT; ADULTS; TASK AB Gestural mode and graphic mode augmentative communication systems offer viable options for young communicators with cognitive and physical disabilities that preclude speech or result in speech that has insufficient intelligibility to be understood by a range of communicative partners. This article examines issues related to strategies of interest to interventionists that focus on navigating displays of aided communication systems utilizing displays of graphic symbols. 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PD JUN PY 2010 VL 22 IS 3 BP 289 EP 311 DI 10.1007/s10882-010-9191-3 PG 23 WC Rehabilitation SC Rehabilitation GA 584AD UT WOS:000276721500006 ER PT J AU Tsuchiya, KJ Matsumoto, K Suda, S Miyachi, T Itoh, H Kanayama, N Hirano, K Ohzeki, T Takei, N AF Tsuchiya, K. J. Matsumoto, K. Suda, S. Miyachi, T. Itoh, H. Kanayama, N. Hirano, K. Ohzeki, T. Takei, N. CA HBC Study Team TI Searching for very early precursors of autism spectrum disorders: the Hamamatsu Birth Cohort for Mothers and Children (HBC) SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE autism; birth cohort study; child development; Japan; low birthweight; parental age ID PERVASIVE DEVELOPMENTAL DISORDERS; UNINTENDED PREGNANCY; POSTNATAL DEPRESSION; PATERNAL AGE; RISK-FACTORS; SOCIOECONOMIC-STATUS; LANGUAGE-DEVELOPMENT; EARLY-CHILDHOOD; JAPANESE WOMEN; YOUNG-CHILDREN AB Autism spectrum disorders (ASD) are life-long neurodevelopmental conditions. The pathophysiology is poorly understood, and the clinical diagnosis can only be made through behavioural assessments. The prevalence of ASD has increased eight-fold over the last three decades. Paralleling this rise, research interest in the disorder has been accumulating, centering on two aspects: risk factors that would explain the increase in prevalence, and precursors that could predict an emergence of ASD prior to 2 years of age. As regard factors responsible for the increased prevalence, an increasing trend of low birthweight (4.2% in 1980 v. 9.6% in 2006 at Japan) and advanced paternal age at birth are potentially implicated. To explore these issues, and to yield an early diagnostic algorithm for ASD, the authors initiated the ongoing Hamamatsu Birth Cohort for Mothers and Children (HBC) in 2007. The strengths of the HBC include frequent, direct face-to-face assessments of all the participating mothers and children during the first 4 years of life (12 assessments); this depth of assessments will disclose subtle changes in the developmental domains of individuals with ASD, which might otherwise be overlooked. A total of 1200 pregnant women are to be recruited by the end of 2010. Assembled information comprises a range of variables related to the mother's characteristics and child development. The comprehensiveness of the HBC will provide an informative data source that will elucidate early trajectories of children with ASD in addition to revealing detailed, developmental properties of typically developing children. C1 [Tsuchiya, K. J.; Matsumoto, K.; Suda, S.; Miyachi, T.; Takei, N.] Hamamatsu Univ Sch Med, Res Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan. [Tsuchiya, K. J.; Ohzeki, T.; Takei, N.] Kanazawa Univ, Osaka Univ, United Grad Sch Child Dev, Dept Child Dev, Hamamatsu, Shizuoka, Japan. [Itoh, H.; Kanayama, N.] Hamamatsu Univ Sch Med, Dept Obstet & Gynaecol, Hamamatsu, Shizuoka 4313192, Japan. [Hirano, K.; Ohzeki, T.] Hamamatsu Univ Sch Med, Dept Paediat, Hamamatsu, Shizuoka 4313192, Japan. [Takei, N.] Kings Coll London, Inst Psychiat, Div Psychol Med, London SE5 8AF, England. RP Tsuchiya, KJ (reprint author), Handayama 1 Higashiku, Hamamatsu, Shizuoka 4313192, Japan. EM tsuchiya@hama-med.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology, Japan [18591280]; National Center for Child Health and Development [21S-3, 19KOU-3]; [14370288] FX The authors thank the following for their help and support: Dr Tetsuo Kato of the Kato Maternity Clinic, Hamamatsu; Professor Toshihiko Terao, the Dean of the Hamamatsu University School of Medicine; and Professor Satoshi Nakamura, the Head of the University Hospital of the Hamamatsu University School of Medicine. The authors also thank Dr Yoko Kamio and Dr Makiko Okuyama for their helpful comments on maintaining the HBC. This study was financially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Dr K. J. Tsuchiya is the recipient of a Grant-in-Aid for Science Research (C) (2) (No. 18591280) and a grant for the National Center for Child Health and Development (21S-3). Professor N. Takei is the recipient of a Grant-in-Aid for Science Research (B) (2) (No. 14370288). Professors T. Ohzeki and N. Takei, Drs K. J. Tsuchiya and T. Miyachi, and Kaori Matsumoto are the recipients of a grant for the National Center for Child Health and Development (19KOU-3). The HBC Study Team includes Ms Riyo Takabayashi, Ms Tsuruko Mori, Ms Hiroko Muraki, Ms Chie Shimmura, Ms Noriko Kodera, Mr Shun Takahashi, Ms Michiyo Nishizawa, Ms Yukiko Suzuki, Ms Rieko Sato, and Drs Keiko Iwata, Anitha A. Pillai, Thanseem Ismail, Hideo Matsuzaki, Shu Takagai, Genichi Sugihara, Mayuko Kamo, Yosuke Kameno, Mariko Shima, Yujiro Yoshihara, Tomoyasu Wakuda, Katsuaki Suzuki, Shigeyuki Yamamoto, Masayoshi Kawai, Kazuhiko Nakamura, Masatsugu Tsujii, Toshirou Sugiyama, Norio Mori, Yusaku Endoh, and Teruhiko Suzuki. The authors thank Drs Kazuhiro Sugihara, Motoi Sugimura, Kinya Takeuchi, Kazunao Suzuki, Toshiyuki Uchida, Yasuhiro Komura, Yuusuke Murakami, Yasuhiro Koumura, Yuuki Miyabe, Kyuya Hirai, Toshiaki Kaga, Yuki Nakamura, Rui Koizumi, Hirotake Murakami, Yukiko Kobayashi, Ayako Mochizuki, Masako Otome, Hiroko Tajima and all the attending obstetricians for enrolling pregnant women to participate in the study and collecting cord blood samples. The authors thank the chief midwife, Ms Kiyomi Hinoki and all the midwives and staff at the maternity clinic of the Hamamatsu University School of Medicine, for enrolling participants and facilitating recruitment. The authors also thank Drs Yuichi Nakagawa, Satoru Iwashima, Masanori Yamamoto, Eiko Nagata and all the paediatricians and staff at the Department of Paediatrics at the Hamamatsu University School of Medicine for collecting the medical history of the children, including the NICU data. 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Dev. Orig. Health Dis. PD JUN PY 2010 VL 1 IS 3 BP 158 EP 173 DI 10.1017/S2040174410000140 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 755DH UT WOS:000289906400003 PM 25141784 ER PT J AU Baas, TH van Raaij, WF AF Baas, Tjerk H. van Raaij, W. Fred TI 'Familiar or risky': The Asperger syndrome affects exploratory consumer behaviour SO JOURNAL OF ECONOMIC PSYCHOLOGY LA English DT Article DE Autism; Asperger syndrome; Consumer behaviour; Exploratory behaviour ID OPTIMUM STIMULATION LEVEL; SPECTRUM QUOTIENT AQ; GENERAL-POPULATION; AUTISTIC TRAITS; PERSONALITY AB The objective of this study is to assess whether Asperger-syndrome characteristics negatively affect exploratory consumer behaviour. The Asperger syndrome is a complex autism syndrome leading to restrictions in people's (non-)verbal communication, imagination, and acquisition and maintenance of social contacts. Exploratory consumer behaviour is defined as the behaviour to discover and to try new products or services. The results show that higher Autism-Spectrum Quotient scores, indicating the Asperger syndrome, lead to lower tendencies for exploratory consumer behaviour, both in general and on six of the seven subscales (repetitive behaviour proneness, innovativeness, risk taking, exploration through shopping, interpersonal communication, and brand switching). Asperger is not a distinct disorder, but many people have a few autism characteristics. This means that these results are relevant for a much larger group than just the people with an Asperger-syndrome diagnosis. (C) 2010 Elsevier B.V. All rights reserved. C1 [van Raaij, W. Fred] Tilburg Univ, Sch Social Sci, NL-5000 LE Tilburg, Netherlands. [Baas, Tjerk H.] Radboud Univ Nijmegen, Inst Appl Social Sci, NL-6525 ED Nijmegen, Netherlands. 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Econ. Psychol. PD JUN PY 2010 VL 31 IS 3 BP 471 EP 477 DI 10.1016/j.joep.2010.02.002 PG 7 WC Economics; Psychology, Multidisciplinary SC Business & Economics; Psychology GA 609IF UT WOS:000278648900019 ER PT J AU Rieth, CA Huber, DE AF Rieth, Cory A. Huber, David E. TI Priming and Habituation for Faces: Individual Differences and Inversion Effects SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article DE face perception; short-term priming; individual differences; habituation ID CONFIGURAL INFORMATION; REPETITION BLINDNESS; SELECTIVE ATTENTION; SYNAPTIC DEPRESSION; NEURAL-NETWORK; RECOGNITION; PERCEPTION; INTEGRATION; MECHANISMS; AUTISM AB Immediate repetition priming for faces was examined across a range of prime durations in a threshold identification task. Similar to word repetition priming results, short duration face primes produced positive priming whereas long duration face primes eliminated or reversed this effect. A habituation model of such priming effects predicted that the speed of identification should relate to the prime duration needed to achieve negative priming. We used face priming to test this prediction in two ways. First, we examined the relationship between priming effects and individual differences in the target duration needed for threshold performance. Second, we compared priming of upright and inverted faces. As predicted, the transition from positive to negative priming as a function of prime duration occurred more slowly for inverted faces and for individuals with longer threshold target durations. Additional experiments ruled out alternative explanations. C1 [Rieth, Cory A.; Huber, David E.] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Rieth, CA (reprint author), Univ Calif San Diego, Dept Psychol, 0109,9500 Gilman Dr, La Jolla, CA 92093 USA. EM crieth@ucsd.edu FU NIMH [MH63993-01, MH063993-04]; NSF IGERT [DGE-0333451] FX This research was supported by NIMH Grants MH63993-01, MH063993-04, and by NSF IGERT Grant DGE-0333451 to GW Cottrell/VR de Sa. The authors would like to thank Jim Tanaka for his generosity in allowing for the use of his real face stimuli. 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Exp. Psychol.-Hum. Percept. Perform. PD JUN PY 2010 VL 36 IS 3 BP 596 EP 618 DI 10.1037/a0018737 PG 23 WC Psychology; Psychology, Experimental SC Psychology GA 602YC UT WOS:000278174000006 PM 20515191 ER PT J AU Sage, KD Jegatheesan, B AF Sage, Kara D. Jegatheesan, Brinda TI Perceptions of siblings with autism and relationships with them: European American and Asian American siblings draw and tell SO JOURNAL OF INTELLECTUAL & DEVELOPMENTAL DISABILITY LA English DT Article DE perception of autism; sibling relationship; diversity ID SPECTRUM DISORDERS; MENTAL-RETARDATION; YOUNG-CHILDREN; DOWN-SYNDROME; BROTHERS; SISTERS; DISABILITIES; FAMILIES; INDIVIDUALS; QUALITY AB Background This study examined typically developing children's perceptions of their siblings with autism and their relationships with them in a European American and an Asian American family. 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TI Early childhood predictors of mothers' and fathers' relationships with adolescents with developmental disabilities SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE developmental disabilities; parent-child relationship; parent-adolescent relationship; parenting stress; behaviour problems; early intervention ID DOWN-SYNDROME ADVANTAGE; BEHAVIOR PROBLEMS; PARENTING STRESS; INTELLECTUAL DISABILITIES; RELATIONSHIP QUALITY; SOCIOECONOMIC-STATUS; SPECTRUM DISORDERS; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; AUTISM AB Background The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of questions regarding these relationships. In particular, we asked: are there differences in the relationships of mothers and fathers with their adolescent with DD? Are there early childhood predictors of the parent-teen relationship and are those based on variables that are amenable to intervention? Finally, do these predictors differ for mothers and fathers? Methods This study focused on the relationships of 72 mothers and 53 fathers with their 15-year-old teens with DD and their predictors from the early childhood years. Data were collected from parents through interviews and self-administered questionnaires, and from their children with disabilities through structured assessment when children were age 3 years and again at age 15 years. Results Analyses indicated that both mother-teen and father-teen relationships were predicted by earlier parenting stress. The father-teen relationship was also predicted by early behaviour problems, but this relation was mediated by parenting stress. Socio-economic status, type of disability and the child's level of functioning were not predictive of later relationships between parents and teens. Mothers and fathers did not differ significantly in their reports of perceived positive relationships with their teens. Conclusions The findings from this study suggest two important points of potential intervention during the early intervention years. First, parenting assistance and support to reduce stress during the early childhood years can benefit both mothers and fathers. Second, helping families and children cope with and diminish problem behaviours is likely to yield multiple advantages for parents and children and deserves emphasis in early intervention and pre-school programmes. C1 [Mitchell, D. B.] Boston Coll, Lynch Sch Educ, Chestnut Hill, MA 02167 USA. RP Mitchell, DB (reprint author), Boston Coll, Lynch Sch Educ, Camp Hall 239, Chestnut Hill, MA 02167 USA. 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PD JUN PY 2010 VL 54 BP 487 EP 500 DI 10.1111/j.1365-2788.2010.01268.x PN 6 PG 14 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 596UF UT WOS:000277710300002 PM 20367745 ER PT J AU Kroeger, K Sorensen, R AF Kroeger, K. Sorensen, R. TI A parent training model for toilet training children with autism SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE autism; continence; parent training; self-initiation; toilet training; voiding ID PERVASIVE DEVELOPMENTAL DISORDER; DIURNAL BLADDER CONTROL; RESPONSE RESTRICTION AB Background Azrin & Foxx pioneered an intensive toilet training protocol for individuals with intellectual disability living in a residential setting. Since the development of the Rapid Toilet Training (RTT) protocol, many have replicated the efficacy, most notably in educational and outpatient treatment settings, but often training over longer periods of time. This study presents data from a parent training model that replicates Azrin and Foxx's results and training time. Method This multiple baseline across subjects design study employs an ABA design where two boys diagnosed with autism were toilet trained using a modified Azrin & Foxx intensive teaching protocol. The first subject, a 4-year-old boy, did not have a history of attempted toilet training. The second subject, a 6-year-old boy, demonstrated a history of failed toilet training attempts in both the home and school settings. The trainings were conducted in the home setting where a novel parent-training approach was implemented. Results Participant 1 was continent at the end of the second day of training, and completely toilet trained (including initiation and communication) by day 10 of the intervention. Participant 2 was continent after day 1 and completely toilet trained by day 5 of the intervention. Conclusions Long-term follow-up demonstrates maintenance of skills 3 years post training. Social validity via parent satisfaction was assessed. Limitations to the current study and recommendations for future research were discussed. C1 [Kroeger, K.; Sorensen, R.] Cincinnati Childrens Hosp, Med Ctr, Kelly OLeary Ctr Autism Spectrum Disorders, Cincinnati, OH USA. RP Kroeger, K (reprint author), ML 4002,3333 Burnet Ave, Cincinnati, OH 45229 USA. 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Intell. Disabil. Res. PD JUN PY 2010 VL 54 BP 556 EP 567 DI 10.1111/j.1365-2788.2010.01286.x PN 6 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 596UF UT WOS:000277710300008 PM 20576064 ER PT J AU Greimel, E Schulte-Ruther, M Fink, GR Piefke, M Herpertz-Dahlmann, B Konrad, K AF Greimel, E. Schulte-Ruether, M. Fink, G. R. Piefke, M. Herpertz-Dahlmann, B. Konrad, K. TI Development of neural correlates of empathy from childhood to early adulthood: an fMRI study in boys and adult men SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE fMRI; Development; Empathy; Mirror neuron system; Fusiform gyrus ID FUSIFORM FACE AREA; MIRROR NEURON; FACIAL EXPRESSIONS; GENDER-DIFFERENCES; AMYGDALA RESPONSE; COGNITIVE EMPATHY; SELF-FACE; ADOLESCENCE; CHILDREN; BRAIN AB Although empathy is rooted early in life, the ability to understand and share the emotions of others continues to develop after childhood. Here, we aimed at exploring developmental changes in the neural mechanisms underlying empathy from childhood to early adulthood. Using functional magnetic resonance imaging, 47 healthy male subjects aged 8-27 years were investigated during an explicit empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). A perceptual decision on the width of faces was used as a control condition. Age-related activity increases were observed in the fusiform gyrus and inferior frontal gyrus, depending on whether subjects attributed emotions to self or other. During the self-task, activity in the right precuneus and right intraparietal sulcus decreased as a function of age. No age-related differences were observed in behavioral performance measures. Increased activity in the fusiform gyrus and in the frontal component of the human mirror neuron system with increasing age may be explained by greater experience and expertise accumulated during socio-emotional interactions. Greater recruitment of right parietal structures in younger as compared to older subjects might reflect developmental differences in the cognitive strategies to infer one's own emotional response. This study is the first to show developmental changes in the neural mechanisms supporting empathy. Our findings may have important implications for the development of novel therapeutic interventions in clinical conditions characterized by empathy deficits, such as autism spectrum disorder. C1 [Greimel, E.; Schulte-Ruether, M.; Konrad, K.] Rhein Westfal TH Aachen, Univ Hosp, Dept Child & Adolescent Psychiat & Psychotherapy, Child Neuropsychol Sect, D-52074 Aachen, Germany. [Greimel, E.; Schulte-Ruether, M.; Fink, G. R.] Res Ctr Julich, Inst Neurosci & Med INM 3, Cognit Neurol Sect, D-52425 Julich, Germany. [Fink, G. R.] Univ Hosp Cologne, Dept Neurol, D-50924 Cologne, Germany. [Piefke, M.] Univ Bielefeld, Dept Biol, Cognit Neurosci Sect, D-33615 Bielefeld, Germany. RP Greimel, E (reprint author), Rhein Westfal TH Aachen, Univ Hosp, Dept Child & Adolescent Psychiat & Psychotherapy, Child Neuropsychol Sect, D-52074 Aachen, Germany. EM egreimel@ukaachen.de RI Schulte-Ruther, Martin /F-4784-2013; Konrad, Kerstin/H-7747-2013; Fink, Gereon/E-1616-2012 OI Schulte-Ruther, Martin /0000-0002-7198-9923; Konrad, Kerstin/0000-0001-9039-2615; Fink, Gereon/0000-0002-8230-1856 FU MR; Cognitive Neurology groups at the Institute of Medicine (Research Center Julich); Interdisciplinary Center of Clinical Research Aachen (IZKF) [N68a]; German Research Foundation [IRTG 1328, DFG-KFO112-II]; German National Academic Foundation FX We are grateful to all participants with their families who took part in this study. We wish to thank our colleagues in the MR and Cognitive Neurology groups at the Institute of Medicine (Research Center Julich) for their support and helpful advice. This work was supported by the Interdisciplinary Center of Clinical Research Aachen (IZKF, N68a; K. K. and G. R. F.); the German Research Foundation (IRTG 1328; DFG-KFO112-II, TP 5; K. K. B.H.-D.); and by a fellowship for doctoral students from the German National Academic Foundation (E. G.). 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Neural Transm. PD JUN PY 2010 VL 117 IS 6 BP 781 EP 791 DI 10.1007/s00702-010-0404-9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 604NY UT WOS:000278286900013 PM 20411397 ER PT J AU Cascio, CJ AF Cascio, Carissa J. TI Somatosensory processing in neurodevelopmental disorders SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Touch; Development; Tactile; Sensory integration; Neurodevelopmental disorders ID SENSORY INTEGRATION THERAPY; MENTAL-RETARDATION SYNDROME; TO-FACE INTERACTIONS; CEREBRAL-PALSY; TACTILE DEFENSIVENESS; MOUSE MODEL; DEVELOPMENTAL DISORDERS; UNMYELINATED AFFERENTS; PRESCHOOL-CHILDREN; MOTOR INTEGRATION AB The purpose of this article is to review the role of somatosensory perception in typical development, its aberration in a range of neurodevelopmental disorders, and the potential relations between tactile processing abnormalities and central features of each disorder such as motor, communication, and social development. Neurodevelopmental disorders that represent a range of symptoms and etiologies, and for which multiple peer-reviewed articles on somatosensory differences have been published, were chosen to include in the review. Relevant studies in animal models, as well as conditions of early sensory deprivation, are also included. Somatosensory processing plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. This is demonstrated in studies of behavior, sensory thresholds, neuroanatomy, and neurophysiology in samples of children with Fragile X syndrome, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and cerebral palsy (CP). Impaired somatosensory processing is found in a range of neurodevelopmental disorders and is associated with deficits in communication, motor ability, and social skills in these disorders. Given the central role of touch in early development, both experimental and clinical approaches should take into consideration the role of somatosensory processing in the etiology and treatment of neurodevelopmental disorders. C1 Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN 37212 USA. RP Cascio, CJ (reprint author), Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Dept Psychiat, 1601 23rd Ave S,Suite 3057, Nashville, TN 37212 USA. 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PD JUN PY 2010 VL 2 IS 2 BP 62 EP 69 DI 10.1007/s11689-010-9046-3 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 608JT UT WOS:000278580700001 PM 22127855 ER PT J AU Losh, M Esserman, D Piven, J AF Losh, Molly Esserman, Denise Piven, Joseph TI Rapid automatized naming as an index of genetic liability to autism SO JOURNAL OF NEURODEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Rapid automatized naming; Endophenotype; Broad autism phenotype ID DEVELOPMENTAL DYSLEXIA; MULTIPLE-INCIDENCE; PHONOLOGICAL AWARENESS; SUSCEPTIBILITY LOCI; CORPUS-CALLOSUM; CHILDREN; PHENOTYPE; PARENTS; FAMILIES; LANGUAGE AB This study investigated rapid automatized naming (RAN) ability in high functioning individuals with autism and parents of individuals with autism. Findings revealed parallel patterns of performance in parents and individuals with autism, where both groups had longer naming times than controls. Significant parent-child correlations were also detected, along with associations with language and personality features of the broad autism phenotype (retrospective reports of early language delay, socially reticent personality). Together, findings point towards RAN as a potential marker of genetic liability to autism. C1 [Losh, Molly] Univ N Carolina, Dept Allied Hlth Sci, Chapel Hill, NC 27599 USA. [Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA. [Esserman, Denise] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP Losh, M (reprint author), Univ N Carolina, Dept Allied Hlth Sci, Chapel Hill, NC 27599 USA. EM molly.losh@unc.edu FU STAART Center [U54 MH66418, R01 MH055284, K20 MH001028, K02 MH001568, R29 MH051217]; Autism Speaks; National Science Foundation [0820394]; CTSA [UL1RR025747] FX This project was funded by STAART Center Grant #1 U54 MH66418, R01 MH055284, K20 MH001028, K02 MH001568, and R29 MH051217 to JP. ML acknowledges support from Autism Speaks and the National Science Foundation (# 0820394). ML and DE acknowledge support from CTSA UL1RR025747. 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Neurodev. Disord. PD JUN PY 2010 VL 2 IS 2 BP 109 EP 116 DI 10.1007/s11689-010-9045-4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 608JT UT WOS:000278580700006 PM 20721307 ER PT J AU Mostafa, GA Shehab, AA AF Mostafa, Gehan A. Shehab, Abeer A. TI The link of C4B null allele to autism and to a family history of autoimmunity in Egyptian autistic children SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Autism; Autoimmunity; Complement 4B null allele; Family history of autoimmunity; Human leukocyte antigen ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; SPECTRUM DISORDERS; RISK-FACTORS; COMPLEMENT; ASSOCIATION; DISEASE; GENES; ANTIBODIES; HLA-DR4 AB The reason behind the initiation of autoimmunity, which may have a role in autism, is not well understood. There is an association between some autoimmune disorders and complement (C) 4B null allele. We aimed to study the association between C4B null allele and autism. In addition, we are the first to investigate the association between this allele and a family history of autoimmune diseases in autistic children. Therefore, we examined the frequency of C4B null allele, by quantitative real-time PCR, in 80 autistic patients and 80 healthy matched-children. The frequency of C4B null allele was significantly higher in autistic patients (37.5%) than healthy controls (8.75%), P<0.001. The frequency of autoimmune diseases in families of autistic children (40%) was significantly higher than healthy children (10%), P<0.001. In addition, a family history of autoimmunity had a significant risk for association with autism (odds ratio = 6, 95%, CI = 2.5-14.1). C4B null allele had a significant risk for association with autism (odds ratio = 6.26, 95% CI = 2.55-15.36) and with a family history of autoimmunity (odds ratio = 21, 95% CI = 6.5-67.8). Conclusions: the link of C4B null allele to autism and to a family history of autoimmunity may indicate its possible contributing role to autoimmunity in autism. (C) 2010 Elsevier B.V. All rights reserved. C1 [Mostafa, Gehan A.] Ain Shams Univ, Fac Med, Dept Pediat, Cairo, Egypt. [Shehab, Abeer A.] Ain Shams Univ, Fac Med, Dept Clin Pathol, Cairo, Egypt. RP Mostafa, GA (reprint author), 9 Ahmed El Samman St Makram Ebaid, Nasr City, Cairo, Egypt. 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PD JUN PY 2010 VL 223 IS 1-2 BP 115 EP 119 DI 10.1016/j.jneuroim.2010.03.025 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 627SG UT WOS:000280062100015 PM 20452682 ER PT J AU Levy, ML Levy, KM Hoff, D Amar, AP Park, MS Conklin, JM Baird, L Apuzzo, MLJ AF Levy, Michael L. Levy, Karen M. Hoff, Dayna Amar, Arun Paul Park, Min S. Conklin, Jordan M. Baird, Lissa Apuzzo, Michael L. J. TI Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry Clinical article SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE epilepsy; epilepsy surgery; failed surgery; autism; autism spectrum disorder; seizure; vagus nerve stimulation ID REFRACTORY EPILEPSY; PEDIATRIC-PATIENTS; SURGERY; SEIZURES; EXPERIENCE; CHILDHOOD; CHILDREN AB Object. The purpose of this study was to determine the effectiveness of vagus nerve stimulation (VNS) therapy on quality-of-life (QOL) variables among patients with both autism spectrum disorder (ASD) and persistent or recurrent intractable epilepsy. Methods. Data were obtained from the VNS therapy patient outcome registry, which was established after US FDA approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. Results. Two cohorts were compared: 1) patients with epilepsy but without ASD (non-ASD [NASD] Group, 315 patients) who were being tracked in the registry (this cohort, which was controlled for age, included patients 20 years of age or younger); and 2) patients with a diagnosis of ASD who underwent implantation of the VNS device (ASD Group, 77 patients). Differences between the ASD and NASD groups were noted in the following categories: sex (male preponderance in ASD); normal imaging results (MR imaging results normal in ASD); depression (less common in ASD); behavioral problems (more common in ASD); neurological deficit (more common in ASD); mental retardation (more common in ASD); and developmental delay. The only QOL difference between the ASD and NASD groups was noted in mood at 12 months postimplant (mood was improved in ASD) (p = 0.04). There were no other differences in the QOL variables. Conclusions. Patients with ASD and intractable epilepsy respond as favorably as all other patients receiving VNS therapy. In addition, they may experience a number of QOL improvements, some of which exceed those classically observed following placement of a VNS device. (DOI: 10.3171/2010.3.PEDS09153) C1 [Levy, Michael L.; Levy, Karen M.; Hoff, Dayna; Park, Min S.; Conklin, Jordan M.; Baird, Lissa] Univ Calif San Diego, Div Pediat Neurosurg, Childrens Hosp San Diego, San Diego, CA 92103 USA. [Amar, Arun Paul; Apuzzo, Michael L. J.] Univ So Calif, Keck Sch Med, Dept Neurosurg, Los Angeles, CA 90033 USA. RP Levy, ML (reprint author), Rady Childrens Hosp San Diego, Div Pediat Neurosurg, 8010 Frost St,Suite 502, San Diego, CA 92123 USA. 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PD JUN PY 2010 VL 5 IS 6 BP 595 EP 602 DI 10.3171/2010.3.PEDS09153 PG 8 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 600YF UT WOS:000278024200011 PM 20515333 ER PT J AU Yap, IKS Angley, M Veselkov, KA Holmes, E Lindon, JC Nicholson, JK AF Yap, Ivan K. S. Angley, Manya Veselkov, Kirill A. Holmes, Elaine Lindon, John C. Nicholson, Jeremy K. TI Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE autism; microbial co-metabolites; metabonomics; metabolic profiling; metabolic phenotype; gut microbiota; NMR; pattern recognition ID SPECTRUM DISORDERS; PARKINSONS-DISEASE; COMPLEX-I; LIQUID-CHROMATOGRAPHY; OXIDATIVE STRESS; GUT MICROBIOTA; HEALTH-CARE; RAT; IDENTIFICATION; PLASMA AB Autism is an early onset developmental disorder with a severe life-long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions. C1 [Yap, Ivan K. S.; Angley, Manya; Veselkov, Kirill A.; Holmes, Elaine; Lindon, John C.; Nicholson, Jeremy K.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Surg & Canc, London SW7 2AZ, England. [Angley, Manya] Univ S Australia, Div Hlth Sci, Sansom Inst, Adelaide, SA 5001, Australia. RP Nicholson, JK (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Surg & Canc, Alexander Fleming Bldg,S Kensington Campus, London SW7 2AZ, England. EM j.nicholson@imperial.ac.uk RI Yap, Ivan/C-9325-2013; Nicholson, Jeremy/B-3395-2012 OI Nicholson, Jeremy/0000-0002-8123-8349 FU Cure Autism Now (CAN); International Study of Macro/micronutrients and Blood Pressure [1-R0I-HL084228-01A1] FX We thank the Autism Research Group, Sansom Institute, Division of Health Sciences, University of South Australia and the Swiss Tropical Institute for urine sample provision. Cure Autism Now (CAN) provided the funding for collection of the urine samples for metabonomic purposes in 2006/2007. We would also like to acknowledge Lv Wang from University of South Australia for her contribution in providing epidemiological data for this study. Our thanks also to Dr. D. Granpeesheh (C.A.R.D, Los Angeles, Ca.) for helpful discussions on the manuscript and related data. This work received financial support from the International Study of Macro/micronutrients and Blood Pressure grant (1-R0I-HL084228-01A1) to I.K.S.Y. 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TI Comparison of the Bender Gestalt-II and VMI-V in Samples of Typical Children and Children with High-Functioning Autism Spectrum Disorders SO JOURNAL OF PSYCHOEDUCATIONAL ASSESSMENT LA English DT Article DE motor skills; visual-motor; Bender Gestalt Test-II; Developmental Test of Visual-Motor Integration; high-functioning autism; Asperger's disorder ID VISUAL-MOTOR INTEGRATION; REGULAR EDUCATION STUDENTS; REVISED DEVELOPMENTAL TEST; ASPERGER-SYNDROME; TEST USAGE; PERFORMANCE; TESTS; SCORES AB The visual-motor skills of 60 children with high-functioning autism spectrum disorders (HFASDs) and 46 typically developing children were assessed using the Bender Visual-Motor Gestalt Test-Second Edition (BG-II) and Beery-Buktenica Developmental Test of Visual-Motor Integration, Fifth Edition (VMI-V). Within-group comparisons yielded substantive mean differences between the BG-II Copy score and VMI-V composite,Visual Perception and Motor Coordination sections of the VMI-V, and Copy and Recall sections of the BG-II, in both samples. Between-groups differences were assessed in a subsample of 27 participants from each group matched on age, gender, ethnicity, and parent education. After statistically controlling for IQ, the HFASD group scored significantly lower than the typically developing group on the two scores from each test with greater motor involvement. Intratest and intertest correlations were similar across the two samples. Correlations between the BG-II Copy score and VMI-V composite were .55 for the HFASD and .48 for the typically developing sample. C1 [Volker, Martin A.; Vujnovic, Rebecca K.; Smerbeck, Audrey M.; Rodgers, Jonathan D.] SUNY Buffalo, Dept Counseling Sch & Educ Psychol, Buffalo, NY 14260 USA. 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Lewis, Shannon TI Update on Autism and Vaccines SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID DIAGNOSTIC SUBSTITUTION; DISORDER; TRENDS AB As the rate of autism spectrum disorders rises, parents are searching for answers. In this article, a small study that fueled the belief in an association between autism and vaccines is reviewed, and the scientific evidence regarding the relationship between autism and vaccines is explored. C1 [McGuinness, Teena M.; Lewis, Shannon] Univ Alabama, Sch Nursing, Birmingham, AL 35294 USA. RP McGuinness, TM (reprint author), Univ Alabama, Sch Nursing, NB 320,1530 3rd Ave S, Birmingham, AL 35294 USA. EM tmcg@uab.edu CR [Anonymous], 2010, LANCET, V375, P445 Bishop DVM, 2008, DEV MED CHILD NEUROL, V50, P341, DOI 10.1111/j.1469-8749.2008.02057.x Centers for Disease Control and Prevention, 2009, MMWR-MORBID MORTAL W, V58, P1 Chatterjee A, 2008, EXPERT REV VACCINES, V7, P275, DOI 10.1586/14760584.7.3.275 Coo H, 2008, J AUTISM DEV DISORD, V38, P1036, DOI 10.1007/s10803-007-0478-x Dales L, 2001, JAMA-J AM MED ASSOC, V285, P1183, DOI 10.1001/jama.285.9.1183 Doidge N., 2007, BRAIN CHANGES ITSELF Doja A, 2006, CAN J NEUROL SCI, V33, P341 Fombonne E, 2001, PEDIATRICS, V108, part. no., DOI 10.1542/peds.108.4.e58 Fombonne E, 2009, PEDIATR RES, V65, P591, DOI 10.1203/PDR.0b013e31819e7203 GREENHALGH T, 2010, BRIT MED J, V340, P644 Grigorenko E.L., 2009, FUTURE NEUROLOGY, V4, P591, DOI 10.2217/fnl.09.29 Halsey N A, 2001, Pediatrics, V107, pE84, DOI 10.1542/peds.107.5.e84 *INF CTR, 2005, NHS IMM STAT ENGL 20 Institutes of Medicine, 2001, IMM SAF REV MEASL MU *NAT I MENT HLTH, 2010, AUT SPECTR DIS PERV *PUBL BOADC SYST, 2010, FRONTL VACC WAR Wakefield AJ, 1998, LANCET, V351, P637, DOI 10.1016/S0140-6736(97)11096-0 NR 18 TC 1 Z9 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD JUN PY 2010 VL 48 IS 6 BP 15 EP 18 DI 10.3928/02793695-20100506-02 PG 4 WC Nursing SC Nursing GA 610OZ UT WOS:000278744300007 ER PT J AU Grossman, RB Bemis, RH Skwerer, DP Tager-Flusberg, H AF Grossman, Ruth B. Bemis, Rhyannon H. Skwerer, Daniela Plesa Tager-Flusberg, Helen TI Lexical and Affective Prosody in Children With High-Functioning Autism SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE autism; prosody; lexical stress; affective prosody; perception; production ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; REVISED VERSION; VOCAL EMOTION; SPEECH; STRESS; LANGUAGE; ADOLESCENTS; EXPRESSION; ADULTS AB Purpose: To investigate the perception and production of lexical stress and processing of affective prosody in adolescents with high-functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody but atypical lexical prosody production. Method: Sixteen children with HFA and 15 typically developing (TD) peers participated in 3 experiments that examined the following: (a) perception of affective prosody (Experiment 1), (b) lexical stress perception (Experiment 2), and (c) lexical stress production (Experiment 3). In Experiment 1, participants labeled sad, happy, and neutral spoken sentences that were low-pass filtered, to eliminate verbal content. In Experiment 2, participants disambiguated word meanings based on lexical stress (HOTdog vs. hot DOG). In Experiment 3, participants produced these words in a sentence completion task. Productions were analyzed with acoustic measures. Results: Accuracy levels showed no group differences. Participants with HFA could determine affect from filtered sentences and disambiguate words on the basis of lexical stress. They produced appropriately differentiated lexical stress patterns but demonstrated atypically long productions, indicating reduced ability in natural prosody production. Conclusions: Children with HFA were as capable as their TD peers in receptive tasks of lexical stress and affective prosody. Prosody productions were atypically long, despite accurate differentiation of lexical stress patterns. Future research should use larger samples and spontaneous versus elicited productions. C1 [Grossman, Ruth B.] Univ Massachusetts, Sch Med, Shriver Ctr, Waltham, MA USA. [Bemis, Rhyannon H.] Univ New Hampshire, Durham, NH 03824 USA. [Skwerer, Daniela Plesa; Tager-Flusberg, Helen] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Grossman, RB (reprint author), Emerson Coll, Dept Commun Sci & Disorders, 120 Boylston St, Boston, MA 02116 USA. 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D., 1990, PROSODY VOICE SCREEN Shriberg L. D., 2003, CLIN PHONETICS, Vthird Shriberg LD, 2001, J SPEECH LANG HEAR R, V44, P1097, DOI 10.1044/1092-4388(2001/087) Skwerer DP, 2007, LANG COGNITIVE PROC, V22, P247, DOI 10.1080/01690960600632671 Smith A, 2004, DEV PSYCHOBIOL, V45, P22, DOI 10.1002/dev.20009 Smith AB, 2005, CLIN LINGUIST PHONET, V19, P1, DOI 10.1080/0269920042000193580 Sparrow S, 1984, VINELAND ADAPTIVE BE Vogel I, 2002, J CHILD LANG, V29, P225, DOI 10.1017/S0305000902005020 Wang AT, 2007, ARCH GEN PSYCHIAT, V64, P698, DOI 10.1001/archpsyc.64.6.698 Wang YT, 2005, FOLIA PHONIATR LOGO, V57, P59, DOI 10.1159/000083569 NR 54 TC 35 Z9 35 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN 1 PY 2010 VL 53 IS 3 BP 778 EP 793 DI 10.1044/1092-4388(2009/08-0127) PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 607GV UT WOS:000278488000017 PM 20530388 ER PT J AU Qiu, AQ Adler, M Crocetti, D Miller, MI Mostofsky, SH AF Qiu, Anqi Adler, Marcy Crocetti, Deana Miller, Michael I. Mostofsky, Stewart H. TI Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys With Autism Spectrum Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE magnetic resonance imaging; large deformation diffeomorphic metric mapping (LDDMM); frontal; striatal; praxis ID HIGH-FUNCTIONING AUTISM; ASPERGERS-SYNDROME; CAUDATE-NUCLEUS; METRIC MAPPINGS; CORTICAL INPUTS; PREMOTOR AREAS; HUMAN BRAIN; TOOL USE; CHILDREN; CORTEX AB Objective: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association with behavioral features of ASD, which may involve multiple frontal subcortical circuits. Method: Basal ganglia were manually delineated from MR images of 32 boys with ASD and 45 typically developing (TD) boys. Large deformation diffeomorphic metric mapping (LDDMM) was used to assess between-group differences in basal ganglia shape and to examine associations with motor, praxis, and reciprocal social and communicative impairments in ASD. Results: Boys with ASD showed changes in right basal ganglia shape as compared with TD boys; surface deformation was present in the caudate, putamen, and globus pallidus but did not stand up to correction for multiple comparisons. Brain-behavior correlation findings were more robust; analyses accounting for multiple comparisons revealed, in boys with ASD, surface inward deformation of the right posterior putamen predicted poorer motor skill, whereas surface inward deformation of the bilateral anterior and posterior putamen predicted poorer praxis. Surface outward deformation in the bilateral medial caudate head predicted greater reciprocal social and communicative impairment. Conclusions: Motor, social, and communicative impairments in boys with ASD are associated with shape abnormalities in the basal ganglia. The findings suggest abnormalities within parallel frontal subcortical circuits are differentially associated with impaired acquisition of motor and reciprocal social and communicative skills in ASD. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(6):539-551. C1 [Qiu, Anqi] Natl Univ Singapore, Div Bioengn, Singapore 117574, Singapore. [Qiu, Anqi] Natl Univ Singapore, Clin Imaging Res Ctr, Singapore 117574, Singapore. [Qiu, Anqi] Singapore Inst Clin Sci, Singapore, Singapore. [Miller, Michael I.; Mostofsky, Stewart H.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Qiu, AQ (reprint author), Natl Univ Singapore, Div Bioengn, 9 Engn Dr 1,Block EA 03-12, Singapore 117574, Singapore. EM bieqa@nus.edu.sg RI Miller, Michael I./A-3213-2010; Qiu, Anqi/H-2267-2011 FU National Alliance for Autism Research, Autism Speaks; National University of Singapore [R-397-000-058-133]; A*STAR SERC [SERC 082 101 0025, SICS-09/1/1/001]; National Institutes of Health (NIH) [R01 NS048527, K02 NS044850, P41 RR15241]; Developmental Disabilities Research Center [HD-24061]; Johns Hopkins University School of Medicine Institute for Clinical and Translational Research; NIH/ NCRR [UL1-RRO25005] FX Work was supported by the National Alliance for Autism Research, Autism Speaks, the National University of Singapore start-up grant R-397-000-058-133 (AQ), A*STAR SERC 082 101 0025 (AQ), A*STAR SICS-09/1/1/001 (AQ), and National Institutes of Health (NIH) grants R01 NS048527 (S.H.M.), K02 NS044850 (S.H.M.), P41 RR15241 (M.I.M), the Developmental Disabilities Research Center (HD-24061), and the Johns Hopkins University School of Medicine Institute for Clinical and Translational Research, an NIH/ NCRR CTSA Program (UL1-RRO25005). 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Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2010 VL 49 IS 6 BP 539 EP 551 DI 10.1016/j.jaac.2010.02.012 PG 13 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 602TA UT WOS:000278160500002 PM 20494264 ER PT J AU Groen, W Teluij, M Buitelaar, J Tendolkar, I AF Groen, Wouter Teluij, Michelle Buitelaar, Jan Tendolkar, Indira TI Amygdala and Hippocampus Enlargement During Adolescence in Autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; emotion; amygdala; hippocampus ID POSTTRAUMATIC-STRESS-DISORDER; RECURRENT MAJOR DEPRESSION; TEMPORAL-LOBE; SPECTRUM DISORDERS; EMOTION PERCEPTION; CEREBRAL-CORTEX; YOUNG-CHILDREN; HUMAN BRAIN; VOLUMES; MRI AB Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse. Method: We measured amygdala and hippocampus volume in a homogeneous group of adolescents with autism (12 through18 years; n = 23) and compared them with an age-, sex-, and IQ-matched control group (n = 29) using a validated automated segmentation procedure in 1.5-T magnetic resonance images. All analyses were adjusted for total brain volume. Results: Repeated-measures analysis revealed a significant group x hemisphere x brain structure interaction (p = .038), even when corrected for total brain volume. Post-hoc analysis showed that the right amygdala and left hippocampus were significantly enlarged (p = .010; p = .015) in the autism compared with the control group. There were no significant correlations between age and amygdala or hippocampus volume. Conclusions: The abnormal enlargement of the amygdala and hippocampus in adolescents with autism adds to previous findings of enlargement of these structures in children with autism. This may reflect increased activity of these structures and thereby altered emotion perception and regulation. Our results could therefore be interpreted in light of developmental adaptation of the autistic brain to a continuous overflow of emotional learning experiences. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(6):552-560. C1 [Groen, Wouter] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands. RP Groen, W (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Reinier Postlaan 10,POB 9101, NL-6500 HB Nijmegen, Netherlands. EM groen@psy.umcn.nl RI Tendolkar, Indira/F-1167-2010; Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 FU Shire FX Disclosure: Dr. Buitelaar has served as a consultant and on the advisory board for Shire, Janssen Cilag, Eli Lilly, Pfizer, Organon, UCB, Servier, and Otsuka. He has served on the speakers' bureau for Janssen Cilag and Eli Lilly. He has received research support from Shire. Drs. Groen, Teluij, and Tendolkar report no biomedical financial interests or potential conflicts of interest. 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Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2010 VL 49 IS 6 BP 552 EP 560 DI 10.1016/j.jaac.2009.12.023 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 602TA UT WOS:000278160500003 PM 20494265 ER PT J AU Liu, AY Li, QZ Liu, CL Yu, K Yu, KF AF Liu, Aiyi Li, Qizhai Liu, Chunling Yu, Kai Yu, Kai F. TI A Rank-Based Test for Comparison of Multidimensional Outcomes SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Autism spectrum disorder; Behrens-Fisher problem; Cardioprotective solution; Case-control studies; Growth hormones; Multiple outcomes; Nonparametrics; Rank-sum statistics ID BEHRENS-FISHER PROBLEM; MULTIPLE END-POINTS; EXPONENTIAL DISTRIBUTION; TRIALS AB For comparison of multiple outcomes commonly encountered in biomedical research, Huang et al. (2005) improved O'Brien's (1984) rank-sum tests through the replacement of the ad hoc variance by the asymptotic variance of the test statistics. The improved tests control the type I error rate at the desired level and gain power when the differences between the two comparison groups in each outcome variable lie in the same direction; however, they may lose power when the differences are in different directions (e.g., some are positive and some are negative). These tests and the popular Bonferroni correction failed to show important significant differences when applied to compare heart rates from a clinical trial to evaluate the effect of a procedure to remove the cardioprotective solution HTK. We propose an alternative test statistic, taking the maximum of the individual rank-sum statistics, which controls the type I error rate and maintains satisfactory power regardless of the direction of the differences. Simulation studies show the proposed test to be of higher power than other tests in a certain alternative parameter space of interest. Furthermore, when used to analyze the heart rate data, the proposed test yields more satisfactory results. C1 [Liu, Aiyi; Liu, Chunling; Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China. [Yu, Kai F.] Natl Canc Inst, Rockville, MD 20852 USA. RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. EM liua@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Young Science Foundation of China [10901155] FX Aiyi Liu is Senior Investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD 20852 (E-mail: liva@mail.nih.gov). Qizhai Li is Assistant Professor, Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, 100190, China. Chunling Liu is Postdoctoral Fellow, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD 20852. Kai Yu is Investigator, National Cancer Institute, Rockville, MD 20852. Kai F. Yu is Senior Investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute. The research of Qizhai Li was partially supported by the National Young Science Foundation of China (grant 10901155). The authors thank two referees, an associate editor, and the editor for their thoughtful comments and suggestions that improved the article, and Dr. B. J. Stone for reading the manuscript. 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Am. Stat. Assoc. PD JUN PY 2010 VL 105 IS 490 BP 578 EP 587 DI 10.1198/jasa.2010.ap09114 PG 10 WC Statistics & Probability SC Mathematics GA 629RF UT WOS:000280216700011 ER PT J AU Lott, IT Dierssen, M AF Lott, Ira T. Dierssen, Mara TI Cognitive deficits and associated neurological complications in individuals with Down's syndrome SO LANCET NEUROLOGY LA English DT Review ID HIGH-RESOLUTION MRI; ATHEROMA-FREE MODEL; ALZHEIMERS-DISEASE; MENTAL-RETARDATION; WORKING-MEMORY; MOUSE MODEL; INFANTILE SPASMS; RISK-FACTORS; CONGENITAL HYPOTHYROIDISM; GENETIC-DISORDERS AB Improvements in medical interventions for people with Down's syndrome have led to a substantial increase in their longevity. Diagnosis and treatment of neurological complications are important in maintaining optimal cognitive functioning. The cognitive phenotype in Down's syndrome is characterised by impairments in morphosyntax, verbal short-term memory, and explicit long-term memory. However, visuospatial short-term memory, associative learning, and implicit long-term memory functions are preserved. Seizures are associated with cognitive decline and seem to cause additional decline in cognitive functioning, particularly in people with Down's syndrome and comorbid disorders such as autism. Vision and hearing disorders as well as hypothyroidism can negatively impact cognitive functioning in people with Down's syndrome. Dementia that resembles Alzheimer's disease is common in adults with Down's syndrome. Early-onset dementia in adults with Down's syndrome does not seem to be associated with atherosclerotic complications. C1 [Lott, Ira T.] Univ Calif Irvine, Sch Med, Dept Pediat, Orange, CA 92868 USA. [Lott, Ira T.] Univ Calif Irvine, Sch Med, Dept Neurol, Orange, CA 92868 USA. [Dierssen, Mara] Ctr Genom Regulat, Gene & Dis Program, Barcelona, Spain. [Dierssen, Mara] CIBER Enfermedades Raras, Barcelona, Spain. RP Lott, IT (reprint author), Univ Calif Irvine, Sch Med, Dept Pediat, Orange, CA 92868 USA. EM itlott@uci.edu FU National Institute Aging [AG 16573]; Generalitat de Catalunya [2009SGR1313]; Spanish Ministry of Science and Technology [SAF2007-60827, SAF2007-31093-E]; Fondo de Investigacion Sanitaria [PI 082038]; Marato TV3 [062230]; Jerome Lejeune Foundation [JMLM/AC/08-044]; Areces Foundation; Reina Sofia Foundation; European Union [LSHG-CT-2006-037627, EU/FIS PS09102673] FX Our work is supported in part by grants from the National Institute Aging (AG 16573), the Generalitat de Catalunya (2009SGR1313), the Spanish Ministry of Science and Technology (SAF2007-60827, SAF2007-31093-E), Fondo de Investigacion Sanitaria (PI 082038), Marato TV3 (062230), the Jerome Lejeune Foundation (JMLM/AC/08-044), the Areces Foundation, the Reina Sofia Foundation, and the European Union (LSHG-CT-2006-037627; EU/FIS PS09102673). We are grateful to Eric Doran for editorial assistance in the preparation of this manuscript. 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PD JUN PY 2010 VL 9 IS 6 BP 623 EP 633 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 607NY UT WOS:000278512000015 PM 20494326 ER PT J AU Wechsler, S AF Wechsler, Stephen TI WHAT 'YOU' AND 'I' MEAN TO EACH OTHER: PERSON INDEXICALS, SELF-ASCRIPTION, AND THEORY OF MIND SO LANGUAGE LA English DT Article DE indexical; person; pronoun; theory of mind; self-reference; acquisition; autism ID BELIEF; PRONOUNS; REPRESENTATION; ACQUISITION; LANGUAGE; SPEECH; CHILD AB This article offers a DE SE THEORY of person indexicals, wherein first- and second-person indexical pronouns indicate REFERENCE DE SE (also called SELF-ASCRIPTION). Long observed for first-person pronouns (Castaneda 1977, Kaplan 1977, Perry 1979, inter alia), self-ascription is extended here to second person as well. The person feature of a pronoun specifies the speech-act roles that must be played by the self-ascribers: the speakers (uttering a first-person pronoun), the addressees (interpreting a second-person pronoun), or both (for first-person inclusive). Other agents who are not among the designated self-ascribers for a given pronoun interpret the pronoun indirectly by inferring the self-ascriber's interpretation, a process requiring THEORY OF MIND, that is, the cognitive ability to impute mental states to others (Premack & Woodruff 1978). This de se theory is supported by convergent evidence from multiple domains: (i) It explains a typological universal: first- and second-person plurals always allow associative semantics ('speaker(s) plus others', 'addressee(s) plus others') rather than requiring regular plural semantics ('speakers only', 'addressees only') (Greenberg 1988, Noyer 1992, Cysouw 2003, Bobaljik 2008). (ii) It belongs to a family of approaches that solve the problem of the essential indexical (Perry 1979). (iii) It correctly predicts observed patterns of indexical pronoun production and comprehension by two populations lacking a fully developed theory of mind: typically developing children in the stage before theory of mind has developed, and children with autism. (iv) It correctly predicts the interpretation of second-person pronouns in utterances with multiple addressees.* C1 Univ Texas Austin, Dept Linguist, Austin, TX 78712 USA. RP Wechsler, S (reprint author), Univ Texas Austin, Dept Linguist, 1 Univ Stn B5100, Austin, TX 78712 USA. 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Despite scientific efforts and huge fundings, less than 20% of cases of autism have been linked to genetic abnormalities. These results do not slow the spread of discourse on the genetic origin of autism, and the concomitant neglect of risks linked to perinatal factors. A detailed analysis of results and assertions in favour of a strong genetic origin of autism reveals methodological biases, misinterpretations and erroneous approximations, as well as an exaggerated media coverage. Studies on twins are illustrative of these biases. The recent demonstration of an excess of twins among sibling pairs with autism, and especially a 10-fold increase for monozygotic twins compared with the general population frequencies, has questioned the relevance of conclusions from earlier twin studies. Indeed, if being a twin is a risk factor for autism, then there may be an upwards bias in estimates of the genetic contribution to autism, and the intrauterine environment, including competition for nutrients, has been neglected. C1 Univ Paris 05, INSERM, Ctr Rech Med Sci Sante Sante Mentale & Soc, CERMES3 CESAMES,EHESS,CNRS,UMR8211, F-75006 Paris 06, France. RP Chamak, B (reprint author), Univ Paris 05, INSERM, Ctr Rech Med Sci Sante Sante Mentale & Soc, CERMES3 CESAMES,EHESS,CNRS,UMR8211, 45 Rue St Peres, F-75006 Paris 06, France. 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PD JUN PY 2010 VL 23 IS 2 BP 115 EP 117 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 618LN UT WOS:000279356100007 PM 20562088 ER PT J AU Murray, AL AF Murray, A. Louise TI Can the existence of highly accessible concrete representations explain savant skills? Some insights from synaesthesia SO MEDICAL HYPOTHESES LA English DT Article ID IDIOTS-SAVANTS; VISUAL-IMAGERY; CALENDAR CALCULATORS; MENTAL-IMAGERY; SYNESTHESIA; PERCEPTION; AUTISM; MEMORY; INFORMATION; BRAIN AB The present review argues that the reification of abstract concepts provides a psychological mediating mechanism for calendar and lightning calculation and possibly even all savant skills. The argument, which draws heavily on the synaesthesia literature has two main strands. First, there is anecdotal evidence for the presence and utilisation of highly accessible concrete representations of abstract concepts in savants. 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TI Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes SO MOLECULAR PSYCHIATRY LA English DT Article DE CNV; ADHD; GRM5; GRM7; PTPRD; autism; schizophrenia ID LONG-TERM POTENTIATION; RESTLESS-LEGS-SYNDROME; COPY-NUMBER VARIATION; RECEPTOR-TYPE-DELTA; REPORT SCALE ASRS; DEFICIT/HYPERACTIVITY DISORDER; REPRESENTATIVE SAMPLE; SCHIZOPHRENIA; ADHD; CHILDREN AB Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD. Molecular Psychiatry (2010) 15, 637-646; doi: 10.1038/mp.2009.57; published online 23 June 2009 C1 [Hakonarson, H.] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. [Elia, J.; deBerardinis, R.; Takeda, T.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA. [Elia, J.; Berrettini, W.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Gai, X.; Xie, H. M.; Perin, J. C.; D'arcy, M.; Muganga, B. M.; Wang, L.; White, P. S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Geiger, E.; Lantieri, F.; Grant, S. F. A.; Devoto, M.; Shaikh, T. H.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Rappaport, E. F.] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA. [Grant, S. F. A.; Devoto, M.; Shaikh, T. H.; Hakonarson, H.; White, P. S.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Devoto, M.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Devoto, M.] Univ Roma La Sapienza, Dipartimento Med Sperimentale, Rome, Italy. [Glessner, J. T.; Frackelton, E.; Kim, C.; Grant, S. F. A.; Hakonarson, H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [White, P. S.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Div Pulm Med, 34th St & Civ Ctr Blvd,Rm 1216E ARC, Philadelphia, PA 19104 USA. EM hakonarson@chop.edu; white@genome.chop.edu RI Gai, Xiaowu/G-4065-2010 FU National Institutes of Health [K23MH066275, GM081519, P30HD026979]; University of Pennsylvania [UL1-RR-024134]; Pennsylvania Department of Health [SAP 4100037707]; Cotswold Foundation; Children's Hospital of Philadelphia FX The Children's Hospital of Philadelphia Institutional Review Board has approved this study. This work was supported in part by National Institutes of Health Grants K23MH066275 (JE), GM081519 (THS), and P30HD026979 (MD and XG); University of Pennsylvania Grant UL1-RR-024134 (JE); Pennsylvania Department of Health Grant SAP 4100037707 (PSW); and a Developmental Research Award from the Cotswold Foundation (SG and HH). All genome-wide genotyping was funded by an Institutional Development Award from the Children's Hospital of Philadelphia (HH). We thank all the participating individuals and families for making this study possible. 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PD JUN PY 2010 VL 42 IS 6 BP 478 EP 479 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 601RN UT WOS:000278081500008 PM 20502490 ER PT J AU Berkel, S Marshall, CR Weiss, B Howe, J Roeth, R Moog, U Endris, V Roberts, W Szatmari, P Pinto, D Bonin, M Riess, A Engels, H Sprengel, R Scherer, SW Rappold, GA AF Berkel, Simone Marshall, Christian R. Weiss, Birgit Howe, Jennifer Roeth, Ralph Moog, Ute Endris, Volker Roberts, Wendy Szatmari, Peter Pinto, Dalila Bonin, Michael Riess, Angelika Engels, Hartmut Sprengel, Rolf Scherer, Stephen W. Rappold, Gudrun A. TI Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation SO NATURE GENETICS LA English DT Article ID POSTSYNAPTIC DENSITY; PROTEINS AB Using microarrays, we identified de novo copy number variations in the SHANK2 synaptic scaffolding gene in two unrelated individuals with autism-spectrum disorder (ASD) and mental retardation. 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[Bonin, Michael; Riess, Angelika] Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany. [Engels, Hartmut] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Sprengel, Rolf] Univ Heidelberg, Max Planck Inst Med Res MPI, Heidelberg, Germany. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Rappold, GA (reprint author), Univ Heidelberg, Dept Human Mol Genet, Heidelberg, Germany. EM gudrun_rappold@med.uni-heidelberg.de RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU international Autism Genome Project; Autism Speaks; German Mental Retardation Network (MRNET); Federal Ministry of Education and Research, Germany; Deutsche Forschungsgesellschaft (DFG) [SFB488]; Medical Faculty of Heidelberg; CellNetworks-Cluster of Excellence [EXC81]; Centre for Applied Genomics, Genome Canada; Ontario Genomics Institute; Canadian Institutes for Health Research (CIHR); Canadian Institute for Advanced Research (CIFAR); McLaughlin Centre; Canada Foundation for Innovation; Ontario Ministry of Research and Innovation; Hospital for Sick Children Foundation FX We gratefully thank E. Fenner, M. Fritsche and S. Peykov for sequencing and technical support, and we thank all the affected individuals' families for their cooperation. We thank A. Fiebig, A. Franke and S. Schreiber at POPGEN (University of Kiel, Kiel, Germany) and A. Stewart, R. McPherson and R. Roberts of the University of Ottawa Heart Institute (University of Ottawa, Ottawa, Canada) for generously providing population control microarray data. The international Autism Genome Project and Autism Speaks is also gratefully acknowledged for support. Funding was provided by the German Mental Retardation Network (MRNET), supported by the Federal Ministry of Education and Research, Germany, by the Deutsche Forschungsgesellschaft (DFG; SFB488) and the Medical Faculty of Heidelberg. S. B. was funded by a fellowship of CellNetworks-Cluster of Excellence (EXC81) and is a member of Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS). S. W. S. is supported by The Centre for Applied Genomics, Genome Canada and Ontario Genomics Institute, the Canadian Institutes for Health Research (CIHR), the Canadian Institute for Advanced Research (CIFAR), the McLaughlin Centre, the Canada Foundation for Innovation, the Ontario Ministry of Research and Innovation and the Hospital for Sick Children Foundation. S.W.S. holds the GlaxoSmithKline-CIHR Chair in Genetics and Genomics at the University of Toronto and the Hospital for Sick Children. G.A.R. is a member of CellNetworks-Cluster of Excellence (EXC81). Dedicated to Mrs. Elisabeth Berkel. 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PD JUN PY 2010 VL 42 IS 6 BP 489 EP 491 DI 10.1038/ng.589 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 601RN UT WOS:000278081500011 PM 20473310 ER PT J AU Welch, MG Anwar, M Chang, CY Gross, KJ Ruggiero, DA Tamir, H Gershon, MD AF Welch, Martha G. Anwar, Muhammad Chang, Christine Y. Gross, Kara J. Ruggiero, David A. Tamir, Hadassah Gershon, Michael D. TI Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE autism; gut-brain signaling; inflammatory bowel disease; interferon-gamma (IFN gamma); neuropeptides; tumor necrosis factor-alpha (TNF alpha) ID VASOACTIVE-INTESTINAL-PEPTIDE; INFLAMMATORY-BOWEL-DISEASE; TNBS-INDUCED COLITIS; AUTISTIC DISORDER; DENDRITIC CELLS; BREAST-MILK; RECEPTOR; RAT; EXPRESSION; BRAIN AB Background The pathogenesis of inflammatory bowel disease is unknown; however, the disorder is aggravated by psychological stress and is itself psychologically stressful. Chronic intestinal inflammation, moreover, has been reported to activate forebrain neurons. We tested the hypotheses that the chronically inflamed bowel signals to the brain through the vagi and that administration of a combination of secretin (S) and oxytocin (OT) inhibits this signaling. Methods Three daily enemas containing 2,4,6-trinitrobenzene sulfonic acid (TNBS), which were given to rats produced chronic colitis and ongoing activation of Fos in brain neurons. Key Results Fos was induced in neurons in the paraventricular nucleus of the hypothalamus, basolateral amygdala, central amygdala, and piriform cortex. Subdiaphragmatic vagotomy failed to inhibit this activation of Fos, suggesting that colitis activates forebrain neurons independently of the vagi. When administered intravenously, but not when given intracerebroventricularly, in doses that were individually ineffective, combined S/OT prevented colitis-associated activation of central neurons. Strikingly, S/OT decreased inflammatory infiltrates into the colon and colonic expression of tumor necrosis factor-alpha and interferon-gamma. Conclusions & Inferences These observations suggest that chronic colonic inflammation is ameliorated by the systemic administration of S/OT, which probably explains the parallel ability of systemic S/OT to inhibit the colitis-associated activation of forebrain neurons. It is possible that S and OT, which are endogenous to the colon, might normally combine to restrict the severity of colonic inflammatory responses and that advantage might be taken of this system to develop novel means of treating inflammation-associated intestinal disorders. C1 [Welch, Martha G.; Anwar, Muhammad; Ruggiero, David A.; Tamir, Hadassah] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Welch, Martha G.; Chang, Christine Y.; Gross, Kara J.; Ruggiero, David A.; Tamir, Hadassah; Gershon, Michael D.] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Gross, Kara J.] Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. RP Welch, MG (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 40, New York, NY 10032 USA. EM mgw13@columbia.edu FU Einhorn Family Charitable Trust [15665] FX We would like to acknowledge the contributions of Robert Ludwig, T. Bramwell Welch-Horan, Nargis Anwar, Lawrence McGill, D. Glen Esplin, Sara Glickstein, Jason Keune and Farrukh Jafri. Funding Columbia Grant # 15665, Einhorn Family Charitable Trust, F. Fairman. Competing interests: the authors have no competing interests. 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Motil. PD JUN PY 2010 VL 22 IS 6 BP 654 EP + DI 10.1111/j.1365-2982.2010.01477.x PG 12 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 591UB UT WOS:000277329200014 PM 20210978 ER PT J AU Riby, DM Back, E AF Riby, Deborah M. Back, Elisa TI Can individuals with Williams syndrome interpret mental states from moving faces? SO NEUROPSYCHOLOGIA LA English DT Article DE Williams syndrome; Facial expression; Mental states; Social cognition ID EXPRESSION RECOGNITION; IMPAIRED RECOGNITION; FACIAL EXPRESSIONS; GENETIC INFLUENCES; ASPERGER-SYNDROME; NORMAL ADULTS; AUTISM; AMYGDALA; PERCEPTION; LANGUAGE AB The Williams syndrome (WS) social phenotype is characterised by a high level of social engagement, heightened empathy and prolonged attention to people's faces. These behaviours appear in contradiction to research reporting problems recognising and interpreting basic emotions and more complex mental states from other people. The current task involved dynamic (moving) face stimuli of an actor depicting complex mental states (e.g., worried, disinterested). Cues from the eye and mouth regions were systematically frozen and kept neutrally expressive to help identify the source of mental state information in typical development and WS. Eighteen individuals with WS (aged 8-23 years) and matched groups of typically developing participants were most accurate inferring mental states from whole dynamic faces. In this condition individuals with WS performed at a level predicted by chronological age. When face parts (eyes or mouth) were frozen and neutrally expressive, individuals with WS showed the greatest decrement in performance when the eye region was uninformative. We propose that using moving whole face stimuli individuals with WS can infer mental states and the eye region plays a particularly important role in performance. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Riby, Deborah M.] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Back, Elisa] Kingston Univ London, Psychol Res Unit, London, England. RP Riby, DM (reprint author), Newcastle Univ, Sch Psychol, Ridley Bldg,Framlington Pl, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. EM D.M.Riby@ncl.ac.uk FU Williams syndrome Foundation, UK FX This work was partly supported by funds from the Williams syndrome Foundation, UK, to D Riby. We would like to thank Adam Combie for helping with data collection for the participants with Williams syndrome and all individuals who took part in the research. 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PD JUN PY 2010 VL 20 IS 2 SI SI BP 209 EP 225 DI 10.1007/s11065-010-9129-7 PG 17 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 607AK UT WOS:000278470400008 PM 20422451 ER PT J AU Munesue, T Yokoyama, S Nakamura, K Anitha, A Yamada, K Hayashi, K Asaka, T Liu, HX Jin, D Koizumi, K Islam, MS Huang, JJ Ma, WJ Kim, UH Kim, SJ Park, K Kim, D Kikuchi, M Ono, Y Nakatani, H Suda, S Miyachi, T Hirai, H Salmina, A Pichugina, YA Soumarokov, AA Takei, N Mori, N Tsujii, M Sugiyama, T Yagi, K Yamagishi, M Sasaki, T Yamasue, H Kato, N Hashimoto, R Taniike, M Hayashi, Y Hamada, J Suzuki, S Ooi, A Noda, M Kamiyama, Y Kido, MA Lopatina, O Hashii, M Amina, S Malavasi, F Huang, EJ Zhang, JS Shimizu, N Yoshikawa, T Matsushima, A Minabe, Y Higashida, H AF Munesue, Toshio Yokoyama, Shigeru Nakamura, Kazuhiko Anitha, Ayyappan Yamada, Kazuo Hayashi, Kenshi Asaka, Tomoya Liu, Hong-Xiang Jin, Duo Koizumi, Keita Islam, Mohammad Saharul Huang, Jian-Jun Ma, Wen-Jie Kim, Uh-Hyun Kim, Sun-Jun Park, Keunwan Kim, Dongsup Kikuchi, Mitsuru Ono, Yasuki Nakatani, Hideo Suda, Shiro Miyachi, Taishi Hirai, Hirokazu Salmina, Alla Pichugina, Yu A. Soumarokov, Andrei A. Takei, Nori Mori, Norio Tsujii, Masatsugu Sugiyama, Toshiro Yagi, Kunimasa Yamagishi, Masakazu Sasaki, Tsukasa Yamasue, Hidenori Kato, Nobumasa Hashimoto, Ryota Taniike, Masako Hayashi, Yutaka Hamada, Junichiro Suzuki, Shioto Ooi, Akishi Noda, Mami Kamiyama, Yuko Kido, Mizuho A. Lopatina, Olga Hashii, Minako Amina, Sarwat Malavasi, Fabio Huang, Eric J. Zhang, Jiasheng Shimizu, Nobuaki Yoshikawa, Takeo Matsushima, Akihiro Minabe, Yoshio Higashida, Haruhiro TI Two genetic variants of CD38 in subjects with autism spectrum disorder and controls SO NEUROSCIENCE RESEARCH LA English DT Article DE CD38; Oxytocin; Mutation; Polymorphism; Autism; High-functioning autism ID CYCLIC ADP-RIBOSE; HIGH-FUNCTIONING AUTISM; DIAGNOSTIC INTERVIEW; SOCIAL-BEHAVIOR; BIPOLAR DISORDER; OXYTOCIN; ASSOCIATION; PREVALENCE; POPULATION; HUMANS AB The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved. C1 [Yokoyama, Shigeru; Hayashi, Kenshi; Liu, Hong-Xiang; Jin, Duo; Koizumi, Keita; Islam, Mohammad Saharul; Huang, Jian-Jun; Ma, Wen-Jie; Pichugina, Yu A.; Lopatina, Olga; Hashii, Minako; Amina, Sarwat; Higashida, Haruhiro] Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan. [Munesue, Toshio; Yokoyama, Shigeru; Liu, Hong-Xiang; Jin, Duo; Koizumi, Keita; Islam, Mohammad Saharul; Huang, Jian-Jun; Ma, Wen-Jie; Hirai, Hirokazu; Sugiyama, Toshiro; Lopatina, Olga; Amina, Sarwat; Minabe, Yoshio; Higashida, Haruhiro] Kanazawa Univ, 21st Century Ctr Excellence COE, Program Innovat Brain Sci Dev Learning & Memory, Kanazawa, Ishikawa 9208640, Japan. [Munesue, Toshio; Koizumi, Keita; Minabe, Yoshio; Higashida, Haruhiro] Kanazawa Univ, Ctr Child Mental Dev, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Kanazawa, Ishikawa 9208640, Japan. [Munesue, Toshio; Kikuchi, Mitsuru] Kanazawa Univ Hosp, Dept Child Psychiat, Kanazawa, Ishikawa 9208641, Japan. [Hayashi, Kenshi] Kanazawa Univ Hosp, Dept Clin Lab, Kanazawa, Ishikawa 9208641, Japan. [Munesue, Toshio; Kikuchi, Mitsuru; Ono, Yasuki; Nakatani, Hideo; Minabe, Yoshio] Kanazawa Univ, Grad Sch Med, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa 9208640, Japan. [Hayashi, Kenshi; Yagi, Kunimasa; Yamagishi, Masakazu] Kanazawa Univ, Grad Sch Med, Dept Internal Med, Kanazawa, Ishikawa 9208640, Japan. [Hayashi, Yutaka; Hamada, Junichiro] Kanazawa Univ, Grad Sch Med, Dept Neurosurg, Kanazawa, Ishikawa 9208640, Japan. [Suzuki, Shioto; Ooi, Akishi] Kanazawa Univ, Grad Sch Med, Dept Mol & Cellular Pathol, Kanazawa, Ishikawa 9208640, Japan. [Munesue, Toshio; Yokoyama, Shigeru; Islam, Mohammad Saharul; Ma, Wen-Jie; Yamasue, Hidenori; Kato, Nobumasa; Lopatina, Olga; Hashii, Minako; Higashida, Haruhiro] Core Res Evolut Sci & Technol, Tokyo 1020075, Japan. [Munesue, Toshio; Koizumi, Keita; Takei, Nori; Mori, Norio; Tsujii, Masatsugu; Hashimoto, Ryota; Taniike, Masako; Minabe, Yoshio; Higashida, Haruhiro] Osaka Kanazawa Hamamatsu Univ, United Grad Sch Child Dev, Osaka 5650871, Japan. [Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro; Miyachi, Taishi; Takei, Nori; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan. [Yamada, Kazuo; Yoshikawa, Takeo] RIKEN Brain Sci Inst, Lab Mol Psychiat, Saitama 3510198, Japan. [Asaka, Tomoya; Matsushima, Akihiro] Nanao Natl Hosp, Nanao 9208531, Japan. [Kim, Uh-Hyun] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju, South Korea. [Kim, Sun-Jun] Chonbuk Natl Univ, Sch Med, Dept Pediat, Jeonju, South Korea. [Park, Keunwan; Kim, Dongsup] Korea Adv Inst Sci & Technol, Seoul, South Korea. [Kikuchi, Mitsuru; Minabe, Yoshio] Hokuriku Innovat Cluster Hlth Sci, Kanazawa, Ishikawa 9208640, Japan. [Hirai, Hirokazu] Gunma Univ, Grad Sch Med, Dept Neurophysiol, Gunma 3718511, Japan. [Salmina, Alla; Lopatina, Olga] Krasnoyarsk State Med Univ, Dept Med Chem & Biochem, Krasnoyarsk 660022, Russia. [Pichugina, Yu A.; Soumarokov, Andrei A.] Krasnoyarsk State Med Univ, Dept Psychiat, Krasnoyarsk 660022, Russia. [Takei, Nori; Mori, Norio] Hamamatsu Univ, Ctr Child Mental Dev, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Hamamatsu, Shizuoka 4313197, Japan. [Tsujii, Masatsugu] Chukyo Univ, Fac Sociol, Aichi 4700393, Japan. [Sugiyama, Toshiro] Aichi Childrens Hlth & Med Ctr, Aichi 4748710, Japan. [Sasaki, Tsukasa] Univ Tokyo, Div Counseling & Support, Off Mental Hlth Support, Tokyo 1130033, Japan. [Sasaki, Tsukasa; Yamasue, Hidenori; Kato, Nobumasa] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138655, Japan. [Kato, Nobumasa] Showa Univ, Sch Med, Dept Psychiat, Tokyo 1578577, Japan. [Hashimoto, Ryota; Taniike, Masako] Osaka Univ, Mol Res Ctr, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Osaka 5650871, Japan. [Noda, Mami; Kamiyama, Yuko] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Pathophysiol, Fukuoka 8128582, Japan. [Kido, Mizuho A.] Kyushu Univ, Grad Sch Dent Sci, Dept Oral Anat & Cell Biol, Fukuoka 8128582, Japan. [Malavasi, Fabio] Univ Turin, Sch Med, Immunogenet Lab, Dept Genet Biol & Biochem, I-10126 Turin, Italy. [Malavasi, Fabio] Univ Turin, Sch Med, CeRMS, I-10126 Turin, Italy. [Huang, Eric J.; Zhang, Jiasheng] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA. [Huang, Eric J.; Zhang, Jiasheng] Vet Affair Med Ctr, Pathol Serv, San Francisco, CA 94121 USA. [Shimizu, Nobuaki] Kanazawa Univ, Inst Nat & Environm Technol, Kanazawa, Ishikawa 9201192, Japan. RP Higashida, H (reprint author), Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan. EM haruhiro@med.kanazawa-u.ac.jp RI Kim, Dongsup/C-1612-2011; Salmina, Alla/L-7977-2013; Lopatina, Olga/I-9610-2014; Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 FU Japanese Ministry of Education, Culture, Sports, Science, and Technology; Fondazione Guido Berlucchi and Compagnia di SanPaolo; Japan Society for the Promotion of Science FX This study was supported by grants from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We thank Takako Ohbayashi, Michiko Hoshii, and Shizuka Aikawa for technical assistance. We thank D.A. Brown for discussion, the AGRE for samples, and are grateful for fundings from Fondazione Guido Berlucchi and Compagnia di SanPaolo and the Japan-Russian Bilateral Science Promotion Program of the Japan Society for the Promotion of Science. 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PD JUN PY 2010 VL 67 IS 2 BP 181 EP 191 DI 10.1016/j.neures.2010.03.004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 611FR UT WOS:000278797800010 PM 20435366 ER PT J AU Shaw, W AF Shaw, William TI Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE m-tyrosine; 3-hydroxyphenylalanine; metronidazole; enkephalins; Lactobacillus acidophilus ID IONIZATION MASS-SPECTROMETRY; COA DEHYDROGENASE-DEFICIENCY; CHLOROGENIC ACID; LIQUID-CHROMATOGRAPHY; ONSET AUTISM; POLYPHENOLS; CHILDREN; PHENOLICS; PRODUCTS; CAPACITY AB A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals. C1 Great Plains Lab Inc, Lenexa, KS 66214 USA. RP Shaw, W (reprint author), Great Plains Lab Inc, 11813 W 77th St, Lenexa, KS 66214 USA. 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Lessin, Herschel R. TI Policy Statement-Increasing Immunization Coverage SO PEDIATRICS LA English DT Article DE immunization; vaccines; immunization coverage; increasing immunization coverage; vaccine financing; vaccine supply; vaccine safety; immunization information system; reminder-recall; missed opportunities; risk communication; refusal to vaccinate ID VACCINATION COVERAGE; UNITED-STATES; CHILDREN; ADOLESCENTS; IMPACT; CARE AB In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the Internet as well as standard media outlets to advance a position, wholly unsupported by any scientific evidence, linking vaccines with various childhood conditions, particularly autism. Much remains to be accomplished by physician organizations; vaccine manufacturers; third-party payers; the media; and local, state, and federal governments to ensure dependable vaccine supply and payments that are sufficient to continue to provide immunizations in public and private settings and to promote effective strategies to combat unjustified misstatements by the antivaccination movement. Pediatricians should work individually and collectively at the local, state, and national levels to ensure that all children without a valid contraindication receive all childhood immunizations on time. Pediatricians and pediatric organizations, in conjunction with government agencies such as the Centers for Disease Control and Prevention, must communicate effectively with parents to maximize their understanding of the overall safety and efficacy of vaccines. Most parents and children have not experienced many of the vaccine-preventable diseases, and the general public is not well informed about the risks and sequelae of these conditions. A number of recommendations are included for pediatricians, individually and collectively, to support further progress toward the goal of universal immunization coverage of all children for whom vaccines are not contraindicated. 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Johnson, Courtney Crosette, Jonathan Ramos, Mark Mindell, Jodi A. TI Prevalence of Diagnosed Sleep Disorders in Pediatric Primary Care Practices SO PEDIATRICS LA English DT Article DE sleep disorders; children; adolescents; primary care ID RESTLESS-LEGS-SYNDROME; SCHOOL-AGED CHILDREN; UNITED-STATES; ADOLESCENTS; CHILDHOOD; OBESITY; DIFFICULTIES; MEDICATION; EDUCATION; PATTERNS AB OBJECTIVES: The primary aim was to determine the prevalence of International Classification of Diseases, Ninth Revision (ICD-9), sleep disorders diagnosed by pediatric providers in a large, primary care network. Secondary aims were to examine demographic variables related to these diagnoses and to examine the frequency of prescriptions for medications potentially used to treat sleep disorders. METHODS: Electronic medical records were reviewed for 154 957 patients (0-18 years) seen for a well-child visit in 2007. Information collected included ICD-9 sleep diagnoses, demographic variables, comorbid attention-deficit/hyperactivity disorder and autism spectrum disorders, provider type, and medications. RESULTS: Across all ages, 3.7% of youths had an ICD-9 diagnosis for a sleep disorder. The most-common diagnoses were sleep disorder not otherwise specified, enuresis, and sleep-disordered breathing. Predictors of sleep disorders varied according to developmental age group and included growth parameters, comorbid attention-deficit/hyperactivity disorder or autism spectrum disorder, and provider type. Potential sleep-related medications were prescribed for 6.1% of the sample subjects. CONCLUSIONS: This study is one of the first to examine comprehensively ICD-9 sleep diagnoses given by primary care providers in a large representative sample of children 0 to 18 years of age. The 3.7% of patients with ICD-9 sleep diagnoses is significantly lower than prevalence rates reported in epidemiological studies, which suggests that primary care providers may be underdiagnosing sleep disorders in children and adolescents. Because sleep disorders are treatable when recognized, the results from this study suggest a significant need for additional education and support for primary care providers in the diagnosis and treatment of pediatric sleep disorders. Pediatrics 2010; 125: e1410-e1418 C1 [Meltzer, Lisa J.; Johnson, Courtney; Mindell, Jodi A.] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. [Crosette, Jonathan; Ramos, Mark] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA. [Meltzer, Lisa J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Johnson, Courtney] Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Mindell, Jodi A.] St Josephs Univ, Dept Psychol, Philadelphia, PA 19131 USA. RP Meltzer, LJ (reprint author), Childrens Hosp Philadelphia, Div Pulm Med, 3535 Market St,14th Floor, Philadelphia, PA 19104 USA. EM meltzerl@email.chop.edu FU National Institutes of Health [K23 MH077662] FX This study was supported in part by National Institutes of Health grant K23 MH077662. 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It is important to assess HC growth accurately because atypical HC growth is an indicator of various developmental disorders. HC growth is determined by both familial and physical factors but, hitherto, no one has considered both factors together. The aim of the present study was thus to investigate the relationship between HC, physical growth, and parental HC. Methods: The study group in the Japan Children's Study consisted of 192 healthy full-term Japanese children. HC (maximum occiptofrontal circumference), height and bodyweight were measured at the ages of 4, 9 and 18 months. Multiple regression analysis were conducted predicting the HC from the body measurements and mid-parental HC (defined as the average of standardized paternal and maternal HC). Results: Adjusted multiple R2 were 0.336, 0.307 and 0.259, measured at the aforementioned three stages. Bodyweight and mid-parental HC predicted the HC on each occasion (P < 0.01). Bodyweight was more relevant than mid-parental HC. Conclusions: HC growth is influenced by physical growth and parental HC; therefore, it is important to consider both physical and familial factors. A formula is herein proposed to assess HC using bodyweight and mid-parental HC. C1 [Tomiwa, Kiyotaka] Kyoto Univ, Dept Clin Genet & Clin Res, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan. [Ikeda, Hiroko] Natl Epilepsy Ctr Shizuoka, Shizuoka, Japan. [Sawada, Akiko; Kimura-Ohba, Shihoko; Matsuzawa, Shigeyuki; Awaya, Tomonori; Shiotani, Yuka; Okada, Masako; Tomiwa, Kiyotaka] Japan Sci & Technol Agcy, Japan Childrens Study, Osaka Res Grp, Osaka, Japan. RP Tomiwa, K (reprint author), Kyoto Univ, Dept Clin Genet & Clin Res, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan. EM tomiwa@pbh.med.kyoto-u.ac.jp FU Research Institute of Science and Technology for Society (RISTEX) of Japan Science and Technology Agency (JST) FX This study was supported by a grant from the Research Institute of Science and Technology for Society (RISTEX) of Japan Science and Technology Agency (JST). We gratefully thank the participating families, Dr T Maeda (Institute of Statistical Mathematics, Japan) for many helpful suggestions on statistics and Kayo Ohmura, Mie Kawajiri, Junko Aota, Kyoko Kobayashi, Akemi Takiishi, and Yumi Yoshida for their assistance. 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Int. PD JUN PY 2010 VL 52 IS 3 BP 343 EP 346 DI 10.1111/j.1442-200X.2009.03002.x PG 4 WC Pediatrics SC Pediatrics GA 611HH UT WOS:000278803000017 PM 19912556 ER PT J AU Frye, CA Bloom, MS Wersinger, S AF Frye, Cheryl A. Bloom, Michael S. Wersinger, Scott TI Androgens, autism and more SO PHYSIOLOGY & BEHAVIOR LA English DT Editorial Material C1 [Frye, Cheryl A.; Bloom, Michael S.] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA. [Wersinger, Scott] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Frye, CA (reprint author), SUNY Albany, Dept Environm Hlth Sci, Life Sci Room 1058, Albany, NY 12222 USA. EM fryeca@gmail.com NR 0 TC 0 Z9 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUN 1 PY 2010 VL 100 IS 3 SI SI BP 197 EP 198 DI 10.1016/j.physbeh.2010.01.017 PG 2 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 603EW UT WOS:000278192400001 PM 20097217 ER PT J AU Bloom, MS Houston, AS Mills, JL Molloy, CA Hediger, ML AF Bloom, Michael S. Houston, Allison S. Mills, James L. Molloy, Cynthia A. Hediger, Mary L. TI Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Autism spectrum disorder; Digit ratio; Hyperandrogenic hypothesis; Measurement error ID 4TH DIGIT RATIO; ETHNIC-DIFFERENCES; RELATIVE LENGTHS; 4TH-DIGIT RATIO; SEX-DIFFERENCES; 2ND; TESTOSTERONE; 2ND-DIGIT; CHILDREN; MALES AB Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4-8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen's D 0.51-0.66, P > 0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r = 0.23, P = 0.039), chronologic age (r = 0.35, P = 0.001), and skeletal age (r = 0.42, P < 0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bloom, Michael S.] SUNY Albany, Dept Environm Hlth Sci, Rensselaer, NY 12214 USA. [Houston, Allison S.] SUNY Albany, Dept Epidemiol & Biostat, Rensselaer, NY 12214 USA. [Mills, James L.; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Molloy, Cynthia A.] Cincinnati Childrens Hosp, Div Neurol, Med Ctr, Cincinnati, OH 45229 USA. RP Bloom, MS (reprint author), Sch Publ Hlth, Dept Environm Hlth Sci, Rm 153,1 Univ Pl, Rensselaer, NY 12144 USA. EM mbloom@albany.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural [Z01 HD008742]; National Institutes of Health [M01 RR08084] FX This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural funding program (Z01 HD008742) and the National Institutes of Health (M01 RR08084). We acknowledge the substantial contributions of Daniel A. Warren, who measured the radiographs as part of his student internship at the NICHD, Scott C. Bello, MD, for critical review of this manuscript at the early stages, and Mark Brasington, who was responsible for all aspects of data collection at the Cincinnati Children's Hospital Medical Center. 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Behav. PD JUN 1 PY 2010 VL 100 IS 3 SI SI BP 221 EP 224 DI 10.1016/j.physbeh.2010.01.005 PG 4 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 603EW UT WOS:000278192400006 PM 20093135 ER PT J AU Messer, A AF Messer, Anne TI Mini-review: Polybrominated diphenyl ether (PBDE) flame retardants as potential autism risk factors SO PHYSIOLOGY & BEHAVIOR LA English DT Review DE Autism; Brominated flame retardants; PBDE; Thyroid hormone ID MAGNETIC PARTICLE IMMUNOASSAY; THYROID-HORMONE LEVELS; SPRAGUE-DAWLEY RATS; GENE-EXPRESSION; INBRED STRAINS; 2,2',4,4',5-PENTABROMODIPHENYL ETHER; NEONATAL EXPOSURE; HEXABROMOCYCLODODECANE HBCD; DEVELOPMENTAL EXPOSURE; SPONTANEOUS BEHAVIOR AB Brominated flame retardants, including Polybrominated diphenyl ethers (PBDEs) have been used at increasing levels in home furnishings and electronics over the past 25 years. They have also become widespread environmental pollutants. High PBDE levels have been detected in food, household dust, and indoor air, with subsequent appearance in animal and human tissues. This minireview summarizes studies on the extent to which these compounds can act as potent thyroid hormone mimetics, and emerging studies on long-term neurological effects of acute administration of PBDEs during development. When these data are considered in combination with the extensive literature on stage-dependent effects of thyroid hormone on aspects of brain development that are also implicated in autistic brains, a hypothesis that PBDEs might also serve as autism risk factors emerges. Studies designed to explicitly test this hypothesis will require chronic exposure paradigms, and specific body burden and behavioral monitoring in animal models. Such testing may help to prioritize extensive human epidemiological studies, as well as offer protocols for evaluation of future compounds. (C) 2010 Elsevier Inc. All rights reserved. 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Behav. PD JUN 1 PY 2010 VL 100 IS 3 SI SI BP 245 EP 249 DI 10.1016/j.physbeh.2010.01.011 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 603EW UT WOS:000278192400010 PM 20100501 ER PT J AU Schaevitz, LR Moriuchi, JM Nag, N Mellot, TJ Berger-Sweeney, J AF Schaevitz, Laura R. Moriuchi, Jennifer M. Nag, Nupur Mellot, Tiffany J. Berger-Sweeney, Joanne TI Cognitive and social functions and growth factors in a mouse model of Rett syndrome SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Autism; Object recognition; Social approach; Social novelty; IGF-1; BDNF; NGF ID MECP2 MUTANT MICE; DIETARY CHOLINE SUPPLEMENTATION; CPG-BINDING PROTEIN-2; FACTOR-I; CEREBROSPINAL-FLUID; GENE-EXPRESSION; RAT-BRAIN; NEUROTROPHIC FACTORS; BDNF TRANSCRIPTION; BASAL FOREBRAIN AB Rett syndrome (RTT) is an autism-spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormalities in social behavior, stereotyped movements, and restricted interests are common features in both RTT and classic autism. While mouse models of both RTT and autism exist, social behaviors have not been explored extensively in mouse models of RTT. Here, we report cognitive and social abnormalities in Mecp2(Ilox) null mice, an animal model of RTT. The null mice show severe deficits in short- and long-term object recognition memories, reminiscent of the severe cognitive deficits seen in RTT girls. Social behavior, however, is abnormal in that the null mice spend more time in contact with stranger mice than do wildtype controls. These findings are consistent with reports of increased reciprocal social interaction in RTT girls relative to classic autism. 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Behav. PD JUN 1 PY 2010 VL 100 IS 3 SI SI BP 255 EP 263 DI 10.1016/j.physbeh.2009.12.025 PG 9 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 603EW UT WOS:000278192400012 PM 20045424 ER PT J AU Frye, CA Llaneza, DC AF Frye, Cheryl A. Llaneza, Danielle C. TI Corticosteroid and neurosteroid dysregulation in an animal model of autism, BTBR mice SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Affect; Learning; Memory; Stress; Neurosteroid; Autism spectrum disorder; Allopregnanolone; Corticosterone ID VENTRAL TEGMENTAL AREA; PLASMA BETA-ENDORPHIN; PROGESTIN CONCENTRATIONS; PSYCHOACTIVE MEDICINES; SOCIAL INTERACTIONS; MAJOR DEPRESSION; RAT HYPOTHALAMUS; SIGMA-RECEPTORS; CORTISOL-LEVELS; INBRED STRAINS AB Autism spectrum disorders (ASD) are a constellation of neurodevelopmental disorders associated with disruptions in social, cognitive, and/or motor behaviors. ASD are more prevalent among males than females and characterized by aberrant social and language development, and a dysregulation in stress-responding. Levels of progesterone (P(4)) and its metabolite 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) are higher and more variable in females compared to males. 3 alpha,5 alpha-THP is also a neurosteroid, which can be rapidly produced de novo in the brain, independent of peripheral gland secretion, and can exert homeostatic effects to modulate stress-responding. An inbred mouse strain that has demonstrated an ASD-like behavioral and neuroendocrine phenotype is BTBR T + tf/J (BTBR). BTBR mice have deficits in cognitive and social behaviors and have high circulating levels of the stress hormone, corticosterone. We hypothesized that central 3 alpha,5 alpha-THP levels would be different among BTBR mice compared to mice on a similar background C57BL/6J (C57/J) and 129S1/SvImJ (129S1). Tissues were collected from BTBR, C57/J and 129S1 male mice and levels of corticosterone, P4, and 3 alpha,5 alpha-THP in plasma and in the hypothalamus, midbrain, hippocampus, and cerebellum were measured by radioimmunoassay. Circulating levels of corticosterone, P4, and 3 alpha,5 alpha-THP were significantly higher among BTBR, than C57/J and 129S1, mice. Levels of P4 in the cerebellum were significantly higher than other brain regions among all mouse strains. Levels of 3 alpha,5 alpha-THP in the hypothalamus of BTBR mice were significantly higher compared to C57/J and 12951 mice. These findings suggest that neuroendocrine dysregulation among BTBR mice extends to 3 alpha,5 alpha-THP. (C) 2010 Elsevier Inc. All rights reserved. C1 [Frye, Cheryl A.; Llaneza, Danielle C.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [Frye, Cheryl A.] SUNY Albany, Dept Biol Sci, Albany, NY 12222 USA. [Frye, Cheryl A.] SUNY Albany, Ctr Life Sci, Albany, NY 12222 USA. [Frye, Cheryl A.] SUNY Albany, Neurosci Res Ctr, Albany, NY 12222 USA. RP Frye, CA (reprint author), SUNY Albany, Dept Psychol, Life Sci Room 1058, Albany, NY 12222 USA. EM fryeca@gmail.com FU NIMH [MH06769801]; NSF [IBN0316083] FX This research was supported by grants from the NIMH (MH06769801), the NSF (IBN0316083) and an intramural Faculty Research Award Program. We thank Dr. Jacqueline Crawley and Dr. Jill Silverman, Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute of Mental Health, who provided scientific input and practical assistance. We also thank the assistance of Dr. Valerie Bolivar and Dr. Derek Symula at Wadsworth Center. Tissues generated for training purposes for Dr. Symula provided the basis for this study. 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TI Communication, interventions, and scientific advances in autism: A commentary SO PHYSIOLOGY & BEHAVIOR LA English DT Editorial Material DE Autism spectrum disorders; Social; Communication; Language; Gender differences; Behavior modeling; Picture Exchange Communication System; Mice; Genetics; BTBR; Center for Autism and Related Disabilities; Education programs; Translational research ID HIGH-FUNCTIONING AUTISM; TUBEROUS SCLEROSIS COMPLEX; SOCIAL APPROACH BEHAVIORS; BTBR-T+TF/J MICE; SPECTRUM DISORDERS; RISK-FACTORS; CANDIDATE GENES; GENOMIC SCREEN; MOLECULAR-GENETICS; ASPERGERS-DISORDER AB Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger Syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its comorbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research. (C) 2010 Elsevier Inc. All rights reserved. C1 [Llaneza, Danielle C.; Frye, Cheryl A.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [DeLuke, Susan V.] Coll St Rose, Dept Literacy & Special Educ, Albany, NY USA. [Batista, Myra] Kevin G Langan Sch, Ctr Disabil Serv, Albany, NY USA. [Crawley, Jacqueline N.] NIMH, Intramural Res Program, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Christodulu, Kristin V.] SUNY Albany, Ctr Autism & Related Disabil, Albany, NY 12222 USA. [Frye, Cheryl A.] SUNY Albany, Dept Biol, Albany, NY 12222 USA. [Frye, Cheryl A.] SUNY Albany, Ctr Life Sci, Albany, NY 12222 USA. RP Frye, CA (reprint author), SUNY Albany, Dept Psychol, Life Sci Room 1058, Albany, NY 12222 USA. 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Behav. PD JUN 1 PY 2010 VL 100 IS 3 SI SI BP 268 EP 276 DI 10.1016/j.physbeh.2010.01.003 PG 9 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 603EW UT WOS:000278192400014 PM 20093134 ER PT J AU Fifer, WP Byrd, DL Kaku, M Eigsti, IM Isler, JR Grose-Fifer, J Tarullo, AR Balsam, PD AF Fifer, William P. Byrd, Dana L. Kaku, Michelle Eigsti, Inge-Marie Isler, Joseph R. Grose-Fifer, Jillian Tarullo, Amanda R. Balsam, Peter D. TI Newborn infants learn during sleep SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EEG; eyelid conditioning; neonate ID AUDITORY EVOKED-POTENTIALS; HEART-RATE; DEATH-SYNDROME; SPEECH SOUNDS; FULL-TERM; CEREBELLUM; DYSLEXIA; AGE; ABNORMALITIES; MATURATION AB Newborn infants must rapidly adjust their physiology and behavior to the specific demands of the novel postnatal environment. This adaptation depends, at least in part, on the infant's ability to learn from experiences. We report here that infants exhibit learning even while asleep. Bioelectrical activity from face and scalp electrodes was recorded from neonates during an eye movement conditioning procedure in which a tone was followed by a puff of air to the eye. Sleeping newborns rapidly learned the predictive relationship between the tone and the puff. Additionally, in the latter part of training, these infants exhibited a frontally maximum positive EEG slow wave possibly reflecting memory updating. As newborns spend most of their time sleeping, the ability to learn about external stimuli in the postnatal environment during non-awake states may be crucial for rapid adaptation and infant survival. 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EM wpf1@columbia.edu FU Sackler Institute of Developmental Psychobiology at Columbia University; National Institutes of Health [R37 HD032774, T32 MH018264, R01 MH068073] FX We thank Elizabeth Alf, Carmen Gennarini, Michael M. Myers, J. David Nugent, Michele Pasamba, Albany Perez, Kimon Violaris, and Jessica Wilson for help with many aspects of this project. This research was supported by the Sackler Institute of Developmental Psychobiology at Columbia University and by National Institutes of Health Grants R37 HD032774 (to W.P.F.), T32 MH018264 (to D.L.B., I.-M.E., and A.R.T.), and R01 MH068073 (to P.D.B.). 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These scans were based on common genetic variants in human populations. This new and powerful technology was then applied to the existing DNA-based datasets with information on psychiatric disorders. As a result, an unprecedented amount of novel scientific insights related to the underlying biology and genetics of psychiatric disorders was obtained. The dominant design of these studies, so called "genome-wide association studies" (GWAS), used statistical methods which minimized the risk of false positive reports and provided much greater power to detect genotype-phenotype associations. All findings were entirely data-driven rather than hypothesis-driven, which often made it difficult for researchers to understand or interpret the findings. Interestingly, this work in genetics is indicating how non-specific some genes are for psychiatric disorders, having associations in common for schizophrenia, bipolar disorder and autism. This suggests that the earlier stages of psychiatric disorders may be multi-valent and that early detection, coupled with a clearer understanding of the environmental factors, may allow prevention. At the present time, the rich "harvest" from GWAS still has very limited power to predict the variation in psychiatric disease status at individual level, typically explaining less than 5% of the total risk variance. The most recent studies of common genetic variation implicated the role of major histocompatibility complex in schizophrenia and other disorders. They also provided molecular evidence for a substantial polygenic component to the risk of psychiatric diseases, involving thousands of common alleles of very small effect. The studies of structural genetic variation, such as copy number variants (CNV), coupled with the efforts targeting rare genetic variation (using the emerging whole-genome "deep" sequencing technologies) will become the area of the greatest interest in the field of genetic epidemiology. This will be complemented by the studies of epigenetic phoenomena, changes of expression at a large scale and understanding gene-gene interactions in complex networks using systems biology approaches. A deeper understanding of the underlying biology of psychiatric disorders is essential to improve diagnoses and therapies of these diseases. New technologies - genome-wide association studies, imaging and the optical manipulation of neural circuits are promising to provide novel insights and lead to new treatments. C1 [Rudan, Igor] Univ Split, Croatian Ctr Global Hlth, Fac Med, Split, Croatia. [Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. RP Rudan, I (reprint author), Univ Split, Croatian Ctr Global Hlth, Fac Med, Split, Croatia. 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Danub. PD JUN PY 2010 VL 22 IS 2 BP 190 EP 192 PG 3 WC Psychiatry SC Psychiatry GA 616JT UT WOS:000279206200008 PM 20562745 ER PT J AU Kantojarvi, K Onkamo, P Vanhala, R Alen, R Hedman, M Sajantila, A Nieminen-von Wendt, T Jarvela, I AF Kantojarvi, Katri Onkamo, Paivi Vanhala, Raija Alen, Reija Hedman, Minttu Sajantila, Antti Nieminen-von Wendt, Taina Jarvela, Irma TI Analysis of 9p24 and 11p12-13 regions in autism spectrum disorders: rs1340513 in the JMJD2C gene is associated with ASDs in Finnish sample SO PSYCHIATRIC GENETICS LA English DT Article DE autism spectrum disorder; autism; JMJD2C; obsessive compulsive disorder; 9p24; SLC1A1 ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN TRANSPORTER GENE; SUSCEPTIBILITY LOCUS; REPETITIVE BEHAVIOR; LINKAGE; SLC1A1; CNTNAP2; RISK; EPIDEMIOLOGY; RETARDATION AB Objective Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic to obsessive-compulsive disorder (OCD). Aberrant glutamate function has been suggested to a risk for both ASDs and OCD. Considering the common metabolic pathway and recent results from association studies both in OCD and ASDs, a question, whether there is common molecular background in ASDs and OCD, was raised. Methods Ten single nucleotide polymorphisms (SNPs) at 9p24 and 11p12-p13 containing glutamate transporter genes SLC1A1 and SLC1A2 and their neighboring regions in 175 patients with ASDs and 216 controls of Finnish origin were analyzed using real-time-PCR or direct sequencing. Results The strongest association was detected with rs1340513 in the JMJD2C gene at 9p24.1 (P=0.007; corrected P=0.011) that is the same SNP associated with infantile autism (P=0.0007) in the autism genome project consortium (2007). No association was detected at 11p12-p13 with ASD. Interestingly, the strongest association in OCD has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24. Conclusion In summary, our results give evidence for a possible common locus for OCD and ASDs at 9p24. We speculate that the area may represent a special candidate region for obsessive repetitive symptoms in ASDs. Psychiatr Genet 20:102-108 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Kantojarvi, Katri; Jarvela, Irma] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. [Onkamo, Paivi] Univ Helsinki, Dept Biol & Environm Sci, FIN-00014 Helsinki, Finland. [Hedman, Minttu; Sajantila, Antti] Univ Helsinki, Dept Forens Med, FIN-00014 Helsinki, Finland. [Vanhala, Raija; Nieminen-von Wendt, Taina] Univ Helsinki, Hosp Children & Adolescents, FIN-00014 Helsinki, Finland. [Alen, Reija] Jyvaskyla Cent Hosp, Dept Child Neurol, Jyvaskyla, Finland. [Jarvela, Irma] Univ Helsinki, Cent Hosp, Mol Genet Lab, FIN-00014 Helsinki, Finland. RP Kantojarvi, K (reprint author), Univ Helsinki, Dept Med Genet, POB 63, FIN-00014 Helsinki, Finland. EM katri.kantojarvi@helsinki.fi RI Jarvela, Irma/L-5836-2013 FU European Union [LSHM-CT-2005-512158]; Helsinki University Hospital [TYH7227] FX The authors are grateful to the families for participation. The authors also thank Milla Ihalainen, Tarja Jarvinen, and Ulla Sarin-Seppanen for their excellent technical assistance. The project was funded by the European Union (LSHM-CT-2005-512158) and Helsinki University Hospital research funding (TYH7227). 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Genet. PD JUN PY 2010 VL 20 IS 3 BP 102 EP 108 DI 10.1097/YPG.0b013e32833a2080 PG 7 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 601OV UT WOS:000278072700003 PM 20410850 ER PT J AU Li, XP Hu, ZM He, YQ Xiong, ZM Long, ZG Peng, Y Bu, FX Ling, J Xun, GL Mo, XY Pan, Q Zhao, JP Xia, K AF Li, Xiaoping Hu, Zhengmao He, Yiqun Xiong, Zhimin Long, Zhigao Peng, Yu Bu, Fengxiao Ling, Jie Xun, Guanglei Mo, Xiaoyun Pan, Qian Zhao, Jingping Xia, Kun TI Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population SO PSYCHIATRIC GENETICS LA English DT Article DE autism; CNTNAP2; single nucleotide polymorphism; transmission disequilibrium test ID SPECTRUM DISORDERS; NEUREXIN SUPERFAMILY; GENOMEWIDE SCREEN; MYELINATED AXONS; K+ CHANNELS; LINKAGE; GENES; ETIOLOGY; CASPR2; MEMBER AB Objectives Autism is a neurodevelopmental disorder, and genetic factors play an important role in its pathogenesis. Earlier findings suggest the CNTNAP2 as a predisposition locus of autism, but no study has been carried out on the possible association of CNTNAP2 with autism in the Chinese Han population. Methods In this study, three single nucleotide polymorphisms located within the CNTNAP2 were genotyped in 185 Chinese Han autistic families by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by a transmission disequilibrium test. Results The results show that a common noncoding variant (rs10500171) is associated with the increased risk for autism, and haplotype T-A (rs7794745-rs10500171, P=0.011) and haplotype A-T-A (rs10244837-rs7794745-rs10500171, P=0.032) also showed evidence of association. Conclusion The results of family-based association study suggested that the CNTNAP2 is a susceptibility gene of autism in the Chinese Han population. Psychiatr Genet 20:113-117 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Li, Xiaoping; Hu, Zhengmao; Long, Zhigao; Peng, Yu; Bu, Fengxiao; Ling, Jie; Mo, Xiaoyun; Pan, Qian; Xia, Kun] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China. [He, Yiqun; Xiong, Zhimin; Xun, Guanglei; Zhao, Jingping] Cent S Univ, Xaingya Hosp 2, Mental Hlth Inst, Changsha 410011, Hunan, Peoples R China. RP Xia, K (reprint author), Cent S Univ, State Key Lab Med Genet, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China. EM zhaojingpinghunan@yahoo.com.cn; xiakun@sklmg.edu.cn FU National Natural Science Foundation of China [30630062, 30600247]; Chinese National Programs for Fundamental Research and Development (973 Program) [2004CB518601] FX The authors thank all families for their understanding and participation in this study. This research is supported by the National Natural Science Foundation of China (Grant No. 30630062 and Grant No. 30600247) and the major Project of Chinese National Programs for Fundamental Research and Development (973 Program) (Grant No. 2004CB518601). CR Abrahams BS, 2007, P NATL ACAD SCI USA, V104, P17849, DOI 10.1073/pnas.0706128104 Alarcon M, 2008, AM J HUM GENET, V82, P150, DOI 10.1016/j.ajhg.2007.09.005 Arking DE, 2008, AM J HUM GENET, V82, P160, DOI 10.1016/j.ajhg.2007.09.015 Auranen M, 2002, AM J HUM GENET, V71, P777, DOI 10.1086/342720 Bailey A, 1996, J CHILD PSYCHOL PSYC, V37, P89, DOI 10.1111/j.1469-7610.1996.tb01381.x Bakkaloglu B, 2008, AM J HUM GENET, V82, P165, DOI 10.1016/j.ajhg.2007.09.017 Barrett JC, 2005, BIOINFORMATICS, V21, P263, DOI 10.1093/bioinformatics/bth457 Dale O, 1996, ACTA ANAESTH SCAND, V40, P771 Folstein SE, 2001, NAT REV GENET, V2, P943, DOI 10.1038/35103559 FOLSTEIN SE, 1991, PEDIATRICS, V87, P767 HIROTA T, 1989, JPN J HUM GENET, V34, P217, DOI 10.1007/BF01900724 Bailey A, 1998, HUM MOL GENET, V7, P571 Palferman S, 2001, AM J HUM GENET, V69, P570 Lord C, 2000, NEURON, V28, P355, DOI 10.1016/S0896-6273(00)00115-X Philippe A, 1999, HUM MOL GENET, V8, P805, DOI 10.1093/hmg/8.5.805 Poliak S, 2003, J CELL BIOL, V162, P1149, DOI 10.1083/jcb.200305018 Poliak S, 1999, NEURON, V24, P1037, DOI 10.1016/S0896-6273(00)81049-1 Poot M, 2009, NEUROGENETICS, V11, P81 SCHOPLER E, 1980, J AUTISM DEV DISORD, V10, P91, DOI 10.1007/BF02408436 Vernes SC, 2008, NEW ENGL J MED, V359, P2337, DOI 10.1056/NEJMoa0802828 Weinberg CR, 1998, AM J HUM GENET, V62, P969, DOI 10.1086/301802 Weinberg CR, 1999, AM J EPIDEMIOL, V150, P428 Zhang X, 2005, BIOMED ENVIRON SCI, V18, P334 NR 23 TC 17 Z9 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD JUN PY 2010 VL 20 IS 3 BP 113 EP 117 DI 10.1097/YPG.0b013e32833a216f PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 601OV UT WOS:000278072700005 PM 20414140 ER PT J AU Doyle, G AF Doyle, Griffin TI Infant/Child Mental Health, Early Intervention, and Relationship-Based Therapies: A Neurorelational Framework for Interdisciplinary Practice SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Book Review ID AUTISM; CHILDREN RP Doyle, G (reprint author), 4400 East West Highway,Suite 329, Bethesda, MD 20814 USA. 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PD SUM PY 2010 VL 73 IS 2 BP 198 EP 204 PG 7 WC Psychiatry SC Psychiatry GA 608MC UT WOS:000278587300012 ER PT J AU Kim, SM Han, DH Lyoo, HS Min, KJ Kim, KH Renshaw, P AF Kim, Sun Mi Han, Doug Hyun Lyoo, Hang Sik Min, Kyung Joon Kim, Kyung Ho Renshaw, Perry TI Exposure to Environmental Toxins in Mothers of Children with Autism Spectrum Disorder SO PSYCHIATRY INVESTIGATION LA English DT Article DE Environmental toxins; Autism spectrum disorders; Child behaviors ID POLYBROMINATED DIPHENYL ETHERS; BROMINATED FLAME-RETARDANT; PERINATAL EXPOSURE; NEONATAL EXPOSURE; BISPHENOL-A; POLYCHLORINATED-BIPHENYLS; SPONTANEOUS BEHAVIOR; BRAIN-DEVELOPMENT; DUTCH CHILDREN; SCHOOL-AGE AB Objective Environmental pollutants, especially environmental toxins (ET), may have the potential to disrupt neurodevelopmental pathways during early brain development. This study was designed to test our hypothesis that mothers with autism spectrum disorder (ASD) children would have less knowledge about ET and more chance to be exposed to ET than mothers with healthy children (MHC). Methods One hundred and six biologic mothers with ASD children (MASD) and three hundred twenty four biologic mothers with healthy children MHC were assessed using two questionnaires asking about ET. Results The total score in response to questions related to knowledge about ET in MHC was higher than that in MASD. The possibility of exposure to ET was higher in MASD than MHC. MASD showed higher sub-scale scores in terms of exposures to canned food, plastics, waste incinerators, old electronics, microwavable food, and textiles. Conclusion The current results show that reduced knowledge about ET and greater exposure to ET may be associated with autism spectrum disorder. 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PD JUN PY 2010 VL 7 IS 2 BP 122 EP 127 DI 10.4306/pi.2010.7.2.122 PG 6 WC Psychiatry SC Psychiatry GA 614PN UT WOS:000279072300007 PM 20577621 ER PT J AU Zander, E Dahlgren, SO AF Zander, Eric Dahlgren, Sven Olof TI WISC-III Index Score Profiles of 520 Swedish Children With Pervasive Developmental Disorders SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE Wechsler Intelligence Scale for Children-Third Edition; profile analysis; autistic disorder; Asperger's disorder; PDD-NOS ID WECHSLER INTELLIGENCE SCALE; HIGH-FUNCTIONING AUTISM; LONG-TERM STABILITY; ASPERGER-SYNDROME; SYMPTOM PROFILES; SUBTEST ANALYSIS; PDD-NOS; DSM-IV; EDITION; ACHIEVEMENT AB WISC-III (Wechsler, 1991) index score profiles and their characteristics were examined with traditional statistics in a large Swedish sample consisting of children with autistic disorder (n = 85). Asperger's disorder (n = 341), or pervasive developmental disorders not otherwise specified (PDD-NOS: n = 94). There was a clear and significant difference in level between children with Asperger's disorder, who performed in the average range according to the Swedish standardization, and children with either autistic disorder or PDD-NOS, who performed below the average range (almost 2 standard deviations below the mean), but few other differences between the diagnostic groups were found. The variation in this sample, compared with the Swedish standardization, was generally larger in regard to the size of standard deviations and to the proportion of individuals who exhibited significant differences between indices. The result implied that a WISC-III profile could not be used to discriminate between the different PDDs. C1 [Zander, Eric] Karolinska Inst, Child & Adolescent Psychiat Div, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Zander, Eric; Dahlgren, Sven Olof] Stockholm Cty Council, Habilitat Serv, Res & Dev Unit, Stockholm, Sweden. [Dahlgren, Sven Olof] Autismforum, Stockholm, Sweden. 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Assess. PD JUN PY 2010 VL 22 IS 2 BP 213 EP 222 DI 10.1037/a0018335 PG 10 WC Psychology, Clinical SC Psychology GA 609OF UT WOS:000278665600002 PM 20528049 ER PT J AU Moines, LESM Allen, DN Puente, AE Neblina, C AF Moines, Liza E. San Miguel Allen, Daniel N. Puente, Antonio E. Neblina, Cris TI Validity of the WISC-IV Spanish for a Clinically Referred Sample of Hispanic Children SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE WISC-IV Spanish; Hispanic children; learning disabilities; ADHD; Puerto Rican children ID TRAUMATIC BRAIN-INJURY; HIGH-FUNCTIONING AUTISM; CRITERION VALIDITY; INTELLIGENCE SCALE; ADOLESCENTS; PROFILES; EDITION AB The Wechsler Intelligence Scale for Children (WISC) is the most commonly used intelligence test for children. Five years ago, a Spanish version of the WISC-IV was published (WISC-IV Spanish: Wechsler. 2005). hut a limited amount of published information is available regarding its utility when assessing clinical samples. The current study included 107 children who were Spanish speaking and of Puerto Rican descent that had been administered the WISC-IV Spanish. They were subdivided into a clinical sample of 35 children with diagnoses of various forms of brain dysfunction (primarily learning disability. attention-deficit/hyperactivity disorder, and epilepsy) and a comparison group made up of 72 normal children who were part of the WISC-IV Spanish version standardization sample. Comparisons between these groups and the standardization sample were performed for the WISC-IV Spanish index and subtest scores. Results indicated that the clinical sample performed worse than the comparison samples on the Working Memory and Processing Speed Indexes, although findings varied to some extent depending on whether the clinical group was compared with the normal comparison group or the standardization sample. These findings provide support for the criterion validity of the WISC-IV Spanish when it is used to assess a clinically referred sample with brain dysfunction. C1 [Moines, Liza E. San Miguel] Univ Puerto Rico, Sch Med, Neurol Sect, Child Neurol Program, San Juan, PR 00936 USA. [Allen, Daniel N.; Neblina, Cris] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Puente, Antonio E.] Univ N Carolina, Dept Psychol, Wilmington, NC USA. RP Moines, LESM (reprint author), Univ Puerto Rico, Sch Med, Neurol Sect, Child Neurol Program, Med Sci Campus, San Juan, PR 00936 USA. EM lsanmiguel@rcm.upr.edu CR Allen DN, 2010, PSYCHOL ASSESSMENT, V22, P57, DOI 10.1037/a0016056 Allen DN, 2009, CHILD NEUROPSYCHOL, V15, P543, DOI 10.1080/09297040902748234 *AM ED RES ORG AM, 1999, STAND ED PSYCH TEST American Psychiatric Association, 2000, DIAGN STAT MAN MENT Ardila A., 1992, NEUROPSYCHOLOGICAL E BRADEN JP, 2007, J PSYCHOEDUCATIONAL, V25, P292, DOI 10.1177/0734282907302955 Mayes Susan Dickerson, 2006, J Atten Disord, V9, P486, DOI 10.1177/1087054705283616 Camara WJ, 2000, PROF PSYCHOL-RES PR, V31, P141, DOI 10.1037/0735-7028.31.2.141 Donders J, 2008, J INT NEUROPSYCH SOC, V14, P651, DOI 10.1017/S1355617708080752 Donders J, 1997, ASSESSMENT, V4, P107 Donders J, 2001, J INT NEUROPSYCH SOC, V7, P892 Goldstein G, 2008, NEUROPSYCHOLOGY, V22, P301, DOI 10.1037/0894-4105.22.3.301 KINSELLA G, 1995, J PEDIATR PSYCHOL, V20, P753, DOI 10.1093/jpepsy/20.6.753 Lezak M, 2004, NEUROPSYCHOLOGICAL A Matarazzo J. D., 1972, WECHSLERS MEASUREMEN Puente A. 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PD JUN PY 2010 VL 22 IS 2 BP 465 EP 469 DI 10.1037/a0018895 PG 5 WC Psychology, Clinical SC Psychology GA 609OF UT WOS:000278665600026 ER PT J AU Welch, KA Stanfield, AC Moorhead, TW Haga, K Owens, DCG Lawrie, SM Johnstone, EC AF Welch, K. A. Stanfield, A. C. Moorhead, T. W. Haga, K. Owens, D. C. G. Lawrie, S. M. Johnstone, E. C. TI Amygdala volume in a population with special educational needs at high risk of schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Amygdala; cognitive impairment; high risk; learning disability; magnetic resonance imaging; schizophrenia ID EDINBURGH HIGH-RISK; MILD LEARNING-DISABILITY; VOXEL-BASED MORPHOMETRY; COMORBID SCHIZOPHRENIA; PSYCHOTIC SYMPTOMS; BRAIN STRUCTURE; METAANALYSIS; ADOLESCENTS; AUTISM; MRI AB Background. The mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia. Method. Assessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated. Results. Right amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p= 0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p <0.05), but not in either control group. Conclusions. Intellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis. C1 [Welch, K. A.; Stanfield, A. C.; Moorhead, T. W.; Haga, K.; Owens, D. C. G.; Lawrie, S. M.; Johnstone, E. C.] Univ Edinburgh, Sch Mol & Clin Med, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. RP Welch, KA (reprint author), Univ Edinburgh, Royal Edinburgh Hosp, Sch Mol & Clin Med, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. EM kwelch1@staffmail.ed.ac.uk FU United Kingdom Medical Research Council Programme; Sackler Foundation; BMA FX We are deeply grateful to the participants and their families for their generous assistance. We thank the staff at the Division of Pyschiatry involved in recruiting the sample and those at the Scottish Higher Education Funding Council Brain Imaging Research Centre. This research was funded by a United Kingdom Medical Research Council Programme Grant awarded to E.C.J. T.W.M. was funded as part of this grant. S.M.L. was supported by the Sackler Foundation. K.H. was funded by a BMA grant to A.C.S. CR Achenbach T. 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Med. PD JUN PY 2010 VL 40 IS 6 BP 945 EP 954 DI 10.1017/S0033291709990870 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 603WZ UT WOS:000278240100007 PM 19732477 ER PT J AU Egan, CE Barnes-Holmes, D AF Egan, Claire E. Barnes-Holmes, Dermot TI ESTABLISHING MAND EMERGENCE: THE EFFECTS OF THREE TRAINING PROCEDURES AND MODIFIED ANTECEDENT CONDITIONS SO PSYCHOLOGICAL RECORD LA English DT Article DE autism; expressive language; mand; receptive language; tact ID YOUNG-CHILDREN; BEHAVIOR; LANGUAGE; AUTISM; TACTS AB This study examined the effects of a modified antecedent during probes for emergent mands following listener versus tact training for children with autism. Eight students, aged 7 to 11, were trained to respond to 3 sets of relational responses (front/back, left/right, on/under), each assigned a nonsense label. Three training types were evaluated: listener training, tact training, and listener-tact training combined. Following the experimental training, probes for emergent mands were conducted under modified antecedent conditions. Results showed that modified antecedent conditions were critical in demonstrating mand emergence for some participants. C1 [Egan, Claire E.; Barnes-Holmes, Dermot] Natl Univ Ireland, Maynooth, Kildare, Ireland. RP Egan, CE (reprint author), Hong Kong Inst Educ, Dept Special Educ & Counselling, 10 Lo Ping Rd, Tai Po, Hong Kong, Peoples R China. EM claire@ied.edu.hk CR Barnes-Holmes D, 2000, BEHAV ANALYST, V23, P69 EGAN CE, 2008, EXAMINING ANTE UNPUB Egan CE, 2009, J APPL BEHAV ANAL, V42, P691, DOI 10.1901/jaba.2009.42-691 GUESS D, 1973, J APPL BEHAV ANAL, V6, P311, DOI 10.1901/jaba.1973.6-311 Hall G, 1987, Anal Verbal Behav, V5, P41 Hayes S. 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L., 1998, TEACHING LANGUAGE CH Sundberg M L, 1990, Anal Verbal Behav, V8, P83 Twyman J., 1996, ANAL VERBAL BEHAV, V13, P1 Wynn JW, 2003, BEHAV INTERVENT, V18, P245, DOI 10.1002/bin.142 NR 23 TC 2 Z9 2 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 SUM PY 2010 VL 60 IS 3 BP 473 EP 487 PG 15 WC Psychology, Multidisciplinary SC Psychology GA 629QU UT WOS:000280215600006 ER PT J AU Murphy, C Barnes-Holmes, D AF Murphy, Carol Barnes-Holmes, Dermot TI ESTABLISHING COMPLEX DERIVED MANDING WITH CHILDREN WITH AND WITHOUT A DIAGNOSIS OF AUTISM SO PSYCHOLOGICAL RECORD LA English DT Article DE autism; children; derived mands; language; more/less relations ID DISCRIMINATION RESPONSE FUNCTIONS; SEVERE DEVELOPMENTAL-DISABILITIES; SKINNERS VERBAL-BEHAVIOR; RELATIONAL FRAME-THEORY; BASE-LINE RELATIONS; STIMULUS EQUIVALENCE; LESS-THAN; TRANSFORMATION; ACCORDANCE; OPERATIONS AB Participants were four 14-year-old adolescent boys with diagnosed autism spectrum disorder and 3 children without diagnosed learning disorders aged 5 to 11. Training trials to establish more/less relational functions for 2 stimuli (X and Y, respectively) were interspersed with training trials to establish comparative relations among 5 other arbitrary stimuli (Le., A is more than B, B is more than C, C is more than D, and D is more than E). Subsequent tests showed a derived transformation of functions for 7 participants (i.e., derived more/less mands). Exemplar training was required with 2 children. An ABA design with 3 participants showed manding was controlled by trained relations. C1 [Murphy, Carol; Barnes-Holmes, Dermot] Natl Univ Ireland, Maynooth, Kildare, Ireland. RP Murphy, C (reprint author), Natl Univ Ireland Maynooth, Dept Psychol, Maynooth, Kildare, Ireland. 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SO PSYCHOLOGICAL REPORTS LA English DT Article ID HIGH-FUNCTIONING AUTISM; MIRROR-NEURON SYSTEM; ASPERGER-SYNDROME; SOCIAL ACKNOWLEDGMENT; RISK-FACTORS; SELF; SCHIZOPHRENIA; COGNITION; TRAUMA; ADULTS AB Trauma survivors with PTSD show social interaction and relationship impairments. It is hypothesized that traumatic experiences lead to known PTSD symptoms, empathic ability impairment, and difficulties in sharing affective, emotional, or cognitive states. A PTSD group (N = 16) and a nontraumatized Control group (N = 16) were compared on empathic abilities, namely the Empathic Resonance Test, Reading the Mind in the Eyes Test, and Faux Pas Test. The Interpersonal Reactivity Index as a self-report measure of empathy and measures of nonsocial cognitive functions, namely the Verbal Fluency Test, the Five-Point Test, and the Stroop Test, were also administered. The PTSD group showed lower empathic resonance. No clear indications of other impairments in social cognitive functions were found. The PTSD group had significantly higher personal distress. Empathic resonance impairments did not correlate with subjective severity of PTSD symptomatology. This article discusses whether impaired empathic resonance in PTSD trauma survivors is a consequence of trauma itself or a protective coping strategy. C1 [Nietlisbach, Gabriela; Maercker, Andreas] Univ Zurich, Dept Psychol, CH-8050 Zurich, Switzerland. [Roessler, Wulf; Haker, Helene] Psychiat Univ Hosp Zurich, Dept Gen & Social Psychiat, Zurich, Switzerland. RP Nietlisbach, G (reprint author), Univ Zurich, Dept Psychol, Binzmuehlestr 14-17, CH-8050 Zurich, Switzerland. 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PD JUN PY 2010 VL 106 IS 3 BP 832 EP 844 DI 10.2466/PR0.106.3.832-844 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 626YS UT WOS:000280005100021 PM 20712172 ER PT J AU Kokkinaki, M Lee, TL He, ZP Jiang, JJ Golestaneh, N Hofmann, MC Chan, WY Dym, M AF Kokkinaki, Maria Lee, Tin-Lap He, Zuping Jiang, Jiji Golestaneh, Nady Hofmann, Marie-Claude Chan, Wai-Yee Dym, Martin TI Age affects gene expression in mouse spermatogonial stem/progenitor cells SO REPRODUCTION LA English DT Article ID COLONY-STIMULATING FACTOR-1; ADVANCING PATERNAL AGE; LINE STEM-CELLS; SELF-RENEWAL; UNDIFFERENTIATED SPERMATOGONIA; NEUROTROPHIC FACTOR; SEMEN QUALITY; NICHE; AUTISM; TESTIS AB Spermatogenesis in man starts with spermatogonial stem cells (SSCs), and leads to the production of sperm in similar to 64 days, common to old and young men. Sperm from elderly men are functional and able to fertilize eggs and produce offspring, even though daily sperm production is more than 50% lower and damage to sperm DNA is significantly higher in older men than in those who are younger. Our hypothesis is that the SSC/spermatogonial progenitors themselves age. To test this hypothesis, we studied the gene expression profile of mouse SSC/progenitor cells at several ages using microarrays. After sequential enzyme dispersion, we purified the SSC/progenitors with immunomagnetic cell sorting using an antibody to GFRA1, a known SSC/progenitor cell marker. RNA was isolated and used for the in vitro synthesis of amplified and labeled cRNAs that were hybridized to the Affymetrix mouse genome microarrays. The experiments were repeated twice with different cell preparations, and statistically significant results are presented. Quantitative RT-PCR analysis was used to confirm the microarray results. 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TI A Modified Hermeneutic Phenomenological Approach Toward Individuals Who Have Autism SO RESEARCH IN NURSING & HEALTH LA English DT Article DE hermeneutic phenomenology; autism; Martin Heidegger ID INTERPRETIVE PHENOMENOLOGY; ASPERGER-SYNDROME; NURSING-RESEARCH; SPECTRUM; DIAGNOSIS AB Individuals with autism have a unique cognitive processing style characterized by impaired abstraction, impaired theory of mind, and visual as opposed to linguistic processing of information. A consequence of this unique cognitive processing style is that traditional ways of hermeneutical phenomenological examination may be inadequate to achieve the kind of understanding of experience toward which this method is directed. 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Gen. Psychol. PD JUN PY 2010 VL 14 IS 2 SI SI BP 122 EP 140 DI 10.1037/a0019438 PG 19 WC Psychology, Multidisciplinary SC Psychology GA 612GY UT WOS:000278886000008 ER PT J AU Koelkebeck, K Pedersen, A Suslow, T Kueppers, KA Arolt, V Ohrmann, P AF Koelkebeck, Katja Pedersen, Anya Suslow, Thomas Kueppers, Kerstin Annika Arolt, Volker Ohrmann, Patricia TI Theory of Mind in first-episode schizophrenia patients: Correlations with cognition and personality traits SO SCHIZOPHRENIA RESEARCH LA English DT Article DE First-episode schizophrenia; Theory of Mind; Trait marker; Neurocognitive functioning; Moving Shapes ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; INTENTIONAL MOVEMENT; EMPATHIC ABILITIES; ANIMATED SHAPES; MENTAL STATES; 1ST EPISODE; RECOGNITION; DEFICITS; ALEXITHYMIA AB Introduction: There is substantial evidence for Theory of Mind (ToM) deficits in patients with schizophrenia. Many psychotic symptoms may best be understood in light of an impaired capacity to infer one's own and other persons' mental states and to relate those to executing behavior. The aim of our study was to investigate ToM abilities in first-episode schizophrenia patients and to analyze them in relation to neuropsychological and psychopathological functioning. Materials and methods: A modified Moving Shapes paradigm was used to assess ToM abilities in 23 first-episode patients with schizophrenia and 23 matched healthy controls. Participants had to describe animated triangles which moved (1) randomly, (2) goal-directed, or (3) in complex, socially interactive ways (TOM video sequences). Neuropsychological functioning, psychopathology, autistic and alexithymic features as well as empathetic abilities were correlated with TOM performance. Results: Compared to healthy controls, first-episode schizophrenia patients gave more incorrect descriptions and used less ToM-related vocabulary when responding to socially complex ToM video sequences. No group differences were revealed for videos with random movements. ToM abilities correlated significantly with positive symptoms, reasoning, verbal memory performance and verbal IQ but not with empathetic abilities or autistic and alexithymic features. When controlling for reasoning, verbal memory performance and verbal IQ, the correctness of video descriptions was still significantly worse in schizophrenia patients. Discussion: The results of our study in first-episode schizophrenia patients underline recent findings on ToM deficits in the early course of schizophrenia. Only a moderate influence of neurocognitive deficits on ToM performance was observed. Impairment in Tom abilities seems to be predominantly independent of clinical state, alexithymia and empathy. (C) 2009 Elsevier B.V. All rights reserved. C1 [Koelkebeck, Katja; Pedersen, Anya; Suslow, Thomas; Kueppers, Kerstin Annika; Arolt, Volker; Ohrmann, Patricia] Univ Munster, Sch Med, Dept Psychiat, D-48149 Munster, Germany. RP Koelkebeck, K (reprint author), Univ Munster, Sch Med, Dept Psychiat, Albert Schweitzer Str 11, D-48149 Munster, Germany. EM katja.koelkebeck@ukmuenster.de; Anya.Pedersen@ukmuenster.de; Thomas.Suslow@ukmuenster.de; Kerstin.Kueppers@ukmuenster.de; Volker.Arolt@ukmuenster.de; Patricia.Ohrmann@ukmuenster.ie RI Koelkebeck, Katja/F-3977-2014 FU Uta and Chris Frith FX We would like to thank Uta and Chris Frith and their staff members for kindly providing the Moving Shapes paradigm and rating descriptions, as well as for their support in the development of this study. Further, we would also like to thank Tins Weimann for preparing the videos in a shortened version. We would also sincerely like to thank all the subjects for their participation in this study and all the staff involved in the data acquisition. 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Kwok, Yvonne T. Y. TI Internalization of stigma for parents of children with autism spectrum disorder in Hong Kong SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Hong Kong; Affiliate stigma; Attribution model; Social support; Parents; Autism spectrum disorder; Children; China ID PERCEIVED SOCIAL SUPPORT; MENTAL-ILLNESS; SELF-STIGMA; CHALLENGING BEHAVIOR; INTELLECTUAL DISABILITIES; PSYCHOLOGICAL DISTRESS; ATTRIBUTION MODEL; COURTESY STIGMA; FAMILY; PEOPLE AB An attribution model was tested to explain the internalization of stigma among parents of children with Autism Spectrum Disorder (ASD). In the model, the internalization paths from courtesy stigma to affiliate stigma and the impact of three types of social support on affiliate stigma and psychological well-being were examined. The study was conducted in Hong Kong, China: one hundred and eighty-eight parents of children with ASD were recruited to complete the questionnaire. The model showed excellent fit to the data. 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Sci. Med. PD JUN PY 2010 VL 70 IS 12 BP 2045 EP 2051 DI 10.1016/j.socscimed.2010.02.023 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 608HL UT WOS:000278574300024 PM 20362379 ER PT J AU Seso-Simic, D Sedmak, G Hof, PR Simic, G AF Seso-Simic, Durdica Sedmak, Goran Hof, Patrick R. Simic, Goran TI RECENT ADVANCES IN THE NEUROBIOLOGY OF ATTACHMENT BEHAVIOR SO TRANSLATIONAL NEUROSCIENCE LA English DT Article DE Aggressiveness; Attachment behavior; Autism; Dopamine; Emotional development Motivation; Oxytocin; Mirror neurons; Parental bonding; Psychopathology ID HUMAN ORBITOFRONTAL CORTEX; PLASMA OXYTOCIN LEVELS; MIRROR-NEURON SYSTEM; FEMALE PRAIRIE VOLES; MATERNAL-BEHAVIOR; FUNCTIONAL NEUROANATOMY; DOPAMINE TRANSPORTER; MESOLIMBIC DOPAMINE; SPEECH PRODUCTION; SOCIAL-BEHAVIOR AB In a biological sense an individual's life is all about survival and reproduction. Beside the selection of a mate, the mutual commitment of a parent to sustain an infant through a period of dependency is amongst the most important aspects of natural selection. Here we review how the highly conserved circuitry of key midbrain and hypothalamic structures, and limbic and frontal cortical regions support these processes, and at the same time are involved in shaping the offspring's emotional development and behavior. Many recent studies provided new findings on how attachment behavior and parental bonding is promoted and maintained through genetic and epigenetic influences on synaptic plasticity of mirror neurons and various neuropeptide systems, particularly oxytocinergic, and how these systems serve to link social cues to the brain reward system. Most of this evidence suggests that stress, early parental deprivation and lack of care during the postnatal period leads to profound and lasting changes in the attachment pattern and motivational development with consequent increased vulnerability of the mesocortical and mesolimbic dopamine-associated reward reinforcement pathways to psychosocial stressors, abuse of stimulants and psychopathology later in life. C1 [Seso-Simic, Durdica] Zagreb E Med Ctr, Dept Paediat, Zagreb, Croatia. [Sedmak, Goran; Simic, Goran] Univ Zagreb, Sch Med, Croatian Inst Brain Res, Dept Neurosci, Zagreb 41001, Croatia. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. RP Seso-Simic, D (reprint author), Zagreb E Med Ctr, Dept Paediat, Zagreb, Croatia. 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Early-stage (i.e. within 200 ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors. C1 [Baruth, Joshua M.; Casanova, Manuel F.] Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA. 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Neurosci. PD JUN PY 2010 VL 1 IS 2 BP 177 EP 187 DI 10.2478/v10134-010-0024-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA V20PY UT WOS:000208153100011 ER PT J AU Korkmaz, B AF Korkmaz, Baris TI Autism: clinical and neurobiological features, early diagnosis, treatment and some current developments SO TURK PEDIATRI ARSIVI-TURKISH ARCHIVES OF PEDIATRICS LA Turkish DT Article DE Autism; clinical features; early diagnosis; neurobiological features; treatment ID SPECTRUM DISORDERS; INFANTILE-AUTISM; CHILDREN; BRAIN; PREVALENCE; CEREBELLUM; GENETICS; BEHAVIOR; AMYGDALA; NEURONS AB Aim: The aim of this study is to review the studies about clinical and neurobiological features, early diagnosis and treatment of autism. Material and Method: A computerized literature search was conducted using PubMed to retrieve studies about clinical and neurobiological features, early diagnosis and treatment of autism in addition to many references given to the textbooks. Results: Autism is a neurobiological syndrome which has many subtypes through different mechanisms. The severity and the profile of clinical presentation depend on the degree and pervasiveness of involvement of overlapping neuroanatomical circuits. Among the clinical signs are impairment in social interaction and communication and restricted repetitive and stereotyped patterns of behavior, interests, and activities, sensory and behavioral disturbances. Conclusions: There is no cure for autism and it is a lifelong disorder. Early diagnosis and beginning of early and appropriate educational intervention may improve adaptive skills. (Turk Arch Ped 2010; 45: 80(th) Year: 37-44) C1 Istanbul Univ, Cerrahpasa Tip Fak, Norol Anabilim Dali, Istanbul, Turkey. RP Korkmaz, B (reprint author), Istanbul Univ, Cerrahpasa Tip Fak, Norol Anabilim Dali, Istanbul, Turkey. 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First, the current definitions and common measurement approaches used to assess differences in both local and global functioning within the visual system are considered. Next, studies assessing local and global processing in the dorsal and ventral visual pathways are reviewed for five developmental conditions for which early to mid level visual abilities have been assessed: developmental dyslexia, autism spectrum disorders, developmental dyspraxia. Williams syndrome and Fragile X syndrome. The reviewed evidence is broadly consistent with the idea that the dorsal visual stream is affected in developmental disorders. However, the potential for a unique profile of visual abilities that distinguish some of the conditions is posited, given that for some of these disorders ventral stream deficits have also been found. We conclude with ideas regarding future directions for the study of visual perception in children with developmental disorders using psychophysical measures. (C) 2010 Elsevier Inc. All rights reserved. C1 [Grinter, Emma J.; Maybery, Murray T.; Badcock, David R.] Univ Western Australia, Sch Psychol, Perth, WA 6008, Australia. RP Grinter, EJ (reprint author), Univ Western Australia, Sch Psychol, 35 Stirling Highway, Perth, WA 6008, Australia. EM emmagrinter@graduate.uwa.edu.au RI Badcock, David/A-4913-2008; Maybery, Murray/H-5390-2014 OI Badcock, David/0000-0002-4517-435X; FU NHMRC Project [403942] FX This research was supported by NH&MRC Project Grant 403942 awarded to M.T. Maybery, D.R. Badcock, J.C. Badcock, and E. Pellicano. 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Bull. PD MAY 31 PY 2010 VL 82 IS 3-4 BP 147 EP 160 DI 10.1016/j.brainresbull.2010.02.016 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 626NM UT WOS:000279972700001 PM 20211706 ER PT J AU Wan, CY Demaine, K Zipse, L Norton, A Schlaug, G AF Wan, Catherine Y. Demaine, Krystal Zipse, Lauryn Norton, Andrea Schlaug, Gottfried TI From music making to speaking: Engaging the mirror neuron system in autism SO BRAIN RESEARCH BULLETIN LA English DT Review DE Autism; Music; Language; Brain; Mirror neuron system; Auditory-motor mapping training ID MELODIC INTONATION THERAPY; SPECTRUM DISORDERS; SPEECH PRODUCTION; PREMOTOR CORTEX; MOTOR SYSTEM; PROFESSIONAL PIANISTS; ACTION RECOGNITION; BROCAS APHASIA; ABSOLUTE PITCH; DOWN-SYNDROME AB Individuals with autism show impairments in emotional tuning, social interactions and communication. These are functions that have been attributed to the putative human mirror neuron system (MNS), which contains neurons that respond to the actions of self and others. It has been proposed that a dysfunction of that system underlies some of the characteristics of autism. Here, we review behavioral and imaging studies that implicate the MNS (or a brain network with similar functions) in sensory-motor integration and speech representation, and review data supporting the hypothesis that MNS activity could be abnormal in autism. In addition, we propose that an intervention designed to engage brain regions that overlap with the MNS may have significant clinical potential. We argue that this engagement could be achieved through forms of music making. Music making with others (e.g., playing instruments or singing) is a multi-modal activity that has been shown to engage brain regions that largely overlap with the human MNS. Furthermore, many children with autism thoroughly enjoy participating in musical activities. Such activities may enhance their ability to focus and interact with others, thereby fostering the development of communication and social skills. Thus, interventions incorporating methods of music making may offer a promising approach for facilitating expressive language in otherwise nonverbal children with autism. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wan, Catherine Y.; Demaine, Krystal; Zipse, Lauryn; Norton, Andrea; Schlaug, Gottfried] Beth Israel Deaconess Med Ctr, Music & Neuroimaging Lab, Dept Neurol, Boston, MA 02215 USA. [Wan, Catherine Y.; Demaine, Krystal; Zipse, Lauryn; Norton, Andrea; Schlaug, Gottfried] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Zipse, Lauryn] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02129 USA. RP Schlaug, G (reprint author), Beth Israel Deaconess Med Ctr, Music & Neuroimaging Lab, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. EM gschlaug@bidmc.harvard.edu FU Nancy Lurie Marks Family Foundation FX We sincerely thank the Nancy Lurie Marks Family Foundation for their support. 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Bull. PD MAY 31 PY 2010 VL 82 IS 3-4 BP 161 EP 168 DI 10.1016/j.brainresbull.2010.04.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 626NM UT WOS:000279972700002 PM 20433906 ER PT J AU Wachtel, LE Hermida, A Dhossche, DM AF Wachtel, Lee E. Hermida, Adriana Dhossche, Dirk M. TI Maintenance electroconvulsive therapy in autistic catatonia: A case series review SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Autism; Catatonia; Electroconvulsive therapy; GABA ID SPECTRUM DISORDERS; ECT; CONTINUATION; ADOLESCENCE; SCHIZOPHRENIA; INDIVIDUALS; CHILDHOOD AB The usage of electroconvulsive therapy for the acute resolution of catatonia in autistic children and adults is a novel area that has received increased attention over the past few years. Reported length of the acute ECT course varies among these patients, and there is no current literature on maintenance ECT in autism. The maintenance ECT courses of three patients with autism who developed catatonia are presented. Clinical, research, legal, and administrative implications for ECT treatment in this special population are discussed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wachtel, Lee E.] Johns Hopkins Sch Med, Dept Psychiat, Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Hermida, Adriana] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Dhossche, Dirk M.] Univ Mississippi, Med Ctr, Dept Psychiat, Jackson, MS 39216 USA. RP Wachtel, LE (reprint author), Johns Hopkins Sch Med, Dept Psychiat, Kennedy Krieger Inst, 707 N Broadway St,Rm 232, Baltimore, MD 21205 USA. 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Psychiatry PD MAY 30 PY 2010 VL 34 IS 4 BP 581 EP 587 DI 10.1016/j.pnpbp.2010.03.012 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 612GV UT WOS:000278885700002 PM 20298732 ER PT J AU Emanuele, E Boso, M Brondino, N Pietra, S Barale, F di Nemi, SU Politi, P AF Emanuele, Enzo Boso, Marianna Brondino, Natascia Pietra, Stefania Barale, Francesco di Nemi, Stefania Ucelli Politi, Pierluigi TI Increased serum levels of high mobility group box 1 protein in patients with autistic disorder SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Autism spectrum disorder; High mobility group box 1; Inflammation; Social interaction ID AGE-RAGE; HMGB1; RECEPTOR; BRAIN; NEUROINFLAMMATION; DYSFUNCTION; ASTROCYTES; ACTIVATION; RELEASE; ROLES AB Background: High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics. Methods: We enrolled 22 adult patients with autistic disorder (mean age: 28.1 +/- 7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7 +/- 8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA). Results: Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8 +/- 2.6 ng/mL versus 5.6 +/- 2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. Conclusions: These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder. (C) 2010 Elsevier Inc. All rights reserved. C1 [Emanuele, Enzo; Boso, Marianna; Brondino, Natascia; Pietra, Stefania; Barale, Francesco; di Nemi, Stefania Ucelli; Politi, Pierluigi] Univ Pavia, Sect Psychiat, Dept Hlth Sci, I-27100 Pavia, Italy. RP Emanuele, E (reprint author), Univ Pavia, Sect Psychiat, Dept Hlth Sci, Via Bassi 21, I-27100 Pavia, Italy. 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TI Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE ADHD; Association; Human post-mortem brain tissue; OXTR; Social cognition ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; AUTISTIC TRAITS; KNOCKOUT MOUSE; GENOME-WIDE; TWIN SAMPLE; HUMAN BRAIN; VASOPRESSIN; BEHAVIOR; AMYGDALA AB Some children with ADHD also have social and communication difficulties similar to those seen in children with autistic spectrum disorders and this may be due to shared genetic liability. As the oxytocin receptor (OXTR) gene has been implicated in social cognition and autistic spectrum disorders, this study investigated whether OXTR polymorphisms previously implicated in autism were associated with ADHD and whether they influenced OXTR mRNA expression in 27 normal human amygdala brain samples. The family-based association sample consisted of 450 DSM-IV diagnosed ADHD probands and their parents. Although there was no association with the ADHD phenotype, an association with social cognitive impairments in a subset of the ADHD probands (N = 112) was found for SNP rs53576 (F = 5.24, p = 0.007) with post-hoc tests demonstrating that the AA genotype was associated with better social ability compared to the AG genotype. Additionally, significant association was also found for rs13316193 (F = 3.09, p = 0.05) with post-hoc tests demonstrating that the CC genotype was significantly associated with poorer social ability than the TT genotype. No significant association between genotype and OXTR mRNA expression was found. This study supports previous evidence that the OXTR gene is implicated in social cognition. (C) 2010 Elsevier Inc. All rights reserved. C1 [Park, J.; Willmott, M.; Vetuz, G.; Toye, C.; Brookes, K. J.; Kent, L.] Univ St Andrews, Bute Med Sch, St Andrews KY16 9TS, Fife, Scotland. [Kirley, A.; Hawi, Z.; Gill, M.] St James Hosp, Dept Psychiat, Trinity Ctr Hlth Sci, Dublin 8, Ireland. RP Kent, L (reprint author), Univ St Andrews, Bute Med Sch, St Andrews KY16 9TS, Fife, Scotland. EM lsk8@st-andrews.ac.uk FU Wellcome Trust; Health Research Board (Dublin) FX The sample collection for this project was partly funded by the Wellcome Trust (LK) and with generous support from the Health Research Board (Dublin) (ZH and EB). The authors declare that there are no competing interests. We would like to thank Dr. Robert Walker from the Edinburgh MRC Sudden Death Brain and Tissue Bank for his assistance and all the families involved in the study for their participation. 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PD MAY 29 PY 2010 VL 206 IS 2762 BP 28 EP 28 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 603MZ UT WOS:000278214000018 ER PT J AU Dawson, M AF Dawson, Michelle TI Autism accuracy SO NEW SCIENTIST LA English DT Letter C1 Univ Montreal, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada. RP Dawson, M (reprint author), Univ Montreal, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD MAY 29 PY 2010 VL 206 IS 2762 BP 28 EP 28 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 603MZ UT WOS:000278214000016 ER PT J AU Keller, E AF Keller, E. 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PD MAY 29 PY 2010 VL 140 IS 21-22 SU 180 BP 29S EP 29S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 610NI UT WOS:000278739300114 ER PT J AU Bruining, H de Sonneville, L Swaab, H de Jonge, M Kas, M van Engeland, H Vorstman, J AF Bruining, Hilgo de Sonneville, Leo Swaab, Hanna de Jonge, Maretha Kas, Martien van Engeland, Herman Vorstman, Jacob TI Dissecting the Clinical Heterogeneity of Autism Spectrum Disorders through Defined Genotypes SO PLOS ONE LA English DT Article ID DIAGNOSTIC OBSERVATION SCHEDULE; KLINEFELTER-SYNDROME; RETT-SYNDROME; 22Q11.2 DELETION; CHILDREN; INTERVIEW; ADOLESCENTS; PHENOTYPES; MUTATIONS; GENETICS AB Background: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. Methodology: The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. Principal Findings: The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. Conclusion: The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population. 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Keehn, Brandon Mueller, Ralph Axel TI Regional homogeneity of fMRI time series in autism spectrum disorders SO NEUROSCIENCE LETTERS LA English DT Article DE Autism spectrum disorder; Functional MRI; Functional connectivity; Regional homogeneity ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RESTING-STATE; FUNCTIONAL CONNECTIVITY; CORTICAL CONNECTIVITY; SPATIAL ATTENTION; BRAIN; ORGANIZATION; CORTEX; ABNORMALITIES; INDIVIDUALS AB Functional magnetic resonance imaging (fMRI) and functional connectivity MRI (fcMRI) studies of autism spectrum disorders (ASD) have suggested atypical patterns of activation and long-distance connectivity for diverse tasks and networks in ASD. We explored the regional homogeneity (ReHo) approach in ASD, which is analogous to conventional fcMRI, but focuses on local connectivity. FMRI data of 26 children with ASD and 29 typically developing (TD) children were acquired during continuous task performance (visual search). Effects of motion and task were removed and Kendall's coefficient of concordance (KCC) was computed, based on the correlation of the blood oxygen level dependent (BOLD) time series for each voxel and its six nearest neighbors. ReHo was lower in the ASD than the TD group in superior parietal and anterior prefrontal regions. Inverse effects of greater ReHo in the ASD group were detected in lateral and medial temporal regions, predominantly in the right hemisphere. Our findings suggest that ReHo is a sensitive measure for detecting cortical abnormalities in autism. However, impact of methodological factors (such as spatial resolution) on ReHo require further investigation. Published by Elsevier Ireland Ltd. C1 [Shukla, Dinesh K.; Keehn, Brandon; Mueller, Ralph Axel] San Diego State Univ, Dept Psychol, Brain Dev Imaging Lab, San Diego, CA 92120 USA. [Keehn, Brandon] Univ Calif, San Diego State Univ, San Diego Joint Doctoral Program Language & Commu, San Diego, CA USA. [Mueller, Ralph Axel] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92093 USA. RP Muller, RA (reprint author), San Diego State Univ, Dept Psychol, Brain Dev Imaging Lab, 6363 Alvarado Ct,Suite 225E, San Diego, CA 92120 USA. EM amueller@sciences.sdsu.edu FU National Institutes of Health [R01-DC006155, R01-MH081023, 1T32 DC007361-03] FX This study was supported by the National Institutes of Health, R01-DC006155, R01-MH081023, and 1T32 DC007361-03 (BK). Thanks to the children and families who participated, to Yufeng Zang, Chao-Gan Yan, and Xiang-Yu Long for technical support, and to Patricia Shih for comments on the manuscript. 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Lett. PD MAY 26 PY 2010 VL 476 IS 1 BP 46 EP 51 DI 10.1016/j.neulet.2010.03.080 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 602WR UT WOS:000278170200011 PM 20381584 ER PT J AU Ghosh, RP Nikitina, T Horowitz-Scherer, RA Gierasch, LM Uversky, VN Hite, K Hansen, JC Woodcock, CL AF Ghosh, Rajarshi P. Nikitina, Tatiana Horowitz-Scherer, Rachel A. Gierasch, Lila M. Uversky, Vladimir N. Hite, Kristopher Hansen, Jeffrey C. Woodcock, Christopher L. TI Unique Physical Properties and Interactions of the Domains of Methylated DNA Binding Protein 2 SO BIOCHEMISTRY LA English DT Article ID CIRCULAR-DICHROISM SPECTRA; RETT-SYNDROME; SECONDARY STRUCTURE; TRANSCRIPTIONAL REPRESSION; DISORDERED PROTEINS; INTRINSIC DISORDER; HUMAN MECP2; IN-VIVO; CPG; CHROMATIN AB Methylated DNA binding protein 2 (MeCP2) is a methyl CpG binding protein whose key role is the recognition of epigenetic information encoded in DNA methylation patterns. Mutation or misregulation of MeCP2 function leads to Rett syndrome as well as a variety of other autism spectrum disorders. Here, we have analyzed in detail the properties of six individually expressed human MeCP2 domains spanning the entire protein with emphasis on their interactions with each other, with DNA, and with nucleosomal arrays. Each domain contributes uniquely to the structure and function of the full-length protein. MeCP2 is similar to 60% unstructured, with nine interspersed alpha-molecular recognition features (alpha-MoRFs), which arc polypeptide segments predicted to acquire secondary structure upon forming complexes with binding partners. Large increases in secondary structure content are induced in some of the isolated MeCP2 domains and in the full-length protein by binding to DNA. Interactions between some MeCP2 domains in cis and Irons seen in our assays likely contribute to the structure and function of the intact protein. We also show that MeCP2 has two functional halves. The N-terminal portion contains the methylated DNA binding domain (MBD) and two highly disordered flanking domains that modulate M BD-mediated DNA binding. One of these flanking domains is also capable of autonomous DNA binding. In contrast, the C-terminal portion of the protein that harbors at least two independent DNA binding domains and a chromatin-specific binding domain is largely responsible for mediating nucleosomal array compaction and oligomerization. These findings led to new mechanistic and biochemical insights regarding the conformational modulations of this intrinsically disordered protein, and its context-dependent in vivo roles. C1 [Nikitina, Tatiana; Horowitz-Scherer, Rachel A.; Woodcock, Christopher L.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. [Ghosh, Rajarshi P.; Gierasch, Lila M.; Woodcock, Christopher L.] Univ Massachusetts, Program Mol & Cellular Biol, Amherst, MA 01003 USA. [Gierasch, Lila M.] Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. [Uversky, Vladimir N.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Inst Intrinsically Disordered Prot Res,Ctr Comput, Indianapolis, IN 46202 USA. [Uversky, Vladimir N.] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Moscow Region, Russia. [Hite, Kristopher; Hansen, Jeffrey C.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Gierasch, Lila M.] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA. RP Woodcock, CL (reprint author), Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. EM chris@bio.umass.edu RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 FU National Institutes of Health (NIH) [GM070897, GM066834, GM027616, OD945, LM007688, GM071714]; Russian Academy of Sciences; IUPUI Signatures Center Initiative FX Supported by National Institutes of Health (NIH) Grant GM070897 and the International Rett Syndrome Foundation (C.L.W.); NIH Grant GM066834 (J.C.H.); NIH Grants GM027616 and OD945 (L.M.G.); and NIH Grants LM007688 and GM071714, the program of the Russian Academy of Sciences for "Molecular and Cellular Biology", and the IUPUI Signatures Center Initiative (V.N.U.). 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We found heightened neural activation of the amygdala in both high functioning adults with ASD and matched controls. Neither the intensity nor the time-course of amygdala activation differed between the groups. However, the adults with ASD showed significantly lower levels of fusiform activation during the trials compared to controls. Our findings suggest that in ASD, the transmission of socially salient information along subcortical pathways is intact: and yet the signaling of this information to structures downstream may be impoverished, and the pathways that facilitate subsequent processing deficient. C1 [Hall, Geoffrey B. C.; Doyle, Krissy A. R.; Goldberg, Jeremy; West, Dianne; Szatmari, Peter] McMaster Univ, Fac Hlth Sci, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Hall, Geoffrey B. C.] St Josephs Healthcare, Brain Body Inst, Hamilton, ON, Canada. [Hall, Geoffrey B. C.; Szatmari, Peter] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON, Canada. RP Hall, GBC (reprint author), McMaster Univ, Fac Hlth Sci, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. 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Huq, Ahm M. Wilson, Benjamin J. Chugani, Harry T. TI Tourette syndrome is associated with recurrent exonic copy number variants SO NEUROLOGY LA English DT Article ID AUTISM; SCHIZOPHRENIA; DISORDER; INHERITANCE; FAMILY; GENES; RISK AB Background: Multiple rare copy number variants (CNVs) including genomic deletions and duplications play a prominent role in neurodevelopmental disorders such as mental retardation, autism, and schizophrenia, but have not been systematically studied in Tourette syndrome (TS). Methods: We performed a genome-wide screening of single nucleotide polymorphism (SNP) genotyping microarray data to identify recurrent or de novo rare exonic CNVs in a case-control association study of patients with TS. Results: We identified 5 exon-affecting rare CNVs that are either de novo or recurrent in 10 out of 111 patients with TS but were not found in 73 ethnically matched controls or in the entries of the Database of Genomic Variants (containing 21,178 CNVs at 6,558 loci). Three out of the 5 CNVs have been implicated previously by other studies in schizophrenia, autism, and attention-deficit hyperactivity disorder, suggesting that these CNVs produce a continuum of neuropsychiatric disturbances that manifest in different ways depending on other genetic, environmental, or stochastic factors. Conclusions: Rare, recurrent exonic copy number variants are associated in a subset of patients with Tourette syndrome. Neurology (R) 2010; 74: 1583-1590 C1 [Sundaram, Senthil K.; Huq, Ahm M.; Wilson, Benjamin J.; Chugani, Harry T.] Wayne State Univ, Dept Pediat & Neurol, Detroit, MI USA. RP Huq, AM (reprint author), Childrens Hosp Michigan, Div Neurol, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM ahuq@med.wayne.edu RI Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 FU National Center for Research Resources, NIH [UL1 RR024139]; NIH (NICHD) [1R01HD059817-01A1, R01HD05981701A1]; Festival of Trees; NIH (NINDS) [R01 NS 34488] FX Supported by the Clinical and Translational Science Award UL1 RR024139, National Center for Research Resources, NIH.Dr. Sundaram receives research support from the NIH (NICHD 1R01HD059817-01A1 [PI]). Dr. Huq serves as an Associate Editor of MedLink Neurology and receives research support from the NIH (NICHD 1R01HD059817-01A1 [Co-I]) and from Festival of Trees. B.J. Wilson reports no disclosures. Dr. Chugani serves on the editorial boards of Journal of Child Neurology, Journal of Pediatric Neurology, Brain and Development, and Pediatric Neurology, and receives research support from the NIH (NINDS R01 NS 34488 [PI] and NICHD R01HD05981701A1[Co-I]). 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TI Region-specific alterations in brain development in one- to three-year-old boys with fragile X syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE early childhood; longitudinal; MRI; voxel-based morphometry ID MENTAL-RETARDATION SYNDROME; MOUSE MODEL; PROTEIN; BEHAVIOR; CORTEX; SYNAPTOGENESIS; ABNORMALITIES; NEUROANATOMY; EXPRESSION; GROWTH AB Longitudinal neuroimaging investigation of fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autism, provides an opportunity to study the influence of a specific genetic factor on neurodevelopment in the living human brain. We examined voxel-wise gray and white matter volumes (GMV, WMV) over a 2-year period in 1- to 3-year-old boys with FXS (n = 41) and compared these findings to age-and developmentally matched controls (n = 28). We found enlarged GMV in the caudate, thalamus, and fusiform gyri and reduced GMV in the cerebellar vermis in FXS at both timepoints, suggesting early, possibly prenatal, genetically mediated alterations in neurodevelopment. In contrast, regions in which initial GMV was similar, followed by an altered growth trajectory leading to increased size in FXS, such as the orbital gyri, basal forebrain, and thalamus, suggests delayed or otherwise disrupted synaptic pruning occurring postnatally. WMV of striatal-prefrontal regions was greater in FXS compared with controls, and group differences became more exaggerated over time, indicating the possibility that such WM abnormalities are the result of primary FMRP-deficiency-related axonal pathology, as opposed to secondary connectional dysregulation between morphologically atypical brain structures. Our results indicate that structural abnormalities of different brain regions in FXS evolve differently over time reflecting time-dependent effects of FMRP deficiency and provide insight into their neuropathologic underpinnings. The creation of an early and accurate human brain phenotype for FXS in humans will significantly improve our capability to detect whether new disease-specific treatments can "rescue" the FXS phenotype in affected individuals. C1 [Hoeft, Fumiko; Carter, John C.; Lightbody, Amy A.; Reiss, Allan L.] Stanford Univ, Sch Med, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. [Hazlett, Heather Cody; Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27514 USA. RP Reiss, AL (reprint author), Stanford Univ, Sch Med, Ctr Interdisciplinary Brain Sci Res, Stanford, CA 94305 USA. EM reiss@stanford.edu FU Canel family fund; National Alliance for Research on Schizophrenia and Depression Young Investigator Award, Stanford Child Health Spectrum; National Institute of Child Health and Human Development [HD054720]; [MH64708-05]; [MH61696]; [HD03110-36]; [MH050047] FX We sincerely thank all of the families who made this study possible. We also thank Chad Chappell, MA; Nancy Garrett, BA; Michael Graves, MChe; Cindy Hagan, BA; Cindy Johnston, MS; Judy Morrow, PhD; Robin Morris, BA; Rachel Smith, BA; Arianna Martin, BA; Cristiana Vattuone, BA; Christa Watson, BA; Anh Weber, PhD; Masanori Nagamine, MD/PhD; Kelly Chen, BS; and Sweta Patnaik, MS who were involved in data collection and/or processing. This study was funded by MH64708-05 (to A.L.R. and J.P.), MH61696 (to J.P.), HD03110-36 (to J.P.), MH050047 (to A.L.R.), and the Canel family fund, and F.H. was funded by National Alliance for Research on Schizophrenia and Depression Young Investigator Award, Stanford Child Health Spectrum, and National Institute of Child Health and Human Development HD054720. 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Roebroeck, Alard Renken, Remco Nanetti, Luca Keysers, Christian TI Mapping the information flow from one brain to another during gestural communication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Granger causality; mirror system; social interaction; theory of mind; functional MRI ID MIRROR-NEURON SYSTEM; SOCIAL COGNITION; ACTION RECOGNITION; FMRI; SIMULATION; IMITATION; CORTEX; MIND; REPRESENTATIONS; MECHANISMS AB Both the putative mirror neuron system (pMNS) and the ventral medial prefrontal cortex (vmPFC) are deemed important for social interaction: the pMNS because it supposedly "resonates" with the actions of others, the vmPFC because it is involved in mentalizing. Strictly speaking, the resonance property of the pMNS has never been investigated. Classical functional MRI experiments have only investigated whether pMNS regions augment their activity when an action is seen or executed. Resonance, however, entails more than only "going on and off together". Activity in the pMNS of an observer should continuously follow the more subtle changes over time in activity of the pMNS of the actor. Here we directly explore whether such resonance indeed occurs during continuous streams of actions. We let participants play the game of charades while we measured brain activity of both gesturer and guesser. We then applied a method to localize directed influences between the brains of the participants: between-brain Granger-causality mapping. Results show that a guesser's brain activity in regions involved in mentalizing and mirroring echoes the temporal structure of a gesturer's brain activity. This provides evidence for resonance theories and indicates a fine-grained temporal interplay between regions involved in motor planning and regions involved in thinking about the mental states of others. Furthermore, this method enables experiments to be more ecologically valid by providing the opportunity to leave social interaction unconstrained. This, in turn, would allow us to tap into the neural substrates of social deficits such as autism spectrum disorder. C1 [Schippers, Marleen B.; Renken, Remco; Nanetti, Luca; Keysers, Christian] Univ Groningen, Univ Med Ctr Groningen, Social Brain Lab, Dept Neurosci, NL-9713 AW Groningen, Netherlands. [Roebroeck, Alard] Univ Maastricht, Dept Cognit Neurosci, Fac Psychol, NL-6229 ER Maastricht, Netherlands. [Keysers, Christian] Royal Netherlands Acad Arts & Sci KNAW, Social Brain Lab, Netherlands Inst Neurosci, NL-1105 BA Amsterdam, Netherlands. RP Keysers, C (reprint author), Univ Groningen, Univ Med Ctr Groningen, Social Brain Lab, Dept Neurosci, NL-9713 AW Groningen, Netherlands. EM c.keysers@nin.knaw.nl RI Keysers, Christian/H-6251-2013 OI Keysers, Christian/0000-0002-2845-5467 FU Dutch Science Foundation (NWO); European Commission FX We thank V. Gazzola and R. Goebel for help in designing the experiment and the latter for providing BrainVoyager, and P. Toffanin, M. Spezio, and D. Arnstein for critical comments on the manuscript. The research was supported by a Vidi grant of the Dutch Science Foundation (NWO) and a Marie Curie Excellence Grant of the European Commission (to C.K.). 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Natl. Acad. Sci. U. S. A. PD MAY 18 PY 2010 VL 107 IS 20 BP 9388 EP 9393 DI 10.1073/pnas.1001791107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 598GH UT WOS:000277822600066 PM 20439736 ER PT J AU Gamer, M Zurowski, B Buchel, C AF Gamer, Matthias Zurowski, Bartosz Buechel, Christian TI Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE eyes; facial expression; functional neuroimaging; neuropeptides; social perception ID FACIAL EXPRESSIONS; SOCIAL-BEHAVIOR; IMPAIRED RECOGNITION; NEURAL CIRCUITRY; FACES; AUTISM; BRAIN; GAZE; ACTIVATION; RESPONSES AB The neuropeptide oxytocin enhances the processing of positive social stimuli and improves the capacity to effectively attend the eye region of conspecifics. To investigate the neural basis of these effects, we combined intranasal oxytocin administration with high-resolution functional magnetic resonance imaging in a unique emotion classification task. Emotional faces were briefly presented while controlling for the initial fixation, and measuring subsequent eye movements. Oxytocin had differential effects on the activity of specific amygdala subregions. On the one hand, it attenuated activation in lateral and dorsal regions of the anterior amygdala for fearful faces but enhanced activity for happy expressions, thus indicating a shift of the processing focus toward positive social stimuli. On the other hand, oxytocin increased the likelihood of reflexive gaze shifts toward the eye region irrespective of the depicted emotional expression. This gazing pattern was related to an increase of activity in the posterior amygdala and an enhanced functional coupling of this region to the superior colliculi. 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TI Sensory Modulation Impairments in Children with Williams Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE Williams syndrome; sensory modulation; intellectual disability; executive function; temperament; adaptive behavior; problem behavior ID YOUNG-CHILDREN; AUTISM; PERSONALITY; INDIVIDUALS; PERFORMANCE; HYPERACUSIS; PREVALENCE; DISORDERS; PHENOTYPE; SYMPTOMS AB The ability to organize information detected by our senses ("sensory modulation") allows us to act or respond effectively to situations encountered, facilitating learning, social behavior, and day-to-day functioning. We hypothesized that children with Williams syndrome (WS) would demonstrate symptoms of poor sensory modulation and that these sensory modulation abnormalities contribute to the phenotype. Participants were 78 children with WS aged 4.00-10.95 years. Based on parent ratings on the Short Sensory Profile [SSP; Dunn, 1999], most children were classified as having definite sensory modulation issues. Cluster analysis identified the presence of two clusters varying in level of sensory modulation impairment. Children in the high impairment group demonstrated poorer adaptive functioning, executive functioning, more problem behaviors, and more difficult temperaments than children in the low impairment group. (C) 2010 Wiley-Liss, Inc. C1 [John, Angela E.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. RP John, AE (reprint author), Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. EM aejohn11@gwise.louisville.edu FU National Institute of Child Health and Human Development [R37 HD29957]; National Institute of Neurological Disorders and Stroke [R01 NS35102] FX Grant sponsor: National Institute of Child Health and Human Development; Grant number: R37 HD29957; Grant sponsor: National Institute of Neurological Disorders and Stroke; Grant number: R01 NS35102. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Anderberg MR, 1973, CLUSTER ANAL APPL Ayres A. J., 1972, SENSORY INTEGRATION Baker AEZ, 2008, J AUTISM DEV DISORD, V38, P867, DOI 10.1007/s10803-007-0459-0 Baranek GT, 2002, AM J OCCUP THER, V56, P538 Ben-Sasson A, 2007, INFANT MENT HEALTH J, V28, P536, DOI 10.1002/imhj.20152 Bruininks R., 1996, SCALES INDEPENDENT B Bundy A., 2002, SENSORY INTEGRATION Cermak SA, 1997, AM J OCCUP THER, V51, P500 Conners C. K., 1997, CONNERS RATING SCALE Dilts C V, 1990, Am J Med Genet Suppl, V6, P126 Dunn L. 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SO PSYCHIATRY RESEARCH LA English DT Article DE Emotion face processing; Visual scanpaths; Eye-gaze avoidance; Social functioning ID CARDIO-FACIAL SYNDROME; HUMAN AMYGDALA; CHILDREN; AUTISM; EMOTION; FEARFUL; SCHIZOPHRENIA; EXPRESSIONS; ACTIVATION; DISORDERS AB Previous research demonstrates that people with 22q11.2 deletion syndrome (22q11DS) have social and interpersonal skill deficits. However, the basis of this deficit is unknown. This study examined, for the first time, how people with 22q11DS process emotional face stimuli using visual scanpath technology. The visual scanpaths of 17 adolescents and age/gender matched healthy controls were recorded while they viewed face images depicting one of seven basic emotions (happy, sad, surprised, angry, fear, disgust and neutral). Recognition accuracy was measured concurrently. People with 22q11DS differed significantly from controls, displaying visual scanpath patterns that were characterised by fewer fixations and a shorter scanpath length. The 22q11DS group also spent significantly more time gazing at the mouth region and significantly less time looking at eye regions of the faces. Recognition accuracy was correspondingly impaired, with 22q11DS subjects displaying particular deficits for fear and disgust. These findings suggest that 22q11DS is associated with a maladaptive visual information processing strategy that may underlie affect recognition accuracy and social functioning deficits in this group. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Campbell, Linda; McCabe, Kathryn; Leadbeater, Kate; Schall, Ulrich; Loughland, Carmel] Univ Newcastle, Prior Res Ctr Brain & Mental Hlth, Callaghan, NSW 2308, Australia. [Campbell, Linda; McCabe, Kathryn; Schall, Ulrich; Loughland, Carmel] Schizophrenia Res Inst Australia, Sydney, NSW, Australia. [Rich, Dominique] Univ Newcastle, Ctr Brain & Mental Hlth Res, Callaghan, NSW 2308, Australia. RP Campbell, L (reprint author), Prior Res Ctr Brain & Mental Hlth Studies, POB 833, Newcastle, NSW 2300, Australia. EM Linda.e.campbell@newcastle.edu.au RI campbell, linda/C-6231-2013; SCHALL, ULRICH/G-7452-2013 OI campbell, linda/0000-0002-8872-9626; FU Velo-Cardio-Facial Foundation of New South Wales; John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development; Hunter Medical Research Institute; NMMRC; NHMRC of Australia, NHMRC ID [455614] FX We thank the Velo-Cardio-Facial Foundation of New South Wales for their support and help with recruitment. We also thank all the participants and their families for helping us with the current study. Development of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at tott0006@tc.umn.edu for more information concerning the stimulus set.Funding for the current study was obtained from the Hunter Medical Research Institute in the form of a Port-Waratah Coal Services post-doctoral fellowship and from the NM&MRC in the form of an Australian Training Fellowship. Infra-structure support was also obtained from the Schizophrenia Research Institute. The work recorded has been supported by a Fellowship awarded by the NHMRC of Australia, NHMRC ID 455614. 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Thorland, Erik C. Vermeesch, Joris R. Waggoner, Darrel J. Watson, Michael S. Martin, Christa Lese Ledbetter, David H. TI Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IDIOPATHIC MENTAL-RETARDATION; COPY-NUMBER VARIATIONS; 17Q21.31 MICRODELETION SYNDROME; ARRAY-BASED TECHNOLOGY; LOW-LEVEL MOSAICISM; STRUCTURAL VARIATION; DYSMORPHIC FEATURES; CYTOGENETIC SURVEY; OLIGONUCLEOTIDE MICROARRAY AB Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages. C1 [Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Miller, David T.] Harvard Univ, Sch Med, Boston, MA USA. [Adam, Margaret P.; Faucett, W. Andrew; Kaminsky, Erin B.; Martin, Christa Lese; Ledbetter, David H.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Adam, Margaret P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Aradhya, Swaroop] GeneDx, Gaithersburg, MD USA. [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Brothman, Arthur R.] Univ Utah, Sch Med, Dept Pediat, Human Genet Lab, Salt Lake City, UT USA. [Brothman, Arthur R.] Univ Utah, Sch Med, Dept Pediat, Pathol Lab, Salt Lake City, UT USA. [Brothman, Arthur R.] Univ Utah, Sch Med, Dept Pediat, ARUP Lab, Salt Lake City, UT USA. [Carter, Nigel P.] Wellcome Trust Sanger Inst, Cambridge, England. [Church, Deanna M.; Ostell, James M.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Crolla, John A.] Natl Genet Reference Lab Wessex, Salisbury, Wilts, England. [Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Sch Med, Seattle, WA 98195 USA. [Epstein, Charles J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Epstein, Charles J.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Feuk, Lars] Uppsala Univ, Rudbeck Lab, Uppsala, Sweden. [Friedman, Jan M.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Friedman, Jan M.] Child & Family Res Inst, Vancouver, BC, Canada. [Hamosh, Ada] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Hamosh, Ada] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Jackson, Laird] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Kok, Klaas] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands. [Krantz, Ian D.; Spinner, Nancy B.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat Human Genet, Philadelphia, PA 19104 USA. [Kuhn, Robert M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Lee, Charles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rosenberg, Carla] Univ Sao Paulo, Dept Genet & Evolutionary Biol, BR-05508 Sao Paulo, Brazil. [Scherer, Stephen W.] Univ Toronto, Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5S 1A1, Canada. [Scherer, Stephen W.] Univ Toronto, Hosp Sick Children, Program Genet & Genet Biol, Toronto, ON M5S 1A1, Canada. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Stavropoulos, Dimitri J.] Hosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. [Tepperberg, James H.] Lab Corp Amer, Res Triangle Pk, NC USA. [Thorland, Erik C.] Mayo Clin, Rochester, MN USA. [Vermeesch, Joris R.] Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium. [Waggoner, Darrel J.] Univ Chicago, Dept Human Genet & Pediat, Chicago, IL 60637 USA. [Watson, Michael S.] Amer Coll Med Genet, Bethesda, MI USA. RP Miller, DT (reprint author), Childrens Hosp, Div Genet, 300 Longwood Ave, Boston, MA 02115 USA. EM david.miller2@childrens.harvard.edu; david.ledbetter@emory.edu RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Oncogenomica, Inct/H-9999-2013; Cetgen, Inct/I-2412-2013 OI Scherer, Stephen /0000-0002-8326-1999; FU National Institutes of Health [RC2FID064525, MH074090]; Simons Foundation [137578]; ACMG Foundation; Luminex FX Workshops and conference calls related to the ISCA Consortium were funded through a grant from the ACMG Foundation and Luminex to D.H.L. and C.L.M., and ongoing standards and database development are funded in part by grants from the National Institutes of Health (RC2FID064525 and MH074090 to D.H.L. and C.L.M.). This work was also supported by Simons Foundation grant 137578 (to FEE.). E.E.E. is an investigator of the Howard Hughes Medical Institute. The opinions expressed here are those of the authors and the ISCA Consortium and do not necessarily reflect the views of the institutions to which the authors are affiliated, the ACMG, or the American Society of Human Genetics (ASHG). The authors would like to thank Dr. Omer Gokcumen for his assistance with summary of population CNV data. Regarding conflict of interest, the majority of authors are involved in CMA testing and/or cytogenetic testing, either as clinicians who order the testing, laboratory professionals who perform the testing, or researchers in the genomics field. S.A. is a director of clinical cytogenetics at GeneDx, a subsidiary of BioReference Laboratories; A.R.B. is a director of clinical cytogenetics and molecular cytogenetics at ARUP Laboratories; E.E.E. is a member of the Pacific Biosciences Scientific Advisory Board. S.W.S. is on the Scientific Advisory Board of Combimatrix Diagnostics and the Scientific Advisory Committee of Autism Speaks. J.T. is a director of clinical cytogenetics at Laboratory Corporation of America. J.V. is on the board of directors of Cartagenia. M.W. raises funds from industry to support the educational activities of the ACMG Foundation. 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LA, 2008, NEW ENGL J MED, V358, P667, DOI 10.1056/NEJMoa075974 Willatt L, 2005, AM J HUM GENET, V77, P154, DOI 10.1086/431653 Wong A, 2005, GENET MED, V7, P264, DOI 10.1097/01.GIM.0000160076.14102.EC Xiang BX, 2008, AM J MED GENET A, V146A, P1942, DOI 10.1002/ajmg.a.32411 Ylstra B, 2006, NUCLEIC ACIDS RES, V34, P445, DOI 10.1093/nar/gkj456 NR 107 TC 573 Z9 597 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 14 PY 2010 VL 86 IS 5 BP 749 EP 764 DI 10.1016/j.ajhg.2010.04.006 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 601GC UT WOS:000278045300011 PM 20466091 ER PT J AU Shah, AK Tioleco, NM Nolan, K Locker, J Groh, K Villa, C Stopkova, P Pedrosa, E Lachman, HM AF Shah, Abhishek K. Tioleco, Nina M. Nolan, Karen Locker, Joseph Groh, Katherine Villa, Catalina Stopkova, Pavla Pedrosa, Erika Lachman, Herbert M. TI Rare NRXN1 promoter variants in patients with schizophrenia SO NEUROSCIENCE LETTERS LA English DT Article DE Neurexin; Schizophrenia; Bipolar disorder; Autism; CNV; Copy variant ID ALPHA-NEUREXINS; TRANSCRIPTION FACTOR; GENE; ASSOCIATION; EXPRESSION; DEPENDENCE; APOPTOSIS; ENHANCER; SYNAPSE; AUTISM AB Copy number variants (CNVs) affecting the neurexin 1 (NRXN1) gene have been found in a subgroup of patients with schizophrenia (SZ). NRXN1 expression is complex, with multiple alternative splice forms generated from two major transcripts; NRXN1 alpha and NRXN1 beta. The majority of CNVs in SZ are deletions affecting the proximal NRXN1 alpha exons and promoter region. Rare chromosomal events are useful in understanding the genetic basis of complex psychiatric disorders since affected genes become feasible targets to analyze for more subtle genetic alterations. As a first step towards this goal, we resequenced the NRXN1 alpha promoter region in 170 patients with SZ and a similar number of controls. Two rare mutations were identified in the patient population. One previously unknown single nucleotide polymorphism (SNP) was found in controls. Bioinformatics analysis suggests that binding to several transcription factors may be affected by the minor alleles. The findings suggest that in addition to chromosomal alterations disrupting the NRXN1 alpha promoter, rare point mutations in the region may also be involved in SZ pathogenesis. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Shah, Abhishek K.; Tioleco, Nina M.; Groh, Katherine; Villa, Catalina; Pedrosa, Erika; Lachman, Herbert M.] Albert Einstein Coll Med, Basic Res Div, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA. [Nolan, Karen] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Nolan, Karen] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Locker, Joseph] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Stopkova, Pavla] Prague Psychiat Ctr, Prague, Czech Republic. RP Lachman, HM (reprint author), Albert Einstein Coll Med, Basic Res Div, Dept Psychiat & Behav Sci, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM Herb.Lachman@einstein.yu.edu FU NIMH [MH073164]; Juvenile Bipolar Research Foundation; New York State Office of Mental Health; NARSAD; MZCR [MZ0PCP2005] FX HML is supported by NIMH (MH073164) and the Juvenile Bipolar Research Foundation. AKS is supported by the New York State Office of Mental Health. KN is supported by a young investigator award from NARSAD. PS is supported by a research grant from MZCR MZ0PCP2005. The authors would like to thank Tomas Novak for recruiting patients in the Czech bipolar cohort, and Hana Fridrichova for administrative support. 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Lett. PD MAY 14 PY 2010 VL 475 IS 2 BP 80 EP 84 DI 10.1016/j.neulet.2010.03.047 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 623ZD UT WOS:000279785000005 PM 20347009 ER PT J AU Zhang, C Atasoy, D Arac, D Yang, XF Fucillo, MV Robison, AJ Ko, JW Brunger, AT Sudhof, TC AF Zhang, Chen Atasoy, Deniz Arac, Demet Yang, Xiaofei Fucillo, Marc V. Robison, Alfred J. Ko, Jaewon Brunger, Axel T. Sudhof, Thomas C. TI Neurexins Physically and Functionally Interact with GABA(A) Receptors SO NEURON LA English DT Article ID EXCITATORY SYNAPSE FORMATION; AUTISM SPECTRUM DISORDER; CELL-SURFACE PROTEINS; ALPHA-NEUREXINS; BETA-NEUREXINS; DROSOPHILA NEUREXIN; INHIBITORY SYNAPSES; SUBUNIT GENES; CA2+ CHANNELS; NEUROLIGIN 1 AB Neurexins are presynaptic cell-adhesion molecules that form trans-synaptic complexes with postsynaptic neuroligins. When overexpressed in nonneuronal cells, neurexins induce formation of postsynaptic specializations in cocultured neurons, suggesting that neurexins are synaptogenic. However, we find that when overexpressed in neurons, neurexins do not increase synapse density, but instead selectively suppressed GABAergic synaptic transmission without decreasing GABAergic synapse numbers. This suppression was mediated by all subtypes of neurexins tested, in a cell-autonomous and neuroligin-independent manner. Strikingly, addition of recombinant neurexin to cultured neurons at submicromolar concentrations induced the same suppression of GABAergic synaptic transmission as neurexin overexpression. Moreover, experiments with native brain proteins and purified recombinant proteins revealed that neurexins directly and stoichiometrically bind to GABA(A) receptors, suggesting that they decrease GABAergic synaptic responses by interacting with GABA(A) receptors. Our findings suggest that besides their other well-documented interactions, presynaptic neurexins directly act on postsynaptic GABA(A) receptors, which may contribute to regulate the excitatory/inhibitory balance in brain. C1 [Zhang, Chen; Arac, Demet; Yang, Xiaofei; Fucillo, Marc V.; Ko, Jaewon; Brunger, Axel T.; Sudhof, Thomas C.] Stanford Univ, Dept Mol & Cellular Physiol, Palo Alto, CA 94304 USA. [Atasoy, Deniz; Brunger, Axel T.; Sudhof, Thomas C.] Stanford Univ, Howard Hughes Med Inst, Palo Alto, CA 94304 USA. [Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA. [Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Biol Struct, Palo Alto, CA 94304 USA. [Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Photon Sci, Palo Alto, CA 94304 USA. [Sudhof, Thomas C.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Sudhof, Thomas C.] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. [Zhang, Chen; Atasoy, Deniz; Yang, Xiaofei; Robison, Alfred J.; Sudhof, Thomas C.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. RP Sudhof, TC (reprint author), Stanford Univ, Dept Mol & Cellular Physiol, 1050 Arastradero Rd, Palo Alto, CA 94304 USA. EM tcs1@stanford.edu FU NIMH [MH52804]; Simons Foundation; Life Sciences Research Foundation; Human Frontier Science Program Organization FX We would like to thank Dr. Robert L. Macdonald (Vanderbilt University) and Dr. Stephen Moss (Tufts University) for gifts of valuable reagents. This paper was supported by grants from the NIMH (MH52804 to T.C.S.) and the Simons Foundation (to T.C.S.), and fellowships from the Life Sciences Research Foundation (to D.A.) and the Human Frontier Science Program Organization (to J.K.). 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TI Normal Movement Selectivity in Autism SO NEURON LA English DT Article ID MIRROR-NEURON SYSTEM; FUNCTIONAL MAGNETIC-RESONANCE; SPECTRUM DISORDERS; CORTICAL ACTIVATION; IMITATION; ADAPTATION; FMRI; REPRESENTATION; CHILDREN; CORTEX AB It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism. C1 [Dinstein, Ilan; Heeger, David J.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Heeger, David J.] NYU, Dept Psychol, New York, NY 10003 USA. [Thomas, Cibu; Humphreys, Kate; Behrmann, Marlene] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Minshew, Nancy] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. RP Dinstein, I (reprint author), NYU, Ctr Neural Sci, 6 Washington Pl, New York, NY 10003 USA. EM ilan.dinstein@weizmann.ac.il FU National Institutes of Health [R01-MH069880]; NICHD/NIDCD [PO1/U19]; Pennsylvania Department of Health [SAP 4100047862]; Cure Autism Now (Young Investigator Award); [F31-MH080457] FX Supported by National Institutes of Health Grants R01-MH069880 (D.J.H.), NICHD/NIDCD PO1/U19 (M.B.; PI: Nancy Minshew), F31-MH080457 (ID.), Pennsylvania Department of Health grant SAP 4100047862, and Cure Autism Now (Young Investigator Award, K.H.). 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Much as they are informative, they also constitute noise as they are salient features of the visual scene potentially interfering with the processing of other features. Here we asked i) whether individuals with autism can exploit the information conveyed by cast shadows; ii) whether they are especially sensitive to noise aspects of shadows. Methodology/Principal Findings: Twenty high-functioning children with autism and twenty typically developing children were asked to recognize familiar objects while the presence, position, and shape of the cast shadow were systematically manipulated. Analysis of vocal reaction time revealed that whereas typically developing children used information from cast shadows to improve object recognition, in autistic children the presence of cast shadows-either congruent or incongruent-interfered with object recognition. Critically, vocal reaction times were faster when the object was presented without a cast shadow. Conclusions/Significance: We conclude that shadow-processing mechanisms are abnormal in autism. As a result, processing shadows becomes costly and cast shadows interfere rather than help object recognition. C1 [Becchio, Cristina] Univ Turin, Dipartimento Psicol, Ctr Cognit Sci, Turin, Italy. [Mari, Morena; Castiello, Umberto] Univ Padua, Dipartimento Psicol Gen, Padua, Italy. RP Becchio, C (reprint author), Univ Turin, Dipartimento Psicol, Ctr Cognit Sci, Turin, Italy. EM umberto.castiello@unipd.it FU Regione Piemonte; bando Scienze Umane e Sociali [4/2006] FX CB was supported by the Regione Piemonte, bando Scienze Umane e Sociali 2008, L.R. n. 4/2006. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Jiang, Yan Matevossian, Anouch Wang, Jie Weng, Zhiping Akbarian, Schahram TI Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral cortex; neuron; histone methylation; human; brain; gene expression ID EPIGENETIC REGULATION; HUMAN GENOME; HUMAN BRAIN; GENE-EXPRESSION; SCHIZOPHRENIA; CHROMATIN; METHYLATION; DISORDER; MATTER; AUTISM AB Little is known about the regulation of neuronal and other cell-type specific epigenomes from the brain. Here, we map the genome-wide distribution of trimethylated histone H3K4 (H3K4me3), a mark associated with transcriptional regulation, in neuronal and nonneuronal nuclei collected from prefrontal cortex (PFC) of 11 individuals ranging in age from 0.5 to 69 years. Massively parallel sequencing identified 12,732-19,704 H3K4me3 enriched regions (peaks), the majority located proximal to (within 2 kb of) the transcription start site (TSS) of annotated genes. These included peaks shared by neurons in comparison with three control (lymphocyte) cell types, as well as peaks specific to individual subjects. We identified 6,213 genes that show highly enriched H3K4me3 in neurons versus control. At least 1,370 loci, including annotated genes and novel transcripts, were selectively tagged with H3K4me3 in neuronal but not in nonneuronal PFC chromatin. Our results reveal age-correlated neuronal epigenome reorganization, including decreased H3K4me3 at approximately 600 genes (many function in developmental processes) during the first year after birth. In comparison, the epigenome of aging (> 60 years) PFC neurons showed less extensive changes, including increased H3K4me3 at 100 genes. These findings demonstrate that H3K4me3 in human PFC is highly regulated in a cell type-and subject-specific manner and highlight the importance of early childhood for developmentally regulated chromatin remodeling in prefrontal neurons. C1 [Cheung, Iris; Jiang, Yan; Matevossian, Anouch; Akbarian, Schahram] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Worcester, MA 01604 USA. [Wang, Jie; Weng, Zhiping] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA 01604 USA. [Weng, Zhiping] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01604 USA. [Shulha, Hennady P.; Weng, Zhiping] Boston Univ, Boston, MA 02215 USA. RP Akbarian, S (reprint author), Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Worcester, MA 01604 USA. EM zhiping.weng@umassmed.edu; schahram.akbarian@umassmed.edu RI Jiang, yan/C-7126-2011; Wang, Jie/F-9747-2011 FU National Institute of Mental Health [5RC1MH088047, 5R01-MH071476]; International Mental Health Research Organization; National Science Foundation [DBI 085008] FX We thank Dr. Ellen Kittler and Dr. Maria Zapp and the staff of theUMMSDeep Sequencing Core for expert advice and support, Dr. Oliver Rando for insightful discussions, and Dr. Yin Guo for excellent technical assistances. We are also grateful for the H3K4me3 datasets on GM12878 and K562, which were produced by the Bradley Bernstein group in the ENCODE consortium and distributed by the ENCODE data coordination center at UCSC. This work was supported by National Institute of Mental Health Grants 5RC1MH088047 and 5R01-MH071476 and by funds from the International Mental Health Research Organization (to S. A.) and National Science Foundation Grant DBI 085008 (to Z.W.). 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S. van Engeland, Herman Wijmenga, Cisca TI Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE autistic disorder; genotype; phenotype; databases; genetic; medical subject headings ID SPECTRUM DISORDERS; MENTAL-RETARDATION; PSYCHIATRIC-DISORDERS; ASSOCIATION ANALYSIS; GENOMEWIDE SCREEN; HUMAN PHENOME; HUMAN HEIGHT; EPILEPSY; CHILDREN; GENETICS AB Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic individuals not only improves understanding and diagnosis but also helps to define biologically more homogeneous groups of patients, improving the potential to detect causative genes. Supported by recent copy number variation findings in autism, we hypothesized that for some susceptibility loci, autism resembles a contiguous gene syndrome, caused by aberrations within multiple (contiguous) genes, which jointly increases autism susceptibility. This would result in various different clinical manifestations that might be rather atypical, but that also co-occur with autism. To test this hypothesis, 13 susceptibility loci, identified through genetic linkage and cytogenetic analyses, were systematically analyzed. The Online Mendelian Inheritance in Man database was used to identify syndromes caused by mutations in the genes residing in each of these loci. Subsequent analysis of the symptoms expressed within these disorders allowed us to identify 33 symptoms (significantly more than expected, P = 0.037) that were over-represented in previous reports mapping to these loci. Some of these symptoms, including seizures and craniofacial abnormalities, support our hypothesis as they are already known to co-occur with autism. These symptoms, together with ones that have not previously been described to co-occur with autism, might be considered for use as inclusion or exclusion criteria toward defining etiologically more homogeneous groups for molecular genetic studies of autism European Journal of Human Genetics (2010) 18, 588-595; doi:10.1038/ejhg.2009.206; published online 25 November 2009 C1 [Franke, Lude; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Buizer-Voskamp, Jacobine E.; Vorstman, Jacob A. S.] Univ Med Ctr, Dept Psychiat, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Buizer-Voskamp, Jacobine E.; Ophoff, Roel A.] Univ Med Ctr, DBG Dept Med Genet, Complex Genet Sect, Utrecht, Netherlands. [Staal, Wouter G.; van Daalen, Emma; Kemner, Chantal; van Engeland, Herman] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. RP Franke, L (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Genet, POB 30001, NL-9700 RB Groningen, Netherlands. EM lude@ludesign.nl RI Wijmenga, Cisca/D-2173-2009 FU Netherlands Genomics Initiative; Celiac Disease Consortium; Dutch government [BSIK03009] FX We thank Jackie Senior, Sasha Zhernakova, Madelien van de Beek, members of the Complex Genetics Section, the Department of Human Genetics, and the Department of Child & Adolescent Psychiatry for a critical reading of the paper. This study was supported by a Fellowship from the Netherlands Genomics Initiative and a grant from the Celiac Disease Consortium, an innovative cluster approved by the Netherlands Genomics Initiative and partially funded by a Dutch government Grant (BSIK03009). 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J. Hum. Genet. PD MAY 10 PY 2010 VL 18 IS 5 BP 588 EP 595 DI 10.1038/ejhg.2009.206 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 586ZO UT WOS:000276955500015 PM 19935830 ER PT J AU Mrozek-Budzyn, D Kieltyka, A Majewska, R AF Mrozek-Budzyn, Dorota Kieltyka, Agnieszka Majewska, Renata TI Lack of Association Between Measles-Mumps-Rubella Vaccination and Autism in Children A Case-Control Study SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE MMR vaccine; autism; children ID MMR VACCINE; DISORDER; VIRUS AB Objective: The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine. Design: Case-control study. Study Population: The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners. Methods: Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score. Results: For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99). Conclusions: The study provides evidence against the association of autism with either MMR or a single measles vaccine. C1 [Mrozek-Budzyn, Dorota; Kieltyka, Agnieszka; Majewska, Renata] Jagiellonian Univ, Coll Med, Chair Epidemiol & Prevent Med, Dept Epidemiol & Prevent Med, PL-31034 Krakow, Poland. RP Mrozek-Budzyn, D (reprint author), Jagiellonian Univ, Coll Med, Chair Epidemiol & Prevent Med, Dept Epidemiol & Prevent Med, Kopernika 7A, PL-31034 Krakow, Poland. 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Infect. Dis. J. PD MAY 10 PY 2010 VL 29 IS 5 BP 397 EP 400 DI 10.1097/INF.0b013e3181c40a8a PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 590IJ UT WOS:000277218600002 PM 19952979 ER PT J AU Handley, MTW Lian, LY Haynes, LP Burgoyne, RD AF Handley, Mark T. W. Lian, Lu-Yun Haynes, Lee P. Burgoyne, Robert D. TI Structural and Functional Deficits in a Neuronal Calcium Sensor-1 Mutant Identified in a Case of Autistic Spectrum Disorder SO PLOS ONE LA English DT Article ID LINKED MENTAL-RETARDATION; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PHOSPHATIDYLINOSITOL 4-OH KINASE; CA2+ SIGNAL-TRANSDUCTION; ACCESSORY PROTEIN-LIKE; TRANS-GOLGI NETWORK; BINDING-PROTEINS; NEURITE OUTGROWTH; IL1RAPL1 GENE; PC12 CELLS AB Neuronal calcium sensor-1 (NCS-1) is a Ca(2+) sensor protein that has been implicated in the regulation of various aspects of neuronal development and neurotransmission. It exerts its effects through interactions with a range of target proteins one of which is interleukin receptor accessory protein like-1 (IL1RAPL1) protein. Mutations in IL1RAPL1 have recently been associated with autism spectrum disorders and a missense mutation (R102Q) on NCS-1 has been found in one individual with autism. We have examined the effect of this mutation on the structure and function of NCS-1. From use of NMR spectroscopy, it appeared that the R102Q affected the structure of the protein particularly with an increase in the extent of conformational exchange in the C-terminus of the protein. Despite this change NCS-1(R102Q) did not show changes in its affinity for Ca(2+) or binding to IL1RAPL1 and its intracellular localisation was unaffected. Assessment of NCS-1 dynamics indicated that it could rapidly cycle between cytosolic and membrane pools and that the cycling onto the plasma membrane was specifically changed in NCS-1(R102Q) with the loss of a Ca(2+)-dependent component. From these data we speculate that impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain. C1 [Handley, Mark T. W.; Haynes, Lee P.; Burgoyne, Robert D.] Univ Liverpool, Sch Biomed Sci, Physiol Lab, Liverpool L69 3BX, Merseyside, England. [Lian, Lu-Yun] Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, England. RP Handley, MTW (reprint author), Univ Liverpool, Sch Biomed Sci, Physiol Lab, Liverpool L69 3BX, Merseyside, England. EM burgoyne@liv.ac.uk RI Burgoyne, Robert/C-6706-2008 OI Burgoyne, Robert/0000-0002-9219-0387 FU Wellcome Trust [080796/Z/06/Z] FX This work was supported by the Wellcome Trust (grant number 080796/Z/06/Z) to RDB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Other Topics GA 593OI UT WOS:000277467800016 PM 20479890 ER PT J AU Tansey, KE Brookes, KJ Hill, MJ Cochrane, LE Gill, M Skuse, D Correia, C Vicente, A Kent, L Gallagher, L Anney, RJL AF Tansey, Katherine E. Brookes, Keeley J. Hill, Matthew J. Cochrane, Lynne E. Gill, Michael Skuse, David Correia, Catarina Vicente, Astrid Kent, Lindsey Gallagher, Louise Anney, Richard J. L. TI Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: Genetic and molecular studies SO NEUROSCIENCE LETTERS LA English DT Article DE Oxytocin; Autism; Oxytocin receptor; Allelic expression imbalance; cis-Acting variation ID PERVASIVE DEVELOPMENTAL DISORDERS; GENOME-WIDE; AFFILIATIVE BEHAVIOR; LINKAGE ANALYSES; ASSOCIATION; AMYGDALA; VASOPRESSIN; EXPRESSION; CHILDREN; POPULATION AB Oxytocin (OXT) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. It is postulated that OXT reduces activation of the amygdala, inhibiting social anxiety, indicating a neural mechanism for the effects of OXT in social cognition. Genetic variation at the oxytocin receptor gene (OXTR) has been reported to be associated with autism. We examined 18 SNPs at the OXTR gene for association in three independent autism samples from Ireland, Portugal and the United Kingdom. We investigated cis-acting genetic effects on OXTR expression in lymphocytes and amygdala region of the brain using an allelic expression imbalance (AEI) assay and by investigating the correlation between RNA levels and genotype in the amygdala region. No marker survived multiple correction for association with autism in any sample or in a combined sample (n = 436). Results from the AEI assay performed in the lymphoblast cell lines highlighted two SNPs associated with relative allelic abundance in OXTR (rs237897 and rs237895). Two SNPs were found to be effecting cis-acting variation through AEI in the amygdala. One was weakly correlated with total gene expression (rs13316193) and the other was highlighted in the lymphoblast cell lines (rs237895). Data presented here does not support the role of common genetic variation in OXTR in the aetiology of autism spectrum disorders in Caucasian samples. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Tansey, Katherine E.; Hill, Matthew J.; Cochrane, Lynne E.; Gill, Michael; Gallagher, Louise; Anney, Richard J. L.] Univ Ireland Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland. [Brookes, Keeley J.; Kent, Lindsey] Univ St Andrews, Bute Med Sch, St Andrews KY16 9AJ, Fife, Scotland. [Skuse, David] UCL, Inst Child Hlth, Behav & Brain Unit, London WC1E 6BT, England. [Correia, Catarina; Vicente, Astrid] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Correia, Catarina; Vicente, Astrid] Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal. [Correia, Catarina; Vicente, Astrid] Ctr Biodivers Funct & Integrat Genom, Lisbon, Portugal. RP Tansey, KE (reprint author), Univ Ireland Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland. EM tanseyk@tcd.ie RI Hill, Matthew/E-7730-2010; Tansey, Katherine/B-1033-2013 OI Hill, Matthew/0000-0001-6776-8709; Tansey, Katherine/0000-0002-9663-3376 FU Health Research Board, Ireland; Wellcome Trust, UK; National Alliance for Autism Research, USA FX We thank the families who took part in this study for their support and cooperation. Family collection in Ireland and data analysis was supported by grants from the Health Research Board, Ireland, The Wellcome Trust, UK, and the National Alliance for Autism Research, USA. We would like to thank Dr. Robert Walker from the Edinburgh MRC Sudden Death Tissue and Brain Bank for providing the brain samples. 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PD MAY PY 2010 VL 99 IS 5 BP 645 EP 647 DI 10.1111/j.1651-2227.2010.01797.x PG 3 WC Pediatrics SC Pediatrics GA 575AG UT WOS:000276034800005 PM 20219042 ER PT J AU Fernell, E Barnevik-Olsson, M Bagenholm, G Gillberg, C Gustafsson, S Saaf, M AF Fernell, Elisabeth Barnevik-Olsson, Martina Bagenholm, Gunnel Gillberg, Christopher Gustafsson, Sven Saaf, Maria TI Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism SO ACTA PAEDIATRICA LA English DT Article DE Autism; 25-hydroxyvitamin D; Somali population ID VITAMIN-D DEFICIENCY; PROTEIN EXPRESSION; BRAIN-DEVELOPMENT; SWEDEN; RAT; SCHIZOPHRENIA; IMMIGRANTS; DISORDERS; BORN AB Aim: To analyse serum levels of 25-hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development. Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring. Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25-hydroxyvitamin D compared with Swedish mothers. The difference of 25-hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant. Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism. C1 [Fernell, Elisabeth] Autism Ctr Young Children Handicap & Habilitat, Stockholm, Sweden. [Fernell, Elisabeth] Skaraborg Hosp, Dept Paediat, Unit Dev Disorders, S-54185 Skovde, Sweden. [Fernell, Elisabeth] Skaraborg Hosp, FoU Ctr, S-54185 Skovde, Sweden. [Barnevik-Olsson, Martina] PRIMA Child & Adolescent Psychiat, Stockholm, Sweden. [Bagenholm, Gunnel] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat, Stockholm, Sweden. [Fernell, Elisabeth; Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol Child & Adolescent Psychi, Gothenburg, Sweden. [Gustafsson, Sven] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Saaf, Maria] Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden. RP Fernell, E (reprint author), Autism Ctr Young Children Handicap & Habilitat, S-54185 Skovde, Sweden. EM elisabeth.fernell@karolinska.se FU Stockholm County Council (Folkhalsoanslaget) FX The authors are grateful to the paediatric nurses Annika Larsson and Annika Svanberg at the Neuropaediatric Department at Astrid Lindgren Children's Hospital, Karolinska University Hospital for the accomplishment of all blood tests. We also thank Dr Mats Humble, psychiatrist, for valuable discussions and for his broad knowledge in the field.We are also indebted to Agneta Hilding at Karolinska University Hospital for help with statistical calculations.Financial support was given from the Stockholm County Council (Folkhalsoanslaget) and from Odd Fellow. 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PD MAY PY 2010 VL 99 IS 5 BP 743 EP 747 DI 10.1111/j.1651-2227.2010.01755.x PG 5 WC Pediatrics SC Pediatrics GA 575AG UT WOS:000276034800024 PM 20219032 ER PT J AU Dealberto, MJ AF Dealberto, M. -J. TI Ethnic origin and increased risk for schizophrenia in immigrants to countries of recent and longstanding immigration SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE schizophrenia; immigration; ethnicity; vitamin D; autism ID NEW-YORK-STATE; PRENATAL VITAMIN-D; MENTAL DISEASE; 1ST-CONTACT INCIDENCE; INCIDENCE RATES; 2ND-GENERATION IMMIGRANTS; PSYCHIATRIC-HOSPITALS; ENVIRONMENTAL-FACTORS; AFFECTIVE-DISORDERS; CHILDHOOD AUTISM AB Objectives: Compare the risk for schizophrenia in immigrants to countries of recent and longstanding immigration. Compare prevalence and incidence rates in black subjects under different conditions. Method: An electronic literature search was complemented by review articles and cross-references. Studies reporting standard diagnosis and incidence or prevalence rates were included. Results: Immigrants had an increased risk for schizophrenia in countries of longstanding immigration, but with lower risk ratios than in those of recent immigration. The risk was higher in black immigrants and the black population living in the United States. But incidence and prevalence rates in Africa and the Caribbean were similar to those of international studies. Conclusion: Comparing the most recent generation of immigrants with descendants of previous ones may account for the lower risk ratios observed in countries of longstanding vs. recent immigration. Two neurobiological hypotheses are proposed to explain the epidemiological findings in black populations and in immigrants. C1 Queens Univ, Dept Epidemiol & Community Hlth, Kingston, ON K7L 3N6, Canada. RP Dealberto, MJ (reprint author), Queens Univ, Dept Epidemiol & Community Hlth, Abramsky Hall,Arch St, Kingston, ON K7L 3N6, Canada. 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Scand. PD MAY PY 2010 VL 121 IS 5 BP 325 EP 339 DI 10.1111/j.1600-0447.2009.01535.x PG 15 WC Psychiatry SC Psychiatry GA 583CP UT WOS:000276650800002 PM 20105146 ER PT J AU Ekas, N Whitman, TL AF Ekas, Naomi Whitman, Thomas L. TI Autism Symptom Topography and Maternal Socioemotional Functioning SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES LA English DT Article ID BEHAVIOR PROBLEMS; STRESS PROLIFERATION; SPECTRUM DISORDERS; CHILDHOOD AUTISM; DEPRESSED MOOD; CHILDREN; MOTHERS; PARENTS; FATHERS; ASD AB Researchers examining the relationship of autism symptomatology and maternal stress have defined symptomatology in terms of level of severity, frequency of occurrence, or symptom type. In the present study, the relationship of maternal perceptions of these dimensions, along with a fourth, symptom diversity, and negative and positive indices of maternal socioemotional functioning was evaluated. 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PD MAY PY 2010 VL 115 IS 3 BP 234 EP 249 DI 10.1352/1944-7558-115.3.234 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 597SM UT WOS:000277781600004 PM 20441393 ER PT J AU Ramocki, MB Tavyev, YJ Peters, SU AF Ramocki, Melissa B. Tavyev, Y. Jane Peters, Sarika U. TI The MECP2 Duplication Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Review DE MECP2; Xq28; mental retardation; autism; recurrent infections; epilepsy; FLNA; IRAK1 ID SEVERE MENTAL-RETARDATION; CPG-BINDING PROTEIN-2; RETT-SYNDROME; COPY-NUMBER; FILAMIN-A; PERIVENTRICULAR HETEROTOPIA; RECURRENT INFECTIONS; CLINICAL VARIABILITY; STRUCTURAL VARIATION; GENOMIC DISORDERS AB In this review, we detail the history, molecular diagnosis, epidemiology, and clinical features of the MECP2 duplication syndrome, including considerations for the care of patients with this X-linked neurodevelopmental disorder. MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or autistic features, poor speech development, recurrent infections, epilepsy, progressive spasticity, and, in some cases, developmental regression. Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes that predate the birth of an affected son. Given what we know of the syndrome to date, we propose that genetic testing is warranted in cases of males with infantile hypotonia and in cases of boys with mental retardation and autistic features with or without recurrent infections, progressive spasticity, epilepsy, or developmental regression. We discuss recommendations for clinical management and surveillance as well as the need for further clinical, genotype phenotype, and molecular studies to assist the patients and their families who are affected by this syndrome. (C) 2010 Wiley-Liss, Inc. C1 [Ramocki, Melissa B.; Tavyev, Y. Jane; Peters, Sarika U.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Ramocki, MB (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, 1 Baylor Plaza,MS 225,BCM T807, Houston, TX 77030 USA. EM mramocki@bcm.edu FU NIH/NINDS [5K08NS062711-02]; NIH General Clinical Research Center [RR000188] FX We are grateful to Dr. James Lupski for critical reading of this manuscript and for helpful suggestions. We also thank Dr. Huda Zoghbi for her unwavering mentorship and support. We are continually grateful to the children and their families who participate in clinical research studies, and we are specifically grateful to the families who consented to the publication of photographs or videos of their sons. We acknowledge the support of NIH/NINDS grant 5K08NS062711-02 (M.B.R.) and NIH General Clinical Research Center grant RR000188. 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A PD MAY PY 2010 VL 152A IS 5 BP 1079 EP 1088 DI 10.1002/ajmg.a.33184 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 597ES UT WOS:000277739800004 PM 20425814 ER PT J AU Lindstrand, A Malmgren, H Verri, A Benetti, E Eriksson, M Nordgren, A Anderlid, BM Golovleva, I Schoumans, J Blennow, E AF Lindstrand, Anna Malmgren, Helena Verri, Annapia Benetti, Elisa Eriksson, Maud Nordgren, Ann Anderlid, Britt-Marie Golovleva, Irina Schoumans, Jacqueline Blennow, Elisabeth TI Molecular and Clinical Characterization of Patients With Overlapping 10p Deletions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE complex chromosomal rearrangement; cryptic deletion; chromosome 10; fluorescence in situ hybridization; array-CGH ID PARTIAL MONOSOMY 10P; RENAL DYSPLASIA SYNDROME; DIGEORGE-SYNDROME LOCUS; HUMAN HDR SYNDROME; SENSORINEURAL DEAFNESS; GENOMIC REARRANGEMENTS; BEHAVIOR CHECKLIST; CHROMOSOME 10P; ALU REPEATS; DE-NOVO AB Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings. (C) 2010 Wiley-Liss, Inc. C1 [Lindstrand, Anna; Malmgren, Helena; Nordgren, Ann; Anderlid, Britt-Marie; Schoumans, Jacqueline; Blennow, Elisabeth] Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden. [Verri, Annapia] C Mondino Fdn, Neurol Inst, Dept Behav Neurol, Pavia, Italy. [Benetti, Elisa] Univ Padua, Dept Pediat, Pediat Nephrol Dialysis & Transplantat Unit, Padua, Italy. [Eriksson, Maud] Karolinska Univ Hosp, Dept Neuropediat, Stockholm, Sweden. [Golovleva, Irina] Umea Univ Hosp, Dept Med Biosci, Med & Clin Genet Unit, S-90185 Umea, Sweden. RP Lindstrand, A (reprint author), Karolinska Univ Hosp Solna, Dept Mol Med & Surg, Clin Genet Unit, S-17176 Stockholm, Sweden. EM anna.lindstrand@ki.se RI Lindstrand, Anna/J-3566-2012 OI Lindstrand, Anna/0000-0003-0806-5602 FU Swedish Medical Research Council; Stockholm County Council; Linnea and Josef Carlsson Foundation FX We are grateful to the patients and their parents who participated in this study. We also thank Emma Tham for help with revision of the English language. The work was supported by grants from the Swedish Medical Research Council, Stockholm County Council, and the Linnea and Josef Carlsson Foundation. 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J. Med. Genet. A PD MAY PY 2010 VL 152A IS 5 BP 1233 EP 1243 DI 10.1002/ajmg.a.33366 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 597ES UT WOS:000277739800018 PM 20425828 ER PT J AU Vazna, A Musova, Z Vlckova, M Novotna, D Dvorakova, L Hrdlicka, M Havlovicova, M Sedlacek, Z AF Vazna, Alzbeta Musova, Zuzana Vlckova, Marketa Novotna, Drahuse Dvorakova, Lenka Hrdlicka, Michal Havlovicova, Marketa Sedlacek, Zdenek TI FMR1 Gene Expansion, Large Deletion of Xp, and Skewed X-Inactivation in a Girl With Mental Retardation and Autism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE fragile X syndrome; Xp deletion; array CGH; skewed X-inactivation; mental retardation; autism ID FULL MUTATION; FEMALES; CHROMOSOME; PHENOTYPE; MICROPHTHALMIA AB We describe a girl with mild facial anomalies, mild mental retardation, and atypical autism with a remarkable behavioral phenotype of persistent anger, aggression, and dysphoria. The occurrence of late-onset tremor and premature ovarian failure in the maternal branch of the family pointed to a possible defect in the FMR1 gene. Indeed, the patient carried a full FMR1 mutation. Unexpectedly, both alleles of the gene were almost completely methylated. Cytogenetic examination of the patient revealed in addition a large de novo deletion in band Xp22 on one of her X chromosomes. The deletion was fine mapped using oligonucleotide array CGH, and its breakpoints were localized using sequencing. The size of the deletion was about 17.4 Mb, and it contained more than 90 protein-coding genes. Microsatellite analysis indicated paternal origin of the aberrant chromosome. The large rearrangement was the most probable cause of the X-inactivation skewing, thus explaining the methylation of not only the expanded (maternal) but also the normal (paternal) FMR1 alleles. This pattern of skewed X-inactivation was confirmed using the analysis of methylation at the AR locus. The relatively mild phenotype of the patient resulted most likely from unmasking of the FMR1 defect. Although the deleted region contained many important genes, the phenotypic contribution of the rearranged X chromosome was probably limited by its almost complete inactivation. However, reduced dose of several genes escaping X-inactivation might also play a role in the phenotype of the patient. (C) 2010 Wiley-Liss, Inc. C1 [Vazna, Alzbeta; Musova, Zuzana; Vlckova, Marketa; Novotna, Drahuse; Havlovicova, Marketa; Sedlacek, Zdenek] Charles Univ Prague, Dept Biol & Med Genet, Fac Med 2, Prague 15006 5, Czech Republic. [Vazna, Alzbeta; Musova, Zuzana; Vlckova, Marketa; Novotna, Drahuse; Hrdlicka, Michal; Havlovicova, Marketa; Sedlacek, Zdenek] Univ Hosp Motol, Prague 15006 5, Czech Republic. [Dvorakova, Lenka] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague 15006 5, Czech Republic. [Dvorakova, Lenka] Gen Univ Hosp, Prague, Czech Republic. [Hrdlicka, Michal] Charles Univ Prague, Dept Child Psychiat, Fac Med 2, Prague 15006 5, Czech Republic. RP Sedlacek, Z (reprint author), Charles Univ Prague, Dept Biol & Med Genet, Fac Med 2, V Uvalu 84, Prague 15006 5, Czech Republic. EM zdenek.sedlacek@lfmotol.cuni.cz FU Ministries of Education and Health of the Czech Republic [NR/9457-3, MZO00064203, MSM0021620806]; European Commission [043318, 223692] FX This work was supported by grants NR/9457-3, MZO00064203, and MSM0021620806 from the Ministries of Education and Health of the Czech Republic, and INCORE (043318) and CHERISH (223692) from the European Commission. 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J. Med. Genet. A PD MAY PY 2010 VL 152A IS 5 BP 1273 EP 1277 DI 10.1002/ajmg.a.33352 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 597ES UT WOS:000277739800025 PM 20425835 ER PT J AU Davies, PL Tucker, R AF Davies, Patricia L. Tucker, Rebecca TI Evidence Review to Investigate the Support for Subtypes of Children With Difficulty Processing and Integrating Sensory Information SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Review DE classification; psychomotor performance; review; sensation disorders; sensory integrative dysfunction; sensory processing ID DEVELOPMENTAL COORDINATION DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; PERCEPTUAL-MOTOR ABILITIES; HIGH-FUNCTIONING AUTISM; LEARNING-DISABILITIES; YOUNG-CHILDREN; TYPICAL DEVELOPMENT; SPECTRUM DISORDERS; PRESCHOOL-CHILDREN AB We investigated the evidence for subtypes in children with difficulty processing and integrating sensory information. Fifty-seven articles were incorporated into a systematic literature review; only 4 articles provided direct evidence for subtypes. These studies did not provide a comprehensive assessment of all sensory functions and sensory-based motor functions (i.e., praxis) and included different diagnostic groups. Therefore, generalized conclusions about subtypes could not be drawn. The other 53 studies reviewed provided meaningful information about strengths and challenges that children with difficulty processing and integrating sensory information demonstrate, but these studies were limited in scope. A principal theme was the importance of conducting comprehensive assessments of sensory-based functions, including multiple measures of sensory integrative functions such as praxis, sensory modulation, and sensory discrimination in children and adolescents with various clinical disorders. 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J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 391 EP 402 DI 10.5014/ajot.2010.09070 PG 12 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500004 PM 20608271 ER PT J AU May-Benson, TA Koomar, JA AF May-Benson, Teresa A. Koomar, Jane A. TI Systematic Review of the Research Evidence Examining the Effectiveness of Interventions Using a Sensory Integrative Approach for Children SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Review DE activities of daily living; evidence-based practice; pediatrics; review; sensory integrative therapy; treatment outcome ID LEARNING-DISABLED CHILDREN; OCCUPATIONAL-THERAPY; MODULATION DISORDER; NYSTAGMUS DURATION; DISABILITIES; EFFICACY; TRIAL; COORDINATION; OUTCOMES; AUTISM AB Twenty-seven studies were systematically reviewed to identify, evaluate, and synthesize the research literature On the effectiveness of sensory integration (SI) intervention on the ability of children with difficulty processing and integrating sensory information to engage in desired occupations and to apply these findings to occupational therapy practice. Results suggest the SI approach may result in positive outcomes in sensorimotor skills and motor planning; socialization, attention, and behavioral regulation; reading-related skills; participation in active play; and achievement of individualized goals. Gross motor skills, self-esteem, and reading gains may be sustained from 3 mo to 2 yr. Findings may be limited by Type II error because of small sample sizes, variable intervention dosage, lack of fidelity to intervention, and selection of outcomes that may not be meaningful to clients and families or may not change with amount of treatment provided. Replication of findings with methodologically and theoretically sound studies is needed to support current findings. C1 [May-Benson, Teresa A.; Koomar, Jane A.] Spiral Fdn, Watertown, MA 02472 USA. [May-Benson, Teresa A.; Koomar, Jane A.] OTA Watertown, Watertown, MA 02472 USA. RP May-Benson, TA (reprint author), Spiral Fdn, 124 Watertown St, Watertown, MA 02472 USA. EM tmay-benson@alum.bu.edu CR Ahn RR, 2004, AM J OCCUP THER, V58, P287 Allen S, 1995, BRIT J OCCUPATIONAL, V58, P385 Arbesman M, 2010, AM J OCCUP THER, V64, P368, DOI 10.5014/ajot.2010.09068 Ayres A. 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M., 2008, AUSTRALASIAN J SPECI, V32, P83, DOI [10.1080/10300110701842653, DOI 10.1080/10300110701842653] Linderman TM, 1999, AM J OCCUP THER, V53, P207 MACDERMID JC, 2004, J HAND THER, V17, P103 Miller L. J., 2006, SENSATIONAL KIDS HOP Miller LJ, 2007, AM J OCCUP THER, V61, P228 Miller LJ, 2007, AM J OCCUP THER, V61, P161 MOHER D, 1994, JAMA-J AM MED ASSOC, V272, P122, DOI 10.1001/jama.272.2.122 MORRISON D, 1986, CHILD CARE HLTH DEV, V12, P99, DOI 10.1111/j.1365-2214.1986.tb00490.x OTTENBACHER K, 1982, AM J OCCUP THER, V36, P571 OTTENBACHER K, 1982, AM J OCCUP THER, V36, P657 OTTENBACHER K, 1979, PERCEPT MOTOR SKILL, V48, P1159 Parham LD, 2007, AM J OCCUP THER, V61, P216 POLATAJKO HJ, 1991, OCCUP THER J RES, V11, P155 POLATJKO HJ, 1992, OCCUP THER J RES, V12, P323 Roberts JE, 2007, AM J OCCUP THER, V61, P555 Rosenthal R., 1991, ESSENTIALS BEHAV RES SCHROEDER E, 1982, SCHOOL PSYCHOL INT, V3, P97 Shaw S. R., 2002, COMMUNIQUE, V31, P5 Storch BA, 1996, AM J OCCUP THER, V50, P662 TICKLEDEGNEN L, 1988, AM J OCCUP THER, V42, P427 Vargas S, 1999, AM J OCCUP THER, V53, P189 WERRY JS, 1990, J PAEDIATR CHILD H, V26, P31, DOI 10.1111/j.1440-1754.1990.tb02375.x WHITE M, 1979, J LEARNING DISABILIT, V12, P26 WILSON B N, 1992, Physical and Occupational Therapy in Pediatrics, V12, P1, DOI 10.1300/J006v12n01_01 WILSON BN, 1994, OCCUP THER J RES, V14, P244 Woodcock R. W., 1977, WOODCOCKJOHNSON PSYC Ziviani J., 1982, AUST OCCUP THER J, V29, P27, DOI 10.1111/j.1440-1630.1982.tb01365.x NR 55 TC 35 Z9 36 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 403 EP 414 DI 10.5014/ajot.2010.09071 PG 12 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500005 PM 20608272 ER PT J AU Polatajko, HJ Cantin, N AF Polatajko, Helene J. Cantin, Noemi TI Exploring the Effectiveness of Occupational Therapy Interventions, Other Than the Sensory Integration Approach, With Children and Adolescents Experiencing Difficulty Processing and Integrating Sensory Information SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE activities of daily living; occupational therapy; pediatrics; review; sensory integrative dysfunction; sensory processing; treatment outcome ID DEVELOPMENTAL COORDINATION DISORDER; WEIGHTED VEST; BALANCE BEAM; AUTISM; ATTENTION; EFFICACY; BEHAVIOR; TASK AB This literature review was completed as part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association to explore the effectiveness of occupational therapy interventions with children and adolescents experiencing difficulty processing and integrating sensory information. This part of the review focused on interventions other than the sensory integration approach. Twenty articles (reporting on 21 studies) met the inclusion criteria. This systematic review found that children with difficulty processing and integrating sensory information and difficulties with the performance of daily occupations can benefit from intervention. However, the great variability that characterizes this literature in terms of populations, interventions, and study quality precludes the formation of any firm conclusions regarding specific approaches. There is an urgent need for well-controlled studies examining the effectiveness of frequently used pediatric occupational therapy interventions with well-defined, homogeneous populations on outcomes that target participation in everyday life. C1 [Polatajko, Helene J.] Univ Toronto, Fac Med, Dept Occupat Therapy, Toronto, ON M5G 1V7, Canada. [Cantin, Noemi] Univ Toronto, Fac Med, Dept Rehabil Sci, Toronto, ON M5G 1V7, Canada. RP Polatajko, HJ (reprint author), Univ Toronto, Fac Med, Dept Occupat Therapy, 160-500 Univ Ave, Toronto, ON M5G 1V7, Canada. EM h.polatajko@utoronto.ca CR Arbesman M, 2010, AM J OCCUP THER, V64, P368, DOI 10.5014/ajot.2010.09068 AYRES AJ, 1979, SENSE INTEGRATION CH Baranek GT, 2002, J AUTISM DEV DISORD, V32, P397, DOI 10.1023/A:1020541906063 Candler Catherine, 2003, Physical & Occupational Therapy in Pediatrics, V23, P51, DOI 10.1300/J006v23n03_04 CHIA LC, 2002, PHYSIOTHERAPY SINGAP, V5, P75 DUNN W, 1990, OCCUP THER J RES, V10, P300 Dunn W, 1997, OCCUPATIONAL THERAPY, P182 Fertel-Daly D, 2001, AM J OCCUP THER, V55, P629 Fisher AG, 1991, SENSORY INTEGRATION, P3 Hall L, 2007, AM J OCCUP THER, V61, P209 Hartshorn K., 2001, EARLY CHILD DEV CARE, V166, P1, DOI DOI 10.1080/0300443011660101 HODGE SR, 1999, CLIN KINESIOLOGY, V53, P76 INDER JM, 2004, CLIN KINESIOLOGY, V58, P9 KAVALE K, 1983, J LEARN DISABIL, V16, P165 Kemmis BL, 1996, AM J OCCUP THER, V50, P709 Kielhofner G., 1997, CONCEPTUAL FDN OCCUP Polatajko Helene J., 2001, Physical and Occupational Therapy in Pediatrics, V20, P83, DOI 10.1300/J006v20n02_06 Martini R, 1998, OCCUP THER J RES, V18, P157 MATHIOWETZ V, 1997, OCCUPATIONAL THERAPY, P157 May-Benson TA, 2010, AM J OCCUP THER, V64, P403, DOI 10.5014/ajot.2010.09071 Miller L T, 2001, Can J Occup Ther, V68, P5 Miller LT, 2001, HUM MOVEMENT SCI, V20, P183, DOI 10.1016/S0167-9457(01)00034-3 Nolan JE, 2004, PERCEPT MOTOR SKILL, V99, P63, DOI 10.2466/pms.99.1.63-82 Pless M, 2000, ADAPT PHYS ACT Q, V17, P381 Schilling DL, 2004, J AUTISM DEV DISORD, V34, P423, DOI 10.1023/B:JADD.0000037418.48587.f4 Sinha Y, 2006, ARCH DIS CHILD, V91, P1018, DOI 10.1136/adc.2006.094649 Sugden DA, 2003, BRIT J EDUC PSYCHOL, V73, P545, DOI 10.1348/000709903322591235 VandenBerg NL, 2001, AM J OCCUP THER, V55, P621 Wilcox A, 1994, THESIS U W ONTARIO L Wilson PH, 2002, J CHILD NEUROL, V17, P491, DOI 10.1177/088307380201700704 World Health Organisation, 2001, INT CLASS FUNCT DIS NR 31 TC 14 Z9 14 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 415 EP 429 DI 10.5014/ajot.2010.09072 PG 15 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500006 PM 20608273 ER PT J AU Koenig, KP Rudney, SG AF Koenig, Kristie Patten Rudney, Sarah G. TI Performance Challenges for Children and Adolescents With Difficulty Processing and Integrating Sensory Information: A Systematic Review SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Review DE activities of daily living; human activities; pediatrics; review; sensory integrative dysfunction; sensory processing ID DEVELOPMENTAL COORDINATION DISORDER; HIGH-FUNCTIONING AUTISM; SCHOOL-AGED CHILDREN; ASPERGERS-DISORDER; YOUNG-CHILDREN; OCCUPATIONAL PERFORMANCE; SPECTRUM DISORDERS; SOCIAL-BEHAVIOR; SELF-REGULATION; SLEEP PATTERNS AB A systematic review of the literature related to performance difficulties for children and adolescents with difficulty processing and integrating sensory information was completed as part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association. The review focused on functional performance difficulties that these children may exhibit in areas of occupation including play and leisure, social participation, activities of daily living, instrumental activities of daily living, rest and sleep, education, and work. The results suggest that children and adolescents with difficulty processing and integrating sensory information do exhibit functional performance difficulties in key areas of occupation. However, further descriptive studies are needed to tie these difficulties to their specific sensory and motor issues. Researchers are encouraged to include functional performance measures and measures of social participation in their studies to further elucidate these relationships. C1 [Koenig, Kristie Patten] NYU, Steinhardt Sch Culture Human Dev & Educ, Dept Occupat Therapy, New York, NY 10012 USA. [Rudney, Sarah G.] Important Steps Inc, New York, NY USA. RP Koenig, KP (reprint author), NYU, Steinhardt Sch Culture Human Dev & Educ, Dept Occupat Therapy, 35 W 4th St,11th Floor, New York, NY 10012 USA. 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J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 430 EP 442 DI 10.5014/ajot.2010.09073 PG 13 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500007 PM 20608274 ER PT J AU Gal, E Dyck, MJ Passmore, A AF Gal, Eynat Dyck, Murray J. Passmore, Anne TI Relationships Between Stereotyped Movements and Sensory Processing Disorders in Children With and Without Developmental or Sensory Disorders SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE autistic disorder; developmental disabilities; hearing disorders; sensory integrative dysfunction; sensory processing; stereotypic movement disorder; visual disorders ID SELF-INJURIOUS-BEHAVIOR; AUTISM; INTEGRATION; DYSFUNCTION; EXPERIENCE; ATTENTION; INFANTS; PROFILE; MOTOR AB OBJECTIVE. Stereotyped movements (SM) are a defining characteristic of autism but are also present in children with a range of sensory and developmental disorders. We examined whether the severity of sensory processing disorders (SPD) was associated with the severity of SM and whether SPD accounted for between-group differences in SM. METHOD. The Short Sensory Profile and the Stereotyped and Self-Injurious Movements Interview were administered to children with autism, intellectual disability, visual impairment, and hearing impairment and to typically developing children. RESULTS. SPD predicted the severity of SM in all samples and accounted for differences in SM between the groups. Other differences in the severity of SM were the result of diagnosis and the interaction between diagnosis and an intellectual disability. CONCLUSION. SPD may be a source of SM, but functional connections between these phenomena will need to be tested in future research. Implications for occupational performance are addressed. C1 [Gal, Eynat] Univ Haifa, Dept Occupat Therapy, IL-31905 Haifa, Israel. [Dyck, Murray J.] Griffith Univ, Sch Psychol, Gold Coast, Australia. [Passmore, Anne] Curtin Univ Technol, Sch Occupat Therapy & Social Work, Curtin Hlth Innovat Res Inst, Ctr Res Disabil & Soc, Curtin, WA, Australia. RP Gal, E (reprint author), Univ Haifa, Dept Occupat Therapy, IL-31905 Haifa, Israel. EM eynatgal@gmail.com CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baum C., 2005, OCCUPATIONAL THERAPY, P242 Baumeister A. 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A., 1997, AUTISM EXECUTIVE DIS, P57 TURNER MA, 1999, REPETITIVE BEH UNPUB van der Maas HLJ, 2006, PSYCHOL REV, V113, P842, DOI 10.1037/0033-295X.113.4.842 WEHMEYER ML, 1989, THESIS U TEXAS DALLA White BP, 2007, AM J OCCUP THER, V61, P154 NR 50 TC 8 Z9 8 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 453 EP 461 DI 10.5014/ajot.2010.09075 PG 9 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500009 PM 20608276 ER PT J AU Cosbey, J Johnston, SS Dunn, ML AF Cosbey, Joanna Johnston, Susan S. Dunn, M. Louise TI Sensory Processing Disorders and Social Participation SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE human activities; interpersonal relations; sensory integrative dysfunction; sensory processing; social behavior ID DAILY-LIFE; CHILDREN; DYSFUNCTION; ADHD; IMPAIRMENT; ATTENTION; RESPONSES; PATTERNS; CONTEXT; AUTISM AB Participation in social aspects of daily life is crucial to children's development. Although disability status is recognized to affect children's ability to participate in social activities, little is understood about the impact of sensory processing disorders (SPD) on children's social participation. We examined the social participation patterns of 2 groups of children (ages 6-9): (1) children with SPD and (2) their typically developing peers. All children participated in a structured interview to report their social participation patterns, including activity patterns and social networks. We used parent and teacher questionnaires to triangulate the data gathered from the children. Results revealed that the 2 groups of children demonstrated generally similar patterns of activity preferences and use of free time but had significant differences in areas related to intensity and enjoyment of involvement and in their social networks. Implications for future research and interventions are discussed. C1 [Cosbey, Joanna] Univ New Mexico, Special Educ Program, Dept Educ Specialties, Albuquerque, NM 87131 USA. [Johnston, Susan S.] Univ Utah, Dept Special Educ, Salt Lake City, UT 84112 USA. [Dunn, M. Louise] Univ Utah, Div Occupat Therapy, Salt Lake City, UT 84112 USA. RP Cosbey, J (reprint author), Univ New Mexico, Special Educ Program, Dept Educ Specialties, Hokona Hall Room 282,MSC05 3040,1 Univ New Mexico, Albuquerque, NM 87131 USA. 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G., 2002, PROMOTING SOCIAL COM World Health Organisation, 2001, INT CLASS FUNCT DIS Yochman A, 2004, AM J OCCUP THER, V58, P294 NR 44 TC 16 Z9 16 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 462 EP 473 DI 10.5014/ajot.2010.09076 PG 12 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500010 PM 20608277 ER PT J AU Brown, NB Dunn, W AF Brown, Natalie Bennett Dunn, Winnie TI Relationship Between Context and Sensory Processing in Children With Autism SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE autistic disorder; child behavior; environment; sensory processing; sensory threshold ID DEVELOPMENTAL DISORDERS; OCCUPATIONAL-THERAPY; YOUNG-CHILDREN; PROFILE; PERFORMANCE; SCHOOL; FRAMEWORK; PARENTS AB OBJECTIVE. The purpose of the study was to determine the relationship between sensory processing and context for children with autism. We examined home and school contexts using the Sensory Profile (Dunn, 1999) and the Sensory Profile School Companion (Dunn, 2006a) questionnaires. METHOD. Teachers of 49 students with autism completed the Sensory Profile School Companion, and parents completed the Sensory Profile. We conducted correlational analyses using the avoiding and seeking quadrant scores from the School Companion and corresponding avoiding and seeking quadrant scores from the Sensory Profile. RESULTS. The avoiding quadrant score coefficient (.59) and the seeking quadrant score coefficient (.45) were statistically significant (p = .01) with good and fair correlations, respectively, suggesting that sensory processing patterns have both universal qualities and context-specific qualities in children with autism. CONCLUSION. Findings from this study provide initial evidence that sensory processing and context for children with autism are related. C1 [Brown, Natalie Bennett] The Manse, London NW8 9PU, England. [Dunn, Winnie] Univ Kansas, Med Ctr, Dept Occupat Therapy Educ, Lawrence, KS 66045 USA. RP Brown, NB (reprint author), The Manse, 9 Hamilton Gardens, London NW8 9PU, England. 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PD MAY-JUN PY 2010 VL 64 IS 3 SI SI BP 474 EP 483 DI 10.5014/ajot.2010.09077 PG 10 WC Rehabilitation SC Rehabilitation GA 612II UT WOS:000278890500011 PM 20608278 ER PT J AU Tu, ZD Cohen, M Bu, H Lin, F AF Tu, Zhidan Cohen, Mark Bu, Hong Lin, Feng TI Tissue Distribution and Functional Analysis of Sushi Domain-Containing Protein 4 SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DECAY-ACCELERATING FACTOR; FRYNS-SYNDROME; COMPLEMENT ACTIVATION; ESCHERICHIA-COLI; RECEPTOR; MICE; INHIBITION; PROTECTION; DEFICIENT; DISCOVERY AB Sushi domain-containing protein 4 (SUSD4) was a hypothetical cell surface protein whose tissue distribution and function were completely unknown. However, recent microarray-based studies have identified deletions of SUSD4 gene in patients with autism or Fryns syndrome, both of which are genetic diseases with severe abnormal neurological development and/or functions. In this article, we described the cloning, expression, refolding, tissue distribution, and functional analysis of this novel protein. Using polyclonal antibodies generated by immunizing chickens with the recombinant SUSD4, we found that SUSD4 is detectable in murine brains, eyes, spinal cords, and testis but not other tissues. In brains, SUSD4 is highly expressed in the white matter on oligodendrocytes/axons, and in eyes, it is exclusively expressed on the photoreceptor outer segments. In in vitro complement assays, SUSD4 augments the alternative but not the classical pathway of complement activation at the C3 convertase step. In in vivo studies, knocking down SUSD4 expression in zebrafish markedly increases ratios of mortality and developmental abnormality. These results provide the first insight into the important physiological roles of SUSD4 and could help to better understand the pathogenesis of autism and Fryns syndrome. (Am J Pathol 2010, 176:2378-2384; DOI: 10.2353/ajpath.2010.091036) C1 [Lin, Feng] Case Western Reserve Univ, Sch Med, Inst Pathol, Dept Pathol, Cleveland, OH 44106 USA. [Tu, Zhidan; Bu, Hong] Sichuan Univ, W China Hosp, Dept Pathol, Chengdu 610041, Peoples R China. RP Lin, F (reprint author), Case Western Reserve Univ, Sch Med, Inst Pathol, Dept Pathol, 2085 Adelbert Rd,Room 306, Cleveland, OH 44106 USA. EM hongbu@scu.edu.cn; feng.lin@case.edu FU National Institutes of Health [NS052471, EY11373]; National Multiple Sclerosis Society [RG3664]; Natural Science Foundation of China [30671988]; Chinese Oversea Postgraduate Program [3019-2008624057] FX Supported by National Institutes of Health (grants NS052471 to F.L. and EY11373 to Vision Science Research Center), National Multiple Sclerosis Society (grant RG3664 to F.L.), Natural Science Foundation of China (grant 30671988 to H.B.), and the Chinese Oversea Postgraduate Program Fellowship (grant 3019-2008624057 to Z.T.). 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Public Health PD MAY PY 2010 VL 100 IS 5 BP 772 EP 773 DI 10.2105/AJPH.2009.187708 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 585ME UT WOS:000276828800001 PM 20299637 ER PT J AU King, M Bearman, P AF King, Marissa Bearman, Peter TI ADVANCING PATERNAL AND MATERNAL AGE ARE BOTH IMPORTANT FOR AUTISM RISK KING AND BEARMAN RESPOND SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [King, Marissa; Bearman, Peter] Columbia Univ, Paul L Lazarsfeld Ctr Social Sci, New York, NY 10027 USA. RP King, M (reprint author), Columbia Univ, Paul L Lazarsfeld Ctr Social Sci, 420 W 118th St, New York, NY 10027 USA. EM mdk2101@columbia.edu CR Grether JK, 2009, AM J EPIDEMIOL, V170, P1118, DOI 10.1093/aje/kwp247 King MD, 2009, AM J PUBLIC HEALTH, V99, P1673, DOI 10.2105/AJPH.2008.149021 Lauritsen MB, 2005, J CHILD PSYCHOL PSYC, V46, P963, DOI 10.1111/j.1469-7610.2004.00391.x NR 3 TC 0 Z9 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2010 VL 100 IS 5 BP 773 EP 773 DI 10.2105/AJPH.2009.187880 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 585ME UT WOS:000276828800002 ER PT J AU Flenthrope, JL Brady, NC AF Flenthrope, Jennifer L. Brady, Nancy C. TI Relationships Between Early Gestures and Later Language in Children With Fragile X Syndrome SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE fragile X; gestural communication; autism spectrum disorders ID AUTISM SPECTRUM DISORDERS; COMMUNICATION PROFILES; YOUNG MALES; 2ND YEAR; INFANTS; LIFE AB Purpose: The authors hypothesized that significant positive relationships would exist between early gesture use and later language attainments in children with fragile X syndrome (FXS), as has been reported in studies with other populations. Method: Participants were young children with FXS and limited expressive language (21 boys, 4 girls), divided into 2 subgroups based on the Childhood Autism Rating Scale (CARS; Schopler, Reichler, & Renner, 1988) scores. Data were collected when participants were about 2 years of age and again when they were about 5 years of age. Communication was assessed through the analysis of video samples obtained in the children's homes for both observation periods. Correlational analyses were completed between early prelinguistic communication and later verbal communication scores for all participants and for children with high (>30) versus low (<30) scores on the CARS. Results: Although no significant relationships were found between prelinguistic gesture use and language outcomes for the group of children as a whole, significant negative correlations were found for the group of children who had high CARS scores. Conclusions: These outcomes did not support the authors' initial hypotheses. It was concluded that extensive use of developmentally early gestures by children with FXS who also have many symptoms of autism may not be a positive indicator of later language. C1 [Brady, Nancy C.] Univ Kansas, Dept Speech Language Hearing Sci & Disorders, Lawrence, KS 66045 USA. 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PD MAY 1 PY 2010 VL 19 IS 2 BP 135 EP 142 DI 10.1044/1058-0360(2009/09-0018) PG 8 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 622OS UT WOS:000279673700005 PM 19948762 ER PT J AU Flippin, M Reszka, S Watson, LR AF Flippin, Michelle Reszka, Stephanie Watson, Linda R. TI Effectiveness of the Picture Exchange Communication System (PECS) on Communication and Speech for Children With Autism Spectrum Disorders: A Meta-Analysis SO AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY LA English DT Article DE autism; Picture Exchange Communication System; communication intervention; speech ID SINGLE-SUBJECT RESEARCH; SEVERE DEVELOPMENTAL-DISABILITIES; SPECIAL-EDUCATION; YOUNG-CHILDREN; PHASE-III; INTERVENTIONS; PRESCHOOLERS; ACQUISITION; BEHAVIOR; ADULTS AB Purpose: The Picture Exchange Communication System (PECS) is a popular communication-training program for young children with autism spectrum disorders (ASD). This meta-analysis reviews the current empirical evidence for PECS in affecting communication and speech outcomes for children with ASD. Method: A systematic review of the literature on PECS written between 1994 and June 2009 was conducted. Quality of scientific rigor was assessed and used as an inclusion criterion in computation of effect sizes. Effect sizes were aggregated separately for single-subject and group studies for communication and speech outcomes. Results: Eight single-subject experiments (18 participants) and 3 group studies (95 PECS participants, 65 in other intervention/control) were included. Results indicated that PECS is a promising but not yet established evidence-based intervention for facilitating communication in children with ASD ages 1-11 years. Small to moderate gains in communication were demonstrated following training. Gains in speech were small to negative. Conclusions: This meta-analysis synthesizes gains in communication and relative lack of gains made in speech across the PECS literature for children with ASD. Concerns about maintenance and generalization are identified. Emerging evidence of potential preintervention child characteristics is discussed. Phase IV was identified as a possibly influential program characteristic for speech outcomes. 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PD MAY 1 PY 2010 VL 19 IS 2 BP 178 EP 195 DI 10.1044/1058-0360(2010/09-0022) PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 622OS UT WOS:000279673700009 PM 20181849 ER PT J AU Yoon, JMD Tennie, C AF Yoon, Jennifer M. D. Tennie, Claudio TI Contagious yawning: a reflection of empathy, mimicry, or contagion? SO ANIMAL BEHAVIOUR LA English DT Editorial Material DE Canis familiaris; chameleon effect; contagion; dog; empathy; mimicry; primate; social cognition; selective breeding; yawning ID DOGS; AFFILIATION; AUTISM; HUMANS C1 [Yoon, Jennifer M. D.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Tennie, Claudio] Max Planck Inst Evolutionary Anthropol, Dept Dev & Comparat Psychol, D-04103 Leipzig, Germany. RP Yoon, JMD (reprint author), Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. 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TI Perception of biological motion in common marmosets (Callithrix jacchus): by females only SO ANIMAL COGNITION LA English DT Article DE Common marmoset; Biological motion; Sex difference; Moving dot patterns ID POINT-LIGHT DISPLAYS; BIOMECHANICAL MOTIONS; RECOGNITION; INFANTS; COLOR; DISCRIMINATION; ADVANTAGE; STIMULI; MONKEYS; AUTISM AB The ability to perceive biological motion (BM) has been demonstrated in a number of species including humans but the few studies of non-human primates have been relatively inconclusive. We investigated whether common marmosets (Callithrix jacchus) are able to perceive biological motion, using a novel method to test non-human primates. Marmosets (7 male and 7 female) were trained to remove a cover from a container and look inside it, revealing a computer screen. Then they were presented with images on this computer screen consisting of a novel BM pattern (a walking hen) and 4 manipulations of that pattern (a static frame of this pattern and inverted, scrambled, and rotating versions of the pattern). The behavioural responses of the marmosets were recorded and used to assess discrimination between stimuli. BM was attended to by females but not males, as shown by active inspection behaviour, mainly movement of the head towards the stimulus. Females paid significantly less attention to all of the other stimuli. This indicates the females' ability to attend to biological motion. Females showed slightly more attention to the inverted BM than to the static, scrambled, and rotating patterns. The males were less attentive to all of the stimuli than were the females and, unlike the females, responded to all stimuli in a similar manner. This sex difference could be due to an inability of males to recognise BM altogether or to a lesser amount of curiosity. Considered together with the findings of previous studies on chicks and humans, the results of the present study support the notion of a common mechanism across species for the detection of BM. C1 [Brown, J.; Kaplan, G.; Rogers, L. J.; Vallortigara, G.] Univ New England, Sch Sci & Technol, Ctr Neurosci & Anim Behav, Armidale, NSW 2351, Australia. [Vallortigara, G.] Univ Trent, Ctr Mind Brain Sci, I-38068 Rovereto, Italy. RP Kaplan, G (reprint author), Univ New England, Sch Sci & Technol, Ctr Neurosci & Anim Behav, Armidale, NSW 2351, Australia. EM julian.brown20@yahoo.com; gkaplan@une.edu.au FU Australian Research Council FX We are grateful to the Australian Research Council for funding to L.J.R. in support of the marmoset colony at UNE. This project was part of the requirements of J.B.'s Honours degree at the University of New England. The housing and testing conditions of the marmosets were in accordance with the principles and regulations of the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (1997) and approved by the Animal Ethics committee at the University of New England (AEC08/037). 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Cogn. PD MAY PY 2010 VL 13 IS 3 BP 555 EP 564 DI 10.1007/s10071-009-0306-0 PG 10 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 582NC UT WOS:000276603500016 PM 20052512 ER PT J AU Bos, KJ Zeanah, CH Smyke, AT Fox, NA Nelson, CA AF Bos, Karen J. Zeanah, Charles H., Jr. Smyke, Anna T. Fox, Nathan A. Nelson, Charles A., III TI Stereotypies in Children With a History of Early Institutional Care SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID EARLY INTERVENTION PROJECT; EARLY EXPERIENCE; YOUNG-CHILDREN; DEPRIVATION; DISORDERS; BEHAVIOR; BRAIN; AUTISM AB Objectives: To investigate the prevalence of stereotypies in children with a history of early institutional care, evaluate the efficacy of a foster care intervention compared with institutional care on the course of stereotypies, and describe correlates in language, cognition, and anxiety for children who exhibit stereotypies. Design: Randomized controlled trial. Setting: Institutions in Bucharest, Romania. Participants: One hundred thirty-six children with a history of early institutional care. Intervention: Comparison of a foster care intervention with continued care as usual in an institution. Main Outcome Measures: The presence of stereotypies as well as outcomes in language, cognition, and anxiety. Results: At the baseline assessment prior to placement in foster care (average age of 22 months), more than 60% of children in institutional care exhibited stereotypies. Follow-up assessments at 30 months, 42 months, and 54 months indicated that being placed in families significantly reduced stereotypies, and with earlier and longer placements, reductions became larger. For children in the foster care group, but not in the care as usual group, stereotypies were significantly associated with lower outcomes on measures of language and cognition. Conclusions: Stereotypies are prevalent in children with a history of institutional care. A foster care intervention appears to have a beneficial/moderating role on reducing stereotypies, underscoring the need for early placement in home based care for abandoned children. Children who continue to exhibit stereotypies after foster care placement are significantly more impaired on outcomes of language and cognition than children without stereotypies and thus may be a target for further assessments or interventions. C1 [Bos, Karen J.; Nelson, Charles A., III] Harvard Univ, Sch Med, Childrens Hosp Boston, Cognit Neurosci Lab, Boston, MA 02115 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Zeanah, Charles H., Jr.; Smyke, Anna T.] Tulane Univ, Dept Psychiat & Behav Sci, New Orleans, LA 70118 USA. RP Nelson, CA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Cognit Neurosci Lab, 1 Autumn St,Off AU621,Mailbox 713, Boston, MA 02115 USA. EM charles.nelson@childrens.harvard.edu FU John D. and Catherine T. MacArthur Foundation; Binder Family Foundation; Richard David Scott Chair; Doris Duke Charitable Foundation FX Funding/Support: The work reported in this article was supported by the John D. and Catherine T. MacArthur Foundation, the Binder Family Foundation, the Richard David Scott Chair (Dr Nelson), and the Doris Duke Charitable Foundation (Ms Bos). 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Pediatr. Adolesc. Med. PD MAY PY 2010 VL 164 IS 5 BP 406 EP 411 PG 6 WC Pediatrics SC Pediatrics GA 590XG UT WOS:000277261100001 PM 20439790 ER PT J AU Atladottir, HO Thorsen, P Schendel, DE Ostergaard, L Lemcke, S Parner, ET AF Atladottir, Hjordis Osk Thorsen, Poul Schendel, Diana E. Ostergaard, Lars Lemcke, Saane Parner, Erik T. TI Association of Hospitalization for Infection in Childhood With Diagnosis of Autism Spectrum Disorders A Danish Cohort Study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID MEDICAL DISORDERS; CHILDREN; REGISTER; PREVALENCE; EXPRESSION; DENMARK; TRENDS; CELLS; TIME AB Objective: To investigate the association between hospitalization for infection in the perinatal/neonatal period or childhood and the diagnosis of autism spectrum disorders (ASDs). Design: A population-based cohort study. Setting: Denmark. Participants: All children born in Denmark from January 1, 1980, through December 31, 2002, comprising a total of 1 418 152 children. Exposure: Infection requiring hospitalization. Main Outcome Measure: The adjusted hazard ratio (HR) for ASDs among children hospitalized for infection compared with other children. Results: A total of 7379 children were diagnosed as having ASDs. Children admitted to the hospital for any infectious disease displayed an increased rate of ASD diagnoses (HR, 1.38 [95% confidence interval, 1.31-1.45]). This association was found to be similar for infectious diseases of bacterial and viral origin. Furthermore, children admitted to the hospital for noninfectious disease also displayed an increased rate of ASD diagnoses (HR, 1.76 [95% confidence interval, 1.68-1.86]), and admissions for infection increased the rate of mental retardation (2.18 [2.06-2.31]). Conclusions: The association between hospitalization for infection and ASDs observed in this study does not suggest causality because a general association is observed across different infection groups. Also, the association is not specific for infection or for ASDs. We discuss a number of noncausal explanatory models. C1 [Atladottir, Hjordis Osk; Lemcke, Saane; Parner, Erik T.] Aarhus Univ, Inst Publ Hlth, Dept Epidemiol, DK-8000 Aarhus C, Denmark. [Parner, Erik T.] Aarhus Univ, Inst Publ Hlth, Dept Biostat, DK-8000 Aarhus, Denmark. [Schendel, Diana E.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Ostergaard, Lars] Arhus Univ Hosp, Dept Infect Dis, Res Unit Q, Skejby, Denmark. RP Atladottir, HO (reprint author), Aarhus Univ, Inst Publ Hlth, Dept Epidemiol, Bartholin Alle 2, DK-8000 Aarhus C, Denmark. EM hoa@soci.au.dk RI Parner, Erik/F-5532-2010 FU Arhus University Research Foundation; Aase and Ejnar Danielsens Foundation; Augustinus Foundation; Familien Hede Nielsens Foundation; Lundbeck Foundation FX This study was supported by the Arhus University Research Foundation, the Aase and Ejnar Danielsens Foundation, the Augustinus Foundation, the Familien Hede Nielsens Foundation, and the Lundbeck Foundation. 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Pediatr. Adolesc. Med. PD MAY PY 2010 VL 164 IS 5 BP 470 EP 477 PG 8 WC Pediatrics SC Pediatrics GA 590XG UT WOS:000277261100012 PM 20439799 ER PT J AU Sung, M Fung, DSS Cai, YM Ooi, YP AF Sung, Min Fung, Daniel S. S. Cai, Yiming Ooi, Yoon Phaik TI Pharmacological management in children and adolescents with pervasive developmental disorder SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Asperger's syndrome; autism; autism spectrum disorder; pervasive developmental; disorder; pharmacological management ID PLACEBO-CONTROLLED CROSSOVER; YOUNG AUTISTIC-CHILDREN; CONTROLLED-RELEASE MELATONIN; OPEN-LABEL TRIAL; DOUBLE-BLIND; SPECTRUM DISORDERS; MENTAL-RETARDATION; RETROSPECTIVE ANALYSIS; REPETITIVE BEHAVIORS; DIVALPROEX SODIUM AB Methods: Electronic literature searches were conducted from the following sources: MEDLINE, Cochrane Library, PSYARTICLES and PsycINFO. 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SO AUTISM LA English DT Editorial Material ID COMPUTER-ASSISTED-INSTRUCTION; VIRTUAL ENVIRONMENTS; CHILDREN; ADOLESCENTS CR Bernard-Opitz V, 2001, J AUTISM DEV DISORD, V31, P377, DOI 10.1023/A:1010660502130 Bolte S, 2006, BEHAV NEUROSCI, V120, P211, DOI 10.1037/0735-7044.120.1.211 Golan O, 2006, DEV PSYCHOPATHOL, V18, P591, DOI 10.1017/S0954579406060305 Golan O, 2010, J AUTISM DEV DISORD, V40, P269, DOI 10.1007/s10803-009-0862-9 Goodwin MS, 2008, FOCUS AUTISM DEV DIS, V23, P125, DOI 10.1177/1088357608316678 MINEO BA, 2008, J AUTISM DEV DISORD, V39, P172 Mitchell P, 2007, J AUTISM DEV DISORD, V37, P589, DOI 10.1007/s10803-006-0189-8 Moore M, 2000, J AUTISM DEV DISORD, V30, P359, DOI 10.1023/A:1005535602064 Parsons S, 2005, AUTISM, V9, P95, DOI 10.1177/1362361305049032 Paul R, 2005, J AUTISM DEV DISORD, V35, P205, DOI 10.1007/s10803-005-1999-9 Bolte S, 2004, FOCUS ON AUTISM RESEARCH, P247 Strickland D, 1996, J AUTISM DEV DISORD, V26, P651, DOI 10.1007/BF02172354 Williams C, 2002, AUTISM, V6, P71, DOI 10.1177/1362361302006001006 Wing L., 1987, HDB AUTISM PERVASIVE Wolfberg P. J., 2009, PLAY IMAGINATION CHI NR 15 TC 12 Z9 12 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 J9 AUTISM JI Autism PD MAY PY 2010 VL 14 IS 3 BP 155 EP 159 DI 10.1177/1362361310365028 PG 5 WC Psychology, Developmental SC Psychology GA 618SV UT WOS:000279376900001 PM 20603897 ER PT J AU Lacava, PG Rankin, A Mahlios, E Cook, K Simpson, RL AF Lacava, Paul G. Rankin, Ana Mahlios, Emily Cook, Katie Simpson, Richard L. TI A single case design evaluation of a software and tutor intervention addressing emotion recognition and social interaction in four boys with ASD SO AUTISM LA English DT Article DE autism spectrum disorders; computers; emotion; social interaction ID ASPERGER-SYNDROME; COMPLEX EMOTION; AUTISM; ADULTS; CHILDREN; EMPATHY; MIND AB Many students with Autism Spectrum Disorders (ASD) have delays learning to recognize emotions. Social behavior is also challenging, including initiating interactions, responding to others, developing peer relationships, and so forth. In this single case design study we investigated the relationship between use of computer software ( Mind Reading: The Interactive Guide to Emotions) and emotion recognition ( ER) and social behavior change. After using Mind Reading for 7 to 10 weeks with a tutor, four boys with ASD improved ER scores and social interactions with peers. However, observed behavior changes were not strong enough to claim a causal relationship between variables. Findings, practice implications, and future research are discussed. C1 [Lacava, Paul G.; Rankin, Ana; Mahlios, Emily; Cook, Katie; Simpson, Richard L.] Univ Kansas, Lawrence, KS 66045 USA. RP Lacava, PG (reprint author), Rhode Isl Coll, 600 Mt Pleasant Ave,Horace Mann Hall Room 061, Providence, RI 02908 USA. 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Vaupel, Manya Fielding, Paul MacDonald, Kevin Cernich, Shannon Symon, Jennifer TI Efficacy of TeachTown: Basics computer-assisted intervention for the Intensive Comprehensive Autism Program in Los Angeles Unified School District SO AUTISM LA English DT Article DE academics; Applied Behavior Aanalysis; cognitive skills; Computer Assisted Instruction; computers; generalization; language; social skills; TeachTown; technology ID CHILDREN; BEHAVIOR AB Computer Assisted Instruction (CAI) has shown increased popularity recently and there are many studies showing promise for this approach for children with Autism Spectrum Disorders (ASD). However, there are no between-subject studies to date assessing the efficacy of CAI with this population. In this study, 47 preschool and K-1 students in ASD classrooms participated from Los Angeles Unified School District. TeachTown: Basics, a CAI program which also includes supplementary off-computer activities, was implemented over 3 months for approximately 20 minutes per day on the computer and 20 minutes per day in supplementary TeachTown: Basics activities. Compared to the students in the control group, the TeachTown: Basics students showed more improvement overall on language and cognitive outcome measures. In addition, students who used TeachTown: Basics demonstrated significant progress overall in the software and those students who used the program for more time demonstrated larger gains within the software and in outcome measures. Although not conclusive, these findings offer possibilities for the use of CAI for remediating many deficits for children with ASD and other special needs. In addition, CAI may offer solutions to schools and parents with insufficient funds for more expensive treatments. C1 [Whalen, Christina; Vaupel, Manya; MacDonald, Kevin; Cernich, Shannon] Jigsaw Learning, TeachTown, Seattle, WA 98102 USA. [Moss, Debbie] Los Angeles Unified Sch Dist, Los Angeles, CA USA. [Symon, Jennifer] Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. RP Whalen, C (reprint author), Jigsaw Learning, TeachTown, 2815 Eastlake Ave E,Suite 300, Seattle, WA 98102 USA. EM chris@jigsawlearning.com CR Ahissar M, 2000, P NATL ACAD SCI USA, V97, P6832, DOI 10.1073/pnas.97.12.6832 Bernard-Opitz V, 2001, J AUTISM DEV DISORD, V31, P377, DOI 10.1023/A:1010660502130 Bondy A. 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T., 1997, EXPRESSIVE VOCABULAR Xiaoming L, 2004, PEDIATRICS, V113, P1715 NR 32 TC 13 Z9 13 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 J9 AUTISM JI Autism PD MAY PY 2010 VL 14 IS 3 BP 179 EP 197 DI 10.1177/1362361310363282 PG 19 WC Psychology, Developmental SC Psychology GA 618SV UT WOS:000279376900003 PM 20484002 ER PT J AU Wallace, S Parsons, S Westbury, A White, K White, K Bailey, A AF Wallace, Simon Parsons, Sarah Westbury, Alice White, Katie White, Kathy Bailey, Anthony TI Sense of presence and atypical social judgments in immersive virtual environments Responses of adolescents with Autism Spectrum Disorders SO AUTISM LA English DT Article DE Autism Spectrum Disorder; virtual reality technology ID DEVELOPMENTAL DISORDERS; REALITY; CHILDREN; SKILLS; INDIVIDUALS; INSTRUCTION; TECHNOLOGY; TOOL AB Immersive virtual environments (IVEs) are potentially powerful educational resources but their application for children with Autism Spectrum Disorder (ASD) is under researched. This study aimed to answer two research questions: (1) Do children with ASD experience IVEs in different ways to typically developing children given their cognitive, perceptual and sensory differences? and (2) Can an IVE accurately simulate ecologically valid social situations? Ten children with ASD and 14 typically developing (TD) adolescents all aged 12-16 years experienced three different IVEs. They completed self-report questionnaires on their sense of 'presence' in the IVEs and rated 'social attractiveness' of a virtual character in socially desirable and undesirable scenarios. The children with ASD reported similar levels of presence to their TD peers and no negative sensory experiences. Although TD adolescents rated the socially desirable character as more socially attractive than the undesirable character, adolescents with ASD rated the two characters as equally socially attractive. These findings suggest that children with ASD do not experience IVEs in different ways to their TD counterparts and that the IVEs are realistic enough to simulate authentic social situations. This study paints a very encouraging picture for the potential uses of IVEs in assessing and educating individuals with ASD. C1 [Parsons, Sarah] Univ Birmingham, Sch Educ, Birmingham B15 2TT, W Midlands, England. [Wallace, Simon; Westbury, Alice; White, Katie; White, Kathy; Bailey, Anthony] Univ Oxford, Oxford OX1 2JD, England. RP Parsons, S (reprint author), Univ Birmingham, Sch Educ, Birmingham B15 2TT, W Midlands, England. 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H. Prud'hommeaux, Emily T. Black, Lois M. Mitchell, Margaret TI Computational prosodic markers for autism SO AUTISM LA English DT Article DE autism; acoustic; computational; prosody; speech ID HIGH-FUNCTIONING AUTISM; DIAGNOSTIC-OBSERVATION-SCHEDULE; LANGUAGE IMPAIRMENT; SPECTRUM DISORDERS; REVISED ALGORITHMS; LINGUISTIC STRESS; CHILDREN; SPEECH; DURATION; VALIDITY AB We present results obtained with new instrumental methods for the acoustic analysis of prosody to evaluate prosody production by children with Autism Spectrum Disorder (ASD) and Typical Development (TD). Two tasks elicit focal stress - one in a vocal imitation paradigm, the other in a picture-description paradigm; a third task also uses a vocal imitation paradigm, and requires repeating stress patterns of two-syllable nonsense words. The instrumental methods differentiated significantly between the ASD and TD groups in all but the focal stress imitation task. The methods also showed smaller differences in the two vocal imitation tasks than in the picture-description task, as was predicted. In fact, in the nonsense word stress repetition task, the instrumental methods showed better performance for the ASD group. The methods also revealed that the acoustic features that predict auditory-perceptual judgment are not the same as those that differentiate between groups. Specifically, a key difference between the groups appears to be a difference in the balance between the various prosodic cues, such as pitch, amplitude, and duration, and not necessarily a difference in the strength or clarity with which prosodic contrasts are expressed. C1 [Van Santen, Jan P. H.] Oregon Hlth & Sci Univ, Div Biomed Comp Sci, Beaverton, OR 97006 USA. [Mitchell, Margaret] Univ Aberdeen, Aberdeen AB9 1FX, Scotland. RP Van Santen, J (reprint author), Oregon Hlth & Sci Univ, Div Biomed Comp Sci, 20000 NW Walker Rd, Beaverton, OR 97006 USA. 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This study assessed the potential of Topobo, a construction toy with programmable movement, to support social interaction in children with Autistic Spectrum Conditions (ASC). Groups of either typically developing (TD) children or those with ASC had group play sessions with Topobo and with LEGO (TM). We recorded the extent and sequence of different categories of play during these sessions. For both participant groups, there were more social forms of play with Topobo than with LEGO (TM). More solitary play occurred for LEGO (TM) and more parallel play occurred with Topobo. Topobo was also associated with more time in onlooker and cooperative play in TD. Finally, we observed differences in play sequences between TD and ASC children, and discuss how different play materials might produce specific patterns of play in these two groups. C1 [Yuill, Nicola] Univ Sussex, Sch Psychol, Brighton BN1 9QH, E Sussex, England. [Raffle, Hayes] Nokia Res, Palo Alto, CA USA. 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NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 755 BP 216S EP 217S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200685 ER PT J AU Guo, YQ Tang, YL Rice, C Lee, LC Wang, YF Cubells, JF AF Guo, Yanqing Tang, Yilang Rice, Catherine Lee, Li-Ching Wang, Yufeng Cubells, Joseph F. TI Validation of the Autism Spectrum Screening Scale (ASSQ), Mandarin Chinese Version SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Guo, Yanqing; Wang, Yufeng] Peking Univ, Hlth Sci Ctr, Inst Mental Hlth, Beijing 100871, Peoples R China. [Tang, Yilang; Cubells, Joseph F.] Emory Univ, Atlanta, GA 30322 USA. [Rice, Catherine] CDC & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Lee, Li-Ching] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 762 BP 219S EP 219S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200692 ER PT J AU Sakurai, T Ramoz, N Barreto, M Gazdoiu, M Takahashi, N Gertner, M Dorr, N Sosa, MAG De Gasperi, R Perez, G Schmeidler, J Mitropoulou, V Le, HC Lupu, M Hof, PR Elder, GA Buxbaum, JD AF Sakurai, Takeshi Ramoz, Nicolas Barreto, Marta Gazdoiu, Mihaela Takahashi, Nagahide Gertner, Michael Dorr, Nathan Sosa, Miguel A. Gama De Gasperi, Rita Perez, Gissel Schmeidler, James Mitropoulou, Vivian Le, H. Carl Lupu, Mihaela Hof, Patrick R. Elder, Gregory A. Buxbaum, Joseph D. TI Slc25a12 Disruption Alters Myelination and Neurofilaments: A Model for a Hypomyelination Syndrome and Childhood Neurodevelopmental Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Malate/aspartate shuttle; mitochondria; N-acetylaspartate (NAA); neuron-oligodendrocyte interactions; pyruvate ID MAGNETIC-RESONANCE-SPECTROSCOPY; AUTISM SPECTRUM DISORDERS; ASPARTATE-GLUTAMATE; BRAIN-METABOLITES; WHITE-MATTER; CARRIER; GENE; ASSOCIATION; CHILDREN; MITOCHONDRIA AB Background: SLC25A12, a susceptibility gene for autism spectrum disorders that is mutated in a neurodevelopmental syndrome, encodes a mitochondrial aspartate-glutamate carrier (aspartate-glutamate carrier isoform 1 [AGC1]). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidative phosphorylation and adenosine triphosphate production. Methods: We characterized mice with a disruption of the Slc25a12 gene, followed by confirmatory in vitro studies. Results: Slc25a12-knockout mice, which showed no AGC1 by immunoblotting, were born normally but displayed delayed development and died around 3 weeks after birth. In postnatal day 13 to 14 knockout brains, the brains were smaller with no obvious alteration in gross structure. However, we found a reduction in myelin basic protein (MBP)-positive fibers, consistent with a previous report. Furthermore, the neocortex of knockout mice contained abnormal neurofilamentous accumulations in neurons, suggesting defective axonal transport and/or neurodegeneration. Slice cultures prepared from knockout mice also showed a myelination defect, and reduction of Slc25a12 in rat primary oligodendrocytes led to a cell-autonomous reduction in MBP expression. Myelin deficits in slice cultures from knockout mice could be reversed by administration of pyruvate, indicating that reduction in AGC1 activity leads to reduced production of aspartate/N-acetylaspartate and/or alterations in the dihydronicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide(+) ratio, resulting in myelin defects. Conclusions: Our data implicate AGC1 activity in myelination and in neuronal structure and indicate that while loss of AGC1 leads to hypomyelination and neuronal changes, subtle alterations in AGC1 expression could affect brain development, contributing to increased autism susceptibility. C1 [Sakurai, Takeshi; Ramoz, Nicolas; Barreto, Marta; Gazdoiu, Mihaela; Takahashi, Nagahide; Gertner, Michael; Dorr, Nathan; Sosa, Miguel A. Gama; De Gasperi, Rita; Perez, Gissel; Schmeidler, James; Mitropoulou, Vivian; Elder, Gregory A.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sakurai, Takeshi; Ramoz, Nicolas; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY 10029 USA. [Hof, Patrick R.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Le, H. Carl; Lupu, Mihaela] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY USA. RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu RI Le, Hongbiao /H-4735-2011; Barreto, Marta/F-5591-2012 OI Barreto, Marta/0000-0001-6464-548X FU New York State Spinal Cord Injury [C020935]; Stanley Medical Research Institute [06R-1427]; Seaver Foundation; National Institute of Mental Health [MH066673]; National Institutes of Health (NIH) [R24CA83084, P30CA08748] FX TS is a Seaver Fellow and supported in part by New York State Spinal Cord Injury contract (C020935) and Stanley Medical Research Institute research grant (06R-1427). This research was supported by the Seaver Foundation (TS and JDB) and the National Institute of Mental Health (MH066673, JDB). Technical services at the Memorial Sloan-Kettering Cancer Center Small-Animal Imaging Core Facility were supported in part by National Institutes of Health (NIH) Small-Animal Imaging Research Program Grant R24CA83084 and NIH Center Grant P30CA08748. 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Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 BP 887 EP 894 DI 10.1016/j.biopsych.2009.08.042 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IW UT WOS:000277064100013 PM 20015484 ER PT J AU Garbern, JY Neumann, M Trojanowski, JQ Lee, VMY Feldman, G Norris, JW Friez, MJ Schwartz, CE Stevenson, R Sima, AAF AF Garbern, James Y. Neumann, Manuela Trojanowski, John Q. Lee, Virginia M. -Y. Feldman, Gerald Norris, Joy W. Friez, Michael J. Schwartz, Charles E. Stevenson, Roger Sima, Anders A. F. TI A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition SO BRAIN LA English DT Article DE mental retardation; corticobasal degeneration; tau expression; SLC9A6; autism ID FRONTOTEMPORAL LOBAR DEGENERATION; PROGRESSIVE SUPRANUCLEAR PALSY; AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONISM-DEMENTIA COMPLEX; PAIRED HELICAL FILAMENTS; CORTICOBASAL INCLUSION-BODIES; SWOLLEN ACHROMATIC NEURONS; ALZHEIMERS-DISEASE; WHITE-MATTER; PICKS-DISEASE AB We have studied a family with severe mental retardation characterized by the virtual absence of speech, autism spectrum disorder, epilepsy, late-onset ataxia, weakness and dystonia. Post-mortem examination of two males revealed widespread neuronal loss, with the most striking finding being neuronal and glial tau deposition in a pattern reminiscent of corticobasal degeneration. Electron microscopic examination of isolated tau filaments demonstrated paired helical filaments and ribbon-like structures. Biochemical studies of tau demonstrated a preponderance of 4R tau isoforms. The phenotype was linked to Xq26.3, and further analysis identified an in-frame 9 base pair deletion in the solute carrier family 9, isoform A6 (SLC9A6 gene), which encodes sodium/hydrogen exchanger-6 localized to endosomal vesicles. Sodium/hydrogen exchanger-6 is thought to participate in the targeting of intracellular vesicles and may be involved in recycling synaptic vesicles. The striking tau deposition in our subjects reveals a probable interaction between sodium/proton exchangers and cytoskeletal elements involved in vesicular transport, and raises the possibility that abnormalities of vesicular targeting may play an important role in more common disorders such as Alzheimer's disease and autism spectrum disorders. C1 [Garbern, James Y.; Sima, Anders A. F.] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. 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Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an 'empathy for pain' paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autism. C1 [Silani, Giorgia; Singer, Tania] Univ Zurich, Inst Empir Res Econ, Lab Social & Neural Syst Res, CH-8006 Zurich, Switzerland. [Bird, Geoffrey] Univ London Birkbeck Coll, Dept Psychol Sci, London WC1E 7HX, England. [Bird, Geoffrey; Brindley, Rachel; White, Sarah; Frith, Uta] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. 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To study the causative gene, the relationship between autism endophenotypes and their closely related genes has been analyzed. There is a subgroup of autism spectrum disorder (ASD) in which the ratio of second digit length to fourth digit length (2D/4D) is low (short digit group, SDG). We studied the relationship between ASD and HOXD genes, which are located in the candidate locus for ASD and are associated with digit morphogenesis, with a particular focus on SDG. We analyzed 25 SNPs of HOXD11, HOXD12, and HOXD13 in the subject of 98 ASD, 89 healthy controls, and 16 non-autistic patients (non-ASD). There was no significant difference in the genotype frequencies between the ASD and the healthy controls. However, the G-112T heterozyeote in the promoter region of HOXD11 was observed in only four patients with ASD and in none of the healthy controls or non-ASD subjects. Moreover, this HOXD11 G-112T was observed in three of 11 SDG with ASD but in none of the 15 non-SDG patients with ASD. There were eight SDG patients among the non-ASD ones, but this polymorphism was observed in none of them. Considering the above results, it is expected that candidate genes will be further identified, using HOXD11 G-112T polymorphism as a marker, by analyzing genes located near 2q in a larger number of ASD subjects with clinical signs of SDG. (c) 2009 Elsevier B.V. All rights reserved. C1 [Sugie, Yoko] Hamamatsu Univ Sch Med, Dept Pediat, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. RP Sugie, Y (reprint author), Hamamatsu Univ Sch Med, Dept Pediat, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. EM y-sugie@umin.ac.jp; sugie@jichi.ac.jp; toki-fukuda@jichi.ac.jp; yusosawa@nifty.com CR Alarcon M, 2008, AM J HUM GENET, V82, P150, DOI 10.1016/j.ajhg.2007.09.005 Alarcon M, 2002, AM J HUM GENET, V70, P60, DOI 10.1086/338241 Alarcon M, 2005, MOL PSYCHIATR, V10, P747, DOI 10.1038/sj.mp.4001666 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Bacchelli E, 2003, MOL PSYCHIATR, V8, P916, DOI 10.1038/sj.mp.4001340 Buxbaum JD, 2001, AM J HUM GENET, V68, P1514, DOI 10.1086/320588 Freitag CM, 2007, MOL PSYCHIATR, V12, P2, DOI 10.1038/sj.mp.4001896 Hamilton SP, 2005, BMC GENET, V6, DOI 10.1186/1471-2156-6-52 Bailey A, 1998, HUM MOL GENET, V7, P571 KUROIWA A, 2002, JIKKEN IGAKU, V17, P2441 Malas MA, 2006, EARLY HUM DEV, V82, P469, DOI 10.1016/j.earlhumdev.2005.12.002 Manning JT, 2001, DEV MED CHILD NEUROL, V43, P160, DOI 10.1017/S0012162201000317 Manning JT, 2007, ARCH SEX BEHAV, V36, P223, DOI 10.1007/s10508-007-9171-6 Manning JT, 2002, MED HYPOTHESES, V59, P334, DOI 10.1016/S0306-9877(02)00181-0 Osawa J, 2005, No To Hattatsu, V37, P424 Paul SN, 2006, TWIN RES HUM GENET, V9, P215, DOI 10.1375/twin.9.2.215 Shao YJ, 2002, AM J MED GENET, V114, P99, DOI 10.1002/ajmg.10153 Trivers R, 2006, HORM BEHAV, V49, P150, DOI 10.1016/j.yhbeh.2005.05.023 Wu SP, 2007, AM J MED GENET B, V144B, P492, DOI 10.1002/ajmg.b.30495 Yang MS, 2007, INT J DEV NEUROSCI, V25, P69, DOI 10.1016/j.ijdevneu.2006.12.002 Zakany J, 1997, P NATL ACAD SCI USA, V94, P13695, DOI 10.1073/pnas.94.25.13695 NR 21 TC 6 Z9 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD MAY PY 2010 VL 32 IS 5 BP 356 EP 361 DI 10.1016/j.braindev.2009.05.005 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 587SA UT WOS:000277011600002 PM 19540081 ER PT J AU Gardener, H Buka, SL AF Gardener, Hannah Buka, Stephen L. TI Fetal androgens and autism Reply SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Gardener, Hannah] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Gardener, H (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. EM hgardener@med.miami.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 2010 VL 196 IS 5 BP 416 EP 417 DI 10.1192/bjp.196.5.416a PG 2 WC Psychiatry SC Psychiatry GA 593AA UT WOS:000277422200020 ER PT J AU Voracek, M AF Voracek, Martin TI Fetal androgens and autism SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter ID DIGIT RATIO 2D4D C1 Univ Vienna, Sch Psychol, Dept Basic Psychol Res, A-1010 Vienna, Austria. RP Voracek, M (reprint author), Univ Vienna, Sch Psychol, Dept Basic Psychol Res, Liebiggasse 5,Rm 03-46, A-1010 Vienna, Austria. EM martin.voracek@univie.ac.at CR Baron-Cohen S, 2005, SCIENCE, V310, P819, DOI 10.1126/science.1115455 Gardener H, 2009, BRIT J PSYCHIAT, V195, P7, DOI 10.1192/bjp.bp.108.051672 Manning JT, 2001, DEV MED CHILD NEUROL, V43, P160, DOI 10.1017/S0012162201000317 McIntyre MH, 2006, REPROD BIOL ENDOCRIN, V4, DOI 10.1186/1477-7827-4-10 Voracek M, 2008, BEHAV BRAIN SCI, V31, P283, DOI 10.1017/S0140525X08004445 Voracek M, 2009, PSYCHOL REP, V104, P922, DOI 10.2466/PR0.104.3.922-956 NR 6 TC 3 Z9 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 2010 VL 196 IS 5 BP 416 EP 416 DI 10.1192/bjp.196.5.416 PG 1 WC Psychiatry SC Psychiatry GA 593AA UT WOS:000277422200019 PM 20435973 ER PT J AU Russell, G Kelly, S Golding, J AF Russell, G. Kelly, S. Golding, J. TI A qualitative analysis of lay beliefs about the aetiology and prevalence of autistic spectrum disorders SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE autism; autistic spectrum disorder; grounded theory; incidence; lay beliefs; lay understanding ID TIME AB Introduction There has been a dramatic increase in the prevalence of autistic spectrum disorders (ASD) in the last 20 years. The reasons for this are disputed. The consensus among epidemiologists and other experts is that greater case load is due to changes in diagnostic practice rather than reflecting changing aetiological factors leading to a true increase in incidence. We set out to examine lay views concerning the aetiology and prevalence of ASD and whether they conflict with or support this consensus position. Methods Over 100 unsolicited communications (letters e mails and several telephone calls) were received by a UK epidemiological study of ASD. We carried out a qualitative analysis of all correspondence in order to examine spontaneously expressed lay beliefs about the prevalence and aetiology of ASD. Results The majority of correspondents suggested theories about environmental causes of ASD. This study demonstrates the strength of lay belief that the true incidence of autism is rising, and this is due to risks from modern technologies and changing lifestyles. Conclusion This study based on unsolicited data highlights the contrast between lay explanations of increasing prevalence and the consensus opinion of medical experts. It also demonstrates how many people in direct contact with ASD have important information to share. C1 [Russell, G.; Kelly, S.] Univ Exeter, ESRC, Ctr Genom Soc, Exeter EX4 4PJ, Devon, England. [Golding, J.] Univ Bristol, Dept Community Based Med, Bristol, Avon, England. RP Russell, G (reprint author), Univ Exeter, ESRC, Ctr Genom Soc, Byrne House,St Germans Rd, Exeter EX4 4PJ, Devon, England. 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PD MAY PY 2010 VL 36 IS 3 BP 431 EP 436 DI 10.1111/j.1365-2214.2009.00994.x PG 6 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA 580ZI UT WOS:000276489300020 PM 19735265 ER PT J AU Mouridsen, SE Rich, B Isager, T AF Mouridsen, S. E. Rich, B. Isager, T. TI A longitudinal study of gastrointestinal diseases in individuals diagnosed with infantile autism as children SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE gastrointestinal diseases; infantile autism; longitudinal study ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; CLINICAL DISORDERS; ASPERGER-SYNDROME; FOLLOW-UP; SYMPTOMS; PREVALENCE; PSYCHOSIS; REGISTER; VALIDITY AB Background A number of studies have indicated a link between gastrointestinal (GI) diseases and autism spectrum disorders. Method The objective of this study was to compare the prevalence and types of GI diseases in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with GI diseases in 336 matched controls from the general population, based on data from the nationwide Danish National Hospital Register (DNHR). The average observation time was 30.3 years (SD 0.4) (range 27-30 years), and mean age at the end of the observation period was 42.7 years (SD 7.7) (range between 27 and 57 years of age). Results Of the 118 individuals with IA, 97 (82.2%) had been in contact with a medical hospital (inpatient hospitalization or outpatient visits) during the observation period, compared with 312/336 (92.9%) in the control group (P = 0.001). A similar proportion of members from the case and comparison group had a diagnosis of any GI disease in the DNHR: 30.5% against 30.7%, but the nature of their diseases may be somewhat different. Only diseases of oral cavity were significantly associated with IA: 20.3% against 1.2%, P < 0.0001. Otherwise, specific GI diseases occurred with low frequency in both groups. Conclusion Overall, no evidence was found that patients with IA were more likely than control persons without IA to have defined GI diseases during the 30.3-year observation period. C1 [Mouridsen, S. E.] Bispebjerg Hosp, Dept Child & Adolescent Psychiat, Copenhagen, Denmark. [Rich, B.] Naestved Hosp, Child & Adolescent Psychiat Ctr, Naestved, Denmark. [Isager, T.] Glostrup Univ Hosp, Ctr Child & Adolescent Psychiat, Copenhagen, Denmark. RP Mouridsen, SE (reprint author), Bispebjerg Hosp, Dept Child & Adolescent Psychiat, Copenhagen, Denmark. 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PD MAY-JUN PY 2010 VL 81 IS 3 BP 797 EP 810 PG 14 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 596NF UT WOS:000277691200009 PM 20573105 ER PT J AU Filippova, E Astington, JW AF Filippova, Eva Astington, Janet Wilde TI Children's Understanding of Social-Cognitive and Social-Communicative Aspects of Discourse Irony SO CHILD DEVELOPMENT LA English DT Article ID VERBAL IRONY; PRETENSE THEORY; MIND; PERCEPTIONS; UTTERANCES; ABILITY; AUTISM AB To bridge the social-reasoning focus of developmental research on irony understanding and the pragmatic focus of research with adult populations, this cross-sectional study examines 5-, 7-, and 9-year-olds' (n = 72) developing understanding of both social-cognitive and social-communicative aspects of discourse irony, when compared with adults (n = 24). 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R., 1979, EXPRESSION MEANING, DOI 10.1017/CBO9780511609213.007 Singer T, 2006, NEUROSCI BIOBEHAV R, V30, P855, DOI 10.1016/j.neubiorev.2006.06.011 Sperber D., 1995, RELEVANCE COMMUNICAT SULLIVAN K, 1995, BRIT J DEV PSYCHOL, V13, P191 Wilson Deirdre, 2000, METAREPRESENTATIONS, P411 WINNER E, 1987, METAPHOR SYMB ACT, V2, P13, DOI 10.1207/s15327868ms0201_2 WINNER E, 1991, BRIT J DEV PSYCHOL, V9, P257 NR 29 TC 12 Z9 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD MAY-JUN PY 2010 VL 81 IS 3 BP 913 EP 928 PG 16 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 596NF UT WOS:000277691200017 PM 20573113 ER PT J AU Deutsch, SI Urbano, MR Neumann, SA Burket, JA Katz, E AF Deutsch, Stephen I. Urbano, Maria R. Neumann, Serina A. Burket, Jessica A. Katz, Elionora TI Cholinergic Abnormalities in Autism: Is There a Rationale for Selective Nicotinic Agonist Interventions? SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE autism; acetylcholine; nicotinic acetylcholine receptors; clinical trials ID MAGNETIC-RESONANCE SPECTROSCOPY; ACETYLCHOLINE-RECEPTORS; YOUNG-CHILDREN; THERAPEUTIC IMPLICATIONS; SPECTRUM DISORDERS; BRAIN; SCHIZOPHRENIA; ACTIVATION; DONEPEZIL; NEURONS AB The core dysfunctions of autism spectrum disorders, which include autistic disorder, Asperger disorder, and pervasive developmental disorder not otherwise specified, include deficits in socialization and communication and a need for the preservation of "sameness;" intellectual impairment and epilepsy are common comorbidities. Data suggest that pathological involvement of cholinergic nuclei and altered expression of acetylcholine receptors, particularly nicotinic acetylcholine receptors, occur in brain of persons with autistic disorder. However, many of these studies involved postmortem tissue from small samples of primarily adult persons. Thus, the findings may reflect compensatory changes and may relate more closely to intellectual impairment and the confounding effects of seizures and medications, as opposed to the core dysfunctions of autism. Nonetheless, because of the roles played by acetylcholine receptors in general, and nicotinic acetylcholine receptors in particular, in normal processes of attention, cognition, and memory, selective cholinergic interventions should be explored for possible therapeutic effects. Additionally, there are electrophysiological data that complement the clinical observations of frequent comorbid seizure disorders in these patients, suggesting a disturbance in the balance of excitatory and inhibitory tone in the brains of persons with autistic disorders. Conceivably, because the alpha 7 nicotinic acetylcholine receptor is located on the surface of gamma-aminobutyric acid inhibitory neurons, selective stimulation of this receptor would promote gamma-aminobutyric acid's release and restore diminished inhibitory tone. The development of agonists and partial agonists for nicotinic acetylcholine receptors and positive allosteric modulators that enhance the efficiency of coupling between the binding of agonist and channel opening should facilitate consideration of clinical trials. C1 [Deutsch, Stephen I.; Urbano, Maria R.; Neumann, Serina A.; Burket, Jessica A.; Katz, Elionora] 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. 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Neuropharmacol. PD MAY-JUN PY 2010 VL 33 IS 3 BP 114 EP 120 DI 10.1097/WNF.0b013e3181d6f7ad PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 606ZH UT WOS:000278467400002 PM 20190638 ER PT J AU Beidas, RS Benjamin, CL Puleo, CM Edmunds, JM Kendall, PC AF Beidas, Rinad S. Benjamin, Courtney L. Puleo, Connor M. Edmunds, Julie M. Kendall, Philip C. TI Flexible Applications of the Coping Cat Program for Anxious Youth SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CLINICAL-TRIAL; CHILDHOOD SOCIAL PHOBIA; AUTISM SPECTRUM DISORDERS; ANXIETY DISORDERS; FOLLOW-UP; CHILDREN; ADOLESCENTS; COMORBIDITY; DEPRESSION AB The current article offers suggestions for ways to adapt empirically supported treatments (ESTs). A specific manualized EST (Coping Cat; Kendall & Hedtke, 2006a) is used to illustrate the concept of "flexibility within fidelity" (Kendall & Beidas, 2007; Kendall, Gosch, Furr, & Sood, 2008). Flexibility within fidelity stresses the importance of using ESTs while considering and taking into account individual client presentations. In this discussion, recommendations are offered for the use of the Coping Cat with younger youth, adolescents, and youth with secondary comorbidities (i.e., social skills deficits, inattentive symptoms, and depressive symptoms). C1 [Beidas, Rinad S.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Beidas, RS (reprint author), Temple Univ, Dept Psychol, 1701 N 13th St,Weiss Hall, Philadelphia, PA 19122 USA. 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Behav. Pract. PD MAY PY 2010 VL 17 IS 2 BP 142 EP 153 PG 12 WC Psychology, Clinical SC Psychology GA 587JI UT WOS:000276987000003 ER PT J AU Cheng, YF Ye, J AF Cheng, Yufang Ye, Jun TI Exploring the social competence of students with autism spectrum conditions in a collaborative virtual learning environment - The pilot study SO COMPUTERS & EDUCATION LA English DT Article DE Collaborative virtual learning environment; 3D Expressive avatar; Social competence; Autism spectrum conditions ID ASPERGER-SYNDROME; CHILDREN; ADOLESCENTS; DISORDERS; BELIEF AB Social reciprocity deficits are a core feature of the autism spectrum conditions (ASCs). Many individual with ASCs have difficulty with social interaction due to a frequent lack of social competence. This study focuses on using a virtual learning environment to help the deficiencies of social competence for people with ASCs, and to increase their social interaction. Specifically, it primitively explores social competence in collaborative virtual learning environment (CVLE) systems, and behavioral performance in social and cognitive interactions. Thus, this CVLE-social interaction system involves a 3D expressive avatar, an animated social situation, and verbal as well as text-communication. A preliminary empirical study involved CVLE-social interaction systems. Three participants who had been diagnosed with ASCs were conducted using a multiple baseline research for evidence of improved social competence through usage of the system. The experimental study consisted of 17 days; and the results showed that using the CVLE-social interaction system had significant positive effects on participants' performance, both within the CVLE-social interaction system and in terms of reciprocal social interaction learning. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Cheng, Yufang; Ye, Jun] Natl Changhua Univ Educ, Grad Inst E Learning, Changhua, Taiwan. 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TI Primate-Accelerated Evolutionary Genes: Novel Routes to Drug Discovery in Psychiatric Disorders SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Psychiatric diseases; schizophrenia; alcoholism; autism; primate-accelerated evolution; positive selection; synaptic transmission; drugable targets ID CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN EVOLUTION; POSITIVE SELECTION; HUMAN GENOME; BIPOLAR DISORDER; HOMO-SAPIENS; SUSCEPTIBILITY GENE; NATURAL-SELECTION; SCHIZOAFFECTIVE DISORDER; ALDEHYDE DEHYDROGENASE AB Novel molecular genetic approaches, at genome-scale in different species allowed characterizing genes that have undergone recent selection. The interest in this research field is not limited to the natural curiosity about our evolutionary past, but it is also to identify novel susceptibility genes for neuropsychiatic disorders by pointing specific human traits, such as behavioral and cognitive abilities. Hypotheses have been proposed to relate specific psychiatric disorders to the origin of modern humans, as evidenced by the theory of Crow about schizophrenia. In the present review, we will focus on genes that underwent positive selection in humans or displayed a human specific evolutionary pattern and which were reported as associated with psychiatric disorders. This will include the (1) DRD4 gene associated with attention-deficit/hyperactivity disorder, located in a locus that underwent a positive selection; the (2) GABRB2 gene, a gene associated with schizophrenia and recently reported as the target of a positive selection; (3) MARK1, a candidate gene for autism that was reported as displaying a signature of adaptative evolution in the human lineage, and (4) the ADH and ALDH2 genes which are associated with alcoholism, and for which evidence of positive selection was identified in the human lineage since the divergence between humans and chimpanzees. Identification of novel candidate genes based on recent evolution selection, coupled to genome-wide strategies designed to detect rare structural variants, could lead to a better knowledge of the molecular mechanisms of neurodevelopmental disorders and might therefore help to develop new medical chemistry. C1 [Gorwood, P.] Ctr Hosp St Anne, CMME, F-75674 Paris 14, France. [Moalic, J. -M.; Le Strat, Y.; Lepagnol-Bestel, A. -M.; Ramoz, N.; Loe-Mie, Y.; Maussion, G.; Gorwood, P.; Simonneau, M.] Univ Paris 05, Ctr Psychiat & Neurosci, INSERM, U675, F-75014 Paris, France. RP Gorwood, P (reprint author), Ctr Hosp St Anne, CMME, 100 Rue Sante, F-75674 Paris 14, France. 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Med. Chem. PD MAY PY 2010 VL 17 IS 13 BP 1300 EP 1316 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 573QZ UT WOS:000275931000004 PM 20166940 ER PT J AU van Spronsen, M Hoogenraad, CC AF van Spronsen, Myrrhe Hoogenraad, Casper C. TI Synapse Pathology in Psychiatric and Neurologic Disease SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Synaptic plasticity; Spine morphology; Synapse pathology; Neurologic diseases; Psychiatric disorders ID AUTISM SPECTRUM DISORDERS; FRAGILE-X-SYNDROME; DENDRITIC SPINES; RECEPTOR TRAFFICKING; MOLECULAR-MECHANISMS; ALZHEIMERS-DISEASE; MENTAL-RETARDATION; IN-VIVO; PLASTICITY; ADDICTION AB Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. 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RP Hoogenraad, CC (reprint author), Erasmus MC, Dept Neurosci, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM c.hoogenraad@erasmusmc.nl RI Hoogenraad, Casper/B-8866-2011 FU Netherlands Organization for Scientific Research (NWO-ALW/ECHO); Netherlands Organization for Health Research and Development (ZonMw-VIDI/TOP); European Science Foundation; EMBO Young Investigators Programme (YIP); Human Frontier Science Program Career Development Award (HFSP-CDA) FX Dr. Hoogenraad is supported by The Netherlands Organization for Scientific Research (NWO-ALW/ECHO), Netherlands Organization for Health Research and Development (ZonMw-VIDI/TOP), European Science Foundation (European Young Investigators [EURYI] Award), EMBO Young Investigators Programme (YIP), and Human Frontier Science Program Career Development Award (HFSP-CDA). 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Neurol. Neurosci. Rep. PD MAY PY 2010 VL 10 IS 3 BP 207 EP 214 DI 10.1007/s11910-010-0104-8 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 602AY UT WOS:000278111700007 PM 20425036 ER PT J AU Williams, MA Sachdev, PS AF Williams, Mark A. Sachdev, Perminder S. TI Magnetoencephalography in neuropsychiatry: ready for application? SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE autism; dementia; depression; magnetoencephalography; schizophrenia ID AUTISM SPECTRUM DISORDERS; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; SCHIZOPHRENIA; MEG; BRAIN; SYNCHRONIZATION; OSCILLATIONS; RECORDINGS AB Purpose of review Magnetoencephalography (MEG) has been available for over 30 years, but the past 10 years have seen serious investigation of its use as a clinical tool. It is therefore an opportune time to review how MEG is able to contribute to neuropsychiatric research and practice. Recent findings We limit this review to the areas of dementia, schizophrenia, depression and autism. MEG can achieve correct classification of individuals with mild cognitive impairment versus Alzheimer's disease, may identify a marker of early disease in schizophrenia, can distinguish bipolar from major depressive disorder, and has been used to study cognitive and other deficits in autism. It provides a valuable tool to study cognitive dysfunction. Summary The most important aspect of MEG is the ability to record neural activity with millisecond precision, allowing coherence analysis of neural data to examine how brain areas are synchronized. Such synchrony is thought to underlie cognitive processes. As cognitive dysfunction is a common marker of neuropsychiatric disorders, MEG is emerging as an important investigatory tool in neuropsychiatry. 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The conservation of L1CAMs in Drosophila and Caenorhabditis elegans allows the opportunity to take advantage of these simple model organisms and their accessible genetic manipulations to dissect L1CAM functions and mechanisms of action. This review summarizes the discoveries of L1CAMs made in C. elegans, showcasing this simple model organism as a powerful system to uncover L1CAM mechanisms and roles in healthy and diseased states. Developmental Dynamics 239:1490-1501, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Chen, Lihsia; Zhou, Shan] Univ Minnesota, Dept Genet Cell Biol & Dev, Ctr Dev Biol, Minneapolis, MN 55455 USA. RP Chen, LH (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Ctr Dev Biol, Minneapolis, MN 55455 USA. 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Dyn. PD MAY PY 2010 VL 239 IS 5 SI SI BP 1490 EP 1501 DI 10.1002/dvdy.22269 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 595GE UT WOS:000277597900019 PM 20225255 ER PT J AU Sharrard, M AF Sharrard, Mark TI Clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Editorial Material ID ENCEPHALOMYOPATHIES; MYOPATHIES; DISORDERS; CHILDHOOD; FEATURES; SPECTRUM; AUTISM C1 Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. RP Sharrard, M (reprint author), Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. 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PD MAY PY 2010 VL 52 IS 5 BP 407 EP 408 DI 10.1111/j.1469-8749.2009.03488.x PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 583DS UT WOS:000276653800002 PM 19817774 ER PT J AU Verity, CM Winstone, AM Stellitano, L Krishnakumar, D Will, R McFarland, R AF Verity, Christopher M. Winstone, Anne Marie Stellitano, Lesley Krishnakumar, Deepa Will, Robert McFarland, Robert TI The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based study SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID RESPIRATORY-CHAIN DISORDERS; CREUTZFELDT-JAKOB-DISEASE; DIAGNOSTIC-CRITERIA; SPECTRUM DISORDERS; AUTISM; EPIDEMIOLOGY; PREVALENCE; SURVEILLANCE; DYSFUNCTION; VARIANT AB Aim Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group. Results By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies. Interpretation This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases. C1 [Verity, Christopher M.] Addenbrookes Hosp, Child Dev Ctr, PIND Surveillance Grp, Cambridge CB2 0QQ, England. [Will, Robert] Western Gen Hosp, Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [McFarland, Robert] Newcastle Univ, Mitochondrial Res Grp, Newcastle Upon Tyne, Tyne & Wear, England. RP Verity, CM (reprint author), Addenbrookes Hosp, Child Dev Ctr, PIND Surveillance Grp, Box 107,Hills Rd, Cambridge CB2 0QQ, England. EM christopher.verity@addenbrookes.nhs.uk FU Department of Health in England FX The PIND study is funded by the Department of Health in England. Many thanks to the BPSU of the Royal College of Paediatrics and Child Health and to Mr Richard Lynn, the Scientific Coordinator. The authors also wish to thank past and present members of the Expert Group. Our grateful thanks go to all the paediatricians who have reported cases to the study. 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Mutations in human neuroligin genes are associated with autism spectrum disorders in some families. The nematode Caenorhabditis elegans has a single neuroligin gene (nlg-1), and approximately a sixth of C. elegans neurons, including some sensory neurons, interneurons and a subset of cholinergic motor neurons, express a neuroligin transcriptional reporter. Neuroligin-deficient mutants of C. elegans are viable, and they do not appear deficient in any major motor functions. However, neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders. Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders. 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The aim of this study was to further evaluate the utility of this gene as a potential marker for schizophrenia. Both-schizophrenia and autism-are suggested to be neuronal maldevelopmental disorders with reports of mitochondrial dysfunction and increased oxidative stress. Therefore we have investigated the expression levels of mitochondrial complex I 75-kDa subunit mRNA in whole blood of children with autistic spectrum disorder (ASD) and a group of adolescent acute first-episode EOS patients in comparison to matched controls. We have found that compared to the respective controls only the group of EOS patients-and not the ASD group-showed a significantly altered expression of the complex I 75-kDa subunit mRNA. Although further studies are necessary to test for the specificity of this marker, our findings point to the potential use of the mitochondrial complex I as a biomarker for schizophrenia. C1 [Taurines, Regina; Klampfl, Karin; Romanos, Jasmin; Gerlach, Manfred] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. [Thome, Johannes; Forbes-Robertson, Sarah; Yang, Liya] Univ Coll Swansea, Inst Life Sci, Sch Med, Swansea SA2 8PP, W Glam, Wales. [Duvigneau, J. Catharina] Univ Vet Med Vienna, Dept Biomed Sci, Vienna, Austria. [Mueller, Sabine; Mehler-Wex, Claudia] Univ Ulm, Dept Child & Adolescent Psychiat & Psychotherapy, D-89075 Ulm, Germany. RP Taurines, R (reprint author), Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Fuchsleinstr 15, D-97080 Wurzburg, Germany. 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Child Adolesc. Psych. PD MAY PY 2010 VL 19 IS 5 BP 441 EP 448 DI 10.1007/s00787-009-0074-z PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 592WR UT WOS:000277412900004 PM 19894076 ER PT J AU Watanabe, K Ikeda, H Miyao, M AF Watanabe, Katsumi Ikeda, Hanako Miyao, Masutomo TI Learning efficacy of explicit visuomotor sequences in children with attention-deficit/hyperactivity disorder and Asperger syndrome SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Visuomotor sequence learning; Developmental disorder; Asperger syndrome; Attention-deficit/hyperactivity disorder; Learning curve ID DEFICIT HYPERACTIVITY DISORDER; HIGH-FUNCTIONING AUTISM; DEVELOPMENTAL DISORDERS; EXECUTIVE FUNCTIONS; MOTOR-AREA; ADHD; INHIBITION; INTERFERENCE; ACTIVATION; SPECTRUM AB Developmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and Asperger syndrome (AS) are often associated with learning disabilities. This study investigated the explicit learning of visuomotor sequences in 17 ADHD children (mean age 12.1), 21 AS children (mean age 12.7), and 15 typically developing children (mean age: 12.3). The participants were required to explore a hidden sequence of button presses by trial and error and elaborate the learned sequence (2 x 10 task: Hikosaka et al. 1996). The results indicated that although ADHD and AS children had a tendency of repeating the same errors and took longer to complete a sequence, both showed a degree and pattern of improvement in accuracy and speed similar to that of typically developing children. These results suggest that the explicit learning of visuomotor sequence in ADHD and AS patients is largely unimpaired. C1 [Watanabe, Katsumi; Ikeda, Hanako] Univ Tokyo, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan. [Watanabe, Katsumi] Natl Inst Adv Ind Sci & Technol, Tsukuba, Japan. [Watanabe, Katsumi] Japan Sci & Technol Agcy, Saitama, Japan. [Ikeda, Hanako] Japan Soc Promot Sci, Tokyo, Japan. [Miyao, Masutomo] Natl Ctr Child Hlth & Dev, Dept Dev & Behav Pediat, Tokyo, Japan. RP Watanabe, K (reprint author), Univ Tokyo, Res Ctr Adv Sci & Technol, Meguro Ku, 4-6-1 Komaba, Tokyo 1538904, Japan. EM kw@fennel.rcast.u-tokyo.ac.jp FU Japan Science and Technology Agency; Japan Society for the Promotion of Science; MEXT Knowledge Custer Initiative (Toyama/Ishikawa Region); New Technology Foundation FX This research was supported by Japan Science and Technology Agency, Japan Society for the Promotion of Science, MEXT Knowledge Custer Initiative (Toyama/Ishikawa Region), Grant-in-Aids for Scientific Research from the MEXT, and New Technology Foundation. 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Brain Res. PD MAY PY 2010 VL 203 IS 1 BP 233 EP 239 DI 10.1007/s00221-010-2217-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 591FC UT WOS:000277283800022 PM 20339839 ER PT J AU Jyonouchi, H AF Jyonouchi, Harumi TI Autism spectrum disorders and allergy: observation from a pediatric allergy/immunology clinic SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Article DE allergy; asthma; autism spectrum disorders; IgE-mediated allergic reactions; non-IgE-mediated 'allergic' reactions ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; REGULATORY T-CELLS; INDUCED ENTEROCOLITIS SYNDROME; POPULATION-BASED SAMPLE; CELIAC-DISEASE; FOOD ALLERGY; MENTAL-RETARDATION; ATOPIC ECZEMA; GASTROINTESTINAL SYMPTOMS; PSYCHIATRIC COMORBIDITY AB IgE-mediated allergic diseases (e.g., allergic rhinoconjunctivitis, atopic asthma and food allergy) are prevalent (up to 30%) in the general population and are increasing in developed countries. In infants and young children, non-IgE-mediated food allergy is also prevalent. In addition to easily recognized organ-specific symptoms, allergic diseases can cause neuropsychiatric symptoms, such as irritability and hyperactivity, in otherwise healthy individuals. This is also likely to occur in children with autism spectrum disorder (ASD). Moreover, the discomfort and pain associated with allergic diseases could aggravate behavioral symptoms in ASD children. Allergic conditions are easily treatable; however, ASD children may be underdiagnosed and/or undertreated for allergic and other common childhood diseases, in part due to their impaired communication skills. Practicing physicians should be aware of the potential impact of allergic diseases on behavioral symptoms and cognitive activity in ASD children. However, they also need to be aware that certain symptoms often attributed to 'allergy' by caregivers may not be immune mediated and should understand that behavioral symptoms can also be affected by many non-IgE-mediated causes. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07101 USA. RP Jyonouchi, H (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07101 USA. EM jyanouha@umdnj.edu FU Autism Research Institute (San Diego, CA, USA); Jonty Foundation (St Paul, MN, USA) FX This study was partly supported by funding from the Autism Research Institute (San Diego, CA, USA) and the Jonty Foundation (St Paul, MN, USA). The author is thankful to Lisa Huguenin for critically reviewing this manuscript. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. 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Clin. Immunol. PD MAY PY 2010 VL 6 IS 3 BP 397 EP 411 DI 10.1586/ECI.10.18 PG 15 WC Immunology SC Immunology GA 602VI UT WOS:000278166600015 PM 20441426 ER PT J AU Chatterjee, A O'Keefe, C AF Chatterjee, Archana O'Keefe, Catherine TI Current controversies in the USA regarding vaccine safety SO EXPERT REVIEW OF VACCINES LA English DT Review DE controversies; immunizations; vaccine safety; vaccines ID HUMAN-PAPILLOMAVIRUS VACCINE; CAUSAL ASSOCIATION; MONONUCLEAR-CELLS; HPV VACCINATION; IMMUNE-SYSTEM; UNITED-STATES; MEASLES-VIRUS; IMMUNIZATION; PERTUSSIS; CHILDREN AB As a result of the vaccines discovered in the 20th Century, parents and many healthcare providers of the 21st Century have limited or no experience with the devastating effects of diseases such as polio, smallpox or measles. Fear of disease has shifted to concerns regarding vaccine safety. Scientific evidence has refuted many of the misconceptions regarding vaccine safety; however, parental refusal of vaccines is increasing. Here we review six of the most prevalent controversies surrounding vaccine safety: the proposed causal relationship between receipt of the measles mumps rubella vaccine and autism; thimerosal as a potential trigger for autism; religious objection based on some vaccine viruses being grown in cell lines from aborted fetal tissues; parental worries that use of the human papillomavirus vaccine may lead to youth promiscuity; fears regarding the purported association between pertussis vaccination and adverse neurological outcomes; and concerns regarding too many vaccines overloading or weakening the infant immune system. Healthcare providers are ideally positioned to correct these misconceptions, but they must recognize and acknowledge parents' concerns, educate themselves on the latest scientific research that addresses these, and dedicate sufficient time to discuss vaccine safety with worried parents. C1 [Chatterjee, Archana] Creighton Univ, Sch Med, Dept Pediat, Omaha, NE 68131 USA. [O'Keefe, Catherine] Creighton Univ, Sch Nursing, Omaha, NE 68131 USA. [O'Keefe, Catherine] Creighton Univ, Div Pediat Infect Dis, Omaha, NE 68131 USA. RP Chatterjee, A (reprint author), Creighton Univ, Sch Med, Dept Pediat, 601 N 30th St,Suite 2329, Omaha, NE 68131 USA. EM achatter@creighton.edu FU Merck; GlaxoSmithKline; Sanofi Pasteur; Novartis; Wyeth; MedImmune FX Archana Chatterjee has received research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Novartis, Wyeth and MedImmune. She has also served on the Speakers Bureau for Merck, GlaxoSmithKline, Sanofi Pasteur, Wyeth and MedImmune. She has served on ad hoc Advisory Boards for Merck, GlaxoSmithKline, Novartis, Sanofi Pasteur and MedImmune. Catherine O'Keefe is involved in research studies funded by Merck, GlaxoSmithKline, Sanofi Pasteur, Novartis, Wyeth and MedImmune. 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Vaccines PD MAY PY 2010 VL 9 IS 5 BP 497 EP 502 DI 10.1586/ERV.10.36 PG 6 WC Immunology SC Immunology GA 599RT UT WOS:000277931500012 PM 20450324 ER PT J AU Fournier, KA Kimberg, CI Radonovich, KJ Tillman, MD Chow, JW Lewis, MH Bodfish, JW Hass, CJ AF Fournier, Kimberly A. Kimberg, Cara I. Radonovich, Krestin J. Tillman, Mark D. Chow, John W. Lewis, Mark H. Bodfish, James W. Hass, Chris J. TI Decreased static and dynamic postural control in children with autism spectrum disorders SO GAIT & POSTURE LA English DT Article DE Center of pressure (COP); Center of mass (COM); Posture; Gait initiation; Stability ID HIGH-FUNCTIONING AUTISM; PARKINSONS-DISEASE; GAIT INITIATION; ASPERGERS-DISORDER; BALANCE; YOUNG; ADULTS; STABILITY; BEHAVIOR; OLDER AB purpose of this study was to investigate postural control in children with Autism Spectrum Disorders (ASD) during static and dynamic postural challenges. We evaluated postural sway during quiet stance and the center of pressure (COP) shift mechanism during gait initiation for 13 children with ASD and 12 age-matched typically developing (TD) children. Children with ASD produced 438% greater normalized mediolateral sway (p<0.05) and 104% greater normalized anteroposterior sway (p < 0.05) than TD children. Consequently, normalized sway area was also significantly greater (p < 0.05) in the group with ASD. Similarly, the maximum separation between the COP and center of mass (COM) during quiet stance was 100% greater in the anteroposterior direction (p < 0.05) and 146% greater in the resultant direction (p<0.05) for children with ASD. No significant difference was observed in the mediolateral direction, in spite of the 123% greater separation detected in children with ASD. During gait initiation, no group differences were detected in the posterior COP shift mechanism, suggesting the mechanism for generating forward momentum is intact. However, significantly smaller lateral COP shifts (p < 0.05) were observed in children with ASD, suggesting instability or an alternative strategy for generating momentum in the mediolateral direction. These results help to clarify some discrepancies in the literature, suggesting an impaired or immature control of posture, even under the most basic conditions when no afferent or sensory information have been removed or modified. Additionally, these findings provide new insight into dynamic balance in children with ASD. (C) 2010 Elsevier B.V. All rights reserved. C1 [Fournier, Kimberly A.] Univ Texas Pan Amer, Dept Hlth & Kinesiol, Edinburg, TX 78541 USA. [Kimberg, Cara I.; Radonovich, Krestin J.; Lewis, Mark H.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Tillman, Mark D.; Hass, Chris J.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA. [Chow, John W.] Mississippi Methodist Rehabil Ctr, Jackson, MS USA. [Bodfish, James W.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Fournier, KA (reprint author), Univ Texas Pan Amer, Dept Hlth & Kinesiol, Edinburg, TX 78541 USA. EM fournierka@utpa.edu RI Fournier, Kimberly/E-5052-2013 OI Fournier, Kimberly/0000-0001-5830-6131 FU Organization for Autism Research; National Institute of Health [R01 MH073402] FX This study was supported in part by grants from the Organization for Autism Research (Graduate Student Grant 2006) and the National Institute of Health (R01 MH073402 - Bodfish). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of OAR or NIH. We would like to thank Michelle Benjamin and Jacquelyn Selbst for their assistance with data collection. 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These clusters are geographically stable. Children born in a primary cluster are at four times greater risk for autism than children living in other parts of the state. This is comparable to the difference between males and females and twice the risk estimated for maternal age over 40. In every year roughly 3% of the new caseload of autism in California arises from the primary cluster we identify-a small zone 20 km by 50 km. We identify a set of secondary clusters that support the existence of the primary clusters. The identification of robust spatial clusters indicates that autism does not arise from a global treatment and indicates that important drivers of increased autism prevalence are located at the local level. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Mazumdar, Soumya; King, Marissa; Liu, Ka-Yuet; Zerubavel, Noam; Bearman, Peter] Columbia Univ, Inst Social & Econ Res & Policy, New York, NY 10027 USA. 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Vaccines PD MAY PY 2010 VL 6 IS 5 BP 368 EP 368 PG 1 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 652GW UT WOS:000281992700002 ER PT J AU Poon, JK LaRosa, AC Pai, GS AF Poon, Jennifer K. LaRosa, Angela C. Pai, G. Shashidhar TI Developmental Delay: Timely Identification and Assessment SO INDIAN PEDIATRICS LA English DT Review ID LOW-BIRTH-WEIGHT; AUTISM SPECTRUM DISORDERS; DEVELOPMENT PROGRAM; INFANT HEALTH; EARLY INTERVENTION; PREMATURE-INFANTS; MENTAL-RETARDATION; YOUNG-CHILDREN; FOLLOW-UP; RECOMMENDATIONS AB This paper outlines the prevalence of developmental delay in children and discusses the recent literature regarding the benefits of early identification and evidence based strategies for developmental surveillance and screening. We describe a systematic approach to the child with developmental delay and the optimal methodology for arriving at the etiologic basis for the delay. A review of the most up-to-date and relevant literature was completed using Pub Med, online databases, and texts. The medical evaluation with specific emphasis on the most recent recommendations for genetic, laboratory and imaging studies is described. The American Academy of Pediatrics algorithm for developmental surveillance and screening is discussed with consideration for the importance of culturally relevant screening tools across populations. In addition, specific screening tools are briefly discussed that may prove beneficial to the primary care provider as he/she implements routine surveillance and screening. C1 [Poon, Jennifer K.; LaRosa, Angela C.; Pai, G. Shashidhar] Med Univ S Carolina, Div Genet & Dev Behav Pediat, Charleston, SC 29425 USA. RP Poon, JK (reprint author), 135 Rutledge Ave,MSC 561, Charleston, SC 29425 USA. 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Isokpehi, Raphael D. Cohly, Hari H. TI Autism from a Biometric Perspective SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE autism; biometric evaluation; electro-photonic emission; gas discharge visualization (GDV) ID CEREBRAL-BLOOD-FLOW; CHILDHOOD AUTISM; BRAIN; DISCHARGE AB Purpose: The aim of this pilot study was to test autistic children, siblings and their parents using a biometric device based on the gas discharge visualization (GDV) technique in order to assess their psycho-emotional and physiological functional state based on the activity of the autonomic nervous system. Hypothesis: We hypothesize that the biometric assessment based on GDV will enable us: (1) to evaluate some specific features associated with autism spectrum disorder (ASD) as well as to compare autistic children to their siblings and to controls; (2) to analyze the differences in individual values of parents of autistic children versus parents of normal children. Results: Out of total of 48 acupuncture points present on ten fingertips of both hands and associated to organs/organ systems, autistic children differed significantly from controls (p < 0.05) in 36 (images without filter) and 12 (images with filter), siblings differed significantly from controls (p < 0.05) in 12 (images without filter) and seven (images with filter), autistic children differed significantly (p < 0.05) from siblings in eight (images without filter) and one (images with filter), fathers of autistic children differed significantly (p < 0.05) from controls in 14 (images without filter) and three (images with filter) and mothers of autistic children differed significantly (p < 0.05) from controls in five (images without filter) and nine (images with filter) acupuncture points. Conclusions: All compared groups have shown significant difference on both psycho-emotional (images without filter) and physiological (images with filter) levels. However, the differences between autistic children and controls expressed on psycho-emotional level were the most significant as compared to the other groups. Therefore, the activity of the sympathetic autonomic nervous system is significantly altered in children with autism. The biometric method based on GDV is a promising step in autism research that may lead towards creating a disease profile and identify unique signature/biomarker for autism. Further work should involve more participants in order to augment our findings. C1 [Kostyuk, Nataliya; Isokpehi, Raphael D.; Cohly, Hari H.] Jackson State Univ, Ctr Bioinformat & Computat Biol, Dept Biol, Jackson, MS 39217 USA. [Rajnarayanan, Rajendram V.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. RP Cohly, HH (reprint author), Jackson State Univ, Ctr Bioinformat & Computat Biol, Dept Biol, 1400 JR Lynch St,Box 18540, Jackson, MS 39217 USA. EM nkostyuk@gmail.com; rajendra@buffalo.edu; raphael.isokpehi@jsums.edu; hari.cohly@jsums.edu FU EPSCoR, National Science Foundation [EPS-0903787]; Research Centers in Minority Institutions (RCMI)-Center for Environmental Health [G12RR13459] FX EPSCoR, National Science Foundation (EPS-0903787) and Research Centers in Minority Institutions (RCMI)-Center for Environmental Health (NIH-NCRR G12RR13459). We acknowledge the RCMI statistical core lab for the use of SAS version 9.1 for data analysis. Additionally, we thank Jennifer Sims, Baraka Williams and Dr. Mark Yeager and Helen Mann for their assistance in obtaining data from autistic children and their family members and in proofreading the manuscript. CR Bell IR, 2003, J ALTERN COMPLEM MED, V9, P25, DOI 10.1089/107555303321222928 Boddaert N, 2002, PEDIATR RADIOL, V32, P1 Cohly HHP, 2005, INT REV NEUROBIOL, V71, P317, DOI 10.1016/S0074-7742(05)71013-8 Critchley HD, 2000, BRAIN, V123, P2203, DOI 10.1093/brain/123.11.2203 Dobson P., 2005, Proceedings. 18th IEEE Symposium on Computer-Based Medical Systems Fombonne E, 1999, J AUTISM DEV DISORD, V29, P349, DOI 10.1023/A:1022123822135 Hashimoto T, 2000, PEDIATR NEUROL, V23, P416, DOI 10.1016/S0887-8994(00)00224-1 Hendry J, 2006, NEUROIMAGE, V29, P1049, DOI 10.1016/j.neuroimage.2005.08.039 IVANOV OC, 2008, P 12 INT SCI C BIOEL, P40 Ivanov VV, 2008, HIGH TEMP+, V46, P3, DOI 10.1134/S0018151X08010021 Just MA, 2004, BRAIN, V127, P1811, DOI 10.1093/brain/awh199 Keller F, 2003, MOL NEUROBIOL, V28, P1, DOI 10.1385/MN:28:1:1 Korotkov K., 2002, HUMAN ENERGY FIELD S Korotkov K, 2004, J ALTERN COMPLEM MED, V10, P49, DOI 10.1089/107555304322848959 KOROTKOV KG, 2002, MED TEKH, V1, P21 Korvatska E, 2002, NEUROBIOL DIS, V9, P107, DOI 10.1006/nbdi.2002.0479 Krause I, 2002, J AUTISM DEV DISORD, V32, P337, DOI 10.1023/A:1016391121003 Lamb JA, 2000, HUM MOL GENET, V9, P861, DOI 10.1093/hmg/9.6.861 London Eric, 2000, Environmental Health Perspectives, V108, P401, DOI 10.2307/3454527 Lord C, 2000, NEURON, V28, P355, DOI 10.1016/S0896-6273(00)00115-X Lu G, 1997, AM J PHYSIOL-GASTR L, V273, pG1233 McGinnis WR, 2004, ALTERN THER HEALTH M, V10, P22 Mutter J, 2005, NEUROENDOCRINOL LETT, V26, P439 Ohnishi T, 2000, BRAIN, V123, P1838, DOI 10.1093/brain/123.9.1838 Pierce K, 2004, BRAIN, V127, P2703, DOI 10.1093/brain/awh289 Starkstein SE, 2000, J NEUROPSYCH CLIN N, V12, P370, DOI 10.1176/appi.neuropsych.12.3.370 Stokstad E, 2001, SCIENCE, V294, P34, DOI 10.1126/science.294.5540.34 Tuchman R, 2002, LANCET NEUROL, V1, P352, DOI 10.1016/S1474-4422(02)00160-6 Wakefield AJ, 1999, ISR MED ASSOC J, V1, P183 WEIZMAN A, 1982, AM J PSYCHIAT, V139, P1462 White JF, 2003, EXP BIOL MED, V228, P639 Wilcox J, 2002, NEUROPSYCHOBIOLOGY, V46, P13, DOI 10.1159/000063570 Zilbovicius M, 2000, AM J PSYCHIAT, V157, P1988, DOI 10.1176/appi.ajp.157.12.1988 CONSTIPATION BEHAV S NR 34 TC 1 Z9 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD MAY PY 2010 VL 7 IS 5 BP 1984 EP 1995 DI 10.3390/ijerph7051984 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 601YW UT WOS:000278105200009 PM 20623006 ER PT J AU Loucas, T Riches, NG Charman, T Pickles, A Simonoff, E Chandler, S Baird, G AF Loucas, Tom Riches, Nick Greatorex Charman, Tony Pickles, Andrew Simonoff, Emily Chandler, Susie Baird, Gillian TI Speech perception and phonological short-term memory capacity in language impairment: preliminary evidence from adolescents with specific language impairment (SLI) and autism spectrum disorders (ASD) SO INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS LA English DT Article DE language disorders; specific language impairment; autism spectrum disorders; non-word repetition tasks; working memory; speech perception. ID PERVASIVE DEVELOPMENTAL DISORDERS; WORKING-MEMORY; NONWORD REPETITION; PRESCHOOL-CHILDREN; DEFICITS; INDIVIDUALS; RECOGNITION; PREVALENCE; VOCABULARY; ATTENTION AB Aims: This study aimed to investigate the contributions of PSTM and speech perception in non-word processing and whether individuals with SLI and ASD plus language impairment (ALI) show similar or different patterns of deficit in these cognitive processes. Method & Procedures: Three groups of adolescents (aged 14-17 years), 14 with SLI, 16 with ALI, and 17 age and non-verbal IQ matched typically developing (TD) controls, made speeded discriminations between non-word pairs. Stimuli varied in PSTM load (two- or four-syllables) and speech perception load (mismatches on a word-initial or word-medial segment). Outcomes & Results: Reaction times showed effects of both non-word length and mismatch position and these factors interacted: four-syllable and word-initial mismatch stimuli resulted in the slowest decisions. Individuals with language impairment showed the same pattern of performance as those with typical development in the reaction time data. A marginal interaction between group and item length was driven by the SLI and ALI groups being less accurate with long items than short ones, a difference not found in the TD group. Conclusions & Implications: Non-word discrimination suggests that there are similarities and differences between adolescents with SLI and ALI and their TD peers. Reaction times appear to be affected by increasing PSTM and speech perception loads in a similar way. However, there was some, albeit weaker, evidence that adolescents with SLI and ALI are less accurate than TD individuals, with both showing an effect of PSTM load. This may indicate, at some level, the processing substrate supporting both PSTM and speech perception is intact in adolescents with SLI and ALI, but also in both there may be impaired access to PSTM resources. 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PD MAY PY 2010 VL 45 IS 3 BP 275 EP + DI 10.3109/13682820902936433 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 587QA UT WOS:000277006300002 PM 20131963 ER PT J AU Marui, T Funatogawa, I Koishi, S Yamamoto, K Matsumoto, H Hashimoto, O Jinde, S Nishida, H Sugiyama, T Kasai, K Watanabe, K Kano, Y Kato, N AF Marui, Tetsuya Funatogawa, Ikuko Koishi, Shinko Yamamoto, Kenji Matsumoto, Hideo Hashimoto, Ohiko Jinde, Seiichiro Nishida, Hisami Sugiyama, Toshiro Kasai, Kiyoto Watanabe, Keiichiro Kano, Yukiko Kato, Nobumasa TI Association between autism and variants in the wingless-type MMTV integration site family member 2 (WNT2) gene SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Association study; autistic disorder; haplotype block; WNT2 gene ID NO ASSOCIATION; SUSCEPTIBILITY; ABNORMALITIES; ETIOLOGY; DISORDER; BRAIN; 7Q31 AB Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time. We conducted a case-control study of nine single nucleotide polymorphisms (SNPs) within the WNT2 gene in 170 patients with autism and 214 normal controls in a Japanese population. We then conducted a TOT analysis in 98 autistic families (trios) to replicate the results of the case-control study. In the case-control study, three SNPs (rs3779547, rs4727847 and rs3729629), two major individual haplotypes (A-T-C and G-G-G, consisting of rs3779547, rs4727847, and rs3729629), and global probability values of the haplotype distributions in the same region (global p=0.0091) showed significant associations with autism. Furthermore, all of these significant associations were also observed in the TOT analysis. Our findings provide evidence for a significant association between WNT2 and autism. Considering the important role of the WNT2 gene in brain development, our results therefore indicate that the WNT2 gene is one of the strong candidate genes for autism. C1 [Marui, Tetsuya; Jinde, Seiichiro; Kasai, Kiyoto; Kato, Nobumasa] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1130033, Japan. [Marui, Tetsuya] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo 1130033, Japan. [Funatogawa, Ikuko] Teikyo Univ, Sch Med, Dept Hyg & Publ Hlth, Tokyo 173, Japan. [Koishi, Shinko; Sugiyama, Toshiro] Aichi Childrens Hlth & Med Ctr, Obu, Japan. [Yamamoto, Kenji] Kitasato Univ, Sch Med, Dept Psychiat, Sagamihara, Kanagawa 228, Japan. [Matsumoto, Hideo] Tokai Univ, Sch Med, Dept Psychiat, Isehara, Kanagawa 25911, Japan. [Hashimoto, Ohiko] Aino Univ, Fac Nursing & Rehabil, Dept Occupat Therapy, Ibaraki, Japan. [Nishida, Hisami] Asunaro Hosp Child & Adolescent Psychiat, Tsu, Mie, Japan. [Watanabe, Keiichiro; Kano, Yukiko] Univ Tokyo, Sch Med, Dept Child Psychiat, Tokyo 1130033, Japan. RP Marui, T (reprint author), Univ Tokyo, Sch Med, Dept Neuropsychiat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. 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J. Neuropsychopharmacol. PD MAY PY 2010 VL 13 IS 4 BP 443 EP 449 DI 10.1017/S1461145709990903 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604KU UT WOS:000278278700004 PM 19895723 ER PT J AU Suzuki, K Nishimura, K Sugihara, G Nakamura, K Tsuchiya, KJ Matsumoto, K Takebayashi, K Isoda, H Sakahara, H Sugiyama, T Tsujii, M Takei, N Mori, N AF Suzuki, Katsuaki Nishimura, Katsuhiko Sugihara, Genichi Nakamura, Kazuhiko Tsuchiya, Kenji J. Matsumoto, Kaori Takebayashi, Kiyokazu Isoda, Haruo Sakahara, Harumi Sugiyama, Toshiro Tsujii, Masatsugu Takei, Nori Mori, Norio TI Metabolite alterations in the hippocampus of high-functioning adult subjects with autism SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Aggression; autism; hippocampus; magnetic resonance spectroscopy ID AGGRESSION QUESTIONNAIRE; AMYGDALA; CHILDREN; BRAIN; DISORDER; SPECTROSCOPY; CEREBELLUM; SPECTRUM; VERSION AB The aim of the present study was to investigate metabolite alterations in the hippocarnpal formation as they relate to aggression in high-functioning adults with autism. We measured concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr + PCr) in the hippocampal formation by proton magnetic resonance spectroscopy in 12 non-medicated male subjects with autism and 12 age- and sex-matched controls. Aggression was scored in the autistic subjects using the Buss-Perry Aggression Questionnaire. The concentrations of Cho and Cr + PCr in the hippocampal formation in autistic subjects were significantly higher than the corresponding values in control subjects, and a significant positive correlation was observed between the concentrations of these metabolites in the hippocampal formation and scores on the Buss-Perry Aggression Questionnaire in autistic subjects. Results suggest that high-functioning adult subjects with autism have abnormal metabolite concentrations in the hippocampal formation, which may in part account for their aggression. C1 [Suzuki, Katsuaki; Sugihara, Genichi; Tsuchiya, Kenji J.; Matsumoto, Kaori; Takei, Nori] Hamamatsu Univ Sch Med, Osaka Hamamatsu Joint Res Ctr Child Mental Dev, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. [Nishimura, Katsuhiko; Nakamura, Kazuhiko; Takebayashi, Kiyokazu; Mori, Norio] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan. [Isoda, Haruo; Sakahara, Harumi] Hamamatsu Univ Sch Med, Dept Radiol, Hamamatsu, Shizuoka 4313192, Japan. [Sugiyama, Toshiro] Aichi Childrens Hlth & Med Ctr, Obu, Japan. [Tsujii, Masatsugu] Chukyo Univ, Fac Sociol, Toyota, Japan. RP Suzuki, K (reprint author), Hamamatsu Univ Sch Med, Osaka Hamamatsu Joint Res Ctr Child Mental Dev, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. EM k-suzuki@hama-med.ac.jp FU Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was supported by Grants-in-Aid for Scientific Research (B) and (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to Dr K. Nakamura and Dr G. Sugihara, respectively. 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J. Neuropsychopharmacol. PD MAY PY 2010 VL 13 IS 4 BP 529 EP 534 DI 10.1017/S1461145709990952 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604KU UT WOS:000278278700012 PM 19895725 ER PT J AU Semrud-Clikeman, M Walkowiak, J Wilkinson, A Minne, EP AF Semrud-Clikeman, Margaret Walkowiak, Jenifer Wilkinson, Alison Minne, Elizabeth Portman TI Direct and Indirect Measures of Social Perception, Behavior, and Emotional Functioning in Children with Asperger's Disorder, Nonverbal Learning Disability, or ADHD SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Behavior; Social perception; Asperger's disorder; Nonverbal learning disabilities; ADHD ID PERVASIVE DEVELOPMENTAL DISORDER; DEFICIT HYPERACTIVITY DISORDER; SYMPTOM SUBTYPES; AUTISM; VALIDATION AB Understanding social interactions is crucial for development of social competence. The present study was one of the first to utilize direct and indirect measures of social perception to explore possible differences among children with nonverbal learning disability (NLD), Asperger's Syndrome (AS), Attention Deficit Hyperactivity Disorder-Combined (ADHD-C), Attention Deficit Hyperactivity Disorder-Predominately Inattentive (ADHD-PI), and controls (N = 342). Multiple informants provided ratings of the child's behavioral and social functioning. Results indicated that the NLD and AS groups experienced the most difficulty understanding emotional and nonverbal cues on the direct measure. In addition, children with AS or NLD showed significant signs of sadness and social withdrawal compared to the other groups. Attentional skills, while related to social perception, did not predict social perception difficulties to the same degree as number of AS symptoms. C1 [Semrud-Clikeman, Margaret] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. 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PD MAY PY 2010 VL 38 IS 4 BP 509 EP 519 DI 10.1007/s10802-009-9380-7 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 577JS UT WOS:000276219800007 PM 20084452 ER PT J AU Wong, VCN Sun, JG AF Wong, Virginia Chun-Nei Sun, Jie-Guang TI Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autism Spectrum Disorder SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID MEDICINE TONGUE ACUPUNCTURE; ALTERNATIVE MEDICINE; CEREBRAL-PALSY; DROOLING PROBLEMS; DOUBLE-BLIND; CHILDREN; CHINESE; COMPLEMENTARY; PLACEBO; PART AB Objective: We aim to study the efficacy of acupuncture versus sham acupuncture in children with autism spectrum disorder. Methods: A single-blind randomized control trial was conducted in 50 children. These children were randomly assigned to the treatment group with tongue acupuncture (40 sessions over 8 weeks) or the control group (sham tongue acupuncture to nonacupoints in the tongue). Results: There was improvement in both the treatment and control groups in all assessed measures but more so in the treatment than in the control group: (1) eye-hand coordination, performance, and practical reasoning of Griffiths Mental Developmental Scale; (2) sensory-motor, social, affectual, language, and total score of Ritvo-Freeman Real Life Scale; (3) Comprehension Language age in the Reynell Language Developmental Scale; and (4) Total Score and Mental Age in Symbolic Play Test. The only statistically significant improvement in the treatment as compared to the control group was seen in self-care and cognition domains of the Functional Independence Measure for children. Conclusions: We had demonstrated that a short course of acupuncture had efficacy in improving various developmental and behavioral aspects of children with autism. The long-term efficacy in functional gain needs to be further explored. 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C. N., 2002, BRAIN DEV, V24, P319 WONG VCN, 2000, 5 WORLD C AC WFAS SE WONG VCN, 2010, J ALTERN CO IN PRESS Wong VCN, 2009, J AUTISM DEV DISORD, V39, P454, DOI 10.1007/s10803-008-0644-9 Wu Y, 2008, J CHILD NEUROL, V23, P1267, DOI 10.1177/0883073808318049 Wu Y, 2008, J ALTERN COMPLEM MED, V14, P1005, DOI 10.1089/acm.2007.0756 YEUNG D, 2002, BRAIN DEV, V24, P320 YEUNG D, 2002, P ANN SCI M NUCL MED YUAN Q, 2004, WORLD J ACUPUNCT, V14, P3 NR 55 TC 10 Z9 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD MAY PY 2010 VL 16 IS 5 BP 545 EP 553 DI 10.1089/acm.2007.0768 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 598AL UT WOS:000277803900007 PM 20804366 ER PT J AU Bertoglio, K James, SJ Deprey, L Brule, N Hendren, RL AF Bertoglio, Kiah James, S. Jill Deprey, Lesley Brule, Norman Hendren, Robert L. TI Pilot Study of the Effect of Methyl B12 Treatment on Behavioral and Biomarker Measures in Children with Autism SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID HOMOCYSTEINE METABOLISM; OXIDATIVE STRESS; RATING-SCALE; DISORDERS; VITAMIN-B12; POPULATION; INTERVIEW; COBALAMIN; VERSION; AGE AB Objectives: The study objectives were to determine whether methyl B12 treatment improves behavioral measures in children with autism and whether improvement is associated with increased plasma concentrations of glutathione (GSH) and an increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), both of which have been previously identified to be low in children with autism. Design: This was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methyl B12. Following this 12-week study, subjects were given the option of entering a 6-month open-label trial of methyl B12. Settings/location: All procedures took place at the UC Davis M.I.N.D. Institute. Subjects: Subjects were 3 to 8 years old with autism. Interventions: All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks. Outcome measures: Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12. Results: Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. Nine (9) subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG. Conclusions: Comparison of the overall means between groups suggests that methyl B12 is ineffective in treating behavioral symptoms of autism. However, detailed data analysis suggests that methyl B12 may alleviate symptoms of autism in a subgroup of children, possibly by reducing oxidative stress. An increase in glutathione redox status (GSH/GSSG) may provide a biomarker for treatment response to methyl B12. Additional research is needed to delineate a subgroup of potential responders and ascertain a biomarker for response to methyl B12. C1 [Hendren, Robert L.] UCSF Dept Psychiat, San Francisco, CA 94143 USA. [Bertoglio, Kiah] Univ Calif, Davis Med Ctr, Dept Psychiat & Behav Sci, Sacramento, CA USA. [Bertoglio, Kiah; Deprey, Lesley; Brule, Norman] Univ Calif, Davis Med Ctr, MIND Inst, Sacramento, CA USA. [James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Arkansas Childrens Hosp Res Inst, Autism Metab Genom Lab, Little Rock, AR 72205 USA. RP Hendren, RL (reprint author), UCSF Dept Psychiat, 401 Parnassus Ave,Box ADM, San Francisco, CA 94143 USA. EM Robert.Hendren@ucsf.edu FU The Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute of the University of California, Davis Medical Center FX The authors would like to thank and acknowledge The Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute of the University of California, Davis Medical Center, for providing funding for this study and to Deb Matsumoto for her assistance in preparing the manuscript. CR Achenbach T. M., 1983, MANUAL CHILD BEHAV C AMAN MG, 1985, AM J MENT DEF, V89, P485 Beaudet Arthur L., 2002, Genetics in Medicine, V4, P399, DOI 10.1097/00125817-200209000-00013 Bertrand J, 2001, PEDIATRICS, V108, P1155, DOI 10.1542/peds.108.5.1155 DALE PS, 1998, INT C INF STUD ATL G DeStefano F, 2004, PEDIATRICS, V113, P259, DOI 10.1542/peds.113.2.259 Dunn L. 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PD MAY PY 2010 VL 16 IS 5 BP 555 EP 560 DI 10.1089/acm.2009.0177 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 598AL UT WOS:000277803900008 PM 20804367 ER PT J AU Solish, A Perry, A Minnes, P AF Solish, Abbie Perry, Adrienne Minnes, Patricia TI Participation of Children with and without Disabilities in Social, Recreational and Leisure Activities SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE activity participation; children with autism spectrum disorder; children with intellectual disability; friendship; social inclusion; typically developing children ID MENTAL-RETARDATION; DEVELOPMENTAL-DISABILITIES; FRIENDSHIP FORMATION; PEER RELATIONSHIPS; YOUNG-CHILDREN; PATTERNS; ADULTS; SCHOOL; INVOLVEMENT; STUDENTS AB Background One method of promoting children's friendship development is through activity participation with peers. However, children with disabilities seem to engage in fewer of these activities, and when they do participate often do so primarily with adults. Materials and Methods This study compared activity participation and friendship in typically developing (TD) children (n = 90), children with an autism spectrum disorder (ASD; n = 65), and children with an intellectual disability (n = 30) between the ages of 5 and 17 years. Parents completed a questionnaire about their child's participation in social, recreational and leisure activities. Results The TD children participated in significantly more social and recreational activities and had more friends than the children with disabilities. Notable differences emerged among groups in the percentage of activities the children participated in with peers, parents and/or other adults. Some significant differences were noted between the ASD and intellectual disability groups. Conclusions Research concerning activity participation should continue to take into account not only whether children are engaging in activities, but explore more precisely 'with whom' these activities are occurring. C1 [Solish, Abbie; Perry, Adrienne] York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. [Minnes, Patricia] Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. RP Perry, A (reprint author), York Univ, Dept Psychol, Behav Sci Bldg,4700 Keele St, Toronto, ON M3J 1P3, Canada. EM perry@yorku.ca CR BROWDER DM, 1994, MENT RETARD, V32, P91 Buttimer John, 2005, J Intellect Disabil, V9, P25, DOI 10.1177/1744629505049728 Buysse V, 2002, EXCEPT CHILDREN, V68, P503 Cowart B., 2004, N AM J PSYCHOL, V6, P27 Freeman S. F. 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C., 1990, CHILDREN DOWN SYNDRO, P369, DOI 10.1017/CBO9780511581786.012 SLOPER P, 1990, CHILD CARE HLTH DEV, V16, P235, DOI 10.1111/j.1365-2214.1990.tb00658.x Solish A, 2003, J DEV DISABILITIES, V10, P115 Weiss J, 2003, RES DEV DISABIL, V24, P281, DOI 10.1016/S0891-4222(03)00043-X NR 23 TC 45 Z9 45 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2322 J9 J APPL RES INTELLECT JI J. Appl. Res. Intellect. Disabil. PD MAY PY 2010 VL 23 IS 3 BP 226 EP 236 DI 10.1111/j.1468-3148.2009.00525.x PG 11 WC Psychology, Educational; Rehabilitation SC Psychology; Rehabilitation GA 584YX UT WOS:000276791900003 ER PT J AU Ling, CYM Mak, WWS Cheng, JNS AF Ling, Candy Y. M. Mak, Winnie W. S. Cheng, Janice N. S. TI Attribution Model of Stigma towards Children with Autism in Hong Kong SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE attribution; autism; special education; stigma ID COGNITIVE-EMOTIONAL ANALYSIS; CHALLENGING BEHAVIOR; MENTAL-ILLNESS; INTELLECTUAL DISABILITIES; CARE STAFF; LEARNING-DISABILITIES; HELPING-BEHAVIOR; PEOPLE; RESPONSES; IMPACT AB Background Accounting for the effects of knowledge of and experience with autism, the relationships of cognitive attribution (perceived controllability), emotions (anger and sympathy), as well as helping and punitive behavioural intentions towards children with autism were examined. Based on the attribution model, mediating effects of anger and sympathy on cognitive attributions and behavioural intentions were tested. Materials and Methods 123 frontline staff in educational settings completed a modified version of the Attribution Questionnaire after reading a hypothetical vignette and completing a quiz on autism. Results Knowledge and experience were only significantly related to punitive behavioural intention towards children with autism. Anger and sympathy mediated the effect between perceived controllability on both helping and punitive behavioural intentions. Conclusions The intentional responses towards children with autism were strongly related to their emotional reactions. Thus, in addition to educating frontline staff about autism, training them on emotion regulation is equally important in autism stigma reduction. C1 [Ling, Candy Y. M.; Mak, Winnie W. S.; Cheng, Janice N. S.] Chinese Univ Hong Kong, Dept Psychol, Shatin, Hong Kong, Peoples R China. RP Mak, WWS (reprint author), Chinese Univ Hong Kong, Dept Psychol, Shatin, Hong Kong, Peoples R China. EM wwsmak@psy.cuhk.edu.hk CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Bailey BA, 2006, J INTELL DISABIL RES, V50, P199, DOI 10.1111/j.1365-2788.2005.00769.x BARON RM, 1986, J PERS SOC PSYCHOL, V51, P1173, DOI 10.1037/0022-3514.51.6.1173 Brown L, 2003, AIDS EDUC PREV, V15, P49, DOI 10.1521/aeap.15.1.49.23844 *CENS STAT DEP HON, 2001, 28 CENS STAT DEP HON Cooney G, 2006, J INTELL DISABIL RES, V50, P432, DOI 10.1111/j.1365-2788.2006.00789.x Corrigan P, 2003, J HEALTH SOC BEHAV, V44, P162, DOI 10.2307/1519806 Corrigan PW, 2001, PSYCHIATR SERV, V52, P953, DOI 10.1176/appi.ps.52.7.953 Corrigan PW, 1999, AM PSYCHOL, V54, P765, DOI 10.1037/0003-066X.54.9.765 Corrigan PW, 2000, CLIN PSYCHOL-SCI PR, V7, P48, DOI 10.1093/clipsy/7.1.48 Dagnan D, 2005, J INTELL DISABIL RES, V49, P95, DOI 10.1111/j.1365-2788.2005.00665.x Dagnan D, 1998, BRIT J CLIN PSYCHOL, V37, P59 Davis D, 1999, JAMA-J AM MED ASSOC, V282, P867, DOI 10.1001/jama.282.9.867 Dowey A, 2007, J APPL RES INTELLECT, V20, P52, DOI 10.1111/j.1468-3148.2006.00339.x *ED BUR, 2007, SPEC ED EISENBERG N, 1992, P57 Goffman E, 1963, STIGMA NOTES MANAGEM GOODMAN LA, 1960, J AM STAT ASSOC, V55, P708, DOI 10.2307/2281592 Graham S, 1997, PERS SOC PSYCHOL B, V23, P331, DOI 10.1177/0146167297234001 GRAY DE, 1993, SOCIOL HEALTH ILL, V15, P102, DOI 10.1111/1467-9566.ep11343802 Grey I. 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PD MAY PY 2010 VL 23 IS 3 BP 237 EP 249 DI 10.1111/j.1468-3148.2008.00456.x PG 13 WC Psychology, Educational; Rehabilitation SC Psychology; Rehabilitation GA 584YX UT WOS:000276791900004 ER PT J AU Janeslatt, G Granlund, M Kottorp, A Almqvist, L AF Janeslatt, Gunnel Granlund, Mats Kottorp, Anders Almqvist, Lena TI Patterns of Time Processing Ability in Children with and without Developmental Disabilities SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE child development; cluster analysis; time management; time orientation; time perception ID DEFICIT HYPERACTIVITY DISORDER; PERSON-ORIENTED APPROACH; AUTISTIC DISORDER; SPINA-BIFIDA; SLEEP; PERCEPTION; ADULTS AB Background Children with developmental disabilities, e.g. intellectual disability or autism, are reported to have problems in time perception, time orientation or time management, i.e. in time-processing ability (TPA). The aim was to investigate whether the problems described are diagnosis specific or reflect differences in age or in level of TPA. Methods Using a cross-sectional design, this study investigated if there were different patterns of TPA in 5- to 10-year-old children with (n = 77) and without disabilities (n = 89). The results indicated that the patterns of TPA mainly follow the chronological age of children without disabilities, all clusters differing as regards levels of TPA. Daily time management (as estimated by the parents) and children's self-rated autonomy differed between clusters and was related to TPA. Conclusions The level of TPA seems to be a more valid overall base than the type of diagnosis for the planning of interventions in daily time management. C1 [Janeslatt, Gunnel] Ctr Clin Res Dalarna, SE-79182 Falun, Sweden. [Janeslatt, Gunnel; Kottorp, Anders] Karolinska Inst, Div Occupat Therapy, Dept NVS, Huddinge, Sweden. [Granlund, Mats] Jonkoping Univ, Sch Hlth Sci, Jonkoping, Sweden. [Janeslatt, Gunnel; Granlund, Mats; Almqvist, Lena] Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden. RP Janeslatt, G (reprint author), Ctr Clin Res Dalarna, Nissers Vag 3, SE-79182 Falun, Sweden. EM gunnel.janeslatt@ltdalarna.se CR Almqvist L, 2005, SCAND J PSYCHOL, V46, P305, DOI 10.1111/j.1467-9450.2005.00460.x Arvidsson Gunnel, 2006, Occup Ther Int, V13, P160, DOI 10.1002/oti.215 BAMBARA LM, 1992, J ASSOC PERS SEVERE, V17, P67 Barkley RA, 2001, NEUROPSYCHOLOGY, V15, P351, DOI 10.1037//0894-4105.15.3.351 Barkley RA, 1997, J DEV BEHAV PEDIATR, V18, P271 Bebko JM, 2006, J CHILD PSYCHOL PSYC, V47, P88, DOI 10.1111/j.1469-7610.2005.01443.x Bergman L R, 2002, STUDYING INDIVIDUAL Bergman LR, 1997, DEV PSYCHOPATHOL, V9, P291 Block R. 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Appl. Res. Intellect. Disabil. PD MAY PY 2010 VL 23 IS 3 BP 250 EP 262 DI 10.1111/j.1468-3148.2009.00528.x PG 13 WC Psychology, Educational; Rehabilitation SC Psychology; Rehabilitation GA 584YX UT WOS:000276791900005 ER PT J AU Manning, MM Wainwright, LD AF Manning, Margaret M. Wainwright, Laurel D. TI The Role of High Level Play as a Predictor Social Functioning in Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Pretend play; Social functioning ID MENTAL-RETARDATION; SYMBOLIC PLAY; PRETEND PLAY; CHILDREN; GENERATIVITY; DEFICITS; LANGUAGE AB Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group early in the play session; however, these differences were no longer apparent by the end of the play session. In addition, a significant association existed between play and social functioning regardless of diagnosis. This suggests that play may act as a current indicator of social ability while providing an arena for social skills practice. C1 [Manning, Margaret M.] Univ Massachusetts, Sch Med, EK Shriver Ctr, Waltham, MA 02452 USA. [Manning, Margaret M.; Wainwright, Laurel D.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP Manning, MM (reprint author), Univ Massachusetts, Sch Med, EK Shriver Ctr, 200 Trapelo Rd, Waltham, MA 02452 USA. 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Evidence from Eye-tracking SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Eye-tracking; Autism; Social scenes; Gaze following; Time-course analysis ID FACE-LIKE STIMULI; SOCIAL ATTENTION; SPECTRUM DISORDERS; ASPERGER-SYNDROME; JOINT ATTENTION; AUTISM; CHILDREN; PERCEPTION; FIXATION; INFANTS AB Visual fixation patterns whilst viewing complex photographic scenes containing one person were studied in 24 high-functioning adolescents with Autism Spectrum Disorders (ASD) and 24 matched typically developing adolescents. Over two different scene presentation durations both groups spent a large, strikingly similar proportion of their viewing time fixating the person's face. However, time-course analyses revealed differences between groups in priorities of attention to the region of the face containing the eyes. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 534 EP 547 DI 10.1007/s10803-009-0893-2 PG 14 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300002 PM 19904597 ER PT J AU Mann, JR McDermott, S Bao, H Hardin, J Gregg, A AF Mann, Joshua R. McDermott, Suzanne Bao, Haikun Hardin, James Gregg, Anthony TI Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Eclampsia; Pre-eclampsia; Birth weight; Epidemiology ID PERVASIVE DEVELOPMENTAL DISORDERS; PERINATAL RISK-FACTORS; PRETERM BIRTH; EPIDEMIOLOGY; POPULATION; DIAGNOSIS; BRAIN; AGE AB Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia/eclampsia was significantly associated with greater odds of ASD (OR = 1.85, p < .0001 without controlling for birth weight; OR = 1.69, p = .0005, when controlling for birth weight). We conclude that reduced birth weight partially mediates the association between pre-eclampsia/eclampsia and ASD. Additional research is needed to investigate the potential mechanism(s) by which pre-eclampsia/eclampsia may influence ASD risk. C1 [Mann, Joshua R.; McDermott, Suzanne] Univ S Carolina, Sch Med, Dept Family & Prevent Med, Columbia, SC 29203 USA. [Bao, Haikun; Hardin, James] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29203 USA. [Gregg, Anthony] Univ S Carolina, Sch Med, Dept Obstet & Gynecol, Columbia, SC 29203 USA. RP Mann, JR (reprint author), Univ S Carolina, Sch Med, Dept Family & Prevent Med, Columbia, SC 29203 USA. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 548 EP 554 DI 10.1007/s10803-009-0903-4 PG 7 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300003 PM 19936906 ER PT J AU Warren, SF Gilkerson, J Richards, JA Oller, DK Xu, DX Yapanel, U Gray, S AF Warren, Steven F. Gilkerson, Jill Richards, Jeffrey A. Oller, D. Kimbrough Xu, Dongxin Yapanel, Umit Gray, Sharmistha TI What Automated Vocal Analysis Reveals About the Vocal Production and Language Learning Environment of Young Children with Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Language development; Assessment; Conversational turn-taking; Language input; Automated vocal analysis ID BEHAVIORS; SPEECH AB The study compared the vocal production and language learning environments of 26 young children with autism spectrum disorder (ASD) to 78 typically developing children using measures derived from automated vocal analysis. A digital language processor and audio-processing algorithms measured the amount of adult words to children and the amount of vocalizations they produced during 12-h recording periods in their natural environments. The results indicated significant differences between typically developing children and children with ASD in the characteristics of conversations, the number of conversational turns, and in child vocalizations that correlated with parent measures of various child characteristics. Automated measurement of the language learning environment of young children with ASD reveals important differences from the environments experienced by typically developing children. C1 [Warren, Steven F.] Univ Kansas, Inst Life Span Studies, Lawrence, KS 66045 USA. [Gilkerson, Jill; Richards, Jeffrey A.; Xu, Dongxin; Yapanel, Umit; Gray, Sharmistha] LENA Fdn, Boulder, CO USA. [Oller, D. Kimbrough] Univ Memphis, Memphis, TN 38152 USA. 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SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Obsessive-compulsive disorder; Attention deficit/hyperactivity disorder; Autism ID OBSESSIVE-COMPULSIVE DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDER; HIGH-FUNCTIONING AUTISM; SPECTRUM QUOTIENT AQ; PSYCHIATRIC-DISORDERS; COGNITIVE CONFIDENCE; SUSTAINED ATTENTION; YOUNG-PEOPLE AB In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD - ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD. C1 [Cath, Danielle C.] Altrecht Anxiety Outpatient Program, NL-3551 DC Utrecht, Netherlands. [Anholt, Gideon E.; van Oppen, Patricia; Eikelenboom, Merijn; Smit, Johannes H.; van Balkom, Anton J. L. M.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Anholt, Gideon E.; van Oppen, Patricia; Eikelenboom, Merijn; Smit, Johannes H.; van Balkom, Anton J. L. M.] Vrije Univ Amsterdam Med Ctr, Inst Extramural Med, Amsterdam, Netherlands. [Cath, Danielle C.; van Oppen, Patricia; van Balkom, Anton J. L. M.] GGZ inGeest, Outpatient Clin Anxiety Disorders, Amsterdam, Netherlands. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 580 EP 589 DI 10.1007/s10803-009-0922-1 PG 10 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300006 PM 20039111 ER PT J AU Ingersoll, B AF Ingersoll, Brooke TI Broader Autism Phenotype and Nonverbal Sensitivity: Evidence for an Association in the General Population SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Broader autism phenotype; Nonverbal sensitivity ID SPECTRUM QUOTIENT AQ; COGNITIVE PHENOTYPE; DIAGNOSTIC VALIDITY; PERSONALITY-TRAITS; ASPERGER-SYNDROME; CENTRAL COHERENCE; FAMILY-HISTORY; PARENTS; RECOGNITION; CHILDREN AB This study examined the relationship between characteristics of the Broader Autism Phenotype (BAP) and nonverbal sensitivity, the ability to interpret nonverbal aspects of communication, in a non-clinical sample of college students. One hundred and two participants completed a self-report measure of the BAP, the Autism Spectrum Quotient (AQ), and two tests of nonverbal sensitivity, the Test of Nonverbal Cue Knowledge (TONCK), and the Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA2). AQ score was correlated with TONCK performance and number of errors on the adult faces subtest of the DANVA2, but not adult paralanguage or postures. These findings suggest that characteristics of ASD in the general population are associated with differences in both explicit and implicit knowledge of nonverbal cues. C1 Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. RP Ingersoll, B (reprint author), Michigan State Univ, Dept Psychol, 105B Psychol Bldg, E Lansing, MI 48824 USA. 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Kim, Soh-Yule Freedland, Robert Heaney, Glenn Pettinger, Jill Brown, W. Ted TI A Large Scale Study of the Psychometric Characteristics of the IBR Modified Overt Aggression Scale: Findings and Evidence for Increased Self-Destructive Behaviors in Adult Females with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Aggression; Self-injury; Prevalence; Psychometrics; Rating scales; Autism; Females ID INTELLECTUAL DISABILITY; CHALLENGING BEHAVIORS; PSYCHIATRIC-DISORDERS; PHYSICAL AGGRESSION; PREVALENCE; CHILDREN; VIOLENCE; RISK AB The psychometric characteristics of the IBR Modified Overt Aggression Scale were studied in over 2,000 people with Intellectual Disability (ID). Reliability ranged from good to excellent. Aggression toward others and objects was highest in the youngest adults, in those in the moderate to severe range of ID, and in those with an autism spectrum diagnosis. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 599 EP 609 DI 10.1007/s10803-009-0908-z PG 11 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300008 PM 19941156 ER PT J AU Griffith, GM Hastings, RP Nash, S Hill, C AF Griffith, Gemma M. Hastings, Richard P. Nash, Susie Hill, Christopher TI Using Matched Groups to Explore Child Behavior Problems and Maternal Well-Being in Children with Down Syndrome and Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Down syndrome; Child behavior; Maternal outcomes; Matched groups ID INTELLECTUAL DISABILITY; YOUNG-CHILDREN; DEVELOPMENTAL-DISABILITIES; MENTAL-RETARDATION; SOCIOECONOMIC POSITION; SYNDROME SPECIFICITY; PRESCHOOL-CHILDREN; FAMILY STRESS; MOTHERS; PARENTS AB Mothers of children with Down syndrome, autism, and mixed etiology intellectual disabilities, matched on child age, gender, and communication skills (n = 19 in each group) completed measures of their child's adaptive and problem behaviors, their own parenting stress, and positive perceptions of their child. Children with autism were rated as having more problem behaviors and lower levels of social competence than children with Down syndrome and mixed etiology intellectual disabilities. Mothers of children with autism scored lower on positive perceptions of their child, and higher on stress than the other two groups. After selecting closely matched groups, we found several group differences in child behavior but little evidence of group differences in maternal outcomes. C1 [Griffith, Gemma M.; Hastings, Richard P.; Nash, Susie; Hill, Christopher] Bangor Univ, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales. RP Griffith, GM (reprint author), Bangor Univ, Sch Psychol, Brigantia Bldg,Penrhalt Rd, Bangor LL57 2AS, Gwynedd, Wales. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 610 EP 619 DI 10.1007/s10803-009-0906-1 PG 10 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300009 PM 19936904 ER PT J AU Sawyer, MG Bittman, M La Greca, AM Crettenden, AD Harchak, TF Martin, J AF Sawyer, Michael G. Bittman, Michael La Greca, Annette M. Crettenden, Angela D. Harchak, Taylor F. Martin, Jon TI Time Demands of Caring for Children with Autism: What are the Implications for Maternal Mental Health? SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Mothers; Caregiving time; Mental health problems; Time use ID SOCIAL SUPPORT; DIFFICULTIES-QUESTIONNAIRE; SPECTRUM DISORDERS; PRESCHOOL-CHILDREN; PSYCHOMETRIC PROPERTIES; BEHAVIOR PROBLEMS; PARENTING STRESS; MOTHERS; IMPACT; STRENGTHS AB This study examined the relationship between maternal mental health problems and both caregiving time and experience of time pressure for 216 mothers of children with autism. Data describing caregiving time was obtained using 24-h time-diaries. Standard questionnaires were used to assess time pressure, social support, children's emotional and behavioural problems, and maternal mental health problems. After adjusting for the effect of children's age, maternal social support, and children's behaviour problems, time pressure but not hours of caregiving, had a significant positive relationship with maternal mental health problems. Findings suggest that the quality of home-based care for children with autism may be adversely affected if time pressure experienced by caregivers compromises their mental health and well being. C1 [Sawyer, Michael G.] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia. [Sawyer, Michael G.; Harchak, Taylor F.] Youth & Womens Hlth Serv, Res & Evaluat Unit, Adelaide, SA 5006, Australia. [Bittman, Michael] Univ New England, Dept Sociol, Armidale, NSW, Australia. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 620 EP 628 DI 10.1007/s10803-009-0912-3 PG 9 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300010 PM 19949845 ER PT J AU Yoder, PJ Lieberman, RG AF Yoder, Paul J. Lieberman, Rebecca G. TI Brief Report: Randomized Test of the Efficacy of Picture Exchange Communication System on Highly Generalized Picture Exchanges in Children with ASD SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Communication; PECS; Intervention; Generalization; Generality ID AUTISM SPECTRUM DISORDERS; SPEECH DEVELOPMENT; PRESCHOOLERS; PECS AB A randomized control trial comparing two social-communication interventions in young children with autism examined far-transfer of the use of picture exchange to communicate. Thirty-six children were randomly assigned to one of two treatment conditions, one of which was the Picture Exchange Communication System (PECS). 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TI Brief Report: Under-Representation of African Americans in Autism Genetic Research: A Rationale for Inclusion of Subjects Representing Diverse Family Structures SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Ethnicity; African American; Minority representation ID MINORITY RECRUITMENT; SPECTRUM DISORDER; MEDICAL-RESEARCH; RISK; STRATEGIES; CHILDREN; DISEASE; PARTICIPATION; SCHIZOPHRENIA; ENROLLMENT AB African American children with autism are seriously under-represented in existing genetic registries and biomedical research studies of autism. We estimated the number of African American children with autism in the St. Louis region using CDC surveillance data and present the outcomes of a concerted effort to enroll approximately one-third of that population into either of two large national genetic autism registries. The results revealed that even after traditional barriers to research participation were addressed and all contacted families expressed a willingness to participate, 67% of the reachable families were disqualified from participation because of family structure alone. Comprehensive efforts-including expansion of eligibility to families of diverse structure-are warranted to facilitate the inclusion of African American children in biomedical research. C1 [Hilton, Claudia L.; Fitzgerald, Robert T.; Jackson, Kelley M.; Bosworth, Christopher C.; Constantino, John N.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Maxim, Rolanda A.] St Louis Univ, Knights Columbus Dev Ctr, St Louis, MO 63103 USA. [Shattuck, Paul T.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63110 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. 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Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 633 EP 639 DI 10.1007/s10803-009-0905-2 PG 7 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300012 PM 19936905 ER PT J AU Martin, JS Poirier, M Bowler, DM AF Martin, Jonathan S. Poirier, Marie Bowler, Dermot M. TI Brief Report: Impaired Temporal Reproduction Performance in Adults with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Asperger's syndrome; Time perception; Temporal reproduction ID AGE-RELATED-CHANGES; TIME PERCEPTION; DURATION JUDGMENTS; MEMORY PROCESSES; ATTENTION; CHILDREN; DEFICIT; CLOCK; YOUNG AB Although temporal processing has received little attention in the autism literature, there are a number of reasons to suspect that people with autism spectrum disorder (ASD) may have particular difficulties judging the passage of time. The present study tested a group of 20 high-functioning adults with ASD and 20 matched comparison participants on a temporal reproduction task. The ASD group made reproductions that were significantly further from the base durations than did the comparison group. They were also more variable in their responses. Furthermore the ASD group showed particular difficulties as the base durations increased, tending to underestimate to a much greater degree than the comparison group. These findings support earlier evidence that temporal processing is impaired in ASD. C1 [Martin, Jonathan S.] Univ Birmingham, Sch Psychol, Dept Clin Psychol, Birmingham B15 2TT, W Midlands, England. [Martin, Jonathan S.; Poirier, Marie; Bowler, Dermot M.] City Univ London, Dept Psychol, London EC1V 0HB, England. RP Martin, JS (reprint author), Univ Birmingham, Sch Psychol, Dept Clin Psychol, Birmingham B15 2TT, W Midlands, England. EM jsm731@bham.ac.uk CR American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Barkley RA, 2001, NEUROPSYCHOLOGY, V15, P351, DOI 10.1037//0894-4105.15.3.351 Baudouin A, 2006, BRAIN COGNITION, V62, P17, DOI 10.1016/j.bandc.2006.03.003 Bennetto L, 1996, CHILD DEV, V67, P1816, DOI 10.1111/j.1467-8624.1996.tb01830.x Block RA, 1997, PSYCHON B REV, V4, P184, DOI 10.3758/BF03209393 BOUCHER J, 2001, TIME MEMORY ISSUES P Bowler D, 2007, AUTISM SPECTRUM DISO Davalos DB, 2003, BRAIN COGNITION, V52, P295, DOI 10.1016/S0278-2626(03)00157-X Gepner B, 2009, NEUROSCI BIOBEHAV R, V33, P1227, DOI 10.1016/j.neubiorev.2009.06.006 Gowen E, 2005, CEREBELLUM, V4, P1 GRONDIN S, 2003, TIME MIND INFORM PRO Hemmer P, 2009, PSYCHON B REV, V16, P80, DOI 10.3758/PBR.16.1.80 Ivry RB, 2008, TRENDS COGN SCI, V12, P273, DOI 10.1016/j.tics.2008.04.002 Kanabus M, 2004, ACTA NEUROBIOL EXP, V64, P395 Lewis PA, 2006, TRENDS COGN SCI, V10, P401, DOI 10.1016/j.tics.2006.07.006 LORD C, 1989, J AUTISM DEV DISORD, V19, P185, DOI 10.1007/BF02211841 *MACR, 2007, AUTH VERS 7 Mangels JA, 1998, COGNITIVE BRAIN RES, V7, P15, DOI 10.1016/S0926-6410(98)00005-6 McGraw KO, 2000, PSYCHOL SCI, V11, P502, DOI 10.1111/1467-9280.00296 Meck WH, 2005, BRAIN COGNITION, V58, P1, DOI 10.1016/j.bandc.2004.09.004 Mostofsky SH, 2000, J INT NEUROPSYCH SOC, V6, P752, DOI 10.1017/S1355617700677020 Perbal S, 2005, BRAIN COGNITION, V58, P35, DOI 10.1016/j.bandc.2005.02.003 Perbal S, 2002, AGING NEUROPSYCHOL C, V9, P201, DOI 10.1076/anec.9.3.201.9609 Picton TW, 2006, NEUROPSYCHOLOGIA, V44, P1195, DOI 10.1016/j.neuropsychologia.2005.10.002 POIRIER M, 2008, MEMORY AUTISM THEORY *PSYCH CORP, 2002, WECHSL AD INT SCAL 3 RADONOVICH KJ, 2004, CHILD NEUROPSYCHOL, V10, P162, DOI 10.1080/09297040490911023 Russell J., 1997, AUTISM EXECUTIVE DIS, P256 Szelag E, 2004, BRIT J PSYCHOL, V95, P269, DOI 10.1348/0007126041528167 Vanneste S, 1999, ANN PSYCHOL, V99, P385 Wallace GL, 2008, RES AUTISM SPECT DIS, V2, P447, DOI 10.1016/j.rasd.2007.09.005 Wearden JH, 2008, Q J EXP PSYCHOL, V61, P569, DOI 10.1080/17470210701282576 Wing L., 1996, AUTISTIC SPECTRUM NR 33 TC 13 Z9 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 640 EP 646 DI 10.1007/s10803-009-0904-3 PG 7 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300013 PM 19924521 ER PT J AU Blankenship, K Erickson, C AF Blankenship, Kelly Erickson, Craig TI Language and Autism: Applied Behavior Analysis, Evidence, and Practice SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Book Review C1 [Blankenship, Kelly; Erickson, Craig] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Blankenship, Kelly; Erickson, Craig] James Whitcomb Riley Hosp Children, Christian Sakrine Autism Treatment Ctr, Indianapolis, IN 46202 USA. RP Blankenship, K (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. EM kellyrachal@yahoo.com CR FITZER A, 2009, LANGUAGE AUTISM NR 1 TC 0 Z9 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2010 VL 40 IS 5 BP 647 EP 648 DI 10.1007/s10803-009-0833-1 PG 2 WC Psychology, Developmental SC Psychology GA 584NM UT WOS:000276759300014 ER PT J AU Frye, RE Butler, I Strickland, D Castillo, E Papanicolaou, A AF Frye, Richard E. Butler, Ian Strickland, David Castillo, Edwardo Papanicolaou, Andrew TI Electroencephalogram Discharges in Atypical Cognitive Development SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE speech delay; attention deficit; pervasive developmental disorder; electroencephalography; magnetoencephalography ID EPILEPTIFORM EEG ABNORMALITIES; ELECTRICAL STATUS EPILEPTICUS; LANGUAGE REGRESSION; PARTIAL EPILEPSY; CHILDREN; AUTISM; BENIGN; DISORDERS; CHILDHOOD; SPECTRUM AB To investigate the significance of electroencephalogram (EEG) discharges and their treatment, we retrospectively reviewed the charts of 22 children with atypical cognitive development that did not respond to standard educational therapy and demonstrated discharges on EEG. Most children demonstrated no obvious symptoms of seizures, and developmental regression and/or fluctuations were uncommon. The majority of children demonstrated a language and attention disorder and autism symptomatology and had multifocal discharges on EEGs. Of the 20 patients treated with antiepileptic medications, 70% demonstrated definite improvement within 1 clinic visit. This study suggests that children with EEG discharges and developmental cognitive disorders demonstrate a unique pattern of symptomatology and discharges on EEG. This study suggests that children with developmental cognitive disorders that do not respond to standard therapy may benefit from screening with an EEG and a trial of antiepileptic mediation if discharges are detected. C1 [Frye, Richard E.; Butler, Ian] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Div Child & Adolescent Neurol, Houston, TX 77030 USA. [Frye, Richard E.; Strickland, David; Castillo, Edwardo; Papanicolaou, Andrew] Univ Texas Hlth Sci Ctr Houston, Childrens Learning Inst, Dept Pediat, Houston, TX 77030 USA. RP Frye, RE (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Div Child & Adolescent Neurol, 7000 Fannin,UCT 2478, Houston, TX 77030 USA. EM Richard.E.Frye@uth.tmc.edu FU [NS046565] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: NS046565 to Dr Richard E. Frye, MD, PhD. 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Child Neurol. PD MAY PY 2010 VL 25 IS 5 BP 556 EP 566 DI 10.1177/0883073809344743 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 586YF UT WOS:000276950800005 PM 20299700 ER PT J AU Meguid, N Fahim, C Yoon, U Nashaat, NH Ibrahim, AS Mancini-Marie, A Brandner, C Evans, AC AF Meguid, Nagwa Fahim, Cherine Yoon, Uicheul Nashaat, Neveen H. Ibrahim, Ahmed S. Mancini-Marie, Adham Brandner, Catherine Evans, Alan C. TI Brain Morphology in Autism and Fragile X Syndrome Correlates With Social IQ: First Report From the Canadian-Swiss-Egyptian Neurodevelopmental Study SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE autism; fragile X syndrome; magnetic resonance imaging; cerebral cortical thickness; medial prefrontal; anterior cingulate ID CEREBRAL-CORTEX; PSYCHIATRIC-DISORDERS; SPECTRUM DISORDER; CHILDHOOD AUTISM; BEHAVIOR PROFILE; YOUNG-CHILDREN; MRI; BOYS; MATURATION; PROTEIN AB Fragile X syndrome shares most of the behavioral phenotypic similarities with autism. How are these similarities reflected in brain morphology? A total of 10 children with autism and 7 with fragile X underwent morphological (T1) 1.5-T magnetic resonance imaging (MRI). The authors found no significant difference in total brain volumes, regional volumes, gyrification index, sulcul depth, and cerebral cortical thickness. However, children with autism showed significant decrease in the medial prefrontal bilaterally and the left anterior cingulate cortices. Regression analysis revealed positive correlation between the medial prefrontal cortical thickness and the social IQ. The authors suggest that the difference between the 2 groups in the medial prefrontal and anterior cingulate cortices thickness may entail an altered social cognitive style. Functional MRI studies directly differentiating between social indifference (autism) and social avoidance (fragile X) are needed to further characterize the spectrum of social abnormalities between these 2 groups. C1 [Evans, Alan C.] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. [Meguid, Nagwa; Nashaat, Neveen H.] Natl Res Ctr, Dept Children Special Needs, Div Med Genet, Cairo, Egypt. [Ibrahim, Ahmed S.] Ain Shams Univ, Dept Radiol, Cairo, Egypt. [Fahim, Cherine; Yoon, Uicheul; Evans, Alan C.] McGill Univ, Dept Neurol & Neurosurg, Fac Med, Montreal, PQ H3A 2B4, Canada. [Fahim, Cherine; Brandner, Catherine] Univ Lausanne, Fac Social Sci & Polit, Lab Expt Study Behav LERB, Lausanne, Switzerland. [Mancini-Marie, Adham] Univ Montreal, Fac Med, Ctr Rech Fernand Seguin, Montreal, PQ H3C 3J7, Canada. [Mancini-Marie, Adham] Univ Geneva, Hop Univ Geneve HUG, Dept Psychiat, Geneva, Switzerland. RP Evans, AC (reprint author), McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, McConnell Brain Imaging Ctr, 3801 Univ St,Webster 2B, Montreal, PQ H3A 2B4, Canada. EM alan.evans@mcgill.ca FU Jeanne Timmins Costello Fellowship at the Montreal Neurological Institute; University of Lausanne, Switzerland; Neuroinsight Foundation for Brain Research Initiative in Egypt FX We would like to thank the individuals and families who participated in this study. NM is an expert in the genetics of childhood neurodevelopmental disorders and the head of the department of children with special needs at the National Research Centre in Egypt. CF is a postdoctoral research associate of the Canadian Institutes of Health Research, the Jeanne Timmins Costello Fellowship at the Montreal Neurological Institute and the Michel Meany training award. We are grateful to AE who offered the Egyptian Neuroimaging Neurodevelopmental Genetics Initiative Network to use the Montreal Neurological Institute facilities to analyze the current study data. This study is part of the Canadian-Swiss-Egyptian Neurodevelopmental Study supported by the University of Lausanne, Switzerland, and Neuroinsight Foundation for Brain Research Initiative in Egypt. We deeply acknowledge the helpful comments and suggestions of the Journal of Child Neurology anonymous reviewers. 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Child Neurol. PD MAY PY 2010 VL 25 IS 5 BP 599 EP 608 DI 10.1177/0883073809341670 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 586YF UT WOS:000276950800010 PM 20110214 ER PT J AU Gupta, S Samra, D Agrawal, S AF Gupta, Sudhir Samra, Daljeet Agrawal, Sudhanshu TI Adaptive and Innate Immune Responses in Autism: Rationale for Therapeutic Use of Intravenous Immunoglobulin SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Cytokines; chemokines; autoantibodies; dendritic cells; CVID; lymphocyte subsets; IVIG; IgG; IgG subclasses ID SPECTRUM DISORDERS; FETAL-BRAIN; CHILDREN; ANTIBODIES; CELLS; CHILDHOOD; MOTHERS AB Autism is a complex polygenic neurodevelopmental disorder characterized by deficits in communication and social interactions as well as specific stereotypical behaviors. Both genetic and environmental factors appear to contribute to the pathogenesis of autism. Accumulating data including changes in immune responses, linkage to major histocompatibility complex antigens, and the presence of autoantibodies to neural tissues/antigens suggest that the immune system plays an important role in its pathogenesis. In this brief review, we discuss the data regarding changes in both innate and adaptive immunity in autism and the evidence in favor of the role of the immune system, especially of maternal autoantibodies in the pathogenesis of a subset of patients with autism. The rationale for possible therapeutic use of intravenous immunoglobulin is also discussed. C1 [Gupta, Sudhir; Samra, Daljeet; Agrawal, Sudhanshu] Univ Calif Irvine, Div Basic & Clin Immunol, Irvine, CA 92697 USA. RP Gupta, S (reprint author), Univ Calif Irvine, Div Basic & Clin Immunol, Med Sci 1,C-240, Irvine, CA 92697 USA. EM sgupta@uci.edu RI zhang, jing/F-3848-2012 CR Agrawal A, 2008, J CLIN IMMUNOL, V28, P14, DOI 10.1007/s10875-007-9127-6 Ashwood P, 2006, J LEUKOCYTE BIOL, V80, P1, DOI 10.1189/jlb.1205707 BORIS M, 2006, J NUTR ENV MED, V15, P1 Braunschweig D, 2008, NEUROTOXICOLOGY, V29, P226, DOI 10.1016/j.neuro.2007.10.010 Cohly HHP, 2005, INT REV NEUROBIOL, V71, P317, DOI 10.1016/S0074-7742(05)71013-8 Dalton P, 2003, ANN NEUROL, V53, P533, DOI 10.1002/ana.10557 DelGiudice-Asch G, 1999, J AUTISM DEV DISORD, V29, P157, DOI 10.1023/A:1023096728131 Enstrom AM, 2010, BRAIN BEHAV IMMUN, V24, P64, DOI 10.1016/j.bbi.2009.08.001 Enstrom AM, 2009, BRAIN BEHAV IMMUN, V23, P124, DOI 10.1016/j.bbi.2008.08.001 Gupta S, 1998, J NEUROIMMUNOL, V85, P106, DOI 10.1016/S0165-5728(98)00021-6 Gupta S, 2000, J AUTISM DEV DISORD, V30, P475, DOI 10.1023/A:1005568027292 Gupta S, 1996, J AUTISM DEV DISORD, V26, P439, DOI 10.1007/BF02172828 Gupta S, 1996, J CHILD NEUROL, V11, P501 Jyonouchi H, 2008, J NEUROINFLAMM, V5, DOI 10.1186/1742-2094-5-52 Lee LC, 2006, PEDIATR NEUROL, V35, P303, DOI 10.1016/j.pediatrneurol.2006.06.006 Li XH, 2009, J NEUROIMMUNOL, V207, P111, DOI 10.1016/j.jneuroim.2008.12.002 Martin LA, 2008, BRAIN BEHAV IMMUN, V22, P806, DOI 10.1016/j.bbi.2007.12.007 OLESKE J, 2004, RESEARCH WIN, P22 Onore C, 2009, J NEUROIMMUNOL, V216, P126, DOI 10.1016/j.jneuroim.2009.09.005 Orange JS, 2006, J ALLERGY CLIN IMMUN, V117, pS525, DOI 10.1016/j.jaci.2006.01.015 Perlmutter SJ, 1999, LANCET, V354, P1153, DOI 10.1016/S0140-6736(98)12297-3 Plioplys AV, 1998, J CHILD NEUROL, V13, P79 Singer HS, 2008, J NEUROIMMUNOL, V194, P165, DOI 10.1016/j.jneuroim.2007.11.004 Torres AR, 2001, FRONT BIOSCI, V6, pD936, DOI 10.2741/Torres Vargas DL, 2005, ANN NEUROL, V57, P67, DOI 10.1002/ana.20315 WARREN RP, 1990, J AM ACAD CHILD PSY, V29, P873, DOI 10.1097/00004583-199011000-00005 WEIZMAN A, 1982, AM J PSYCHIAT, V139, P1462 Zimmerman AW, 2005, PEDIATR NEUROL, V33, P195, DOI 10.1016/j.pediatrneurol.2005.03.014 Zykov V P, 2009, Neurosci Behav Physiol, V39, P635, DOI 10.1007/s11055-009-9184-9 NR 29 TC 12 Z9 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2010 VL 30 SU 1 BP S90 EP S96 DI 10.1007/s10875-010-9402-9 PG 7 WC Immunology SC Immunology GA 608YQ UT WOS:000278622300018 ER PT J AU Valdovinos, MG Bailey, L Taylor, SL AF Valdovinos, Maria G. Bailey, Linda Taylor, Steve L. TI Examining Risperidone Use in Those Diagnosed With Autism 1 Year After FDA Approval SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID CONTROLLED-TRIAL; CHILDREN; ADOLESCENTS; HALOPERIDOL; DISORDER; PLACEBO C1 [Valdovinos, Maria G.] Drake Univ, Dept Psychol, Des Moines, IA 50311 USA. [Taylor, Steve L.] Glenwood Resource Ctr, Glenwood, IA USA. RP Valdovinos, MG (reprint author), Drake Univ, Dept Psychol, Des Moines, IA 50311 USA. EM maria.valdovinos@drake.edu RI Valdovinos, Maria/F-5721-2014 CR Akhondzadeh S, 2008, CHILD PSYCHIAT HUM D, V39, P237, DOI 10.1007/s10578-007-0084-3 Gencer O, 2008, EUR CHILD ADOLES PSY, V17, P217, DOI 10.1007/s00787-007-0656-6 Hellings JA, 2006, J AUTISM DEV DISORD, V36, P401, DOI 10.1007/s10803-006-0078-1 LEVITAS AS, 2007, MENT HLTH ASPECTS DE, V10, P31 McCracken JT, 2002, NEW ENGL J MED, V347, P314, DOI 10.1056/NEJMoa013171 Shea S, 2004, PEDIATRICS, V114, P634 Tyrer P, 2008, LANCET, V371, P57, DOI 10.1016/S0140-6736(08)60072-0 NR 7 TC 0 Z9 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2010 VL 71 IS 5 BP 651 EP 652 DI 10.4088/JCP.09l05665yel PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599XC UT WOS:000277946400018 PM 20492856 ER PT J AU Levy, SE Giarelli, E Lee, LC Schieve, LA Kirby, RS Cunniff, C Nicholas, J Reaven, J Rice, CE AF Levy, Susan E. Giarelli, Ellen Lee, Li-Ching Schieve, Laura A. Kirby, Russell S. Cunniff, Christopher Nicholas, Joyce Reaven, Judy Rice, Catherine E. TI Autism Spectrum Disorder and Co-occurring Developmental, Psychiatric, and Medical Conditions Among Children in Multiple Populations of the United States SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism; autism spectrum; pervasive developmental disorder-not otherwise specified; Asperger Syndrome; co-occurring diagnoses; medical disorders ID DEFICIT HYPERACTIVITY DISORDER; HEALTH-CARE USE; ASPERGER-SYNDROME; PRESCHOOL-CHILDREN; PREVALENCE; DISABILITIES; ATTENTION; SURVEILLANCE; COMORBIDITY; DIAGNOSIS AB Background: Autism spectrum disorders (ASDs) often co-occur with other developmental, psychiatric, neurologic, or medical diagnoses. Objective: This study examined co-occurring non-ASD diagnoses and symptoms in a population-based cohort of 8 year olds identified with ASD. Method: Data on 2,568 children meeting surveillance case definition for ASD were collected by a multi-site surveillance program. Information was systematically abstracted and reviewed from existing health and education source records and systematically entered into a summary record in a secure database. Results: Eighty-one percent of study children were male; 63% white, 23% black, 14% Hispanic, Asian, or not stated. When age of ASD classification was available, 20% were classified before age 3 years, 36% between ages 3 and 5 years, and 44% after age 5 years. The co-occurrence of >= 1 non-ASD developmental diagnoses was 83%, >= 1 psychiatric diagnoses was 10%, >= 1 neurologic diagnoses was 16%, and at least one possibly causative genetic or neurologic diagnosis was 4%. Children with a previous ASD classification and co-occurring psychiatric or neurologic conditions were more likely to be diagnosed or classified at a later age. Each category of co-occurring non-ASD diagnosis was significantly increased in children whose records did not include an ASD diagnosis or educational classification but who met surveillance criteria for ASD. Conclusions: These data highlight the need for clinicians to keep in mind the high prevalence of associated diagnoses with an ASD diagnosis, and the possibility that in younger children other symptoms or disorders may be masking or obscuring core symptoms of ASD, which would lead to a diagnosis. C1 [Levy, Susan E.] Childrens Hosp Philadelphia, Reg Autism Ctr, Div Child Dev Rehabil & Metab Dis, Philadelphia, PA 19104 USA. [Giarelli, Ellen] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Lee, Li-Ching] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Schieve, Laura A.; Rice, Catherine E.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Kirby, Russell S.] Univ S Florida, Coll Publ Hlth, Dept Community & Family Hlth, Tampa, FL USA. [Cunniff, Christopher] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA. [Nicholas, Joyce] Med Univ S Carolina, Charleston, SC 29425 USA. [Reaven, Judy] Univ Colorado, Sch Med, JFK Partners, Denver, CO USA. RP Levy, SE (reprint author), Childrens Hosp Philadelphia, Reg Autism Ctr, Div Child Dev Rehabil & Metab Dis, Childrens Seashore House,3405 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM levys@email.chop.edu FU Centers for Disease Control and Prevention (CDC) FX The data represented in this paper were collected by the Autism and Developmental Disabilities Monitoring (ADDM) Network Surveillance Year 2002 supported by the Centers for Disease Control and Prevention (CDC). CR Abdul-Rahman OA, 2006, GENET MED, V8, P50, DOI 10.1097/01.gim.0000195304.45116.96 American Psychiatric Association, 2000, DIAGN STAT MAN MENT Autism and Developmental Disabilities Monitoring Network Surveillance Year 2002 Principal Investigators, 2007, MMWR SURVEILL SUMM, V56, P12 Bishop DVM, 2003, NOVART FDN SYMP, V251, P226 Bishop DVM, 2003, NOVART FDN SYMP, V251, P281 Bishop DVM, 2003, NOVART FDN SYMP, V251, P213 Boulet SL, 2009, ARCH PEDIAT ADOL MED, V163, P19, DOI 10.1001/archpediatrics.2008.506 Chakrabarti S, 2005, AM J PSYCHIAT, V162, P1133, DOI 10.1176/appi.ajp.162.6.1133 Croen LA, 2002, J AUTISM DEV DISORD, V32, P207, DOI 10.1023/A:1015453830880 de Bruin EI, 2007, J AUTISM DEV DISORD, V37, P877, DOI 10.1007/s10803-006-0215-x Freitag CM, 2007, MOL PSYCHIATR, V12, P2, DOI 10.1038/sj.mp.4001896 Gadow KD, 2004, J AUTISM DEV DISORD, V34, P379, DOI 10.1023/B:JADD.0000037415.21458.93 Gadow KD, 2008, J AUTISM DEV DISORD, V38, P1302, DOI 10.1007/s10803-007-0516-8 Ghaziuddin M, 2005, J AUTISM DEV DISORD, V35, P177, DOI 10.1007/s10803-005-1996-z Gillberg C, 2003, ARCH DIS CHILD, V88, P904, DOI 10.1136/adc.88.10.904 Gillberg C, 2000, ACTA PSYCHIAT SCAND, V102, P321, DOI 10.1034/j.1600-0447.2000.102005321.x Goldstein S, 2004, J AUTISM DEV DISORD, V34, P329, DOI 10.1023/B:JADD.0000029554.46570.68 Gurney JG, 2006, ARCH PEDIAT ADOL MED, V160, P825, DOI 10.1001/archpedi.160.8.825 Holtmann M, 2007, PSYCHOPATHOLOGY, V40, P172, DOI 10.1159/000100007 Howlin P, 1999, DEV MED CHILD NEUROL, V41, P834, DOI 10.1017/S0012162299001656 LAINHART JE, 1994, J AUTISM DEV DISORD, V24, P587, DOI 10.1007/BF02172140 Leyfer OT, 2006, J AUTISM DEV DISORD, V36, P849, DOI 10.1007/s10803-006-0123-0 Mandell DS, 2002, J AM ACAD CHILD PSY, V41, P1447, DOI 10.1097/01.CHI.0000024863.60748.53 Rice C, 2004, AM J MED GENET C, V125C, P22, DOI 10.1002/ajmg.c.30006 Rice CE, 2007, PAEDIATR PERINAT EP, V21, P179, DOI 10.1111/j.1365-3016.2007.00801.x SATO T, 1990, ENVIRON HEALTH PERSP, V87, P95, DOI 10.2307/3431011 Simonoff E, 2008, J AM ACAD CHILD PSY, V47, P921, DOI 10.1097/CHI.0b013e318179964f Ventola P, 2007, J AUTISM DEV DISORD, V37, P425, DOI 10.1007/s10803-006-0177-z Wiggins LD, 2009, AUTISM, V13, P357, DOI 10.1177/1362361309105662 Yeargin-Allsopp M, 2003, JAMA-J AM MED ASSOC, V289, P49, DOI 10.1001/jama.289.1.49 NR 30 TC 47 Z9 47 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 MAY PY 2010 VL 31 IS 4 BP 267 EP 275 DI 10.1097/DBP.0b013e3181d5d03b PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 597PE UT WOS:000277769600001 PM 20431403 ER PT J AU Indredavik, MS Vik, T Evensen, KAI Skranes, J Taraldsen, G Brubakk, AM AF Indredavik, Marit S. Vik, Torstein Evensen, Kari Anne I. Skranes, Jon Taraldsen, Gunnar Brubakk, Ann-Mari TI Perinatal Risk and Psychiatric Outcome in Adolescents Born Preterm With Very Low Birth Weight or Term Small for Gestational Age SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE mental health; behavior; very low birth weight; small for gestational age; perinatal risk ID ASPERGER-SYNDROME; CHILDREN; DISORDERS; ADULTHOOD; SYMPTOMS; GROWTH; ABNORMALITIES; DEPRESSION; BEHAVIOR; AUTISM AB Objective: To study perinatal risk factors for psychiatric symptoms in adolescents born preterm with very low birth weight or at term, but small for gestational age (GA). Method: Mental health was assessed in 65 adolescents born with very low birth weight (VLBW) (birth weight <= 1500 g), 59 born term small for GA (birth weight <10th centile) and 81 control adolescents using Schedule for Affective Disorders and Schizophrenia for School-Age Children, Children's Global Assessment Scale, Autism Spectrum Screening Questionnaire, Attention-Deficit Hyperactivity Disorder-Rating Scale IV and Achenbach System of Empirically Based Assessment. Perinatal data included birth weight, GA, head circumference, Apgar scores, intraventricular hemorrhage, days in neonatal intensive care unit, and days on mechanical ventilation. Results: In the very low birth weight group, lower birth weight was associated with inattention (p < .01), psychiatric diagnoses, and reduced psychosocial function (p <= .05). Intraventricular hemorrhage increased the risk for a high inattention score (odds ratio = 7.5; 95% confidence intervals: 1.2-46.8). Lower Apgar score at 1 min was associated with a high Autism Spectrum Screening Questionnaire score and lower Apgar score at 5 min with a high internalizing score (p <= .05). In the subgroup born appropriate for GA, internalizing symptoms were also associated with lower GA. In the term small for GA group, perinatal events were not associated with psychiatric problems. In contrast, low socioeconomic status was associated with externalizing symptoms. Conclusion: Lower birth weight, shorter gestation, and intraventricular hemorrhage were risk factors for psychiatric problems in the very low birth weight group. Lower Apgar score increased the risk for autism spectrum symptoms and internalizing symptoms. Among adolescents born term small for GA, the main risk factor for psychiatric symptoms was low socioeconomic status. C1 [Indredavik, Marit S.] Norwegian Univ Sci & Technol, Dept Neurosci, Fac Med, NO-7489 Trondheim, Norway. [Indredavik, Marit S.] St Olavs Univ Hosp, Dept Child & Adolescent Psychiat, Trondheim, Norway. [Vik, Torstein; Evensen, Kari Anne I.; Skranes, Jon; Brubakk, Ann-Mari] Norwegian Univ Sci & Technol, Dept Lab Med, Childrens & Womens Hlth, NO-7489 Trondheim, Norway. [Skranes, Jon; Brubakk, Ann-Mari] St Olavs Univ Hosp, Dept Pediat, Trondheim, Norway. [Evensen, Kari Anne I.] St Olavs Univ Hosp, Dept Phys Med & Rehabil, Trondheim, Norway. [Taraldsen, Gunnar] SINTEF Informat & Commun Technol, Trondheim, Norway. RP Indredavik, MS (reprint author), Norwegian Univ Sci & Technol, Dept Neurosci, Fac Med, NO-7489 Trondheim, Norway. EM marit.s.indredavik@ntnu.no FU US National Institute of Child Health and Human Development, NIH (NICHD) [1-HD-4-2803, 1-HD-1-3127]; Regional Centre for Child and Adolescent Mental Health; Norwegian University of Science and Technology; St. Olav's University Hospital FX The investigation was funded by Regional Centre for Child and Adolescent Mental Health, Norwegian University of Science and Technology, and Research Funds at St. Olav's University Hospital.Part of the study population was recruited from a multicenter study sponsored by the US National Institute of Child Health and Human Development, NIH (NICHD contract No. 1-HD-4-2803 and No. 1-HD-1-3127). CR Achenbach TM, 2001, MANUAL ASEBA SCH AGE American Psychiatric Association, 2000, DIAGN STAT MAN MENT Angold A, 2006, CHILD ADOL PSYCH CL, V15, P919, DOI 10.1016/j.chc.2006.05.013 Barkley R. 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Dev. Behav. Pediatr. PD MAY PY 2010 VL 31 IS 4 BP 286 EP 294 DI 10.1097/DBP.0b013e3181d7b1d3 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 597PE UT WOS:000277769600004 PM 20431402 ER PT J AU Stevens, L Tartaglia, N Hagerman, R Riley, K AF Stevens, Lindsay Tartaglia, Nicole Hagerman, Randi Riley, Karen TI Clinical Report A Male With Down Syndrome, Fragile X Syndrome, and Autism SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE Down syndrome; fragile X syndrome; autism; intellectual disability ID SPECTRUM DISORDER; STANDARDS AB A case of a 14-year-old boy with both fragile X syndrome and Down syndrome is described. This is the third reported case of a patient with fragile X syndrome plus Down syndrome and the first reported case in a male. Facial features are generally consistent with Down syndrome; however, a prominent forehead and jaw and maccroorchidism were consistent with fragile X syndrome. Joint laxity is also present, which is consistent with both disorders. Cognitive impairment is more significant than in his siblings with fragile X syndrome, and he meets criteria for autistic disorder. Ongoing behavioral dysregulation has been significant, leading to disruption of home and school environments despite many attempted psychopharmacologic and behavioral strategies and a supportive family. Identification and treatment of underlying medical problems (esophagitis) led to improvements in sleep and behavior. We emphasize discussion of challenges in his behavioral management and present a collaborative approach to behavioral management. C1 [Riley, Karen] Univ Denver, Morgridge Coll Educ, Denver, CO 80208 USA. [Stevens, Lindsay] Lucile Packard Childrens Hosp Stanford, Palo Alto, CA USA. 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Dev. Behav. Pediatr. PD MAY PY 2010 VL 31 IS 4 BP 333 EP 337 DI 10.1097/DBP.0b013e3181d5aa56 PG 5 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 597PE UT WOS:000277769600010 PM 20453578 ER PT J AU Farber, JM AF Farber, Jon Matthew TI Autism, Cognition, and Parent Counseling SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article AB Parents often have an inaccurate understanding of outcomes in autism, and developmentalists contribute to this when they omit consideration of cognitive functioning in their discussions with parents. Developmentalists need to incorporate information about cognitive levels (including intellectual disability, when present), in order to properly educate parents about prognosis for their child with autism. RP Farber, JM (reprint author), 1990 Old Bridge Rd, Woodbridge, VA 22192 USA. EM jmfpeds@msn.com CR KANNER L, 1971, J AUTISM CHILD SCHIZ, V1, P119, DOI 10.1007/BF01537953 King M, 2009, INT J EPIDEMIOL, V38, P1224, DOI 10.1093/ije/dyp261 QUINE L, 1987, DEV MED CHILD NEUROL, V29, P232 NR 3 TC 1 Z9 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD MAY PY 2010 VL 31 IS 4 BP 341 EP 342 DI 10.1097/DBP.0b013e3181da779d PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 597PE UT WOS:000277769600012 PM 20453580 ER PT J AU Gupta, VB AF Gupta, Vidya Bhushan TI Communicating With Parents of Children With Autism About Vaccines and Complementary and Alternative Approaches SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article ID RISK PERCEPTION; BAD-NEWS; IMMUNIZATION AB Despite incontrovertible evidence that vaccines do not cause autism, some parents continue to refuse them and many parents of children with autism seek hope in unproven and potentially harmful complementary and alternative (CAM) approaches. This commentary explores the reasons for such behaviors and proposes that pediatricians may support parents in their pursuit of hope in unproven treatments as long as these are not potentially harmful to the child or prohibitively expensive. While respecting parental autonomy and hope the pediatricians should share with parents their concerns about lack of scientific evidence about CAM and potential for harm by some approaches. C1 [Gupta, Vidya Bhushan] Metropolitan Hosp Ctr, Dept Pediat, New York, NY 10029 USA. [Gupta, Vidya Bhushan] Morristown Mem & Overlook Hosp, Child Dev Ctr, Morristown, NJ USA. RP Gupta, VB (reprint author), 12 Red Rock Trail, Saddle River, NJ 07458 USA. 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Dev. Behav. Pediatr. PD MAY PY 2010 VL 31 IS 4 BP 343 EP 345 DI 10.1097/DBP.0b013e3181d6b6e4 PG 3 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 597PE UT WOS:000277769600014 PM 20453581 ER PT J AU Menghini, D Addona, F Costanzo, F Vicari, S AF Menghini, D. Addona, F. Costanzo, F. Vicari, S. TI Executive functions in individuals with Williams syndrome SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE behavioural phenotypes; genetic syndrome; intellectual disability; neuropsychological profile ID FRAGILE-X-SYNDROME; WORKING-MEMORY; DOWN-SYNDROME; HYPERKINETIC DISORDER; SPECTRUM DISORDERS; SHIFTING ATTENTION; DORSAL-STREAM; CHILDREN; DEFICIT; AUTISM AB Background The present study was aimed at investigating working memory (WM) and executive functions capacities in individuals with Williams syndrome (WS) as compared with mental-age matched typically developing (TD) children. Method In order to serve the study goal, a sizeable battery of tasks tapping WM as well as attention, memory, planning, categorisation, shifting and inhibition abilities was administered to 15 individuals with WS (mean chronological age of 19.11 and mean mental age of 6.10), and to a group of 15 TD children (mean chronological age of 7.6 and mean mental age of 6.9). Results Participants with WS showed deficits in both verbal and visual-spatial modalities for selective and sustained attention, short-term memory and WM, planning and inhibition. However, considering categorisation and shifting abilities, relatively unimpaired performance emerged on those tasks relying on verbal materials. Conclusions These findings are both relevant to improve our knowledge about certain qualitative aspects of the anomalous cognitive development in WS as well as for its eventual clinical implications. 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Intell. Disabil. Res. PD MAY PY 2010 VL 54 BP 418 EP 432 DI 10.1111/j.1365-2788.2010.01287.x PN 5 PG 15 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 586SS UT WOS:000276933900003 PM 20537048 ER PT J AU Bruno, DL Anderlid, BM Lindstrand, A van Ravenswaaij-Arts, C Ganesamoorthy, D Lundin, J Martin, CL Douglas, J Nowak, C Adam, MP Kooy, RF Van der Aa, N Reyniers, E Vandeweyer, G Stolte-Dijkstra, I Dijkhuizen, T Yeung, A Delatycki, M Borgstrom, B Thelin, L Cardoso, C van Bon, B Pfundt, R de Vries, BBA Wallin, A Amor, DJ James, PA Slater, HR Schoumans, J AF Bruno, Damien L. Anderlid, Britt-Marie Lindstrand, Anna van Ravenswaaij-Arts, Conny Ganesamoorthy, Devika Lundin, Johanna Martin, Christa Lese Douglas, Jessica Nowak, Catherine Adam, Margaret P. Kooy, R. Frank Van der Aa, Nathalie Reyniers, Edwin Vandeweyer, Geert Stolte-Dijkstra, Irene Dijkhuizen, Trijnie Yeung, Alison Delatycki, Martin Borgstrom, Birgit Thelin, Lena Cardoso, Carlos van Bon, Bregje Pfundt, Rolph de Vries, Bert B. A. Wallin, Anders Amor, David J. James, Paul A. Slater, Howard R. Schoumans, Jacqueline TI Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MENTAL-RETARDATION; GENOMIC HYBRIDIZATION; NUMBER VARIATION; DIEKER-SYNDROME; ALU REPEATS; REARRANGEMENTS; ARRAY; DELETIONS; IMPACT; GENE AB Background Chromosome 17p13.3 contains extensive repetitive sequences and is a recognised region of genomic instability. Haploinsufficiency of PAFAH1B1 (encoding LIS1) causes either isolated lissencephaly sequence or Miller-Dieker syndrome, depending on the size of the deletion. More recently, both microdeletions and microduplications mapping to the Miller-Dieker syndrome telomeric critical region have been identified and associated with distinct but overlapping phenotypes. Methods Genome-wide microarray screening was performed on 7678 patients referred with unexplained learning difficulties and/or autism, with or without other congenital abnormalities. Eight and five unrelated individuals, respectively, were identified with microdeletions and microduplications in 17p13.3. Results Comparisons with six previously reported microdeletion cases identified a 258 kb critical region, encompassing six genes including CRK (encoding Crk) and YWHAE (encoding 14-3-3 epsilon). Clinical features included growth retardation, facial dysmorphism and developmental delay. Notably, one individual with only subtle facial features and an interstitial deletion involving CRK but not YWHAE suggested that a genomic region spanning 109 kb, encompassing two genes (TUSC5 and YWHAE), is responsible for the main facial dysmorphism phenotype. Only the microduplication phenotype included autism. The microduplication minimal region of overlap for the new and previously reported cases spans 72 kb encompassing a single gene, YWHAE. These genomic rearrangements were not associated with low-copy repeats and are probably due to diverse molecular mechanisms. Conclusions The authors further characterise the 17p13.3 microdeletion and microduplication phenotypic spectrum and describe a smaller critical genomic region allowing identification of candidate genes for the distinctive facial dysmorphism (microdeletions) and autism (microduplications) manifestations. C1 [Bruno, Damien L.; Ganesamoorthy, Devika; Yeung, Alison; Delatycki, Martin; Amor, David J.; James, Paul A.; Slater, Howard R.] Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Murdoch, WA, Australia. [Bruno, Damien L.; Ganesamoorthy, Devika; Slater, Howard R.] Univ Melbourne, Royal Childrens Hosp, Dept Pediat, Melbourne, Vic, Australia. [Anderlid, Britt-Marie; Lindstrand, Anna; Lundin, Johanna; Schoumans, Jacqueline] Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden. [van Ravenswaaij-Arts, Conny; Stolte-Dijkstra, Irene; Dijkhuizen, Trijnie] Univ Groningen, Dept Genet, Univ Med Ctr Groningen, Groningen, Netherlands. [Martin, Christa Lese; Adam, Margaret P.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Douglas, Jessica; Nowak, Catherine] Natl Birth Defects Ctr, Waltham, MA USA. [Kooy, R. Frank; Van der Aa, Nathalie; Reyniers, Edwin; Vandeweyer, Geert] Univ Antwerp, B-2020 Antwerp, Belgium. [Kooy, R. Frank; Van der Aa, Nathalie; Reyniers, Edwin; Vandeweyer, Geert] Univ Antwerp Hosp, Antwerp, Belgium. [Borgstrom, Birgit] Karolinska Univ Hosp, Dept Endocrinol, Pediat Clin, Huddinge, Sweden. [Thelin, Lena] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Cardoso, Carlos] Univ Aix Marseille 2, INSERM, INMED, U901, Marseille, France. [van Bon, Bregje; Pfundt, Rolph; de Vries, Bert B. A.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Wallin, Anders] Malar Hosp, Eskilstuna, Sweden. RP Slater, HR (reprint author), Royal Childrens Hosp, Dept Cytogenet, VCGS Pathol, MCRI, Flemington Rd, Parkville, Vic 3052, Australia. EM howard.slater@ghsv.org.au RI Delatycki, Martin/A-5409-2013; van Bon, Bregje/D-3720-2013; Bruno, Damien/C-3665-2013; Lindstrand, Anna/J-3566-2012; James, Paul/G-2943-2014; Ganesamoorthy, Devika/J-8359-2014 OI Lindstrand, Anna/0000-0003-0806-5602; Ganesamoorthy, Devika/0000-0001-8149-6703 FU Swedish Research Council; Karolinska Institute foundation; Stockholm County Council; Perpetual Trustees Australia; EU; Netherlands Organisation for Health Research and Development FX We are grateful to all individuals and parents who participated in this study. This work was supported by grants from The Swedish Research Council (BMA), The Karolinska Institute foundation and Stockholm County Council (to JS, BMA), Perpetual Trustees Australia (to HRS), and the EU-funded AnEUploidy Project (to BBAdV and BvB) and the Netherlands Organisation for Health Research and Development (to BBAdV). We also thank Z Bowman, M Lagerberg, J Wincent and C Ngo for technical assistance and J Senior for critically reading the manuscript. 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TI Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID 17Q21.31 MICRODELETION SYNDROME; GENOMIC DISORDERS; MENTAL-RETARDATION; INCREASE RISK; AUTISM; DELETIONS; PROTEIN; BRAIN; SCHIZOPHRENIA; EXPRESSION AB Background Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay. Method We indentified 27 deletions and 18 duplications of 16p11.2 were identified in 0.6% of all samples submitted for clinical array-CGH (comparative genomic hybridisation) analysis. Detailed molecular and phenotypic characterisations were performed on 17 deletion subjects and ten subjects with the duplication. Results The most common clinical manifestations in 17 deletion and 10 duplication subjects were speech/language delay and cognitive impairment. Other phenotypes in the deletion patients included motor delay (50%), seizures (similar to 40%), behavioural problems (similar to 40%), congenital anomalies (similar to 30%), and autism (similar to 20%). The phenotypes among duplication patients included motor delay (6/10), behavioural problems (especially attention deficit hyperactivity disorder (ADHD)) (6/10), congenital anomalies (5/10), and seizures (3/10). Patients with the 16p11.2 deletion had statistically significant macrocephaly (p<0.0017) and 6 of the 10 patients with the duplication had microcephaly. One subject with the deletion was asymptomatic and another with the duplication had a normal cognitive and behavioural phenotype. Genomic analyses revealed additional complexity to the 16p11.2 region with mechanistic implications. The chromosomal rearrangement was de novo in all but 2 of the 10 deletion cases in which parental studies were available. Additionally, 2 de novo cases were apparently mosaic for the deletion in the analysed blood sample. Three de novo and 2 inherited cases were observed in the 5 of 10 duplication patients where data were available. Conclusions Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders. C1 [Shinawi, Marwan; Liu, Pengfei; Kang, Sung-Hae L.; Belmont, John W.; Scott, Daryl A.; Probst, Frank J.; Craigen, William J.; Graham, Brett H.; Patel, Ankita; Stankiewicz, Pawel; Beaudet, Arthur L.; Cheung, Sau Wai; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Clark, Gary; Lee, Jennifer; Proud, Monica; Stocco, Amber; Rodriguez, Diana L.] Texas Childrens Hosp, Dept Pediat, Neurol Sect, Houston, TX 77030 USA. [Shen, Joseph] Childrens Hosp Cent Calif, Madera, CA USA. [Kozel, Beth A.] Washington Univ, Sch Med, Div Genet & Genom Med, St Louis, MO USA. [Sparagana, Steven] Texas Scottish Rite Hosp Children, Dept Neurol, Dallas, TX 75219 USA. [Sparagana, Steven] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Roeder, Elizabeth R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, Div Genet & Metab Disorders, San Antonio, TX 78229 USA. [McGrew, Susan G.] Vanderbilt Univ, Sch Med, Dept Pediat, Monroe Carell Jr Childrens Hosp Vanderbilt, Nashville, TN 37212 USA. [Kurczynski, Thaddeus W.] Akron Childrens Hosp, Dept Pediat, Akron, OH USA. [Allison, Leslie J.] Monarch Med Clin, Katy, TX USA. [Amato, Stephen; Savage, Sarah] Eastern Maine Med Ctr, Dept Med Genet, Bangor, ME USA. [Stankiewicz, Pawel] Inst Mother & Child Hlth, Dept Med Genet, Warsaw, Poland. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Cheung, SW (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza,NAB 2015, Houston, TX 77030 USA. EM scheung@bcm.tmc.edu FU Polish Ministry of Science and Higher Education [R13-0005-04/2008]; National Institute of Neurological Disorders and Stroke, N. I. H. [RO1 NS058529] FX The authors thank the patients and parents for their willingness to participate in our research study. We thank Dr Feng Zhang for assistance in the design of the high-resolution 16p11.2 specific array. P. S. was supported in part by grant R13-0005-04/2008 from the Polish Ministry of Science and Higher Education. This work was supported in part by National Institute of Neurological Disorders and Stroke, N. I. H. grant RO1 NS058529 to J.R.L. 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Med. Genet. PD MAY PY 2010 VL 47 IS 5 BP 332 EP 341 DI 10.1136/jmg.2009.073015 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 592FW UT WOS:000277363500005 PM 19914906 ER PT J AU Orr, AG Sharma, A Binder, NB Miller, AH Pearce, BD AF Orr, Anna G. Sharma, Anup Binder, Nikolaus B. Miller, Andrew H. Pearce, Bradley D. TI Interleukin-1 Mediates Long-Term Hippocampal Dentate Granule Cell Loss Following Postnatal Viral Infection SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Hippocampus; Autism; Schizophrenia; Lymphocytic choriomeningitis virus; Neurodevelopment; Neuroprotection ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CENTRAL-NERVOUS-SYSTEM; RECEPTOR ANTAGONIST; CYTOKINE EXPRESSION; ADULT NEUROGENESIS; NEONATAL INFECTION; NEURONAL INJURY; RAT HIPPOCAMPUS; PERINATAL RATS; BRAIN-INJURY AB Viral infections of the developing CNS can cause long-term neuropathological sequela through undefined mechanisms. Proinflammatory cytokines such as IL-1 beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. Little is known concerning the spatial-temporal pattern of IL-1 beta induction in the developing hippocampus following live virus infection, and there are few studies addressing the long-term consequences of this cytokine induction. We report that infection of rats with lymphocytic choriomeningitis virus on postnatal day 4 induces IL-1 beta protein in select regions of the hippocampus on 6, 15, 21, and 45 days after infection. This infection resulted in a 71% reduction of dentate granule cell neurons by the time the rats reached mid-adulthood. We further investigated the causative role of IL-1 in this dentate granule cell loss by blocking IL-1 activity using an IL-1ra-expressing adenoviral vector administered at the time of infection. Blockade of IL-1 abrogated the infection-associated neuron loss in this vivo model. Considering that IL-1 can be triggered by multiple perinatal insults, our findings suggest that early therapy with anti-inflammatory agents that block IL-1 may be effective for reducing adulthood neuropathology. C1 [Pearce, Bradley D.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Pearce, Bradley D.] Emory Univ, Grad Div Biol & Biomed Sci, Atlanta, GA 30322 USA. [Orr, Anna G.; Sharma, Anup; Binder, Nikolaus B.; Miller, Andrew H.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Pearce, BD (reprint author), Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. EM bpearce@emory.edu FU NIMH [5R29NS037068]; Theodore and Vada Stanley Foundation FX This work was supported by NIMH grant 5R29NS037068 (to B. D. P.) and the Theodore and Vada Stanley Foundation. We are grateful to Dr. Nancy Bliwise (Emory University Department of Psychology) for her advice on statistical analysis. We thank the University of Iowa Gene Vector Core and Dr. Beverly Davidson for supplying the adenovirus vectors. 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TI Oxytocin Signal and Social Behaviour: Comparison among Adult and Infant Oxytocin, Oxytocin Receptor and CD38 Gene Knockout Mice SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE oxytocin; oxytocin receptor; social recognition; maternal nurturing; CD38; ADP-ribosyl cyclase; autism ID CYCLIC ADP-RIBOSE; MATERNAL-BEHAVIOR; BRAIN; VASOPRESSIN; HUMANS; AUTISM; MOUSE; SYSTEM; CONSEQUENCES; VOCALIZATION AB Oxytocin in the hypothalamus is the biological basis of social recognition, trust, love and bonding. Previously, we showed that CD38, a proliferation marker in leukaemia cells, plays an important role in the hypothalamus in the process of oxytocin release in adult mice. Disruption of Cd38 (Cd38 -/-) elicited impairment of maternal behaviour and male social recognition in adult mice, similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene knockout (Oxt -/- and Oxtr -/-, respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalisation calls was lower in Cd38 -/- than Cd38 +/+ pups. However, these behavioural changes were much milder than those observed in Oxt -/- and Oxtr -/- mice, indicating less impairment of social behaviour in Cd38 -/- pups. These phenotypes appeared to be caused by the high plasma oxytocin levels during development from the neonatal period to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of plasma oxytocin differentiation. Breastfeeding was an important exogenous source of plasma oxytocin regulation before weaning as a result of the presence of oxytocin in milk and the dam's mammary glands. The dissimilarity between Cd38 -/- infant behaviour and those of Oxt -/- or Oxtr -/- mice can be explained partly by this exogenous source of oxytocin. These results suggest that secretion of oxytocin into the brain in a CD38-dependent manner may play an important role in the development of social behaviour. C1 [Higashida, H.; Lopatina, O.; Pichugina, Y. A.; Korshunova, N.] Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan. [Higashida, H.; Yoshihara, T.; Munesue, T.; Minabe, Y.] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa 9208640, Japan. [Higashida, H.; Lopatina, O.] Core Res Evolut Sci & Technol, Tokyo, Japan. [Lopatina, O.; Salmina, A. B.] Krasnoyarsk State Med Univ, Dept Biochem Med Pharmaceut & Toxicol Chem, Krasnoyarsk, Russia. [Pichugina, Y. A.; Soumarokov, A. A.] Krasnoyarsk State Med Univ, Dept Psychiat, Krasnoyarsk, Russia. [Munesue, T.; Minabe, Y.; Kikuchi, M.; Ono, Y.] Kanazawa Univ, Grad Sch Med, Dept Psychaitry & Neurobiol, Kanazawa, Ishikawa 9208640, Japan. RP Higashida, H (reprint author), Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, 13-1 Takara Machi, Kanazawa, Ishikawa 9208640, Japan. EM haruhiro@med.kanazawa-u.ac.jp RI Salmina, Alla/L-7977-2013; Lopatina, Olga/I-9610-2014 FU Russian Foundation for Basic Research [08-04-91209]; Russian Foundation for Basic Research and the Japan Society for the Promotion of Science (RFBR-JSPS) [08-04-91209] FX This work was supported by the bilateral grant 08-04-91209 from the Russian Foundation for Basic Research and the Japan Society for the Promotion of Science (RFBR-JSPS) (A.B.S., H.H.). 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PD MAY PY 2010 VL 22 IS 5 BP 373 EP 379 DI 10.1111/j.1365-2826.2010.01976.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 585WW UT WOS:000276862100007 PM 20141571 ER PT J AU Salmina, AB Lopatina, O Ekimova, MV Mikhutkina, SV Higashida, H AF Salmina, A. B. Lopatina, O. Ekimova, M. V. Mikhutkina, S. V. Higashida, H. TI CD38/Cyclic ADP-ribose System: A New Player for Oxytocin Secretion and Regulation of Social Behaviour SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE oxytocin; CD38; cyclic ADP-ribose; autism; social behaviour ID RAT SUPRAOPTIC NEURONS; METABOTROPIC GLUTAMATE RECEPTORS; DENDRITIC PEPTIDE RELEASE; CENTRAL-NERVOUS-SYSTEM; MAGNOCELLULAR NEURONS; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; NEUROSECRETORY-SYSTEM; INTRACELLULAR CALCIUM; ADENINE-DINUCLEOTIDE; THERAPEUTIC TARGET AB Oxytocin is important for regulating a number of physiological processes. Disruption of the secretion, metabolism or action of oxytocin results in an impairment of reproductive function, social and sexual behaviours, and stress responses. This review discusses current views on the regulation and autoregulation of oxytocin release in the hypothalamic-neurohypophysial system, with special focus on the activity of the CD38/cADP-ribose system as a new component in this regulation. Data from our laboratories indicate that an impairment of this system results in alterations of oxytocin secretion and abnormal social behaviour, thus suggesting new clues that help in our understanding of the pathogenesis of neurodevelopmental disorders. C1 [Salmina, A. B.; Ekimova, M. V.; Mikhutkina, S. V.] Krasnoyarsk State Med Univ, Dept Biochem Med Pharmaceut & Toxicol Chem, Krasnoyarsk 660022, Russia. [Lopatina, O.; Higashida, H.] Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa, Japan. 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Titone, Debra TI The genetic basis of thought disorder and language and communication disturbances in schizophrenia SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE Schizophrenia; Thought disorder; Language disorders; Communication disorders; Semantic anomalies; Genetics; Family studies; Linkage analyses; Endophenotypes ID AUTISM SPECTRUM DISORDER; LINKAGE ANALYSIS; FOLLOW-UP; COGNITIVE DEFICITS; ROSCOMMON FAMILY; SPEECH DISORDER; PARENTS; FOXP2; IMPAIRMENT; RISK AB Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself. These findings suggest that deviant verbalizations may be more penetrant expressions of schizophrenia susceptibility genes than schizophrenia. This paper reviews the evidence documenting the presence of thought, language and communication disorders in schizophrenic patients and in their first-degree relatives. This familial aggregation potentially implicates genetic factors in the etiology of thought disorder, language anomalies, and communication disturbances in schizophrenia families. We also present two examples of ways in which thought, language and communication disorders can enrich genetic studies, including those involving schizophrenia. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Levy, Deborah L.; Coleman, Michael J.; Matthysse, Steven] McLean Hosp, Psychol Res Lab, Belmont, MA 02478 USA. [Sung, Heejong] Natl Human Genome Res Inst, Genometr Sect, Inherited Dis Res Branch, NIH, Bethesda, MD USA. [Ji, Fei] Stat Collaborat Inc, Washington, DC USA. 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PD MAY PY 2010 VL 69 IS 5 MA 102 BP 547 EP 548 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 594WV UT WOS:000277571500111 ER PT J AU Tekin-Iftar, E Birkan, B AF Tekin-Iftar, Elif Birkan, Bunyamin TI Small Group Instruction for Students With Autism General Case Training and Observational Learning SO JOURNAL OF SPECIAL EDUCATION LA English DT Article DE small group teaching; autism; general case training; observational learning; progressive time delay; food and drink preparation skills ID TIME-DELAY PROCEDURES; DAILY LIVING SKILLS; SEVERE DISABILITIES; ACQUISITION; RESPONSES; CHILDREN; STIMULI AB A multiple-probe design across response chains and students was used to evaluate the combined instructional effects of progressive time delay, general case training, and observational learning on the food and drink preparation skills of three children with autism. All instruction was delivered in a group learning arrangement. 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PD MAY PY 2010 VL 44 IS 1 BP 50 EP 63 DI 10.1177/0022466908325219 PG 14 WC Education, Special SC Education & Educational Research GA 580PT UT WOS:000276462100004 ER PT J AU Johnson, S Hollis, C Kochhar, P Hennessy, E Wolke, D Marlow, N AF Johnson, Samantha Hollis, Chris Kochhar, Puja Hennessy, Enid Wolke, Dieter Marlow, Neil TI Psychiatric Disorders in Extremely Preterm Children: Longitudinal Finding at Age 11 Years in the EPICure Study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE extremely preterm; psychiatric disorders; risk factors; ADHD; autism ID LOW-BIRTH-WEIGHT; BEHAVIORAL OUTCOMES; DIFFICULTIES-QUESTIONNAIRE; NEUROBEHAVIORAL OUTCOMES; DEVELOPMENTAL-DISABILITY; SOCIAL COMPETENCES; PREMATURE BIRTH; MENTAL-HEALTH; FOLLOW-UP; BORN AB Objective: To investigate the prevalence and risk factors for psychiatric disorders in extremely preterm children. Method: All babies born <26 weeks gestation in the United Kingdom and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors at 11 years of age, 219 (71%) were assessed alongside 153 term-born classmates. Parents completed a structured psychiatric interview about their child, and teachers completed a corresponding questionnaire from which DSM-IV diagnoses were assigned for 219 (100%) extremely preterm children and 152 (99%) classmates. An IQ test and a physical evaluation were also administered. Longitudinal data were available for extremely preterm children. Results: Extremely preterm children were more than three times more likely to have a psychiatric disorder than classmates (23% vs. 9%; odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7, 6.2). Risk was significantly increased for: attention-deficit/hyperactivity disorder (ADHD; 11.5% vs. 2.9%; OR = 4.3; CI = 1.5 to 13.0), with increased risk for ADHD inattentive subtype (OR = 10.5; CI = 1.4 to 81.1) but not ADHD combined subtype (OR = 2.1; CI = 0.5 to 7.9); emotional disorders (9.0% vs. 2.1%; OR = 4.6; CI = 1.3 to 15.9), with increased risk for anxiety disorders (OR = 3.5; CI = 1.0 to 12.4); and autism spectrum disorders (8.0% vs. 0%; p = .000). Psychiatric disorders were significantly associated with cognitive impairment (OR = 3.5; CI = 1.8 to 6.4). Parent-reported behavioral problems at 2.5 and 6 years were independent predictors of psychiatric disorders at 11 years. Conclusions: Extremely preterm children are at increased risk for ADHD, emotional disorders, and autism spectrum disorders at 11 years of age. The mechanism of association with psychiatric disorder may include both cognitive impairment and early traumatic experiences that have an impact on both child and parent. Early screening for cognitive and behavioral problems may identify those at greatest risk. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(5):453-463. C1 [Johnson, Samantha] Univ Nottingham, Sch Clin Sci, Nottingham NG7 2RD, England. [Johnson, Samantha] UCL, Inst Womens Hlth, London WC1E 6BT, England. [Hollis, Chris; Kochhar, Puja] Univ Nottingham, Div Psychiat, Dev Psychiat Sect, Nottingham NG7 2RD, England. [Hennessy, Enid] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. [Wolke, Dieter] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England. RP Hollis, C (reprint author), Queens Med Ctr, South Block,E Floor, Nottingham NG7 2UH, England. EM chris.hollis@nottingham.ac.uk RI Wolke, Dieter/C-5372-2008; Marlow, Neil/D-2918-2009 OI Wolke, Dieter/0000-0003-0304-268X; Marlow, Neil/0000-0001-5890-2953 FU Medical Research Council (MRC), UK FX This study was supported by the Medical Research Council (MRC), UK. 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Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2010 VL 49 IS 5 BP 453 EP 463 DI 10.1016/j.jaac.2010.02.002 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 589FD UT WOS:000277131100005 PM 20431465 ER PT J AU Lionello-DeNouf, KM Dube, WV McIlvane, WJ AF Lionello-DeNouf, Karen M. Dube, William V. McIlvane, William J. TI EVALUATION OF RESISTANCE TO CHANGE UNDER DIFFERENT DISRUPTER CONDITIONS IN CHILDREN WITH AUTISM AND SEVERE INTELLECTUAL DISABILITY SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE behavioral momentum; autism spectrum disorders; intellectual disability; computer screen touch; human children ID BEHAVIORAL MOMENTUM; LONGITUDINAL DATA; ATTENTION; REINFORCEMENT; INDIVIDUALS; TRANSITIONS; EXTINCTION; SCHEDULES AB Translational research inspired by behavioral momentum theory in the area of developmental disabilities has shown effects in individuals over a range of functioning levels. In the current study, behavioral momentum was assessed in 6 children diagnosed with autism and severe intellectual disability. In a repeated measures design, participants were exposed to relatively rich versus lean reinforcement contingencies in a multiple schedule with food reinforcers. This was followed by exposure to each of four disrupting conditions: prefeeding, presentation of a concurrent alternative stimulus, presentation of a movie, and the presence of a researcher dispensing response-independent reinforcers on a variable-time schedule. Consistently greater resistance to disruption in the component with the richer schedule occurred with the alternative stimulus disrupter but not with the other disrupters. These results suggest parameters that may be more (or less) effective if behavioral momentum inspired techniques are to be exploited in therapeutic environments. C1 [Lionello-DeNouf, Karen M.; Dube, William V.; McIlvane, William J.] Univ Massachusetts, Sch Med, Shriver Ctr, Shrewsbury, MA 01545 USA. RP Lionello-DeNouf, KM (reprint author), Univ Massachusetts, Sch Med, Shriver Ctr, 333 South St, Shrewsbury, MA 01545 USA. EM Karen.Lionello-DeNolf@umassmed.edu FU NICHD [HD 046666, HD04147] FX This research was supported by NICHD grants HD 046666 and HD04147. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of NICHD. We thank Jeff Kilpatrick, Steven Meyer, Emily Wheeler, and Lauren Abraham for their assistance in data collection. 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Associations between family income [Below 100% Federal Poverty Level (FPL), 100-199% FPL, 200-299% FPL, 300-399% FPL, 400% FPL or Greater] and a set of 32 health and health care indicators were examined using linear polynomial testing and multivariate logistic regression. The percentage of children in better health increased with family income for 15 health outcomes. In multivariate logistic regression models that controlled for health insurance coverage and socio-demographic confounders, odds ratios > 2 comparing the lowest to the highest income groups were noted for health conditions across both physical and developmental domains (diabetes, headaches, ear infections, learning disabilities, behavior/conduct problems, speech problems). Parent-reported global child health status, activity limitation, and oral health status showed steeper gradients than specific chronic and acute conditions. Ten measures of health care access and utilization were associated with family income in multivariate logistic regression models. Income gradients are pervasive across many health indicators at an early age. Social and health policy interventions are needed to address the multitude of factors that can affect children's health and initiate disparities in development. C1 [Larson, Kandyce; Halfon, Neal] Univ Calif Los Angeles, Ctr Healthier Children Families & Communities, Los Angeles, CA 90024 USA. [Larson, Kandyce; Halfon, Neal] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. [Halfon, Neal] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Halfon, Neal] Univ Calif Los Angeles, Sch Publ Affairs, Dept Publ Policy, Los Angeles, CA 90024 USA. RP Larson, K (reprint author), Univ Calif Los Angeles, Ctr Healthier Children Families & Communities, 10990 Wilshire Blvd,Suite 900, Los Angeles, CA 90024 USA. 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PD MAY PY 2010 VL 14 IS 3 BP 332 EP 342 DI 10.1007/s10995-009-0477-y PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 590RD UT WOS:000277244000003 PM 19499315 ER PT J AU Pinborough-Zimmerman, J Bilder, D Satterfield, R Hossain, S McMahon, W AF Pinborough-Zimmerman, Judith Bilder, Deborah Satterfield, Robert Hossain, Shaheen McMahon, William TI The Impact of Surveillance Method and Record Source on Autism Prevalence: Collaboration with Utah Maternal and Child Health Programs SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Autism spectrum disorders; Surveillance; Prevalence; Maternal child health; Epidemiology ID SPECTRUM DISORDERS; SPECIAL-EDUCATION; TRENDS AB With the increasing number of Utah children identified with autism spectrum disorders (ASDs), information on the prevalence and characteristics of these children could help Maternal Child Health (MCH) programs develop population building activities focused on prevention, screening, and education. The purpose of this study is to describe Utah's autism registry developed in collaboration with state MCH programs and assess the impact of different record-based surveillance methods on state ASD prevalence rates. The study was conducted using 212 ASD cases identified from a population of 26,217 eight year olds living in one of the three most populous counties in Utah (Davis, Salt Lake, and Utah) in 2002. ASD prevalence was determined using two records based approaches (administrative diagnoses versus abstraction and clinician review) by source of record ascertainment (education, health, and combined). ASD prevalence ranged from 7.5 per 1000 (95% CI 6.4-8.5) to 3.2 per 1000 (95% CI 2.5-3.9) varying significantly (P < .05) based on method and record source. The ratio of male-to-female ranged from 4.7:1 to 6.4:1. No significant differences were found between the two case ascertainment methods on 18 of the 23 case characteristics including median household income, parental education, and mean age of diagnosis. Broad support is needed from both education and health sources as well as collaboration with MCH programs to address the growing health concerns, monitoring, and treatment needs of children and their families impacted by autism spectrum disorders. C1 [Pinborough-Zimmerman, Judith; Bilder, Deborah; McMahon, William] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA. [Satterfield, Robert; Hossain, Shaheen] Utah Dept Hlth, Salt Lake City, UT 84116 USA. RP Pinborough-Zimmerman, J (reprint author), Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA. 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Child Health J. PD MAY PY 2010 VL 14 IS 3 BP 392 EP 400 DI 10.1007/s10995-009-0472-3 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 590RD UT WOS:000277244000010 PM 19475366 ER PT J AU Hadjikhani, N AF Hadjikhani, Nouchine TI Serotonin, pregnancy and increased autism prevalence: Is there a link? SO MEDICAL HYPOTHESES LA English DT Article ID REUPTAKE INHIBITORS; PLATELET SEROTONIN; 1ST-DEGREE RELATIVES; TRYPTOPHAN DEPLETION; SPECTRUM DISORDERS; MENTAL-RETARDATION; OXYTOCIN; CHILDREN; AMYGDALA; BRAIN AB The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. In this paper, we hypothesize that increased serotonemia during pregnancy, including due to SSRI intake, could be one of the causes of the raising prevalence in autism. If our hypothesis is confirmed, it will not only shed light on one of the possible reason for autism prevalence, but also offer new preventive and treatment options. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Hadjikhani, Nouchine] MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hadjikhani, Nouchine] EPFL Lausanne, Brain Mind Inst, Lausanne, Switzerland. RP Hadjikhani, N (reprint author), EPFL SV BMI AAB 133, Stn 15, CH-1015 Lausanne, Switzerland. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU Swiss National Foundation [PP00B-110741] FX This work was supported by the Swiss National Foundation Grant PP00B-110741 to NH. 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Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the interpretation of risks posed by heredity and the environment and the search for neuropsychiatric candidate genes. (C) 2009 Published by Elsevier Ltd. 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Hypotheses PD MAY PY 2010 VL 74 IS 5 BP 911 EP 918 DI 10.1016/j.mehy.2009.05.039 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 599BY UT WOS:000277886400037 PM 20138440 ER PT J AU Brang, D Ramachandran, VS AF Brang, David Ramachandran, V. S. TI Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism SO MEDICAL HYPOTHESES LA English DT Article ID SPECTRUM DISORDERS; OXYTOCIN; CHILDREN; VOLUME; SCHIZOPHRENIA; BEHAVIORS AB Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection. (C) 2009 Published by Elsevier Ltd. C1 [Brang, David; Ramachandran, V. S.] Univ Calif San Diego, Ctr Brain & Cognit, La Jolla, CA 92093 USA. RP Ramachandran, VS (reprint author), Univ Calif San Diego, Ctr Brain & Cognit, La Jolla, CA 92093 USA. 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Hypotheses PD MAY PY 2010 VL 74 IS 5 BP 919 EP 921 DI 10.1016/j.mehy.2008.11.048 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 599BY UT WOS:000277886400038 PM 20149551 ER PT J AU Kuno, K Ishii, Y Ueda, T Kurokawa, T Chen, ZY Tanaka, T Tominaga, R Watanabe, K AF Kuno, Katashi Ishii, Yoshimasa Ueda, Takashi Kurokawa, Takashi Chen, Zhouye Tanaka, Toru Tominaga, Ryo Watanabe, Kazuhiko TI The Effects Of Physical Training On Standing Long Jump Among The People With Autism And The Down Syndrome SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural World Congress on Exercise is Medicine CY JUN 05, 2010 CL Baltimore, MD SP Amer Coll Sports Med C1 [Kuno, Katashi; Ishii, Yoshimasa; Ueda, Takashi; Kurokawa, Takashi; Chen, Zhouye; Tanaka, Toru; Tominaga, Ryo; Watanabe, Kazuhiko] Hiroshima Univ, Higashihiroshima 724, Japan. NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2010 VL 42 IS 5 SU 1 MA 1610 BP 335 EP 336 PG 2 WC Sport Sciences SC Sport Sciences GA 759FO UT WOS:000290226301266 ER PT J AU Hand, BD Bush, JA Crabtree, L Newhouse, R Fagan, L Stinar, R AF Hand, Brian D. Bush, Jill A. Crabtree, Lisa Newhouse, Rebecca Fagan, Lisa Stinar, Raymond TI The Influence of Exercise on Neuromuscular Function in Adults on the Autism Spectrum SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural World Congress on Exercise is Medicine CY JUN 05, 2010 CL Baltimore, MD SP Amer Coll Sports Med C1 [Hand, Brian D.; Bush, Jill A.; Crabtree, Lisa; Newhouse, Rebecca; Fagan, Lisa; Stinar, Raymond] Towson Univ, Towson, MD USA. EM BHand@towson.edu NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2010 VL 42 IS 5 SU 1 MA 1960 BP 459 EP 459 PG 1 WC Sport Sciences SC Sport Sciences GA 759FO UT WOS:000290226301614 ER PT J AU Pan, CY Hsieh, KW Tsai, CL AF Pan, Chien-Yu Hsieh, Kai-Wen Tsai, Chia-Liang TI Motivation and Physical Activity of Adolescents With and Without Autism in Inclusive Physical Education SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-College-Sports-Medicine/Inaugural World Congress on Exercise is Medicine CY JUN 05, 2010 CL Baltimore, MD SP Amer Coll Sports Med C1 [Pan, Chien-Yu] Natl Kaohsiung Normal Univ, Kaohsiung, Taiwan. [Hsieh, Kai-Wen; Tsai, Chia-Liang] Natl Cheng Kung Univ, Tainan 70101, Taiwan. EM chpan@nknucc.nknu.edu.tw NR 0 TC 0 Z9 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2010 VL 42 IS 5 SU 1 MA 2133 BP 519 EP 520 PG 2 WC Sport Sciences SC Sport Sciences GA 759FO UT WOS:000290226301787 ER PT J AU Hogart, A Wu, D LaSalle, JM Schanen, NC AF Hogart, Amber Wu, David LaSalle, Janine M. Schanen, N. Carolyn TI The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13 SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Autism; Autism spectrum disorders; Prader-Willi syndrome; Angelman syndrome; Interstitial duplication chromosome 15; Isodicentric chromosome 15; Low copy repeats; Imprinting ID PRADER-WILLI-SYNDROME; SYNDROME CRITICAL REGION; PERVASIVE DEVELOPMENTAL DISORDERS; AMINOBUTYRIC-ACID RECEPTOR; ANGELMAN SYNDROME GENE; INV DUP(15); PROXIMAL 15Q; UNIPARENTAL DISOMY; IMPRINTING-CENTER; INTERSTITIAL DUPLICATIONS AB A cluster of low copy repeats on the proximal long arm of chromosome 15 mediates various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that an increased copy number of maternally derived alleles contributes to autism susceptibility. Notably, nonimprinted, biallelically expressed genes within the interval also have been shown to be misexpressed in brains of patients with chromosome 15q11.2-q13 genomic disorders, indicating that they also likely play a role in the phenotypic outcome. This review provides an overview of the phenotypes of these disorders and their relationships with ASD and outlines the regional genes that may contribute to the autism susceptibility imparted by copy number variation of the region. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hogart, Amber; LaSalle, Janine M.] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Wu, David; Schanen, N. Carolyn] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. [Schanen, N. Carolyn] Alfred I duPont Hosp Children, Nemours Biomed Res, Wilmington, DE 19803 USA. [Schanen, N. Carolyn] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. RP Schanen, NC (reprint author), Alfred I duPont Hosp Children, Nemours Biomed Res, 1600 Rockland Rd,Room RC1-241, Wilmington, DE 19803 USA. EM schanen@medsci.udel.edu RI LaSalle, Janine/A-4643-2008 OI LaSalle, Janine/0000-0002-3480-2031 FU National Institutes of Health [NIH F31 MH078377, NIH R01 HD48799, NIH P3P01 HD35470, NIH R01 HD37874, P20-RR020173]; Nemours FX The authors are supported by grants from the National Institutes of Health [NIH F31 MH078377 (AH), NIH R01 HD48799 (JML), NIH P3P01 HD35470 (NCS), NIH R01 HD37874 (NCS), P20-RR020173 (NCS)], and Nemours (NCS and DW). We are indebted to the Isodicentric Exchange, Advocacy and Support Group and families with idic(15) for their participation in the ongoing research into the investigation of the phenotype of patients with idic(15) and interstitial duplication 15 chromosomes. The authors also thank Suzanne Cassidy for providing detailed information on an unpublished case interstitial triplication chromosome 15 and the relationship with PWS and ASD. 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Uchiyama, Hitoshi Morita, Tomoyo Kikuchi, Mitsuru Mizukami, Kimiko Okazawa, Hidehiko Sadato, Norihiro Wada, Yuji TI Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders SO NEUROIMAGE LA English DT Article DE Pervasive developmental disorders (PDD); Autistic spectrum disorders (ASD); Voxel-based morphometry (VBM); Insula; Inferior frontal gyrus (IFG); Mirror neuron system (MNS) ID VOXEL-BASED MORPHOMETRY; MIRROR-NEURON SYSTEM; AUTISM-SPECTRUM; COMMUNICATION DISORDERS; DIAGNOSTIC INTERVIEW; FUNCTIONING AUTISM; ASPERGERS-SYNDROME; PREFRONTAL CORTEX; CHILDHOOD AUTISM; BRAIN STRUCTURE AB Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with POD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with POD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8 +/- 4.2 years: Full Scale Intelligence Quotient [FSIQ] = 101.6 +/- 15.6) and 40 age-matched normal male control subjects (22.5 +/- 4.3 years: FSIQ = 109.7 +/- 7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subject's FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning POD group. The insular cortex. which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ. (C) 2010 Elsevier Inc. All rights reserved. C1 [Kosaka, Hirotaka; Ishitobi, Makoto; Matsumura, Yukiko; Takahashi, Tetsuya; Narita, Kousuke; Murata, Tetsuhito; Wada, Yuji] Univ Fukui, Dept Neuropsychiat, Fac Med Sci, Fukui 9101193, Japan. [Kosaka, Hirotaka; Okazawa, Hidehiko; Sadato, Norihiro] Univ Fukui, Biomed Imaging Res Ctr, Fukui 9101193, Japan. [Omori, Masao] Fukui Prefectural Univ, Fac Nursing & Social Welf Sci, Fukui 9101195, Japan. [Munesue, Toshio] Kanazawa Univ, Res Ctr Child Mental Dev, Kanazawa, Ishikawa 9208641, Japan. [Narita, Kousuke] Gunma Univ, Grad Sch Med, Dept Psychiat & Human Behav, Gunma 3718511, Japan. [Saito, Daisuke N.] Univ Fukui, Res & Educ Program Life Sci, Fukui 9101193, Japan. [Uchiyama, Hitoshi] Tottori Univ, Fac Reg Sci, Dept Educ, Tottori 6900265, Japan. [Morita, Tomoyo] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Sensory Motor Integrat, Okazaki, Aichi 4448585, Japan. [Kikuchi, Mitsuru] Kanazawa Univ, Grad Sch Med Sci, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa 9208641, Japan. [Mizukami, Kimiko] Jin Ai Univ, Fac Human Studies, Dept Psychol, Fukui 9158586, Japan. [Sadato, Norihiro] Japan Sci & Technol Agcy & Technol Soc RISTEX, Kawaguchi, Saitama 3320012, Japan. [Sadato, Norihiro] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Cerebral Res, Okazaki, Aichi 4448585, Japan. RP Kosaka, H (reprint author), Univ Fukui, Dept Neuropsychiat, Fac Med Sci, Fukui 9101193, Japan. EM hirotaka@u-fukui.ac.jp FU Japan Society for the Promotion of Science [17100003, 17209040, 21791120, 21220005]; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This study was funded in part by the Fukui Prefectural Government's Grant-in-Aid for Collaboration Research Projects and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17100003, 17209040, 21791120, and 21220005). Part of this study is the result of the project "Development of biomarker candidates for social behavior", which was carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. 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Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 574VY UT WOS:000276023500002 PM 20123027 ER PT J AU Redcay, E Dodell-Feder, D Pearrow, MJ Mavros, PL Kleiner, M Gabrieli, JDE Saxe, R AF Redcay, Elizabeth Dodell-Feder, David Pearrow, Mark J. Mavros, Penelope L. Kleiner, Mario Gabrieli, John D. E. Saxe, Rebecca TI Live face-to-face interaction during fMRI: A new tool for social cognitive neuroscience SO NEUROIMAGE LA English DT Article ID SUPERIOR TEMPORAL SULCUS; JOINT ATTENTION; NEURAL BASIS; PERCEPTION; AUTISM; GAZE; INTENTIONS; OTHERS; EXPERIENCE; REGION AB Cooperative social interaction is critical for human social development and learning. Despite the importance of social interaction, previous neuroimaging studies lack two fundamental components of everyday face-to-face interactions: contingent responding and joint attention. In the current studies, functional MRI data were collected while participants interacted with a human experimenter face-to-face via live video feed as they engaged in simple cooperative games. In Experiment 1, participants engaged in a live interaction with the experimenter ("Live") or watched a video of the same interaction ("Recorded"). During the "Live" interaction, as compared to the Recorded conditions, greater activation was seen in brain regions involved in social cognition and reward, including the right temporoparietal junction (rTPJ), anterior cingulate cortex (ACC), right superior temporal sulcus (rSTS), ventral striatum, and amygdala. Experiment 2 isolated joint attention, a critical component of social interaction. Participants either followed the gaze of the live experimenter to a shared target of attention ("Joint Attention") or found the target of attention alone while the experimenter was visible but not sharing attention ("Solo Attention"). The right temporoparietal junction and right posterior STS were differentially recruited during Joint, as compared to Solo, attention. These findings suggest the rpSTS and rTPJ are key regions for both social interaction and joint attention. This method of allowing online, contingent social interactions in the scanner could open up new avenues of research in social cognitive neuroscience, both in typical and atypical populations. (C) 2010 Elsevier Inc. All rights reserved. C1 [Redcay, Elizabeth; Dodell-Feder, David; Pearrow, Mark J.; Mavros, Penelope L.; Gabrieli, John D. E.; Saxe, Rebecca] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Kleiner, Mario] Max Planck Inst Biol Cybernet, Dept Human Percept Cognit & Act, D-72076 Tubingen, Germany. RP Redcay, E (reprint author), MIT, Dept Brain & Cognit Sci, 43 Vassar St, Cambridge, MA 02139 USA. EM redcay@mit.edu RI Redcay, Elizabeth/C-7818-2011 FU Simons Foundation; National Research Service FX We thank Rebecca Cox for help with data collection, Jasmine Wang for assistance with figures, and Dr. Marina Bedny, Mike Frank, Dr. Frida Polli, Zeynep Saygin, and Todd Thompson for discussion of the analyses and manuscript. We also thank Steve Shannon, Dr. Oliver Hinds and Todd Thompson for technical advice and Dr. Christina Triantafyllou for assistance with scanner protocols. We are grateful to the Simons Foundation for funding awarded to RS for this project and for an NIH Postdoctoral National Research Service Award for support of ER. 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TI Neurological signs in the adult with fragile-X premutation SO NEUROLOGIA LA Spanish DT Article DE Fragile X permutation; Tremor/ataxia syndrome; Parkinsonism; Cognitive deficit ID TREMOR/ATAXIA SYNDROME FXTAS; PREMATURE OVARIAN FAILURE; FMR1 MESSENGER-RNA; CGG-REPEAT LENGTH; ESSENTIAL TREMOR; FULL-MUTATION; MOVEMENT-DISORDERS; PARKINSON-DISEASE; BRAIN ANATOMY; MALE CARRIERS AB Introduction: Fragile X syndrome is an inherited form of mental retardation. It results from an abnormally expanded number of trinucleotide CGG repeats. Some grandfathers of these children become forgetful, have frequent falls and other neurological problems. Researchers have found a connection between fragile X syndrome and the neurological symptoms in elderly men. This resulted in the recognition of a syndrome originally referred to as "intention tremor, parkinsonism and generalised brain atrophy in carriers of a fragile X premutation". This premutation is also associated with premature ovarian failure. Methodology: This paper reviews the literature on the neurological signs of fragile X premutation. Conclusions: Fragile X premutation is a risk for movement disorders and cognitive dysfunction and it should be considered in patients with a family history of mental retardation or autism, and particularly in those females with premature ovarian failure. (C) 2009 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved. C1 Univ Complutense, Dept Neurol & Neurocirugia, Univ Navarra Clin, Secc Dept Personolidad,Fac Educ, E-28040 Madrid, Spain. RP Cabanyes-Truffino, J (reprint author), Univ Complutense, Dept Neurol & Neurocirugia, Univ Navarra Clin, Secc Dept Personolidad,Fac Educ, E-28040 Madrid, Spain. 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Kamp-Becker, Inge Remschmidt, Helmut Konrad, Kerstin TI Coherent motion processing in autism spectrum disorder (ASD): An fMRI study SO NEUROPSYCHOLOGIA LA English DT Article DE Autism; Functional MRI; Visual; Motion perception ID HIGH-FUNCTIONING AUTISM; VISUAL-MOTION; CYTOARCHITECTONIC MAPS; HUMAN BRAIN; PERCEPTION; CHILDREN; FORM; PERFORMANCE; TASK; UNDERCONNECTIVITY AB A deficit in global motion processing caused by a specific dysfunction of the visual dorsal pathway has been suggested to underlie perceptual abnormalities in subjects with autism spectrum disorders (ASD). However, the neural mechanisms associated with abnormal motion processing in ASD remain poorly understood. We investigated brain responses related to the detection of coherent and random motion in 15 male subjects with ASD and 15 age- and IQ-matched healthy controls (aged 13-19 years) using event-related functional magnetic resonance imaging (fMRI). Behaviorally, no significant group differences were observed between subjects with ASD and controls. Neurally, subjects with ASD showed increased brain activation in the left primary visual cortex across all conditions compared with controls. A significant interaction effect between group and condition was observed in the right superior parietal cortex resulting from increased neural activity in the coherent compared with the random motion conditions only in the control group. In addition, neural activity in area V5 was not differentially modulated by specific motion conditions in subjects with ASD. Functional connectivity analyses revealed positive correlations between the primary visual cortex and area V5 within both hemispheres, but no significant between-group differences in functional connectivity patterns along the dorsal stream. The data suggest that motion processing in ASD results in deviant activations in both the lower and higher processing stages of the dorsal pathway. This might reflect differences in the perception of visual stimuli in ASD, which possibly result in impaired integration of motion signals. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Brieber, Sarah; Konrad, Kerstin] Univ Hosp RWTH Aachen, Child Neuropsychol Sect, Dept Child & Adolescent Psychiat & Psychotherapy, D-52074 Aachen, Germany. [Brieber, Sarah; Fink, Gereon R.] Res Ctr Juelich, Inst Neurosci & Med INM 3, Cognit Neurol Sect, Julich, Germany. [Fink, Gereon R.] Univ Hosp Cologne, Dept Neurol, Cologne, Germany. [Kamp-Becker, Inge; Remschmidt, Helmut] Univ Marburg, Dept Child & Adolescent Psychiat, D-35032 Marburg, Germany. RP Konrad, K (reprint author), Univ Hosp RWTH Aachen, Child Neuropsychol Sect, Dept Child & Adolescent Psychiat & Psychotherapy, D-52074 Aachen, Germany. EM kkonrad@ukaachen.de RI Konrad, Kerstin/H-7747-2013; Fink, Gereon/E-1616-2012 OI Konrad, Kerstin/0000-0001-9039-2615; Fink, Gereon/0000-0002-8230-1856 FU AstraZeneca; Eli Lilly; Novartis; Janssen Cilag; Interdisciplinary Centre for Clinical Research [IZKF N68a] FX Dr. Herpertz-Dahlmann is a consultant for Eli Lilly and has received industry research funding from AstraZeneca, Eli Lilly, Novartis, and Janssen Cilag. The other authors declare that no conflicts of interest exist.We are grateful to all our volunteers and our colleagues at the Institute of Neuroscience and Biophysics, Department of Medicine, Research Center Juelich. Furthermore we wish to thank Andre Knops for his support in programming the experiment and Ralph Weidner for his helpful comments on an earlier version of the manuscript. This study was supported by a grant to K.K. and G.R.F. by the Interdisciplinary Centre for Clinical Research (IZKF N68a). 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Bowman, Lindsay C. Sabbagh, Mark A. TI Dopaminergic functioning and preschoolers' theory of mind SO NEUROPSYCHOLOGIA LA English DT Article DE Theory of mind; Executive functioning; Dopamine; Developmental neuropsychology; Social neuroscience ID SPONTANEOUS EYEBLINK RATE; FALSE-BELIEF; BLINK RATE; EXECUTIVE FUNCTION; PREFRONTAL CORTEX; COGNITIVE CONTROL; CHILDREN; SCHIZOPHRENIA; DISORDER; BRAIN AB Representational theory of mind (RTM) development follows a universal developmental timetable whereby major advances in reasoning about mental representations occur between the ages of 3 and 5 years old. This progression appears to be only absent in the case of specific neurodevelopmental impairments, such as autism. Taken together, this suggests that neuromaturational factors may play a role in RTM development. Recent EEG work has shown that one neuromaturational factor pacing this universal developmental timetable is the functional maturation of medial prefrontal cortex. The neurotransmitter dopamine (DA) is thought to play a crucial role in typical frontal lobe development. Therefore, the goal of the present study was to investigate the role that DA may play in RIM development. Ninety-one 48-62-month olds were given a battery of RIM tasks along with EEG measurement. EEG recordings were analyzed for eyeblinks, a reliable indicator of DA functioning, and we calculated their average eyeblinks per minute (EBR). Regression analyses showed that EBR was associated with RIM after controlling for children's performance on a Stroop-like measure, language ability, gender, and age. These findings provide evidence that DA functioning is associated with RTM in the preschool years, and are discussed with respect to how DA might provide a mechanism that helps to account for both neurobiological and experiential factors that are known to affect the timetable of preschoolers' RIM development. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Sabbagh, Mark A.] Queens Univ, Dept Psychol, Kingston, ON K7L 3L3, Canada. [Bowman, Lindsay C.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Sabbagh, MA (reprint author), Queens Univ, Dept Psychol, 62 Arch St, Kingston, ON K7L 3L3, Canada. EM sabbagh@queensu.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) FX This research was supported by a Alexander Graham Bell Graduate Fellowship from the Natural Sciences and Engineering Research Council of Canada (NSERC) to Lackner, and by an NSERC Discovery Grant to Sabbagh. We thank Lyndsay Evraire, Jennie Ito, and Tracy Ma for their assistance with data collection and coding. We also thank Rick Beninger and Tom Hollenstein for helpful discussions of the work. 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Hayek, Joseph TI Silent increase of urinary ethylmalonic acid is an indicator of nonspecific brain dysfunction SO NMR IN BIOMEDICINE LA English DT Article DE autism; CNS dysfunction; ethylmalonic acid; excretion; mental delay; proton nuclear magnetic resonance; spectroscopy; urine ID DEHYDROGENASE SCAD DEFICIENCY; CHAIN ACYL-COENZYME; DISORDERS; METABOLISM; CHILDREN; CRITERIA; DISEASE; GENE AB Our aim was to compare urinary ethylmalonic acid (EMA) levels in subjects who had no apparent clinical reason to have increased levels of this substance but were suffering from non-specific CNS impairment, and healthy controls. Urinary EMA concentrations detected by (1)H-NMR spectroscopy were studied in 130 subjects with CNS impairment of unknown origin (with no definite diagnosis, no specific symptoms or signs, and normal common biochemical and metabolic screening results) and 130 age- and sex-matched healthy subjects. EMA levels exceeding two standard deviations (SD) above normal (i.e. 8.1 mmol/molCn) were found in a subgroup of CNS-impaired patients and healthy controls. EMA levels exceeding 2 SD above normal were fourfold prevalent in the urine of patients with non-specific CNS impairment compared to from the EMA levels in healthy controls. Moreover, we found that the level exceeding > 8.1 mmol/molCn (i.e. > + 2 SD) had sufficient discrimination accuracy in identifying subjects with non-specific CNS impairment; the level exceeding 12 mmol/molCn (i.e. > + 6 SD) reaches suitable accuracy (i.e. 100% specificity and 78.6% sensitivity). These observations are of importance, as we found that subtle increases in urinary EMA levels are frequent in patients with non-specific CNS impairment. The reasons for this association remain unknown. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Zannolli, Raffaella; Buoni, Sabrina; De Nicola, Anna; Orsi, Alessandra; Strambi, Mirella; Hayek, Joseph] Azienda Osped Univ Senese, Child Neurol & Psychiat Unit, Policlin Le Scotte, Siena, Italy. [Tassini, Maria; Wevers, Ron A.] Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol, NL-6525 ED Nijmegen, Netherlands. [Tassini, Maria; Vivi, Antonio] Univ Siena, NMR Ctr, I-53100 Siena, Italy. [Betti, Gianni] Univ Siena, Dept Quantitat Methods, I-53100 Siena, Italy. [De Felice, Claudio] Azienda Osped Univ Senese, Neonatal Intens Care Unit, Policlin Le Scotte, Siena, Italy. [Varetti, Maria Concetta; Ferrara, Francesco; Messina, Mario] Azienda Osped Univ Senese, Dept Pediat Surg, Policlin Le Scotte, Siena, Italy. [Giannini, Cosimo; Mohn, Angelika; Chiarelli, Francesco] Univ G dAnnunzio, Dept Pediat, Chieti, Italy. [Liberati, Marco] Univ G dAnnunzio, Dept Obstet & Gynecol, Chieti, Italy. [Funghini, Silvia] Meyer Hosp, Azienda Osped Univ, Florence, Italy. RP Zannolli, R (reprint author), Azienda Osped Univ Senese, Child Neurol & Psychiat Unit, Policlin Le Scotte, Siena, Italy. 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PD MAY PY 2010 VL 23 IS 4 BP 353 EP 358 DI 10.1002/nbm.1468 PG 6 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 594HA UT WOS:000277525800003 PM 20187168 ER PT J AU Hallerod, SLH Larson, T Stahlberg, O Carlstrom, E Gillberg, C Anckarsater, H Rastam, M Lichtenstein, P Gillberg, C AF Hallerod, Sara Lina Hansson Larson, Tomas Stahlberg, Ola Carlstrom, Eva Gillberg, Carina Anckarsater, Henrik Rastam, Maria Lichtenstein, Paul Gillberg, Christopher TI The Autism-Tics, AD/HD and other Comorbidities (A-TAC) telephone interview: Convergence with the Child Behavior Checklist (CBCL) SO NORDIC JOURNAL OF PSYCHIATRY LA English DT Article DE AD/HD; Autism; Child psychiatry; Screening; Validity ID ASPERGER-SYNDROME; DISORDER; DIAGNOSES; TWIN; PSYCHOPATHOLOGY; POPULATION; PREVALENCE; DEPRESSION; PHENOTYPE; ANXIETY AB Objective: To compare telephone interview screening for child psychiatric/neuropsychiatric disorders using the inventory of Autism-Tics, Attention deficit/hyperactivity disorder (AD/HD) and other Comorbidities (A-TAC) with results from the Child Behavior Checklist (CBCL). 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Neurol. PD MAY PY 2010 VL 42 IS 5 BP 309 EP 314 DI 10.1016/j.pediatrneurol.2009.10.009 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 591SR UT WOS:000277325000001 PM 20399382 ER PT J AU McCabe, ERB AF McCabe, Edward R. B. TI Nanopediatrics: Enabling Personalized Medicine for Children SO PEDIATRIC RESEARCH LA English DT Review ID RARE GENETIC-DISEASES; COPY-NUMBER-VARIATION; VAULT NANOPARTICLES; GENOMIC MEDICINE; DRUG-DELIVERY; SYSTEM; AUTISM; NANOMEDICINE; NANOCAPSULES; MUTATIONS AB The topic of the special series of reviews in this issue will be nanobiology and nanomedicine, with a focus on the impact of nanotechnology on children and their health; hence, the title of this collection and this introduction, Nanopediatrics: Enabling Personalized Medicine for Children. We will address what is meant when we discuss these nanodisciplines and why we developed a NanoPediatries Program at University of California, Los Angeles. We will consider the implications of these nanodisciplines for individuals and society. The nature of research, diagnosis, and screening in nanomedicine and nanopediatrics will be illustrated by selected projects in nanodiagnostics and nanotherapeutics by our group and our collaborators, and the combined use of diagnostics and therapeutics in a single nanodevice referred to as "theranostics." We will conclude this introductory review with a summary of the reasons for developing the discipline of nanopediatrics. (Pediatr Res 67: 453-457, 2010) C1 [McCabe, Edward R. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [McCabe, Edward R. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [McCabe, Edward R. B.] Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Dept Bioengn, Los Angeles, CA 90095 USA. 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Res. PD MAY PY 2010 VL 67 IS 5 BP 453 EP 457 PG 5 WC Pediatrics SC Pediatrics GA 587DJ UT WOS:000276968000001 PM 20118826 ER PT J AU Landgren, M Svensson, L Stromland, K Gronlund, MA AF Landgren, Magnus Svensson, Leif Stromland, Kerstin Gronlund, Marita Andersson TI Prenatal Alcohol Exposure and Neurodevelopmental Disorders in Children Adopted From Eastern Europe SO PEDIATRICS LA English DT Article DE fetal alcohol syndrome; autism; attention-deficit/hyperactivity disorder; developmental coordination disorder; adopted children; mental retardation; microcephalus; ocular malformations ID PRACTICAL CLINICAL APPROACH; FETAL ALCOHOL; SPECTRUM DISORDERS; ATTENTION; ABNORMALITIES; DYSFUNCTION; PREVALENCE; DIAGNOSIS; DEFICITS; SCHOOLS AB OBJECTIVES: The purposes of this investigation were to determine the frequencies of and associations between different neurodevelopmental disorders and to study the potential lasting effects of alcohol on children adopted from eastern Europe. METHODS: In a population-based, prospective, observational, multidisciplinary, cross-sectional, cohort study of 71 children adopted from eastern Europe, children were assessed 5 years after adoption, from pediatric, neuropsychological, and ophthalmologic perspectives. RESULTS: Fetal alcohol spectrum disorders, that is, fetal alcohol syndrome (FAS), partial FAS, and alcohol-related neurodevelopmental disorders, were identified for 52% of children; FAS was found for 30%, partial FAS for 14%, and alcohol-related neurodevelopmental disorders for 9%. Alcohol-related birth defects were found for 11% of children, all of whom also were diagnosed as having FAS. Mental retardation or significant cognitive impairment was found for 23% of children, autism for 9%, attention-deficit/hyperactivity disorder for 51%, and developmental coordination disorder for 34%. CONCLUSIONS: Fetal alcohol spectrum disorders and neurodevelopmental disorders were common in this long-term follow-up study of children adopted from orphanages in eastern Europe. Maternal alcohol consumption during pregnancy has long-lasting adverse effects, causing structural, behavioral, and cognitive damage despite a radically improved environment. Pediatrics 2010; 125: e1178-e1185 C1 [Landgren, Magnus; Svensson, Leif] Skaraborg Hosp, Dept Pediat, SE-54185 Skovde, Sweden. [Stromland, Kerstin; Gronlund, Marita Andersson] Univ Gothenburg, Inst Neurosci & Physiol Ophthalmol, Sahlgrenska Acad, Gothenburg, Sweden. RP Landgren, M (reprint author), Skaraborg Hosp, Dept Pediat, SE-54185 Skovde, Sweden. 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Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. 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We first remind that TSPDs consist in difficulties and peculiarities perceiving and integrating online the temporal and spatial characteritics of the incoming sensory events in the visual, auditory and proprioceptive modalities. Via the clinical manifestations exhibited by a baby at risk for autism, some self reports of autistic adults, and several experimental results, we show how the TSPDs might be central for the main behavioral, imitative, sensory-motor and cognitive disorders of at least some autistic persons. Then we present a new concept, the Multi-system Brain Disconnectivity-Dissynchrony (MBD), which represents the various degrees of under- or over- functional connectivity and hypo- or hyper-synchronization between numerous brain regions, and show that MBD might consitute the neurophysiological basis of TSPDs. 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PD MAY PY 2010 VL 7 IS 2 BP 103 EP 113 DI 10.1037/a0018791 PG 11 WC Psychology, Clinical SC Psychology GA 789QF UT WOS:000292529700005 ER PT J AU Baines, C AF Baines, Chris TI Autism in the Early Years: A Practical Guide, 2nd edition SO PSYCHOLOGIST LA English DT Book Review CR CUMINE V, 2010, AUTISM EARLY YEARS A NR 1 TC 0 Z9 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0952-8229 J9 PSYCHOLOGIST JI Psychologist PD MAY PY 2010 VL 23 IS 5 BP 403 EP 403 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 599HZ UT WOS:000277903300031 ER PT J AU Fernell, E Gillberg, C AF Fernell, Elisabeth Gillberg, Christopher TI Autism spectrum disorder diagnoses in Stockholm preschoolers SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Developmental disorders; Prevalence; Assessment ID PERVASIVE DEVELOPMENTAL DISORDERS; PREVALENCE; CHILDREN; COMMUNICATION; SUBSTITUTION; EPIDEMIOLOGY; DEFICITS; EPILEPSY AB The aims of this study were to estimate prevalence rates of children with autism spectrum disorder (ASD) diagnoses in a cohort of 6-year-old children with birth year 2002, referred to the Autism Centre for Young Children, serving the whole of Stockholm county and on the basis of the available data discuss clinical aspects of assessment, habilitation and follow-up. Records of 142 of a total of 147 (123 boys and 24 girls) identified children with ASD diagnoses were scrutinised with respect to type of diagnosis, cognitive level, other developmental disorders and medical/neurological disorders. The overall prevalence of such disorders was 6.2/1000(95% confidence interval 5.2-7.2/1000). The rates of learning disability/mental retardation, developmental delay without a specified cognitive level and normal intelligence constituted about one third, respectively. AS and atypical autism tended to be diagnosed more often at age 5-6 years while AD with learning disability/mental retardation was more often diagnosed at age 3-4 years. The awareness of ASDs has resulted in increasing numbers of children being diagnosed at young ages. We conclude that it is important to take into account these children's broader developmental profiles, need for repeated assessment of cognitive functions and follow-up over time and also the requirement for medical/neurological consideration and work-up. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Fernell, Elisabeth] Autism Ctr Young Children Handicap & Habilitat, S-10462 Stockholm, Sweden. [Fernell, Elisabeth] Karolinska Univ Hosp, Stockholm, Sweden. [Fernell, Elisabeth] FoU Ctr Skovde, Skovde, Sweden. [Gillberg, Christopher] Sahlgrens Acad, Inst Neurosci & Physiol Child & Adolescent Psychi, Gothenburg, Sweden. RP Fernell, E (reprint author), Autism Ctr Young Children Handicap & Habilitat, Box 170 56, S-10462 Stockholm, Sweden. 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Dev. Disabil. PD MAY-JUN PY 2010 VL 31 IS 3 BP 680 EP 685 DI 10.1016/j.ridd.2010.01.007 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400007 PM 20149593 ER PT J AU Gennaro, L Russo, L Losito, L Zaccaria, A De Rinaldis, M Trabacca, A AF Gennaro, Leonarda Russo, Luigi Losito, Luciana Zaccaria, Alessia De Rinaldis, Marta Trabacca, Antonio TI Movement disorders in a twins pair: A casual expression or genetic determination? SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Movement disorders; Stereotypy; Children; Mental retardation; Heritability; Twin method ID SELF-INJURIOUS-BEHAVIOR; MONOZYGOTIC TWINS; MOTOR STEREOTYPIES; BRAIN-DEVELOPMENT; RETT SYNDROME; CHILDREN; AUTISM; CONNECTIVITY; SEVERITY AB A twin study is an excellent means of assessing the contribution of heritability to motor behaviour. We present a movement video-analysis of a monozygotic twins pair with a motor repertoire which is almost totally constituted by persistent and subcontinuous motor stereotypies. Purpose: The specific aim of this study is to verify the heritable quantum of motor behaviour and to determine which among the motor patterns we analysed are more likely to be conditioned by inheritance. Methods: Stereotyped movements were videotaped in two standardized sessions: at rest and in relation to preordained sensory stimulations. We estimated the concordance index (Cl) between the observers to evaluate the reliability of the observations. The validity was accepted as being Cl > 0.80. Results: The results showed a very high concordance rate (>90%) for all the stereotypies analysed. An almost superimposable trend of the stereotyped movements was found both at rest and in relation to the sensory stimulations. Conclusions: Such strong data suggest that genetic factors have a primary influence on all the movement disorders analysed. This study contributes to a better understanding of the complex relationships between genes and functions. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Gennaro, Leonarda; Russo, Luigi; Losito, Luciana; Zaccaria, Alessia; De Rinaldis, Marta; Trabacca, Antonio] La Nostra Famiglia Assoc, E Medea Sci Inst, IRCCS, Unit Neurorehabil Dev Neurol & Funct Rehabil 1, I-72017 Ostuni, Brindisi, Italy. RP Trabacca, A (reprint author), La Nostra Famiglia Assoc, E Medea Sci Inst, IRCCS, Unit Neurorehabil Dev Neurol & Funct Rehabil 1, Via Colli 5-7, I-72017 Ostuni, Brindisi, Italy. 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Dev. Disabil. PD MAY-JUN PY 2010 VL 31 IS 3 BP 692 EP 697 DI 10.1016/j.ridd.2010.01.009 PG 6 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400009 PM 20153949 ER PT J AU Oeseburg, B Jansen, DEMC Dijkstra, GJ Groothoff, JW Reijneveld, SA AF Oeseburg, B. Jansen, D. E. M. C. Dijkstra, G. J. Groothoff, J. W. Reijneveld, S. A. TI Prevalence of chronic diseases in adolescents with intellectual disability SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Mental retardation; Chronic diseases; Adolescents; Epidemiology ID SEVERE MENTAL-RETARDATION; PSYCHIATRIC-DISORDERS; DEVELOPMENTAL DELAY; VISUAL DYSFUNCTIONS; OCULAR DISORDERS; HEALTH-PROBLEMS; BIRTH-DEFECTS; YOUNG-PEOPLE; CHILDREN; AUTISM AB Valid community-based data on the prevalence of chronic diseases in adolescents (12-18 years) with intellectual disability (ID-adolescents) are scarce. The aim of this study was to assess the prevalence rates and the nature of chronic diseases in a population of ID-adolescents and to compare them with the rates among adolescents in the general population. Therefore, we obtained data on 1083 ID-adolescents attending secondary schools, day care centers or living in residential centers fully covering one region of the Netherlands. Parents of the adolescents completed a questionnaire about the occurrence of chronic diseases in their child during the previous 12 months and about background characteristics. The questionnaire was derived from the Dutch National Permanent Survey on Living Conditions questionnaire periodically administered in a representative population sample (n approximate to 10,000). Prevalence rates of chronic diseases in ID-adolescents were compared with those in adolescents in the Dutch general population. Among ID-adolescents, high prevalence rates of a wide range of chronic diseases were found. The five most prevalent were: ADHD (21.1%), PDD-NOS (14.0%), dyslexia (13.9%), migraine or chronic headache (12.7%), and autistic disorder (10.9%). These prevalence rates were all higher (p<0.05) than among adolescents in the general population. Of all ID-adolescents, 62.9% was reported to have at least one chronic disease. The burden of chronic diseases among ID-adolescents is very high, showing a high need for adequate care. These high prevalence rates should alert policymakers and clinicians regarding the widespread of chronic diseases among ID-adolescents. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Oeseburg, B.; Jansen, D. E. M. C.; Dijkstra, G. J.; Groothoff, J. W.; Reijneveld, S. A.] Univ Groningen, Dept Hlth Sci, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands. [Oeseburg, B.; Jansen, D. E. M. C.; Dijkstra, G. J.; Groothoff, J. W.; Reijneveld, S. A.] Univ Groningen, Grad Sch Hlth Res, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands. [Oeseburg, B.] Univ Med Ctr Groningen, Wenckebach Inst, Sch Nursing & Hlth, NL-9713 AV Groningen, Netherlands. [Jansen, D. E. M. C.] Univ Groningen, Dept Sociol, Fac Behav & Social Sci, NL-9700 RB Groningen, Netherlands. RP Oeseburg, B (reprint author), Univ Groningen, Dept Hlth Sci, Univ Med Ctr Groningen, POB 30-001, NL-9700 RB Groningen, Netherlands. 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Dev. Disabil. PD MAY-JUN PY 2010 VL 31 IS 3 BP 698 EP 704 DI 10.1016/j.ridd.2010.01.011 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400010 PM 20188511 ER PT J AU Bhaumik, S Tyrer, F Barrett, M Tin, N McGrother, CW Kiani, R AF Bhaumik, Sabyasachi Tyrer, Freya Barrett, Mary Tin, Nyunt McGrother, Catherine W. Kiani, Reza TI The relationship between carers' report of autistic traits and clinical diagnoses of autism spectrum disorders in adults with intellectual disability SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autistic traits; Autism spectrum disorders; Autism; Asperger syndrome; Intellectual disability; Learning disability ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; LEARNING-DISABILITIES; PREVALENCE; CHILDREN; PEOPLE; HARMONIZATION; EPIDEMIOLOGY; ADOLESCENTS; POPULATION AB It is often difficult to determine the triad of impairments and whether autistic features are the consequence of intellectual impairment or autism spectrum disorders in people with intellectual disability (ID). The aim of the current study was to investigate the relationship between carer-reported autistic traits and independent diagnoses of autism spectrum disorders (ASD). Data were collected on carers' subjective report of autistic traits and clinical diagnoses of ASD. Of 1145 adults with ID identified, 220 (19%) individuals had a diagnosis of ASD, and 778 (68%) individuals had at least one autistic trait. Optimal sensitivity and specificity were achieved with two or more autistic traits (sensitivity 63%; specificity 79%) and the positive predictive value increased substantially as the number of autistic traits increased. However, a significant proportion of individuals with ID who did not have a diagnosis of ASD also displayed autistic traits. Our findings suggest that in the absence of other measures, the presence of autistic traits can serve as a useful proxy measure for ASD in research (and/or clinical settings). However, although information on autistic traits may help healthcare practitioners to identify people with possible ASD, it cannot be used alone to make a formal diagnosis. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Tyrer, Freya; McGrother, Catherine W.] Univ Leicester, Dept Hlth Sci, Leicester LE1 6TP, Leics, England. [Bhaumik, Sabyasachi; Barrett, Mary; Tin, Nyunt; Kiani, Reza] Leicestershire Partnership NHS Trust, Leicestershire Learning Disabil Serv, Leicester, Leics, England. RP Tyrer, F (reprint author), Univ Leicester, Dept Hlth Sci, 22-28 Princess Rd W, Leicester LE1 6TP, Leics, England. 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Dev. Disabil. PD MAY-JUN PY 2010 VL 31 IS 3 BP 705 EP 712 DI 10.1016/j.ridd.2010.01.012 PG 8 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400011 PM 20188512 ER PT J AU Kirby, A Woodward, A Jackson, S Wang, Y Crawford, MA AF Kirby, A. Woodward, A. Jackson, S. Wang, Y. Crawford, M. A. TI Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Omega-3; Children; Behaviour; Cognition; Cheek cells ID DEFICIT-HYPERACTIVITY-DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOCOSAHEXAENOIC ACID; PRESCHOOL-CHILDREN; AUTISTIC SPECTRUM; CONTROLLED-TRIAL; MOTOR-SKILLS; SUPPLEMENTATION; CHILDHOOD; SYMPTOMS AB Increasing interest in the role of omega-3 fatty acids in relation to neurodevelopmental disorders (e.g. ADHD, dyslexia, autism) has occurred as a consequence of some international studies highlighting this link. In particular, some studies have shown that children with ADHD may have lower concentrations of polyunsaturated fatty acids (PUFAs), particularly omega-3, in their red blood cells and plasma, and that supplementation with omega-3 fatty acids may alleviate behavioural symptoms in this population. However, in order to compare levels it seems appropriate to establish fatty acid levels in a mainstream school aged population and if levels relate to learning and behaviour. To date no study has established this. For this study, cheek cell samples from 411 typically developing school children were collected and analysed for PUFA content, in order to establish the range in this population. In addition, measures of general classroom attention and behaviour were assessed in these children by teachers and parents. Cognitive performance tests were also administered in order to explore whether an association between behaviour and/or cognitive performance and PUFA levels exists. Relationships between PUFA levels and socio-economic status were also explored. Measures of reading, spelling and intelligence did not show any association with PUFA levels, but some associations were noted with the level of omega-3 fatty acids and teacher and parental reports of behaviour, with some evidence that higher omega-3 levels were associated with decreased levels of inattention, hyperactivity, emotional and conduct difficulties and increased levels of prosocial behaviour. These findings are discussed in relation to previous findings from omega-3 supplementation studies with children. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Kirby, A.; Woodward, A.; Jackson, S.] Univ Wales, Dyscovery Ctr, Newport NP20 5DA, Wales. [Wang, Y.; Crawford, M. A.] London Metropolitan Univ, Inst Brain Chem & Human Nutr, London N7 8DB, England. RP Jackson, S (reprint author), Univ Wales, Dyscovery Ctr, Allt Yr Yn Campus, Newport NP20 5DA, Wales. 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PD MAY-JUN PY 2010 VL 31 IS 3 BP 731 EP 742 DI 10.1016/j.ridd.2010.01.015 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400014 PM 20172688 ER PT J AU Smith, KRM Matson, JL AF Smith, Kimberly R. M. Matson, Johnny L. TI Psychopathology: Differences among adults with intellectually disabled, comorbid autism spectrum disorders and epilepsy SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Psychopathology; Assessment; Intellectual disability; Autism; Epilepsy ID MENTAL-RETARDATION; PSYCHIATRIC-DISORDERS; DUAL DIAGNOSIS; DISABILITY; PEOPLE; PREVALENCE; DEPRESSION; BEHAVIOR AB The goal of this study was to systematically examine group differences among adults with intellectual disabilities (ID), comorbid autism spectrum disorders (ASD), and epilepsy through a detailed exploration of the characteristics that these disorders present in the area of psychopathology. Previous studies indicating that individuals with ID have comorbid ASD and epilepsy tend to stop short of addressing these disorders' impact on the full range of psychosocial issues, particularly in adult samples. Assessment of psychopathology was made with the ASD-comorbidity-adult version (ASD-CA). One hundred participants, with ID held constant, were matched and compared across four equal groups comprising 25 participants with ID, 25 participants with epilepsy, 25 participants with ASD, and 25 participants with combined ASD and epilepsy. When controlling for age, gender, race, level of ID, and hearing and visual impairments, results of the MANOVA revealed significant differences among groups, Wilks's Lambda =.76, F(15, 254)= 1.82, p <.05, eta(2) =.09. A one-way ANOVA was conducted for each of the five subscales of the ASD-CA as follow-up tests to the MANOVA. Groups differed significantly Anxiety/Repetitive Behavior subscale, F(3, 96) = 2.93, p <.05, eta(2) =.08, Irritability/Behavior excess subscale, F(3, 96) = 4.74, p <.01, eta(2) =.13, Attention/Hyperactivity subscale, F(3, 96) = 5.18, p <.01, eta(2) =.14, and Depressive Symptoms subscale, F(3, 96) = 3.73, p <.01, eta(2) = .10. Trend analysis demonstrated that individuals with ID expressing combined comorbid ASD and epilepsy were significantly more impaired than the control group (ID only) or groups containing only a single comorbid factor with ID (ASD or epilepsy only). Implications of these findings elucidate the nature of these disorders and their influence on patient care and management. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Smith, Kimberly R. M.] Louisiana State Univ, Dept Psychol, Beatrice State Dev Ctr, Beatrice, NE 68310 USA. RP Smith, KRM (reprint author), Louisiana State Univ, Dept Psychol, Beatrice State Dev Ctr, Beatrice, NE 68310 USA. 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PD MAY-JUN PY 2010 VL 31 IS 3 BP 743 EP 749 DI 10.1016/j.ridd.2010.01.016 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400015 PM 20206472 ER PT J AU Fernell, E Hedvall, A Norrelgen, F Eriksson, M Hoglund-Carlsson, L Barnevik-Olsson, M Svensson, L Holm, A Westerlund, J Gillberg, C AF Fernell, Elisabeth Hedvall, Asa Norrelgen, Fritiof Eriksson, Mats Hoglund-Carlsson, Lotta Barnevik-Olsson, Martina Svensson, Liselotte Holm, Annette Westerlund, Joakim Gillberg, Christopher TI Developmental profiles in preschool children with autism spectrum disorders referred for intervention SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism spectrum disorder; Developmental disorder; Cognitive function; Language delay ID INTENSIVE BEHAVIORAL INTERVENTION; SWEDISH CHILDREN; COMMUNICATIVE DEVELOPMENT; ATTENTION; DEFICITS; MOTOR; REGRESSION; LANGUAGE; SAMPLE AB The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of "classic" autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Fernell, Elisabeth] Karolinska Univ Hosp, Autism Ctr Young Children Handicap & Habilitat &, Stockholm, Sweden. [Fernell, Elisabeth] Autism Ctr Young Children Handicap & Habilitat, Stockholm, Sweden. [Fernell, Elisabeth] FoU Ctr, Skovde, Sweden. [Fernell, Elisabeth] Skaraborgs Hosp, Unit Neurodev Disorders, Mariestad, Sweden. [Norrelgen, Fritiof; Svensson, Liselotte] Karolinska Univ Hosp, Dept Speech & Language Pathol, Stockholm, Sweden. [Hoglund-Carlsson, Lotta] Astrid Lindgren Childrens Hosp, Dept Paediat, Stockholm, Sweden. [Barnevik-Olsson, Martina] PRIMA Child & Adolescent Psychiat, Stockholm, Sweden. [Svensson, Liselotte] Karolinska Inst, Div Speech & Language Pathol, CLINTEC, S-10401 Stockholm, Sweden. [Holm, Annette] Karolinska Univ Hosp, Dept Psychol, Stockholm, Sweden. [Westerlund, Joakim] Stockholm Univ, Dept Psychol, Stockholm, Sweden. [Gillberg, Christopher] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol Child & Adolescent Psychi, Gothenburg, Sweden. RP Fernell, E (reprint author), Karolinska Univ Hosp, Autism Ctr Young Children Handicap & Habilitat &, Stockholm, Sweden. 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Dev. Disabil. PD MAY-JUN PY 2010 VL 31 IS 3 BP 790 EP 799 DI 10.1016/j.ridd.2010.02.003 PG 10 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400021 PM 20207104 ER PT J AU Al Anbar, NN Dardennes, RM Prado-Netto, A Kaye, K Contejean, Y AF Al Anbar, Nebal N. Dardennes, Roland M. Prado-Netto, Arthur Kaye, Kelley Contejean, Yves TI Treatment choices in autism spectrum disorder: The role of parental illness perceptions SO RESEARCH IN DEVELOPMENTAL DISABILITIES LA English DT Article DE Autism; Parents; Illness beliefs; Health behavior; IPQ-R ID QUESTIONNAIRE IPQ-R; ALTERNATIVE MEDICINE; SELF-REGULATION; CHILDREN; COMPLEMENTARY; MEDICATION; MANAGEMENT; BELIEFS AB A cross-sectional design was employed. Parents of a child with Autism Spectrum Disorder (ASH) were asked to complete a modified version of the Revised Illness-Perception Questionnaire (IPQ-RA) and answer questions about information-seeking activities and treatments used. Internal consistency, construct validity, and factor structure were assessed. Multivariate logistic regressions were performed. Eighty-nine parents having a child with ASD took part in the study. Five subscales of the IPQ-R were replicated. Causes were split into personal, external and hereditary factors. The most highly rated main cause was a genetic cause. Perception of seriousness of the disease was associated with the use of educative methods and unpredictable course of disorder associated with drug use. A higher sense of personal control was associated with reduced use of nutritional or pharmaceutical treatments. Attendance to training programs was associated with higher hereditary beliefs and lower perception of cyclical timeline. The IPQ-RA captures components of representations of autism and provides a reliable mean for exploring illness concept in parents of a child with ASH. Some illness dimensions may prevent parents from having the opportunity to modify their concept of autism. Such measure may be useful for assessing the modification of potentially malleable beliefs with psychoeducational interventions. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Al Anbar, Nebal N.; Prado-Netto, Arthur] Univ Paris 05, Fac Psychol, Grad Sch 261, F-92774 Boulogne, France. [Dardennes, Roland M.] Fac Med Paris Descartes, F-75270 Paris 06, France. [Dardennes, Roland M.; Kaye, Kelley; Contejean, Yves] Hosp St Anne, F-75014 Paris, France. [Dardennes, Roland M.] INSERM, Ctr Psychiat & Neurosci, UMR 894, F-75014 Paris, France. RP Dardennes, RM (reprint author), Serv Pr ROUILLON, Clin Malad Mentales & Encephale, 100 Rue Sante, F-75674 Paris 14, France. 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PD MAY-JUN PY 2010 VL 31 IS 3 BP 817 EP 828 DI 10.1016/j.ridd.2010.02.007 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 583GT UT WOS:000276662400025 PM 20299185 ER PT J AU Martinez-Levy, GA Vasquez-Medina, JA Cruz-Fuentes, CS AF Ariadna Martinez-Levy, Gabriela Alberto Vasquez-Medina, Josue Sabas Cruz-Fuentes, Carlos TI Genome diversity of the Mexican Mestizo population: Scopes and perspectives for develop Genetic Psychiatric Research SO SALUD MENTAL LA Spanish DT Article DE Genome; HapMap; Mexican; polymorphisms; psychiatry; complex disorders ID WIDE ASSOCIATION; MENTAL-HEALTH; DISORDERS; DISEASES; ENDOPHENOTYPES; PROJECT; PANEL; ERA; DSM AB A few months ago the paper entitled "Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico" by Solezzi et at was published in the Proceedings of the Notional Academy of Medicine USA Beyond its genuine scientific merits, we consider important to comment and discuss it, as some of their scopes and implications have caused not only D wide interest but also some concern in the scientific community and in society as a whole. We focused particularly in the possible impact that it could have in the development of psychiatric genetics in Mexico and Latin America. Firstly, a brief recapitulation of the published work is showed, and its principal data are discussed on the ground of the specialized literature What is the background of this study and why it is important to develop a HapMap of the Mexican population(2) It is well known that most of the complex diseases, as is the case for psychiatric conditions, have an important genetic associated component. It is expected that the identification of these genetic factors will be of the most importance in the understanding of etiology, diagnosis, prognosis and therapeutic improvement for psychiatric medicine The information provided by the collection of millions of single nucleotide polymorphisms (SNPs) has been used to develop the so-called international haplotype map (HapMap) Protect. The human haplotype blocks catalog allows an important reduction in the number of SNPs that are necessary to perform linkage and genetic association studies, mainly those of the Genome Wide Association Studies (GWAS) category However, it is recognized that the frequency of these polymorphisrns differs significantly among ethnic groups, so the data published by Solezzi et at are aimed to develop a HapMap particularly oriented to the Mexican mestizo population This information will be of outstanding importance in studies including Mexican subtracts in order to select the most informative group of SNPs and also to control for possible population stratification flaws. However, achievement of these objectives will need much more work to be done, as for example should it be mandatory to analyze a greater number of polymorphisms, develop genome re-sequenciation protects and include other Mexican subpopulations in the analysis How this results will help psychiatric genetics in Mexico(2) As noted above, there is substantial evidence that genetics plays an important influence in the phenotypic expression of mental disorders, however, the effort to identify the specific genetic variants associated with psychiatric conditions has not been very successful Although multiple reasons could be invoked related to this limited success, here we focus in two specific topics The first one is related to the candidate gene approach in genetic association studies, in which researchers based on a logic scientific hypothesis evaluate specific genetic variants putatively related to the disorder of interest e the candidate genes hypothesis) However, the possibility of identification of the associated genetic risk variants is importantly reduced, as the knowledge about complex disorders and particularly those related with mental problems is mostly incomplete. The continuous advances in neurobiological and psychological knowledge provides hope for future improvement and the generation of new ideas On the other hand, the alternative and technically feasible approach to analyze simultaneously hundred of thousands, even millions, of genetic variants all along the human genome with no regarding of a priori candidate genes (as in the Genome Wide Association Studies, GWAS), has reached the psychiatric genetics arena In this regard, it is worth noting that several published studies of GWAS and psychiatric disorders have recently appeared and have contributed to develop important clues Particularly interesting are those pointing out to the until recently unexplored role of Copy Number Variants (CNVs) associated to some forms of autism and schizophrenia It is worth noting that most GWAS are based in the common disorder-common variant hypothesis (where genetic polymorphisms studied have a frequency >5% in the general population) However, the alternative view of the common disorder-rare variant hypothesis have also been proposed As most of the rare SNPs have not been identified in the current effort of the HapMap protect, a re-sequenciation analysis of human genomes of particular ethnic groups seems to be mandatory The other relevant issue is related to the following question Are current psychiatric diagnostic categories proper phenotypes for the study of genetic aspects associated with mental disorders(2) Diagnosis in psychiatry is based mainly in the identification and interpretation from clinicians of the patient 's cardinal symptoms However, overlapping of symptoms between nosological categories, comorbidity and changes in natural history of the disorder associated or not to therapeuthical improvements are issues hampering efforts in psychiatric genetics. At this point it is important to recall that psychiatric diagnostic categories have evolved along the last four or five decades after intense discussion among experts However, even recognizing the clinical virtues of current consensus (integrated for example in the DSM-IV-R), it is clear that is still a pending issue, awaiting the most recent contributions from different areas of knowledge, including genetics Moreover, unlike other complex disorders like hypertension or diabetes, where use of clinical and relevant phenotypes, such as blood pressure and levels of blood glucose, can increase the power of genetic analysis, in mental disorders this kind of quantitative phenotypes are rare or unknown, which restrains the process to find genetic variants associated with psychiatric disorders, independently of the study design and the technology of analysis In brief, in countries as ours, composed mainly by mestizo population, is of the utmost importance for molecular genetics studies to obtain specific information about its genetic composition In this sense, the National Institute of Genomic Medicine has made an important contribution, however, and as correctly stated by Solezzi et al., "much more work needs to be done. We argue that the even the deepest knowledge in genetic variation or use of state-of-the-art technology is not enough to boost the development of psychiatric genetics research Re-evaluation of current clinical phenotypes and/or identification of new and relevant intermediate or endo- phenotypes in psychiatry are no less important. Additionally, it will be necessary to integrate to the complex equation of the genetics of complex disorders the seminal role of "environment. In this respect we are strong advocates of multidisciplinary research as the clue for better understanding the etiology of mental disorders Finally, we hope this work will help to elucidate some of the questions and concerns originated from the published article by Silva-Solezzi et al C1 [Ariadna Martinez-Levy, Gabriela; Sabas Cruz-Fuentes, Carlos] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Subdirecc Invest Clin, Dept Genet, Mexico City 14370, DF, Mexico. RP Cruz-Fuentes, CS (reprint author), Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Subdirecc Invest Clin, Dept Genet, Calz Mexico Xochimilco 101, Mexico City 14370, DF, Mexico. 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PD MAY-JUN PY 2010 VL 33 IS 3 BP 273 EP 280 PG 8 WC Psychiatry SC Psychiatry GA 627MV UT WOS:000280044800008 ER PT J AU Leitman, DI Laukka, P Juslin, PN Saccente, E Butler, P Javitt, DC AF Leitman, David I. Laukka, Petri Juslin, Patrik N. Saccente, Erica Butler, Pamela Javitt, Daniel C. TI Getting the Cue: Sensory Contributions to Auditory Emotion Recognition Impairments in Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; social cognition; prosody; emotion; speech; multidimensional scaling ID DIFFERENTIAL DEFICIT; MISMATCH NEGATIVITY; PERCEPTION; DYSFUNCTION; EXPRESSION; FACES; 1ST-EPISODE; PERFORMANCE; INTONATION; AUTISM AB Individuals with schizophrenia show reliable deficits in the ability to recognize emotions from vocal expressions. Here, we examined emotion recognition ability in 23 schizophrenia patients relative to 17 healthy controls using a stimulus battery with well-characterized acoustic features. We further evaluated performance deficits relative to ancillary assessments of underlying pitch perception abilities. As predicted, patients showed reduced emotion recognition ability across a range of emotions, which correlated with impaired basic tone matching abilities. Emotion identification deficits were strongly related to pitch-based acoustic cues such as mean and variability of fundamental frequency. Whereas healthy subjects' performance varied as a function of the relative presence or absence of these cues, with higher cue levels leading to enhanced performance, schizophrenia patients showed significantly less variation in performance as a function of cue level. In contrast to pitch-based cues, both groups showed equivalent variation in performance as a function of intensity-based cues. Finally, patients were less able than controls to differentiate between expressions with high and low emotion intensity, and this deficit was also correlated with impaired tone matching ability. Both emotion identification and intensity rating deficits were unrelated to valence of intended emotions. Deficits in both auditory emotion identification and more basic perceptual abilities correlated with impaired functional outcome. Overall, these findings support the concept that auditory emotion identification deficits in schizophrenia reflect, at least in part, a relative inability to process critical acoustic characteristics of prosodic stimuli and that such deficits contribute to poor global outcome. C1 [Leitman, David I.; Saccente, Erica; Butler, Pamela; Javitt, Daniel C.] Nathan S Kline Inst Psychiat Res, Program Cognit Neurosci & Schizophrenia, Orangeburg, NY 10962 USA. [Leitman, David I.; Javitt, Daniel C.] CUNY City Coll, Program Cognit Neurosci, New York, NY 10031 USA. [Leitman, David I.] Univ Penn, Dept Neuropsychiat, Brain Behav Lab, Philadelphia, PA 19104 USA. [Laukka, Petri; Juslin, Patrik N.] Uppsala Univ, Dept Psychol, Uppsala, Sweden. [Butler, Pamela; Javitt, Daniel C.] NYU, Sch Med, Dept Psychiat, New York, NY USA. RP Javitt, DC (reprint author), Nathan S Kline Inst Psychiat Res, Program Cognit Neurosci & Schizophrenia, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM javitt@nki.rfmh.org RI Laukka, Petri/B-5259-2008 FU National Institute of Mental Health (NRSA) [F1-MH067339, K02 MH01439, R01 MH49334] FX FundingNational Institute of Mental Health (NRSA F1-MH067339 to D. I. L., K02 MH01439 to D.C.J., R01 MH49334 to D.C.J.). 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Bull. PD MAY PY 2010 VL 36 IS 3 BP 545 EP 556 DI 10.1093/schbul/sbn115 PG 12 WC Psychiatry SC Psychiatry GA 606RH UT WOS:000278444400016 PM 18791077 ER PT J AU Fatemi, SH AF Fatemi, S. Hossein TI Co-occurrence of neurodevelopmental genes in etiopathogenesis of autism and schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID CEREBELLAR CORTICES; EXPRESSION; PARIETAL; REELIN; BRAIN C1 [Fatemi, S. Hossein] Univ Minnesota, Sch Med, 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. RP Fatemi, SH (reprint author), Univ Minnesota, Sch Med, Dept Psychiat, 420 Delaware St SE,MMC 392, Minneapolis, MN 55455 USA. 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PD MAY PY 2010 VL 118 IS 1-3 BP 303 EP 304 DI 10.1016/j.schres.2010.01.018 PG 2 WC Psychiatry SC Psychiatry GA 603NE UT WOS:000278214500044 PM 20153953 ER PT J AU Kronk, R Bishop, EE Raspa, M Bickel, JO Mandel, DA Bailey, DB AF Kronk, Rebecca Bishop, Ellen E. Raspa, Melissa Bickel, Julie O. Mandel, Daniel A. Bailey, Donald B., Jr. TI Prevalence, Nature, and Correlates of Sleep Problems Among Children with Fragile X Syndrome Based on a Large Scale Parent Survey SO SLEEP LA English DT Article DE Sleep; Fragile X syndrome; survey ID ASSIGNING ICF CODES; DEVELOPMENTAL-DISABILITIES; INTELLECTUAL DISABILITY; SYNAPTIC PLASTICITY; ANGELMAN-SYNDROME; DISORDERS; MELATONIN; PATTERNS; AUTISM; BEHAVIOR AB Study Objectives: This study reports on current child sleep difficulties reported by parents of children with Fragile X syndrome (FXS). We address prevalence and type of sleep problems (e.g., difficulty falling asleep, frequent awakenings); type and effectiveness of medical and behavioral treatments (e.g., medication, surgery, environmental changes); and explore specific child and family characteristics (e.g., child age, child gender, co-occurring conditions) as possible predictors of child sleep difficulties. Design/Participants: This study is part of a larger survey addressing needs of families with children with FXS. This article focuses on the families who responded to the survey sleep questions, had one or more children with the full mutation FXS, and who reside in the United States. The mean age for male and female children in this group was 15 years and 16 years respectively (N = 1,295). Results: Parents reported that 32% of the children with FXS currently experience sleep difficulties; 84% of those children are reported to have >= 2 current sleep problems. Problems falling asleep and frequent night awakenings were the most frequently reported difficulties; 47% of males and 40% of females received >= 1medication to help with sleep. Children with more problematic health or behavioral characteristics had a higher likelihood of having current sleep problems. Conclusions: Our survey provides the most representative sample to date of sleep problems in children with FXS or any other neurodevelopmental disability. This large scale survey establishes a foundation for the prevalence of sleep disorders in children with FXS. C1 [Kronk, Rebecca] Univ Pittsburgh, Childrens Hosp Pittsburgh, UPMC, UCLID Ctr,Child Dev Unit,Fragile Ctr 10, Pittsburgh, PA 15201 USA. [Bishop, Ellen E.; Raspa, Melissa; Bailey, Donald B., Jr.] RTI Int, Res Triangle Pk, NC USA. [Bickel, Julie O.] Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA. [Mandel, Daniel A.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Mandel, Daniel A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP Kronk, R (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, UPMC, UCLID Ctr,Child Dev Unit,Fragile Ctr 10, 45th & Penn, Pittsburgh, PA 15201 USA. EM becky.kronk@chp.edu FU Centers for Disease Control and Prevention (CDC); Association for Prevention Teaching and Research (APTR) [U50/CCU300860, TS-1380] FX Preparation of this article was supported in part by the Centers for Disease Control and Prevention (CDC) and the Association for Prevention Teaching and Research (APTR) Cooperative Agreement No. U50/CCU300860, Project TS-1380. 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Martins, Carla Healy, Sarah Murray, Lynne TI Early Social Experience and Individual Differences in Infants' Joint Attention SO SOCIAL DEVELOPMENT LA English DT Article DE joint attention; infancy; longitudinal; maternal sensitivity ID POSTNATAL DEPRESSION SCALE; MOTHER-INFANT; COGNITIVE SKILLS; VISUAL-ATTENTION; COMMUNICATION; AUTISM; CHILDREN; INTERSUBJECTIVITY; SENSITIVITY; BEHAVIORS AB Fifty-nine healthy infants were filmed with their mothers and with a researcher at two, four, six and nine months in face-to-face play, and in toy-play at six and nine months. During toy-play at both ages, two indices of joint attention (JA)-infant bids for attention, and percent of time in shared attention-were assessed, along with other behavioural measures. Global ratings were made at all four ages of infants' and mothers' interactive style. The mothers varied in psychiatric history (e.g., half had experienced postpartum depression) and socioeconomic status, so their interactive styles were diverse. Variation in nine-month infant JA-with mother and with researcher-was predicted by variation in maternal behaviour and global ratings at six months, but not at two or four months. Concurrent adult behaviour also influenced nine-month JA, independent of infant ratings. Six-month maternal behaviours that positively predicted later JA (some of which remained important at nine months) included teaching, conjoint action on a toy, and global sensitivity. Other behaviours (e.g., entertaining) negatively predicted later JA. Findings are discussed in terms of social-learning and neurobiological accounts of JA emergence. C1 [Gaffan, Elizabeth A.] Univ Reading, Sch Psychol & Clin Language Sci, Dept Psychol, Reading RG6 6AL, Berks, England. [Martins, Carla] Univ Minho, P-4719 Braga, Portugal. RP Gaffan, EA (reprint author), Univ Reading, Sch Psychol & Clin Language Sci, Dept Psychol, Reading RG6 6AL, Berks, England. 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There is no agreement between investigators who in fact may be considered a left-handed person, about the percentage of left-handers in the population and about the etiology of left-handedness. In the scientific literature left-handedness has been related to health disorders (spine deformities, immunological disorders, migraine, neurosis, depressive psychosis, schizophrenia, insomnia, homosexuality, diabetes mellitus, arterial hypertension, sleep apnea, enuresis nocturna and Down Syndrome), developmental disorders (autism, dislexia and sttutering) and traumatism. The most reliable scientific evidences have been published about the relationship between left-handedness and spinal deformities in school children in puberty and with traumatism in general population. The controversy of other results in up-to-now investigations of health aspects of left-handedness may partly be explained by a scientific disagreement whether writing with the left hand is a sufficient criterium for left-handedness, or is it necessary to investigate other parameters for laterality assessment. Explanation of health aspects of left-handedness is dominantly based on Geschwind-Galaburda model about "anomalous" cerebral domination, as a consequence of hormonal disbalance. C1 [Milenkovic, Sanja] Univ Belgrade, Sch Med, Fak Med, Inst Hyg & Med Ecol, Belgrade 11000, Serbia. RP Milenkovic, S (reprint author), Univ Belgrade, Sch Med, Fak Med, Inst Hyg & Med Ecol, Dr Subotica 8, Belgrade 11000, Serbia. 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How can the self in autism be both 'absent' (i.e., impaired self-referential cognition), yet 'all too present' (i.e., egocentric)? In this paper, we first review evidence in support of both claims. Second, we highlight new evidence illustrating atypical function of neural systems underlying self-representation in autism. We suggest that egocentrism and impaired self-referential cognition are not independent phenomena. Instead, both egocentrism and impaired self-referential cognition in autism can be resolved as expressions of one common mechanism linked to the atypical function of neural circuitry coding for self-relevant information. We discuss how autism provides a unique window into the neurodevelopmental mechanisms enabling a critical developmental transition in self-awareness. This transition involves a dual understanding that one is similar to, yet distinct from others. The neural and cognitive basis of this developmental transition is central to understanding the development of social cognition as well as the paradox of the autistic self and its relation to social impairment in autism. (C) 2010 John Wiley & Sons, Ltd. WIREs Cogn Sci 2010 1 393-403 C1 [Lombardo, Michael V.; Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Dept Psychiat, Cambridge CB2 8AH, England. RP Lombardo, MV (reprint author), Univ Cambridge, Autism Res Ctr, Dept Psychiat, Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. 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Rev.-Cogn. Sci. PD MAY-JUN PY 2010 VL 1 IS 3 BP 393 EP 403 DI 10.1002/wcs.45 PG 11 WC Psychology, Experimental SC Psychology GA 863NT UT WOS:000298172200008 ER PT J AU Russell, PSS Daniel, A Russell, S Mammen, P Abel, JS Raj, LE Shankar, SR Thomas, N AF Russell, Paul S. S. Daniel, Anna Russell, Sushila Mammen, Priya Abel, Julie S. Raj, Lydia E. Shankar, Satya Raj Thomas, Naveen TI Diagnostic accuracy, reliability and validity of Childhood Autism Rating Scale in India SO WORLD JOURNAL OF PEDIATRICS LA English DT Article DE autism; diagnostic accuracy; India; reliability; validation ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; DSM-IV; BEHAVIOR CHECKLIST; TOKYO VERSION; CARS; ADOLESCENTS; CRITERIA; CHILDREN; PREVALENCE AB Background: Since there is no established measure for autism in India, we evaluated the diagnostic accuracy, reliability and validity of Childhood Autism Rating Scale (CARS). Methods: Children and adolescents suspected of having autism were identified from the unit's database. Scale and item level scores of CARS were collected and analyzed. Sensitivity, specificity, likelihood ratios and predictive values for various CARS cut-off scores were calculated. Test-retest reliability and inter-rater reliability of CARS were examined. The dichotomized CARS score was correlated with the ICD-10 clinical diagnosis of autism to establish the criterion validity of CARS as a measure of autism. Convergent and divergent validity was calculated. The factor structure of CARS was demonstrated by principal components analysis. Results: A CARS score of >= 33 (sensitivity = 81.4%, specificity = 78.6%; area under the curve = 81%) was suggested for diagnostic use in Indian populations. The inter-rater reliability (ICC=0.74) and test-retest reliability (ICC=0.81) for CARS were good. Besides the adequate face and content validity, CARS demonstrated good internal consistency (Cronbach's alpha=0.79) and item-total correlation. There was moderate convergent validity with Binet-Kamat Test of Intelligence or Gessell's Developmental Schedule (r=0.42; P=0.01), divergent validity (r=-0.18; P=0.4) with ADD-H Comprehensive Teacher Rating Scale, and high concordance rate with the reference standard, ICD-10 diagnosis (82.52%; Cohen's kappa=0.40, P=0.001) in classifying autism. A 5-factor structure explained 65.34% of variance. Conclusion: The CARS has strong psychometric properties and is now available for clinical and research work in India. C1 [Russell, Paul S. S.; Daniel, Anna; Russell, Sushila; Mammen, Priya; Abel, Julie S.; Raj, Lydia E.; Shankar, Satya Raj; Thomas, Naveen] Christian Med Coll & Hosp, Dept Psychiat, Autism Clin, Child & Adolescent Psychiat Unit, Vellore 632002, Tamil Nadu, India. 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It has been suggested that this function sometimes recruits emotional processes. The present fMRI study examined the neural mechanisms associated with understanding others' mental states, and the conditions that determine the recruitment of the emotional processes. The false belief paradigm, a traditional behavioral paradigm to investigate comprehension of others, was applied to an event-related fMRI analysis, allowing for the extraction of brain activity time-locked to successful understanding of others' mental states. Prominent brain activity was observed in multiple cortical regions including the medial prefrontal cortex, temporo-parietal junction, precuneus, and temporal pole. Then, correlational analyses were performed between the activations and individuals' scores of neuroticism, a personality trait that reflects emotional instability in daily life. It was revealed that the neuroticism scores were positively correlated with the activity in the temporal pole region, but not in the other regions. These results suggest that the emotional processes implemented in the temporal pole are recruited during successful understanding of other persons' mental states, and that the recruitment may be modulated by an emotional personality trait of individual subjects. (C) 2010 Elsevier B.V. All rights reserved. C1 [Jimura, Koji; Konishi, Seiki; Asari, Tomoki; Miyashita, Yasushi] Univ Tokyo, Sch Med, Dept Physiol, Tokyo 1138654, Japan. RP Jimura, K (reprint author), Washington Univ, Dept Psychol, CB1125 1 Brookings Dr, St Louis, MO 63108 USA. EM kjimura@wustl.edu FU Takeda Foundation; Ministry of Education, Culture, Sports, Science and Technology of Japan [17500203]; Japan Society for the Promotion of Science [11149]; Uehara Memorial Foundation; [19002010] FX This work was supported by a Grant-in-Aid for Specially Promoted Research (19002010), and Takeda Foundation to Y. M., a Grant-in-Aid for Scientific Research C (17500203) to S. K. from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Research Fellowship for young scientists (11149) from the Japan Society for the Promotion of Science, and Research Fellowship from the Uehara Memorial Foundation to K. J. We also thank Dr. Bruna Martins for proofreading the manuscript. 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Here we report the case of a woman affected by a severe epileptic disorder with an onset at 14 years old. She is affected by a cryptogenetic focal epilepsy with complex partial (psychomotor) and secondarily generalized tonic-clonic seizures, which are drug resistant. The woman is married to a healthy man and has six children: two girls are healthy, a girl and two boys are affected by autism while one boy shows partial seizures. The three children with autism show moderate mental retardation and an EEG with no epileptiform alterations. The child with epileptic seizures shows an asymmetric EEG that is not necessarily pathological. In this family, no chromosomal rearrangements were detected by means of classical cytogenetic analyses. The presence of FRAXA alterations and of microdeletions of the 15q11-g13 chromosome region were also excluded. A genome-wide linkage analysis using microsatellite markers revealed several chromosome regions as possible susceptibility loci. (C) 2010 Elsevier Inc. All rights reserved. C1 [Redaelli, S.; Clerici, M.; Cornaggia, C. M.; Dalpra, L.] Univ Milano Bicocca, Dept Neurosci & Biomed Technol, I-20052 Monza, Italy. [Combi, R.] Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy. [Beghi, M.] S Gerardo Hosp, Monza, Italy. RP Dalpra, L (reprint author), Univ Milano Bicocca, Dept Neurosci & Biomed Technol, Via Cadore 48, I-20052 Monza, Italy. 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[Pfeiffer, Brad E.; Zang, Tong; Wilkerson, Julia R.; Maksimova, Marina A.; Hubert, Kimberly M.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. RP Cowan, CW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. EM christopher.cowan@utsouthwestern.edu; kimberly.huber@utsouthwestern.edu FU NIH [1F31NS050992, NS045711, HD052731, DA08227, T32DA07290, F32DA27265]; Autism Speaks; Whitehall Foundation; Simons Foundation FX This research was supported by NIH grants 1F31NS050992 (B.E.P.), NS045711, HD052731 (K.M.H.), DA08227 (C.W.C.), T32DA07290 and F32DA27265 (L.N.S.), and grants from Autism Speaks (K.M.H.), the Whitehall (C.W.C.) and Simons Foundations (K.M.H. and C.W.C.). We would like to thank K. Loerwald and C. Hale for technical assistance; E. Kavalali for helpful discussions; and E. Olson for providing the MEF2-EN construct. K.M.H. is a paid SAB member of Seaside Therapeutics. 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MacKinlay, Elizabeth E. Dick, James R. Cheseldine, Sally Boyle, Rose M. Graham, Catriona O'Hare, Anne E. TI The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Blood fatty acids; Autism; Child health; n-3 Highly unsaturated fatty acids; Fish oils ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; SPECTRUM DISORDERS; PSYCHIATRIC-DISORDERS; METABOLISM; PREVALENCE; OMEGA-3-FATTY-ACIDS; SUPPLEMENTATION; POPULATION AB The erythrocyte and plasma fatty acid compositions of children with autism were compared in a case-control study with typically developing (TD) children and with children showing developmental delay (DD). Forty-five autism subjects were age-matched with TD controls and thirty-eight with DD controls. Fatty acid data were compared using paired t tests. In addition, blood fatty acids from treatment-naive autism subjects were compared with autism subjects who had consumed fish oil supplements by two-sample t tests. Relatively few differences were seen between erythrocyte fatty acids in autism and TD subjects although the former had an increased arachidonic acid (ARA):EPA ratio. This ratio was also increased in plasma samples from the same children. No changes in n-3 fatty acids or ARA:EPA ratio were seen when comparing autism with DD subjects but some SFA and MUFA were decreased in the DD subjects, most notably 24 : 0 and 24 : 1, which are essential components of axonal myelin sheaths. However, if multiple comparisons are taken into account, and a stricter level of significance applied, most of these values would not be significant. Autism subjects consuming fish oil showed reduced erythrocyte ARA, 22 : 4n-6, 22 : 5n-6 and total n-6 fatty acids and increased EPA, 22 : 5n-3, 22: 6n-3 and total n-3 fatty acids along with reduced n-6:n-3 and ARA:EPA ratios. Collectively, the autism subjects did not have an underlying phospholipid disorder, based on erythrocyte fatty acid compositions, although the increased ARA:EPA ratio observed suggested that an imbalance of essential highly unsaturated fatty acids may be present in a cohort of autism subjects. C1 [Bell, John Gordon; MacKinlay, Elizabeth E.; Dick, James R.] Univ Stirling, Inst Aquaculture, Nutr Grp, Stirling FK9 4LA, Scotland. [Miller, Deborah; O'Hare, Anne E.] Univ Edinburgh, Dept Child Life & Hlth, Edinburgh EH9 1UW, Midlothian, Scotland. [MacDonald, Donald J.; Boyle, Rose M.] Victoria Infirm, Dept Biochem, Glasgow G42 9TY, Lanark, Scotland. [Cheseldine, Sally] CFMHS, Edinburgh EH9 1LL, Midlothian, Scotland. 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J. Nutr. PD APR 28 PY 2010 VL 103 IS 8 BP 1160 EP 1167 DI 10.1017/S0007114509992881 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 590ST UT WOS:000277248800010 PM 19995470 ER PT J AU Mevorach, C Hodsoll, J Allen, H Shalev, L Humphreys, G AF Mevorach, Carmel Hodsoll, John Allen, Harriet Shalev, Lilach Humphreys, Glyn TI Ignoring the Elephant in the Room: A Neural Circuit to Downregulate Salience SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HUMAN VISUAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; POSTERIOR PARIETAL CORTEX; HUMAN EXTRASTRIATE CORTEX; CONCURRENT TMS-FMRI; DIRECTED ATTENTION; BRAIN IMAGES; SUPPRESSION; SELECTION; SEARCH AB How do we ignore stimuli that are salient but irrelevant when our task is to select a lower salient stimulus? Since bottom-up processes favor high saliency, detection of a low-salient target in the presence of highly salient distractors requires top-down attentional guidance. Previous studies have demonstrated that top-down attention can modulate perceptual processing and also that the control of attention is driven by frontoparietal regions. However, to date, there is no direct evidence on the cause and effect relationship between control regions and perceptual processing. Here, we report the first evidence demonstrating a neural circuit for the downregulation of salient distractors when a low-salient target is selected, combining brain imaging using functional magnetic resonance imaging with brain stimulation by transcranial magnetic stimulation. Using these combined techniques, we were able to identify a cause and effect relationship in the suppression of saliency, based on an interaction between the left intraparietal sulcus (IPS) and a region implicated in visual processing in our task (the left occipital pole). In particular, low-salient stimuli were selected by the left IPS suppressing early visual areas that would otherwise respond to a high-saliency distractor in the task. Apart from providing a first documentation of the neural circuit supporting selection by saliency, these data can be critical for understanding the underlying causes of problems in ignoring irrelevant salience that are found in both acquired and neurodevelopmental disorders (e.g., attention deficit/hyperactivity disorder or autism). C1 [Mevorach, Carmel; Hodsoll, John; Allen, Harriet; Humphreys, Glyn] Univ Birmingham, Sch Psychol, Behav Brain Sci Ctr, Birmingham B15 2TT, W Midlands, England. [Shalev, Lilach] Hebrew Univ Jerusalem, Sch Educ, Div Learning Disabil, IL-91905 Jerusalem, Israel. RP Mevorach, C (reprint author), Univ Birmingham, Sch Psychol, Behav Brain Sci Ctr, Birmingham B15 2TT, W Midlands, England. 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Carbonetto, Salvatore Drapeau, Pierre Rouleau, Guy A. CA S2D Team TI De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMOSOME 22Q; BIPOLAR DISORDER; PREMORBID IQ; LINKAGE; EXPRESSION; GENOME; TRANSMISSION; ZEBRAFISH; ALLELES; LOCUS AB Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders. C1 [Gauthier, Julie; Lafreniere, Ronald G.; Xiong, Lan; Spiegelman, Dan; Cote, Melanie; Noreau, Anne; Marineau, Claude; Rouleau, Guy A.] Univ Montreal, CHU Montreal, Res Ctr, Ctr Excellence Neurom, Montreal, PQ H2L 2W5, Canada. [Gauthier, Julie; Lafreniere, Ronald G.; Xiong, Lan; Spiegelman, Dan; Cote, Melanie; Noreau, Anne; Marineau, Claude; Rouleau, Guy A.] Univ Montreal, Dept Med, Montreal, PQ H2L 2W5, Canada. [Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Peng, Huashan; Drapeau, Pierre] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada. [Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Peng, Huashan; Drapeau, Pierre] Univ Montreal, Grp Rech Syst Nerveux Cent, Montreal, PQ H3T 1J4, Canada. [Hamdan, Fadi F.; Samuels, Mark E.; S2D Team] Univ Montreal, Ctr Excellence Neurom, CHU St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada. [Addington, Anjene M.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Brockton, MA 02301 USA. [Krebs, Marie-Odile; Mouaffak, Faycal] Univ Paris 05, Lab Pathophysiol Psychiat Dis, U894, Hop St Anne, F-75014 Paris, France. [Joober, Ridha; Fathalli, Ferid] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada. [Haghighi, Ali P.; Carbonetto, Salvatore] McGill Univ, Dept Physiol, Montreal, PQ H3G 0B1, Canada. [Neri, Christian] Ctr Paul Broca, INSERM, U857, F-75014 Paris, France. [Dube, Marie-Pierre] Univ Montreal, Ctr Rech, Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada. [Dube, Marie-Pierre] Univ Montreal, Dept Pharmacol, Montreal, PQ H1T 1C8, Canada. [Stone, Eric A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Awadalla, Philip] Univ Montreal, Res Ctr, CHU St Justine, Montreal, PQ H3T 1C5, Canada. [Awadalla, Philip] Univ Montreal, Dept Pediat & Biochem, Montreal, PQ H3T 1C5, Canada. [Barker, Philip A.] McGill Univ, Montreal Neurol Inst, Ctr Neuronal Survival, Montreal, PQ H3A 2B4, Canada. [Carbonetto, Salvatore] McGill Univ, Ctr Res Neurosci, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. RP Gauthier, J (reprint author), Univ Montreal, CHU Montreal, Res Ctr, Ctr Excellence Neurom, Montreal, PQ H2L 2W5, Canada. EM julie.gauthier@crchum.qc.ca; guy.rouleau@umontreal.ca RI Neri, Christian/F-6729-2013; Dube, Marie-Pierre/B-9364-2008 OI Dube, Marie-Pierre/0000-0001-8442-4393 FU Genome Canada and Genome Quebec; Universite de Montreal for the Synapse to Disease; Canadian Foundation for Innovation FX We thank all the families involved in this study. We would like to thank Dr. Chawki Benkelfat for several helpful discussions. We also acknowledge the efforts of the members of the Genome Quebec Innovation Centre Sequencing (Pierre Lepage, Sebastien Brunet, and Hao Fan Yam) and Bioinformatic (Louis Letourneau and Louis Dumond Joseph) groups. This work was supported by Genome Canada and Genome Quebec, and received cofunding from Universite de Montreal for the Synapse to Disease (S2D) project as well as funding from the Canadian Foundation for Innovation. G. A. R. holds the Canada Research Chair in Genetics of the Nervous System; P. D. holds the Canada Research Chair in Neuroscience. A. P. H. holds the Canada Research Chair in Drosophila Neurobiology. P. A. holds a career award from the Fonds de la recherche en Sante du Quebec. A portion of the schizophrenia cohort was collected through the Collaborative Network for Family Study in Psychiatry (Reseau d'etude Familiale en Psychiatry), supported by the Fondation Pierre Deniker. 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Natl. Acad. Sci. U. S. A. PD APR 27 PY 2010 VL 107 IS 17 BP 7863 EP 7868 DI 10.1073/pnas.0906232107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 588QQ UT WOS:000277088700048 PM 20385823 ER PT J AU Churches, O Wheelwright, S Baron-Cohen, S Ring, H AF Churches, Owen Wheelwright, Sally Baron-Cohen, Simon Ring, Howard TI The N170 is not modulated by attention in autism spectrum conditions SO NEUROREPORT LA English DT Article DE attention; autism; event-related potentials; face processing ID FUNCTIONING AUTISM; ASPERGERS-SYNDROME; FUSIFORM GYRUS; FACE; CHILDREN; INDIVIDUALS; RECOGNITION; ACTIVATION; DISORDERS; RESPONSES AB Face processing deficits are characteristic of autism spectrum conditions. However, event-related potential studies of autism spectrum conditions have found inconsistent results for the face selective N170 component. In this study, 15 adult males with autism spectrum conditions and 15 matched, typically developing controls completed a task in which pictures of faces were either attended to or ignored. In the control group, the N170 was larger when faces were attended to. However, there was no such modulation in the autism spectrum conditions group. This finding helps clarify the results from the earlier event-related potential studies of face processing in autism spectrum conditions and suggests that visual attention does not enhance face processing in autism spectrum conditions as it does in typical development. NeuroReport 21: 399-403 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Churches, Owen; Wheelwright, Sally; Baron-Cohen, Simon] Univ Cambridge, Autism Res Ctr, Cambridge CB2 8AH, England. [Churches, Owen] Univ Cambridge, Cambridge Intellectual & Dev Disabil Res Grp, Dept Psychiat, Cambridge CB2 8AH, England. RP Churches, O (reprint author), Univ Cambridge, Autism Res Ctr, 2nd Floor,Douglas House,18B Trumpington Rd, Cambridge CB2 8AH, England. EM ofc20@cam.ac.uk RI Ring, Howard/G-6684-2011 FU Cambridge Australia Trust; MRC UK FX OC is supported by the Cambridge Australia Trust. This research was supported by a grant to SBC from the MRC UK and was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust. The authors would like to thank Michael Lombardo and Chris Ashwin for their comments on the manuscript. This study was conducted at Douglas House, 18b Trumpington Road, Cambridge CB2 8AH, United Kingdom. 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Controversy exists, however, over whether human functional brain measures reveal mirror neuron activity. Claims have been made that measures such as electroencephalographic mu suppression reflect a human mirror neuron system such as that seen in monkeys, but more data are needed to support these claims. Here we report significantly greater mu suppression for participants' execution of an action compared with observation of the same action, similar to the pattern seen in monkeys. Current data therefore support the claim that electroencephalographic mu suppression reflects mirror neuron activity in humans. NeuroReport 21: 432-435 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Woodruff, Christopher Chad; Maaske, Shannon] No Arizona Univ, Dept Psychol, Flagstaff, AZ 86011 USA. RP Woodruff, CC (reprint author), No Arizona Univ, Dept Psychol, Flagstaff, AZ 86011 USA. 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Misri, Amit Bartlett, Jackie Orabona, Guilherme Friedman, Richard D. Sexton, David Maheshwari, Sunita Morgan, Thomas M. TI Consanguinity Mapping of Congenital Heart Disease in a South Indian Population SO PLOS ONE LA English DT Article ID VAN-CREVELD-SYNDROME; PARENTAL CONSANGUINITY; GENE; AUTISM; LINKAGE; DISEQUILIBRIUM; CITRULLINE; CHILDREN; SURGERY; TRAITS AB Background: Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents. Methodology/Principal Findings: In this linkage scan involving single nucleotide polymorphism (SNP) markers, the threshold for genome-wide statistical significance was set at the standard log-of-odds (LOD) score threshold of 3.3, corresponding to 1995:1 odds in favor of linkage. We identified a maximal single-point LOD score of 3.76 (5754:1 odds) implicating linkage of CHD with the major allele (G) of rs1055061 on chromosome 14 in the HOMEZ gene, a ubiquitously expressed transcription factor containing leucine zipper as well as zinc finger motifs. Re-sequencing of HOMEZ exons did not reveal causative mutations in Indian probands. In addition, genotyping of the linked allele (G) in 325 U. S. CHD cases revealed neither genotypic nor allele frequency differences in varied CHD cases compared to 605 non-CHD controls. Conclusions/Significance: Despite the statistical power of the consanguinity mapping approach, no single gene of major effect could be convincingly identified in a clinically heterogeneous sample of Indian CHD cases born to consanguineous parents. However, we are unable to exclude the possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD in the Indian population. Further research involving large multinational cohorts of patients with specific subtypes of CHD is needed to attempt replication of the observed linkage peak on chromosome 14. In addition, we anticipate that a targeted re-sequencing approach may complement linkage analysis in future studies of recessive mutation detection in CHD. C1 [McGregor, Tracy L.; Orabona, Guilherme; Friedman, Richard D.; Morgan, Thomas M.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. 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PD APR 15 PY 2010 VL 340 AR c1127 DI 10.1136/bmj.c1127 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 586KC UT WOS:000276905500001 PM 20395277 ER PT J AU Cheng, YW Chou, KH Chen, IY Fan, YT Decety, J Lin, CP AF Cheng, Yawei Chou, Kun-Hsien Chen, I-Yun Fan, Yang-Teng Decety, Jean Lin, Ching-Po TI Atypical development of white matter microstructure in adolescents with autism spectrum disorders SO NEUROIMAGE LA English DT Article DE Autism spectrum disorders; Diffusion tensor imaging; Frontal; Development; Adolescence ID SUPERIOR LONGITUDINAL FASCICULUS; HIGH-FUNCTIONING AUTISM; TEMPORAL-LOBE EPILEPSY; TENSOR IMAGING DETECTS; SUBJECT DIFFUSION DATA; MULTIPLE-SCLEROSIS; SPATIAL STATISTICS; ASPERGER-SYNDROME; WORKING-MEMORY; CORPUS-CALLOSUM AB Diffusion tensor imaging (DTI) studies in adolescents with autism spectrum disorders (ASD) indicate aberrant neurodevelopment of frontal white matter (WM), potentially underlying abnormal social cognition and communication in ASD. Here, we further use tract-based spatial statistics (TBSS) to examine the developmental change of WM skeleton (i.e., the most compact whole-brain WM) during adolescence in ASD. This whole-brain DTI used TBSS measures fractional anisotropy (FA) and longitudinal and radial diffusivities in fifty adolescents, 25 ASD and 25 controls. Results show that adolescents with ASD versus controls had significantly reduced FA in the right posterior limb of internal capsule (increased radial diffusivity distally and reduced longitudinal diffusivity centrally). Adolescents with ASD versus controls (covarying for age and IQ) had significantly greater FA in the frontal lobe (reduced radial diffusivity), right cingulate gyrus (reduced radial diffusivity), bilateral insula (reduced radial diffusivity and increased longitudinal diffusivity), right superior temporal gyrus (reduced radial diffusivity), and bilateral middle cerebellar peduncle (reduced radial diffusivity). Notably, a significant interaction with age by group Was found in the right paracentral lobule and bilateral superior frontal gyrus as indicated by an age-related FA gain in the controls whilst an age-related FA loss in the ASD. To our knowledge, this is the first Study to use TBSS to examine WM in individuals with ASD. Our findings indicate that the frontal lobe exhibits abnormal WM microstructure as well as an aberrant neurodevelopment during adolescence in ASD. which support the frontal disconnectivity theory of autism. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cheng, Yawei; Chen, I-Yun; Fan, Yang-Teng; Lin, Ching-Po] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. [Cheng, Yawei] Natl Yang Ming Univ, Dept Phys Med & Rehabil, Yilan, Taiwan. [Chou, Kun-Hsien] Natl Yang Ming Univ, Inst Bioengn, Taipei 112, Taiwan. [Decety, Jean] Univ Chicago, Dept Psychol, Ctr Cognit & Social Neurosci, Chicago, IL 60637 USA. [Decety, Jean] Univ Chicago, Dept Psychiat, Ctr Cognit & Social Neurosci, Chicago, IL 60637 USA. RP Lin, CP (reprint author), Natl Yang Ming Univ, Inst Neurosci, 155 Li Nong St,Sec 2, Taipei 112, Taiwan. EM cplin@ym.edu.tw FU National Science Council [NSC 97-2410-H-010-003-MY2, NSC 98-2923-B-010-001-MY3]; National Yang-Ming University Hospital [RD2008-015]; National Health Institute of Research [NHRI-EX98-9813EC]; Healthy Department of Taipei City Hospital [97001-62-020] FX The study was in part sponsored by the National Science Council (NSC 97-2410-H-010-003-MY2; NSC 98-2923-B-010-001-MY3), the National Yang-Ming University Hospital (RD2008-015), the National Health Institute of Research (NHRI-EX98-9813EC) and the Healthy Department of Taipei City Hospital (97001-62-020). The authors thank the children and parents who participated in this study. 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Kraegeloh-Mann, Ingeborg TI Cortical response to social interaction is affected by gender SO NEUROIMAGE LA English DT Article DE Visual social perception; Cortical activity; Magnetoencephalography (MEG); Induced gamma oscillations; Gender differences; Heider-and-Simmel animations ID SUPERIOR TEMPORAL SULCUS; BIOLOGICAL MOTION PERCEPTION; AUTISM SPECTRUM DISORDERS; DECISION-MAKING; OSCILLATORY ACTIVITY; BRAIN CONNECTIVITY; ANIMATED SHAPES; SEX-DIFFERENCES; MIRROR SYSTEM; MENTAL STATES AB The ability of humans to predict and explain other people's actions is of immense value for adaptive behavior and nonverbal communication. Gender differences are often evident in the comprehension of social signals, but the underlying neurobiological basis for these differences is unclear. Combining visual psychophysics with an analysis of neuromagnetic activity, we assessed gender effects an the induced oscillatory response to visual social interaction revealed by motion. A robust difference in the induced gamma response was found between females and males over the left prefrontal cortex, a region implicated in perceptual decision making. The induced gamma neuromagnetic response peaked earlier in females than in males. Moreover, it appears that females anticipate social interaction predicting others' actions ahead of their realization, whereas males require accumulation of more sensory evidence for proper social decisions. The findings reflect gender-dependent modes in cortical processing of visually acquired social information. Contrary to popular wisdom, the Outcome of this Study indicates that gender effects are not evident in the neural circuitry underpinning visual social perception, but in the regions engaged in perceptual decision making. (C) 2009 Elsevier Inc. All rights reserved. C1 [Pavlova, Marina; Guerreschi, Michele; Kraegeloh-Mann, Ingeborg] Univ Tubingen, Dev Cognit & Social Neurosci Unit, Dept Paediat Neurol & Child Dev, Childrens Hosp,Sch Med, D-72076 Tubingen, Germany. [Pavlova, Marina; Lutzenberger, Werner] Univ Tubingen, Sch Med, Inst Med Psychol & Behav Neurobiol, MEG Ctr, D-72076 Tubingen, Germany. [Guerreschi, Michele] Univ Padua, Dept Gen Psychol, Padua, Italy. [Sokolov, Alexander N.] Univ Tubingen, Sch Med, Low Vis Clin, D-72076 Tubingen, Germany. [Sokolov, Alexander N.] Univ Tubingen, Sch Med, Res Lab, Ctr Ophthalmol, D-72076 Tubingen, Germany. RP Pavlova, M (reprint author), Univ Tubingen, Dev Cognit & Social Neurosci Unit, Dept Paediat Neurol & Child Dev, Childrens Hosp,Sch Med, Hoppe Seyler Str 1, D-72076 Tubingen, Germany. EM marina.pavlova@uni-tuebingen.de FU Else Kroner-Fresenius-Stiftung [P63/2008] FX We thank the participants for their kind cooperation, and Jurgen Dax at the MEG Center of the University of Tubingen Medical School for substantial technical assistance. This work was supported by the Else Kroner-Fresenius-Stiftung (research grant P63/2008 to M.P.). This paper is devoted to the memory of Werner Lutzenberger who passed away on November 22, 2008. 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Sudhof, Thomas C. Powell, Craig M. TI RIM1 alpha and Interacting Proteins Involved in Presynaptic Plasticity Mediate Prepulse Inhibition and Additional Behaviors Linked to Schizophrenia SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AUTISM SPECTRUM DISORDER; LONG-TERM PLASTICITY; PREFRONTAL CORTEX; NEUROTRANSMITTER RELEASE; KNOCKOUT MICE; SYNAPSIN-II; ANIMAL-MODEL; ACTIVE ZONE; ANTIPSYCHOTIC TREATMENT; SYNAPTIC PLASTICITY AB Several presynaptic proteins involved in neurotransmitter release in the CNS have been implicated in schizophrenia in human clinical genetic studies, in postmortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1 alpha mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1 alpha exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1 alpha-deficient mice, as mice bearing mutations in the RIM1 alpha binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1 alpha's involvement in multiple behavioral abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating. C1 [Blundell, Jacqueline; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Blundell, Jacqueline; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Kaeser, Pascal S.; Sudhof, Thomas C.] Stanford Univ, Dept Cellular & Mol Physiol, Palo Alto, CA 94304 USA. [Kaeser, Pascal S.; Sudhof, Thomas C.] Stanford Univ, Howard Hughes Med Inst, Palo Alto, CA 94304 USA. RP Powell, CM (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM craig.powell@utsouthwestern.edu FU National Alliance for Research on Schizophrenia and Depression; National Institute of Mental Health; National Institute of Child Health and Human Development; Howard Hughes Medical Institute; Hartwell Foundation FX This work was supported by grants from the National Alliance for Research on Schizophrenia and Depression (C.M.P.; Constance and Stephen Lieber Investigator, P.S.K.), the National Institute of Mental Health (C.M.P., T.C.S.), the National Institute of Child Health and Human Development (C.M.P.), the Howard Hughes Medical Institute (T.C.S.), and the Hartwell Foundation (C.M.P.). T.C.S.and P.S.K. supplied the mice, C.M.P. conceived and designed the experiments, C.M.P.and J.B.performed the experiments, C.M.P. performed statistical analysis, and C.M.P.wrote the paper with input from J.B., P.S.K., and T.C.S.We thank current members of the Powell lab for critical reading of this manuscript. 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Recent studies suggest a role of glia in causing neuronal dysfunction via a non-cell-autonomous effect in RTT. Here we report a potent neurotoxic activity in the conditioned medium (CM) obtained from Mecp2-null microglia. Hippocampal neurons treated with CM from Mecp2-null microglia showed an abnormal stunted and beaded dendritic morphology, and signs of microtubule disruption and damage of postsynaptic glutamatergic components within 24 h. We identified that the toxic factor in the CM is glutamate, because (1) Mecp2-null microglia released a fivefold higher level of glutamate, (2) blockage of microglial glutamate synthesis by a glutaminase inhibitor abolished the neurotoxic activity, (3) blockage of microglial glutamate release by gap junction hemichannel blockers abolished the neurotoxic activity, and (4) glutamate receptor antagonists blocked the neurotoxicity of the Mecp2-null microglia CM. Wefurther identified that increased levels of glutaminase and connexin 32 in Mecp2-null microglia are responsible for increased glutamate production and release, respectively. In contrast, theCMfrom highly pure Mecp2-null astrocyte cultures showed no toxic effect. Our results suggest that microglia may influence the onset and progression of RTT and that microglia glutamate synthesis or release could be a therapeutic target for RTT. C1 [Jin, Lee-Way] Univ Calif Davis, Med Ctr, Dept Pathol & Lab Med, MIND Inst, Sacramento, CA 95817 USA. RP Jin, LW (reprint author), Univ Calif Davis, Med Ctr, Dept Pathol & Lab Med, MIND Inst, 2805 50th St, Sacramento, CA 95817 USA. EM Lee-Way.Jin@ucdmc.ucdavis.edu FU University of California Davis FX This work was funded by the University of California Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute. We thank Dr. Janine LaSalle for helpful comments on this manuscript. 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PD APR 12 PY 2010 VL 8 AR 42 DI 10.1186/1741-7007-8-42 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 601IX UT WOS:000278052900003 PM 20385034 ER PT J AU Hess, J Matson, J Neal, D Mahan, S Fodstad, J Bamburg, J Holloway, J AF Hess, Julie Matson, Johnny Neal, Daniene Mahan, Sara Fodstad, Jill Bamburg, Jay Holloway, Jodie TI A Comparison of Psychotropic Drug Side Effect Profiles in Adults Diagnosed With Intellectual Disabilities and Autism Spectrum Disorders SO JOURNAL OF MENTAL HEALTH RESEARCH IN INTELLECTUAL DISABILITIES LA English DT Article DE autism spectrum disorders; drug side effects; Matson Evaluation of Drug Side Effects (MEDS); psychotropic medication; intellectual disability AB Forty-eight adults diagnosed with intellectual disabilities and Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified were examined with regard to psychotropic medication side effects. Participants were divided into 4 groups: no psychotropic medication group (n = 9); atypical antipsychotic medication group (n = 13); atypical antipsychotic and antiepileptic drug group (AEDs/mood stabilizers; n = 13); and a group of individuals receiving atypical antipsychotic medication, AEDs/mood stabilizers, and anxiolytics (n = 13). Those participants not currently prescribed any psychotropic medications evinced the fewest side effects. Participants prescribed psychotropic medication across multiple classes evinced more side effects. Thus, persons receiving atypical antipsychotic medication, AEDs/mood stabilizers, and anxiolytics had the greatest number of side effects. More specifically, the greatest number of side effects pertained to the CNS-Parkinsonism/Dyskinesia subscale. C1 [Hess, Julie; Matson, Johnny; Neal, Daniene; Mahan, Sara; Fodstad, Jill] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. 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PD APR 9 PY 2010 VL 3 IS 2 BP 85 EP 96 DI 10.1080/19315861003690588 PG 12 WC Education, Special; Psychiatry; Rehabilitation SC Education & Educational Research; Psychiatry; Rehabilitation GA V37ZW UT WOS:000209314700002 ER PT J AU Jonsson, L Ljunggren, E Bremer, A Pedersen, C Landen, M Thuresson, K Giacobini, M Melke, J AF Jonsson, Lina Ljunggren, Elin Bremer, Anna Pedersen, Christin Landen, Mikael Thuresson, Kent Giacobini, MaiBritt Melke, Jonas TI Mutation screening of melatonin-related genes in patients with autism spectrum disorders SO BMC MEDICAL GENOMICS LA English DT Article ID CHILDREN; SLEEP; ASMT; TWIN AB Background: One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene. Methods: In the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample. Results: Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A, and MTNR1B. Conclusions: Our report of another ASD patient carrying the splice site mutation IVS5+2T> C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders. C1 [Jonsson, Lina; Ljunggren, Elin; Pedersen, Christin; Melke, Jonas] Gothenburg Univ, Dept Pharmacol, Inst Neurosci & Physiol, S-41124 Gothenburg, Sweden. [Bremer, Anna; Giacobini, MaiBritt] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Landen, Mikael] Karolinska Inst, Stockholm Ctr Psychiat Res, Stockholm, Sweden. [Thuresson, Kent] Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Neuropsychiat Unit,Molndals Hosp, Gothenburg, Sweden. RP Melke, J (reprint author), Gothenburg Univ, Dept Pharmacol, Inst Neurosci & Physiol, S-41124 Gothenburg, Sweden. EM jonas.melke@pharm.gu.se FU Swedish Research Council [2004-6588]; Wilhelm and Martina Lundgren Foundation; Magnus Bergvall Foundation; Ahlens Foundation; Frimurarna Barnhuset Foundation; Linnea and Josef Carlsson Foundation; Knut and Alice Wallenberg Foundation FX We are grateful to the patients and their relatives who have made this study possible. Technicians Gunilla Bourghardt and Inger Oscarsson and nurse Carina Algede are warmly thanked for their skilful assistance, and professor Goran Holm for collecting and characterizing the control samples. This work has been supported by the Swedish Research Council (2004-6588), the Wilhelm and Martina Lundgren Foundation, the Magnus Bergvall Foundation, the Ahlens Foundation, the Frimurarna Barnhuset Foundation and the Linnea and Josef Carlsson Foundation. We also would like to thank the SWEGENE Goteborg Genomics Core Facility platform, funded by a grant from the Knut and Alice Wallenberg Foundation. 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We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that SOX13 regulates angiogenesis, and that SEC23IP is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks-many predating the plant-animal divergence-capable of identifying candidate disease genes. C1 [McGary, Kriston L.; Park, Tae Joo; Woods, John O.; Cha, Hye Ji; Wallingford, John B.; Marcotte, Edward M.] Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Syst & Synthet Biol, Austin, TX 78712 USA. [Park, Tae Joo; Wallingford, John B.] Univ Texas Austin, Howard Hughes Med Inst, Austin, TX 78712 USA. [Park, Tae Joo; Wallingford, John B.] Univ Texas Austin, Dept Mol Cell & Dev Biol, Austin, TX 78712 USA. [Marcotte, Edward M.] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA. RP Marcotte, EM (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Syst & Synthet Biol, Austin, TX 78712 USA. EM marcotte@icmb.utexas.edu RI Park, Tae Joo/G-1460-2011 FU Texas Advanced Research Program; National Science Foundation; National Institutes of Health; Welch Foundation [F-1515]; National Institute of General Medical Sciences and The March of Dimes (; Texas Institute for Drug and Diagnostic Development FX We thank Greg Weiss for Fig. 1A, and Andrew Fraser, Andrew Ellington, and Jim Bull for critical discussion. This work was supported by grants from the Texas Advanced Research Program, the National Science Foundation, the National Institutes of Health, and the Welch Foundation (F-1515), and a Packard Fellowship (to E. M. M.), a National Science Foundation graduate fellowship (to J.O.W.), and grants from the National Institute of General Medical Sciences and The March of Dimes (to J.B.W.). J.B.W. is an Early Career Scientist of the Howard Hughes Medical Institute. T.J.P. is supported by a Postdoctoral Research Initiative Seed Grant from the Texas Institute for Drug and Diagnostic Development. 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PD APR PY 2010 VL 27 IS 2 BP 113 EP 126 PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 580RF UT WOS:000276466400003 PM 20440023 ER PT J AU Bradstreet, JJ Smith, S Baral, M Rossignol, DA AF Bradstreet, James Jeffrey Smith, Scott Baral, Matthew Rossignol, Daniel A. TI Biomarker-Guided Interventions of Clinically Relevant Conditions Associated with Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder SO ALTERNATIVE MEDICINE REVIEW LA English DT Review DE autism; autistic; ADD; ADHD; ASD; attention deficit; biomarkers ID INFLAMMATORY-BOWEL-DISEASE; PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE BEHAVIORAL TREATMENT; ENVIRONMENTAL MERCURY RELEASE; OXIDATIVE STRESS; DEFICIT/HYPERACTIVITY DISORDER; GASTROINTESTINAL SYMPTOMS; IRON-DEFICIENCY; MITOCHONDRIAL DYSFUNCTION; FECAL CALPROTECTIN AB Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are common and complex neurodevelopmental conditions. Diagnostic criteria for these conditions have traditionally relied solely on behavioral criteria without consideration for potential biomedical underpinnings. Newer evidence, however, reveals that ASDs are associated with: oxidative stress; decreased methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal dysbiosis; increased toxic metal burden; immune dysregulation, characterized by a unique inflammatory bowel disease and immune activation of neuroglial cells; and ongoing brain hypoperfusion. Many of these same problems are common features in children with ADHD. These medical conditions, whether co-morbidities or etiopathogenic, would be expected to have synergistically negative effects on the development, cognition, focus, and attention of affected children. It is likely these biological abnormalities contribute significantly to the behavioral symptoms intrinsic in these diagnoses. However, treatment for these underlying medical disorders is clinically justified, even if no clear immediate behavioral improvements are observed. This article reviews the medical literature and discusses the authors' clinical experience using various biomarkers for measuring oxidative stress, methylation capacity and transsulfuration, immune function, gastrointestinal problems, and toxic metal burden. These biomarkers provide useful guides for selection, efficacy, and sufficiency of biomedical interventions. The use of these biomarkers is of great importance in young children with ADHD or individuals of any age with ASD, because typically they cannot adequately communicate regarding their symptoms. (Altern Med Rev 2010;15(1)15-32) C1 [Bradstreet, James Jeffrey; Smith, Scott; Rossignol, Daniel A.] Int Child Dev Resource Ctr, Melbourne, FL 32934 USA. [Bradstreet, James Jeffrey; Baral, Matthew] SW Coll Naturopath Med, Tempe, AZ USA. [Baral, Matthew] Pediat Med program, Tempe, AZ USA. 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Med. Rev. PD APR PY 2010 VL 15 IS 1 BP 15 EP 32 PG 18 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 595SB UT WOS:000277632000003 PM 20359266 ER PT J AU Erturk, O Bilguvar, K Korkmaz, B Bayri, Y Bayrakli, F Arlier, Z Ozturk, AK Yalcinkaya, C Tuysuz, B State, MW Gunel, M AF Erturk, Ozdem Bilguvar, Kaya Korkmaz, Baris Bayri, Yasar Bayrakli, Fatih Arlier, Zulfikar Ozturk, Ali K. Yalcinkaya, Cengiz Tuysuz, Beyhan State, Matthew W. Gunel, Murat TI A Patient With Duchenne Muscular Dystrophy and Autism Demonstrates a Hemizygous Deletion Affecting Dystrophin SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID FRAGILE-X-SYNDROME; INTELLECTUAL IMPAIRMENT; SPECTRUM DISORDER; GENETICS; ISOFORM; DEFICIT; MALES; MODEL; MICE C1 [Gunel, Murat] Yale Univ, Sch Med, Dept Neurosurg & Neurobiol, Program Neurogenet, New Haven, CT 06510 USA. [Bilguvar, Kaya; Bayri, Yasar; Bayrakli, Fatih; Arlier, Zulfikar; Ozturk, Ali K.; Gunel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. [Erturk, Ozdem; Korkmaz, Baris; Yalcinkaya, Cengiz] Istanbul Univ, Cerrahpasa Fac Med, Dept Neurol, Div Child Neurol, Istanbul, Turkey. [Tuysuz, Beyhan] Istanbul Univ, Cerrahpasa Fac Med, Dept Pediat, Div Genet, Istanbul, Turkey. [State, Matthew W.; Gunel, Murat] Yale Univ, Dept Genet, New Haven, CT 06510 USA. [State, Matthew W.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Gunel, Murat] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. RP Gunel, M (reprint author), Yale Univ, Sch Med, Dept Neurosurg & Neurobiol, Program Neurogenet, 333 Cedar St,Tompkins 4, New Haven, CT 06510 USA. 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J. Med. Genet. A PD APR PY 2010 VL 152A IS 4 BP 1039 EP 1042 DI 10.1002/ajmg.a.33312 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 584LS UT WOS:000276754000041 PM 20358624 ER PT J AU Burdick, KE DeRosse, P Kane, JM Lencz, T Malhotra, AK AF Burdick, Katherine E. DeRosse, Pamela Kane, John M. Lencz, Todd Malhotra, Anil K. TI Association of Genetic Variation in the MET Proto-Oncogene With Schizophrenia and General Cognitive Ability SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDER; HEPATOCYTE GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; INTERNEURON DEVELOPMENT; CANCER-RISK; POPULATION; SUSCEPTIBILITY; DISRUPTION; MEDICATION; RELATIVES AB Objective: Despite increased exposure to cancer risk factors, several studies have demonstrated a lower incidence of cancer in schizophrenia patients than in the general population. Lower cancer rates in first-degree relatives of schizophrenia patients suggest that the inverse relationship between cancer and schizophrenia may be related to genetic factors. Few studies of schizophrenia have focused on cancer-related genes. The MET proto-oncogene is primarily linked to tumor metastasis, but MET is also involved in neurodevelopment and influences risk for autism. Thus, MET may be of particular interest as a candidate gene for neuropsychiatric diseases with a developmental etiology, including schizophrenia. Method: The authors examined the relationship between 21 single-nucleotide polymorphisms in MET and schizophrenia in 173 Caucasian patients and 137 comparison subjects. They then genotyped a second independent sample (107 patients and 112 comparison subjects) for replication. Finally, they tested for MET's effects on general cognitive ability (g). Results: In the initial cohort, the authors identified four haplotype blocks and found one block to be globally associated with schizophrenia. In block 3, the most common haplotype was over-represented in comparison subjects (frequency, 47%) relative to schizophrenia patients (frequency, 33%) (p=4.0x10(-4); odds ratio=0.56). The authors replicated the block 3 finding in the second sample with similar frequencies: 46% in comparison subjects and 36% in schizophrenia patients (p=0.03; odds ratio=0.66). Moreover, the protective haplotype was associated with a higher g in the combined comparison sample. Conclusions: These data suggest that MET variation influences schizophrenia risk and neurocognition, supporting a neurodevelopmental role across CNS-relevant phenotypes. These results add to the growing evidence suggesting an intriguing relationship between cancer-related genes and schizophrenia susceptibility. C1 [Burdick, Katherine E.] Zucker Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Dept Psychiat Res, Glen Oaks, NY 11004 USA. Albert Einstein Coll Med, Dept Psychiat, New York, NY USA. Feinstein Inst Med Res, Manhasset, NY USA. RP Burdick, KE (reprint author), Zucker Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Dept Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM kburdick@lij.edu RI Burdick, Katherine/G-6124-2012 FU Bristol-Myers Squibb; Eli Lilly; Janssen Pharmaceuticals; Pfizer FX Drs. Burdick and DeRosse report no financial relationships with commercial interests. Dr. Kane has served as a consultant or speaker or on advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb, Clinical Data, Inc., Eli Lilly, Janssen, Johnson & Johnson PRD, Lundbeck, Otsuka, Pfizer, Vanda Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. Lencz has served as a consultant to Eli Lilly, GoldenHelix, Clinical Data, Inc., and InforMed Insights. Dr. Malhotra has served as a consultant or speaker for Bristol-Myers Squibb, Clinical Data, Inc., Eli Lilly, AstraZeneca, and Vanda Pharmaceuticals and has received research support from Bristol-Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, and Pfizer. 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Craddock, Nick CA Wellcome Trust Case Control TI Rare Copy Number Variants A Point of Rarity in Genetic Risk for Bipolar Disorder and Schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIO-FACIAL SYNDROME; INCREASE RISK; MICRODELETION; 22Q11.2; MICRODUPLICATION; PHENOTYPES; DELETIONS; DISEASE; AUTISM AB Context: Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date. Objectives: To determine whether large (> 100 000 base pairs) and rare (found in < 1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia. Design: A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray. Setting: The Wellcome Trust Case Control Consortium. Participants: There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents. Main Outcome Measures: Overall load of CNVs and presence of rare CNVs. Results: The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder. Conclusions: Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder. C1 [Grozeva, Detelina; Kirov, George; Ivanov, Dobril; Jones, Ian R.; Green, Elaine K.; Holmans, Peter A.; Owen, Michael J.; O'Donovan, Michael C.; Craddock, Nick] Cardiff Univ, Sch Med, Ctr Neuropsychiat Genet & Genom, MRC, Cardiff CF14 4XN, S Glam, Wales. [Ivanov, Dobril; Holmans, Peter A.] Cardiff Univ, Sch Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, S Glam, Wales. [Jones, Lisa] Univ Birmingham, Dept Psychiat, Natl Ctr Mental Hlth, Birmingham, W Midlands, England. [St Clair, David M.] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Young, Allan H.; Ferrier, Nicol] Royal Victoria Infirm, Sch Neurol Neurobiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Young, Allan H.] Univ British Columbia, Inst Mental Hlth, Vancouver, BC V5Z 1M9, Canada. [Farmer, Anne E.; McGuffin, Peter] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Craddock, N (reprint author), Cardiff Univ, Sch Med, Ctr Neuropsychiat Genet & Genom, MRC, Cardiff CF14 4XN, S Glam, Wales. EM craddockn@cardiff.ac.uk RI Brown, Matthew/E-5749-2010; McGuffin, Peter/A-1565-2012; Breen, Gerome/A-5540-2010; Holmans, Peter/F-4518-2015 OI Brown, Matthew/0000-0003-0538-8211; McGuffin, Peter/0000-0002-9888-2907; Breen, Gerome/0000-0003-2053-1792; Holmans, Peter/0000-0003-0870-9412 FU Wellcome Trust; Medical Research Council FX Funding for recruitment and phenotype assessment was provided by the Wellcome Trust and the Medical Research Council. The genotype analyses were funded by the Wellcome Trust and undertaken within the context of the Wellcome Trust Case Control Consortium. Online-Only Material: The supplementary Results section, eTables, and eFigures are available at http://www.archgenpsychiatry.com. 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Gen. Psychiatry PD APR PY 2010 VL 67 IS 4 BP 318 EP 327 PG 10 WC Psychiatry SC Psychiatry GA 578RM UT WOS:000276312800002 PM 20368508 ER PT J AU Dziobek, I Bahnemann, M Convit, A Heekeren, HR AF Dziobek, Isabel Bahnemann, Markus Convit, Antonio Heekeren, Hauke R. TI The Role of the Fusiform-Amygdala System in the Pathophysiology of Autism SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORTICAL AREAS TE; SPECTRUM DISORDERS; CEREBRAL-CORTEX; FACE AREA; ASPERGER-SYNDROME; BRAIN-DEVELOPMENT; VISUAL AWARENESS; SOCIAL COGNITION; MACAQUE MONKEY; PERCEPTION AB Context: Autism is a condition of unknown origin with well-documented impairments in social perception and cognition. Objective: To assess the relevance of the fusiform-amygdala system to the pathophysiology of autism spectrum conditions. Design: Cross-sectional case-control study. Setting: University hospital. Participants: A total of 27 adults with autism spectrum conditions and 29 age-, sex-, and intelligence quotient-matched typically developed healthy controls. Patients were assessed according to DSM-IV criteria using the Autism Diagnostic Interview-Revised. Interventions: We applied an automated measurement to estimate fusiform gyrus cortical thickness and a manual tracing method to obtain amygdala volumes. We analyzed volumetric covariance among these brain regions and assessed the functional relevance of anatomical findings by analyzing correlations with emotional face processing performance. Main Outcome Measures: Fusiform gyrus cortical thickness, amygdala volume, emotional face processing. Results: We found a specific local increase in cortical thickness of the fusiform gyrus and associated impairments in face processing in individuals with autism. Anatomical covariance between amygdala volume and the increase in fusiform gyrus local thickness was significantly smaller in the group with autism spectrum conditions. Conclusions: Our data provide the first anatomical evidence of an abnormal amygdala-fusiform system and its behavioral relevance to face-processing deficits in autism spectrum conditions. In light of recent evidence of the involvement of the fusiform gyrus and amygdala in social perception as well as the areas of social cognition and emotional awareness, all of which are relevant to autism, our findings might represent a core pathophysiological mechanism of autism. C1 [Dziobek, Isabel; Bahnemann, Markus; Heekeren, Hauke R.] Max Planck Inst Human Dev, D-14195 Berlin, Germany. [Dziobek, Isabel; Heekeren, Hauke R.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany. [Dziobek, Isabel; Heekeren, Hauke R.] Free Univ Berlin, Berlin, Germany. [Bahnemann, Markus; Heekeren, Hauke R.] Charite, Berlin NeuroImaging Ctr, D-13353 Berlin, Germany. [Convit, Antonio] NYU, Sch Med, Ctr Brain Hlth, New York, NY USA. [Convit, Antonio] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Heekeren, HR (reprint author), Max Planck Inst Human Dev, Lentzeallee 94, D-14195 Berlin, Germany. EM heekeren@mpib-berlin.mpg.de RI Heekeren, Hauke/B-7739-2008 OI Heekeren, Hauke/0000-0001-7912-6826 FU National Alliance for Autism Research; Organization for Autism Research; German Federal Ministry for Research; Max Planck Society FX This study was supported by a grant from the National Alliance for Autism Research; Organization for Autism Research; German Federal Ministry for Research; and the Max Planck Society. 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Understanding genetic data within an anatomical context will be critical to explain how individual risk factors operate to shape phenotypic presentation in patients. Arch Neurol. 2010; 67(4): 395-399 C1 [Geschwind, Daniel H.] Univ Calif Los Angeles, Neurogenet Program, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, Program Neurobehav Genet, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Behav, Los Angeles, CA 90095 USA. RP Geschwind, DH (reprint author), Univ Calif Los Angeles, Neurogenet Program, Dept Neurol, David Geffen Sch Med, Gonda Bldg 2506, Los Angeles, CA 90095 USA. EM dhg@mednet.ucla.edu FU Autism Speaks; Cure Autism Now Foundation; National Institute of Mental Health [U54 MH68172, P50 HD055784, R01 MH64547, R37 MH60233] FX The work in the Geschwind laboratory is supported by Autism Speaks, the Cure Autism Now Foundation, and grants U54 MH68172, P50 HD055784, R01 MH64547, and R37 MH60233 from the National Institute of Mental Health. 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Neurol. PD APR PY 2010 VL 67 IS 4 BP 490 EP 492 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 581XQ UT WOS:000276559500018 PM 20385917 ER PT J AU Allen-Brady, K Cannon, D Robison, R McMahon, WM Coon, H AF Allen-Brady, Kristina Cannon, Dale Robison, Reid McMahon, William M. Coon, Hilary TI Unified Theory of Autism Revisited: Linkage Evidence Points to Chromosome X using a High-Risk Subset of AGRE Families SO AUTISM RESEARCH LA English DT Article DE autism spectrum disorder; genetic linkage; dominant model; pedigree structure; chromosome Xp ID LINKED MENTAL-RETARDATION; NEURONAL CALCIUM SENSOR-1; IL1RAPL1 GENE; UTAH PEDIGREES; LOD SCORES; HETEROGENEITY; DISSECTION; DISORDERS; MUTATION; LOCI AB Zhao et al. [2007] in their "Unified Theory of Autism" hypothesized that incidence of autism in males could be explained by essentially two types of family structures: majority of autism cases are from low-risk autism families with de novo mutations, and a minority of cases are from high-risk multiplex families, where risk to male offspring approximates 50% consistent with a dominant model and high penetrance. Using the Autism Genetic Resource Exchange (AGRE) data set, Zhao et al. identified 86 high-risk families with likely dominant transmission. As genotype data are now available for many members of the AGRE resource, the objective of this manuscript was to determine if dominant linkage evidence for an autism predisposition gene exists in these 86 high-risk families. HumanHap550K Illumina SNP data were available for 92% of 455 total family members in these 86 high-risk families. We performed a linkage analysis using a pruned subset of markers where markers in high linkage disequilibrium were removed. We observed a single suggestive peak (maximum LOD 2.01, maximum HLOD 2.08) under a dominant model on chromosome Xp22.11-p21.2 that encompasses the 1L1RAPL1 gene. Mutations or deletions in 1L1RAPL1 have been previously reported in three families with autism. In our study, 11 families contributed nominally (P<0.05, HLOD > 0.588) to the chromosome X peak. These results demonstrate that identification of a more homogeneous subset of autism cases, which was based on family structure in this study, may help to identify, localize and further our understanding of autism predisposition genes. C1 [Allen-Brady, Kristina; Cannon, Dale; Robison, Reid; McMahon, William M.; Coon, Hilary] Univ Utah, Dept Psychiat, Utah Autism Res Project, Salt Lake City, UT 84108 USA. [McMahon, William M.; Coon, Hilary] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA. RP Allen-Brady, K (reprint author), Univ Utah, Dept Psychiat, Utah Autism Res Project, 650 Komas Dr,Suite 206, Salt Lake City, UT 84108 USA. EM Kristina.allen@utah.edu FU [R01 MH069359] FX We thank Jim Farnham for his assistance with generation of the linkage subset of markers. This work was supported by R01 MH069359. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium* and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). 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PD APR PY 2010 VL 3 IS 2 BP 47 EP 52 DI 10.1002/aur.119 PG 6 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100001 PM 20437600 ER PT J AU Scott-Van Zeeland, AA Dapretto, M Ghahremani, DG Poldrack, RA Bookheimer, SY AF Scott-Van Zeeland, Ashley A. Dapretto, Mirella Ghahremani, Dara G. Poldrack, Russell A. Bookheimer, Susan Y. TI Reward Processing in Autism SO AUTISM RESEARCH LA English DT Article DE functional MRI (fMRI); social cognition; reward; learning ID SOCIAL COGNITION; ORBITOFRONTAL CORTEX; DIAGNOSTIC INTERVIEW; REPETITIVE BEHAVIORS; BASAL GANGLIA; FMRI; OXYTOCIN; BRAIN; SCHIZOPHRENIA; PREDICTION AB The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded implicit learning in children with and without autism spectrum disorders (ASD). Sixteen males with ASD and sixteen age- and IQ-matched typically developing (TO) males were scanned while performing two versions of a rewarded implicit learning task. In addition to examining responses to reward, we investigated the neural circuitry supporting rewarded learning and the relationship between these factors and social development. We found diminished neural responses to both social and monetary rewards in ASD, with a pronounced reduction in response to social rewards (SR). Children with ASD also demonstrated a further deficit in frontostriatal response during social, but not monetary, rewarded learning. Moreover, we show a relationship between ventral striatum activity and social reciprocity in TD children. Together, these data support the hypothesis that children with ASD have diminished neural responses to SR, and that this deficit relates to social learning impairments. C1 [Scott-Van Zeeland, Ashley A.; Poldrack, Russell A.; Bookheimer, Susan Y.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Dapretto, Mirella; Ghahremani, Dara G.; Poldrack, Russell A.; Bookheimer, Susan Y.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Dapretto, Mirella; Poldrack, Russell A.; Bookheimer, Susan Y.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Poldrack, Russell A.; Bookheimer, Susan Y.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Scott-Van Zeeland, Ashley A.] Univ Calif Los Angeles, Neurosci Interdept Program, Los Angeles, CA USA. [Scott-Van Zeeland, Ashley A.] Scripps Translat Sci Inst, La Jolla, CA USA. [Poldrack, Russell A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. RP Bookheimer, SY (reprint author), Semel Inst Psychiat & Biobehav Sci, 760 Westwood Plaza,C8-881, Los Angeles, CA 90095 USA. EM sbook@ucla.edu FU NICHD [P01 HD035470]; NIH/NICHO IPSO [HD0557841, R01 HD065280-01, UL1 12R025774] FX This work was in part supported by grants from the NICHD (P01 HD035470 and NIH/NICHO IPSO HD055784; 1R01 HD065280-01; UL1 12R025774), the National Alliance for Autism Research, Autism Speaks, Whitehall Foundation, as well as by the Training Program in Neurobehavioral Genetics (T32 MH073526), and a NRSA predoctoral fellowship (F31 MH079645) and Dickinson Fellowship to Ashley Scott-Van Zeeland. The authors wish to thank J. Cohen for her technical assistance. For generous support the authors also wish to thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, PiersonLovelace Foundation, Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family and Northstar Fund. The project described was in part also supported by grants (121212169, RR13642 and RI200865) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NTH); its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCR or NWT. 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PD APR PY 2010 VL 3 IS 2 BP 53 EP 67 DI 10.1002/aur.122 PG 15 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100002 PM 20437601 ER PT J AU Travers, BG Klinger, MR Mussey, JL Klinger, LG AF Travers, Brittany G. Klinger, Mark R. Mussey, Joanna L. Klinger, Laura G. TI Motor-Linked Implicit Learning in Persons with Autism Spectrum Disorders SO AUTISM RESEARCH LA English DT Article DE neuropsychology; implicit learning; sequence learning; autism spectrum disorders; serial response task ID SKILL; DISSOCIATION; EQUIVALENCE; ATTENTION; KNOWLEDGE; EXPLICIT; DEFICIT; SPEED; TIME AB Fifteen adolescents and young adults with high-functioning autism spectrum disorders (ASD) and 18 age- and IQ-matched adults with typical development (TD) completed a serial reaction time task (SRT) to examine possible motor-linked implicit learning impairments in persons with ASD. Measures were taken to decrease the role of explicit learning in the SRT. Results showed that participants with AS!) demonstrated intact motor-linked implicit learning. Furthermore, the motor-linked implicit learning appeared to take place at a similar rate across trials in the group with ASD compared to the group with TD. These results suggest that persons with AS!) are successful in implicit learning of motor-linked behavior. The results of this study, coupled with past findings, suggest that people with AS!) may be able to learn motor movements without conscious awareness, especially if the individual is older and is learning fine motor sequences. C1 [Travers, Brittany G.; Klinger, Mark R.; Mussey, Joanna L.; Klinger, Laura G.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. RP Travers, BG (reprint author), Univ Alabama, Dept Psychol, Box 870348, Tuscaloosa, AL 35487 USA. EM bgtravers@crimson.ua.edu CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Barnes KA, 2008, NEUROPSYCHOLOGY, V22, P563, DOI 10.1037/0894-4105.22.5.563 COHEN NJ, 1980, SCIENCE, V210, P207, DOI 10.1126/science.7414331 Constantino JN, 2002, SOCIAL RESPONSIVENES Dawson G, 2000, J AUTISM DEV DISORD, V30, P415, DOI 10.1023/A:1005547422749 Destrebecqz A, 2003, ATTENTION IMPLICIT L, P181 Destrebecqz A, 2001, PSYCHON B REV, V8, P343, DOI 10.3758/BF03196171 Gomez RL, 1999, COGNITION, V70, P109, DOI 10.1016/S0010-0277(99)00003-7 Gordon B., 2007, FOCUS AUTISM OTHER D, V22, P14, DOI DOI 10.1177/10883576070220010201 Greenwald AG, 2003, J PERS SOC PSYCHOL, V85, P197, DOI 10.1037/0022-3514.85.2.197 Imam AA, 2006, J EXP ANAL BEHAV, V85, P107, DOI 10.1901/jeab.2006.58-04 Jimenez L, 2005, PSYCHOL RES-PSYCH FO, V69, P352, DOI 10.1007/s00426-004-0210-9 Kaufman A. 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PD APR PY 2010 VL 3 IS 2 BP 68 EP 77 DI 10.1002/aur.123 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100003 PM 20437602 ER PT J AU Boyd, BA Baranek, GT Sideris, J Poe, MD Watson, LR Patten, E Miller, H AF Boyd, Brian A. Baranek, Grace T. Sideris, John Poe, Michele D. Watson, Linda R. Patten, Elena Miller, Heather TI Sensory Features and Repetitive Behaviors in Children with Autism and Developmental Delays SO AUTISM RESEARCH LA English DT Article DE autism; repetitive behaviors; responses to sensory stimuli; sensory symptoms ID OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM DISORDERS; YOUNG-CHILDREN; TYPICAL DEVELOPMENT; ABNORMALITIES; INTEGRATION; ANNOTATION; ATTENTION; SYMPTOMS; TODDLERS AB This study combined parent and observational measures to examine the association between aberrant sensory features and restricted, repetitive behaviors in children with autism (N = 67) and those with developmental delays (N = 42). Confirmatory factor analysis was used to empirically validate three sensory constructs of interest: hyperresponsiveness, hyporesponsiveness, and sensory seeking. Examining the association between the three derived sensory factor scores and scores on the Repetitive Behavior Scales-Revised revealed the co-occurrence of these behaviors in both clinical groups. Specifically, high levels of hyperresponsive behaviors predicted high levels of repetitive behaviors, and the relationship between these variables remained the same controlling for mental age. We primarily found non-significant associations between hyporesponsiveness or sensory seeking and repetitive behaviors, with the exception that sensory seeking was associated with ritualistic/sameness behaviors. These findings suggest that shared neurobiological mechanisms may underlie hyperresponsive sensory symptoms and repetitive behaviors and have implications for diagnostic classification as well as intervention. C1 [Boyd, Brian A.; Baranek, Grace T.; Sideris, John; Poe, Michele D.; Watson, Linda R.; Patten, Elena; Miller, Heather] Univ N Carolina, Chapel Hill, NC USA. RP Boyd, BA (reprint author), Div Occupat Sci, CB 7122,UNC CH Bondurant Hall, Chapel Hill, NC 27599 USA. EM brian_boyd@med.unc.edu RI Poe, Michele/K-6615-2012 OI Poe, Michele/0000-0001-9693-3638 FU National Institute for Child Health and Human Development [R01-HD42168] FX This research was supported in part by a grant from the National Institute for Child Health and Human Development (R01-HD42168). We thank the families whose participation made this study possible. CR Abramowitz JS, 2005, BEHAV THER, V36, P55, DOI 10.1016/S0005-7894(05)80054-1 American Psychiatric Association, 1994, DIAGN STAT MAN MENT, V4th Aouizerate B, 2004, PROG NEUROBIOL, V72, P195, DOI 10.1016/j.pneurobio.2004.02.004 Baranek G. T., 1998, TACTILE DEFENS UNPUB Baranek G. T., 1999, SENSORY PROCES UNPUB Baranek G. 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T., 1999, SENSORY EXPERI UNPUB Baranek GT, 2007, AM J MENT RETARD, V112, P233, DOI 10.1352/0895-8017(2007)112[233:HSPIYC]2.0.CO;2 BARANEK GT, 1994, J AUTISM DEV DISORD, V24, P457, DOI 10.1007/BF02172128 Baranek GT, 2006, J CHILD PSYCHOL PSYC, V47, P591, DOI 10.1111/j.1469-7610.2005.01546.x Baron-Cohen S, 2009, PHILOS T R SOC B, V364, P1377, DOI 10.1098/rstb.2008.0337 Beck C T, 2001, J Nurs Meas, V9, P201 Ben-Sasson A, 2009, J AUTISM DEV DISORD, V39, P1, DOI 10.1007/s10803-008-0593-3 Ben-Sasson A, 2008, J CHILD PSYCHOL PSYC, V49, P817, DOI 10.1111/j.1469-7610.2008.01899.x Bishop SL, 2006, CHILD NEUROPSYCHOL, V12, P247, DOI 10.1080/09297040600630288 Blue CL, 2008, HEALTH EDUC BEHAV, V35, P316, DOI 10.1177/1090198106297060 Bodfish J.W., 1999, REPETITIVE BEHAV SCA Bodfish JW, 2000, J AUTISM DEV DISORD, V30, P237, DOI 10.1023/A:1005596502855 Boyd BA, 2009, RES AUTISM SPECT DIS, V3, P959, DOI 10.1016/j.rasd.2009.05.003 Dawson G, 2008, DEV PSYCHOPATHOL, V20, P775, DOI 10.1017/S0954579408000370 Dunn W., 1999, SENSORY PROFILE Dziobek I, 2006, NEUROPSYCHOLOGIA, V44, P1891, DOI 10.1016/j.neuropsychologia.2006.02.005 Evans DW, 1999, CHILD PSYCHIAT HUM D, V29, P261, DOI 10.1023/A:1021392931450 Fiske AP, 1997, J NERV MENT DIS, V185, P211, DOI 10.1097/00005053-199704000-00001 Fitzner K, 2007, DIABETES EDUCATOR, V33, P775, DOI 10.1177/0145721707308172 Gabriels RL, 2008, RES AUTISM SPECT DIS, V2, P660, DOI 10.1016/j.rasd.2008.02.002 GAY E, 2008, GATL C RES THEOR INT Gomot M, 2008, BRAIN, V131, P2479, DOI 10.1093/brain/awn172 Gould J, 2008, J LEISURE RES, V40, P47 Grant JS, 1997, RES NURS HEALTH, V20, P269, DOI 10.1002/(SICI)1098-240X(199706)20:3<269::AID-NUR9>3.3.CO;2-3 Greenspan S. 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PD APR PY 2010 VL 3 IS 2 BP 78 EP 87 DI 10.1002/aur.124 PG 10 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100004 PM 20437603 ER PT J AU Best, CA Minshew, NJ Strauss, MS AF Best, Catherine A. Minshew, Nancy J. Strauss, Mark S. TI Gender Discrimination of Eyes and Mouths by Individuals with Autism SO AUTISM RESEARCH LA English DT Article DE autism; gender discrimination; face perception; facial features ID HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; FACE; RECOGNITION; INFORMATION; FIXATION; CHILDREN; GAZE; COMPETENCE; ATTENTION AB Evidence remains mixed about whether individuals with autism look less to eyes and whether they look more at mouths. Few studies have examined how spontaneous attention to facial features relates to face processing abilities. This study tested the ability to discriminate gender from facial features, namely eyes and mouths, by comparing accuracy scores of 17 children with autism and 15 adults with autism to 17 typically developing children and 15 typically developing adults. Results indicated that all participants regardless of diagnosis discriminated gender more accurately from eyes than from mouths. However, results indicated that compared to adults without autism, adults with autism were significantly worse at discriminating gender from eyes. C1 [Best, Catherine A.; Strauss, Mark S.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat & Neurol, Pittsburgh, PA 15260 USA. RP Strauss, MS (reprint author), Univ Pittsburgh, Dept Psychol, 210 S Bouquet St, Pittsburgh, PA 15260 USA. EM strauss@pitt.edu FU NIH [P01-HD354-69] FX This research was supported by a NIH Collaborative Program of Excellence in Autism (CPEA) Grant P01-HD354-69 to Nancy J. Minshew and Mark S. Strauss. We are grateful to the participants and their families for making this research possible and to the CPEA staff for their efforts in recruiting and scheduling participants. We especially thank Holly Gastgeb and Keiran Rump for their time testing participants. 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PD APR PY 2010 VL 3 IS 2 BP 88 EP 93 DI 10.1002/aur.125 PG 6 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100005 PM 20437604 ER PT J AU Shelton, JF Tancredi, DJ Hertz-Picciotto, I AF Shelton, Janie F. Tancredi, Daniel J. Hertz-Picciotto, Irva TI Independent and Dependent Contributions of Advanced Maternal and Paternal Ages to Autism Risk (vol 3, pg 30, 2010) SO AUTISM RESEARCH LA English DT Correction C1 [Shelton, Janie F.; Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Tancredi, Daniel J.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. [Tancredi, Daniel J.] Univ Calif Davis, Ctr Healthcare Policy & Res, Davis, CA 95616 USA. [Hertz-Picciotto, Irva] UC Davis MIND Inst, Sacramento, CA USA. RP Shelton, JF (reprint author), Univ Calif Davis, Dept Publ Hlth Sci, MS1C, Davis, CA 95616 USA. EM jfshelton@ucdavis.edu CR Shelton JF, 2010, AUTISM RES, V3, P30, DOI 10.1002/aur.116 NR 1 TC 1 Z9 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD APR PY 2010 VL 3 IS 2 BP 98 EP 98 DI 10.1002/aur.135 PG 1 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 590ED UT WOS:000277206100006 ER PT J AU Arntzen, E Halstadtro, LB Bjerke, E Halstadtro, M AF Arntzen, Erik Halstadtro, Lill-Beathe Bjerke, Eli Halstadtro, Monica TI TRAINING AND TESTING MUSIC SKILLS IN A BOY WITH AUTISM USING A MATCHING-TO-SAMPLE FORMAT SO BEHAVIORAL INTERVENTIONS LA English DT Article ID STIMULUS-EQUIVALENCE; EMERGENCE; INDIVIDUALS; PROBABILITY; SEQUENCE; CHILDREN; DESIGN AB A 16-year old boy with autism was taught music skills using a matching to sample procedure. He was trained and subsequently tested for the formation of four 4-member classes, including different visual music stimuli, and Norwegian and Vietnamese labels for different major and minor chords. Four different stimuli sets were trained both in one-to-many (OTM) and many-to-one (MTO) training structures. Further, we explored if the reaction times to comparison stimuli increased from training to testing. Results showed that the participant formed equivalence classes with music relations. Furthermore, there were small differences only between OTM and MTO with respect to stimulus equivalence responding. The reaction times to comparison stimuli increased from training to testing, and were most pronounced for the equivalence trials. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Arntzen, Erik] Akershus Univ Coll, N-2001 Lillestrom, Norway. [Halstadtro, Lill-Beathe] St Olavs Hosp, Trondsletten Habilitat Serv, Trondheim, Norway. [Bjerke, Eli; Halstadtro, Monica] Byasen High Sch, Trondheim, Norway. RP Arntzen, E (reprint author), Akershus Univ Coll, POB 423, N-2001 Lillestrom, Norway. 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Intervent. PD APR PY 2010 VL 25 IS 2 BP 129 EP 143 DI 10.1002/bin.301 PG 15 WC Psychology, Clinical SC Psychology GA 584XN UT WOS:000276787700003 ER PT J AU Taylor, SA Anderson, K Mudford, OC AF Taylor, Sarah Ann Anderson, Kerrie Mudford, Oliver C. TI EFFECTS OF TEXTUAL RESPONSE PROMPTS FOR ADOLESCENTS IN A SUBSTANCE ABUSE TREATMENT PROGRAM SO BEHAVIORAL INTERVENTIONS LA English DT Article ID CHILDREN; AUTISM AB Adolescents in a drug and alcohol treatment facility had behavioral deficits in having essential items ready for organized group adventure activities. Checklists (i.e., textual response prompts) were introduced. The data from five participants showed increases in the percentage' of required items ready. Generalization was demonstrated across checklists for different activities, across staff and peer leaders, and a different day of the week. Performance was also maintained when the checklist was removed. 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Intervent. PD APR PY 2010 VL 25 IS 2 BP 145 EP 155 DI 10.1002/bin.303 PG 11 WC Psychology, Clinical SC Psychology GA 584XN UT WOS:000276787700004 ER PT J AU Thomas, BR Lafasakis, M Sturmey, P AF Thomas, Benjamin R. Lafasakis, Michael Sturmey, Peter TI THE EFFECTS OF PROMPTING, FADING, AND DIFFERENTIAL REINFORCEMENT ON VOCAL MANDS IN NON-VERBAL PRESCHOOL CHILDREN WITH AUTISM SPECTRUM DISORDERS SO BEHAVIORAL INTERVENTIONS LA English DT Article AB There are few procedures to teach non-vocal children vocal mands. This study evaluated the effects of prompting, fading, and differential reinforcement on eye contact, pointing, vocal approximations, independent requests and immature mands in three children with Autism Spectrum Disorders who in baseline emitted almost no independent vocal mands. This procedure resulted in a large and socially valid increase in independent vocal mands, other appropriate responses and near elimination of immature mands. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Sturmey, Peter] CUNY, Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Lafasakis, Michael; Sturmey, Peter] CUNY, Grad Ctr, Flushing, NY 11367 USA. [Lafasakis, Michael] CUNY, Queens Coll, Hosp Clin Home Ctr Inc, Flushing, NY 11367 USA. RP Sturmey, P (reprint author), CUNY, Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. EM psturmey@aol.com CR Bourret J, 2004, J APPL BEHAV ANAL, V37, P129, DOI 10.1901/jaba.2004.37-129 DRASGOW E, 2008, APPL BEHAV ANAL LANG Drasgow E, 1998, J APPL BEHAV ANAL, V31, P357, DOI 10.1901/jaba.1998.31-357 Lovaas O. 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SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Conference on Synaptopathies - Dysfunction of Synaptic Function CY SEP 02-04, 2009 CL Newquay, ENGLAND DE brain disease; neurodegeneration; synaptic dysfunction; synaptopathy AB Synaptopathy is an increasingly popular term used to define key features of neurodegenerative and psychiatric disease. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases. The Synaptopathies: Dysfunction of Synaptic Function Biochemical Society Focused Meeting brought together several invited speakers, supplemented with short communications from young scientists, who addressed this possibility. The talks spanned the full gamut of approaches that brought molecular, cellular, systems and whole-animal experimentation together to address how fundamental synaptic biology was increasingly informing on dysfunction in disease. The disease and models thereof discussed included Alzheimer's disease, prions, Huntington's disease, Parkinson's disease, schizophrenia and autism. The audience were asked to reflect on whether synaptopathy, although attractive and conceptually useful, provided a significant explanation as the cause of these major diseases. The breadth of the meeting reinforced the complexity of these brain diseases, supported the significance of synaptic dysfunction in disease, but left open the issue as to whether the prime cause of these disorders could be resolved as simple synaptic dysfunction. Thus, despite revealing a value of synaptopathy, further investigation will be required to reveal its balance in the cause and effect in each of the major brain diseases. C1 [Brose, Nils] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37077 Gottingen, Germany. [O'Connor, Vincent] Univ Southampton, Sch Biol Sci, Southampton SO16 7PX, Hants, England. 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Soc. Trans. PD APR PY 2010 VL 38 BP 498 EP 506 DI 10.1042/BST0380498 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 585DR UT WOS:000276805000036 PM 20298210 ER PT J AU Ploeger, A Raijmakers, MEJ van der Maas, HLJ Galis, F AF Ploeger, Annemie Raijmakers, Maartje E. J. van der Maas, Han L. J. Galis, Frietson TI The Association Between Autism and Errors in Early Embryogenesis: What Is the Causal Mechanism? SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Autism; critical periods; early organogenesis; medical comorbidities; physical anomalies; prenatal complications ID EMBRYONIC PERIOD PROPER; OF-THE-LITERATURE; CONGENITAL-RUBELLA; NEUROFIBROMATOSIS TYPE-1; TUBEROUS SCLEROSIS; SPECTRUM DISORDERS; MATERNAL RUBELLA; DOWNS-SYNDROME; SEQUENCE; EVENTS AB The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development early organogenesis can explain this association. In humans early organogenesis is an embryonic stage, spanning Day 20 to Day 40 after fertilization, which is characterized by intense interactivity among body parts of the embryo. This implies that a single mutation or environmental disturbance affecting development at this stage can have several phenotypic effects (i.e., pleiotropic effects). Disturbances during early organogenesis can lead to many different anomalies, including limb deformities, craniofacial malformations, brain pathology, and anomalies in other organs. We reviewed the literature and found ample evidence for the association between autism and different kinds of physical anomalies, which agrees with the hypothesis that pleiotropic effects are involved in the development of autism. The proposed mechanism integrates findings from a variety of studies on autism, including neurobiological studies and studies on physical anomalies and prenatal influences on neurodevelopmental outcomes. The implication is that the origin of autism can be much earlier in embryologic development than has been frequently reported. C1 [Ploeger, Annemie; Raijmakers, Maartje E. J.; van der Maas, Han L. J.] Univ Amsterdam, Dept Psychol, NL-1018 WB Amsterdam, Netherlands. [Galis, Frietson] Leiden Univ, Dept Biol, Leiden, Netherlands. RP Ploeger, A (reprint author), Univ Amsterdam, Dept Psychol, Roetersstr 15, NL-1018 WB Amsterdam, Netherlands. EM a.ploeger@uva.nl FU Netherlands Organisation for Scientific Research (NWO) FX We would like to thank Conor Dolan, Catharina Hartman, Chantel Kemner, Claus Rueffler, and Andrew Shaner for their continents on earlier drafts of the manuscript. Dr. Ploeger reports having received research funding from the Evolution and Behavior program of the Netherlands Organisation for Scientific Research (NWO). Drs. Raijmakers, Van der Maas, and Galls reported no biomedical financial interests or potential conflicts of interest. 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Giustetto, Maurizio Pizzorusso, Tommaso TI Early Environmental Enrichment Moderates the Behavioral and Synaptic Phenotype of MeCP2 Null Mice SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anxiety; BDNF; environmental enrichment; learning; memory; LTP; Rett syndrome ID VISUAL-SYSTEM DEVELOPMENT; CPG-BINDING PROTEIN-2; RETT-SYNDROME; MOUSE MODEL; MATERNAL-CARE; MUTANT MICE; TRANSCRIPTIONAL REPRESSOR; BDNF TRANSCRIPTION; PLASTICITY; EXPRESSION AB Background: Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder characterized by a variety of symptoms including motor abnormalities, mental retardation, anxiety, and autism. Most of RTT cases are caused by mutations of MeCP2. In mice, impaired MeCP2 function results in synaptic deficits associated with motor, cognitive, and emotional alterations. Environmental enrichment (EE) is a rearing condition that enhances synapse formation and plasticity. Previous studies analyzing the effects of postweaning EE found limited effects on motor performance of male MeCP2 mutants. However, EE during early postnatal development produces powerful effects on neural development and plasticity. Thus, we tested whether early EE could ameliorate several phenotypes of male homozygous and female heterozygous MeCP2 mutants. Methods: We investigated the effects of early EE on motor coordination, structural and functional synaptic plasticity, and brain-derived neurotrophic factor expression in male MeCP2 null mice. Anxiety-related behavior and spatial learning was analyzed in heterozygous MeCP2 female mice. Results: In male mutants, EE modified excitatory and to a lesser extent inhibitory synaptic density in cerebellum and cortex, reversed the cortical long-term potentiation deficit and augmented cortical brain-derived neurotrophic factor levels. Environmental enrichment also ameliorated motor coordination and motor learning. In female heterozygous mice, a model closely mimicking some aspects of RTT symptoms, EE rescued memory deficits in the Morris water maze and decreased anxiety-related behavior. Conclusions: Early EE dramatically improves several phenotypes of MeCP2 mutants. Thus, environmental factors should be taken into account when analyzing phenotypes of MeCP2 knockout mice, an accepted model of RTT. Early EE might be beneficial in RTT patients. C1 [Pizzorusso, Tommaso] CNR, Neurosci Inst Pisa, Area Ric, I-56100 Pisa, Italy. [Pizzorusso, Tommaso] Univ Florence, Dip Psicol, Florence, Italy. [Morando, Laura; Boggio, Elena M.; Giustetto, Maurizio] Univ Turin, Dip Anat, Turin, Italy. Natl Inst Neurosci Italy, Turin, Italy. RP Pizzorusso, T (reprint author), CNR, Neurosci Inst Pisa, Area Ric, Via Moruzzi 1, I-56100 Pisa, Italy. EM pizzorusso@in.cnr.it RI giustetto, maurizio/D-6606-2011 OI giustetto, maurizio/0000-0003-1323-4060 FU Telethon [GGP05236, GGP09196]; Regione Piemonte [142]; European Union [STRP 033378]; EuroRETT FX This work was supported by the Telethon Grants GGP05236 and GGP09196 (to TP and MG), Regione Piemonte (n. 142 to MIUR-PRIN (to MG and TP) and the Non Invasive Nanotransducer for In Vivo gene thErapy (STRP 033378) FP6 European Union project to TP. We thank Dr. Federica Cirimbilli for help behavioral experiments. We thank Professor E. Castren and Dr. T. Rantamaki the kind gift of BDNF KO tissue samples. We thank the EuroRETT project for financial support. 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Psychiatry PD APR 1 PY 2010 VL 67 IS 7 BP 657 EP 665 DI 10.1016/j.biopsych.2009.12.022 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574QY UT WOS:000276008700009 PM 20172507 ER PT J AU Vattikuti, S Chow, CC AF Vattikuti, Shashaank Chow, Carson C. TI A Computational Model for Cerebral Cortical Dysfunction in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cognitive shifting; cortical circuit; fragile X syndrome; minicolumn; saccade; synaptic balance ID LATERAL INTRAPARIETAL AREA; FRAGILE-X-SYNDROME; GABAERGIC INHIBITION; DOWN-REGULATION; NETWORK MODEL; MOUSE MODEL; OCULOMOTOR; ABNORMALITIES; CATATONIA; DEFICITS AB Background: Perturbations to the microscopic level balance between synaptic excitation and inhibition and neuron organization in the cerebral cortex are suggested to underlie autism spectrum disorder (ASD) traits. The mechanism linking these perturbations to cognitive behaviors in ASD is unknown. This study strives to bridge this gap by generating clinically testable diagnostic and pharmacological predictions based on the effect of synaptic imbalance and neuron distribution on a computational local circuit model of the cerebral cortex. Methods: We use a computational microscopic model of the cerebral cortex that incorporates N-methyl-D-aspartate and gamma-aminobutyric acid synaptic kinetics. We employ the model circuit during model tasks similar to visually guided and gap oculomotor saccade tasks and interpret qualitative model predictions of saccade hypometria and dysmetria. We consider the effects of varying the excitatory to inhibitory synaptic balance, neuron density, and neuron clustering in this model. Results: An increase of synaptic excitation over synaptic inhibition results in increased hypometria and dysmetria. Similar effects by either reduced inhibition or increased excitation suggest that a variety of pharmacological compounds can be used for both screening and medical management. On the other hand, any change to the microscopic neuron anatomy that increases the effective maximum distance between excitatory neurons decreases hypometria but has no affect on dysmetria. Conclusions: Perturbations to a computational model of a local cerebral cortical circuit can account for saccade hypometria and dysmetria reported in ASD studies. This approach may provide a direct link between cerebral cortical function and ASD behaviors. C1 [Vattikuti, Shashaank; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Chow, CC (reprint author), NIDDK, Lab Biol Modeling, NIH, Bldg 12A,Room 4007, Bethesda, MD 20892 USA. 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TI Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autoimmunity; immune deficiency; immunoglobulins; Group A beta-hemolytic streptococcus; PANDAS; Tourette's syndrome ID NECROSIS-FACTOR-ALPHA; STREPTOCOCCAL INFECTION; MOVEMENT-DISORDERS; TIC DISORDER; T-CELLS; LYMPHOCYTES; PNEUMONIAE; ANTIBODIES; AUTISM; BLOOD AB Background: Postinfectious autoimmunity has been implicated in burette's syndrome and obsessive-compulsive disorder (TS/OCD), whereas increased frequency of upper respiratory tract infections (URTI) in TS/OCD patients suggests immune deficiency. We hypothesized that antineuronal antibodies may be elevated in patients (reflecting autoimmune processes), and levels of total immunoglobulins (Igs) may be decreased (reflecting immune deficiency). Methods: We analyzed plasma of TS/OCD patients (n = 24) and healthy age- and sex-matched control subjects (n = 22) by enzyme-linked immunosorbent assay (ELISA) for the levels of total and specific IgG, IgM, and IgA against antigens previously identified in multiple sclerosis (myelin basic protein and myelin-associated glycoprotein) and Sydenham's chorea (ganglioside-GM1, lysoganglioside, and tubulin). Results: Total IgA was decreased in TS/OCD patients (median 115 mg/100 mL) compared with control subjects (141 mg/100 mL; p = .02). Specific IgA against all antigens, except tubulin were also decreased in the patients (MPB 0 vs. 13 [ELISA units [EU]; myelin-associated glycoprotein 29 vs. 44 EU, p = .04; ganglioside GM1 21 vs. 35 EU, p = .01; lysoganglioside 44 vs. 56 EU, p = .03; tubulin 44 vs. 44 EU, p = .8). The levels of total IgA and anti-myelin basic protein (MBP) IgA were significantly lower in the subgroup of pediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS) cases (n = 10) than in non-PANDAS cases (n = 9; total IgA 98 mg/100 mL vs. 133 mg/mL, p = .03; anti-MBP IgA 1 vs. 6 EU, p = .03) or healthy control subjects (total IgA 141 mg/100 mL, p = .02; anti-MBP IgA 13 EU, p = .005). Conclusions: At least some TS/OCD patients may suffer IgA dysgammaglobulinemia, possibly rendering the children more prone to URTI. C1 [Kawikova, Ivana; Grady, Bart P. X.; Tobiasova, Zuzana; Zhang, Yan; Bothwell, Alfred L. M.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Katsovich, Liliya; Richmand, Brian J.; Park, Tae Won; Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. [Vojdani, Aristo] Immunosci Lab Inc, Beverly Hills, CA USA. RP Kawikova, I (reprint author), Yale Univ, Sch Med, Dept Immunobiol, 630 TAC,300 Cedar St, New Haven, CT 06520 USA. EM ivana.kawikova@yale.edu RI Grady, Bart/F-3410-2013 FU Tourette's Syndrome Association; National Institutes of Health; Echlin Foundation FX The study was supported by a Tourette's Syndrome Association Research Grant (IK), National Institutes of Health grants (JFL), and additional funds to Dr. Leckman from Brian and Linda Richmond (B. Richmand is one of the coauthors), Betsey Henley-Cohn, Scott D, and Amy I. Horwitz, Marty and Susan Kravet, Samuel Gejdenson, and the Echlin Foundation. We thank Mrs. Heidi Grantz for coordination of the clinical studies. 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Psychiatry PD APR 1 PY 2010 VL 67 IS 7 BP 679 EP 683 DI 10.1016/j.biopsych.2009.09.034 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574QY UT WOS:000276008700012 PM 20006327 ER PT J AU Guastella, AJ Einfeld, SL Gray, KM Rinehart, NJ Tonge, BJ Lambert, TJ Hickie, IB AF Guastella, Adam J. Einfeld, Stewart L. Gray, Kylie M. Rinehart, Nicole J. Tonge, Bruce J. Lambert, Timothy J. Hickie, Ian B. TI Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; developmental disorders; emotion; emotion recognition; face; oxytocin; social cognition ID DEVELOPMENTAL BEHAVIOR CHECKLIST; COMMUNICATION; HUMANS; ADULTS; FACES; MIND AB Background: A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. Methods: In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger's Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. Results: In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. Conclusions: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders. C1 [Guastella, Adam J.; Einfeld, Stewart L.; Lambert, Timothy J.; Hickie, Ian B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2050, Australia. [Einfeld, Stewart L.] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2050, Australia. [Gray, Kylie M.; Rinehart, Nicole J.; Tonge, Bruce J.] Monash Univ, Ctr Dev Psychiat & Psychol, Sch Psychol Psychiat & Psychol Med, Melbourne, Vic 3004, Australia. RP Guastella, AJ (reprint author), Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2050, Australia. EM aguastella@med.usyd.edu.au RI Gray, Kylie/H-3345-2014 OI Gray, Kylie/0000-0001-6518-4240 FU Brain & Mind Research Institute; National Health and Medical Research Council [570897] FX This study was funded by both the Brain & Mind Research Institute and National Health and Medical Research Council Project Grant Number 570897. CR American Psychiatric Association, 2000, DIAGN STAT MAN MENT Baron-Cohen S, 2000, NEUROSCI BIOBEHAV R, V24, P355, DOI 10.1016/S0149-7634(00)00011-7 Baron-Cohen S, 2001, J CHILD PSYCHOL PSYC, V42, P241, DOI 10.1017/S0021963001006643 Born J, 2002, NAT NEUROSCI, V5, P514, DOI 10.1038/nn849 Brereton AV, 2002, J AM ACAD CHILD PSY, V41, P1369, DOI 10.1097/01.CHI.0000024838.94814.A5 Domes G, 2007, BIOL PSYCHIAT, V61, P731, DOI 10.1016/j.biopsych.2006.07.015 Domes G, 2007, BIOL PSYCHIAT, V62, P1187, DOI 10.1016/j.biopsych.2007.03.025 Donaldson ZR, 2008, SCIENCE, V322, P900, DOI 10.1126/science.1158668 EINFELD SL, 1995, J AUTISM DEV DISORD, V25, P81, DOI 10.1007/BF02178498 Guastella AJ, 2008, BIOL PSYCHIAT, V64, P256, DOI 10.1016/j.biopsych.2008.02.008 Guastella AJ, 2008, BIOL PSYCHIAT, V63, P3, DOI 10.1016/j.biopsych.2007.06.026 Haxby JV, 2002, BIOL PSYCHIAT, V51, P59, DOI 10.1016/S0006-3223(01)01330-0 Hollander E, 2003, NEUROPSYCHOPHARMACOL, V28, P193, DOI 10.1038/sj.npp.1300021 Hollander E, 2007, BIOL PSYCHIAT, V61, P498, DOI 10.1016/j.bipsych.2006.05.030 Klin A, 2002, ARCH GEN PSYCHIAT, V59, P809, DOI 10.1001/archpsyc.59.9.809 Losh M, 2009, ARCH GEN PSYCHIAT, V66, P518, DOI 10.1001/archgenpsychiatry.2009.34 Parr LA, 2005, CURR OPIN NEUROBIOL, V15, P716, DOI 10.1016/j.conb.2005.10.017 Wechsler D, 1997, WECHSLER ADULT INTEL, V3rd Wechsler D., 2005, WECHSLER INTELLIGENC, V4th NR 19 TC 250 Z9 256 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2010 VL 67 IS 7 BP 692 EP 694 DI 10.1016/j.biopsych.2009.09.020 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574QY UT WOS:000276008700014 PM 19897177 ER PT J AU Keen, DV Reid, FD Arnone, D AF Keen, D. V. Reid, F. D. Arnone, D. TI Autism, ethnicity and maternal immigration SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; PERINATAL RISK-FACTORS; SPECTRUM DISORDERS; PATERNAL AGE; DIAGNOSTIC INTERVIEW; INFANTILE-AUTISM; CHILDREN BORN; POPULATION; PREVALENCE; CALIFORNIA AB Background A growing number of European studies, particularly from Nordic countries, suggest an increased frequency of autism in children of immigrant parents. In contrast, North American studies tend to conclude that neither maternal ethnicity nor immigrant status are related to the rate of autism-spectrum disorders. Aims To examine the hypotheses that maternal ethnicity and/or immigration are linked to the rate of childhood autism-spectrum disorders. Method Retrospective case-note analysis of all 428 children diagnosed with autism-spectrum disorders presenting to the child development services in two centres during a 6-year period. Results Mothers born outside Europe had a significantly higher risk of having a child with an autism-spectrum disorder compared with those born in the UK, with the highest risk observed for the Caribbean group (relative risks (RRs) in the two centres: RR = 10.01, 95% CI 5.53-18.1 and RR = 8.89, 95% CI 5.08-15.5). Mothers of Black ethnicity had a significantly higher risk compared with White mothers (RR = 8.28, 95% CI 5.41-12.7 and RR = 3.84, 95% CI 2.93-5.02). Analysis of ethnicity and immigration factors together suggests the increased risk is predominately related to immigration. Conclusions Maternal immigration is associated with substantial increased risk of autism-spectrum disorders with differential risk according to different region of birth and possibly ethnicity. C1 [Keen, D. V.] St Georges Healthcare NHS Trust, London, England. [Reid, F. D.] Univ London, London WC1E 7HU, England. [Arnone, D.] Univ Manchester, Neurosci & Psychiat Unit, Oxford, England. [Arnone, D.] Warneford Hosp, Univ Dept Psychiat, Oxford OX3 7JX, England. RP Keen, DV (reprint author), St George Hosp, Room 2-35,2nd Floor Clare House,Blackshaw Rd, London SW17 0QT, England. EM daphne.keen@stgeorges.nhs.uk RI Arnone, Danilo/A-3974-2012 FU Medical Research Council UK FX D.A. is currently supported by the Medical Research Council UK. 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J. Psychiatry PD APR PY 2010 VL 196 IS 4 BP 274 EP 281 DI 10.1192/bjp.bp.109.065490 PG 8 WC Psychiatry SC Psychiatry GA 578JF UT WOS:000276288900006 PM 20357302 ER PT J AU Donno, R Parker, G Gilmour, J Skuse, DH AF Donno, R. Parker, G. Gilmour, J. Skuse, D. H. TI Social communication deficits in disruptive primary-school children SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID AUTISTIC SPECTRUM DISORDERS; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; REVISED VERSION; MIND; ASSOCIATIONS; RECOGNITION; POPULATION; PREVALENCE; INTERESTS AB Background Parent and teacher data, from questionnaire surveys, suggest that school-identified disruptive children often have pragmatic language deficits of an autistic type. Aims This replication study aimed to confirm earlier findings, using individual clinical assessment to investigate traits of autism-spectrum disorder in disruptive children. Method Persistently disruptive children (n = 26) and a comparison group (n = 22) were recruited from primary schools in a deprived inner-city area. Measures included standardised autism diagnostic interviews (with parents) and tests of IQ, social cognition, theory of mind and attention (with children). Results The disruptive children possessed poorer pragmatic language skills (P<0.0001) and mentalising abilities (P<0.05) than comparisons. Nine disruptive children (35%) met ICD-10 criteria for atypical autism or Asperger syndrome. Conclusions Many persistently disruptive children have undetected disorders of social communication, which are of potential aetiological significance. C1 [Skuse, D. H.] UCL, Inst Child Hlth, Behav & Brain Sci Unit, London WC1N 1EH, England. [Donno, R.] Great Ormond St Hosp Sick Children, Psychosocial & Family Serv, London WC1N 3JH, England. [Parker, G.] Mile End Hosp, Rehabil & Hlth Psychol Serv, London, England. 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J. Psychiatry PD APR PY 2010 VL 196 IS 4 BP 282 EP 289 DI 10.1192/bjp.bp.108.061341 PG 8 WC Psychiatry SC Psychiatry GA 578JF UT WOS:000276288900007 PM 20357304 ER PT J AU Johansson, CF AF Johansson, Carl Fredrik TI The Imprinted Brain: How Genes Set the Balance between Autism and Psychosis SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Johansson, Carl Fredrik] S Kensington & Chelsea NHS Fdn Trust, London, England. RP Johansson, CF (reprint author), S Kensington & Chelsea NHS Fdn Trust, London, England. EM freddie.johansson@nhs.net CR BADCOCK C, 2009, IMPRINTED BRAIN HOW NR 1 TC 0 Z9 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2010 VL 196 IS 4 BP 334 EP 335 DI 10.1192/bjp.bp.109.071084 PG 2 WC Psychiatry SC Psychiatry GA 578JF UT WOS:000276288900024 ER PT J AU Begue, P AF Begue, Pierre TI Consequences of opposition to vaccination in France and Europe. How to maintain effective vaccine coverage in 2010? SO BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE LA French DT Article DE VACCINATION; MASS VACCINATION; TREATMENT REFUSAL ID MMR VACCINATION; IMMUNIZATION; MEASLES; RUBELLA; MUMPS; PERTUSSIS; DISEASES; PARENTS; REFUSAL; AUTISM AB Refusal of vaccination can result in inadequate vaccine coverage. The collective benefit of immunisation depends on a sufficient and sustained level of vaccine coverage. Low vaccine coverage can lead to the persistence of preventable diseases and, in some cases, to a dangerous shift in the age of pathogen encounter towards adulthood. This is the case of measles in Europe, where some countries, including France, have not reached the effective vaccine coverage rate of 95 %. Outbreaks are occurring, leading to complications (encephalitis and pneumonia) in adolescents and adults, necessitating hospitalization in nearly one-third of cases. The French population is also under-vaccinated against hepatitis B, due to fears of a risk of demyelinating disorders: the coverage rate is currently only about 30 % in infants and 10 % in adolescents. These difficulties are due to negligence and to vaccine refusal by parents. Refusal of immunisation has a long history in Europe, and explains for example why pertussis remained endemic in many countries until 1995, and also the resurgence of diphtheria in the Russian federation during the 1990s. Sections of Western society are now questioning the need for some routine vaccines, overlooking the fact that they have eradicated some diseases (polio, diphtheria, etc.) and protect effectively against lesser-known pathogens such as hepatitis B virus and HP V. In France, it will be necessary to restructure healthcare professional training programs in vaccinology and to provide the public with more thorough information on the risk-benefit ratio of vaccination. The recent controversy surrounding pandemic H1N1 influenza vaccination demonstrates that the public and the media tend to focus more on the potential risks of vaccination than on its benefits. A vigorous ethical and political debate is needed to shape an effective and acceptable vaccine policy for the 21(st) century. 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Acad. Natl. Med. PD APR-MAY PY 2010 VL 194 IS 4-5 BP 719 EP 732 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 683YO UT WOS:000284514400004 PM 21568045 ER PT J AU Santha, JC AF Santha, Josiane Caron TI Group work for Children with Autism Spectrum Disorder, Ages 5-11, An Integrated Approach SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Book Review CR HOWE C, 2008, GROUP WORK CHILDREN NR 1 TC 0 Z9 0 PU CANADIAN ASSOC OCCUPATIONAL THERAPISTS PI OTTAWA PA CTTC BLDG, 3400-1125 COLONEL BY DRIVE, OTTAWA, ONTARIO K1S 5R1, CANADA SN 0008-4174 J9 CAN J OCCUP THER JI Can. J. Occup. Ther. PD APR PY 2010 VL 77 IS 2 BP 100 EP 100 PG 1 WC Rehabilitation SC Rehabilitation GA V20TP UT WOS:000208162600007 ER PT J AU Santha, JC AF Santha, Josiane Caron TI Group work for Children with Autism Spectrum Disorder, Ages 3-5, An Integrated Approach SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Book Review CR DAVIDSON LA, 2007, GROUP WORK CHILDREN NR 1 TC 0 Z9 0 PU CANADIAN ASSOC OCCUPATIONAL THERAPISTS PI OTTAWA PA CTTC BLDG, 3400-1125 COLONEL BY DRIVE, OTTAWA, ONTARIO K1S 5R1, CANADA SN 0008-4174 J9 CAN J OCCUP THER JI Can. J. Occup. Ther. PD APR PY 2010 VL 77 IS 2 BP 100 EP 100 PG 1 WC Rehabilitation SC Rehabilitation GA V20TP UT WOS:000208162600008 ER PT J AU Surridge, MS AF Surridge, M. Sian TI STOP That Seemingly Senseless Behaviour! FBA-Based Interventions for People with Autism SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Book Review CR Glasberg BA, 2008, STOP SEEMINGLY SENSE NR 1 TC 0 Z9 0 PU CANADIAN ASSOC OCCUPATIONAL THERAPISTS PI OTTAWA PA CTTC BLDG, 3400-1125 COLONEL BY DRIVE, OTTAWA, ONTARIO K1S 5R1, CANADA SN 0008-4174 J9 CAN J OCCUP THER JI Can. J. Occup. Ther. PD APR PY 2010 VL 77 IS 2 BP 112A EP 112A PG 1 WC Rehabilitation SC Rehabilitation GA V20TP UT WOS:000208162600010 ER PT J AU Leew, SV Stein, NG Ben Gibbard, W AF Leew, Shirley V. Stein, Nicole G. Ben Gibbard, W. TI Weighted vests' effect on social attention for toddlers with Autism Spectrum Disorders SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Article DE Autistic disorder; Infancy and childhood; Sensory motor integration; Weighted vests AB Background. There is limited research validating the use of weighted vests for problem behaviours/social attention in toddlers with autism spectrum disorders (ASD) although vests are commonly used in early intervention to improve attention. Purpose. The effect of weighted vests on competing behaviours and joint attention (a pivotal skill for development and a core deficit for toddlers with ASD) in semi-structured play with their mothers was investigated. Methods. A multiple baseline design that included generalization probes to provide evidence of treatment effects across adult female play partners. Unambiguous definitions were created for competing behaviours and joint attention resulting in good inter-observer reliability. Mothers' morale was measured pre- and post-intervention. Findings. There were no replicated effects of vests on competing behaviours or joint attention. Mothers experienced increased morale in spite of null effects of the intervention. Implications. The findings suggest needed re-evaluation of the use of weighted vests with toddlers. C1 [Leew, Shirley V.; Stein, Nicole G.] Univ Alberta, Alberta Hlth Serv, Child Dev Ctr, Calgary, AB T3B 6A8, Canada. [Leew, Shirley V.] Univ Alberta, Alberta Childrens Hosp, Calgary, AB T3B 6A8, Canada. RP Leew, SV (reprint author), Univ Alberta, Alberta Hlth Serv, Child Dev Ctr, Rm C4-316,2888 Shaganappi Tr NW, Calgary, AB T3B 6A8, Canada. EM Shirley.leew@albertahealthservices.ca FU Alberta Centre for Child, Family, and Community Research [E-20119]; Allied Health Research Award; Alberta Children's Hospital Foundation; Decision Support Research Team, Alberta Children's Hospital FX Alberta Centre for Child, Family, and Community Research (E-20119); Allied Health Research Award, Alberta Children's Hospital Foundation; and research support from the Decision Support Research Team, Alberta Children's Hospital. 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PD APR PY 2010 VL 77 IS 2 BP 113 EP 123 DI 10.2182/cjot.2010.77.2.7 PG 11 WC Rehabilitation SC Rehabilitation GA V20TP UT WOS:000208162600011 PM 20464896 ER PT J AU Asher, A AF Asher, Asha TI Seeing is Believing: Video Self-Modeling For People With Autism and Developmental Disabilities SO CANADIAN JOURNAL OF OCCUPATIONAL THERAPY-REVUE CANADIENNE D ERGOTHERAPIE LA English DT Book Review CR BUGGEY T, 2009, SEEING BELIEVING VID NR 1 TC 0 Z9 0 PU CANADIAN ASSOC OCCUPATIONAL THERAPISTS PI OTTAWA PA CTTC BLDG, 3400-1125 COLONEL BY DRIVE, OTTAWA, ONTARIO K1S 5R1, CANADA SN 0008-4174 J9 CAN J OCCUP THER JI Can. J. Occup. Ther. PD APR PY 2010 VL 77 IS 2 BP 125 EP 125 PG 1 WC Rehabilitation SC Rehabilitation GA V20TP UT WOS:000208162600013 ER PT J AU Minami, T Miyata, E Sakamoto, Y Yamazaki, H Ichida, S AF Minami, Takeshi Miyata, Eriko Sakamoto, Yamato Yamazaki, Hideo Ichida, Seiji TI Induction of metallothionein in mouse cerebellum and cerebrum with low-dose thimerosal injection SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE Thimerosal; Ethyl mercury; Metallothionein; Cerebellum; Cerebrum; Capillary zone electrophoresis ID NEURODEVELOPMENTAL DISORDERS; MERCURY CONCENTRATIONS; ASTROCYTE CULTURES; RAT-BRAIN; METHYLMERCURY; AUTISM; EXPRESSION; VACCINES; LOCALIZATION; ETHYLMERCURY AB Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine preservative. We previously observed that the mercury concentration in mouse brains did not increase with the clinical dose of thimerosal injection, but the concentration increased in the brain after the injection of thimerosal with lipopolysaccharide, even if a low dose of thimerosal was administered. Thimerosal may penetrate the brain, but is undetectable when a clinical dose of thimerosal is injected; therefore, the induction of metallothionein (MT) messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA expression in the cerebellum was three times higher than that in the cerebrum after the injection of 12 A mu g/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3 mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 A mu g/kg of thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h, and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than in the cerebrum by the injection of low-dose thimerosal. It is thought that the cerebellum is a sensitive organ against thimerosal. As a result of the present findings, in combination with the brain pathology observed in patients diagnosed with autism, the present study helps to support the possible biological plausibility for how low-dose exposure to mercury from thimerosal-containing vaccines may be associated with autism. C1 [Minami, Takeshi; Miyata, Eriko; Yamazaki, Hideo] Kinki Univ, Dept Life Sci, Sch Sci & Engn, Osaka 5778502, Japan. [Sakamoto, Yamato; Ichida, Seiji] Kinki Univ, Dept Clin Pharm, Sch Pharmaceut Sci, Osaka 5778502, Japan. RP Minami, T (reprint author), Kinki Univ, Dept Life Sci, Sch Sci & Engn, 3-4-1 Kowakae, Osaka 5778502, Japan. 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Toxicol. PD APR PY 2010 VL 26 IS 2 BP 143 EP 152 DI 10.1007/s10565-009-9124-z PG 10 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA 562XU UT WOS:000275090000006 PM 19357975 ER PT J AU Crepel, A Breckpot, J Fryns, JP De la Marche, W Steyaert, J Devriendt, K Peeters, H AF Crepel, A. Breckpot, J. Fryns, J-P De la Marche, W. Steyaert, J. Devriendt, K. Peeters, H. TI DISC1 duplication in two brothers with autism and mild mental retardation SO CLINICAL GENETICS LA English DT Article DE 1q42; 2; autism; DISC1; duplication ID COPY-NUMBER VARIATION; SPECTRUM DISORDER; HUMAN GENOME; SCHIZOPHRENIA; ASSOCIATION; POPULATION; FAMILY; GENES; SCALE; TRANSLOCATION AB We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigate the causal relationship of the duplication to the autism phenotype. We conclude that the 1q42.2 microduplication probably confers susceptibility to autism in the current family. This study is a typical illustration of the difficult interpretation of causality of a very rare variant in neuropsychiatric disease and the challenge of genetic counselling in a particular family. C1 [Crepel, A.; Breckpot, J.; Fryns, J-P; Steyaert, J.; Devriendt, K.; Peeters, H.] Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium. 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During the picture sequences participants responded to an unpredictable probe picture about where the character believed the object to be located or where the object was located in reality. In Experiment 1 participants were not directly instructed to track the character's beliefs about the object. There was a significant reaction time cost for belief probes compared with matched reality probes, whether the character's belief was true or false. In Experiment 2, participants were asked to track where the character thought the object was located, responses to belief probes were faster than responses to reality probes, suggesting that the difference observed in Experiment 1 was not due to intrinsic differences between the probes, but was more likely to be due to participants inferring beliefs ad hoc in response to the probe. In both Experiments 1 and 2, responses to belief and reality probes were faster in the true belief condition than in the false belief condition. In Experiment 3 this difference was largely eliminated when participants had fewer reasons to make belief inferences spontaneously. These two lines of evidence are neatly explained by the proposition that neither true nor false beliefs are ascribed automatically, but that belief ascription may occur spontaneously in response to task demands. (C) 2009 Elsevier B.V. All rights reserved. C1 [Back, Elisa] Kingston Univ London, Psychol Res Unit, Kingston upon Thames KT1 2EE, Surrey, England. [Apperly, Ian A.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. RP Back, E (reprint author), Kingston Univ London, Psychol Res Unit, Kingston upon Thames KT1 2EE, Surrey, England. 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Here, we directly tested this hypothesis by evaluating the distracting strength of eye contact on concurrent visual processing in the well-known Stroop's paradigm. As expected, participants showed stronger Stroop interference under concomitant eye contact as compared to closed eyes. Two control experiments allowed ruling out low-level account of this effect as well as non-specific effect of the presence of open eyes. This suggests that refraining from processing eye contact is actually as difficult as refraining from word reading in the Stroop task. Crucially, the eye contact effect was obtained while gaze was not under the direct focus of attention and the participants were faced with another powerful distracter (the incongruent word) in the task at hand. Thus, there is a cost of being watched even in circumstances where the processing of direct gaze is strongly disfavored. The present results emphasize the crucial status of eye contact in human cognition. (C) 2010 Elsevier B.V. All rights reserved. C1 [Conty, Laurence] Ecole Normale Super, INSERM, U970, Cognit Neurosci Lab, F-75005 Paris, France. [George, Nathalie] Hop La Pitie Salpetriere, Ctr Rech, CNRS, Inst Cerveau Moelle,UMR 7225, F-75651 Paris 13, France. [George, Nathalie] Univ Paris 06, UPMC, UMR 7225, CRICM,UMRS 975, F-75013 Paris, France. [Gimmig, David; Belletier, Clement; Huguet, Pascal] Univ Aix Marseille 1, F-13331 Marseille 3, France. [Gimmig, David; Belletier, Clement; Huguet, Pascal] CNRS, UMR 6146, LPC, F-13331 Marseille 3, France. RP Conty, L (reprint author), Ecole Normale Super, INSERM, U970, Cognit Neurosci Lab, 29 Rue Ulm, F-75005 Paris, France. 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Our source of data were four published studies [14]. We first applied a two-step enrichment strategy for autism-specific genes. We fished out from the four mentioned studies a list of 2928 genes overall overlapping 328 CNVs in patients and we first selected a sub-group of 2044 genes after excluding those ones that are also involved in CNVs reported in the Database of Genomic Variants (enrichment step 1). We then selected from the step 1-enriched list a sub-group of 514 genes each of which was found to be deleted or duplicated in at least two patients (enrichment step 2). The number of statistically significant processes and pathways identified by the Database for Annotation, Visualization and Integrated Discovery and Ingenuity Pathways Analysis softwares with the step 2-enriched list was significantly higher compared to the step 1-enriched list. In addition, statistically significant GO terms, biofunctions and pathways related to nervous system development and function were exclusively identified by the step 2-enriched list of genes. Interestingly, 21 genes were associated to axon growth and pathfinding. The latter genes and other ones associated to nervous system in this study represent a new set of autism candidate genes deserving further investigation. In summary, our results suggest that the autism's "connectivity genes" in some patients affect very early phases of neurodevelopment, i.e., earlier than synaptogenesis. C1 [Sbacchi, Silvia; Calo, Ignazio; Romano, Valentino] Univ Palermo, Dipartimento Oncol Sperimentale & Applicaz Clin, Palermo, Italy. [Acquadro, Francesco] CNIO, Mol Cytogenet Grp, Madrid, Spain. [Acquadro, Francesco] CIBERER, Madrid, Spain. [Cali, Francesco; Romano, Valentino] IRCCS, Assoc Oasi Maria SS, Troina, EN, Italy. RP Romano, V (reprint author), Univ Palermo, Dipartimento Oncol Sperimentale & Applicaz Clin, Via S Lorenzo Colli 312, Palermo, Italy. EM vromano@unipa.it FU University of Palermo [ORPA07P5PP] FX This research was funded by the University of Palermo Grant # "Ex quota 60 %" ORPA07P5PP. Project's title: "Analisi genomica funzionale in cellule di sangue periferico di pazienti autistici". The Authors wish to thank Dr. Adam Corner (I. P. A., UK), Dr. Claudia Coronnello, Prof. Salvatore Micciche and Prof. Rosario Nunzio Mantegna (D. I. F. T. E. R., University of Palermo), Dr. Maurizio Elia (Oasi Institute, Troina, Italy) for their valuable comments and suggestions in the preparation of this manuscript. 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PD APR PY 2010 VL 23 IS 2 BP 95 EP 96 DI 10.1097/WCO.0b013e3283377644 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700001 PM 20216345 ER PT J AU Zwaigenbaum, L AF Zwaigenbaum, Lonnie TI Advances in the early detection of autism SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; early diagnosis; infants; longitudinal design; screening ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; HIGH-RISK; CLINICAL-ASSESSMENT; MODIFIED CHECKLIST; INFANT SIBLINGS; YOUNG-CHILDREN; 2ND YEAR; TODDLERS; INTERVENTION AB Purpose of review Early detection and diagnosis of autism spectrum disorders (ASDs) allows opportunities for children and their families to benefit more fully from early supports and interventions. Recent findings Recent advances in early detection research have resulted from prospective studies of high-risk infants and large ASD screening studies conducted in community settings. With improvement in early detection of autism, exciting progress has been made in establishing the efficacy of ASD-specific interventions for toddlers as young as 18 months on the basis of controlled clinical trials. Summary There has been increasing emphasis on opportunities to link early behavioral expression to the underlying neurobiology of ASD, potentially bringing us closer to the fundamental mechanisms underlying this disorder. C1 [Zwaigenbaum, Lonnie] Univ Alberta, Glenrose Rehabil Hosp, Dept Pediat, Edmonton, AB T5G 0B7, Canada. RP Zwaigenbaum, L (reprint author), Univ Alberta, Glenrose Rehabil Hosp E209, Dept Pediat, 10230-111 Ave, Edmonton, AB T5G 0B7, Canada. EM lonnie.zwaigenbaum@albertahealthservices.ca FU Alberta Heritage Foundation for Medical Research FX Dr. Zwaigenbaum holds the Stollery Children's Hospital Foundation Endowed Chair in Autism Research and is supported by a Health Scholar Award from the Alberta Heritage Foundation for Medical Research. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 97 EP 102 DI 10.1097/WCO.0b013e3283372430 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700002 PM 20154615 ER PT J AU Herbert, MR AF Herbert, Martha R. TI Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; dynamic encephalopathy; environment; glutathione; oxidative stress; pathophysiology ID INCLUDING DEVELOPMENTAL IMMUNOTOXICITY; BLOOD-BRAIN-BARRIER; DIAGNOSTIC SUBSTITUTION; IMMUNE-RESPONSE; PRENATAL STRESS; ONSET AUTISM; CHILDREN; PREVALENCE; VACCINES; EXPOSURE AB Purpose of review This review presents a rationale and evidence for contributions of environmental influences and environmentally vulnerable physiology to autism spectrum disorders (ASDs). Recent findings Recent studies suggest a substantial increase in ASD prevalence above earlier Centers for Disease Control figures of one in 150, only partly explicable by data artifacts, underscoring the possibility of environmental contributors to increased prevalence. Some gene variants in ASD confer altered vulnerability to environmental stressors and exposures. De-novo mutations and advanced parental age as a risk factor for ASD also suggest a role for environment. Systemic and central nervous system pathophysiology, including oxidative stress, neuroinflammation, and mitochondrial dysfunction can be consistent with a role for environmental influence (e. g. from air pollution, organophosphates, heavy metals) in ASD, and some of the underlying biochemical disturbances (such as abnormalities in glutathione, a critical antioxidant and detoxifier) can be reversed by targeted nutritional interventions. Dietary factors and food contaminants may contribute risk. Improvement and loss of diagnosis in some with ASD suggest brain circuitry amenable to environmental modulation. Summary Prevalence, genetic, exposure, and pathophysiological evidence all suggest a role for environmental factors in the inception and lifelong modulation of ASD. This supports the need for seeking targets for early and ongoing medical prevention and treatment of ASD. C1 Massachusetts Gen Hosp, TRANSCEND Res Program, Charlestown, MA 02129 USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, TRANSCEND Res Program, 149 13th St,Room 10-018, Charlestown, MA 02129 USA. EM mherbert1@partners.org FU National Institute of Health (NINDS); Department of Defense Autism Spectrum Disorders Research Program; Nancy Lurie Marks Family Foundation; Autism Society FX The present study was supported by National Institute of Health (NINDS), Department of Defense Autism Spectrum Disorders Research Program, Nancy Lurie Marks Family Foundation, Autism Society. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 103 EP 110 DI 10.1097/WCO.0b013e328336a01f PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700003 PM 20087183 ER PT J AU Goines, P Van de Water, J AF Goines, Paula Van de Water, Judy TI The immune system's role in the biology of autism SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; autoantibodies; cytokines; immune system; immunoglobulin ID MIGRATION INHIBITORY FACTOR; SPECTRUM DISORDERS; UNAFFECTED SIBLINGS; FETAL-BRAIN; ANTIBRAIN ANTIBODIES; CYTOKINE PRODUCTION; CHILDREN; AUTOANTIBODIES; AUTOIMMUNITY; RESPONSES AB Purpose of review The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. Recent findings The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed toward fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. Although studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. Summary In summary, the exciting research regarding the role of the immune system in autism spectrum disorders may have profound implications for diagnosis and treatment of this devastating disease. C1 [Goines, Paula; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Goines, Paula; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Goines, Paula; Van de Water, Judy] Univ Calif Davis, NIEHS, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Div Rheumatol, 451 Hlth Sci Dr, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU NIEHS [1 P01 ES11269-01, 1 R01-ES015359]; U. S. Environmental Protection Agency (U. S. EPA) [R829388]; UC Davis M. I. N. D. Institute; Autism Speaks FX The author's studies cited herein were supported by grants NIEHS 1 P01 ES11269-01, the U. S. Environmental Protection Agency (U. S. EPA) through the Science to Achieve Results (STAR) program (grant R829388), NIEHS 1 R01-ES015359, the UC Davis M. I. N. D. Institute, and Autism Speaks. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 111 EP 117 DI 10.1097/WCO.0b013e3283373514 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700004 PM 20160651 ER PT J AU Rubenstein, JLR AF Rubenstein, John L. R. TI Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; brain development; cortex size; excitation/inhibition ratio; frontal cortex; genetics; sex steroid ID DLX GENES; CEREBRAL-CORTEX; FRONTAL-CORTEX; DEVELOPING FOREBRAIN; HOMEOBOX GENES; DIFFERENTIATION; MIGRATION; FGF17; BRAIN; MICE AB Purpose of review Molecular and genetic insights into the etiology of autism spectrum disorders are now available. The field now needs to understand how these perturbations affect development and function of the brain. Recent findings Herein I review the genetic mechanisms known to predispose to autism spectrum disorders, and attempt to consolidate many of these within cellular/molecular pathways that regulate development of neural systems that underlie cognition and social behaviors. In addition to the clear relationship of many susceptibility genes to activity-dependent neural responses, I propose the existence of three additional mechanisms that may contribute to autism spectrum disorders: evolutionary-driven expansion of cerebrum and cerebellar size; imbalance in the excitatory/inhibitory ratio in local and extended circuits; the hormonal effects of the male genotype. Summary Understanding these mechanisms opens the possibility to therapeutic interventions. C1 Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, Ctr Neurobiol & Psychiat, Dept Psychiat, San Francisco, CA 94158 USA. RP Rubenstein, JLR (reprint author), Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, Ctr Neurobiol & Psychiat, Dept Psychiat, Rock Hall,Room RH 284C,UCSF MC 2611,1550 4th St, San Francisco, CA 94158 USA. EM john.rubenstein@ucsf.edu FU Nina Ireland; Simons and Weston Havens Foundations; NINDS; NIMH FX JLRR is funded by Nina Ireland, the Simons and Weston Havens Foundations, NINDS and NIMH. I thank Susan Yu for her help with the references. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 118 EP 123 DI 10.1097/WCO.0b013e328336eb13 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700005 PM 20087182 ER PT J AU Minshew, NJ Keller, TA AF Minshew, Nancy J. Keller, Timothy A. TI The nature of brain dysfunction in autism: functional brain imaging studies SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; connectivity; fMRI ID SENTENCE COMPREHENSION; SPECTRUM DISORDERS; DEFAULT NETWORK; CONNECTIVITY; UNDERCONNECTIVITY; FMRI; SYNCHRONIZATION; ABNORMALITIES; PERFORMANCE; CHILDREN AB Purpose of review Functional magnetic resonance imaging studies have had a profound impact on the delineation of the neurobiologic basis for autism. Advances in fMRI technology for investigating functional connectivity, resting state connectivity, and a default mode network have provided further detail about disturbances in brain organization and brain-behavior relationships in autism to be reviewed in this article. Recent findings Recent fMRI studies have provided evidence of enhanced activation and connectivity of posterior, or parietal-occipital, networks and enhanced reliance on visuospatial abilities for visual and verbal reasoning in high functioning individuals with autism. Evidence also indicates altered activation in frontostriatal networks for cognitive control, particularly involving anterior cingulate cortex, and altered connectivity in the resting state and the default mode network. The findings suggest that the specialization of many cortical networks of the human brain has failed to develop fully in high functioning individuals with autism. Summary This research provides a growing specification of to the neurobiologic basis for this complex syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With this knowledge has come new neurobiologically based opportunities for intervention. C1 [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Keller, Timothy A.] Carnegie Mellon Univ, Ctr Cognit Brain Imaging, Pittsburgh, PA 15213 USA. RP Minshew, NJ (reprint author), Univ Pittsburgh, Sch Med, Webster Hall,Suite 300,3811 OHara St, Pittsburgh, PA 15213 USA. EM minshewnj@upmc.edu FU NIH [HD055748] FX This work is funded by NIH HD055748. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 124 EP 130 DI 10.1097/WCO.0b013e32833782d4 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700006 PM 20154614 ER PT J AU Coury, D AF Coury, Daniel TI Medical treatment of autism spectrum disorders SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism spectrum disorders; epilepsy; gastrointestinal conditions; genetic testing; immune function; medical treatment ID FRAGILE-X-SYNDROME; GASTROINTESTINAL SYMPTOMS; EPILEPTIFORM DISCHARGES; BEHAVIORAL TREATMENT; TYPICAL DEVELOPMENT; ROLANDIC EPILEPSY; EEG ABNORMALITIES; SLEEP PROBLEMS; CHILDREN; REGRESSION AB Purpose of review There are several common medical conditions occurring in people with autism spectrum disorders (ASD) that can benefit from treatment and can in turn improve the health and quality of life of people with ASD. This review will primarily focus on these medical comorbidities, with a brief review of potential future treatments. Recent findings There continues to be disagreement regarding the exact prevalence and etiological significance of gastrointestinal conditions, epilepsy and other abnormal electroencephalographic findings, and sleep problems. It is not clear whether gastrointestinal conditions occur more frequently than in typically developing children, and whether there are distinct conditions that occur more often in ASD than in non-ASD populations. Abnormal electroencephalographic findings have been reported in up to 60% of children with ASD, and some believe that these abnormalities may be responsible for parts of the ASD phenotype. Sleep problems are reported more frequently than in the general population, and effective treatments are available. Future medical treatments for ASD may be directed at underlying core symptoms and have greater impact than today's symptomatic approach. Summary Further research in these areas is needed to better guide diagnosis and treatment of a variety of medical conditions experienced by people with ASD. C1 [Coury, Daniel] Ohio State Univ, Coll Med Dev & Behav Pediat, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43205 USA. RP Coury, D (reprint author), Ohio State Univ, Coll Med, Dept Pediat, 700 Childrens Dr,Timken G-350, Columbus, OH 43205 USA. EM Daniel.Coury@NationwideChildrens.org RI Coury, Daniel/E-2925-2011 FU U. S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054] FX This work was supported in part by the following: Autism Speaks and a cooperative agreement (UA3 MC 11054) from the U. S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 131 EP 136 DI 10.1097/WCO.0b013e32833722fa PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700007 PM 20087181 ER PT J AU Kasari, C Lawton, K AF Kasari, Connie Lawton, Kathy TI New directions in behavioral treatment of autism spectrum disorders SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; behavior; intervention ID HIGH-FUNCTIONING AUTISM; IMPROVISATIONAL MUSIC-THERAPY; EXCHANGE COMMUNICATION-SYSTEM; JOINT ATTENTION; YOUNG-CHILDREN; SOCIAL INTERACTIONS; TEACHING-CHILDREN; ASPERGER-SYNDROME; CONTROLLED-TRIAL; PLAY SKILLS AB Purpose of review The review explores current trends in the behavioral intervention literature for children with an autism spectrum disorder (ASD) during 2008 and 2009. Noteworthy findings and intervention strategies are highlighted. Additionally, the quality of all reviewed studies is systematically evaluated. Recent findings During 2008 and 2009, there was nearly a quarter increase in the number of behavioral intervention studies, as well as more randomized controlled trials and approaches other than applied behavior analysis. Many of the studies investigated commonly used ASD intervention practices or novel treatments. A few were conducted with underserved populations, such as toddlers and adults with ASD. Social impairment was the focus of the largest number of intervention studies. A small percentage of studies were rated as high-quality. Summary Overall, the reviewed studies suggest that ASD-specific deficits can be improved through behavioral intervention. However, whereas progress continues to be made in our understanding of effective treatments for children with ASD, confidence in these findings would be improved with higher-quality studies. C1 [Kasari, Connie] Univ Calif Los Angeles, Semel Inst 68 268, Ctr Autism Res & Treatment, Los Angeles, CA 90024 USA. RP Kasari, C (reprint author), Univ Calif Los Angeles, Semel Inst 68 268, Ctr Autism Res & Treatment, Los Angeles, CA 90024 USA. EM kasari@gseis.ucla.edu RI Lawton, Kathy/D-7835-2012 FU U. S. Dept. of Health and Human Services HRSA, Maternal and Child Health Branch [UA3MC11055]; NIH [R01 MH084864] FX The research was supported by the Autism Intervention Research-Network funded by U. S. Dept. of Health and Human Services HRSA, Maternal and Child Health Branch, Grant # UA3MC11055, Autism Speaks grant on Characterizing Cognition in Nonverbal Individuals with Autism, and NIH R01 MH084864 to Connie Kasari. We also appreciate the research assistance of Marina Farberov and Janet Bang. CR American Psychiatric Association, DIAGN STAT MAN MENT Anan RM, 2008, BEHAV INTERVENT, V23, P165, DOI 10.1002/bin.262 Angermeier K, 2008, RES AUTISM SPECT DIS, V2, P430, DOI 10.1016/j.rasd.2007.09.004 Austin D. 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Y., 2008, DEV DISABIL B, V36, P81 WHITE SW, 2009, J AUTISM DEV DISORD Wood JJ, 2009, J CHILD PSYCHOL PSYC, V50, P224, DOI 10.1111/j.1469-7610.2008.01948.x Wood JJ, 2009, J AUTISM DEV DISORD, V39, P1608, DOI 10.1007/s10803-009-0791-7 NR 77 TC 29 Z9 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 137 EP 143 DI 10.1097/WCO.0b013e32833775cd PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700008 PM 20160648 ER PT J AU Ess, KC AF Ess, Kevin C. TI Tuberous sclerosis complex: a brave new world? SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; cortical development; epilepsy; mammalian target of rapamycin; mammalian target of rapamycin complex 1; progenitor cell; tuber ID MUTATIONAL ANALYSIS; TUMOR-DEVELOPMENT; INFANTILE SPASMS; MOUSE MODEL; TSC2 GENES; RAPAMYCIN; MTOR; MICE; EPILEPSY; LYMPHANGIOLEIOMYOMATOSIS AB Purpose of review Tuberous sclerosis complex (TSC) is a multiorgan genetic disease caused by mutations in the TSC1 or TSC2 genes. TSC has been recognized for many years as an important cause of severe neurological disease with patients suffering from epilepsy, developmental delay, autism, and psychiatric problems. During the last year, there have been enormous advances in basic and translational research pertaining to TSC. Recent findings In this review, I discuss the basic science findings that position the TSC1 and TSC2 genes as critical regulators of the mammalian target of rapamycin kinase within mammalian target of rapamycin complex 1. In addition, I will discuss the development of new animal models, translational data, and recent clinical trials using mammalian target of rapamycin complex 1 inhibitors such as rapamycin. Summary The past few years have seen spectacular advances that have energized TSC-related research and challenged existing symptomatic treatments. Although it remains to be seen whether use of mammalian target of rapamycin complex 1 inhibitors will revolutionize the care of patients with TSC, the application of basic and translational research towards a specific clinical disorder emphasizes the potential and promise of molecular medicine. C1 [Ess, Kevin C.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37232 USA. [Ess, Kevin C.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. RP Ess, KC (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 465 21st Ave S,MRBIII 6158, Nashville, TN 37232 USA. EM kevin.ess@vanderbilt.edu FU National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); Tuberous Sclerosis Alliance; Vanderbilt Kennedy Center for Research on Human Development FX Dr Ess is supported by the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), and the Tuberous Sclerosis Alliance. The support was also provided by the Vanderbilt Kennedy Center for Research on Human Development. 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Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 189 EP 193 DI 10.1097/WCO.0b013e32832c4ff5 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700016 PM 20087180 ER PT J AU Landrigan, PJ AF Landrigan, Philip J. TI What causes autism? Exploring the environmental contribution SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE autism; developmental neurotoxicity; national children's study; toxicity testing; vaccines ID ORGANOPHOSPHATE PESTICIDE EXPOSURE; CHILDRENS INTELLECTUAL FUNCTION; MEXICAN-AMERICAN CHILDREN; DEVELOPMENTAL NEUROTOXICITY; IN-UTERO; POLYCHLORINATED-BIPHENYLS; THIMEROSAL EXPOSURE; RUBELLA VACCINATION; SPECTRUM DISORDERS; DEVELOPING BRAIN AB Purpose of review Autism is a biologically based disorder of brain development. Genetic factors - mutations, deletions, and copy number variants - are clearly implicated in causation of autism. However, they account for only a small fraction of cases, and do not easily explain key clinical and epidemiological features. This suggests that early environmental exposures also contribute. This review explores this hypothesis. Recent findings Indirect evidence for an environmental contribution to autism comes from studies demonstrating the sensitivity of the developing brain to external exposures such as lead, ethyl alcohol and methyl mercury. But the most powerful proof-of-concept evidence derives from studies specifically linking autism to exposures in early pregnancy - thalidomide, misoprostol, and valproic acid; maternal rubella infection; and the organophosphate insecticide, chlorpyrifos. There is no credible evidence that vaccines cause autism. Summary Expanded research is needed into environmental causation of autism. Children today are surrounded by thousands of synthetic chemicals. Two hundred of them are neurotoxic in adult humans, and 1000 more in laboratory models. Yet fewer than 20% of high-volume chemicals have been tested for neurodevelopmental toxicity. I propose a targeted discovery strategy focused on suspect chemicals, which combines expanded toxicological screening, neurobiological research and prospective epidemiological studies. C1 Mt Sinai Sch Med, Childrens Environm Hlth Ctr, Dept Pediat, Dept Community & Prevent Med, New York, NY 10029 USA. RP Landrigan, PJ (reprint author), Mt Sinai Sch Med, Childrens Environm Hlth Ctr, Dept Pediat, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM phil.landrigan@mssm.edu FU NIEHS [5P01ES9584]; EPA [RD-83171101] FX The work was supported by NIEHS grant number 5P01ES9584 and EPA grant number RD-83171101. 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In addition, MECP2 mutations and duplications are observed in a spectrum of neurodevelopmental disorders, including severe neonatal encephalopathy, X-linked mental retardation, and autism, implicating MeCP2 as an essential regulator of postnatal brain development. In this review, we compare the mutation types and inheritance patterns of the human disorders associated with MECP2. In addition, we summarize the current understanding of MeCP2 as a central epigenetic regulator of activity-dependent synaptic maturation. As MeCP2 occupies a central role in the pathogenesis of multiple neurodevelopmental disorders, continued investigation into MeCP2 function and regulatory pathways may show promise for developing broad-spectrum therapies. C1 [Gonzales, Michael L.; LaSalle, Janine M.] Univ Calif Davis, Sch Med Med Microbiol & Immunol, Davis, CA 95616 USA. RP LaSalle, JM (reprint author), Univ Calif Davis, Sch Med Med Microbiol & Immunol, 1 Shields Ave, Davis, CA 95616 USA. 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Psychiatry Rep. PD APR PY 2010 VL 12 IS 2 BP 127 EP 134 DI 10.1007/s11920-010-0097-7 PG 8 WC Psychiatry SC Psychiatry GA 752YK UT WOS:000289731200009 PM 20425298 ER PT J AU Patterson, SY Smith, V Jelen, M AF Patterson, Stephanie Y. Smith, Veronica Jelen, Michaela TI Behavioural intervention practices for stereotypic and repetitive behaviour in individuals with autism spectrum disorder: a systematic review SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Review ID SINGLE-SUBJECT RESEARCH; NONCONTINGENT REINFORCEMENT; PSYCHOSOCIAL INTERVENTIONS; RESPONSE BLOCKING; CHILDREN; STIMULATION; METHODOLOGY; VALIDATION; EFFICACY AB AIM The purpose of this systematic review was to examine the quality of conduct of experimental studies contributing to our empirical understanding of function-based behavioural interventions for stereotypic and repetitive behaviours (SRBs) in individuals with autism spectrum disorders (ASDs). METHOD Systematic review methodology was used to identify relevant articles, to rate the level of evidence and quality of conduct of the studies, and to extract data systematically. RESULTS Ten single case studies examining 17 participants (14 males, 3 females; age 2y 11mo-26y) diagnosed with various ASDs were included. Overall, studies reported decreases in SRBs using behavioural interventions and some collateral increase in desirable behaviours. INTERPRETATION Only a small number of intervention studies for SRBs explicitly state the function of the behaviour; therefore, relatively little is known about the efficacy of SRB interventions in relation to the range of possible behavioural functions. Evidence supporting SRB interventions is preliminary in nature, and caution should be used in choosing and implementing SRB intervention practices for individuals with ASDs. 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Pinto-Martin, Jennifer Mandell, David TI Sex differences in the evaluation and diagnosis of autism spectrum disorders among children SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Autism spectrum disorder; Children; Sex differences ID PERVASIVE DEVELOPMENTAL DISORDERS; EARLY IDENTIFICATION; CHILDHOOD AUTISM; PREVALENCE; SURVEILLANCE; DISABILITIES; CHALLENGES; INTERVIEW; SAMPLE; AGE AB Background: One of the most consistent features of the autism spectrum disorders (ASDs) is the predominance among males, with approximately four males to every female. We sought to examine sex differences among children who met case definition for ASD in a large, population-based cohort with respect to age at first developmental evaluation, age of diagnosis, influence of cognitive impairment on these outcomes, and sex-specific behavioral characteristics. Methods: We conducted a secondary analysis of data collected for a population-based study of the prevalence of ASD. The sample comprised 2,568 children born in 1994 who met the case definition of ASD as established by the Autism and Developmental Disabilities Monitoring (ADDM) Network for ASD surveillance. Children who had a history of developmental disability and behavioral features consistent with the DSM-IV-TR criteria for autistic disorder, Asperger's disorder, and Pervasive Developmental Disorder Not Otherwise Specified in existing evaluation records were classified as ASD cases via two paths: streamlined and nonstreamlined. Streamlined reviews were conducted if there was an ASD diagnosis documented in the records. Data were collected in 13 sites across the United States through the ADDM Network, funded by the Centers for Disease Control and Prevention. Results: Males constituted 81% of the sample. There were no differences by sex in average age at first evaluation or average age of diagnosis among those with an existing documented chart diagnosis of an ASD. Girls were less likely than boys to have a documented diagnosis (odds ratio [OR] = 0.76, p = .004). This analysis was adjusted for cognitive impairment status. In the logistic model, with the interaction term for sex and cognitive impairment, girls with IQ of 70 or less were less likely than boys with IQ of 70 or less to have a documented diagnosis (OR = 0.70, 95% confidence interval [CI] = 0.50-0.97, p = .035). Boys with IQ greater than 70 were less likely than boys with IQ of 70 or less to have a documented diagnosis (OR = 0.60, 95% CI = 0.49-0.74, p < .001). This finding (less likely to have a documented diagnosis) was also true for girls with IQ greater than 70 (OR = 0.45, 95% CI = 0.32-0.66, p < .001). Girls were more likely to have notations of seizure-like behavior (p < .001). Boys were more likely to have notations of hyperactivity or a short attention span and aggressive behavior (p < .01). Conclusions: Girls, especially those without cognitive impairment, may be formally identified at a later age than boys. This may delay referral for early intervention. Community education efforts should alert clinicians and parents to the potential of ASDs in boys and girls. (C) 2010 Elsevier Inc. All rights reserved. C1 [Giarelli, Ellen; Pinto-Martin, Jennifer] Univ Penn, Sch Nursing, Div Biobehav Hlth Syst, Philadelphia, PA 19104 USA. [Wiggins, Lisa D.; Rice, Catherine E.] Ctr Dis Control & Prevent, Dev Disabil Branch, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Levy, Susan E.] Childrens Hosp Philadelphia, Div Child Dev Rehabil & Metab Dis, Reg Autism Ctr, Philadelphia, PA 19104 USA. [Kirby, Russell S.] Univ S Florida, Coll Publ Hlth, Dept Community & Family Hlth, Tampa, FL 33647 USA. [Mandell, David] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Autism Res, Philadelphia, PA 19104 USA. [Kirby, Russell S.] Univ Alabama, Birmingham, AL USA. EM giarelli@nursing.upenn.edu RI Mandell, David/H-2730-2012 OI Mandell, David/0000-0001-8240-820X FU Centers for Disease Control and Prevention (CDC) FX The authors of this manuscript were principal investigators or co-investigators participating in the ADDM Network Surveillance Project. The principal investigators and co-investigators received salary support over several years during the collection of data that was provided by the Centers for Disease Control and Prevention (CDC). There are no conflicts of interest, financial or otherwise, relevant to the subject matter of the manuscript that have occurred over the last 2 years or that are expected in the foreseeable future, beyond participation in the ADDM network. These projects were funded by the CDC. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC. For additional information, see www.cdc.gov/autism. 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Serum protein pre-fractionation with C8-magnetic beads and protein profiling by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-ToF-MS) were used to identify possible differences in protein profiles in patients and controls. Serum was obtained from 16 patients (aged 8-18) and age-matched controls. Three peaks in the MALDI-ToF-MS significantly differentiated the ASD sample from the control group. Sub-grouping the ASD patients into children with and without comorbid Attention Deficit and Hyperactivity Disorder, ADHD (ASD/ADHD+ patients, n = 9; ASD/ADHD- patients, n = 7), one peak distinguished the ASD/ADHD+ patients from controls and ASD/ADHD- patients. Our results suggest that altered protein levels in peripheral blood of patients with ASD might represent useful biomarkers for this devastating psychiatric disorder. C1 [Taurines, Regina; Conner, Alexander C.; Grassl, Julia; Thome, Johannes] Swansea Univ, Sch Med, Inst Life Sci, Acad Unit Psychiat, Swansea SA2 8PP, W Glam, Wales. [Dudley, Edward] Swansea Univ, SOTEAS, Biochem Res Grp, Swansea SA2 8PP, W Glam, Wales. [Jans, Thomas; Guderian, Frank; Warnke, Andreas; Gerlach, Manfred] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Wurzburg, Germany. [Mehler-Wex, Claudia] Univ Ulm, Dept Child & Adolescent Psychiat & Psychotherapy, Ulm, Germany. RP Thome, J (reprint author), Swansea Univ, Sch Med, Inst Life Sci, Acad Unit Psychiat, Singleton Pk, Swansea SA2 8PP, W Glam, Wales. EM j.thome@swan.ac.uk RI Grassl, Julia/D-1047-2011 FU German Research Council [HU1536/1-1, HU1536/1-2] FX The study was supported by the German Research Council (DFG HU1536/1-1, HU1536/1-2). 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Potocki, Lorraine van Bokhoven, Hans Kleefstra, Tjitske TI Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE 16q24.3 microdeletion; ANKRD11; ZNF778; cognitive impairment; autism ID LINKED MENTAL-RETARDATION; COMPARATIVE GENOMIC HYBRIDIZATION; RUBINSTEIN-TAYBI-SYNDROME; STRUCTURAL VARIATION; CHARGE-SYNDROME; COPY NUMBER; MUTATIONS; DUPLICATION; DELETION; REARRANGEMENTS AB The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. European Journal of Human Genetics (2010) 18, 429-435; doi:10.1038/ejhg.2009.192; published online 18 November 2009 C1 [Willemsen, Marjolein H.; de Brouwer, Arjan P. M.; Pfundt, Rolph; van Bokhoven, Hans; Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Fernandez, Bridget A.] Mem Univ Newfoundland, Disciplines Genet & Med, St John, NF, Canada. [Fernandez, Bridget A.] Eastern Hlth, Prov Med Genet Program, St John, NF, Canada. [Bacino, Carlos A.; Potocki, Lorraine] Texas Childrens Hosp, Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Gerkes, Erica; Sikkema-Raddatz, Birgit] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Scherer, Stephen W.; Marshall, Christian R.] Univ Toronto, Toronto, ON, Canada. [Scherer, Stephen W.; Marshall, Christian R.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. RP Willemsen, MH (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 849, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.willemsen@antrg.umcn.nl RI van Bokhoven, Hans/D-8764-2012; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Willemsen, Marjolein/G-9491-2013; Kleefstra, Tjitske/G-2619-2012 OI Scherer, Stephen /0000-0002-8326-1999; FU Consortium VG Oost-Nederland; Genome Canada/Ontario Genomics Institute; SickKids Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD) FX We thank the parents of patients who participated in this study. This work was supported by grants from the Consortium VG Oost-Nederland (to TK and MHW) and the Genome Canada/Ontario Genomics Institute (to SWS and BF). CRM is supported by the SickKids Foundation and the National Alliance for Research on Schizophrenia and Depression (NARSAD). SWS holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto and Hospital for Sick Children. Patient consent was obtained from the patient's parents for publishing patient pictures in Figure 1. We also thank Dr Zhinshuo Ou and the Kleberg Cytogenetics Laboratory at Baylor College of Medicine. 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J. Hum. Genet. PD APR PY 2010 VL 18 IS 4 BP 429 EP 435 DI 10.1038/ejhg.2009.192 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 571CF UT WOS:000275726900010 PM 19920853 ER PT J AU Benony, H AF Benony, Herve TI Infantile sexuality and attachment relations. Notes on the revision of metapsychology proposed by Laplanche SO EVOLUTION PSYCHIATRIQUE LA French DT Article DE Infant; Attachment relations; Infantile sexuality; Metapsychology; Psychic birth; Earliest interactions; Inter-subjectivity; Theorical study; Laplanche J; Psychoanalytic therapy; Clinical case; Transfert ID AUTISM AB The idea of a unified model of mental life makes it necessary to take account of the role of the recent ideas issuing from attachment theory while simultaneously reconsidering Freudian metapsychology. The revisited and then revised basis of metapsychology proposed by Laplanche (1970, 1993, 2007) considers that interhuman adult-infant communication emerges from an instinctual genetic basis but that, from the very beginning, this communication is compromised by the adult's infantile unconscious. In other words, this situation of adult-infant communication or Fundamental Anthropological Situation reignites the parent's unconscious conflictuality - in his relations to his own parents and points him back towards his own history as a child. In this way, unconscious adult sexuality infuses the care bestowed by the other involved in the attachment and puts the child's psyche "to work", with the child thus attempting to translate the enigma of this message and forming the basis for his or her own unconscious. A case study of child psychoanalysis is presented to illustrate this model. (C) 2010 Elsevier Masson SAS. All rights reserved. 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Psychiatr. PD APR-JUN PY 2010 VL 75 IS 2 BP 287 EP 301 DI 10.1016/j.evopsy.2010.04.007 PG 15 WC Psychiatry SC Psychiatry GA 620TA UT WOS:000279521600008 ER PT J AU Nevels, RM Dehon, EE Alexander, K Gontkovsky, ST AF Nevels, Robert M. Dehon, Erin E. Alexander, Katrina Gontkovsky, Samuel T. TI Psychopharmacology of Aggression in Children and Adolescents With Primary Neuropsychiatric Disorders: A Review of Current and Potentially Promising Treatment Options SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Review DE pediatric psychopharmacology; aggression in children and adolescents; disorders with comorbid aggression; treatment ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; AUTISM SPECTRUM DISORDERS; CYCLING BIPOLAR DISORDER; PLACEBO-CONTROLLED TRIAL; FRAGILE-X SYNDROME; DOUBLE-BLIND; OPEN-LABEL; DIVALPROEX SODIUM AB Research examining the role of pharmacological therapy in the treatment of children and adolescents with clinical disorders is growing. Clinical disorders that present with comorbid aggression can add a challenge to treatment. Child and adolescent neuropsychiatric disorders associated with aggression include attention-deficit hyperactivity disorder, various mood disorders and in particular bipolar disorders/pediatric mania, schizophrenia, mental retardation, oppositional defiant disorder, conduct disorder, and autism spectrum disorders. This review describes the psychopharmacy to treat these disorders and the aggression that often appears comorbidly. Existing literature regarding the efficacy and safety of psychotropics for youth with neuropsychiatric disorders also is discussed. In addition, general guidelines for psychopharmacy of aggression in children and adolescents are presented. Studies reviewed in this article provide evidence for the use of psychostimulants, alpha-2 agonists, beta blockers, lithium, anticonvulsant mood-stabilizers, atypical antipsychotics, traditional antipsychotics, and selective serotonin reuptake inhibitors in treating pediatric aggression with the choice of medication dependent on symptomology. Despite increased support for pediatric psychotropic use, there is a need for more long-term safety and efficacy studies of existing medications and newer, safer, and more effective agents with fewer side effects for the pharmacological treatment of all childhood disorders in which aggression is prominent. C1 [Gontkovsky, Samuel T.] Methodist Rehabil Ctr, Ctr Neurosci & Neurol Recovery, Jackson, MS 39216 USA. [Nevels, Robert M.; Dehon, Erin E.; Alexander, Katrina] Jackson State Univ, Dept Psychol, Jackson, MS USA. 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PD APR PY 2010 VL 18 IS 2 BP 184 EP 201 DI 10.1037/a0018059 PG 18 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 582CU UT WOS:000276573900009 PM 20384430 ER PT J AU Zalla, T Labruyere, N Clement, A Georgieff, N AF Zalla, Tiziana Labruyere, Nelly Clement, Amelie Georgieff, Nicolas TI Predicting ensuing actions in children and adolescents with autism spectrum disorders SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Scripts; Action understanding; Mirror neurons; Frontal cortex ID MIRROR NEURON SYSTEM; LATERAL PREFRONTAL CORTEX; FRONTAL-LOBE DAMAGE; ACTION RECOGNITION; ACTION REPRESENTATION; MOTOR SIMULATION; SOCIAL COGNITION; BROCAS AREA; IMITATION; INTENTIONS AB This study investigated the ability to predict others' action in a group of children and adolescents with autism spectrum disorders (ASD) (n = 18). Their performance was compared with a group of children with mental retardation (n = 13) and a group of children with typical development (n = 19). Participants were presented with short incomplete videotaped movies showing an actor executing familiar and non-familiar actions. When asked to predict the outcome, participants with ASD produced fewer correct responses and their performance did not improve for familiar actions, as compared to both comparison groups. In addition, they committed a greater number of errors of temporal inversion. These results provide new evidence that an impaired means-end analysis process, leading to a diminished sensitivity to the sequence structure of goal-directed actions, would disrupt the ability to understand and predict others' actions. The comprehension of abnormalities in event knowledge provides a better insight of some of the problems that individuals with ASD encounter in spontaneously understanding real-life social situations. 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PD APR PY 2010 VL 201 IS 4 BP 809 EP 819 DI 10.1007/s00221-009-2096-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 569VT UT WOS:000275631300018 PM 19956934 ER PT J AU Brown, A Chow, D Murakami, S Goh, W Perreira, A Kwee, S Sil, P LeRoy, M AF Brown, Amy Chow, Dominic Murakami, Satona Goh, William Perreira, Aimee Kwee, Sandi Sil, Payel LeRoy, Majdouline TI Possible gastrointestinal symptoms in a subset of children with autism SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material ID CELIAC-DISEASE; TURNER-SYNDROME; RETT-SYNDROME; INCREASED PREVALENCE; CONSTIPATION; DISORDERS; TRANSGLUTAMINASE; RECOMMENDATIONS; ANTIBODIES; DIAGNOSIS C1 [Brown, Amy] Univ Hawaii, Dept Complementary & Alternat Med, John A Burns Sch Med, Honolulu, HI 96813 USA. [Chow, Dominic] Univ Hawaii, Dept Pediat, Honolulu, HI 96813 USA. [Chow, Dominic; Kwee, Sandi] Univ Hawaii, Dept Med, Honolulu, HI 96813 USA. [Murakami, Satona] Nagoya City Univ, Grad Sch Med Sci, Dept Orthoped Surg, Nagoya, Aichi, Japan. [Goh, William] Univ Hawaii, Dept Obstet & Gynecol, Honolulu, HI 96813 USA. [LeRoy, Majdouline] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96816 USA. RP Brown, A (reprint author), Univ Hawaii, Dept Complementary & Alternat Med, John A Burns Sch Med, 651 Ilalo St,MEB 223, Honolulu, HI 96813 USA. 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Gastroenterol. Hepatol. PD APR PY 2010 VL 4 IS 2 BP 125 EP 127 DI 10.1586/EGH.10.17 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 860XS UT WOS:000297982300001 PM 20350258 ER PT J AU Lopalco, PL Johansen, K Ciancio, B Gomes, HDC Kramarz, P Giesecke, J AF Lopalco, Pier Luigi Johansen, Kari Ciancio, Bruno Gomes, Helena De Carvalho Kramarz, Piotr Giesecke, Johan TI Monitoring and assessing vaccine safety: a European perspective SO EXPERT REVIEW OF VACCINES LA English DT Article DE adverse effects; European Union; immunization program; vaccination; vaccine safety ID HEPATITIS-B VACCINATION; MULTIPLE-SCLEROSIS; CAUSAL ASSOCIATION; IMMUNIZATION; CAMPAIGN; AUTISM; RISK; MMR AB The success of vaccination programs is an uncontroversial reality in Europe as well as worldwide. On the other hand, the perceived risk of adverse events in the general public is the most important threat for implementing successful vaccination programs in Europe. For this reason, monitoring and assessing vaccine safety is a priority for public health. Vaccine safety is assessed both before and after vaccine authorization. In postmarketing settings, different activities related to vaccine safety usually involve several different stakeholders. In 2005, a new EU agency, the European Centre for Disease Prevention and Control, was established with the aim to strengthen Europe's defences against infectious diseases. Implementing stable links between different stakeholders and defining clear roles in the EU is paramount in order to provide optimal and transparent information on adverse reactions following immunization, with the final goal of increasing compliance to safe and effective vaccination programs. C1 [Lopalco, Pier Luigi; Johansen, Kari; Ciancio, Bruno; Gomes, Helena De Carvalho; Kramarz, Piotr; Giesecke, Johan] European Ctr Dis Prevent & Control, Sci Advice Unit, SE-17183 Stockholm, Sweden. RP Lopalco, PL (reprint author), European Ctr Dis Prevent & Control, Sci Advice Unit, SE-17183 Stockholm, Sweden. 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Vaccines PD APR PY 2010 VL 9 IS 4 BP 371 EP 380 DI 10.1586/ERV.10.20 PG 10 WC Immunology SC Immunology GA 590GV UT WOS:000277214200011 PM 20370548 ER PT J AU Shamberger, RJ AF Shamberger, Raymond Joseph TI AUTISM LINKED TO NUTRITION SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shamberger, Raymond Joseph] King James Med Lab, Cleveland, OH USA. NR 0 TC 0 Z9 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500404 ER PT J AU Vidal, J Bonnet-Brilhault, F Barthelemy, C Bruneau, N AF Vidal, J. Bonnet-Brilhault, F. Barthelemy, C. Bruneau, N. TI Electrophysiological evidence of atypical auditory-visual interactions in children with autism SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Vidal, J.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bonnet-Brilhault, F.; Barthelemy, C.; Bruneau, N.] CNRS, INSERM, UMR U ERL 3106, F-75700 Paris, France. [Bonnet-Brilhault, F.; Barthelemy, C.; Bruneau, N.] Univ Tours, F-37041 Tours, France. [Bonnet-Brilhault, F.; Barthelemy, C.] CHRU Tours, Tours, France. NR 0 TC 0 Z9 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD APR PY 2010 VL 24 SU 1 MA 6 BP 2 EP 2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 576PH UT WOS:000276156800007 ER PT J AU Darbari, A Rawal, N Jhaveri, PN Jhaveri, PB AF Darbari, Anil Rawal, Nidhi Jhaveri, Punit N. Jhaveri, Pooja B. TI Children With Autism and Feeding Problems Have Significant Endoscopic Findings SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT Digestive Disease Week/111th Annual Meeting of the American-Gastroenterological-Association CY MAY 01-06, 2010 CL New Orleans, LA SP Amer Gastroenterol Assoc NR 0 TC 0 Z9 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2010 VL 71 IS 5 BP AB257 EP AB257 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 583WJ UT WOS:000276710401100 ER PT J AU Clarke, GM Cardon, LR AF Clarke, Geraldine M. Cardon, Lon R. TI Aspects of Observing and Claiming Allele Flips in Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE SNPs; linkage disequilibrium; association; power; genetic effect; type I error rate ID SEROTONIN TRANSPORTER GENE; LINKAGE DISEQUILIBRIUM; POPULATION STRATIFICATION; PARKINSONS-DISEASE; 6P22.3 GENE; AUTISM; POLYMORPHISM; PROMOTER; GENOME; LOCI AB Significant allele flipping, where associations for the same disease occur at opposite alleles of the same bi-allelic locus, is increasing. But when is a significant allele flip genuine? We address the statistical issues of claiming and observing genuine allele flips in actual samples. We show that unless an allele flip is genuine, the probability of observing a significant allele flip in samples ascertained similarly from a common population is negligible. We derive expressions for the expected values of commonly used measures of association, which confirm previous findings that the underlying mechanism of a genuine allele flip is variation in the haplotype frequencies and show further how this variation interacts with variation in the genetic effects to impact allele flipping. We show that for association testing at proxy SNPs, common in genome-wide association studies, variation in haplotype frequencies must coincide with a reversal in the sign of linkage disequilibrium (LD) to trigger genuine allele flips. Using HapMap data and r, rather than r(2), to highlight previously unobserved effects, we show that unless genetic effects are large, variation in LD is unlikely to cause genuine allele flips in samples drawn from the same population. However, as populations diverge, it is an increasingly viable cause of a genuine allele flip for sufficiently large genetic effect and/or sample sizes. We conclude that evidence of variation in local patterns of LD, ancestral composition of study samples, and environmental exposures between study populations can provide compelling practical evidence in defense of a genuine allele flip. Genet. Epidemiol. 34:266-274, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Clarke, Geraldine M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Cardon, Lon R.] GlaxoSmithKline Inc, Philadelphia, PA USA. RP Clarke, GM (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. EM gclarke@well.ox.ac.uk FU Wellcome Trust FX Contract grant sponsor: Wellcome Trust. 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Mottron, Laurent TI Neuroanatomical Differences in Brain Areas Implicated in Perceptual and Other Core Features of Autism Revealed by Cortical Thickness Analysis and Voxel-Based Morphometry SO HUMAN BRAIN MAPPING LA English DT Article DE autism; brain; MRI; enhanced perceptual functioning model; cortical thickness; voxel-based-morphometry ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; AUTOMATED 3-D EXTRACTION; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDER; HEAD CIRCUMFERENCE; ASPERGERS-SYNDROME; PLANUM TEMPORALE; SOCIAL COGNITION; MATTER VOLUME AB Autism spectrum disorder is a complex neurodevelopmental variant thought to affect 1 in 166 [Fombonne (2003): J Autism Dev Disord 33:365-382]. Individuals with autism demonstrate atypical social interaction, communication, and repetitive behaviors, but can also present enhanced abilities, particularly in auditory and visual perception and nonverbal reasoning. Structural brain differences have been reported in autism, in terms of increased total brain volume (particularly in young children with autism), and regional gray/white matter differences in both adults and children with autism, but the reports are inconsistent [Amaral et al. (2008): Trends Neurosci 31:137-145]. These inconsistencies may be due to differences in diagnostic/inclusion criteria, and age and Intelligence Quotient of participants. Here, for the first time, we used two complementary magnetic resonance imaging techniques, cortical thickness analyses, and voxel-based morphometry (VBM), to investigate the neuroanatomical differences between a homogenous group of young adults with autism of average intelligence but delayed or atypical language development (often referred to as "high-functioning autism"), relative to a closely matched group of typically developing controls. The cortical thickness and VBM techniques both revealed regional structural brain differences (mostly in terms of gray matter increases) in brain areas implicated in social cognition, communication, and repetitive behaviors, and thus in each of the core atypical features of autism. Gray matter increases were also found in auditory and visual primary and associative perceptual areas. We interpret these results as the first structural brain correlates of atypical auditory and visual perception in autism, in support of the enhanced perceptual functioning model [Mottron et al. (2006): J Autism Dev Disord 36:27-43]. Hum Brain Mapp 31:556-566, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Hyde, Krista L.; Evans, Alan C.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. [Samson, Fabienne; Mottron, Laurent] Univ Montreal, Hop Riviere Prairies, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ H1E 1A4, Canada. 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Brain Mapp. PD APR PY 2010 VL 31 IS 4 BP 556 EP 566 DI 10.1002/hbm.20887 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 581PZ UT WOS:000276537800006 PM 19790171 ER PT J AU Castermans, D Volders, K Crepel, A Backx, L De Vos, R Freson, K Meulemans, S Vermeesch, JR Schrander-Stumpel, CTRM De Rijk, P Del-Favero, J Van Geet, C Van De Ven, WJM Steyaert, JG Devriendt, K Creemers, JWM AF Castermans, Dries Volders, Karolien Crepel, An Backx, Liesbeth De Vos, Rita Freson, Kathleen Meulemans, Sandra Vermeesch, Joris R. Schrander-Stumpel, Connie T. R. M. De Rijk, Peter Del-Favero, Jurgen Van Geet, Chris Van De Ven, Wim J. M. Steyaert, Jean G. Devriendt, Koen Creemers, John W. M. TI SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles SO HUMAN MOLECULAR GENETICS LA English DT Article ID 15Q24 MICRODELETION SYNDROME; MENTAL-RETARDATION; SPECTRUM DISORDER; NEUROBEACHIN GENE; NEUROLIGIN GENES; MEMBRANE-FUSION; MUTATIONS; EXOCYTOSIS; IDENTIFICATION; ASSOCIATION AB Autism is a neurodevelopmental disorder characterized by impaired social reciprocity, impaired communication and stereotypical behaviors. Despite strong evidence for a genetic basis, few susceptibility genes have been identified. Here, we describe the positional cloning of SCAMP5, CLIC4 and PPCDC as candidate genes for autism, starting from a person with idiopathic, sporadic autism carrying a de novo chromosomal translocation. One of these genes, SCAMP5 is silenced on the derivative chromosome, and encodes a brain-enriched protein involved in membrane trafficking, similar to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold increase in stimulated secretion of large dense-core vesicles (LDCVs), while overexpression suppressed secretion. Moreover, ultrastructural analysis of blood platelets from the patients with haploinsufficieny of one of the three candidate genes, showed morphological abnormalities of dense-core granules, which closely resemble LDCVs. Taken together, this study shows that in three independent patients with autism three different negative regulators of LDCV secretion are affected, respectively, suggesting that in at least a subgroup of patients the regulation of neuronal vesicle trafficking may be involved in the pathogenesis of autism. C1 [Castermans, Dries; Volders, Karolien; Meulemans, Sandra; Creemers, John W. M.] Catholic Univ Louvain, Dept Human Genet, Biochem Neuroendocrinol Lab, B-3000 Louvain, Belgium. [Crepel, An; Backx, Liesbeth; Vermeesch, Joris R.; Steyaert, Jean G.; Devriendt, Koen] Catholic Univ Louvain, Ctr Human Genet, Div Clin Genet, B-3000 Louvain, Belgium. [De Vos, Rita] Catholic Univ Louvain, Dept Med Diagnost Sci, Morphol & Mol Pathol Sect, B-3000 Louvain, Belgium. [Freson, Kathleen; Van Geet, Chris] Catholic Univ Louvain, Dept Mol & Cellular Med, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium. [Van De Ven, Wim J. M.] Catholic Univ Louvain, Dept Human Genet, Mol Oncol Lab, B-3000 Louvain, Belgium. [Van Geet, Chris] Catholic Univ Louvain, Dept Pediat, B-3000 Louvain, Belgium. [Steyaert, Jean G.] Catholic Univ Louvain, Dept Child Psychiat, B-3000 Louvain, Belgium. [Schrander-Stumpel, Connie T. R. M.] Univ Maastricht, Clin Genet Ctr, NL-6201 BL Maastricht, Netherlands. [De Rijk, Peter; Del-Favero, Jurgen; Steyaert, Jean G.] VIB, Dept Mol Genet, Appl Mol Genom Grp, Louvain, Belgium. [De Rijk, Peter; Del-Favero, Jurgen] Univ Antwerp, B-2610 Antwerp, Belgium. RP Creemers, JWM (reprint author), Catholic Univ Louvain, Dept Human Genet, Biochem Neuroendocrinol Lab, Herestr 49, B-3000 Louvain, Belgium. EM john.creemers@med.kuleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 FU Cure Autism Now; Interuniversity Attraction Poles Program-Belgian Science Policy [IUAP 5/25]; 'Geconcerteerde Onderzoeksacties' [GOA/2006/12, GOA/2008/16]; 'Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO)' [G0264.04, G.0124.02]; 'interdisciplinaire onderzoeksprogramma (IDO)'; Instituut voor de aanmoediging van Innovatie door wetenschap en technologie in Vlaanderen (IWT); Clinical Research Fund U.Z. Leuven FX This work was supported by grants from Cure Autism Now, the Interuniversity Attraction Poles Program-Belgian Science Policy (IUAP 5/25), 'Geconcerteerde Onderzoeksacties' GOA/2006/12 and GOA/2008/16, 'Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO)' G0264.04 and G.0124.02 and 'interdisciplinaire onderzoeksprogramma (IDO)'. K. V. is supported by a grant from the Instituut voor de aanmoediging van Innovatie door wetenschap en technologie in Vlaanderen (IWT). J. S. is supported by a grant of the Clinical Research Fund U.Z. Leuven. K.D. is a Senior Clinical Investigator of FWO, K. F. is postdoctoral fellow of FWO, A.C. is PhD fellow of FWO. 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Mol. Genet. PD APR PY 2010 VL 19 IS 7 BP 1368 EP 1378 DI 10.1093/hmg/ddq013 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 572HK UT WOS:000275818500019 PM 20071347 ER PT J AU Riedmann, EM AF Riedmann, Eva M. TI Lancet retracts controversial Autism Study SO HUMAN VACCINES LA English DT News Item NR 0 TC 0 Z9 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD APR PY 2010 VL 6 IS 4 BP 286 EP 286 PG 1 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 652GH UT WOS:000281990800001 ER PT J AU Gorczowski, K Styner, M Jeong, JY Marron, JS Piven, J Hazlett, HC Pizer, SM Gerig, G AF Gorczowski, Kevin Styner, Martin Jeong, Ja Yeon Marron, J. S. Piven, Joseph Hazlett, Heather Cody Pizer, Stephen M. Gerig, Guido TI Multi-Object Analysis of Volume, Pose, and Shape Using Statistical Discrimination SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE Shape; size and shape; shape analysis ID DEFORMABLE M-REPS; CAUDATE-NUCLEUS; SEGMENTATION; SCHIZOPHRENIA; AUTISM; MODELS; LEVEL; MRI; HIPPOCAMPUS; DISORDER AB One goal of statistical shape analysis is the discrimination between two populations of objects. Whereas traditional shape analysis was mostly concerned with single objects, analysis of multi-object complexes presents new challenges related to alignment and pose. In this paper, we present a methodology for discriminant analysis of multiple objects represented by sampled medial manifolds. Non-euclidean metrics that describe geodesic distances between sets of sampled representations are used for alignment and discrimination. Our choice of discriminant method is the distance-weighted discriminant because of its generalization ability in high-dimensional, low sample size settings. Using an unbiased, soft discrimination score, we associate a statistical hypothesis test with the discrimination results. We explore the effectiveness of different choices of features as input to the discriminant analysis, using measures like volume, pose, shape, and the combination of pose and shape. Our method is applied to a longitudinal pediatric autism study with 10 subcortical brain structures in a population of 70 subjects. It is shown that the choices of type of global alignment and of intrinsic versus extrinsic shape features, the latter being sensitive to relative pose, are crucial factors for group discrimination and also for explaining the nature of shape change in terms of the application domain. C1 [Gorczowski, Kevin; Styner, Martin; Jeong, Ja Yeon; Pizer, Stephen M.] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA. [Styner, Martin; Piven, Joseph; Hazlett, Heather Cody] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Marron, J. S.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA. [Gerig, Guido] Univ Utah, Sci Comp & Imaging Inst SCI, Salt Lake City, UT 84112 USA. RP Gorczowski, K (reprint author), Univ N Carolina, Dept Comp Sci, CB 3175, Chapel Hill, NC 27599 USA. EM kgorcz@unc.edu; styner@cs.unc.edu; jjeong@email.unc.edu; marron@email.unc.edu; jpiven@med.unc.edu; hcody@med.unc.edu; smp@cs.unc.edu; gerig@sci.utah.edu FU NIH NIBIB [P01 EB002779]; NIH Conte Center [MH064065]; UNC Neurodevelopmental Research Core NDRC; NIH [RO1 MH61696]; NIMH [MH64580] FX This research is supported by the NIH NIBIB grant P01 EB002779, the NIH Conte Center MH064065, and the UNC Neurodevelopmental Research Core NDRC. The MRI images of infants and expert manual segmentations are funded by NIH RO1 MH61696 and NIMH MH64580. 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Pattern Anal. Mach. Intell. PD APR PY 2010 VL 32 IS 4 BP 652 EP 661 DI 10.1109/TPAMI.2009.92 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 555XA UT WOS:000274548800007 PM 20224121 ER PT J AU Coakley, T AF Coakley, Tom TI State Guidance Documents for Young Children With Autism Spectrum Disorders Content and Comparison SO INFANTS AND YOUNG CHILDREN LA English DT Article DE autism; ASD; IDEA Part C; IDEA Section 619; state systems AB The dramatic increase in the identification of young children with autism spectrum disorders (ASD) beginning in the 1980s presented many challenges to State Education Agencies responsible for Special Education for school aged children and State Part C Lead Agencies responsible for Early Intervention services for infants and toddlers under the IDEA. This expanding population was being identified at younger ages and required intensive treatment by qualified personnel, straining system capacity. As part of their efforts to provide evidence based, comprehensive, accessible, and effective services for these children, many states have developed guidance documents about ASD for their early childhood systems. A review and comparison of nine of these documents shows them to have many differences in focus and content, even though they have similar intent. Further inquiry is required to understand the impact of these documents have had in meeting the needs of young children with ASD. C1 Housaton Community Coll, Bridgeport, CT 06604 USA. RP Coakley, T (reprint author), Housaton Community Coll, 900 Lafayette Blvd, Bridgeport, CT 06604 USA. 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Martin, Alex Wallace, Gregory L. TI Adaptive Behavior Ratings Correlate With Symptomatology and IQ Among Individuals With High-Functioning Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Adaptive behavior; Social skills; IQ; Symptomatology; Asperger's syndrome ID DIAGNOSTIC INTERVIEW; DEVELOPMENTAL DISORDERS; CHILDREN; VINELAND; PREDICTORS; SCALES; RELIABILITY; DEFICITS; DOMAINS; AGE AB Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD group, adaptive communication skills were positively related to IQ while global adaptive functioning was negatively associated with autism symptomatology. 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